Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.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.Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Spleen: An encapsulated lymphatic organ through which venous blood filters.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Carbon Radioisotopes: Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.Alternative Splicing: A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Testis: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Area Under Curve: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Gene Library: A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.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.Organic Cation Transport Proteins: A family of proteins involved in the transport of organic cations. They play an important role in the elimination of a variety of endogenous substances, xenobiotics, and their metabolites from the body.Immunoenzyme Techniques: Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.Mice, Inbred BALB CBrain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Sea Bream: A species of PERCIFORMES commonly used in saline aquaculture.Autoradiography: The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)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.Mice, Inbred C57BLMembrane 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.Adipose Tissue: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.Drug Carriers: Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.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.Oncorhynchus mykiss: A large stout-bodied, sometimes anadromous, TROUT found in still and flowing waters of the Pacific coast from southern California to Alaska. It has a greenish back, a whitish belly, and pink, red, or lavender stripes on the sides, with usually a sprinkling of black dots. It is highly regarded as a sport and food fish. Its former name was Salmo gairdneri. The sea-run rainbow trouts are often called steelheads. Redband trouts refer to interior populations of rainbows.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).Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Molecular Weight: The sum of the weight of all the atoms in a molecule.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Gallium Radioisotopes: Unstable isotopes of gallium that decay or disintegrate emitting radiation. Ga atoms with atomic weights 63-68, 70 and 72-76 are radioactive gallium isotopes.Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.Canthaxanthin: A trans-carotenoid pigment widely distributed in nature. The compound is used as an oral suntanning agent and as a food and drug coloring agent. Oral ingestion of the compound causes canthaxanthin retinopathy.Bile: An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.Lymphoid Tissue: Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.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.Kinetics: The rate dynamics in chemical or physical systems.Radioactivity: The spontaneous transformation of a nuclide into one or more different nuclides, accompanied by either the emission of particles from the nucleus, nuclear capture or ejection of orbital electrons, or fission. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Fetus: The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN.Animal Structures: Organs and other anatomical structures of non-human vertebrate and invertebrate animals.Gills: Paired respiratory organs of fishes and some amphibians that are analogous to lungs. They are richly supplied with blood vessels by which oxygen and carbon dioxide are exchanged directly with the environment.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.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Organic Cation Transporter 1: An organic cation transporter found in kidney. It is localized to the basal lateral membrane and is likely to be involved in the renal secretion of organic cations.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Digestive System: A group of organs stretching from the MOUTH to the ANUS, serving to breakdown foods, assimilate nutrients, and eliminate waste. In humans, the digestive system includes the GASTROINTESTINAL TRACT and the accessory glands (LIVER; BILIARY TRACT; PANCREAS).Astatine: Astatine. A radioactive halogen with the atomic symbol At, atomic number 85, and atomic weight 210. Its isotopes range in mass number from 200 to 219 and all have an extremely short half-life. Astatine may be of use in the treatment of hyperthyroidism.Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.Intestine, Small: The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM.Organic Anion Transporters: Proteins involved in the transport of organic anions. They play an important role in the elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body.Takifugu: A genus of pufferfish commonly used for research.Radioisotopes: Isotopes that exhibit radioactivity and undergo radioactive decay. (From Grant & Hackh's Chemical Dictionary, 5th ed & McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Thymus Gland: A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.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.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Fish Proteins: Proteins obtained from species of fish (FISHES).Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Drug Delivery Systems: Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.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.Biological Availability: The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.Scandium: Scandium. An element of the rare earth family of metals. It has the atomic symbol Sc, atomic number 21, and atomic weight 45.Adrenal Glands: A pair of glands located at the cranial pole of each of the two KIDNEYS. Each adrenal gland is composed of two distinct endocrine tissues with separate embryonic origins, the ADRENAL CORTEX producing STEROIDS and the ADRENAL MEDULLA producing NEUROTRANSMITTERS.Isotope Labeling: Techniques for labeling a substance with a stable or radioactive isotope. It is not used for articles involving labeled substances unless the methods of labeling are substantively discussed. Tracers that may be labeled include chemical substances, cells, or microorganisms.Antigens, Surface: Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.Time Factors: Elements of limited time intervals, contributing to particular results or situations.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Body Fat Distribution: Deposits of ADIPOSE TISSUE throughout the body. The pattern of fat deposits in the body regions is an indicator of health status. Excess ABDOMINAL FAT increases health risks more than excess fat around the hips or thighs, therefore, WAIST-HIP RATIO is often used to determine health risks.Mice, Inbred ICRSodium Acetate: The trihydrate sodium salt of acetic acid, which is used as a source of sodium ions in solutions for dialysis and as a systemic and urinary alkalizer, diuretic, and expectorant.Lysinoalanine: N(6)-(2-Amino-2-carboxyethyl)-L-lysine. An unusual amino acid, not a dipeptide, which has been found in proteins of cooked foods. It is formed in food that is heated or treated with alkali. Has been implicated in nephrocytomegalia in rats.Injections, Intraperitoneal: Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Maackia: A plant genus of the family FABACEAE. It contains a hemagglutinin.Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)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.Antibody Specificity: The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.Zinc Radioisotopes: Unstable isotopes of zinc that decay or disintegrate emitting radiation. Zn atoms with atomic weights 60-63, 65, 69, 71, and 72 are radioactive zinc isotopes.Cellular Structures: Components of a cell.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Sambucus nigra: A plant species in the genus SAMBUCUS, known for the elderberry fruit. The plant is also a source of Sambucus nigra lectins and ribosome-inactivating protein.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Administration, Intravenous: Delivery of substances through VENIPUNCTURE into the VEINS.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Molindone: An indole derivative effective in schizophrenia and other psychoses and possibly useful in the treatment of the aggressive type of undersocialized conduct disorder. Molindone has much lower affinity for D2 receptors than most antipsychotic agents and has a relatively low affinity for D1 receptors. It has only low to moderate affinity for cholinergic and alpha-adrenergic receptors. Some electrophysiologic data from animals indicate that molindone has certain characteristics that resemble those of CLOZAPINE. (From AMA Drug Evaluations Annual, 1994, p283)Blotting, Southern: A method (first developed by E.M. Southern) for detection of DNA 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.Arctium: A plant genus of the family ASTERACEAE. Arctiin (LIGNANS) is in the seed.Epithelium: One or more layers of EPITHELIAL CELLS, supported by the basal lamina, which covers the inner or outer surfaces of the body.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Fluoride PoisoningFluorine Radioisotopes: Unstable isotopes of fluorine that decay or disintegrate emitting radiation. F atoms with atomic weights 17, 18, and 20-22 are radioactive fluorine isotopes.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.Technetium: The first artificially produced element and a radioactive fission product of URANIUM. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. All technetium isotopes are radioactive. Technetium 99m (m=metastable) which is the decay product of Molybdenum 99, has a half-life of about 6 hours and is used diagnostically as a radioactive imaging agent. Technetium 99 which is a decay product of technetium 99m, has a half-life of 210,000 years.Ranunculaceae: The buttercup plant family of the order Ranunculales, subclass Magnoliidae, class Magnoliopsida. The leaves are usually alternate and stalkless. The flowers usually have two to five free sepals and may be radially symmetrical or irregular.Particle Size: Relating to the size of solids.Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the ESOPHAGUS and the beginning of the DUODENUM.Urogenital System: All the organs involved in reproduction and the formation and release of URINE. It includes the kidneys, ureters, BLADDER; URETHRA, and the organs of reproduction - ovaries, UTERUS; FALLOPIAN TUBES; VAGINA; and CLITORIS in women and the testes; SEMINAL VESICLES; PROSTATE; seminal ducts; and PENIS in men.Macroglobulins: Serum globulins with high molecular weight. (Dorland, 28th ed)Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Eye: The organ of sight constituting a pair of globular organs made up of a three-layered roughly spherical structure specialized for receiving and responding to light.Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.Placenta: A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES).Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Antiporters: Membrane transporters that co-transport two or more dissimilar molecules in the opposite direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Parrots: BIRDS of the large family Psittacidae, widely distributed in tropical regions and having a distinctive stout, curved hooked bill. The family includes LOVEBIRDS; AMAZON PARROTS; conures; PARAKEETS; and many other kinds of parrots.Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Multigene Family: A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Aldehyde Oxidase: An aldehyde oxidoreductase expressed predominantly in the LIVER; LUNGS; and KIDNEY. It catalyzes the oxidation of a variety of organic aldehydes and N-heterocyclic compounds to CARBOXYLIC ACIDS, and also oxidizes quinoline and pyridine derivatives. The enzyme utilizes molybdenum cofactor and FAD as cofactors.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Drug Stability: The chemical and physical integrity of a pharmaceutical product.Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Eels: Common name for an order (Anguilliformes) of voracious, elongate, snakelike teleost fishes.Muscles: Contractile tissue that produces movement in animals.Macaca fascicularis: A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula.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.Mice, Nude: Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.Symporters: Membrane transporters that co-transport two or more dissimilar molecules in the same direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.Fluorine Compounds: Inorganic compounds that contain fluorine as an integral part of the molecule.Radionuclide Imaging: The production of an image obtained by cameras that detect the radioactive emissions of an injected radionuclide as it has distributed differentially throughout tissues in the body. The image obtained from a moving detector is called a scan, while the image obtained from a stationary camera device is called a scintiphotograph.Indium Radioisotopes: Unstable isotopes of indium that decay or disintegrate emitting radiation. In atoms with atomic weights 106-112, 113m, 114, and 116-124 are radioactive indium isotopes.Nucleic Acid Hybridization: Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Oxyquinoline: An antiseptic with mild fungistatic, bacteriostatic, anthelmintic, and amebicidal action. It is also used as a reagent and metal chelator, as a carrier for radio-indium for diagnostic purposes, and its halogenated derivatives are used in addition as topical anti-infective agents and oral antiamebics.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.Tilapia: A freshwater fish used as an experimental organism and for food. This genus of the family Cichlidae (CICHLIDS) inhabits Central and South America (one species extends north into Texas), West Indies, Africa, Madagascar, Syria, and coastal India.Neoplasms, Experimental: Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.Sequence Homology: The degree of similarity between sequences. Studies of AMINO ACID SEQUENCE HOMOLOGY and NUCLEIC ACID SEQUENCE HOMOLOGY provide useful information about the genetic relatedness of genes, gene products, and species.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Drug Administration Routes: The various ways of administering a drug or other chemical to a site in a patient or animal from where the chemical is absorbed into the blood and delivered to the target tissue.Whole-Body Counting: Measurement of radioactivity in the entire human body.Rats, Inbred F344TritiumAnion Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of negatively charged molecules (anions) across a biological membrane.Neoplasm Transplantation: Experimental transplantation of neoplasms in laboratory animals for research purposes.Polyethylene Glycols: Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.Introns: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.Emulsifying Agents: SURFACE-ACTIVE AGENTS that induce a dispersion of undissolved material throughout a liquid.Monocarboxylic Acid Transporters: A family of proteins involved in the transport of monocarboxylic acids such as LACTIC ACID and PYRUVIC ACID across cellular membranes.Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin.Vitamin K 1: A family of phylloquinones that contains a ring of 2-methyl-1,4-naphthoquinone and an isoprenoid side chain. Members of this group of vitamin K 1 have only one double bond on the proximal isoprene unit. Rich sources of vitamin K 1 include green plants, algae, and photosynthetic bacteria. Vitamin K1 has antihemorrhagic and prothrombogenic activity.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Receptors, Corticotropin: Cell surface receptors that bind CORTICOTROPIN; (ACTH, adrenocorticotropic hormone) with high affinity and trigger intracellular changes. Pharmacology suggests there may be multiple ACTH receptors. An ACTH receptor has been cloned and belongs to a subfamily of G-protein-coupled receptors. In addition to the adrenal cortex, ACTH receptors are found in the brain and immune systems.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Immunosorbent Techniques: Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.Protein PrecursorsGene Components: The parts of the gene sequence that carry out the different functions of the GENES.Subcutaneous Fat: Fatty tissue under the SKIN through out the body.Indium: A metallic element, atomic number 49, atomic weight 114.82, symbol In. It is named from its blue line in the spectrum. (From Dorland, 28th ed)Nanoparticles: Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.Endocrine Glands: Ductless glands that secrete HORMONES directly into the BLOOD CIRCULATION. These hormones influence the METABOLISM and other functions of cells in the body.

Separation of shoot and floral identity in Arabidopsis. (1/18708)

The overall morphology of an Arabidopsis plant depends on the behaviour of its meristems. Meristems derived from the shoot apex can develop into either shoots or flowers. The distinction between these alternative fates requires separation between the function of floral meristem identity genes and the function of an antagonistic group of genes, which includes TERMINAL FLOWER 1. We show that the activities of these genes are restricted to separate domains of the shoot apex by different mechanisms. Meristem identity genes, such as LEAFY, APETALA 1 and CAULIFLOWER, prevent TERMINAL FLOWER 1 transcription in floral meristems on the apex periphery. TERMINAL FLOWER 1, in turn, can inhibit the activity of meristem identity genes at the centre of the shoot apex in two ways; first by delaying their upregulation, and second, by preventing the meristem from responding to LEAFY or APETALA 1. We suggest that the wild-type pattern of TERMINAL FLOWER 1 and floral meristem identity gene expression depends on the relative timing of their upregulation.  (+info)

Novel regulation of the homeotic gene Scr associated with a crustacean leg-to-maxilliped appendage transformation. (2/18708)

Homeotic genes are known to be involved in patterning morphological structures along the antero-posterior axis of insects and vertebrates. Because of their important roles in development, changes in the function and expression patterns of homeotic genes may have played a major role in the evolution of different body plans. For example, it has been proposed that during the evolution of several crustacean lineages, changes in the expression patterns of the homeotic genes Ultrabithorax and abdominal-A have played a role in transformation of the anterior thoracic appendages into mouthparts termed maxillipeds. This homeotic-like transformation is recapitulated at the late stages of the direct embryonic development of the crustacean Porcellio scaber (Oniscidea, Isopoda). Interestingly, this morphological change is associated with apparent novelties both in the transcriptional and post-transcriptional regulation of the Porcellio scaber ortholog of the Drosophila homeotic gene, Sex combs reduced (Scr). Specifically, we find that Scr mRNA is present in the second maxillary segment and the first pair of thoracic legs (T1) in early embryos, whereas protein accumulates only in the second maxillae. In later stages, however, high levels of SCR appear in the T1 legs, which correlates temporally with the transformation of these appendages into maxillipeds. Our observations provide further insight into the process of the homeotic leg-to-maxilliped transformation in the evolution of crustaceans and suggest a novel regulatory mechanism for this process in this group of arthropods.  (+info)

Transcriptional repression by the Drosophila giant protein: cis element positioning provides an alternative means of interpreting an effector gradient. (3/18708)

Early developmental patterning of the Drosophila embryo is driven by the activities of a diverse set of maternally and zygotically derived transcription factors, including repressors encoded by gap genes such as Kruppel, knirps, giant and the mesoderm-specific snail. The mechanism of repression by gap transcription factors is not well understood at a molecular level. Initial characterization of these transcription factors suggests that they act as short-range repressors, interfering with the activity of enhancer or promoter elements 50 to 100 bp away. To better understand the molecular mechanism of short-range repression, we have investigated the properties of the Giant gap protein. We tested the ability of endogenous Giant to repress when bound close to the transcriptional initiation site and found that Giant effectively represses a heterologous promoter when binding sites are located at -55 bp with respect to the start of transcription. Consistent with its role as a short-range repressor, as the binding sites are moved to more distal locations, repression is diminished. Rather than exhibiting a sharp 'step-function' drop-off in activity, however, repression is progressively restricted to areas of highest Giant concentration. Less than a two-fold difference in Giant protein concentration is sufficient to determine a change in transcriptional status of a target gene. This effect demonstrates that Giant protein gradients can be differentially interpreted by target promoters, depending on the exact location of the Giant binding sites within the gene. Thus, in addition to binding site affinity and number, cis element positioning within a promoter can affect the response of a gene to a repressor gradient. We also demonstrate that a chimeric Gal4-Giant protein lacking the basic/zipper domain can specifically repress reporter genes, suggesting that the Giant effector domain is an autonomous repression domain.  (+info)

A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. (4/18708)

Morphogenesis depends on the precise control of basic cellular processes such as cell proliferation and differentiation. Wnt5a may regulate these processes since it is expressed in a gradient at the caudal end of the growing embryo during gastrulation, and later in the distal-most aspect of several structures that extend from the body. A loss-of-function mutation of Wnt5a leads to an inability to extend the A-P axis due to a progressive reduction in the size of caudal structures. In the limbs, truncation of the proximal skeleton and absence of distal digits correlates with reduced proliferation of putative progenitor cells within the progress zone. However, expression of progress zone markers, and several genes implicated in distal outgrowth and patterning including Distalless, Hoxd and Fgf family members was not altered. Taken together with the outgrowth defects observed in the developing face, ears and genitals, our data indicates that Wnt5a regulates a pathway common to many structures whose development requires extension from the primary body axis. The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells.  (+info)

The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping. (5/18708)

Left-right asymmetry in vertebrates is controlled by activities emanating from the left lateral plate. How these signals get transmitted to the forming organs is not known. A candidate mediator in mouse, frog and zebrafish embryos is the homeobox gene Pitx2. It is asymmetrically expressed in the left lateral plate mesoderm, tubular heart and early gut tube. Localized Pitx2 expression continues when these organs undergo asymmetric looping morphogenesis. Ectopic expression of Xnr1 in the right lateral plate induces Pitx2 transcription in Xenopus. Misexpression of Pitx2 affects situs and morphology of organs. These experiments suggest a role for Pitx2 in promoting looping of the linear heart and gut.  (+info)

Mrj encodes a DnaJ-related co-chaperone that is essential for murine placental development. (6/18708)

We have identified a novel gene in a gene trap screen that encodes a protein related to the DnaJ co-chaperone in E. coli. The gene, named Mrj (mammalian relative of DnaJ) was expressed throughout development in both the embryo and placenta. Within the placenta, expression was particularly high in trophoblast giant cells but moderate levels were also observed in trophoblast cells of the chorion at embryonic day 8.5, and later in the labyrinth which arises from the attachment of the chorion to the allantois (a process called chorioallantoic fusion). Insertion of the ROSAbetageo gene trap vector into the Mrj gene created a null allele. Homozygous Mrj mutants died at mid-gestation due to a failure of chorioallantoic fusion at embryonic day 8.5, which precluded formation of the mature placenta. At embryonic day 8.5, the chorion in mutants was morphologically normal and expressed the cell adhesion molecule beta4 integrin that is known to be required for chorioallantoic fusion. However, expression of the chorionic trophoblast-specific transcription factor genes Err2 and Gcm1 was significantly reduced. The mutants showed no abnormal phenotypes in other trophoblast cell types or in the embryo proper. This study indicates a previously unsuspected role for chaperone proteins in placental development and represents the first genetic analysis of DnaJ-related protein function in higher eukaryotes. Based on a survey of EST databases representing different mouse tissues and embryonic stages, there are 40 or more DnaJ-related genes in mammals. In addition to Mrj, at least two of these genes are also expressed in the developing mouse placenta. The specificity of the developmental defect in Mrj mutants suggests that each of these genes may have unique tissue and cellular activities.  (+info)

Requirement of a novel gene, Xin, in cardiac morphogenesis. (7/18708)

A novel gene, Xin, from chick (cXin) and mouse (mXin) embryonic hearts, may be required for cardiac morphogenesis and looping. Both cloned cDNAs have a single open reading frame, encoding proteins with 2,562 and 1,677 amino acids for cXin and mXin, respectively. The derived amino acid sequences share 46% similarity. The overall domain structures of the predicted cXin and mXin proteins, including proline-rich regions, 16 amino acid repeats, DNA-binding domains, SH3-binding motifs and nuclear localization signals, are highly conserved. Northern blot analyses detect a single message of 8.9 and 5.8 kilo base (kb) from both cardiac and skeletal muscle of chick and mouse, respectively. In situ hybridization reveals that the cXin gene is specifically expressed in cardiac progenitor cells of chick embryos as early as stage 8, prior to heart tube formation. cXin continues to be expressed in the myocardium of developing hearts. By stage 15, cXin expression is also detected in the myotomes of developing somites. Immunofluorescence microscopy reveals that the mXin protein is colocalized with N-cadherin and connexin-43 in the intercalated discs of adult mouse hearts. Incubation of stage 6 chick embryos with cXin antisense oligonucleotides results in abnormal cardiac morphogenesis and an alteration of cardiac looping. The myocardium of the affected hearts becomes thickened and tends to form multiple invaginations into the heart cavity. This abnormal cellular process may account in part for the abnormal looping. cXin expression can be induced by bone morphogenetic protein (BMP) in explants of anterior medial mesoendoderm from stage 6 chick embryos, a tissue that is normally non-cardiogenic. This induction occurs following the BMP-mediated induction of two cardiac-restricted transcription factors, Nkx2.5 and MEF2C. Furthermore, either MEF2C or Nkx2.5 can transactivate a luciferase reporter driven by the mXin promoter in mouse fibroblasts. These results suggest that Xin may participate in a BMP-Nkx2.5-MEF2C pathway to control cardiac morphogenesis and looping.  (+info)

Regulation of body length and male tail ray pattern formation of Caenorhabditis elegans by a member of TGF-beta family. (8/18708)

We have identified a new member of the TGF-beta superfamily, CET-1, from Caenorhabditis elegans, which is expressed in the ventral nerve cord and other neurons. cet-1 null mutants have shortened bodies and male tail abnormal phenotype resembling sma mutants, suggesting cet-1, sma-2, sma-3 and sma-4 share a common pathway. Overexpression experiments demonstrated that cet-1 function requires wild-type sma genes. Interestingly, CET-1 appears to affect body length in a dose-dependent manner. Heterozygotes for cet-1 displayed body lengths ranging between null mutant and wild type, and overexpression of CET-1 in wild-type worms elongated body length close to lon mutants. In male sensory ray patterning, lack of cet-1 function results in ray fusions. Epistasis analysis revealed that mab-21 lies downstream and is negatively regulated by the cet-1/sma pathway in the male tail. Our results show that cet-1 controls diverse biological processes during C. elegans development probably through different target genes.  (+info)

  • Such studies are designed to investigate the distribution (integration, expression, persistence and dissemination) of viral, plasmid or other DNA sequences to target or non-target tissues in clinically-relevant animals, and it is possible to evaluate the risk of vector dissemination in parallel. (citoxlab.com)
  • The choice of tissues in a biodistribution study depends on the nature of the tested product, the formulation, the dose-level and the route of administration. (citoxlab.com)
  • In the high-dose (80 mg/kg) and medium-dose (40 mg/kg) groups, the kinetic profile of PUE in blood and kidney samples showed two absorption peaks, while that of the other tissues showed only one peak. (preprints.org)
  • Full-length cDNA gene of sodium-dependent dicarboxylate co-transporter protein 1 (SDCT1) is cloned from normal human kidney tissue and inserted into EGFP (enhanced green fluorescent protein) expression vector along with N-terminal and C-terminal truncated SDCT1 genes, so to construct the eukaryotic expression vectors of EGFP/SDCT1 fusion proteins, which are transfected into human renal tubular epithelial cells (HKC). (springer.com)
  • The results demonstrated that the three strains Italy02 genotype emerging in Moroccan poultry farms have a wide distribution for respiratory system, without kidney damage and without causing mortality. (biomedcentral.com)
  • Localization of a drug molecule's distribution in its targeted tissue provides very important in vivo biological information. (waters.com)
  • Therefore this approach is sub-optimal for studies focusing on the nature and distribution of mucins and mucus in vivo . (jove.com)
  • Magnetic resonance imaging (MRI) has become an established method for the in vivo quantification of fat tissue. (bmj.com)
  • The utility of x-ray computed tomography (CT) scanning in predicting carcass tissue distribution and fat partitioning in vivo in terminal sire sheep was examined using data from 160 lambs representing combinations of 3 breeds (Charollais, Suffolk, and Texel), 3 genetic lines, and both sexes. (unl.edu)
  • To explore the question of what is decisive for arthritogenicity, we have determined the chemical composition and tissue distribution as well as the arthritogenic capacity in vivo and resistance to lysozyme in vitro of cell walls isolated from three strains of Lactobacillus casei and one strain of Lactobacillus fermentum . (asm.org)
  • In vivo experiments were conducted to assess the correlation of Se and MeHg in previously tested rat nail samples and various rat organ tissue samples. (umsystem.edu)
  • The broad tissue and phylogenetic distribution of CyP, its highly conserved structure, and its increased content after mitogenic stimulation suggest a fundamental role in cellular metabolism. (jimmunol.org)
  • These data indicate that pharmacokinetic models for arsenic metabolism and disposition need to include mechanisms for organ-specific accumulation of some arsenicals and that urinary metabolite profiles are not necessarily reflective of target tissue dosimetry. (biomedsearch.com)
  • Primary leaf tissues undergo a programmed shift from isoflavonoid to flavonoid metabolism 3 days after germination and become largely predominated by glycosides of the flavonols kampferol, quercetin, and isorhamnetin by 5 days. (plantphysiol.org)
  • Data originally obtained in studies using the mouse and rat indicated that the tissue distribution of WR-2721 was possibly more closely related to dose per unit surface area than to dose per unit weight. (unt.edu)
  • This document provides guidance on circumstances when repeated dose tissue distribution studies should be considered. (europa.eu)
  • Tumor levels ranged from 27 to 71 μg/g at C max levels across the three dose ranges, and ZD6474 was distributed to all of the tissues in a dose-dependent manner. (aspetjournals.org)
  • However, very few chloroplasts were observed in leaf tissues of rubescent, etiolated, and albino, except that some stomata cells were distributed with relatively rich chloroplasts (Figures 2B-E). Surprisingly chloroplast distribution pattern in petioles of all 4 mutants was similar to the wild type (Figures 2G-J). (nih.gov)
  • Traditionally, autoradiography and fluorescence spectroscopy have been used for molecular imaging of biological tissues. (waters.com)
  • Florescent labeling of AAV capsids aids in understanding the physical barriers associated with AAV mediated retinal gene delivery and to track the progressive steps of vector distribution, surface recognition and transduction at the cellular and molecular levels. (arvojournals.org)
  • Because the descriptors used in the LFERs can be calculated from structure, distribution coefficients for air to blood or tissue for VOCs and for blood/plasma/serum to tissue for VOCs and drugs can be predicted directly from the molecular structures of the VOCs and drugs. (bl.uk)
  • 24) in Atlantic salmon: Cloning, functional characterisation, and tissue distribution of an Elovl4 elongase, Comparative Biochemistry and Physiology - Part B: Biochemistry and Molecular Biology, 159 (2), pp. 122-129. (stir.ac.uk)
  • Most of these studies did not detect the vCJD agent outside the nervous system (central, peripheral, and autonomic) and lymphoid tissues. (cdc.gov)
  • Persistent infection led to a disruption of the normal immunodominance hierarchy of CD8 T-cell responses seen following acute infection and dramatically altered the tissue distribution of LCMV-specific CD8 T cells in lymphoid and nonlymphoid tissues. (asm.org)
  • This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. (harvard.edu)
  • In this study, we used in vitro amplification of prions by protein misfolding cyclic amplification (PMCA) to estimate distribution and level of the vCJD agent in 21 tissues from 4 patients who died of clinical vCJD and from 1 asymptomatic person with vCJD. (cdc.gov)
  • A key event in the pathogenesis of TSEs is the conversion of the normal cellular prion protein (PrP C , encoded by the PRNP gene) into an abnormal disease-associated isoform (PrP Sc ) in tissues of infected animals. (cdc.gov)
  • 4. Metabolically produced 25-hydroxycholecalciferol is also taken up from the blood into many tissues, probably by protein-binding. (portlandpress.com)
  • Sequence and tissue distribution of a second protein of hepatic gap junctions, Cx26, as deduced from its cDNA. (rupress.org)
  • The distribution of the Wnt5 protein in the tissues of the holothurian Eupentacta fraudatrix. (deepdyve.com)
  • Lamash, N. 2014-04-05 00:00:00 The Wnt5 protein localization in holothurian Eupentacta fraudatrix tissues was examined in the norm and during regeneration. (deepdyve.com)
  • The Wnt5 protein localization in holothurian Eupentacta fraudatrix tissues was examined in the norm and during regeneration. (deepdyve.com)
  • WAT extracellular matrix (ECM) remodeling, which plays a pivotal role in adipogenesis ( 4 ) and tissue architecture ( 5 ), is crucial to accommodate obesity-induced cellular alterations ( 6 ). (diabetesjournals.org)
  • We report simulation of experimental data for heterogeneous distribution of extracellular potassium , by developing and applying a mathematical model formulated by incorporating a Luo-Rudy representation of the cell membrane current into the bidomain model of the cardiac tissue . (omicsonline.org)
  • We believe stem cells to be the next frontier in spine surgeryand the Tissue Genesis cell isolation system rapidly processes a smallquantity of a patient's own fat tissue to produce large quantities of cells,including adult stem cells and microvascular cells. (medindia.net)
  • In summary, the results demonstrate that NBBS distributes rapidly to tissues, including brain. (sigmaaldrich.com)
  • Here, we characterize the spatial distribution of efavirenz (EFV) within suspected reservoir tissues of a primate model using a novel approach to mass spectrometry imaging (MSI). (natap.org)
  • Pre-irradiation intravenous administration of the radioprotective drug S- 2-[3-aminopropylamino]ethylphosphorothioic acid (WR-2721) has potential value in radiotherapy because it doubles the radiation resistance of normal mouse tissues while affording only minimal protection to tumors. (unt.edu)
  • Considering the size, the optical property of tumors and their difference from surrounding normal tissue, a two-layer tissue configuration model for LITT is set up, and then energy distribution in the configuration is simulated with Monte Carlo method. (cnki.com.cn)
  • Fibrosis, attributed to excessive deposition of ECM proteins, is a ubiquitous tissue response to an unresolved chronic inflammation ( 7 ). (diabetesjournals.org)
  • CONCLUSIONS There are differences in neck fat deposition between the sexes which, together with the greater overall soft tissue loading on the airway in men, may be factors in the sex distribution of SAHS. (bmj.com)
  • Although there is a clear relationship between overall neck size and airway obstruction in men, 3 there is still controversy about the significance of the precise anatomical distribution of fat deposition in the neck. (bmj.com)
  • Distribution of clusterin in Alzheimer brain tissue. (nih.gov)
  • Reservoir tissues (GALT, lymph nodes, brain, testes) were removed at necropsy from an uninfected rhesus macaque dosed orally to steady-state with EFV. (natap.org)
  • In most other tissues such as brain, testis and parotid gland, the ratio of synthase/hydrolase activity was 0.7-1.6. (nih.gov)
  • In order to visualize myelin sheaths and astroglia in a rat brain sagittal tissue section (shown above), the specimen was immunofluorescently labeled with mouse anti-myelin BP and rabbit anti-GFAP primary antibodies followed by goat anti-mouse and anti-rabbit secondary antibodies conjugated to Alexa Fluor 488 and Alexa Fluor 568, respectively. (microscopyu.com)
  • This paper presents (1) an improved hierarchical method for segmenting the component tissue regions in fast spin echo T2 and PD images of the brain of Multiple Sclerosis (MS) patients, and (2) a methodology to characterize the disease utilizing the distributions of standardized T2 and PD intensities in the segmented tissue regions. (spie.org)
  • The segmentation method imposes a feedback-like procedure on our previously developed hierarchical brain tissue segmentation method. (spie.org)
  • In order to facilitate collaborative research and increase the ability of Brain Tissue Repositories to serve a diverse set of constituents, the participating Institutes are exploring approaches to extend and enhance these resources, including collaborations and partnerships with other governmental and non-governmental organizations and groups. (nih.gov)
  • The NIH is also seeking information from individuals, groups, and organizations on best practices to develop and manage a coordinated network and/or centralized Brain Tissue Repository. (nih.gov)
  • During Toxoplasma gondii infection, a fraction of the multiplying parasites, the tachyzoites, converts into bradyzoites, a dormant stage, which form tissue cysts localized mainly in brain, heart, and skeletal muscles that persist for several years after infection. (asm.org)
  • Tissue cysts can persist for several years in the brain, the heart, and the skeletal muscle of individuals who had been previously infected with T. gondii ( 34 , 46 , 49 ). (asm.org)
  • This thesis investigates the use of automated image analysis to quantify peptide analogue distribution in mouse brain tissue. (dtu.dk)
  • The work demonstrates the use of automated image analysis based on image registration to quantify LSFM data of the peptide brain distribution following peripheral administration. (dtu.dk)
  • CollPlant is a regenerative medicine company focused on 3D bioprinting of tissues and organs, medical aesthetics, and on developing and commercializing tissue repair products for orthobiologics, and advanced wound care markets. (medindia.net)
  • Our flagship rhCollagen BioInk product line is ideal for 3D bioprinting of tissues and organs. (medindia.net)
  • The distribution of flavonoids, isoflavonoids, and their conjugates in developing soybean ( Glycine max L.) seedling organs and in root and seed exudates has been examined. (plantphysiol.org)
  • Therefore, in healthy individuals the persistence of T. gondii cysts in tissues and organs does not represent a cause for concern. (asm.org)
  • These results confirm that body composition was altered in RA and AS, affecting distinct soft tissue compartments. (frontiersin.org)
  • Platelets contain growth factors which are responsible for stimulating tissue generation and repair, including soft tissue repair, bone regeneration, development of new blood vessels, and stimulation of the healing process. (medindia.net)
  • CollPlant's unique Vergenix line of rhCollagen products includes a soft tissue repair matrix for treating tendinopathy and a wound repair matrix to promote a rapid optimal healing of acute and chronic wounds. (medindia.net)
  • Compared with men, a greater proportion of total body soft tissue in normal women is fat and obesity is more frequent in women. (bmj.com)
  • In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. (asm.org)
  • We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections. (asm.org)
  • Soft tissue infections are among the most frequent infections worldwide and may lead to serious ( 25 ) and even life-threatening ( 10 , 14 ) complications. (asm.org)
  • Although promising but preliminary clinical data show the high degree of effectiveness of fosfomycin treatment for soft tissue infections ( 27 ), the administration of fosfomycin has still not been established for this condition. (asm.org)
  • Due to its chemical structure, its pharmacokinetic properties, and antibacterial spectrum, however, fosfomycin may qualify as an alternative candidate for the treatment of soft tissue infections. (asm.org)
  • The pattern of EDB distribution in the tissues as determined in this study is completely consistent with earlier studies of the pathologic changes brought about through exposure to this compound. (cdc.gov)
  • The rich presence of Grx2 in these tissues is also consistent with their known sensitivity to oxidative stress. (ovid.com)
  • However, the exact organ distribution is not known. (waters.com)
  • Our products address indications for the diverse fields of organ and tissue repair, and are ushering in a new era in regenerative medicine. (medindia.net)
  • Animal studies suggest that a potential mechanism is that selenium causes the redistribution of methyl mercury from critical organ tissue to muscle. (umsystem.edu)
  • The organ tissue samples were irradiated for 50 hours at a flux of ca. 5 X 1013 n·cm-2·s-1 and allowed to decay for ten or more days. (umsystem.edu)
  • The ratio of selenium to mercury in the nails and organ tissue will be used to verify if the nail is a viable biological marker for selenium and mercury uptake in various organ tissues. (umsystem.edu)
  • Antibodies to all four proteins showed staining of dystrophic neurites and neuropil threads in AD tissue, and residual serum in normal tissue, but only antibodies to clusterin and vitronectin strongly stained amyloid deposits in senile plaques. (nih.gov)
  • Predictive LFER equations for blood/plasma/serum to tissue for a large number of drugs, has been achieved and their predictive capability has been assessed. (bl.uk)
  • The study of such biological interactions usually involves histological methods for tissue collection and staining. (jove.com)
  • Easy accessibility to advanced technologies, government initiatives for screening cancer patients, favourable reimbursement scenario for pathology diagnostic tests, increasing healthcare expenditure, and high-quality infrastructure for hospitals and clinical laboratories in this region are the major factors driving the growth of the tissue diagnostic market in North America. (express-press-release.net)
  • At that time there was great hope that three measurable tissue parameters, T1 and T2 relaxation times and proton density, would provide better specificity than other imaging modalities. (springer.com)
  • While image quality has improved remarkably, results of studies investigating the value of MR tissue parameters have been contradictory. (springer.com)
  • Pedrosa P., Jungke M., Grigat M., Higer H.P., Meindl S., Bielke G. (1990) Differentiation of Gliomas Using Tissue Parameters and a Three-dimensional Density Distribution Model. (springer.com)
  • Intensity histograms and their parameters (peak height, peak location, and 25 th , 50 th and 75 th percentile values) are computed for both T2 and PD images within each tissue region. (spie.org)
  • a disorder of fatty tissue distribution over the thighs, lower legs and hips. (medi.de)
  • If the disorder spreads further down the legs, we talk of the "drawstring trouser phenomenon" because the deformities always end at the ankles, which are, however, overlapped by the fatty tissue. (medi.de)
  • If the fatty pads are immune to every diet and sporting activity, jodhpurs can be a sign of lipoedema, a congenital disorder of fatty tissue distribution. (medi.de)
  • 12 13 Fat has a relatively short T1 relaxation time, so fatty tissue has a higher intensity than other soft tissues in T1 weighted spin echo MRI images. (bmj.com)
  • Methods to accurately evaluate ARV biodistribution within tissues are needed to design effective HIV therapy and eradication strategies. (natap.org)
  • The two most commonly used histological methods for tissue collection and preservation in the clinic and in research laboratories are: formalin fixation followed by paraffin embedding, and tissue freezing, followed by embedding in cryo-protectant media. (jove.com)
  • However, during the paraffin embedding process a number of epitopes become altered and in order to study these epitopes, tissue sections have to be further processed with one of many epitope retrieval methods 13 . (jove.com)
  • As a results, the proposed methods were demonstrated to be accurate, precise and stable for the analysis of the SM-1 in plasma and tissue samples. (medworm.com)
  • In parallel, this requires the development of objective and sensitive methods enhancing the diagnostic algorithm and reliably measuring alterations in affected muscle tissue over time to prove effectiveness and validity of therapeutic interventions. (frontiersin.org)
  • Recruitment of relevant subjects, including methods of outreach and education to encourage tissue donation. (nih.gov)
  • Cathepsin L activity and anti-papain inhibitory effect of cysteine protease inhibitors were quantified in extracts of separated umbilical cord tissues using fluorogenic substrates. (sigmaaldrich.com)
  • Toxoplasma gondii is transmitted to humans by the ingestion of either undercooked meat containing tissue cysts or poorly washed vegetables contaminated with oocysts from cat feces. (asm.org)
  • We would like to gain a better understanding of the mechanisms of cholesterol movement in cells and tissues,' said Jiang, a lecturer from the University of Western Australia's Centre for Microscopy, Characterisation and Analysis. (news-medical.net)
  • Multivariable logistic regression examined the association between BMI categories and tertiles of waist circumference (WC), visceral fat area (VFA), and periprostatic adipose tissue area (PPAT) with high-grade prostate cancer risk (Gleason score ≥7 vs. ≤6). (aacrjournals.org)
  • Although breed-line-sex combination significantly affected fit of the regression for some tissue distribution variables, the values predicted were changed only trivially. (unl.edu)
  • Linear regression analysis was performed for each tissue. (ovid.com)
  • Slope factors for the regression ranged from 0.2 (blood) to 3.8 (Harderian gland) and were correlated with neutral lipid contents in tissues. (ovid.com)