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.Mice, Inbred C57BLHuntington Disease: A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4)Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Probability Theory: The branch of mathematics dealing with the purely logical properties of probability. Its theorems underlie most statistical methods. (Last, A Dictionary of Epidemiology, 2d ed)1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.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.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Genetic Diseases, Inborn: Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Induced Pluripotent Stem Cells: Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Parkinsonian Disorders: A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)Adenoviruses, Porcine: Species of the genus MASTADENOVIRUS, causing neurological disease in pigs.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Mice, Inbred BALB CDrug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Oxidopamine: A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Dopaminergic Neurons: Neurons whose primary neurotransmitter is DOPAMINE.Nervous System Diseases: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.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.Animals, Genetically Modified: ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.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.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Encephalomyelitis, Autoimmune, Experimental: An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5)Epistasis, Genetic: A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.alpha-Synuclein: A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.Ethylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.Communicable DiseasesCytokines: 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.Mice, Inbred DBANerve Degeneration: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.Nerve Tissue ProteinsMutation: 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.Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.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.Arthritis, Experimental: ARTHRITIS that is induced in experimental animals. Immunological methods and infectious agents can be used to develop experimental arthritis models. These methods include injections of stimulators of the immune response, such as an adjuvant (ADJUVANTS, IMMUNOLOGIC) or COLLAGEN.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.Pemphigoid, Bullous: A chronic and relatively benign subepidermal blistering disease usually of the elderly and without histopathologic acantholysis.Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone.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.Disease: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.Mice, 129 Strain: Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations.Models, Statistical: Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Amyloid beta-Peptides: Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.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.Myelin-Oligodendrocyte Glycoprotein: A transmembrane protein present in the MYELIN SHEATH of the CENTRAL NERVOUS SYSTEM. It is one of the main autoantigens implicated in the pathogenesis of MULTIPLE SCLEROSIS.Amyloid beta-Protein Precursor: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.Neostriatum: The phylogenetically newer part of the CORPUS STRIATUM consisting of the CAUDATE NUCLEUS and PUTAMEN. It is often called simply the striatum.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Germ-Free Life: Animals not contaminated by or associated with any foreign organisms.Rats, Inbred LewGenetic 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.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.Spleen: An encapsulated lymphatic organ through which venous blood filters.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.High-Throughput Screening Assays: Rapid methods of measuring the effects of an agent in a biological or chemical assay. The assay usually involves some form of automation or a way to conduct multiple assays at the same time using sample arrays.Parkinson Disease, Secondary: Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42)Transgenes: Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.Rotenone: A botanical insecticide that is an inhibitor of mitochondrial electron transport.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.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.Drugs, Chinese Herbal: Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China.Zebrafish: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Models, Animal: Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Glomerulonephritis: Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.Embryonic Stem Cells: Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.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.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 NOD: A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.Substantia Nigra: The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis.Maze Learning: Learning the correct route through a maze to obtain reinforcement. It is used for human or animal populations. (Thesaurus of Psychological Index Terms, 6th ed)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.Diagnostic Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.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.)Presenilin-1: Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.Immunization: Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.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)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.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.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.Injections, Intraperitoneal: Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.Immunoglobulin G: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Real-Time Polymerase Chain Reaction: Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.Trinucleotide Repeat Expansion: An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.Genetic Therapy: Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.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.Multiple Sclerosis: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)Myelin Basic Protein: An abundant cytosolic protein that plays a critical role in the structure of multilamellar myelin. Myelin basic protein binds to the cytosolic sides of myelin cell membranes and causes a tight adhesion between opposing cell membranes.Behavior, Animal: The observable response an animal makes to any situation.Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue.Sample Size: The number of units (persons, animals, patients, specified circumstances, etc.) in a population to be studied. The sample size should be big enough to have a high likelihood of detecting a true difference between two groups. (From Wassertheil-Smoller, Biostatistics and Epidemiology, 1990, p95)CD4-Positive T-Lymphocytes: A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.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.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).Interleukin-17: A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.Th1 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.Amyotrophic Lateral Sclerosis: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94)Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.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.Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.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.Drug Design: The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Immunity, Innate: The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.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.Genome-Wide Association Study: An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.T-Lymphocyte Subsets: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.Stem Cell Transplantation: The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.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.ArthritisAmino 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.Caenorhabditis elegans: A species of nematode that is widely used in biological, biochemical, and genetic studies.Animals, Newborn: Refers to animals in the period of time just after birth.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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Pluripotent Stem Cells: Cells that can give rise to cells of the three different GERM LAYERS.Dependovirus: A genus of the family PARVOVIRIDAE, subfamily PARVOVIRINAE, which are dependent on a coinfection with helper adenoviruses or herpesviruses for their efficient replication. The type species is Adeno-associated virus 2.Models, Theoretical: Theoretical representations that simulate the behavior or activity of systems, processes, or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Data Interpretation, Statistical: Application of statistical procedures to analyze specific observed or assumed facts from a particular study.Phytotherapy: Use of plants or herbs to treat diseases or to alleviate pain.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Mitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Gene Transfer Techniques: The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms.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.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Permeability: Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.Cell Count: The number of CELLS of a specific kind, usually measured per unit volume or area of sample.Inflammation Mediators: The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.Cell Culture Techniques: Methods for maintaining or growing CELLS in vitro.Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.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.Th2 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.Bayes Theorem: A theorem in probability theory named for Thomas Bayes (1702-1761). In epidemiology, it is used to obtain the probability of disease in a group of people with some characteristic on the basis of the overall rate of that disease and of the likelihood of that characteristic in healthy and diseased individuals. The most familiar application is in clinical decision analysis where it is used for estimating the probability of a particular diagnosis given the appearance of some symptoms or test result.CD8-Positive T-Lymphocytes: A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.Lung Diseases: Pathological processes involving any part of the LUNG.Mice, Inbred C3HAmides: Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed)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.Microarray Analysis: The simultaneous analysis, on a microchip, of multiple samples or targets arranged in an array format.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).tau Proteins: Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).Staining and Labeling: The marking of biological material with a dye or other reagent for the purpose of identifying and quantitating components of tissues, cells or their extracts.Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Ubiquitin: A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.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.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.Proteinuria: The presence of proteins in the urine, an indicator of KIDNEY DISEASES.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.

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In the present study, we evaluated the efficacy of TRC210258, a novel TGR5 agonist, in clinically relevant animal models of ... Patients with diabesity have a significantly increased risk of developing cardiovascular disease. Therefore, therapy addressing ... reduces glycemic and dyslipidemic cardiovascular risk in animal models of diabesity Shitalkumar Zambad, Davinder Tuli, Anoop ... TRC210258, a novel TGR5 agonist, reduces glycemic and dyslipidemic cardiovascular risk in animal models of diabesity. ...
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Furthermore, this method applies to animal disease models. These results will provide valuable information regarding oxidative ... of fluorescent and mass spectrometry multi-probe for lipid derived radicals and application to animal disease models. ... of fluorescent and mass spectrometry multi-probe for lipid derived radicals and application to animal disease models ... Metabolic products of lipid peroxides have been reported to involve in the pathogenesis of various diseases. However, lipid ...
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... allowing them to study the biology of the disease and test potential treatments. ... Animal models are used by scientists to replicate human diseases in another living animal, ... Animal models are used by scientists to replicate human diseases in another living animal, allowing them to study the biology ... A new opossum model has been developed to mimic nonalcoholic steatohepatitis, which resembles alcoholic liver disease but ...
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Gross pathology: Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of surgical specimen processing or an autopsy.HuntingtonCentre for Research in Neurodegenerative DiseasesCatalog of articles in probability theory: This page lists articles related to probability theory. In particular, it lists many articles corresponding to specific probability distributions.Neuroprotection: Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation.Hereditary Disease Foundation: The Hereditary Disease Foundation (HDF) aims to cure genetic disorders by supporting basic biomedical research.Causes of Parkinson's disease: Parkinson's disease (PD) is a degenerative disorder of the central nervous system. Most people with PD have idiopathic Parkinson's disease (having no specific known cause).Stemgent: Stemgent is an American privately funded biotech company focused on providing reagents and technology developed by some of the world's leading stem cell scientists. Founded in 2008, Stemgent has two fully operational facilities in both San Diego, California and Cambridge, Massachusetts.Alzheimer's Disease Neuroimaging Initiative: Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a worldwide project that provides reliable clinical data for the research of pathology principle, prevention and treatment of Alzheimer’s disease (AD). Multiple research groups contribute their findings of the biological markers to the understanding of the progression of Alzheimer’s disease in the human brain.Porcine adenovirus: Porcine adenovirus (aka pADV 1-5 or pADV A-C) is a member of the adenoviridae family. It causes gastrointestinal disease in young pigs and is thought to contribute to multifactorial porcine respiratory diseases complexes.HSD2 neurons: HSD2 neurons are a small group of neurons in the brainstem which are uniquely sensitive to the mineralocorticosteroid hormone aldosterone, through expression of HSD11B2. They are located within the caudal medulla oblongata, in the nucleus of the solitary tract (NTS).Matrix model: == Mathematics and physics ==Phenotype microarray: The phenotype microarray approach is a technology for high-throughput phenotyping of cells.Interval boundary element method: Interval boundary element method is classical boundary element method with the interval parameters.
Autoimmune diseaseInflammation: Inflammation (Latin, [is part of the complex biological response of body tissues to harmful stimuli, such as pathogen]s, damaged cells, or irritants.CCL20: Chemokine (C-C motif) ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly attracts neutrophils.Alpha-synuclein: Alpha-synuclein is a protein that is abundant in the human brain. Smaller amounts are found in the heart, muscles, and other tissues.Forward genetics: Forward genetics is the approach of determining the genetic basis responsible for a phenotype. This was initially done by generating mutants by using radiation, chemicals, or insertional mutagenesis (e.Global Infectious Disease Epidemiology Network: Global Infectious Diseases Epidemiology Network (GIDEON) is a web-based program for decision support and informatics in the fields of Infectious Diseases and Geographic Medicine. As of 2005, more than 300 generic infectious diseases occur haphazardly in time and space and are challenged by over 250 drugs and vaccines.Proinflammatory cytokine: A proinflammatory cytokine is a cytokine which promotes systemic inflammation.Silent mutation: Silent mutations are mutations in DNA that do not significantly alter the phenotype of the organism in which they occur. Silent mutations can occur in non-coding regions (outside of genes or within introns), or they may occur within exons.Chromosome regionsDopamine receptorList of target antigens in pemphigoid: Circulating auto-antibodies in the human body can target normal parts of the skin leading to disease. This is a list of antigens in the skin that may become targets of circulating auto-antibodies leading to the various types of pemphigoid.Disequilibrium (medicine): Disequilibrium}}DBASS3/5Inverse probability weighting: Inverse probability weighting is a statistical technique for calculating statistics standardized to a population different from that in which the data was collected. Study designs with a disparate sampling population and population of target inference (target population) are common in application.Genetic linkage: Genetic linkage is the tendency of alleles that are located close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Genes whose loci are nearer to each other are less likely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be genetically linked.Senile plaquesMyelin oligodendrocyte glycoprotein: Myelin Oligodendrocyte Glycoprotein (MOG) is a glycoprotein believed to be important in the myelination of nerves in the central nervous system (CNS). In humans this protein is encoded by the MOG gene.Amyloid precursor proteinWGAViewer: WGAViewer is a bioinformatics software tool which is designed to visualize, annotate, and help interpret the results generated from a genome wide association study (GWAS). Alongside the P values of association, WGAViewer allows a researcher to visualize and consider other supporting evidence, such as the genomic context of the SNP, linkage disequilibrium (LD) with ungenotyped SNPs, gene expression database, and the evidence from other GWAS projects, when determining the potential importance of an individual SNP.Multiple cloning site: A multiple cloning site (MCS), also called a polylinker, is a short segment of DNA which contains many (up to ~20) restriction sites - a standard feature of engineered plasmids. Restriction sites within an MCS are typically unique, occurring only once within a given plasmid.Periarteriolar lymphoid sheaths: Periarteriolar lymphoid sheaths (or periarterial lymphatic sheaths, or PALS) are a portion of the white pulp of the spleen. They are populated largely by T cells and surround central arteries within the spleen; the PALS T-cells are presented with blood borne antigens via myeloid dendritic cells.High throughput biologyRotenoneTumor progression: Tumor progression is the third and last phase in tumor development. This phase is characterised by increased growth speed and invasiveness of the tumor cells.Frontostriatal circuit: Frontostriatal circuits are neural pathways that connect frontal lobe regions with the basal ganglia (striatum) that mediate motor, cognitive, and behavioural functions within the brain. They receive inputs from dopaminergic, serotonergic, noradrenergic, and cholinergic cell groups that modulate information processing.Gene signature: A gene signature is a group of genes in a cell whose combined expression patternItadani H, Mizuarai S, Kotani H. Can systems biology understand pathway activation?Mingmu Dihuang Wan: Mingmu Dihuang Pills () is a blackish-brown pill used in Traditional Chinese medicine to "nourish yin of the liver and the kidney, and to improve eyesight". State Pharmacopoeia Commission of the PRC (2005).Morphant: An organism which has been treated with a morpholino antisense oligo to temporarily knock down expression of a targeted gene is called a morphant.Protective autoimmunity: Protective autoimmunity is a condition in which cells of the adaptive immune system contribute to maintenance of the functional integrity of a tissue, or facilitate its repair following an insult. The term ‘protective autoimmunity’ was coined by Prof.GlomerulonephritisHuman embryonic stem cells clinical trials: ==Human Embryonic Stem Cell Clinical Trials==Coles PhillipsPMHC cellular microarray: PMHC cellular microarrays are a type of cellular microarray that has been spotted with pMHC complexes peptide-MHC class I or peptide-MHC class II.Rolf Hassler: Rolf Hassler (1914-1984) was a German pathologist who made important discoveries on the pathophisiology and treatment of Parkinson's disease (PD).Learning Plan: A Learning Plan is a document (possibly an interactive or on-line document) that is used to plan learning, usually over an extended period of time.Autoantibody: An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases, (notably lupus erythematosus), are caused by such autoantibodies.Nephtheis fascicularisTemporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingIndy (gene): Indy, short for I'm not dead yet, is a gene of the model organism, the fruit fly Drosophila melanogaster. Mutant versions of this gene have doubled the average life span of fruit flies in at least one set of experiments, but this result has been subject to controversy.Tingible body macrophage: A tingible body macrophage is a type of macrophage predominantly found in germinal centers, containing many phagocytized, apoptotic cells in various states of degradation, referred to as tingible bodies (tingible meaning stainable).Horst Ibelgaufts' COPE: Cytokines & Cells Online Pathfinder Encyclopaedia > tingible body macrophages Retrieved on June 27, 2010 Tingible body macrophages contain condensed chromatin fragments.PresenilinImmunization

(1/64177) New perspectives on biliary atresia.

An investigation into the aetiology, diagnosis, and treatment of biliary atresia was carried out because the prognosis remains so poor.In an electron microscopical study no viral particles or viral inclusion bodies were seen, nor were any specific ultrastructural features observed. An animal experiment suggested that obstruction within the biliary tract of newborn rabbits could be produced by maternal intravenous injection of the bile acid lithocholic acid.A simple and atraumatic method of diagnosis was developed using(99) (m)Tc-labelled compounds which are excreted into bile. Two compounds, (99m)Tc-pyridoxylidene glutamate ((99m)Tc-PG) and (99m)Tc-dihydrothioctic acid ((99m)Tc-DHT) were first assessed in normal piglets and piglets with complete biliary obstruction. Intestinal imaging correlated with biliary tract patency, and the same correlation was found in jaundiced human adults, in whom the (99m)Tc-PG scan correctly determined biliary patency in 21 out of 24 cases. The (99m)Tc-PG scan compared well with liver biopsy and (131)I-Rose Bengal in the diagnosis of 11 infants with prolonged jaundice.A model of extrahepatic biliary atresia was developed in the newborn piglet so that different methods of bile drainage could be assessed. Priorities in biliary atresia lie in a better understanding of the aetiology and early diagnosis rather than in devising new bile drainage procedures.  (+info)

(2/64177) The evolution of early fibromuscular lesions hemodynamically induced in the dog renal artery. I. Light and transmission electron microscopy.

In view of the important roles of arterial intimal fibromuscular lesions as precursors of atherosclerotic plaque and occlusive lesions in arterial reconstructions, a model has been developed for the rapid hemodynamic induction of these lesions by anastomosis of the dog right renal artery to the inferior vena cava. Light and transmission electron microscopic observations were made on the arterial shunt after periods of rapid flow ranging form 10 minutes to 2 hours to identify initial factor(s) and evolutionary mechanisms in the etiology of the lesions. The sequence of events included aberrations in ruthenium red staining of the endothelial luminal membrane at 10 minutes, multilayered thickening of the subendothelial basement membrane (BM) at 15 minutes, and initial reorientation and migration of smooth muscle cells (SMC) into the intima along with the appearance of areas of degeneration of the internal elastic lamina (IEL) at 30 minutes. The endothelial cells were still intact in some areas overlying the SMC migration and IEL degeneration, but they were separating from the surface in other such areas. As subendothelium became exposed, some platelet adherence was noted. By 2 hours, the entire wall reaction was fully developed. Initial observations indicate that in the evolution of this hemodynamically induced lesion visible alteration in the endothelial cells is not prerequisite to degeneration of the underlying IEL and reorientation and migration of medial SMC.  (+info)

(3/64177) Site of myocardial infarction. A determinant of the cardiovascular changes induced in the cat by coronary occlusion.

The influence of site of acute myocardial infarction on heart rate, blood pressure, cardiac output, total peripheral resistance (TPR), cardiac rhythm, and mortality was determined in 58 anesthetized cats by occlusion of either the left anterior descending (LAD), left circumflex or right coronary artery. LAD occlusion resulted in immediate decrease in cardiac output, heart rate, and blood pressure, an increase in TPR, and cardiac rhythm changes including premature ventricular beats, ventricular tachycardia, and occasionally ventricular fibrillation. The decrease in cardiac output and increase in TPR persisted in the cats surviving a ventricular arrhythmia. In contrast, right coronary occlusion resulted in a considerably smaller decrease in cardiac output. TPR did not increase, atrioventricular condition disturbances were common, and sinus bradycardia and hypotension persisted in the cats recovering from an arrhythmia. Left circumflex ligation resulted in cardiovascular changes intermediate between those produced by occlusion of the LAD or the right coronary artery. Mortality was similar in each of the three groups. We studied the coronary artery anatomy in 12 cats. In 10, the blood supply to the sinus node was from the right coronary artery and in 2, from the left circumflex coronary artery. The atrioventricular node artery arose from the right in 9 cats, and from the left circumflex in 3. The right coronary artery was dominant in 9 cats and the left in 3. In conclusion, the site of experimental coronary occlusion in cats is a major determinant of the hemodynamic and cardiac rhythm changes occurring after acute myocardial infarction. The cardiovascular responses evoked by ligation are related in part to the anatomical distribution of the occluded artery.  (+info)

(4/64177) Hierarchy of ventricular pacemakers.

To characterize the pattern of pacemaker dominance in the ventricular specialized conduction system (VSCS), escape ventricular pacemakers were localized and quantified in vivo and in virto, in normal hearts and in hearts 24 hours after myocardial infarction. Excape pacemaker foci were localized in vivo during vagally induced atrial arrest by means of electrograms recorded from the His bundle and proximal bundle branches and standard electrocardiographic limb leads. The VSCS was isolated using a modified Elizari preparation or preparations of each bundle branch. Peacemakers were located by extra- and intracellular recordings. Escape pacemaker foci in vivo were always in the proximal conduction system, usually the left bundle branch. The rate was 43+/-11 (mean+/-SD) beats/min. After beta-adrenergic blockade, the mean rate fell to 31+/-10 beats/min, but there were no shifts in pacemaker location. In the infarcted hearts, pacemakers were located in the peripheral left bundle branch. The mean rate was 146+/-20 beats/min. In isolated normal preparations, the dominant pacemakers usually were in the His bundle, firing at a mean rate of 43+/-10 beats/min. The rates of pacemakers diminished with distal progression. In infarcted hearts, the pacemakers invariably were in the infarct zone. The mean firing rates were not influenced by beta-adrenergic blockade. The results indicate that the dominant pacemakers are normally in the very proximal VSCS, but after myocardial infarction pacemaker dominance is shifted into the infarct. Distribution of pacemaker dominance is independent of sympathetic influence.  (+info)

(5/64177) A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder.

Inherited defects in the degradation of glycosphingolipids (GSLs) cause a group of severe diseases known as GSL storage disorders. There are currently no effective treatments for the majority of these disorders. We have explored a new treatment paradigm, substrate deprivation therapy, by constructing a genetic model in mice. Sandhoff's disease mice, which abnormally accumulate GSLs, were bred with mice that were blocked in their synthesis of GSLs. The mice with simultaneous defects in GSL synthesis and degradation no longer accumulated GSLs, had improved neurologic function, and had a much longer life span. However, these mice eventually developed a late-onset neurologic disease because of accumulation of another class of substrate, oligosaccharides. The results support the validity of the substrate deprivation therapy and also highlight some limitations.  (+info)

(6/64177) DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model.

Myotonic dystrophy (DM) is the most common form of muscular dystrophy and is caused by expansion of a CTG trinucleotide repeat on human chromosome 19. Patients with DM develop atrioventricular conduction disturbances, the principal cardiac manifestation of this disease. The etiology of the pathophysiological changes observed in DM has yet to be resolved. Haploinsufficiency of myotonic dystrophy protein kinase (DMPK), DM locus-associated homeodomain protein (DMAHP) and/or titration of RNA-binding proteins by expanded CUG sequences have been hypothesized to underlie the multi-system defects observed in DM. Using an in vivo murine electrophysiology study, we show that cardiac conduction is exquisitely sensitive to DMPK gene dosage. DMPK-/- mice develop cardiac conduction defects which include first-, second-, and third-degree atrioventricular (A-V) block. Our results demonstrate that the A-V node and the His-Purkinje regions of the conduction system are specifically compromised by DMPK loss. Importantly, DMPK+/- mice develop first-degree heart block, a conduction defect strikingly similar to that observed in DM patients. These results demonstrate that DMPK dosage is a critical element modulating cardiac conduction integrity and conclusively link haploinsufficiency of DMPK with cardiac disease in myotonic dystrophy.  (+info)

(7/64177) Alternative sulfonylurea receptor expression defines metabolic sensitivity of K-ATP channels in dopaminergic midbrain neurons.

ATP-sensitive potassium (K-ATP) channels couple the metabolic state to cellular excitability in various tissues. Several isoforms of the K-ATP channel subunits, the sulfonylurea receptor (SUR) and inwardly rectifying K channel (Kir6.X), have been cloned, but the molecular composition and functional diversity of native neuronal K-ATP channels remain unresolved. We combined functional analysis of K-ATP channels with expression profiling of K-ATP subunits at the level of single substantia nigra (SN) neurons in mouse brain slices using an RT-multiplex PCR protocol. In contrast to GABAergic neurons, single dopaminergic SN neurons displayed alternative co-expression of either SUR1, SUR2B or both SUR isoforms with Kir6.2. Dopaminergic SN neurons expressed alternative K-ATP channel species distinguished by significant differences in sulfonylurea affinity and metabolic sensitivity. In single dopaminergic SN neurons, co-expression of SUR1 + Kir6.2, but not of SUR2B + Kir6.2, correlated with functional K-ATP channels highly sensitive to metabolic inhibition. In contrast to wild-type, surviving dopaminergic SN neurons of homozygous weaver mouse exclusively expressed SUR1 + Kir6.2 during the active period of dopaminergic neurodegeneration. Therefore, alternative expression of K-ATP channel subunits defines the differential response to metabolic stress and constitutes a novel candidate mechanism for the differential vulnerability of dopaminergic neurons in response to respiratory chain dysfunction in Parkinson's disease.  (+info)

(8/64177) DEF-1, a novel Src SH3 binding protein that promotes adipogenesis in fibroblastic cell lines.

The Src homology 3 (SH3) motif is found in numerous signal transduction proteins involved in cellular growth and differentiation. We have purified and cloned a novel protein, DEF-1 (differentiation-enhancing factor), from bovine brain by using a Src SH3 affinity column. Ectopic expression of DEF-1 in fibroblasts resulted in the differentiation of a significant fraction of the culture into adipocytes. This phenotype appears to be related to the induction of the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma), since DEF-1 NIH 3T3 cells demonstrated augmented levels of PPARgamma mRNA and, when treated with activating PPARgamma ligands, efficient induction of differentiation. Further evidence for a role for DEF-1 in adipogenesis was provided by heightened expression of DEF-1 mRNA in adipose tissue isolated from obese and diabetes mice compared to that in tissue isolated from wild-type mice. However, DEF-1 mRNA was detected in multiple tissues, suggesting that the signal transduction pathway(s) in which DEF-1 is involved is not limited to adipogenesis. These results suggest that DEF-1 is an important component of a signal transduction process that is involved in the differentiation of fibroblasts and possibly of other types of cells.  (+info)

  • transgenic
  • Furthermore, oral administration of CEppt to an aggressive AD transgenic mice model led to marked decrease in 56 kDa Aβ oligomers, reduction of plaques and improvement in cognitive behavior. (pubfacts.com)
  • We orally administered the flavonoid tannic acid (TA) to the transgenic PSAPP mouse model of cerebral amyloidosis (bearing mutant human APP and presenilin-1 transgenes) and evaluated cognitive function and AD-like pathology. (pubfacts.com)
  • In the current study, we examined the effects of L-NBP on learning and memory in a triple-transgenic AD mouse model (3xTg-AD) that develops both plaques and tangles with aging, as well as cognitive deficits. (pubfacts.com)
  • Transgenic animal production consists of injecting each construct into 300-350 eggs, typically representing three days' work. (wikipedia.org)
  • The number of transgenic animals typically varies from two to eight. (wikipedia.org)
  • multiple sclerosis
  • This review aims to provide an update on the most recent evidence of therapeutically-relevant neuro-immuneinteractions following NPC transplants in animal models of multiple sclerosis, cerebral stroke and traumas of the spinal cord, and consideration of the forthcoming challenges related to the early translation of some of these exciting experimental outcomes into clinical medicines. (wingsforlife.com)
  • mice
  • Whereas mice and rats are often not susceptible to human pathogens, replicate them at low levels or require rodent-adapted pathogen strains, the cotton rat has proven susceptible to a wide variety of human pathogens and to be a model system to simulate a number of important parameters of human disease. (osu.edu)
  • Specifically, 56 kDa oligomeric species were shown to be correlated with impaired cognitive function in AD model mice. (pubfacts.com)
  • More recently a dodecameric form of Aβ with a 56 kDa molecular weight, denoted Aβ*56, was shown to cause memory impairment in AD model mice. (pubfacts.com)
  • Fleming operates its own Animal House, which can house up to 20,000 mice and has its own complete mouse histopathology unit. (wikipedia.org)
  • The Animal House has a capacity to house more than 20,000 mice and is currently the largest Mouse Unit in Greece in terms of number and variety of mice. (wikipedia.org)
  • This close relationship, the associated high homology with humans, their ease of maintenance and handling, and their high reproduction rate, make mice particularly suitable models for human-oriented research. (wikipedia.org)
  • In 1902 Lucien Cuénot published the results of his experiments using mice which showed that Mendel's laws of inheritance were also valid for animals - results that were soon confirmed and extended to other species. (wikipedia.org)
  • Rodents are commonly used in animal testing, particularly mice and rats, but also guinea pigs, hamsters, gerbils and others. (wikipedia.org)
  • While mice, rats and other rodents are by far the most widely used animals in biomedical research, recent studies have highlighted their limitations. (wikipedia.org)
  • Regarding experiments on mice in particular, some researchers have complained that "years and billions of dollars have been wasted following false leads" as a result of a preoccupation with the use of these animals in studies. (wikipedia.org)
  • Many laboratory animals, including mice and rats, are chronically stressed which can also negatively affect research outcomes and the ability to accurately extrapolate findings to humans. (wikipedia.org)
  • research
  • We cover all aspects of animal research with snapshots of biomedical advances from scientific journals, staff blogs and video links. (understandinganimalresearch.org.uk)
  • CAMARADES is currently leading the way in advancing education about systematic reviews in animal research. (wikipedia.org)
  • Prof. Macleod is on the Methodology Advisory Board of the charity SABRE Research UK which raises awareness of the need for systematic reviews of existing animal studies. (wikipedia.org)
  • Fleming's Animal house (certified with ISO 9001) provides husbandry of animals and services to the biomedical research community since 2001. (wikipedia.org)
  • Further research by Goddard on the characteristics of the kindling phenomenon led to his conclusion that kindling can be used to model human epileptogenesis, learning and memory. (wikipedia.org)
  • The publication of these results opened a completely new niche for epilepsy research and has stimulated a significant amount of studies on the subject of kindling and its relevance to human epilepsy Kindling (sedative-hypnotic withdrawal) Epileptogenesis Racine Stages (a method by which seizure severity is quantified in animal models of epilepsy) Bertram E (2007). (wikipedia.org)
  • Some of the most publicized attacks on animal research facilities by animal rights groups have occurred because of primate research. (wikipedia.org)
  • Diabetes & Vascular Disease Research. (wikipedia.org)
  • They are the most commonly used mammalian research model and are used for research in genetics, psychology, medicine and other scientific disciplines. (wikipedia.org)
  • In 2006-07, Syrian hamsters accounted for 19% of the total animal research participants in the United States. (wikipedia.org)
  • Altogen Labs maintains a GLP-compliant laboratory performing preclinical research and biotechnology studies, pharmacology and toxicology assays, and in vivo experiments including: cancer xenograft models, pharmacokinetics, pharmacodynamics, and toxicology testing. (wikipedia.org)
  • Robert J. Desnick, Ph.D., M.D., (born July 12, 1943) is a human geneticist whose basic and translational research accomplishments include significant discoveries in genomics, pharmacogenetics, gene therapy, personalized medicine, and the treatment of genetic diseases. (wikipedia.org)
  • His translational research has led to the development of enzyme replacement therapy for Fabry disease and Niemann-Pick disease Type B (in "breakthrough" clinical trials). (wikipedia.org)
  • viral
  • To date, viral PD models comprise α-synuclein and LRRK-2-based overexpression models, as well as models that mimic parkin loss of function by overexpression of the parkin substrates Pael-R, CDCrel-1, p38/JTV or synphilin-1. (epfl.ch)
  • The following animal models of viral infections have either been established or are under development at the BRL. (gmu.edu)
  • human
  • Neuro-immune interactions of neural stem cell transplants: from animal disease models to human trials. (wingsforlife.com)
  • Stem cell technology is a promising branch of regenerative medicine that is aimed at developing new approaches for the treatment of severely debilitating human diseases, including those affecting the central nervous system (CNS). (wingsforlife.com)
  • Animal models are used by scientists to replicate human diseases in another living animal, allowing them to study the biology of the disease and test potential treatments. (understandinganimalresearch.org.uk)
  • This was shown in human Muse cells infused into animal models with fulminant hepatitis, partial hepatectomy, muscle degeneration, skin injury, stroke and spinal cord injury. (wikipedia.org)
  • Although kindling is a widely used model, its applicability to human epilepsy is controversial. (wikipedia.org)
  • However, in both human epilepsy and in some animal models, evidence suggests that a process like that found in kindling does occur. (wikipedia.org)
  • The directive stresses the use of the 3R principle (replacement, refinement, reduction) and animal welfare when conducting animal testing on non-human primates. (wikipedia.org)
  • treatments
  • Further understanding of the pathogenicity of autoreactive CD4 + T cells may lead to disease-specific treatments. (wiley.com)
  • brains
  • Amyloid precursor protein (APP) proteolysis is essential for production of amyloid-β (Aβ) peptides that form β-amyloid plaques in brains of Alzheimer disease (AD) patients. (pubfacts.com)
  • commonly
  • Kindling is a commonly used model for the development of seizures and epilepsy in which the duration and behavioral involvement of induced seizures increases after seizures are induced repeatedly. (wikipedia.org)
  • Discoveries
  • The mouse has since been used extensively as a model organism and is associated with many important biological discoveries of the 20th and 21st Centuries. (wikipedia.org)
  • Strain
  • Commercial suppliers for this inbred strain are in the USA Harlan Inc., Ace Animals and Virion Systems, and in Europe Charles River. (osu.edu)
  • nervous
  • It induces hepatotoxicity and Zamia staggers, a fatal nervous disease affecting cattle resulting from browsing on the leaves or fruit of cycads. (wikipedia.org)
  • researchers
  • The Boyd Group, a British group comprising animal researchers, philosophers, primatologists, and animal advocates, has recommended a global prohibition on the use of great apes. (wikipedia.org)
  • Species
  • When administered to an AD fly model, CEppt rectified their reduced longevity, fully recovered their locomotion defects and totally abolished tetrameric species of Aβ in their brain. (pubfacts.com)
  • One of the uses of this ontology is to integrate data from different biological databases, and other species-specific ontologies such as the Foundational Model of Anatomy. (wikipedia.org)
  • occurs
  • The Lytico-bodig disease, also known as lateral sclerosis-parkinsonism-dementia, is a neurodegenerative disease of unknown origin that occurs exclusively in the Chamorro people of the island of Guam that has characteristics of both amyotrophic lateral sclerosis (ALS) and parkinsonism. (wikipedia.org)
  • structures
  • Uberon is a comparative anatomy ontology representing a variety of structures found in animals, such as lungs, muscles, bones, feathers and fins. (wikipedia.org)
  • Center
  • The Disease BioPortal is operated and maintained by the Center for Animal Disease Modeling and Surveillance (CADMS) at the University of California, Davis and is supported through a consortium of national and international institutions, agencies, and organizations. (ucdavis.edu)
  • Experiments
  • In December 2005, Austria outlawed experiments on any apes, unless it is conducted in the interests of the individual animal. (wikipedia.org)