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.Down Syndrome: A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cell Line, Tumor: A cell line derived from cultured tumor cells.Phorbol Esters: Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Phorbol 12,13-Dibutyrate: A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.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.Antigens, CD46: A ubiquitously expressed complement receptor that binds COMPLEMENT C3B and COMPLEMENT C4B and serves as a cofactor for their inactivation. CD46 also interacts with a wide variety of pathogens and mediates immune response.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.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.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.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.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.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.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Kinetics: The rate dynamics in chemical or physical systems.Receptor, Insulin: A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.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.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.Phorbols: The parent alcohol of the tumor promoting compounds from CROTON OIL (Croton tiglium).Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Measles virus: The type species of MORBILLIVIRUS and the cause of the highly infectious human disease MEASLES, which affects mostly children.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Receptors, Virus: Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.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.RNA, Neoplasm: RNA present in neoplastic tissue.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.MicroRNAs: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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.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.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.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.Cell Adhesion: Adherence of cells to surfaces or to other cells.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.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.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).Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Cadherins: Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.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.Leucine: An essential branched-chain amino acid important for hemoglobin formation.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Proto-Oncogene Proteins c-akt: A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.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.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.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.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.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.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.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)Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.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.Mice, Inbred C57BLBreast Neoplasms: Tumors or cancer of the human BREAST.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.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.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.PhosphoproteinsGenetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.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.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).Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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.)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.Mice, Inbred BALB CChromosomes, Human, Pair 21: A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation EMBRYO; FETUS; or pregnant female before birth.Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.Maternal Age: The age of the mother in PREGNANCY.Estriol: A hydroxylated metabolite of ESTRADIOL or ESTRONE that has a hydroxyl group at C3, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During PREGNANCY, a large amount of estriol is produced by the PLACENTA. Isomers with inversion of the hydroxyl group or groups are called epiestriol.Pregnancy Trimester, Second: The middle third of a human PREGNANCY, from the beginning of the 15th through the 28th completed week (99 to 196 days) of gestation.Leukemia, Megakaryoblastic, Acute: An acute myeloid leukemia in which 20-30% of the bone marrow or peripheral blood cells are of megakaryocyte lineage. MYELOFIBROSIS or increased bone marrow RETICULIN is common.Amniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions.Fetal Diseases: Pathophysiological conditions of the FETUS in the UTERUS. Some fetal diseases may be treated with FETAL THERAPIES.Abortion, Eugenic: Abortion performed because of possible fetal defects.alpha-Fetoproteins: The first alpha-globulins to appear in mammalian sera during FETAL DEVELOPMENT and the dominant serum proteins in early embryonic life.Nasal Bone: Either one of the two small elongated rectangular bones that together form the bridge of the nose.Infant, Newborn: An infant during the first month after birth.Karyotyping: Mapping of the KARYOTYPE of a cell.Nuchal Translucency Measurement: A prenatal ultrasonography measurement of the soft tissue behind the fetal neck. Either the translucent area below the skin in the back of the fetal neck (nuchal translucency) or the distance between occipital bone to the outer skin line (nuchal fold) is measured.Nondisjunction, Genetic: The failure of homologous CHROMOSOMES or CHROMATIDS to segregate during MITOSIS or MEIOSIS with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Pregnancy Trimester, First: The beginning third of a human PREGNANCY, from the first day of the last normal menstrual period (MENSTRUATION) through the completion of 14 weeks (98 days) of gestation.Pregnancy, High-Risk: Pregnancy in which the mother and/or FETUS are at greater than normal risk of MORBIDITY or MORTALITY. Causes include inadequate PRENATAL CARE, previous obstetrical history (ABORTION, SPONTANEOUS), pre-existing maternal disease, pregnancy-induced disease (GESTATIONAL HYPERTENSION), and MULTIPLE PREGNANCY, as well as advanced maternal age above 35.Ultrasonography, Prenatal: The visualization of tissues during pregnancy through recording of the echoes of ultrasonic waves directed into the body. The procedure may be applied with reference to the mother or the fetus and with reference to organs or the detection of maternal or fetal disease.Chorionic Gonadotropin, beta Subunit, Human: The beta subunit of human CHORIONIC GONADOTROPIN. Its structure is similar to the beta subunit of LUTEINIZING HORMONE, except for the additional 30 amino acids at the carboxy end with the associated carbohydrate residues. HCG-beta is used as a diagnostic marker for early detection of pregnancy, spontaneous abortion (ABORTION, SPONTANEOUS); ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA; or DOWN SYNDROME.Pregnancy-Associated Plasma Protein-A: A product of the PLACENTA, and DECIDUA, secreted into the maternal circulation during PREGNANCY. It has been identified as an IGF binding protein (IGFBP)-4 protease that proteolyzes IGFBP-4 and thus increases IGF bioavailability. It is found also in human FIBROBLASTS, ovarian FOLLICULAR FLUID, and GRANULOSA CELLS. The enzyme is a heterotetramer of about 500-kDa.Paternal Age: Age of the biological father.

Stromal cells mediate retinoid-dependent functions essential for renal development. (1/25249)

The essential role of vitamin A and its metabolites, retinoids, in kidney development has been demonstrated in vitamin A deficiency and gene targeting studies. Retinoids signal via nuclear transcription factors belonging to the retinoic acid receptor (RAR) and retinoid X receptor (RXR) families. Inactivation of RARaplpha and RARbeta2 receptors together, but not singly, resulted in renal malformations, suggesting that within a given renal cell type, their concerted function is required for renal morphogenesis. At birth, RARalpha beta2(-) mutants displayed small kidneys, containing few ureteric bud branches, reduced numbers of nephrons and lacking the nephrogenic zone where new nephrons are continuously added. These observations have prompted us to investigate the role of RARalpha and RARbeta2 in renal development in detail. We have found that within the embryonic kidney, RARalpha and RARbeta2 are colocalized in stromal cells, but not in other renal cell types, suggesting that stromal cells mediate retinoid-dependent functions essential for renal development. Analysis of RARalpha beta2(-) mutant kidneys at embryonic stages revealed that nephrons were formed and revealed no changes in the intensity or distribution of molecular markers specific for different metanephric mesenchymal cell types. In contrast the development of the collecting duct system was greatly impaired in RARalpha beta2(-) mutant kidneys. Fewer ureteric bud branches were present, and ureteric bud ends were positioned abnormally, at a distance from the renal capsule. Analysis of genes important for ureteric bud morphogenesis revealed that the proto-oncogene c-ret was downregulated. Our results suggest that RARalpha and RARbeta2 are required for generating stromal cell signals that maintain c-ret expression in the embryonic kidney. Since c-ret signaling is required for ureteric bud morphogenesis, loss of c-ret expression is a likely cause of impaired ureteric bud branching in RARalpha beta2(-) mutants.  (+info)

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells. (2/25249)

Increased breast cancer growth has been associated with increased expression of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases (RTKs). Upon activation, RTKs may transmit their oncogenic signals by binding to the growth factor receptor bound protein-2 (Grb2), which in turn binds to SOS and activates the Ras/Raf/MEK/mitogen-activated protein (MAP) kinase pathway. Grb2 is important for the transformation of fibroblasts by EGFR and ErbB2; however, whether Grb2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear. We have used liposomes to deliver nuclease-resistant antisense oligodeoxynucleotides (oligos) specific for the GRB2 mRNA to breast cancer cells. Grb2 protein downregulation could inhibit breast cancer cell growth; the degree of growth inhibition was dependent upon the activation and/or endogenous levels of the RTKs. Grb2 inhibition led to MAP kinase inactivation in EGFR, but not in ErbB2, breast cancer cells, suggesting that different pathways might be used by EGFR and ErbB2 to regulate breast cancer growth.  (+info)

A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation. (3/25249)

Mouse cytomegalovirus (MCMV) early gene expression interferes with the major histocompatibility complex class I (MHC class I) pathway of antigen presentation. Here we identify a 48 kDa type I transmembrane glycoprotein encoded by the MCMV early gene m06, which tightly binds to properly folded beta2-microglobulin (beta2m)-associated MHC class I molecules in the endoplasmic reticulum (ER). This association is mediated by the lumenal/transmembrane part of the protein. gp48-MHC class I complexes are transported out of the ER, pass the Golgi, but instead of being expressed on the cell surface, they are redirected to the endocytic route and rapidly degraded in a Lamp-1(+) compartment. As a result, m06-expressing cells are impaired in presenting antigenic peptides to CD8(+) T cells. The cytoplasmic tail of gp48 contains two di-leucine motifs. Mutation of the membrane-proximal di-leucine motif of gp48 restored surface expression of MHC class I, while mutation of the distal one had no effect. The results establish a novel viral mechanism for downregulation of MHC class I molecules by directly binding surface-destined MHC complexes and exploiting the cellular di-leucine sorting machinery for lysosomal degradation.  (+info)

Epstein-barr virus regulates c-MYC, apoptosis, and tumorigenicity in Burkitt lymphoma. (4/25249)

Loss of the Epstein-Barr virus (EBV) genome from Akata Burkitt lymphoma (BL) cells is coincident with a loss of malignant phenotype, despite the fact that Akata and other EBV-positive BL cells express a restricted set of EBV gene products (type I latency) that are not known to overtly affect cell growth. Here we demonstrate that reestablishment of type I latency in EBV-negative Akata cells restores tumorigenicity and that tumorigenic potential correlates with an increased resistance to apoptosis under growth-limiting conditions. The antiapoptotic effect of EBV was associated with a higher level of Bcl-2 expression and an EBV-dependent decrease in steady-state levels of c-MYC protein. Although the EBV EBNA-1 protein is expressed in all EBV-associated tumors and is reported to have oncogenic potential, enforced expression of EBNA-1 alone in EBV-negative Akata cells failed to restore tumorigenicity or EBV-dependent down-regulation of c-MYC. These data provide direct evidence that EBV contributes to the tumorigenic potential of Burkitt lymphoma and suggest a novel model whereby a restricted latency program of EBV promotes B-cell survival, and thus virus persistence within an immune host, by selectively targeting the expression of c-MYC.  (+info)

Control of growth and differentiation by Drosophila RasGAP, a homolog of p120 Ras-GTPase-activating protein. (5/25249)

Mammalian Ras GTPase-activating protein (GAP), p120 Ras-GAP, has been implicated as both a downregulator and effector of Ras proteins, but its precise role in Ras-mediated signal transduction pathways is unclear. To begin a genetic analysis of the role of p120 Ras-GAP we identified a homolog from the fruit fly Drosophila melanogaster through its ability to complement the sterility of a Schizosaccharomyces pombe (fission yeast) gap1 mutant strain. Like its mammalian homolog, Drosophila RasGAP stimulated the intrinsic GTPase activity of normal mammalian H-Ras but not that of the oncogenic Val12 mutant. RasGAP was tyrosine phosphorylated in embryos and its Src homology 2 (SH2) domains could bind in vitro to a small number of tyrosine-phosphorylated proteins expressed at various developmental stages. Ectopic expression of RasGAP in the wing imaginal disc reduced the size of the adult wing by up to 45% and suppressed ectopic wing vein formation caused by expression of activated forms of Breathless and Heartless, two Drosophila receptor tyrosine kinases of the fibroblast growth factor receptor family. The in vivo effects of RasGAP overexpression required intact SH2 domains, indicating that intracellular localization of RasGAP through SH2-phosphotyrosine interactions is important for its activity. These results show that RasGAP can function as an inhibitor of signaling pathways mediated by Ras and receptor tyrosine kinases in vivo. Genetic interactions, however, suggested a Ras-independent role for RasGAP in the regulation of growth. The system described here should enable genetic screens to be performed to identify regulators and effectors of p120 Ras-GAP.  (+info)

Down-regulation of RpS21, a putative translation initiation factor interacting with P40, produces viable minute imagos and larval lethality with overgrown hematopoietic organs and imaginal discs. (6/25249)

Down-regulation of the Drosophila ribosomal protein S21 gene (rpS21) causes a dominant weak Minute phenotype and recessively produces massive hyperplasia of the hematopoietic organs and moderate overgrowth of the imaginal discs during larval development. Here, we show that the S21 protein (RpS21) is bound to native 40S ribosomal subunits in a salt-labile association and is absent from polysomes, indicating that it acts as a translation initiation factor rather than as a core ribosomal protein. RpS21 can interact strongly with P40, a ribosomal peripheral protein encoded by the stubarista (sta) gene. Genetic studies reveal that P40 underexpression drastically enhances imaginal disc overgrowth in rpS21-deficient larvae, whereas viable combinations between rpS21 and sta affect the morphology of bristles, antennae, and aristae. These data demonstrate a strong interaction between components of the translation machinery and showed that their underexpression impairs the control of cell proliferation in both hematopoietic organs and imaginal discs.  (+info)

Transformation of intestinal epithelial cells by chronic TGF-beta1 treatment results in downregulation of the type II TGF-beta receptor and induction of cyclooxygenase-2. (7/25249)

The precise role of TGF-beta in colorectal carcinogenesis is not clear. The purpose of this study was to determine the phenotypic alterations caused by chronic exposure to TGF-beta in non-transformed intestinal epithelial (RIE-1) cells. Growth of RIE-1 cells was inhibited by >75% following TGF-beta1 treatment for 7 days, after which the cells resumed a normal growth despite the presence of TGF-beta1. These 'TGF-beta-resistant' cells (RIE-Tr) were continuously exposed to TGF-beta for >50 days. Unlike the parental RIE cells, RIE-Tr cells lost contact inhibition, formed foci in culture, grew in soft agarose. RIE-Tr cells demonstrated TGF-beta-dependent invasive potential in an in vitro assay and were resistant to Matrigel and Na-butyrate-induced apoptosis. The RIE-Tr cells were also tumorigenic in nude mice. The transformed phenotype of RIE-Tr cells was associated with a 95% decrease in the level of the type II TGF-beta receptor (TbetaRII) protein, a 40-fold increase in cyclooxygenase-2 (COX-2) protein, and 5.9-fold increase in the production of prostacyclin. Most RIE-Tr subclones that expressed low levels of TbetaRII and high levels of COX-2 were tumorigenic. Those subclones that express abundant TbetaRII and low levels of COX-2 were not tumorigenic in nude mice. A selective COX-2 inhibitor inhibited RIE-Tr cell growth in culture and tumor growth in nude mice. The reduced expression of TbetaRII, increased expression of COX-2, and the ability to form colonies in Matrigel were all reversible upon withdrawal of exogenous TGF-beta1 for the RIE-Tr cells.  (+info)

Downregulation of metallothionein-IIA expression occurs at immortalization. (8/25249)

Metallothioneins (MTs) may modulate a variety of cellular processes by regulating the activity of zinc-binding proteins. These proteins have been implicated in cell growth regulation, and their expression is abnormal in some tumors. In particular, MT-IIA is expressed 27-fold less in human colorectal tumors and tumor cell lines compared with normal tissue (Zhang et al., 1997). Here we demonstrate that MT-IIA downregulation occurs when human cells become immortal, a key event in tumorigenesis. After immortalization MT-IIA expression remains inducible but the basal activity of the MT-IIA promoter is decreased. MT-IIA downregulation at immortalization is one of the most common immortalization-related changes identified to date, suggesting that MT-IIA has a role in this process.  (+info)

Xie, W., Xie, H., Liu, F., Li, W., Dan, J., Mei, Y., Dan, L., Xiao, X., Li, J. and Chen, X. (2013), Propranolol induces apoptosis of human umbilical vein endothelial cells through downregulation of CD147. British Journal of Dermatology, 168: 739-748. doi: 10.1111/bjd.12193 ...
Dr. Katzmanns Protein Sorting and Receptor Downregulation Lab at Mayo Clinic looks at ESCRTs and associated factors facilitate the MVB sorting process.
(KudoZ) English to Portuguese translation of marked down-regulation: regulação descendente marcante, regulação descendente acentuada [Medical (general) (Medical)].
TY - JOUR. T1 - Tiazofurin down-regulates expression of c-Ki-ras oncogene in a leukemic patient. AU - Weber, G.. AU - Nagai, M.. AU - Natsumeda, Y.. AU - Eble, J. N.. AU - Jayaram, H. N.. AU - Paulik, E.. AU - Zhen, W.. AU - Hoffman, R.. AU - Tricot, G.. PY - 1991/1/1. Y1 - 1991/1/1. UR - http://www.scopus.com/inward/record.url?scp=0025806199&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0025806199&partnerID=8YFLogxK. M3 - Article. C2 - 1705812. AN - SCOPUS:0025806199. VL - 3. SP - 61. EP - 66. JO - Oncology Research. JF - Oncology Research. SN - 0965-0407. IS - 3. ER - ...
In addition to initiating signaling events, the activation of cell surface receptors also triggers regulatory processes that restrict the duration of signaling. Acute attenuation of signaling can be accomplished either via ligand-induced internalization of receptors (endocytic downregulation) or via ligand-induced receptor desensitization. These phenomena have traditionally been viewed in the context of adaptation wherein the receptor system enters a refractory state in the presence of sustained ligand stimuli and thereby prevents the cell from over-responding to the ligand. Here we use the epidermal growth factor receptor (EGFR) and G-protein coupled receptors (GPCR) as model systems to respectively examine the effects of downregulation and desensitization on the ability of signaling receptors to decode time-varying ligand stimuli. Using a mathematical model, we show that downregulation and desensitization mechanisms can lead to tight and efficient input-output coupling thereby ensuring synchronous
Oncogenic Ras downregulates CD24 expression in NIH/3T3 cells. CD24 mRNA expression in vector control (Control) and RasV12 cells was determined by (A) RT-PCR and
RESULTS: 775 genes were differentially expressed and clustered in terms of their growth factor responsiveness. As well as identifying uncharacterized genes as novel targets of ErbB2-dependent signalling, ErbB2 overexpression augmented the induction of multiple genes involved in proliferation (e.g. MYC, MAP2K1, MAP2K3), autocrine growth factor signalling (VEGF, PDGF) and adhesion/cytoskeletal regulation (ZYX, THBS1, VCL, CNN3, ITGA2, ITGA3, NEDD9, TAGLN), linking them to the hyper-poliferative and altered adhesive phenotype of the ErbB2-overexpressing cells. We also report ErbB2-dependent down-regulation of multiple interferon-stimulated genes that may permit ErbB2-overexpressing cells to resist the anti-proliferative action of interferons. Finally, IGFBP3 was unique in its pattern of regulation and we further investigated a possible role for IGFBP3 down-regulation in ErbB2-dependent transformation through suppressed IGF1 signalling. We show that IGF1-dependent signalling and proliferation were ...
when a ligan binds, the signal produced by the liogand must be stopped. one way is receptor downregulation, in which the receptor is internalized and degraded in the lysosome ...
I have more to say on some of the ensuing discussion on the direction of causality when I procure some other references, but for now lets fast forward a bit. Taubes goes on to describe metabolic adaptation, regulation and homeostasis. The implication he makes in this discussion is that human metabolism is extremely varied and adaptable. Yes, there are differences due to hormonal levels (e.g. hypothyroidism is a basic example), and different macronutrients elicit different thermogenic effects, but there are limits. Hormonal signals can downregulate metabolism, lower body temp, etc. But theres only so far this can go ... or we die! By the same token, overfeeding studies have demonstrated time and again that whatever signalling and adaptations (futile cycling) may occur in response cannot prevent considerable weight gain. Taubes basically implies that no matter what we may do consciously to (a) maintain caloric balance, (b) induce positive caloric balance, or (c) induce a caloric deficit, our ...
Down-regulation of Akt1 in IGF-IR cells induces migration and EMT. (A, top) The motility of IGF-IR cells with isoform-specific down-regulation of Akt was assess
Book now at Article One - American Grill in Washington, explore menu, see photos and read 217 reviews: A very nice atmosphere. We did, however, have to contend with a screaming baby at the front desk. Otherwise, the staff was very polite and attentive.
Our recent work established the essential role of β-arrestin in the internalization of the M2 mAChR [9]. The present study extends the observations of previous work and demonstrates that the agonist-promoted down-regulation of M1 and M2 mAChRs is β-arrestin dependent, and that the ubiquitination pattern of β-arrestin has a critical role in the differential down-regulation for M1 vs M2 mAChRs.. It has been previously established in a variety of cell lines that a prolonged activation of M1 or M2 mAChRs induces receptor down-regulation. In agreement with these findings, long-term stimulation of M1 or M2 mAChRs induced receptor down-regulation with the M1 mAChR showing significantly more down-regulation than M2 subtype. This observation suggests that the two subtypes are differentially regulated by endogenous β-arrestins. No down-regulation of either mAChR subtype occurred in the absence of β-arrestin and either β-arrestin subtype was able to rescue receptor down-regulation.. The observations ...
The disialoganglioside GD3 plays a major role in proliferation, differentiation, and apoptosis. It has been reported that ganglioside GD3 can induce apoptosis through bcl-2 mediated mitochondrial pathway. However, the relationship between ganglioside GD3 and B-cell/CLL lymphoma 2 (Bcl-2) is not full …
In chronic heart failure (HF), sympathetic nervous system overdrive induces the upregulation of G-protein-coupled receptor kinase 2 (GRK2) with a consequent β-adrenergic receptor downregulation/desensitization. Importantly, in failing myocardium, β-adrenergic receptor dysregulation is clinically seen by loss of inotropic reserve. Currently, β-blockers represent a solid "pillar" of HF therapy that at the molecular level efficiently counteracts both β-adrenergic receptor downregulation and GRK2 upregulation. GRK2 inhibition represents a promising new strategy to rescue the failing heart, and we have recently demonstrated that in some animal models, it could be used as a substitute for or in conjunction with β-blockers. GRK2 inhibition may be effective by interfering with other intracellular processes. The present study provides the first evidence of a direct and GRK2-dependent interaction between the β1-adrenergic receptor and the sphingosine-1-phosphate receptor 1 (S1PR1). We show that the ...
This study further elucidates the role of CYP33 in gene transcription by studying the effects of CYP33 overexpression and siRNA-mediated down-regulation on the expression of MLL target genes such as c-MYC, p21, p27, and HOXA9. CYP33 is a cis-trans prolyl isomerase (PPIase) which mediates repression of HOX gene expression after binding to the 3rd PHD finger of MLL through its own RRM domain. Upon binding to MLL, CYP33 increases recruitment of HDAC to the MLL repression domain which in turn leads to deacetylation of histone H3. This ultimately causes repression of MLL target genes (Xia et al. 2003). Chromosomal translocations involving the MLL gene (Mixed Lineage Leukemia) can lead to the production of fusion proteins with any of more than 60 different partner proteins and is implicated in the initiation of leukemia. Expression of MLL fusion proteins leads to increased expression of MLL target genes such as HOXA7, HOXA9 and MEIS1 (Hess et al., 2010). MLL-fusion proteins lack the 3rd PHD finger and ...
Head and thorax development in the Drosophila embryo requires the maternal determinant of the anterior patterning system bicoid (bcd) (Frohnhofer and Nusslein-Volhard, 1986). The Bcd protein is expressed as a maternal anteroposterior concentration gradient in the early developing embryo (Driever and Nusslein-Volhard, 1988b; Struhl et al., 1989) and it is necessary for the expression of numerous zygotic genes in distinct anterior domains. Among them, the gap gene hunchback (hb), which is required for the formation of the segmented part of the head and of the thorax, is activated by low levels of Bcd and expands from 54% to 100% of egg length (EL). In contrast to hb, the expression of another Bcd target gene, the head gap gene orthodenticle (otd), which is involved in the development of antennal and pre-antennal segments, is restricted to 100-70% of EL in the domain where high levels of Bcd concentration are found. Bcd is a homeodomain (HD)-containing transcription factor that probably activates ...
By studying activated DC, it was found that CD82 appeared to have an opposing function to CD37. Whereas CD37 expression was down-regulated following activation of DC, CD82 was up-regulated and restrained DC migration to lymph nodes. DC that were deficient in either CD37 or CD82 were unable to become fully functional and DC that were deficient in CD82 were able to spread much further than CD37 deficient DC. Thus, unactivated DC were observed to have high CD37 expression and low CD82 expression leading to a highly mobile cell that is able to travel easily around the body. Activated DC (DC that have sensed an infection) have low CD37 expression and high CD82 expression which limits mobility of the DC but is able to efficiently signal to immune cells that an infection is present ...
Interferon regulatory aspect (IRF)-3 may have a crucial function in viral and bacterial innate immune system replies by regulating the creation of type We interferon (IFN). cells. This inhibition was because of its suppression from the transcriptional activation TC-E 5001 of IRF-3, as proven by inhibition of IRF-3 PRD (III-I) luciferase activity along with the phosphorylation design of IRF-3 within the immunoblotting test. Furthermore, TQ targeted the autophosphorylation of TANK-binding kinase 1 (TBK1), an upstream essential enzyme in charge of IRF-3 activation. Used together, these results claim that TQ can downregulate IRF-3 activation via inhibition of TBK1, which would eventually decrease the creation of type I IFN. TQ also governed IRF-3, among the inflammatory transcription elements, offering a novel understanding into its anti-inflammatory actions. (TRIF). Upon arousal by LPS, TLR-4 recruits the adaptor proteins TRIF, which in turn recruits tumor necrosis TC-E 5001 aspect ...
Androgen suppression mediates transcriptional downregulation of DNA repair genes. Stimulation with supraphysiologic levels of dihydrotestosterone induces formation of lethal DNA breaks through recruitment of topoisomerase II enzymes to fragile DNA sites. Bipolar castration and stimulation that contributes to increasing DNA damage represents a novel strategy of sensitizing prostate cancer to cytotoxic therapies, including radiotherapy. Clin Cancer Res; 22(13); 1-3. ©2016 AACR.. See related article by Hedayati et al., p. 3310 ...
Sigma-Aldrich offers abstracts and full-text articles by [Fei Gao, Jiyu Guan, Limei Liu, Sheng Zhang, Peipei An, Anran Fan, Guangqi Song, Peng Zhang, Tianchuang Zhao, Bo Tang, Xueming Zhang, Ziyi Li].
Evidence-Based Complementary and Alternative Medicine (eCAM) is an international peer-reviewed, Open Access journal that seeks to understand the sources and to encourage rigorous research in this new, yet ancient world of complementary and alternative medicine.
In the original manuscript, the text in figure 1 is illegible. Furthermore, there is an unnecessary carriage return (page 1716, ~line 18) crystallographic ... methods. [...]
Curcumin blocks CCL2 induced adhesion, motility and invasion, in part, through down-regulation of CCL2 expression and proteolytic activity is an eagle-i resource of type Journal article at Oregon Health & Science University.
Mutations in the parkin gene, which encodes a ubiquitin ligase, has been implicated as one of causative factor for genetic parkinsonism. Interestingly, parkin role has also been implicated in cancer as a putative tumor suppressor with the gene been frequently targeted by deletion and inactivation in several human malignant tumors. Here, we demonstrated a potential tumor suppressor role for parkin in gliomas. We found that parkin expression was dramatically reduced in glioma cells and that the restoration of parkin expression promoted G1 phase cell-cycle arrest and mitigated the proliferation rate of glioma cells in vitro and in vivo. Furthermore, parkin-expressing glioma cells showed a reduction in levels of cyclin D1, but not cyclin E, and a selective downregulation of Akt serine-473 phosphorylation and VEGF receptor levels. In accordance, cells derived from a parkin-null mouse model exhibited increased levels of cyclin D1, VEGF receptor, and Akt phosphorylation, and divided significantly ...
Conversely, if one supposes that internalized receptor is immune to down-regulation and that down-regulation occurs proportionately to occupancy of receptor by agonist in the membrane, then again, down-regulation is greater at low fenoterol concentrations than the model predicts. As before this proposal cannot be saved by supposing a saturable process because the down-regulation is a first order process.. Kinetic models that are consistent with the data can be constructed if a pool of receptor in addition to the endocytosed pool can be invoked. Here we propose a scheme (Fig. 7A, model II), the key features of which are that down-regulation can occur by either of two pathways; one pathway involving a high agonist affinity component with a low capacity that is independent of internalization and a second pathway using a low-affinity, high-capacity event that is closely correlated with internalization. This scheme provides an explanation for the dissociation of internalization from down-regulation ...
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Wei, W.,Ming, X.,Yi, Z. Y.,et al. Autoimmunity Mediated Down-regulation Of B 2-adrenergic Receptor In COPD[J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE,2010,181 ...
This morning I had my Down Regulation appointment. This consisted of yet another internal scan. And being taught how to use the pen that holds my next lot of drugs. Somehow I get the feeling that sticking a needle in me is a whole lot different to sticking a needle into the little pad thing…
Mouse monoclonal antibody MX35 was developed against ovarian cancer. The antibody showed homogeneous reactivity with approximately 90% of human ovarian epithelial cancers and with a limited number of normal tissues by immunohistochemistry. Although mAb MX35 has been used in a number of clinical trials in ovarian cancer, it has been difficult to define the molecular identity of MX35. We report here that mAb MX35 recognizes the sodium-dependent phosphate transport protein 2b (NaPi2b) in human cancer cells. This conclusion is based on several lines of experimental evidence, including 1) the identification of SLC34A2, the gene coding for NaPi2b, by immunoscreening an ovarian cancer cell line cDNA expression library with mAb MX35; 2) mass spectrometry sequencing of peptides obtained by fragmentation from mAb MX35 affinity-purified antigen, which show complete sequence homology to amino acid sequences in NaPi2b; 3) selective down-regulation of SLC34A2 gene expression by RNA interference and the ...
miRNAs (microRNAs) have been shown to play a role in myocardial fibrosis. The present study was designed to analyse whether alterations in miRNA expression contribute to the progression of myocardial fibrosis in AS (aortic valve stenosis) patients through up-regulation of the pro-fibrotic factor TGF-β1 (transforming growth factor-β type 1). Endomyocardial biopsies were obtained from 28 patients with severe AS, and from the necropsies of 10 control subjects. AS patients presented increased myocardial CVF (collagen volume fraction) and TGF-β1 compared with the controls, these parameters being correlated in all patients. Patients were divided into two groups by cluster analysis according to their CVF: SF (severe fibrosis; CVF ,15%; n=15) and non-SF (CVF ≤15%; n=13). TGF-β1 was increased in patients with SF compared with those with non-SF. To analyse the involvement of miRNAs in SF, the miRNA expression profile of 10 patients (four with non-SF and six with SF) was analysed showing that 99 ...
Dopamine is one of the key neurotransmitters actively involved in the brain. Research shows that by increasing the levels of dopamine within the reward circuits in the brain, nicotine acts as a chemical with intense addictive qualities. In many studies it has been shown to be more addictive than cocaine and heroin.[citation needed] Like other physically addictive drugs, nicotine withdrawal causes down-regulation of the production of dopamine and other stimulatory neurotransmitters as the brain attempts to compensate for artificial stimulation. As dopamine regulates the sensitivity of nicotinic acetylcholine receptors decreases. To compensate for this compensatory mechanism, the brain in turn upregulates the number of receptors, convoluting its regulatory effects with compensatory mechanisms meant to counteract other compensatory mechanisms. An example is the increase in norepinephrine, one of the successors to dopamine, which inhibit reuptake of the glutamate receptors,[45] in charge of memory ...
Over the past few years, the discovery of miRNAs has changed the landscape of human genetics and they have been widely studied in the field of oncology, where altered miRNA expression has been observed in a variety of human cancers [28]. Indeed, miRNA-expression profiling of human epithelial malignancies has led to the identification of signatures associated with diagnosis, staging, progression, prognosis and even response to treatment [29, 30]. However, few mechanistic studies have been carried out to dissect the functional role of miRNA in RCC, particularly in the context of "immune dysfunction" which may underlie disease progression. In fact, attaining effective tumor immunity is a major goal of the modern biologic therapy, limited by the tumor microenvironment and regulatory mechanisms affecting T cell and NK cell effectors [31].. The major finding in this report is that CD8+ T cells isolated from RCC patients exhibit defects in proliferation and a propensity to undergo apoptotic cell death ...
Research on the regulation of fish muscle physiology and growth was addressed originally by classical in vivo approaches; however, systemic interactions resulted in many questions that could be better considered through in vitro myocyte studies. The first paper published by our group in this field was with Tom Moon on brown trout cardiomyocytes, where the insulin and IGF-I receptors were characterized and the down-regulatory effects of an excess of peptides demonstrated. We followed the research on cultured skeletal muscle cells through the collaboration with INRA focused on the characterization of IGF-I receptors and its signaling pathways through in vitro development. Later on, we showed the important metabolic role of IGFs, although these studies were only the first stage of a prolific area of work that has offered a useful tool to advance in our knowledge of the endocrine and nutritional regulation of fish growth and metabolism. Obviously, the findings obtained in vitro serve the purpose to ...
The central dogma postulates that genes are first copied into messenger RNAs, which are then decoded into proteins with the help of transfer RNAs and ribosomal RNAs. It has long been known that there is more to the world of RNA than just these three classes, but the development of high-throughput RNA sequencing has revealed just how active RNAs can be. Much of the genome is transcribed, without these transcripts being translated into proteins. As these non-coding RNAs have been characterized, it is clear that many of them have regulatory roles. It has also been revealed how chemical modifications to all classes of RNAs affect their behavior, such as what they interact with and when, and how long they hang around for before being degraded.. Genome Biology has recently published a special issue on RNA & gene regulation, exploring this new world.. Perhaps some of the best understood regulatory RNAs are the microRNAs, short RNAs that bind to mRNA which mostly causes downregulation by either ...
Tryndyak, V. P., Ross, S. A., Beland, F. A. and Pogribny, I. P. (2009), Down-regulation of the microRNAs miR-34a, miR-127, and miR-200b in rat liver during hepatocarcinogenesis induced by a methyl-deficient diet. Mol. Carcinog., 48: 479-487. doi: 10.1002/mc.20484 ...
PIK-93 is a potent PI3K inhibitor. PIK93 selectively inhibits the type III PI 4-kinase beta enzyme, and small interfering RNA-mediated down-regulation of the individual PI 4-kinase enzymes, revealed that PI 4-kinase beta has a dominant role in ceramide transport between the ER and Golgi.
Our results show that genetic elimination of BAMBI as a modulator of the signaling of the family of TGF cytokines renders the almost-resistant C57BL/6 mouse strain more susceptible to the development of diabetic glomerular abnormalities, as determined by proteinuria with a widening of the FPs. This is associated with increased activation of ERK1/2 and Smad1/5 alternative TGF-β signaling pathways. The Vegfr2 and Angpt1 genes, which control glomerular endothelial survival and microvascular stability, were downmodulated in glomeruli from diabetic BAMBI−/− mice compared with BAMBI+/+ mice. Incubation of glomeruli from nondiabetic BAMBI+/+ or BAMBI−/− mice with TGF-β resulted in further downregulation of Angpt1 and Vegfr2 in glomeruli from BAMBI−/− compared with BAMBI+/+ mice. The enhanced downregulation of Vegfr2 in glomeruli of diabetic mice by eliminating BAMBI could be localized to glomerular endothelial cells using an H2B-EYFP reporter under the control of Vegfr2/Flk1 regulatory ...
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TY - JOUR. T1 - Copper Depletion Down-regulates Expression of the Alzheimers Disease Amyloid-β Precursor Protein Gene. AU - Bellingham, Shayne A.. AU - Lahiri, Debomoy K.. AU - Maloney, Bryan. AU - La Fontaine, Sharon. AU - Multhaup, Gerd. AU - Camakaris, James. PY - 2004/5/7. Y1 - 2004/5/7. N2 - Alzheimers disease is characterized by the accumulation of amyloid-β peptide, which is cleaved from the amyloid-β precursor protein (APP). Reduction in levels of the potentially toxic amyloid-β has emerged as one of the most important therapeutic goals in Alzheimers disease. Key targets for this goal are factors that affect the regulation of the APP gene. Recent in vivo and in vitro studies have illustrated the importance of copper in Alzheimers disease neuropathogenesis and suggested a role for APP and amyloid-β in copper homeostasis. We hypothesized that metals and in particular copper might alter APP gene expression. To test the hypothesis, we utilized human fibroblasts overexpressing the ...
In the present study, we demonstrate a novel mechanism that causes down-regulation of TβRII. This mechanism involves the binding of an Sp1-HDAC1 complex to a specific Sp1 site of the TβRII promoter in PDAC cells. Treatment of BxPC-3 and MIA PaCa-2 cells with a HDAC inhibitor, TSA, strongly activates TβRII promoter and induces TβRII expression. An increase in the association of TβRII promoter chromatin with acetylated histone H4 was observed after TSA treatment. These findings suggest that histone deacetylation plays a role in repression of the TβRII gene in PDAC. Luciferase reporter assays using serial deletion constructs revealed that a major TSA response region is located within the NRE-2 (−100 to −67) region of the TβRII promoter. Analysis using site-specific mutation constructs demonstrated that a specific Sp1 site (Sp1C) and an inverted CCAAT element located at −102 and −83 bp relative to the transcription start site of TβRII promoter are required for TSA-mediated reversal ...
TY - JOUR. T1 - Potent suppression of HIV type 1 infection by a short hairpin anti-CXCR4 siRNA. AU - Anderson, Joseph S. AU - Banerjea, Akhil. AU - Planelles, Vicente. AU - Akkina, Ramesh. PY - 2003/8/1. Y1 - 2003/8/1. N2 - The phenomenon of RNA interference (RNAi) sparked a new surge in the area of posttranscriptional gene silencing methodologies and their potential application for HIV-1 gene therapy. A potentially promising strategy is to exploit siRNAs to prevent viral entry at the cell surface by down-regulating essential cell surface HIV-1 coreceptors. In the present studies we targeted the CXCR4 coreceptor for disruption with siRNA to inhibit HIV-1 entry as a first step toward the ultimate goal of translating this to gene therapy for AIDS. A stem-loop hairpin structured anti-CXCR4 siRNA was designed and synthesized in vitro by transcription with T7 polymerase. Down-regulation of the coreceptor was assayed in U373-Magi-CXCR4 cells. FACS analysis showed marked down-regulation of CXCR4 on the ...
Statins have action mechanisms that may work nicely in preventing recurrence during acute stage of infarction!. First, statins have antithrombotic effects and lower thrombogenicity. Statins prolong time to arterial thrombosis in endothelial injury model, inhibit P-selectin expression and platelet aggregation, reduce platelet PAR-1 thrombin receptor, and reduce tissue factor levels in plasma, its expression on monocyte surface, and atherosclerotic plaques. Second, statins enhance thrombolysis. They reduce PAI-1, increase t-PA activity and reduce fibrinogen level. Combined treatment of statins and t-PA in rats reduces the infarct size and downregulates expression of tissue factor, ICAM-1, vWF, and MMP-9. In addition, t-PA induced toxicity is reversed by statins.. Third, statins have anti-inflammatory actions that can stabilize and even regress plaques. Statins reduce the number of T-lymphocytes within plaques, inhibit migration and activation of monocyte/macrophage system, and reduce matrix ...
Systemic loss of one IL-6 cytokine member exhibits mild or unexpected morphological vascular phenotypes (19), e.g., systemic deletion of IL-6 in a mouse model prone to atherosclerosis elicits detrimental effects on atherosclerotic plaque development, potentially via an IL-6−dependent down-regulation of its counteracting cytokine IL-10 (20). The complete systemic gp130 knockout, in contrast, shows profound defects in cardiac and hematopoetic development, resulting in premature death in utero or soon after birth. Thus, to delineate the role of the hepatic APR in atherosclerosis, we selectively deleted the gp130 receptor in hepatocytes using the Cre-loxP system. The genetic modification was confirmed by a PCR reaction demonstrating the gene inactivation exclusively in liver, but not in heart, aorta, or spleen, and by functional analysis of gp130-dependent, LIF-induced STAT3 phosphorylation and SAA release from hepatocytes from controls, but not from gp130− mice. Thus, the introduction of loxP ...
FOXO3, also known as FOXO3a (and previously as FKHRL1), is a Forkhead protein of the O subclass. FOXOs have overlapping expression profiles and activities, but FOXO3a is known to be particularly important in cell cycle control and apoptosis, the immune system, fertility, and longevity [1][2][3]. It has a widespread distribution in the body, although expression levels are not equal throughout tissues. It contains a characteristic Forkhead box DNA binding domain, and is able to up- and downregulate expression of a variety of genes via binding of its consensus Forkhead Recognition Element, or similar sequences (including Insulin Response Elements). DNA recognition is performed by helix 3 of the DBD, although other parts of the DBD also contact the DNA to increase binding stability. FOXO3 is a human orthologue of C. eleganss daf-16, a gene required for the long-lived phenotype of daf-2-null nematodes. FOXO3s involvement in longevity, aging and senescence may be linked to its roles in oxidative ...
The addition of high-dose cytarabine to the treatment of mantle cell lymphoma (MCL) has significantly prolonged survival of patients, but relapses are common and are normally associated with increased resistance. To elucidate the mechanisms responsible for cytarabine resistance, and to create a tool for drug discovery investigations, we established a unique and molecularly reproducible cytarabine resistant model from the Z138 MCL cell line. Effects of different substances on cytarabine-sensitive and resistant cells were evaluated by assessment of cell proliferation using [methyl-14C]-thymidine incorporation and molecular changes were investigated by protein and gene expression analyses. Gene expression profiling revealed that major transcriptional changes occur during the initial phase of adaptation to cellular growth in cytarabine containing media, and only few key genes, including SPIB, are deregulated upon the later development of resistance. Resistance was shown to be mediated by down-regulation of
Down-regulation of apoptosis genes has been implicated in the development and progression of malignant melanoma. We used cDNA microarray to evaluate pro-apoptotic gene expression comparing normal skin
Cell surface glycoprotein CD200 receptor 1 is a protein that in humans is encoded by the CD200R1 gene. This gene encodes a receptor for the OX-2 membrane glycoprotein. Both the receptor and substrate are cell surface glycoproteins containing two immunoglobulin-like domains. This receptor is restricted to the surfaces of myeloid lineage cells and the receptor-substrate interaction may function as a myeloid downregulatory signal. Mouse studies of a related gene suggest that this interaction may control myeloid function in a tissue-specific manner. Alternative splicing of this gene results in multiple transcript variants. GRCh38: Ensembl release 89: ENSG00000163606 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000022667 - Ensembl, May 2017 "Human PubMed Reference:". "Mouse PubMed Reference:". Wright GJ, Puklavec MJ, Willis AC, Hoek RM, Sedgwick JD, Brown MH, Barclay AN (Sep 2000). "Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in ...
These effects are mediated by nuclear accumulation of the p27(Kip1) inhibitor induced by the downregulation of the p45(Skp2) and Cks1 proteins, which target p27(Kip1) for degradation ...
A liquid crystal device includes a pair of transparent substrates disposed with a prescribed gap therebetween and each having a transparent electrode thereon, a photoelectric conversion semiconductor layer not subjected to rubbing formed on one of the pair of transparent substrates, and alignment film subjected to rubbing formed on the other of the pair of transparent substrates, an a liquid crystal disposed between the photoelectric conversion semiconductor layer and the alignment film. As the photoelectric conversion semiconductor is freed from an aligning performance, the material thereof is freed from the constraint and can be selected so as to optimize the photoelectric conversion performance.
We have reported recently that sodium butyrate suppressed IFN-γ, but not the LPS-mediated induction of nitric oxide and TNF-α in microglia via the specific inhibition of NF-κB. In order to further determine the upstream signaling mechanism involved in the IFN-γ-specific down-regulation of iNOS by sodium butyrate in microglia, this study investigated the effect of sodium butyrate on the MAP kinase activities. Sodium butyrate significantly repressed the phosphorylation of ERK induced by IFN-γ, but had little effect on that induced by LPS. This suggests that sodium butyrate suppresses the IFN-γ-induced iNOS expression by inhibiting the ERK to NF-κB pathway. In addition, it was found that sodium butyrate suppressed the IFN-γ-induced interferon regulatory factor 1 (IRF-1) expression via the inhibition of ERK. Therefore, the ERK signaling pathway appears to play a key role in the sodium butyrate-mediated down-regulation of iNOS in the IFN-γ-stimulated microglia. © 2005 Elsevier B.V. All ...
Mycobacterium tuberculosis (Mtb) causes death of 2-3 million people every year. The persistence of the pathogenic mycobacteria inside the macrophage occurs through modulation of host cell signaling which allows them, unlike the other non-pathogenic species, to survive inside the host. The secretory proteins of M. tuberculosis have gained attention in recent years both as vaccine candidates and diagnostic tools; they target the immune system and trigger a putatively protective response; however, they may also be involved in the clinical symptoms of the disease. Our studies showed that RD-1-encoded secretory protein ESAT-6 is involved in modulation of the mitogen-activated protein (MAP) kinase-signaling pathway inside the macrophage. ESAT-6 induced phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the cytoplasm but not in the nucleus, which normally is the case for MAP kinases. ESAT-6 also antagonized LPS-induced ERK1/2 phosphorylation in the nucleus. Stimulation of cells by ESAT-6
AIM: To investigate whether Tg737 is regulated by microRNA-548a-5p (miR-548a-5p) and correlates with hepatocellular carcinoma (HCC) cell proliferation and apoptosis. was evaluated by flow cytometry. RESULTS: Down-regulation of Tg737 which is a target gene of miR-548a-5p accelerated HCC cell proliferation and miR-548a-5p promoted HCC cell proliferation and and and < 0.05. RESULTS Down-regulation of Tg737 promotes HCC cell proliferation in vitro To illuminate the role of Tg737 in HCC cell proliferation HCC cell lines HepG2 and MHCC97H were transfected with a si-Tg737 sequence or negative control (Figure ?(Figure1A).1A). Down-regulation of Tg737 significantly promoted the proliferation of HepG2 and MHCC97H cells and enhanced colony forming capability (Figure ?(Figure1B1B and C). The distribution JTC-801 of HepG2 and MHCC97H cell cycles showed that the percentage of cells in G0/G1 phase significantly decreased in Tg737 down-regulated cells compared with their counterparts while the cells in S phase ...
AR plays an important role in the development of prostate cancer as well as in the transition to castration-resistant state, which is highly aggressive and resistant to chemotherapy (4, 38). Thus, the preclinical/clinical development of novel agents that are safe but can suppress AR signaling is highly desirable. The present study shows that DATS treatment suppresses protein level of AR in both LNCaP cells and their androgen-independent variant. The DATS-mediated AR protein down-regulation is maintained for at least up to 24 hours even after removal of the drug. In addition, DATS treatment exhibits significant antiproliferative effect against androgen-stimulated growth of LNCaP cells.. We also conclude that the DATS-mediated suppression of AR protein level leads to inhibition of transcriptional activity of AR as evidenced by a significant decrease in secreted as well as intracellular levels of PSA in both LNCaP and C4-2 cells. Structure-activity analysis reveals that even a subtle change in the ...
In ,ralph.1146355927D at news.arizona.edu,, ralph at ccit.arizona.edu (Ralph M Bernstein) writes: ,chan wrote: , ,,In article ,3kolh2$b8k at styx.uwa.edu.au, Alec Redwood, ,,aredwood at uniwa.uwa.edu.au writes: ,,,: Can anyone tell me about TH3 cells and/or direct me to an article. ,, ,, ,,These cells were coined by those working in EAE model. They found high ,,TGFb producers when fed MBF orally. The cells did not fit into neat TH1 ,,or TH2 so they coined the term. I think this is bunk. There is no clear ,,Th1 or Th2 anyway. These cells are far more versatile than those in , ^^^^^^^^^^ , ,,Huh?!? , ,,CD4+ TH1 cells have decidedly different cytokine production than CD4+TH2 ,,cells. There is evidence that one cell type can downregulate the other ,,cell type (or phenotype, if you think they are the same cell). However, ,,its interesting to note that Fas Ligand-mediated cytoxicity/apoptosis is ,,mediated by TH1 CD4+ cells and not the TH2 CD4+ cells (This doesnt ,,exclude the CD8+ cells from ...
Leptin deficiency down-regulates IL-23 production in glomerular podocytes resulting in an attenuated immune response in nephrotoxic serum nephritis., 2016 ...
The density and affinity of beta-2-adrenoceptors on mononuclear cells from peripheral blood were studied in fifteen patients with cirrhosis of different severity and in thirteen controls. There was no significant difference between cirrhotic patients and controls in density or affinity of beta-2 binding sites. Within the cirrhotic group, however, the number of binding sites per cell was significantly lower in patients with severe ascites than in patients with mild to moderate or no ascites. This down-regulation of beta-adrenoceptors could influence the haemodynamic response to beta-blockers. ...
Chen, G.; Peng, J.; Zhu, W.; Tao, G.; Song, Y.; Zhou, X.; Wang, W., 2015: Combined downregulation of microRNA-133a and microRNA-133b predicts chemosensitivity of patients with esophageal squamous cell carcinoma undergoing paclitaxel-based chemotherapy
Glutathione, present in low millimolar concentrations in most cells, constitutes the chief water-soluble intracellular oxidant scavenger, protecting the membranes, DNA and proteins of oxidatively stressed tissues. (Ascorbate is likewise of importance in this regard.) It also opposes the proinflammatory/proapoptotic signalling effects of hydrogen peroxide, both by enabling the degradation of this compound via glutathione peroxidase and by working with glutaredoxin to promote the restoration of sulfenic acids to sulfhydryl form.36-40 As we have seen, it can also oppose IL-1β-induced inflammation via its inhibitory impact on NSMase-2. A further role of glutathione is to aid excretion of relatively hydrophobic compounds via conjugation reactions catalysed by glutathione-S-transferases.41. Intracellular cysteine availability is rate limiting for glutathione synthesis, such that increased cysteine levels boost this synthesis.42 N-acetylcysteine (NAC) is a venerable nutraceutical which acts as a ...
Background: A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8(+) T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings: In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any ...
Background A major group of murine inhibitory receptors on Natural Killer (NK) cells belong to the Ly49 receptor family and recognize MHC class I molecules. Infected or transformed target cells frequently downmodulate MHC class I molecules and can thus avoid CD8+ T cell attack, but may at the same time develop NK cell sensitivity, due to failure to express inhibitory ligands for Ly49 receptors. The extent of MHC class I downregulation needed on normal cells to trigger NK cell effector functions is not known. Methodology/Principal Findings In this study, we show that cells expressing MHC class I to levels well below half of the host level are tolerated in an in vivo assay in mice. Hemizygous expression (expression from only one allele) of MHC class I was sufficient to induce Ly49 receptor downmodulation on NK cells to a similar degree as homozygous expression, despite a strongly reduced cell surface level of MHC class I. Co-expression of weaker MHC class I ligands in the host did not have any further
Cytokines are thought to cause the depression of cytochrome P-450 (CYP)-associated drug metabolism in humans during inflammation and infection. We have examined the role of five cytokines, i.e., interleukin-1 beta, interleukin-4, interleukin-6, tumor necrosis factor-alpha, and interferon-gamma, on the expression of CYP1A2, CYP2C, CYP2E1, CYP3A, and epoxide hydrolase in primary human hepatocyte cultures. Steady state P-450 and epoxide hydrolase mRNA levels, as well as ethoxyresorufin-O-deethylase and nifedipine oxidation activities, which are mainly supported by CYP1A1/1A2 and CYP3A, respectively, were measured. Interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha were found to be the most potent depressors of P-450 enzymes. After 3 days of treatment, both mRNA levels and enzyme activities were depressed, typically by at least 40%, whatever the cytokine and the enzyme considered. Interferon-gamma also suppressed CYP1A2 and CYP2E1 mRNA levels and ethoxyresorufin-O-deethylase activity ...
MicroRNA-200c (miR-200c) is one of the short noncoding RNAs that play crucial roles in tumorigenesis and tumor progression. It also acts as considerable modulator in the process of epithelial-to-mesenchymal transition (EMT), a cell development regulating process that affects tumor development and metastasis. However, the role of miR-200c in bladder cancer cells and its mechanism has not been well studied. The purpose of this study was to determine the potential role of miR-200c in regulating EMT and how it contributed to bladder cancer cells in invasion, migration and proliferation. Real-time reverse transcription-PCR was used to identify and validate the differential expression of MiR-200c involved in EMT in 4 bladder cancer cell lines and clinical specimens. A list of potential miR-200 direct targets was identified through the TargetScan database. The precursor of miR-200c was over-expressed in UMUC-3 and T24 cells using a lentivirus construct, respectively. Protein expression and signaling pathway
The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis. Here, we utilized three human sources of monocyte derived macrophages (MDM), from THP-1 monocytes, healthy peripheral blood monocytes and synovial fluid monocytes from patients with rheumatoid arthritis, to undertake a detailed investigation of TSPO expression in activated macrophages. In this work, we demonstrate a consistent down-regulation of TSPO mRNA and protein in macrophages activated to a pro-inflammatory, or M1 phenotype. Conversely, stimulation of
Background Thymoma and thymic carcinoma will be the most frequent subtypes of thymic epithelial tumors (TETs). Carcinoma (TC1889) cell collection. Epigenetic transcriptional legislation of miR-145-5p was analyzed by dealing with the TC1889 cell series using the HDAC inhibitor Valproic Acidity (VPA). Results Beginning with the identification of the 69-gene personal of miR-145-5p putative focus on mRNAs, whose appearance was correlated compared to that of miR-145-5p inversely, the expression was accompanied by us of a few of them in vitro upon overexpression of miR-145-5p; we observed that led to the down-regulation of the mark genes, impacting on TETs cancerous phenotype. We also discovered that VPA treatment of TC1889 cells resulted in miR-145-5p up-regulation and concomitant down-regulation of miR-145-5p focus on genes and exhibited antitumor results, as indicated with the induction of cell routine arrest and by the reduced amount of cell viability, colony forming migration and capability ...
PRIMARY OBJECTIVES:. I. To assess the activity of A6, as measured by the 6-month progression-free survival (PFS) rate and objective tumor response (complete or partial) rate, in patients with persistent or recurrent ovarian epithelial, fallopian tube, or primary peritoneal carcinoma.. II. To determine the frequency and severity of adverse events as assessed by CTCAE v3.0.. SECONDARY OBJECTIVES:. I. To characterize the duration of PFS and overall survival. II. To identify biomarkers of drug effect on peripheral blood mononuclear cells (PBMCs).. TERTIARY OBJECTIVES:. I. To explore whether genes identified as being up- or down-regulated by exposure of human PBMCs to A6 in vitro are also up- or down-regulated following treatment of patients with A6 in vivo.. II. To explore whether there is an association between the expression of candidate A6 receptors in the tumor prior to treatment with A6 (as determined by IHC) and response and PFS.. III. To explore whether there is an association between change ...
Tripartite motif-containing 22, also known as TRIM22, is a protein which in humans is encoded by the TRIM22 gene. The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein localizes to the cytoplasm and its expression is induced by interferon. TRIM22 is also a target gene of the tumor suppressor protein p53. TRIM22 possesses E3 ubiquitin ligase activity and is able to ubiquitinate itself with the assistance of the E2 enzyme UbcH5B. Furthermore, TRIM22 is located in the nucleus and therefore may function as a nuclear E3 ubiquitin ligase. The protein down-regulates transcription from the HIV-1 long terminal repeat promoter region, suggesting that function of this protein may be to mediate interferons antiviral effects. Other proteins that function to restrict HIV replication include TRIM5alpha and APOBEC3G. It has been demonstrated that ...
The ETS gene Fli-1 is involved in the induction of erythroleukemia in mice by Friend murine leukemia virus and Ewings sarcoma in children. Mice with a targeted null mutation in the Fli-1 locus die at day 11.5 of embryogenesis with loss of vascular integrity leading to bleeding within the vascular plexus of the cerebral meninges and specific downregulation of Tek/Tie-2, the receptor for angiopoietin-1. We also show that dysmegakaryopoiesis in Fli-1 null embryos resembles that frequently seen in patients with terminal deletions of 11q (Jacobsen or Paris-Trousseau Syndrome). We map the megakaryocytic defects in 14 Jacobsen patients to a minimal region on 11q that includes the Fli-1 gene and suggest that dysmegakaryopoiesis in these patients may be caused by hemizygous loss of Fli-1 ...
Manni I., Tunici P., Cirenei N., Albarosa R., Colombo B.M., Roz L., Sacchi A., Piaggio G., Finocchiaro G.. Mxi1 is a Mad family member that plays a role in cell proliferation and differentiation. To test the role of Mxi1 on tumorigenesis of glioma cells we transfected a CMV-driven MXI1 cDNA in U87 human glioblastoma cells. Two clones were isolated expressing MXI1 levels 18- and 3.5-fold higher than wild-type U87 cells (clone U87.Mxi1.14 and U87.Mxi1.22, respectively). In vivo, U87.Mxi1.14 cells were not tumorigenic in nude mice and delayed development of tumours was observed with U87.Mxi1.22 cells. In vitro, the proliferation rate was partially and strongly inhibited in U87.Mxi1.22 and U87.Mxi1.14 cells respectively. The cell cycle analysis revealed a relevant accumulation of U87.Mxi1.14 cells in the G(2)/M phase. Interestingly, the expression of cyclin B1 was inhibited to about 60% in U87.Mxi1.14 cells. This inhibition occurs at the transcriptional level and depends, at least in part, on the ...
TY - JOUR. T1 - Down-regulation of osteoprotegerin expression as a novel biomarker for colorectal carcinoma. AU - Kim, Hyun Soo. AU - Yoon, Gun. AU - Do, Sung Im. AU - Kim, Sung Joo. AU - Kim, Youn Wha. PY - 2016/3/22. Y1 - 2016/3/22. N2 - A better understanding of tumor biology is important in the identification of molecules that are down-regulated in malignancy and in determining their role in tumor suppression. The aim of this study was to analyze osteoprotegerin (OPG) expression in colorectal carcinoma (CRC) and to investigate the underlying mechanism for changes in the expression of OPG. OPG expression was assessed in CRC tissue samples and cell lines. The methylation status of the OPG promoter region was determined, and the effects of demethylation on OPG expression were analyzed. The effects of recombinant OPG (rOPG) administration on cellular functions were also investigated. Clinical and prognostic implications of OPG protein expression in CRC patients were analyzed. The CRC tissues and ...
Specific metabolic programs are activated by immune cells to fulfill their functional roles, which include adaptations to their microenvironment. B1 B cells are tissue-resident, innate-like B cells. They have many distinct properties, such as the capacity to self-renew and the ability to rapidly respond to a limited repertoire of epitopes. The metabolic pathways that support these functions are unknown. We show that B1 B cells are bioenergetically more active than B2 B cells, with higher rates of glycolysis and oxidative phosphorylation, and depend on glycolysis. They acquire exogenous fatty acids and store lipids in droplet form. Autophagy is differentially activated in B1a B cells, and deletion of the autophagy gene Atg7 leads to a selective loss of B1a B cells caused by a failure of self-renewal. Autophagy-deficient B1a B cells down-regulate critical metabolic genes and accumulate dysfunctional mitochondria. B1 B cells, therefore, have evolved a distinct metabolism adapted to their residence and
Purpose : Activation of the Epidermal Growth Factor Receptor (EGFR) is critical in corneal epithelial regeneration and homeostasis. The clinical use of EGFR ligands (e.g. epidermal growth factor - EGF) are not reliable tools to restore and maintain the epithelial layer, likely due to high endogenous EGF levels and intrinsic mechanisms of receptor down-regulation. One mediator of EGFR down-regulation is the E3 ubiquitin ligase, c-Cbl. Ubiquitylation of the EGFR targets it for lysosomal degradation; using RNAi to attenuate c-Cbl expression enhanced the kinetics of corneal epithelial wound healing. We postulate that supplementing the relatively high, endogenous levels of EGF (~2-3 ng/ml) in human tears with a c-Cbl antagonist will prevent EGFR down-regulation and enhance receptor activity and promote homeostasis of the epithelial layer. In this study, we identify and test potential c-Cbl antagonist for binding and inhibitory activity ...
Durham, NC - Alejandro Aballay, PhD, Professor in the Department of Molecular Genetics and Microbiology and Director of the Center for Host Microbial Interactions at Duke University, will be receiving an NIH MERIT Award from NIGMS for his research project on the role of the nervous system in controlling immunity in the model host C. elegans.. Dr. Aballays project will be a multidisciplinary research program regarding the study of neural circuits involved in the control of stress responses and innate immunity. Recent studies from his laboratory indicate that different immune mechanisms are controlled at the organismal level by the nervous system. His laboratory has demonstrated that specific neurons suppress innate immunity in the intestinal cells of the nematode Caenorhabditis elegans, in part by down-modulating a mitogen-activated protein kinase signaling pathway similar to the mammalian p38 MAPK pathway that is highly conserved across metazoans. They found that NPR-1, a G-protein coupled ...
Abstract. A phase III clinical trial showed gemcitabine chemotherapy combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib significantly improved overall survival in patients with advanced pancreatic cancer. Therefore, we studied whether addition of gemcitabine to erlotinib in cancer cells having intrinsic or acquired erlotinib resistance could restore chemosensitization in these cells. We studied the synergistic effect of erlotinib and gemcitabine in EGFR-overexpressing A-431 cells with acquired erlotinib resistance and in intrinsic erlotinib-resistant triple negative breast cancer (TNBC) BT-549, MDA-MB-231 and MDA-MB-468 cell lines. Erlotinib and gemcitabine were synergistic in both parental intrinsically erlotinib-sensitive A-431 cells (combination index = 0.69 at the effective dose [ED50]) and in two A-431 cell pools that had acquired erlotinib resistance (combination indices = 0.63 and 0.49 at ED50). The synergistic effect of erlotinib and gemcitabine on ...
Amphetamine has complex behavioral actions in the rat that depend upon the release of dopamine in striatal and mesolimbic brain regions. To explore a possible role of the dopamine-sensitive cAMP second-messenger system in mediating these effects, we examined the effects of in vivo amphetamine treatments on the D1 receptor-coupled adenylate cyclase system in membranes from striatal and mesolimbic rat brain regions. The results show that amphetamine produces a regional, dose- and time- dependent down-regulation of adenylate cyclase activity. Intermediate and high doses of amphetamine (2.5 and 7.5 mg/kg, respectively), but not a low dose (1.0 mg/kg), resulted in a decrease in the apparent Vmax and/or an increase in the apparent Ka for the selective D1 partial agonist, SKF38393, in striatal membranes 30 min after amphetamine treatment. Treatment of rats with 7.5 mg/kg amphetamine for 30 and 60 min, but not 10 min, similarly resulted in a down-regulation of D1- mediated adenylate cyclase activity in ...
Vertebrate neurogenesis involves sequential actions of transcription factors. neurogenins, encoding Atonal-related bHLH transcription factors, function as neuronal determination genes in Xenopus. neurogenins and antother bHLH factor gene, Mash1, are expressed in distinct subsets or areas of cells giving rise to neurons, suggesting that these genes play important roles to generate distinct populations of neurons. A mammalian homologue of BarH (MBH1) is expressed in a complementary pattern to Mash1 expression in the developing nervous system like neurogenins. Forced expression of MBH1 down-regulates expression of Mash1 and up-regulates neurogenin2/Math4A, a member of neurogenins, in P19 cells during neuronal differentiation. This suggests that MBH1 is a potential regulator of mammalian neural bHLH genes, thereby establishing distinct pathways of neuronal differentiation ...
Some of us may remember conferences with sessions entitled Why 3D? Such sessions are a thing of the past now because there is an accumulating body of evidence - joined by the recent article from Leslie and colleagues [1] - demonstrating the importance and utility of 3D culture systems to discover and model biological process with in vivo relevance. For example, when normal and malignant human breast cells are placed in 3D cultures of laminin-rich gels, the former cells form growth-arrested, lumen-containing acini and the latter cells form disorganized structures [2]. Inhibitors of epidermal growth factor receptor and β1-integrin can revert the malignant phenotype, and each inhibitor downmodulates its own target as well as the other targets only in 3D but not in cells grown as monolayer cultures - suggesting that signaling pathways reciprocally regulate each other to maintain the transformed state [3]. ErbB2/HER2-induced transformation of 3D structures, but not cell proliferation, requires ...
The Zrt/Irt-related protein 8 (ZIP8) encoded by slc39a8 is now emerging as an important zinc transporter involved in cellular cadmium incorporation. We have previously shown that mRNA and protein levels of ZIP8 were decreased in cadmium-resistant metallothionein-null (A7) cells, leading to a decreas …
Interferon regulatory factor 6 (IRF6) is a novel and unique member of the IRF family of transcription factors, and the regulation and function of IRF6 remain unknown. Recently, IRF6 was shown to be...
Nemeckova, S.; Smahel, M.; Hainz, P.; Mackova, J.; Zurkova, K.; Gabriel, P.; Indrova, M.; Kutinova, L.. Combination of intratumoral injections of vaccinia virus MVA expressing GM-CSF and immunization with DNA vaccine prolongs the survival of mice bearing HPV16 induced tumors with downregulated expression of MHC class I molecules. [rok vydání 2008, impact factor 1.208]. ...
In this article explain the finer points of the delta-delta-CT method to calculate up-/down- regulations. The following text is a writeup of a course I gave at a local highschool.
TY - JOUR. T1 - Stability of surface NMDA receptors controls synaptic and behavioral adaptations to amphetamine. AU - Mao, Li Min. AU - Wang, Wei. AU - Chu, Xiang Ping. AU - Zhang, Guo Chi. AU - Liu, Xian Yu. AU - Yang, Yuan Jian. AU - Haines, Michelle. AU - Papasian, Christopher J.. AU - Fibuch, Eugene E.. AU - Buch, Shilpa. AU - Chen, Jian Guo. AU - Wang, John Q.. PY - 2009/5/1. Y1 - 2009/5/1. N2 - Plastic changes in glutamatergic synapses that lead to endurance of drug craving and addiction are poorly understood. We examined the turnover and trafficking of NMDA receptors and found that chronic exposure to the psychostimulant amphetamine (AMPH) induced selective downregulation of NMDA receptor NR2B subunits in the confined surface membrane pool of rat striatal neurons at synaptic sites. This downregulation was a long-lived event and was a result of the destabilization of surface-expressed NR2B caused by accelerated ubiquitination and degradation of crucial NR2B-anchoring proteins by the ...
Aberrant monocyte mediator production is pivotal in the development of posttrauma immunosuppression. We have previously shown that immunodepressed trauma patients monocytes produce elevated interleukin-6, suggesting their in vivo preactivation. This study confirms that preactivated patients Mo produce greater levels of IL-6 than normals Mo to the same in the in vitro Fc gamma RI stimulation. We also demonstrate the capacity of interleukin-4 to downregulate the elevated interleukin-6 production of trauma patients in vivo preactivated monocytes. Monocyte interleukin-6 downregulation by interleukin-4 is dose dependent and occurs whether Fc gamma RI cross-linking, muramyl dipeptide, indomethacin plus muramyl dipeptide, or interferon-gamma plus muramyl dipeptide is the interleukin-6 inducing stimulus. Furthermore, interleukin-4-dependent downregulation of monocyte interleukin-6 expression is confirmed at both the supernatant and the mRNA levels. Simultaneous downregulation of posttrauma elevated
We then investigated how AIMP2 can mediate the ubiquitylation of TRAF2. AIMP2 itself did not show any of the E1, E2 or E3 enzyme activities that are the key components of ubiquitin coupling systems (data not shown). We then checked the possibility that AIMP2 facilitates the association of E3 ubiquitin ligase to its target proteins using c-IAP1, which is the known ubiquitin ligase responsible for the ubiquitylation of TRAF2 (Li et al., 2002; Wu et al., 2005). To determine the importance of c-IAP1 for AIMP2-dependent downregulation of TRAF2, we suppressed the expression of c-IAP1 and checked whether AIMP2 could still reduce the TRAF2 level. In control-siRNA-transfected cells, transfection of AIMP2 decreased TRAF2 levels (Fig. 5A, left). However, when c-IAP1 expression was suppressed with its specific siRNA, this effect of AIMP2 on TRAF2 levels was not observed (Fig. 5A, right), implying the importance of c-IAP1 for the effect of AIMP2 on TRAF2. To see whether AIMP2 would facilitate the binding of ...
Toxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechanisms. During early infection, nuclear translocation of NFkB is temporally blocked and p38 MAPK phosphorylation is prevented, suppressing IL-12 production. Another pathway for IL-12 induction occurs through CCR5 dependent pathway, but parasitic induction of an eicosanoid LXA4 contributes to the downregulation of IL-12. Direct activation of STAT3 by the parasite enhance anti-inflammatory function of IL-10 and TGF beta. T. gondii can cause lifelong chronic infection by establishing an anti-apoptotic environment through induction of bcl-2 or IAPs and by redirecting LDL-mediated cholesterol transport to scavenge nutrients from the host ...
Toxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechanisms. During early infection, nuclear translocation of NFkB is temporally blocked and p38 MAPK phosphorylation is prevented, suppressing IL-12 production. Another pathway for IL-12 induction occurs through CCR5 dependent pathway, but parasitic induction of an eicosanoid LXA4 contributes to the downregulation of IL-12. Direct activation of STAT3 by the parasite enhance anti-inflammatory function of IL-10 and TGF beta. T. gondii can cause lifelong chronic infection by establishing an anti-apoptotic environment through induction of bcl-2 or IAPs and by redirecting LDL-mediated cholesterol transport to scavenge nutrients from the host ...
Toxoplasma gondii is an obligate intracellular parasite that is prevalent worldwide. The tachyzoite form acquired by oral ingestion downmodulates proinflammatory signaling pathways via various mechanisms. During early infection, nuclear translocation of NFkB is temporally blocked and p38 MAPK phosphorylation is prevented, suppressing IL-12 production. Another pathway for IL-12 induction occurs through CCR5 dependent pathway, but parasitic induction of an eicosanoid LXA4 contributes to the downregulation of IL-12. Direct activation of STAT3 by the parasite enhance anti-inflammatory function of IL-10 and TGF beta. T. gondii can cause lifelong chronic infection by establishing an anti-apoptotic environment through induction of bcl-2 or IAPs and by redirecting LDL-mediated cholesterol transport to scavenge nutrients from the host ...
Increased Renal Methylglyoxal Formation with Down-Regulation of PGC-1α-FBPase Pathway in Cystathionine γ-Lyase Knockout Mice. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Methods and results We confirmed that AGXT2L1 was down-regulated in liver cancer samples by immunohistochemical (IHC) staining. We also demonstrated that this down-regulation was associated with several clinicopathological features such as alpha fetoprotein (AFP) serum level and T stage. Furthermore, we showed with Kaplan-Meier analysis that expression of AGXT2L1 in tumour samples was significantly correlated with patient prognosis. The bioinformatic tool indicated that AGXT2L1 plays a role in the lipid metabolic process of HCC tissue, while siRNA silenced the expression of AGXT2L1 in HCC 97H and LM3 cells, confirming that down-regulation of AGXT2L1 promotes the lipogenesis of cancer cells. ...
miR-145 was reproducibly elevated in all the resistant sub-lines tested within one of the experimental sets; however, modulation of miR-145 levels alone in these cells did not affect their response to cisplatin. A potential target of miR-145 is cyclin dependent kinase 6 (CDK6), an important regulator of cell proliferation. Both mRNA and protein levels of CDK6 are down regulated in the resistant sub-lines. An inhibitor of CDK4/6 (PD0332991) protected cells from cisplatin cytotoxicity. ...
The present invention concerns methods and compositions for identifying genes or genetic pathways modulated by miR-15, miR-26, miR-31, miR-145, miR-147, miR-188, miR-215, miR-216, miR-331, mmu-miR-292-3p, and using nucleic acid comprising all or part of the miR-15, miR-26, miR-31, miR-145, miR-147, miR-188, miR-215, miR-216, miR-331, mmu-miR-292-3p sequences to modulate a gene or gene pathway, using this profile in assessing the condition of a patient and/or treating the patient with an appropriate miRNA.
Astrocytes secrete ATP by exocytosis from synaptic-like vesicles, activating neuronal P2X receptors, which contribute to postsynaptic GABA receptor down-regulation, ultimately mediating the communication between astrocytes and neurons required for brain function.
The levels of hepatocyte growth factor (HGF) in gastric cancer tissues increased significantly according to the tumor progression and well correlated with the expression of E-cadherin. After treatment with HGF, a more invasive morphologic change was observed in gastric cancer cells, accompanied by down-regulation of functional E-cadherin in the membrane, and invasion into the matrigel. Thus, we suggest that HGF can modulate the expression of E-cadherin in gastric carcinoma ...
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Tetracyclines downregulate the production of LPS-induced cytokines and chemokines in THP-1 cells via ERK, p38, and nuclear factor-κB signaling pathwaysTetracyclines downregulate the production of LPS-induced cytokines and chemokines in THP-1 cells via ERK, p38, and nuclear factor-κB signaling pathways ...
M induced an inhibitory effect against the proliferation of HL-60 and colony potential of HCT-116 cells. The apoptosis in HL-60 cells was associated with down-regulation of Bcl-2 and activation of Bax, while in HCT-116 cells, necrotic features were observed; size of cells was dramatically increased by swelling of cytoplasm and loss of membrane integrity, cell rupture and release of cellular contents. ...
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Addition of ammonium ions to yeast cells growing on proline as the sole nitrogen source induces internalization of the general amino acid permease Gap1p and its subsequent degradation in the vacuole. An essential step in this down-regulation is Gap1p ubiquitination through a process requiring the Npi1p/Rsp5p ubiquitin ligase. We show in this report that NPI2, a second gene required for NH4+-induced down-regulation of Gap1p, codes for the ubiquitin hydrolase Doa4p/Ubp4p/Ssv7p and that NH4+-induced Gap1p ubiquitination is strongly reduced in npi2 cells. The npi2 mutation results in substitution of an aromatic amino acid located in a 33-residue sequence shared by some ubiquitin hydrolases of the Ubp family. In this mutant, as in doa4(delta) cells, the amount of free monomeric ubiquitin is at least four times lower than in wild-type cells. Both ubiquitination and down-regulation of the permease can be restored in npi2 cells by over-expression of ubiquitin. In proline-grown wild-type and npi2/doa4 ...
"Safety and regulation of chiropractic". NHS Choices. 20 August 2014. Retrieved 22 September 2016.. ... Education, licensing, and regulation. Main articles: Chiropractic education and List of chiropractic schools ... is the statutory governmental body responsible for the regulation of chiropractic in the UK.[175][176] The U.S. CCE requires a ...
Early regulation[edit]. Before the production of the pituitary hormone luteinizing hormone (LH) by the embryo starting at about ... Androgen regulation decreases the likelihood of depression in males. In preadolescent male rats, neonatal rats treated with ... Social isolation has a hindering effect in AHN whereas normal regulation of androgens increases AHN. A study using male rats ... Androgen levels have been implicated in the regulation of human aggression and libido. Indeed, androgens are capable of ...
"eCFR - Code of Federal Regulations". www.ecfr.gov.. *^ Beau Jackson, FAA to launch eight-year additive manufacturing road map ( ... a b Jason Dickstein, Additive Manufacturing - Does it Fit into the Regulations?, ARSA Hotline (May 5, 2017) (explaining how to ... Aerospace regulation[edit]. In the United States, the FAA has anticipated a desire to use additive manufacturing techniques and ... "Proposed new regulations for 3D printed medical devices must go further". The Conversation. Retrieved 2018-10-03.. ...
regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion. • positive regulation of ... Regulation[edit]. The activity of CaV1.2 channels is tightly regulated by the Ca2+ signals they produce. An increase in ... regulation of ion transmembrane transport. • ion transport. • calcium-mediated signaling using extracellular calcium source. • ... regulation of heart rate by cardiac conduction. • membrane depolarization during cardiac muscle cell action potential. • ...
Examples of histone modifications in transcriptional regulation Type of. modification Histone H3K4 H3K9 H3K14 H3K27 H3K79 H3K36 ... Chromatin regulation[edit]. Histones undergo posttranslational modifications that alter their interaction with DNA and nuclear ... This affects their function of gene regulation. In general, genes that are active have less bound histone, while inactive genes ... Johansen KM, Johansen J (2006). "Regulation of chromatin structure by histone H3S10 phosphorylation". Chromosome Research. 14 ( ...
Regulation[edit]. Glycogen phosphorylase is regulated by both allosteric control and by phosphorylation. ... "The protein phosphatases involved in cellular regulation". European Journal of Biochemistry. 156 (1): 101-110. doi:10.1111/j. ... of the catalytic site to the surface is significant in that it makes the protein activity highly susceptible to regulation, as ...
Regulations & FDA Codes[edit]. The US Code of Food Regulations defines what the fat and moisture content of brick cheese must ...
Labeling regulations have been modified to provide for mandatory labeling of ingredients plus voluntary labeling, termed ... Popping B, Diaz-Amigo C (2018). "European Regulations for Labeling Requirements for Food Allergens and Substances Causing ... The European Union has initiated a process to create labeling regulations for unintentional contamination but is not expected ... The EU Food Information for Consumers Regulation 1169/2011 - requires food businesses to provide allergy information on food ...
Regulation[edit]. See also: Financial regulation in Australia. Formally, there is extensive and detailed regulation of ... A change in regulations allowed building societies and credit unions to become banks without having to demutualise, and several ... A change in regulations allowed building societies and credit unions to become banks without having to demutualise, and several ... This was in an environment where little government control or regulation of banks had been established and led to the failure ...
Regulation[edit]. As of 2019[update], the European Food Safety Authority has rejected all petitions by commercial manufacturers ... "Regulation (EC) No 1924/2006 of the European Parliament and of the Council on 20 December 2006 on nutrition and health claims ... Million M, Raoult D (February 2013). "Species and strain specificity of Lactobacillus probiotics effect on weight regulation". ... of Regulation (EC) No 1924/2006 (example, search EFSA for other opinion reports on probiotics". EFSA Journal. 11 (2): 3085. ...
positive regulation of leukocyte migration. • platelet degranulation. • regulation of integrin activation. • cell adhesion. • ... Gene and regulation[edit]. P-selectin is located on chromosome 1q21-q24, spans , 50 kb and contains 17 exons in humans.[7] P- ... positive regulation of platelet activation. • leukocyte migration. • response to lipopolysaccharide. • calcium-dependent cell- ... positive regulation of phosphatidylinositol 3-kinase signaling. • inflammatory response. • calcium-mediated signaling using ...
Regulation[edit]. Some jurisdictions over the world restrict the publication of the results of opinion polls, especially during ... most of them have no regulation and some only prohibit it in the final days or hours until the relevant poll closes.[42] A ...
Regulation[edit]. From 1969 to 1992, the US Food and Drug Administration (FDA) received 157 reports of health problems related ... "COMMISSION IMPLEMENTING REGULATION (EU) No 872/2012". EUR-Lex. Official Journal of the European Union. Retrieved 9 October 2017 ...
Production and regulation[edit]. POMC, ACTH and β-lipotropin are secreted from corticotropes in the anterior lobe (or ... "Mitochondrial-genome-encoded RNAs: differential regulation by corticotropin in bovine adrenocortical cells". Proceedings of ...
Gene regulation[edit]. Main article: Regulation of gene expression. At the cellular level, homeostasis is carried out by ... Main articles: Blood sugar regulation and Glycolysis § Regulation of the rate limiting enzymes ... Copper regulation[edit]. Main article: Copper in health § Homeostasis. This section needs expansion. You can help by adding to ... receptors include nuclear receptors that bring about changes in gene expression through up-regulation or down-regulation, and ...
Government regulations[edit]. The World Health Organization (WHO), the specialized agency of the United Nations (UN) that is ... Canadian regulations are described by the Natural and Non-prescription Health Products Directorate which requires an eight- ... FDA Issues Regulation Prohibiting Sale of Dietary Supplements Containing Ephedrine Alkaloids and Reiterates Its Advice That ... and to assure self-regulation for protection of public health and safety.[60] In the United Kingdom, the training of herbalists ...
Canadian regulations[edit]. According to Canadian regulations, icing sugar shall be powdered sugar and may contain food color.[ ... "Consolidated federal laws of canada, Food and Drug Regulations". laws.justice.gc.ca. Retrieved 2019-07-16 ...
Regulations[edit]. Homeowner associations have been criticized for having excessively restrictive rules and regulations on how ... Reasonable Rules and Regulations[edit]. The neutrality of this section is disputed. Relevant discussion may be found on the ... The HOA board should follow legal requirements to inform homeowners about any changes made to the rules and regulations. The ... The benefits that a homeowner association (HOA) provides to homeowners vary depending on the specific regulations and practices ...
"Commission Regulation (EU) No 432/2012 of 16 May 2012 establishing a list of permitted health claims made on foods, other than ... There have been allegations, particularly in Italy and Spain, that regulation can be sometimes lax and corrupt.[81] Major ... of Regulation (EC) No 1924/2006". EFSA Journal. 9 (4): 2044 [19 pp]. doi:10.2903/j.efsa.2011.2044.. ... Customs regulations on "country of origin" state that if a non-origin nation is shown on the label, then the real origin must ...
positive regulation of B cell proliferation. • negative regulation of cell growth. • cell cycle arrest. • response to ... negative regulation of gene expression. • cellular response to DNA damage stimulus. • negative regulation of G1/S transition of ... positive regulation of programmed cell death. • negative regulation of apoptotic process. • response to glucocorticoid. • ... regulation of cell cycle. • intrinsic apoptotic signaling pathway. • cellular senescence. • positive regulation of reactive ...
Regulations, sportsmanship, and safety[edit]. Waterfowl hunting is highly regulated in most western countries. Hunters are ... There were no regulations on waterfowl hunting from when the Paleo Indians arrived in North America to the early 20th century. ... Although edible, swans are not hunted in many Western cultures due to hunting regulations, and swans were historically a royal ... We need regulations to make sure we leave ducks for years to come. ...
Regulation of GAD65 and GAD67[edit]. Despite an extensive sequence similarity between the two genes, GAD65 and GAD67 fulfill ... Both GAD65 and GAD67 are regulated via phosphorylation of a dynamic catalytic loop,[10][11] but the regulation of these ... contribution of altered regulation by Zif268". The American Journal of Psychiatry. 171 (9): 969-78. doi:10.1176/appi.ajp. ... implications for the regulation of GABA synthesis". Journal of Neurochemistry. 86 (4): 879-87. doi:10.1046/j.1471-4159.2003. ...
a b c School bus pedestrian safety standards Code of Federal Regulations Title 49, Section 571.131. Retrieved 2010-4-15. ... "Code of Federal Regulations Title 49, Volume 6, Section 571.108" (PDF): 361.. Cite journal requires ,journal=. (help). ... Industry safety regulations[edit]. From 1939 to 1973, school bus production was largely self-regulated. In 1973, the first ... 131 regulates the specifications of the stop arm as a double-faced regulation octagonal red stop sign at least 45 cm (17.7 in) ...
Regulation of dose uptake[edit]. The ICRP uses the following overall principles for all controllable exposure situations.[7] ... The public information dose chart of the USA Department of Energy, shown here on the right, applies to USA regulation, which is ...
Regulation of the industry[edit]. The International Spa and Body Wrap Association (ISBWA) is an international association for ... Adhere to the laws, rules and regulations governing the provision of treatments and services as required by their local ... spas and body wrap centers around the world.[29] The main concern of the ISBWA is the regulation of the industry and the ...
... S.I. 1998/2451. References[edit]. *^ Mack, Jon; Sampson, Richard (2014). " ... Provisions of the regulations with which the public is most familiar are: *the duties of landlords to ensure the safety of gas ... The regulations cover various aspects of the supply and use of gas, and qualifications and duties of people involved with doing ... Gas Safety (Installation and Use) Regulations 1998. From Wikipedia, the free encyclopedia ...
Cellular microRNAs play an integral part in the post-transcriptional regulation of. May 19, 2017 ... Cellular microRNAs play an integral part in the post-transcriptional regulation of almost every cellular gene regulatory ...
"Fire Code" means Ontario Regulation 213/07 (Fire Code) made under the Fire Protection and Prevention Act, 1997. R.R.O. 1990, ... "spray booth" means a spray booth as defined in Ontario Regulation 213/07 (Fire Code) made under the Fire Protection and ... 1. In this Regulation,. "adequate", when used in relation to a procedure, plan, material, device, object or thing, means that ... a) details of the measures to be taken for compliance with the relevant provisions of this Regulation that are listed in the ...
But without stricter regulation, urban poultry farming is risky for both humans and birds. ... Very few regulations required humane slaughter or disease reporting. Only four municipalities required owners to provide birds ... In a recent study with University of California, Davis animal scientist Joy Mench, we examined urban poultry regulations in ... Based on our survey of Colorado, we believe cities need to carefully consider their backyard chicken regulations and develop ...
The Solicitors Regulation Authority (SRA) regulates solicitors in England and Wales. Report a solicitor, check a solicitors ... Who are the Solicitors Regulation Authority (SRA)? What do we do? And how can we help you? ...
OHS Regulation or Related Materials. Submit your email address to receive a copy of the OHS regulation or related materials you ... The online OHS Regulation is not the official version of the OHS Regulation, which may be purchased from Crown Publications. ... iii) the requirements of this Regulation.. (2) Unless otherwise specified by this Regulation, the installation, inspection, ... See also section 4.4 of the of the OHS Regulation.. 4.36 Glass. (1) Repealed. [B.C. Reg. 312/2003, effective October 29, 2003.] ...
In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule ... Allosteric regulations are a natural example of control loops, such as feedback from downstream products or feedforward from ... Long-range allostery is especially important in cell signaling.[1] Allosteric regulation is also particularly important in the ... The sequential model of allosteric regulation holds that subunits are not connected in such a way that a conformational change ...
Christensen SK, Dagenais N, Chory J, Weigel D (2000) Regulation of auxin response by the protein kinase PINOID. Cell 100: 469- ... Regulation of ABCB1/PGP1‐catalysed auxin transport by linker phosphorylation. Sina Henrichs, Bangjun Wang, Yoichiro Fukao, ... and as such defines the impact of ABCB1 phosphorylation and regulation. ABCB1 activity regulation by PID is reverted by binding ... Direct regulation of ABCB1 by PID was specific since it was found for effluxed auxin but not for the diffusion control, BA, and ...
regulation (countable and uncountable, plural regulations). *(uncountable) The act of regulating or the condition of being ... regulation (not comparable). *In conformity with applicable rules and regulations. * 1969, Thomas Wiseman, The Quick and the ... regulation in Websters Revised Unabridged Dictionary, G. & C. Merriam, 1913. *regulation in The Century Dictionary, The ... It is regulation that these directives are to be destroyed on receipt.. ...
... specifies that banks must institute internal rules that regulate the amount of risk that they can take in their ... A regulation set forth by the Federal Reserve. ... DEFINITION of Regulation F. A regulation set forth by the ... BREAKING DOWN Regulation F. Regulation F covers the collection of checks as well as various other services that larger banks ... interest rate swaps and repurchase agreements fall under this regulation. Regulation F may also allow banks that are highly ...
Regulation of the European Parliament and of the Council. Regulation (EU) No 524/2013 of the European Parliament and of the ... Commission Regulation. Commission Regulation (EC) No 2257/94 of 16 September 1994 laying down quality standards for bananas ( ... Commission Implementing Regulation. Commission Implementing Regulation (EU) No 923/2012 of 26 September 2012 laying down the ... There are Council regulations and Commission regulations. Article 288 does not clearly distinguish between legislative acts and ...
CDC and other agencies implement public health laws passed by Congress through Federal Regulations. After a Congressional bill ... CDC has certain authorities to implement regulations related to protecting America from health and safety threats, both foreign ... becomes law, federal agencies may be responsible for putting the law into action through the development of regulations-also ... You can also find the official text of CDC regulations published in the Code of Federal Regulations under Title 42-Public ...
If we looked at the FDA more like a neutral broker, a source of authoritative and up-to-date information on the food and drugs out there, I think wed be much better off. But instead, weve turned them into the Drug Nannies.. Similarly, the SEC, indeed the entire financial regulatory apparatus, revolves around writing rules, and then making sure that companies live up to them. Some of those rules, like financial statement filings, enhance transparency. But many others jealously guard the perogatives of the SEC and its minions--the safe harbor provisions for the three big regulatory agencies, for example, which lets the SEC control the definition of what a good, safe security is. From what I understand, one of the reasons that so many at the SEC opposed GLB was that merging investment banks with commercial banks meant handing over some of their regulatory power to the agencies that oversaw the commercial sector.. ...
The Division is responsible for the regulation of biocides, pesticides, detergents, chemicals as they are regulated by REACH, ... and duties under the Classification, Labelling and Packaging (CLP) regulation. ... The Chemicals Regulation Division (CRD) is a Division of the Health & Safety Executive (HSE). ... Chemicals Regulation Division. The Chemicals Regulation Division (CRD) is responsible for the regulation of biocides, ...
Latest Tobacco industry regulation News. The Latest: Vaping industry slams ban on flavored products. Nov. 27, 2019 5:18 PM EST ... The regulations conform to the constitution and its goal of protecting the lives of Kenyans, the... ... NAIROBI, Kenya (AP) - Kenyas Supreme Court on Tuesday dismissed a British American Tobacco challenge to regulations that ...
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Regulation. There are laws on the books worldwide that constrain the activity of corporations. The problem is enforcing them ... However, Mexico remains the world s Number One cruise ship destination; and with little regulation, allegations of onboard ... and how the private sector manages to set the regulation agenda itself. ... page document to defend itself against an international lawsuit challenging the countrys tough tobacco packaging regulations. ...
... of innate immunity. Key cytokines in the innate immune response include: TNF-α, IL-1, IL-10, IL-12, type I ... Although cytokine regulation of inflammation and immunity is essential for defending against infection and injury, excess ... Further activation of the adaptive immune response depends on cytokine regulation of T-cell differentiation into subsets of T- ... Cytokine Regulation. News-Medical. 21 September 2019. ,https://www.news-medical.net/life-sciences/Cytokine-Regulation.aspx,. ...
Our research is concentrated on the regulation of processes responsible for the concerted action of cells, tissues, and organs ... Our research is concentrated on the regulation of processes responsible for the concerted action of cells, tissues, and organs ... The Department of Biological Regulation is comprised of approximately 160 people organized in 13 research groups. We are ...
JOHANNESBURG - Supporting free speech and majority rule is a hallmark of the European Union. But in the fight against fake news, those values are nothing short of obstacles.. Thats according to several media experts and stakeholders, who all told Poynter that recent efforts by the European Union and individual countries to regulate online misinformation will likely fail due to governance issues and legal restrictions in the region. ...
The survey below (in English, French, Spanish, Russian and Arabic) is directed at ICAOs Contracting States to whom State letter SC 5/2-01/50 was sent. In this letter, it was mentioned that the Survey attached to the letter would be posted on the ICAO Web site for ease of reference (not for on-line reply, however ...
Contact details for monitoring organisations/competent authorities in Member States dealing with the EU Timber Regulation (EUTR ... Interested private entities that fulfil the requirements within the regulation may apply to become monitoring organisations. ... Interested private entities that fulfil the requirements within the regulation may apply to become monitoring organisations. ... More recent information is available under http://ec.europa.eu/environment/forests/timber_regulation.htm ...
Privacy, Regulation, and the Internet (Exploring Liberty) - Duration: 25:18. Libertarianism.org 4,415 views ... Internet regulation, Internet freedom, Internet activism - Duration: 30:03. AdamVsTheManRT 10,611 views ... Terrys Floor Speech on Keeping the Internet Free From Government Regulation - Duration: 5:52. NebraskaTerry 233 views ... The Internet and International Telecommunications Regulation - the ITRs - Duration: 3:16. Internet Society 11,216 views ...
... such as the Food and Drug Administrations premature call for regulation of nitrites, which later had to be retracted. ...
Code of Federal Regulations (CFR). Code of Federal Regulations (CFR). Regulation No.. Title. ... The NIOSH regulations are found in the following parts of the Code of Federal Regulations (CFR) and are linked below. ... NIOSH is also directly responsible for several regulations. These regulations mostly outline procedures and requirements for ... Also, OSHAs regulation at 29 CFR 1910.1020(h)(2) requires that: "Whenever an employer is ceasing to do business and there is ...
  • These regulations outline the statewide standards and licensing requirements for commercial cannabis manufacturers, became effective on December 7, 2017 and were re-adopted with some changes on June 6, 2018. (ca.gov)
  • MCSB published proposed regulations on July 13, 2018. (ca.gov)
  • On March 23, 2018, MCSB released proposed emergency regulations that would allow cannabis manufacturers to utilize shared-use facilities. (ca.gov)
  • The emergency regulations for shared-use facilities were approved and went into effect on April 13, 2018. (ca.gov)
  • The European Union's General Data Protection Regulation (GDPR), which comes into effect in May 2018, has far-reaching implications that extend far beyond the EU. (cmswire.com)
  • On July 11, 2013, the EU Cosmetics Regulation entered into effect replacing the EU Cosmetics Directive which had been in place since the 1970s. (export.gov)
  • Section 1 of this report provides information on the categories of products covered by the Cosmetics Regulation. (export.gov)
  • The Cosmetics Regulation requires that non-EU based exporters of cosmetic products retain a Responsible Person. (export.gov)
  • Guinea pigs, rats, and rabbits can sleep safe and sound in Europe as of today (11 March) after the last deadline specified in the Cosmetics Regulation entered into force across the European Union, forbidding the industry from using animal testing. (euractiv.com)
  • Today the NAI is joining leading advertising and marketing associations in the launch of the cross-industry program for self-regulation of online behavioral advertising. (networkadvertising.org)
  • Newsnight's political editor Allegra Stratton was told Privy Council members felt proposals for self-regulation put forward by newspapers did not meet the requirements of Lord Justice Leveson's report. (bbc.co.uk)
  • Acting editor of the Times John Witherow described the proposals for self-regulation as robust but said they would not affect press freedom. (bbc.co.uk)
  • In some countries (in particular the Scandinavian countries) industrial relations are to a very high degree regulated by the labour market parties themselves (self-regulation) in contrast to state regulation of minimum wages etc. (wikipedia.org)
  • When a regulation comes into force, it overrides all national laws dealing with the same subject matter and subsequent national legislation must be consistent with and made in the light of the regulation. (wikipedia.org)
  • CDC and other agencies implement public health laws passed by Congress through Federal Regulations. (cdc.gov)
  • To understand how FDA regulates pet food, it's important to first understand several key concepts and some of the laws and regulations regarding food for animals. (fda.gov)
  • The links below provide additional information on the requirements and exceptions under the AWA, and complying with other applicable Federal, state, and local laws and regulations. (usda.gov)
  • For a complete list of U.S. laws and regulations pertaining to biotechnology under the Coordinated Framework, click here . (usda.gov)
  • EPA is called a regulatory agency because Congress authorizes us to write regulations that explain the technical, operational, and legal details necessary to implement laws. (epa.gov)
  • 2) European Accessibility Act (EAA) - will be the basis for European Union (EU) member states to create new laws, regulations, and administrative provisions for accessible products and services in support of the United Nations Convention on the Rights of People with Disabilities (UNCRPD). (ibm.com)
  • Congress added this section to the AWA in 2008 and APHIS published specific regulations in 2014. (usda.gov)
  • The proposed regulations and executive orders are directly related to parts of the president's agenda that have been rejected by Congress and the American people - most recently in the November presidential election. (americanthinker.com)
  • On behalf of our activist community, I urge you to contact your representative and ask him or her to support the Reset Act, H.R. 3442, introduced by Rep. Ted Budd (R-N.C.). The bill would require a review of all major federal regulations and allow Congress the option to overturn any such regulation through a majority vote in both houses. (freedomworks.org)
  • Agencies create regulations (also known as "rules") under the authority of Congress to help government carry out public policy. (hhs.gov)
  • The Chemicals Regulation Division (CRD) is responsible for the regulation of biocides, pesticides, detergents, chemicals covered by REACH, and for compliance with the Classification, Labelling and Packaging (CLP) Regulation. (hse.gov.uk)
  • These Compliance & Disclosure Interpretations ("C&DIs") comprise the Division's interpretations of Regulation S-K. Some of these C&DIs were first published in prior Division publications and have been revised in some cases. (sec.gov)
  • The Gateway to State-by-State Resource Locators Exit , sponsored by EPA's Office of Enforcement and Compliance Assistance , provides access to state-by-state environmental regulations, compliance assistance, and where applicable, permits and forms for a variety of topics. (epa.gov)
  • From a close-up investigation of Canadian financial regulations before and since the global financial crisis, to a profile of New Zealand's regulation and governance of its non-bank financial sector, to insight for international banks on compliance with anti-money-laundering legislation in Malaysia, the journal presents sophisticated analysis, and in-depth, expert advice. (palgrave.com)
  • This complexity has created a financial regulation industry - an army of compliance officers, regulators, consultants and advisers - with a vested interest in the regulation industry's expansion. (truth-out.org)
  • Institutions engaging in most HHS-supported human subject research must have an approved assurance of compliance with protective HHS regulations. (hhs.gov)
  • Consequently, Cerf said, regulators could not differentiate between regulation of normal telephony and VoIP, because to a casual observer they appeared to be the same technology, even though they were delivered over radically different mediums. (zdnet.com)
  • Regulators come to see the industry through the eyes of market participants rather than the end users they exist to serve, because market participants are the only source of the detailed information and expertise this type of regulation requires. (truth-out.org)
  • The newspaper industry has rejected a plan for press regulation agreed by the three main political parties in the wake of the Leveson Inquiry. (bbc.co.uk)
  • Our research is concentrated on the regulation of processes responsible for the concerted action of cells, tissues, and organs. (weizmann.ac.il)
  • Motivational and behavioral models of developmental regulation form the framework for research on the central processes of agency over the lifespan. (springer.com)
  • The motivational theory of development over the lifespan conceptualizes processes of developmental regulation as a sequence of behavioral phases (goal selection, goal striving, and goal realization) with their own respective control strategies. (springer.com)
  • Strategies for effective regulation require policies, institutional capacities and processes for the development of "fit for purpose" regulations. (oecd.org)
  • There are a series of key differences between the industry's plan for press regulation and that agreed by politicians and campaigners. (bbc.co.uk)
  • Canned pet food must also comply with the regulations for low-acid canned food . (fda.gov)
  • Although many U.S. exporters of cosmetic products have already taken steps to comply with this regulation, this report assists all U.S. cosmetics manufacturers understand the new requirements so they can better prepare to compete in the EU market. (export.gov)
  • We provide a number of tools for you to keep track of and participate in the development of new EPA regulations, and to learn how to comply with existing regulations. (epa.gov)
  • Under the definition of "smaller reporting company" in Item 10(f) of Regulation S-K, does the corporate parent of a majority-owned subsidiary have to satisfy the public float or revenue requirements of the definition in order for the majority-owned subsidiary to qualify as a smaller reporting company? (sec.gov)
  • Under the definition of "smaller reporting company" in Item 10(f) of Regulation S-K, must the corporate parent of a majority-owned subsidiary be required to file reports under Section 13(a) or Section 15(d) of the Exchange Act in order for the majority-owned subsidiary to qualify as a smaller reporting company? (sec.gov)
  • The technical definition of a midnight regulation is one issued between Election Day and the inauguration of a new president. (americanthinker.com)
  • BRS derives its authority to write regulations from provisions of the Plant Protection Act , which is a part of the larger Agriculture Risk Protection Act of 2000 . (usda.gov)
  • As the nation's public health protection agency, CDC has certain authorities to implement regulations related to protecting America from health and safety threats, both foreign and within the United States, and increasing public health security. (cdc.gov)
  • EPA docket centers provide access to the same information as Regulations.gov for those people without access to the Internet. (epa.gov)
  • You may also submit comments to the docket centers, in addition to submitting them via Regulations.gov. (epa.gov)
  • If EPA decides to proceed with regulation development, then the agency conducts a variety of economic analyses when developing the proposed and final regulations. (epa.gov)
  • EPA rulemakings (i.e., regulations that are under development) could impact you once they become final regulations. (epa.gov)
  • Actually implementing this rule for a large company with lots of projects going on and many loans at varying interest rates requires fairly complex regulations. (forbes.com)
  • This information complements the contact list of persons requiring notification due to medical conditions as required under Regulation 637, Rule 5. (michigan.gov)
  • Maintenance of cholesterol homeostasis requires constant metabolic adjustment, achieved partly through the fine regulation of the classical transcription factors (e.g., by SREBP and LXR), but also through members of a class of noncoding RNAs termed miRNAs. (hindawi.com)
  • Media caption One minute catch up: Press regulation where are we now? (bbc.co.uk)
  • Maria Miller, Secretary of State for Culture, Media and Sport, will make a statement on press regulation in the House of Commons later. (bbc.co.uk)
  • Press regulation options are being considered in the wake of the Leveson Inquiry, which was set up in July 2011 after it emerged journalists working for the now-closed News of the World had hacked into the mobile phone of murdered Surrey schoolgirl Milly Dowler. (bbc.co.uk)
  • In the latest Viewpoints Breakfast series, Laurence Fink, Chairman and CEO of BlackRock Inc. talk about the role of regulation coming out of the recession and in the future, with Alan Murray. (wsj.com)
  • For WSJ's 'Viewpoints' series, late Lazard Chairman and CEO Bruce Wasserstein speaks to Alan Murray about government regulation. (wsj.com)
  • Regulation F specifies that banks must institute internal rules that regulate the amount of risk that they can take in their business proceedings with other institutions. (investopedia.com)
  • Senate approves bill that would regulate airline seat sizes The government is another step closer to coming up with regulations on minimum seat sizes for airline flights after the Senate passed an FAA reauthorization bill. (usatoday.com)
  • PSCs in some states pioneered regulations and policies that led to the development and practice of utility "demand-side management," which includes customer energy efficiency programs . (aceee.org)
  • The list now includes any independent contractor or "any other person" who knowingly or recklessly participates in any violation of law or regulation, breach of fiduciary duty, or unsafe or unsound practice. (reuters.com)
  • Regulations may create costs as well as benefits and may produce unintended reactivity effects, such as defensive practice. (wikipedia.org)
  • After a Congressional bill becomes law, federal agencies may be responsible for putting the law into action through the development of regulations-also known as "rules. (cdc.gov)
  • Water Environment Regulation Watch provides concise reports of related bills, regulations, legal decisions, congressional hearings, and other federal government actions, following key issues from introduction to final determination. (wef.org)
  • Opponents contend the rules were crafted so broadly that almost any spot where water collects naturally on private property would invite intrusive federal regulation. (voanews.com)
  • Regulation that is at once extensive and intrusive, yet ineffective and largely captured by financial sector interests. (truth-out.org)
  • Chairman Hensarling, Ranking Member Waters, and other members of the committee, I appreciate the opportunity to testify on the Federal Reserve's regulation and supervision of financial institutions. (federalreserve.gov)
  • Ensemble models of allosteric regulation enumerate an allosteric system's statistical ensemble as a function of its potential energy function , and then relate specific statistical measurements of allostery to specific energy terms in the energy function (such as an intermolecular salt bridge between two domains). (wikipedia.org)
  • As a result, our regulation of that system should support and promote the system's efficiency just as it supports its safety. (federalreserve.gov)
  • The California Department of Public Health (CDPH) developed emergency regulations to implement the mandates of the Medicinal and Adult-Use Cannabis Regulation and Safety Act (MAUCRSA). (ca.gov)
  • These regulations were developed to provide opportunities for small manufacturing businesses and in response to demand from cities and counties wishing to implement equity programs. (ca.gov)
  • You may be continuing to implement the changes that will align your organization with this data protection regulation. (mcafee.com)
  • State-mandated regulation is government intervention in the private market in an attempt to implement policy and produce outcomes which might not otherwise occur, ranging from consumer protection to faster growth or technological advancement. (wikipedia.org)
  • The human lifespan provides an age-based timetable for the regulation of development. (springer.com)
  • Photosynthate supply and phytohormones, particularly cytokinins, interact with nitrogen supply to control the expression of photosynthesis genes, the development of leaves and the whole plant nitrogen distribution, which provides the dominant basis for sink regulation of photosynthesis. (nih.gov)
  • It lists all HHS regulations under development or review. (hhs.gov)
  • Common examples of regulation include controls on market entries, prices, wages, development approvals, pollution effects, employment for certain people in certain industries, standards of production for certain goods, the military forces and services. (wikipedia.org)
  • But ministers "do look set to reject" the form of regulation put forward by newspapers, BBC political editor Nick Robinson said . (bbc.co.uk)
  • Regulations are mandatory requirements that can apply to individuals, businesses, state or local governments, non-profit institutions, or others. (epa.gov)
  • Besides its value as a textbook, Mechanisms of Gene Regulation will be a useful reference for individuals working in biomedical laboratories. (springer.com)
  • Established as a formal policy in 1986, the Coordinated Framework for Regulation of Biotechnology describes the Federal system for evaluating products developed using modern biotechnology. (usda.gov)
  • A regulation set forth by the Federal Reserve. (investopedia.com)
  • Federal regulations give the public details or specific requirements of how the law will be applied. (cdc.gov)
  • Federal rulemaking usually involves a notice-and-comment process in which regulations are published in the Federal Register External for public comment over a specified time. (cdc.gov)
  • You can provide your comments by going to the federal government's regulations website External to view CDC's rules that are open for public comment External . (cdc.gov)
  • The Unified Agenda, published in the spring and fall of each year, provides information about regulations that the federal government is considering or reviewing within the next 12 months. (cdc.gov)
  • Comment on regulations, and access rules that have been published in the Federal Register and related documents. (epa.gov)
  • In many cases, state-level environmental agencies administer the federal regulations that EPA puts in place. (epa.gov)
  • At issue is whether those rules, crafted by the Environmental Protection Agency, constitute a reasonable attempt to safeguard America's freshwater supply or a massive bureaucratic power grab that will subject farmers and other landowners to onerous federal oversight and regulations. (voanews.com)
  • This report deals with the regulation of logistics infrastructures in Brazil, focusing in particular on the federal level. (rand.org)
  • It also covers certain types of transactions in the financial markets - interest rate swaps and repurchase agreements fall under this regulation. (investopedia.com)
  • Pushing an overhaul plan for financial regulation on Thursday, the president said, 'Unless your business model depends on bilking people, there is little to fear from these new rules. (nytimes.com)
  • Consequently, leading states have enacted regulations and policies to create new business models for their investor-owned utilities - models that eliminate the financial disincentives that prevent utilities from saving energy and provide incentives for developing successful and effective energy efficiency programs. (aceee.org)
  • The tragicomic events of the past few months-the London Whale (what are we up to now, $6 billion), Barclays-Libor, HSBC laundering money have prompted renewed interest in better, stronger regulation of the financial sector. (truth-out.org)
  • Do senior managers in financial services have a legitimate complaint when it comes to being overwhelmed by regulation? (thersa.org)
  • Many financial regulations implemented over the past decade and a half were done so in the name of investor protection, and for good reason. (forbes.com)
  • Uruguay has presented a 500 page document to defend itself against an international lawsuit challenging the country's tough tobacco packaging regulations. (corpwatch.org)
  • To understand the complexity of the vertical piano action and theprimary cause of an action going out of regulation, consider the cut-away photo ofthe action from an actual piano on the next page. (slideshare.net)
  • In conformity with applicable rules and regulations. (wiktionary.org)
  • The process of creating regulations or rules is called rulemaking. (cdc.gov)
  • We explore the role of government in setting and enforcing rules for fairness and competition in the private sector, and how the private sector manages to set the regulation agenda itself. (corpwatch.org)
  • These regulations mostly outline procedures and requirements for specific health and safety related matters involving a particular industry or set forth rules for NIOSH to follow in administering programs assigned to the Institute. (cdc.gov)
  • They included smaller rules on workplace hazards, gun sellers, nutrition labels and energy efficiency, as well as giant regulations (costing billions) on retirement advice and overtime pay. (americanthinker.com)
  • Regulation of March 26, 2013, on the Exclusion of Some Provisions of the Aviation Law Act for Certain Types of Aircraft and Determining the Conditions and Requirements Relating to the Use of Such Aircraft, which sets out the rules for operation of UAS weighing less than 25 kg. (loc.gov)
  • Regulation of April 26, 2013, on the Technical and Operational Rules on Aircraft of Special Category, Not Subject to the Supervision of the European Aviation Safety Agency, which mostly applies to UAS weighing more than 25 kg. (loc.gov)
  • Obtaining a VLOS operation certificate requires the applicant to sign a declaration of knowledge of relevant regulations and basic theory (airspace, emergencies, flight rules, etc.), and pass theoretical and practical tests conducted by a CAA examiner. (loc.gov)
  • Rules and Notices from each HHS Operating Division are available on Regulations.gov. (hhs.gov)
  • Regulation is an abstract concept of management of complex systems according to a set of rules and trends. (wikipedia.org)
  • A breakthrough in decoding gene regulation of Helicobacter pylori has been made by an international research team led by Jörg Vogel of the Max Planck Institute for Infection Biology in Berlin. (redorbit.com)
  • Turn to this journal for briefings, analyses and updates on all aspects of law and regulation affecting banking institutions. (palgrave.com)
  • Information about Regulation (EU) 649/2012 regarding the export or import of chemicals or articles containing chemicals (commonly known as the Prior Informed Consent (PIC) Regulation). (hse.gov.uk)
  • Our findings suggest that as backyard chicken farming spreads, states need to develop regulations to better protect animal welfare and human health. (theconversation.com)
  • At the regional level, WHO supports countries in building effective medicines regulation systems that promote and protect public health by ensuring certain standards. (who.int)
  • When appropriately implemented, regulation ensures public health benefit and the safety of patients, health care workers and the community. (who.int)
  • The regulation is intended to ensure adequate supplies for local infants and young children, Mead Johnson said. (yahoo.com)
  • Neil Wallis, a former executive editor of the News of the World, said the press was honouring the spirit of the Leveson report but wanted to prevent politicians having a say in regulation. (bbc.co.uk)
  • In a recent study with University of California, Davis animal scientist Joy Mench , we examined urban poultry regulations in Colorado - the only state that collects and makes public animal shelter surrender data. (theconversation.com)
  • Army regulations state a soldier AWOL over 30 days is a deserter. (wiktionary.org)
  • Car service app Uber has built a sizable business, and hasn't been too concerned about state and city regulations. (cnbc.com)
  • A voltmeter is then connected in parallel to the resistors and the measured values of voltage for each load state can be used to calculate the load regulation as given in the equation above. (wikipedia.org)