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.Complement Pathway, Alternative: Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Animal Testing Alternatives: Procedures, such as TISSUE CULTURE TECHNIQUES; mathematical models; etc., when used or advocated for use in place of the use of animals in research or diagnostic laboratories.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.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.Complementary Therapies: Therapeutic practices which are not currently considered an integral part of conventional allopathic medical practice. They may lack biomedical explanations but as they become better researched some (PHYSICAL THERAPY MODALITIES; DIET; ACUPUNCTURE) become widely accepted whereas others (humors, radium therapy) quietly fade away, yet are important historical footnotes. Therapies are termed as Complementary when used in addition to conventional treatments and as Alternative when used instead of conventional treatment.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.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.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.RNA Splice Sites: Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICEOSOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.RNA Splicing: The ultimate exclusion of nonsense sequences or intervening sequences (introns) before the final RNA transcript is sent to the cytoplasm.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 Precursors: RNA transcripts of the DNA that are in some unfinished stage of post-transcriptional processing (RNA PROCESSING, POST-TRANSCRIPTIONAL) required for function. RNA precursors may undergo several steps of RNA SPLICING during which the phosphodiester bonds at exon-intron boundaries are cleaved and the introns are excised. Consequently a new bond is formed between the ends of the exons. Resulting mature RNAs can then be used; for example, mature mRNA (RNA, MESSENGER) is used as a template for protein production.Complement Factor B: A glycine-rich, heat-labile serum glycoprotein that contains a component of the C3 CONVERTASE ALTERNATE PATHWAY (C3bBb). Bb, a serine protease, is generated when factor B is cleaved by COMPLEMENT FACTOR D into Ba and Bb.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Complement Activation: The sequential activation of serum COMPLEMENT PROTEINS to create the COMPLEMENT MEMBRANE ATTACK COMPLEX. Factors initiating complement activation include ANTIGEN-ANTIBODY COMPLEXES, microbial ANTIGENS, or cell surface POLYSACCHARIDES.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.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.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Time Factors: Elements of limited time intervals, contributing to particular results or situations.RNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.Cell Line: Established cell cultures that have the potential to propagate indefinitely.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.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.Complement C3: A glycoprotein that is central in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C3 can be cleaved into COMPLEMENT C3A and COMPLEMENT C3B, spontaneously at low level or by C3 CONVERTASE at high level. The smaller fragment C3a is an ANAPHYLATOXIN and mediator of local inflammatory process. The larger fragment C3b binds with C3 convertase to form C5 convertase.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.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.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.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.Polyadenylation: The addition of a tail of polyadenylic acid (POLY A) to the 3' end of mRNA (RNA, MESSENGER). Polyadenylation involves recognizing the processing site signal, (AAUAAA), and cleaving of the mRNA to create a 3' OH terminal end to which poly A polymerase (POLYNUCLEOTIDE ADENYLYLTRANSFERASE) adds 60-200 adenylate residues. The 3' end processing of some messenger RNAs, such as histone mRNA, is carried out by a different process that does not include the addition of poly A as described here.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.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.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.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)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.Complement C3 Convertase, Alternative Pathway: A serine protease that is the complex of COMPLEMENT C3B and COMPLEMENT FACTOR BB. It cleaves multiple COMPLEMENT C3 into COMPLEMENT C3A (anaphylatoxin) and COMPLEMENT C3B in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY.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.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).Complement Pathway, Classical: Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)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.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Properdin: A 53-kDa protein that is a positive regulator of the alternate pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It stabilizes the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb) and protects it from rapid inactivation, thus facilitating the cascade of COMPLEMENT ACTIVATION and the formation of MEMBRANE ATTACK COMPLEX. Individuals with mutation in the PFC gene exhibit properdin deficiency and have a high susceptibility to infections.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.RNA Isoforms: The different gene transcripts generated from a single gene by RNA EDITING or ALTERNATIVE SPLICING of RNA PRECURSORS.Complement Factor D: A serum protein which is important in the ALTERNATIVE COMPLEMENT ACTIVATION PATHWAY. This enzyme cleaves the COMPLEMENT C3B-bound COMPLEMENT FACTOR B to form C3bBb which is ALTERNATIVE PATHWAY C3 CONVERTASE.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.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.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another 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.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Complement C3-C5 Convertases: Serine proteases that cleave COMPLEMENT C3 into COMPLEMENT C3A and COMPLEMENT C3B, or cleave COMPLEMENT C5 into COMPLEMENT C5A and COMPLEMENT C5B. These include the different forms of C3/C5 convertases in the classical and the alternative pathways of COMPLEMENT ACTIVATION. Both cleavages take place at the C-terminal of an ARGININE residue.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.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.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Choice Behavior: The act of making a selection among two or more alternatives, usually after a period of deliberation.Genetic Variation: Genotypic differences observed among individuals in a population.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Expressed Sequence Tags: Partial cDNA (DNA, COMPLEMENTARY) sequences that are unique to the cDNAs from which they were derived.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.Kinetics: The rate dynamics in chemical or physical systems.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.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.Complement C3b: The larger fragment generated from the cleavage of COMPLEMENT C3 by C3 CONVERTASE. It is a constituent of the ALTERNATIVE PATHWAY C3 CONVERTASE (C3bBb), and COMPLEMENT C5 CONVERTASES in both the classical (C4b2a3b) and the alternative (C3bBb3b) pathway. C3b participates in IMMUNE ADHERENCE REACTION and enhances PHAGOCYTOSIS. It can be inactivated (iC3b) or cleaved by various proteases to yield fragments such as COMPLEMENT C3C; COMPLEMENT C3D; C3e; C3f; and C3g.Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.Bacterial Proteins: Proteins found in any species of bacterium.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)Cost-Benefit Analysis: A method of comparing the cost of a program with its expected benefits in dollars (or other currency). The benefit-to-cost ratio is a measure of total return expected per unit of money spent. This analysis generally excludes consideration of factors that are not measured ultimately in economic terms. Cost effectiveness compares alternative ways to achieve a specific set of results.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.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Cell Line, Tumor: A cell line derived from cultured tumor cells.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Sequence Analysis, RNA: A multistage process that includes cloning, physical mapping, subcloning, sequencing, and information analysis of an RNA SEQUENCE.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.Heterogeneous-Nuclear Ribonucleoproteins: A family of ribonucleoproteins that were originally found as proteins bound to nascent RNA transcripts in the form of ribonucleoprotein particles. Although considered ribonucleoproteins they are primarily classified by their protein component. They are involved in a variety of processes such as packaging of RNA and RNA TRANSPORT within the nucleus. A subset of heterogeneous-nuclear ribonucleoproteins are involved in additional functions such as nucleocytoplasmic transport (ACTIVE TRANSPORT, CELL NUCLEUS) of RNA and mRNA stability in the CYTOPLASM.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Complement Factor H: An important soluble regulator of the alternative pathway of complement activation (COMPLEMENT ACTIVATION PATHWAY, ALTERNATIVE). It is a 139-kDa glycoprotein expressed by the liver and secreted into the blood. It binds to COMPLEMENT C3B and makes iC3b (inactivated complement 3b) susceptible to cleavage by COMPLEMENT FACTOR I. Complement factor H also inhibits the association of C3b with COMPLEMENT FACTOR B to form the C3bB proenzyme, and promotes the dissociation of Bb from the C3bBb complex (COMPLEMENT C3 CONVERTASE, ALTERNATIVE PATHWAY).Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Phytotherapy: Use of plants or herbs to treat diseases or to alleviate pain.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.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.Regulatory Sequences, Ribonucleic Acid: Sequences within RNA that regulate the processing, stability (RNA STABILITY) or translation (TRANSLATION, GENETIC) of RNA.Mice, Inbred C57BL5' Untranslated Regions: The sequence at the 5' end of the messenger RNA that does not code for product. This sequence contains the ribosome binding site and other transcription and translation regulating sequences.Complement System Proteins: Serum glycoproteins participating in the host defense mechanism of COMPLEMENT ACTIVATION that creates the COMPLEMENT MEMBRANE ATTACK COMPLEX. Included are glycoproteins in the various pathways of complement activation (CLASSICAL COMPLEMENT PATHWAY; ALTERNATIVE COMPLEMENT PATHWAY; and LECTIN COMPLEMENT PATHWAY).Polypyrimidine Tract-Binding Protein: A RNA-binding protein that binds to polypyriminidine rich regions in the INTRONS of messenger RNAs. Polypyrimidine tract-binding protein may be involved in regulating the ALTERNATIVE SPLICING of mRNAs since its presence on an intronic RNA region that is upstream of an EXON inhibits the splicing of the exon into the final mRNA product.Complement C3b Inactivator Proteins: Endogenous proteins that inhibit or inactivate COMPLEMENT C3B. They include COMPLEMENT FACTOR H and COMPLEMENT FACTOR I (C3b/C4b inactivator). They cleave or promote the cleavage of C3b into inactive fragments, and thus are important in the down-regulation of COMPLEMENT ACTIVATION and its cytolytic sequence.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Membrane 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.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.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.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.Biological Evolution: The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.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.Sigma Factor: A protein which is a subunit of RNA polymerase. It effects initiation of specific RNA chains from DNA.Animal Use Alternatives: Alternatives to the use of animals in research, testing, and education. The alternatives may include reduction in the number of animals used, replacement of animals with a non-animal model or with animals of a species lower phylogenetically, or refinement of methods to minimize pain and distress of animals used.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Open Reading Frames: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).United StatesNucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Heterogeneous-Nuclear Ribonucleoprotein Group A-B: A class of closely related heterogeneous-nuclear ribonucleoproteins of approximately 34-40 kDa in size. Although they are generally found in the nucleoplasm, they also shuttle between the nucleus and the cytoplasm. Members of this class have been found to have a role in mRNA transport, telomere biogenesis and RNA SPLICING.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.Ribonucleoproteins: Complexes of RNA-binding proteins with ribonucleic acids (RNA).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.3' Untranslated Regions: The sequence at the 3' end of messenger RNA that does not code for product. This region contains transcription and translation regulating sequences.Genomics: The systematic study of the complete DNA sequences (GENOME) of organisms.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Data Interpretation, Statistical: Application of statistical procedures to analyze specific observed or assumed facts from a particular study.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Genetic 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.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.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.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.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.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.RNA Processing, Post-Transcriptional: Post-transcriptional biological modification of messenger, transfer, or ribosomal RNAs or their precursors. It includes cleavage, methylation, thiolation, isopentenylation, pseudouridine formation, conformational changes, and association with ribosomal protein.Transcription Initiation Site: The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.Equipment Design: Methods of creating machines and devices.Codon, Initiator: A codon that directs initiation of protein translation (TRANSLATION, GENETIC) by stimulating the binding of initiator tRNA (RNA, TRANSFER, MET). In prokaryotes, the codons AUG or GUG can act as initiators while in eukaryotes, AUG is the only initiator codon.Genome: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.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).)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.Spliceosomes: Organelles in which the splicing and excision reactions that remove introns from precursor messenger RNA molecules occur. One component of a spliceosome is five small nuclear RNA molecules (U1, U2, U4, U5, U6) that, working in conjunction with proteins, help to fold pieces of RNA into the right shapes and later splice them into the message.Evaluation Studies as Topic: Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. For drugs and devices, CLINICAL TRIALS AS TOPIC; DRUG EVALUATION; and DRUG EVALUATION, PRECLINICAL are available.Feasibility Studies: Studies to determine the advantages or disadvantages, practicability, or capability of accomplishing a projected plan, study, or project.Columbidae: Family in the order COLUMBIFORMES, comprised of pigeons or doves. They are BIRDS with short legs, stout bodies, small heads, and slender bills. Some sources call the smaller species doves and the larger pigeons, but the names are interchangeable.Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)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.Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly.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)Questionnaires: Predetermined sets of questions used to collect data - clinical data, social status, occupational group, etc. The term is often applied to a self-completed survey instrument.Mice, Inbred BALB CSequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Complement Inactivator Proteins: Serum proteins that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host. The complement system is tightly regulated by inactivators that accelerate the decay of intermediates and certain cell surface receptors.Pregnancy: The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.Reading Frames: The three possible sequences of CODONS by which GENETIC TRANSLATION may occur from one nucleotide sequence. A segment of mRNA 5'AUCCGA3' could be translated as 5'AUC.. or 5'UCC.. or 5'CCG.., depending on the location of the START CODON.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.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.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Poly A: A group of adenine ribonucleotides in which the phosphate residues of each adenine ribonucleotide act as bridges in forming diester linkages between the ribose moieties.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Faith Healing: The use of faith and spirit to cure disease.Databases, Genetic: Databases devoted to knowledge about specific genes and gene products.Toxicity Tests: An array of tests used to determine the toxicity of a substance to living systems. These include tests on clinical drugs, foods, and environmental pollutants.Nerve Tissue ProteinsComplement C2: A component of the CLASSICAL COMPLEMENT PATHWAY. C2 is cleaved by activated COMPLEMENT C1S into COMPLEMENT C2B and COMPLEMENT C2A. C2a, the COOH-terminal fragment containing a SERINE PROTEASE, combines with COMPLEMENT C4B to form C4b2a (CLASSICAL PATHWAY C3 CONVERTASE) and subsequent C4b2a3b (CLASSICAL PATHWAY C5 CONVERTASE).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.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.Clinical Trials as Topic: Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Animal Welfare: The protection of animals in laboratories or other specific environments by promoting their health through better nutrition, housing, and care.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)Codon, Nonsense: An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.Reinforcement (Psychology): The strengthening of a conditioned response.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.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.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.Randomized Controlled Trials as Topic: Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Integrative Medicine: The discipline concerned with using the combination of conventional ALLOPATHIC MEDICINE and ALTERNATIVE MEDICINE to address the biological, psychological, social, and spiritual aspects of health and illness.Databases, Nucleic Acid: Databases containing information about NUCLEIC ACIDS such as BASE SEQUENCE; SNPS; NUCLEIC ACID CONFORMATION; and other properties. Information about the DNA fragments kept in a GENE LIBRARY or GENOMIC LIBRARY is often maintained in DNA databases.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.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.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.Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea.Breast Neoplasms: Tumors or cancer of the human BREAST.Genes, Reporter: Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.Arabidopsis: A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.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).Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with well-defined distribution patterns in relation to time or place or both.Internet: A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.

Characterization of an amphioxus paired box gene, AmphiPax2/5/8: developmental expression patterns in optic support cells, nephridium, thyroid-like structures and pharyngeal gill slits, but not in the midbrain-hindbrain boundary region. (1/9069)

On the basis of developmental gene expression, the vertebrate central nervous system comprises: a forebrain plus anterior midbrain, a midbrain-hindbrain boundary region (MHB) having organizer properties, and a rhombospinal domain. The vertebrate MHB is characterized by position, by organizer properties and by being the early site of action of Wnt1 and engrailed genes, and of genes of the Pax2/5/8 subfamily. Wada and others (Wada, H., Saiga, H., Satoh, N. and Holland, P. W. H. (1998) Development 125, 1113-1122) suggested that ascidian tunicates have a vertebrate-like MHB on the basis of ascidian Pax258 expression there. In another invertebrate chordate, amphioxus, comparable gene expression evidence for a vertebrate-like MHB is lacking. We, therefore, isolated and characterized AmphiPax2/5/8, the sole member of this subfamily in amphioxus. AmphiPax2/5/8 is initially expressed well back in the rhombospinal domain and not where a MHB would be expected. In contrast, most of the other expression domains of AmphiPax2/5/8 correspond to expression domains of vertebrate Pax2, Pax5 and Pax8 in structures that are probably homologous - support cells of the eye, nephridium, thyroid-like structures and pharyngeal gill slits; although AmphiPax2/5/8 is not transcribed in any structures that could be interpreted as homologues of vertebrate otic placodes or otic vesicles. In sum, the developmental expression of AmphiPax2/5/8 indicates that the amphioxus central nervous system lacks a MHB resembling the vertebrate isthmic region. Additional gene expression data for the developing ascidian and amphioxus nervous systems would help determine whether a MHB is a basal chordate character secondarily lost in amphioxus. The alternative is that the MHB is a vertebrate innovation.  (+info)

The role of gene splicing, gene amplification and regulation in mosquito insecticide resistance. (2/9069)

The primary routes of insecticide resistance in all insects are alterations in the insecticide target sites or changes in the rate at which the insecticide is detoxified. Three enzyme systems, glutathione S-transferases, esterases and monooxygenases, are involved in the detoxification of the four major insecticide classes. These enzymes act by rapidly metabolizing the insecticide to non-toxic products, or by rapidly binding and very slowly turning over the insecticide (sequestration). In Culex mosquitoes, the most common organophosphate insecticide resistance mechanism is caused by co-amplification of two esterases. The amplified esterases are differentially regulated, with three times more Est beta 2(1) being produced than Est alpha 2(1). Cis-acting regulatory sequences associated with these esterases are under investigation. All the amplified esterases in different Culex species act through sequestration. The rates at which they bind with insecticides are more rapid than those for their non-amplified counterparts in the insecticide-susceptible insects. In contrast, esterase-based organophosphate resistance in Anopheles is invariably based on changes in substrate specificities and increased turnover rates of a small subset of insecticides. The up-regulation of both glutathione S-transferases and monooxygenases in resistant mosquitoes is due to the effects of a single major gene in each case. The products of these major genes up-regulate a broad range of enzymes. The diversity of glutathione S-transferases produced by Anopheles mosquitoes is increased by the splicing of different 5' ends of genes, with a single 3' end, within one class of this enzyme family. The trans-acting regulatory factors responsible for the up-regulation of both the monooxygenase and glutathione S-transferases still need to be identified, but the recent development of molecular tools for positional cloning in Anopheles gambiae now makes this possible.  (+info)

Expression of the naturally occurring truncated trkB neurotrophin receptor induces outgrowth of filopodia and processes in neuroblastoma cells. (3/9069)

We have investigated the effects of the truncated trkB receptor isoform T1 (trkB.T1) by transient transfection into mouse N2a neuroblastoma cells. We observed that expression of trkB.T1 leads to a striking change in cell morphology characterized by outgrowth of filopodia and processes. A similar morphological response was also observed in SH-SY5Y human neuroblastoma cells and NIH3T3 fibroblasts transfected with trkB.T1. N2a cells lack endogenous expression of trkB isoforms, but express barely detectable amounts of its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). The morphological change was ligand-independent, since addition of exogenous BDNF or NT-4 or blockade of endogenous trkB ligands did not influence this response. Filopodia and process outgrowth was significantly suppressed when full-length trkB.TK+ was cotransfected together with trkB.T1 and this inhibitory effect was blocked by tyrosine kinase inhibitor K252a. Transfection of trkB.T1 deletion mutants showed that the morphological response is dependent on the extracellular, but not the intracellular domain of the receptor. Our results suggest a novel ligand-independent role for truncated trkB in the regulation of cellular morphology.  (+info)

Differential stability of the DNA-activated protein kinase catalytic subunit mRNA in human glioma cells. (4/9069)

DNA-dependent protein kinase (DNA-PK) functions in double-strand break repair and immunoglobulin [V(D)J] recombination. We previously established a radiation-sensitive human cell line, M059J, derived from a malignant glioma, which lacks the catalytic subunit (DNA-PKcs) of the DNA-PK multiprotein complex. Although previous Northern blot analysis failed to detect the DNA-PKcs transcript in these cells, we show here through quantitative studies that the transcript is present, albeit at greatly reduced (approximately 20x) levels. Sequencing revealed no genetic alteration in either the promoter region, the kinase domain, or the 3' untranslated region of the DNA-PKcs gene to account for the reduced transcript levels. Nuclear run-on transcription assays indicated that the rate of DNA-PKcs transcription in M059J and DNA-PKcs proficient cell lines was similar, but the stability of the DNA-PKcs message in the M059J cell line was drastically (approximately 20x) reduced. Furthermore, M059J cells lack an alternately spliced DNA-PKcs transcript that accounts for a minor (5-20%) proportion of the DNA-PKcs message in all other cell lines tested. Thus, alterations in DNA-PKcs mRNA stability and/or the lack of the alternate mRNA may result in the loss of DNA-PKcs activity. This finding has important implications as DNA-PKcs activity is essential to cells repairing damage induced by radiation or radiomimetric agents.  (+info)

Selection and characterization of pre-mRNA splicing enhancers: identification of novel SR protein-specific enhancer sequences. (5/9069)

Splicing enhancers are RNA sequences required for accurate splice site recognition and the control of alternative splicing. In this study, we used an in vitro selection procedure to identify and characterize novel RNA sequences capable of functioning as pre-mRNA splicing enhancers. Randomized 18-nucleotide RNA sequences were inserted downstream from a Drosophila doublesex pre-mRNA enhancer-dependent splicing substrate. Functional splicing enhancers were then selected by multiple rounds of in vitro splicing in nuclear extracts, reverse transcription, and selective PCR amplification of the spliced products. Characterization of the selected splicing enhancers revealed a highly heterogeneous population of sequences, but we identified six classes of recurring degenerate sequence motifs five to seven nucleotides in length including novel splicing enhancer sequence motifs. Analysis of selected splicing enhancer elements and other enhancers in S100 complementation assays led to the identification of individual enhancers capable of being activated by specific serine/arginine (SR)-rich splicing factors (SC35, 9G8, and SF2/ASF). In addition, a potent splicing enhancer sequence isolated in the selection specifically binds a 20-kDa SR protein. This enhancer sequence has a high level of sequence homology with a recently identified RNA-protein adduct that can be immunoprecipitated with an SRp20-specific antibody. We conclude that distinct classes of selected enhancers are activated by specific SR proteins, but there is considerable sequence degeneracy within each class. The results presented here, in conjunction with previous studies, reveal a remarkably broad spectrum of RNA sequences capable of binding specific SR proteins and/or functioning as SR-specific splicing enhancers.  (+info)

Alterations in the conserved SL1 trans-spliced leader of Caenorhabditis elegans demonstrate flexibility in length and sequence requirements in vivo. (6/9069)

Approximately 70% of mRNAs in Caenorhabditis elegans are trans spliced to conserved 21- to 23-nucleotide leader RNAs. While the function of SL1, the major C. elegans trans-spliced leader, is unknown, SL1 RNA, which contains this leader, is essential for embryogenesis. Efforts to characterize in vivo requirements of the SL1 leader sequence have been severely constrained by the essential role of the corresponding DNA sequences in SL1 RNA transcription. We devised a heterologous expression system that circumvents this problem, making it possible to probe the length and sequence requirements of the SL1 leader without interfering with its transcription. We report that expression of SL1 from a U2 snRNA promoter rescues mutants lacking the SL1-encoding genes and that the essential embryonic function of SL1 is retained when approximately one-third of the leader sequence and/or the length of the leader is significantly altered. In contrast, although all mutant SL1 RNAs were well expressed, more severe alterations eliminate this essential embryonic function. The one non-rescuing mutant leader tested was never detected on messages, demonstrating that part of the leader sequence is essential for trans splicing in vivo. Thus, in spite of the high degree of SL1 sequence conservation, its length, primary sequence, and composition are not critical parameters of its essential embryonic function. However, particular nucleotides in the leader are essential for the in vivo function of the SL1 RNA, perhaps for its assembly into a functional snRNP or for the trans-splicing reaction.  (+info)

Mammalian staufen is a double-stranded-RNA- and tubulin-binding protein which localizes to the rough endoplasmic reticulum. (7/9069)

Staufen (Stau) is a double-stranded RNA (dsRNA)-binding protein involved in mRNA transport and localization in Drosophila. To understand the molecular mechanisms of mRNA transport in mammals, we cloned human (hStau) and mouse (mStau) staufen cDNAs. In humans, four transcripts arise by differential splicing of the Stau gene and code for two proteins with different N-terminal extremities. In vitro, hStau and mStau bind dsRNA via each of two full-length dsRNA-binding domains and tubulin via a region similar to the microtubule-binding domain of MAP-1B, suggesting that Stau cross-links cytoskeletal and RNA components. Immunofluorescent double labeling of transfected mammalian cells revealed that Stau is localized to the rough endoplasmic reticulum (RER), implicating this RNA-binding protein in mRNA targeting to the RER, perhaps via a multistep process involving microtubules. These results are the first demonstration of the association of an RNA-binding protein in addition to ribosomal proteins, with the RER, implicating this class of proteins in the transport of RNA to its site of translation.  (+info)

Expression of novel alternatively spliced isoforms of the oct-1 transcription factor. (8/9069)

Analysis of the alternatively spliced isoforms of the human and mouse oct-1 genes, combined with their exon-intron structure, show a high level of evolutionary conservation between these two species. The differential expression of several oct-1 isoforms was examined by reverse transcription-polymerase chain reaction performed on the 3' region of the murine oct-1 cDNA. Variations in the relative levels and patterns of expression of the isoforms were found among different tissues. Three novel isoforms originating from the 3'-distal region of oct-1, were isolated and sequenced: Two were derived from testis, and one from myeloma cells. Splicing out of different exons as revealed in the structure of these isoforms results in reading frameshifts that presumably lead to the expression of shortened Oct-1 proteins, with distinct C-terminal tails. Altogether, six out of the eight known murine oct-1 isoforms may have distinct C-termini, implying that these multiple tails have different functional roles in cellular differentiation and physiology.  (+info)

[115 Pages Report] Check for Discount on Global Neutral Alternative Protein Market by Manufacturers, Countries, Type and Application, Forecast to 2022 report by Global Info Research. Alternative proteins, such as plant-based meat substitutes and edible...
Production of mRNA in eukaryotic cells involves not only transcription but also various processing reactions such as splicing. Recent experiments have indicated that there are direct physical connections between components of the transcription and processing machinery, supporting previous suggestions that pre-mRNA splicing occurs co-transcriptionally. Here we have used a novel functional approach to demonstrate co-transcriptional regulation of alternative splicing. Exon 3 of the alpha-tropomyosin gene is specifically repressed in smooth muscle cells. By delaying synthesis of an essential downstream inhibitory element, we show that the decision to splice or repress exon 3 occurs during a limited window of opportunity following transcription, indicating that splice site selection proceeds rapidly after transcription.
How to silence two different alternative splicing sequences - posted in siRNA, microRNA and RNAi: I need to silence 2 different alternative splicing sequences. does anyone knows how can i do it? Thanx Dr. andrew [email protected]
The market for alternative proteins - beyond fish and meat - will grow at 14% annually by 2024. Developers will race to explore new sources and create new formulations to mitigate the negative environmental impact of the existing protein supply chain, as total protein demand will double to 943.5 million metric tons in 2054, according to Lux Research. Based on their nutritional content and commercial value, soybean, pea and oat have emerged as the dominant plant sources. Still, technology is key to improving protein flavor . . .
London, 13 February 2018 - As alternative proteins become mainstream, Nestlé and Tesco are named the best declared companies, while Costco has been called out for its inadequate response
Immune responses must be tightly controlled for dose, location, strength and duration using genetic, epigenetic or biochemical regulation. Among these, the generation of alternatively-spliced transcripts is an efficient and dynamic way to increase transcriptional and proteomic diversity. Specifically, this thesis explains how splice variation dictates the biological functions of interleukin-22 (IL-22) binding protein (IL-22BP) and interferon lambda 4 (IFNλ4), two proteins that participate in key cytokine responses to infection and inflammation. IL-22BP is a soluble receptor for IL-22 that is expressed as three isoforms in humans, IL-22BPi1, IL-22BPi2 and IL-22BPi3. The murine homolog of IL-22BPi2 has been characterized as an antagonist of IL-22 while the physiological relevance of IL-22BPi1 and IL-22BPi3 are unknown. Here, we present findings demonstrating that alternative splicing tailors IL-22BP activity to specific spatiotemporal conditions. Inclusion of a unique third exon renders IL-22BPi1 ...
Susceptibility to prostate or endometrial cancer is linked with obesity, a state of oestrogen excess. Oestrogen receptor (ER) splice variants may be responsible for the tissue-level of ER activity. Such micro-environmental regulation may modulate cancer initiation and/or progression mechanisms. Real-time reverse transcriptase (RT) polymerase chain reaction (PCR) was used to quantitatively assess the levels of four ER splice variants (ERαΔ3, ERαΔ5, ERβ2 and ERβ5), plus the full-length parent isoforms ERα and ERβ1, in high-risk [tumour-adjacent prostate (n = 10) or endometrial cancer (n = 9)] vs. low-risk [benign prostate (n = 12) or endometrium (n = 9)], as well as a comparison of UK (n = 12) vs. Indian (n = 15) benign prostate. All three tissue groups expressed the ER splice variants at similar levels, apart from ERαΔ5. This splice variant was markedly raised in all of the tumour-adjacent prostate samples compared to benign tissues. Immunofluorescence analysis for ERβ2 in prostate tissue
Because this is the first large-scale study relating ribosome loading to transcript structure, the frequency with which these regulated changes in transcript structure occur across nature is unknown. However, the suggestion that 9-18% of mammalian transcripts may have alternative first exons [12] is provocative. Two mammalian genes, in which alternative first exons were found to modify translation, are the gene encoding TIMP (tissue inhibitor of metalloproteinases) and the oncogene mdm2. With both of these genes, the translational efficiencies of the transcripts are regulated by changes in promoter utilization, which lead to altered 5 leaders [36, 37].. In yeast, use of alternative promoters has been shown in some cases to produce different proteins. The SUC2 and KAR4 genes both contain multiple promoters, which generate different protein products with different biologic activities [38, 39]. Similarly, the short forms of the CRH1, KAR5, PRM2, PRP39, PRY3, ASP3, and AQY1 mRNAs identified in this ...
p>This subsection of the ,a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence,/a> section indicates if the ,a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence,/a> displayed by default in the entry is complete or not.,p>,a href=/help/sequence_status target=_top>More...,/a>,/p>Sequence statusi: Complete.. This entry describes 4 ,p>This subsection of the Sequence section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.,p>,a href=/help/alternative_products target=_top>More...,/a>,/p> isoformsi produced by alternative splicing. Align. Add to basketAdded to ...
My PhD project focused on the cloning and characterization of mRNA alternative splice variants of the human prostaglandin F2 alpha (FP) receptor. Initially, our hypothesis was based on identification of an ovine FPB but includes any splice variant of the FP receptor. Interestingly, we identified a 6-TM mRNA splice variant designated hFPs. hFPs is the first putative 6-TM prostaglandin receptor splice variant identified in humans and was cloned from human heart and placenta. Methods include utilizing Rapid Amplification of cDNA Ends (RACE) PCR, subcloning, southern and northern blot analysis, and DNA sequencing to obtain FP receptor clones. DNA sequences were analyzed using MacVector computer software. Once FP isoforms were identified, sequences were confirmed using RT-PCR and receptor characterization was determined utilizing radioligand binding assays, functional studies as well as protein chemistry and immunohistochemical labeling of human tissue. Radioligand binding assays were done using cell ...
The full-length oestrogen receptor (ER) exists in most vertebrates as two separately encoded isoforms. ER splice variants represent truncated or otherwise modified versions of the full-length alpha or beta isoforms of the parent receptor. ERalpha is found on chromosome 6q and encodes a 595 amino acid protein, while ERbeta is found on chromosome 14q and encodes a 530 amino acid protein. These receptors possess differing ligand affinities, are differentially expressed in a tissue-specific fashion and may act antagonistically. Their altered expression has been implicated in the pathophysiology of a diverse range of conditions from cancer progression in hormone-responsive tissues to neurodegenerative disease. Variously co-expressed with full-length ERs, ER splice variants may have a positive or negative influence on transcription either by modifying the effect of the parent receptor or through their own intrinsic activity. To date, the vast majority of studies have used generic primers or antibodies against
Iain F Davidson, Daniela Goetz, Maciej P Zaczek, Maxim I Molodtsov, Pim J Huis in t Veld, Florian Weissmann, Gabriele Litos, David A Cisneros, Maria Ocampo‐Hafalla, Rene Ladurner, Frank Uhlmann, Alipasha Vaziri, Jan‐Michael Peters ...
OpenHelix provides on-line and onsite training on bioinformatics and genomics resources. OpenHelix encourages faster and more effective research by enabling the efficient use of publicly available tools to access biological data. OpenHelix tutorial suites on publicly available biomedical resources include an online narrated tutorial as well as PowerPoint slides, handouts and exercises. Customers can effectively and efficiently learn to use a resource and save time and money when teaching others by using the downloadable materials.
Recent data show the IL32 gene has at least nine transcript variants. The aim of this current study is to characterize the different transcript variants based on the latest sequencing data deposited in the National Center for Biotechnology Information (NCBI) and determine which variants are responsible for the differential pattern of gene expression previously observed in MCF7 compared to MDA MB231 cell lines. Analyses of the nine transcript variants showed their sequences were incredibly similar. Other than variant 9, all of the variants differed from variant 1 by deletions. PCR analyses showed that the longer transcript variants contributed more to differential gene expression observed in the MDA MB231 compared to MCF7 cell lines. Because of the similarities between the variant sequences, when determining differential expression in the breast cell lines, investigators should consider strategies that target analyses of a combination of the longer IL32 transcript variants.
Prior to this study, cancer researchers lacked a comprehensive survey of alternative promoters in cancer genes, and whether different promoters leads to differences in clinical behaviour of cancer patients.. To fill the gap, the team designed a specialised software called proActiv to detect activated promoters on a genome-wide scale. The underlying algorithm in proActiv is applicable to RNA-profiling data, which is routinely produced by hundreds of laboratories worldwide to study cancer. The team applied proActiv to a large collection of publicly-available data from over 18,000 cancer samples, and discovered that promoters in cancer genes are frequently different from their cancer-free counterparts. They also uncovered specific activated promoters that are linked to the survival rate of cancer patients, representing a new class of biomarkers.. Dr Jonathan Göke, Computational Biologist at the GIS and co-senior author of the study, explained, "We designed proActiv to work on RNA-profiling and it ...
I run this as an assessed practical, students must choose their own recipe from http://www.bbcgoodfood.com/ and should change the protein for a vegetarian alternative.
Here are three statements that shouldnt come as a shock to anyone in the foodservice industry: Todays diners are increasingly health-conscious, they care more about where their food comes from than generations past, and a rapidly growing number consider themselves
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PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
A typical fully processed mRNA includes one reference-protein coding ORF (RefORF) or coding sequence. This overly simplistic view is however challenged by recent evidence of translation of alternative ORFs (AltORFs). AltORFs are defined as ORFs occurring either in untranslated regions, or overlapping the RefORF in the non-canonical +2 and +3 reading frames. The use of alternative translation initiation is well-described for viruses and provide small viral genomes with an increased coding capacity, but has been overlooked in eukaryotes. To address this issue, we generated a database of predicted AltORFs in the human transcriptome. We identified 83,886 AltORFs with a minimum size of 40 codons. This threshold was established to increase the chances of detecting the predicted alternative proteins by proteomic techniques, including tryptic digestion and mass spectrometry, and SDS-PAGE. For the majority of mRNAs (87.58 %) we found at least one predicted AltORF and, on average, 3.88 predicted AltORFs ...
I recently had a chance to talk science with my old friend and colleague Jack Greenblatt. He has recently teamed up with some of my other colleagues at the University of Toronto to publish a paper on alternative splicing in mouse cells. Over the years I have had numerous discussions with these colleagues since they are proponents of massive alternative splicing in mammals. I think most splice variants are due to splicing errors.. Theres always a problem with terminology whenever we get involved in this debate. My position is that its easy to detect splice variants but they should be called "splice variants" until it has been firmly established that the variants have a biological function. This is not a distinction thats acceptable to proponents of massive alternative splicing. They use the term "alternative splicing" to refer to any set of processing variants regardless of whether they are splicing errors or real examples of regulation. This sometimes makes it difficult to have a discussion ...
Hospitals called on HHS to relax anti-kickback rules that could affect alternative pay models, saying payments between providers in the models shouldnt violate the regulations.
Alternative splicing is pervasive among complex eukaryote species. For some genes shared by numerous species, dozens of alternative transcripts are already annotated in databases. Most recent studies
Cette s lection propose, par institution dappartenance des coauteurs, la liste des publications cosign es par le Cirad et ses partenaires depuis 2008 : articles de revues, ouvrages et chapitres douvrages, actes de congr s, th ses et m moires HDR r f renc s dans la base de donn es documentaires du Cirad, Agritrop. Un acc s au texte int gral est propos lorsquil est disponible. ...
p,Transcript Support Level 1, when transcripts are supported by at least one non-suspect mRNA.,/p,,p,The ,a href=https://genome.ucsc.edu/cgi-bin/hgc?hgsid=423831555_sqRhAapgi8atmzzBPBAz8Me5797J&c=chr14&o=94517268&t=94547548&g=wgEncodeGencodeCompV19&i=ENST00000544005.1#tsl target=_self,Transcript Support Level,/a, (TSL) is a method to highlight the well-supported and poorly-supported transcript models for users. The method relies on the primary data that can support full-length transcript structure: mRNA and EST alignments supplied by UCSC and Ensembl.,/p,TSL:1The GENCODE set is the gene set for human and mouse. ,a href=/Help/Glossary?id=500 class=popup,GENCODE Basic,/a, is a subset of representative transcripts (splice variants).GENCODE basic,p,PRINCIPAL1 - APPRIS candidate principal isoform.,/p,,p,,a class=popup href=/Homo_sapiens/Help/Glossary?id=521,APPRIS,/a, is a system to annotate alternatively spliced transcripts based on a range of computational methods.,/p,APPRIS P1 ...
Detection of BORIS expression from different alternative promoters and stability of BORIS alternative transcripts. (A) Unique BORIS cDNA sequences attached to p
p,Transcript Support Level 1, when transcripts are supported by at least one non-suspect mRNA.,/p,,p,The ,a href=https://genome.ucsc.edu/cgi-bin/hgc?hgsid=423831555_sqRhAapgi8atmzzBPBAz8Me5797J&c=chr14&o=94517268&t=94547548&g=wgEncodeGencodeCompV19&i=ENST00000544005.1#tsl target=_self,Transcript Support Level,/a, (TSL) is a method to highlight the well-supported and poorly-supported transcript models for users. The method relies on the primary data that can support full-length transcript structure: mRNA and EST alignments supplied by UCSC and Ensembl.,/p,TSL:1The GENCODE set is the gene set for human and mouse. ,a href=/Help/Glossary?id=500 class=popup,GENCODE Basic,/a, is a subset of representative transcripts (splice variants).GENCODE basic,p,PRINCIPAL1 - APPRIS candidate principal isoform.,/p,,p,,a class=popup href=/Homo_sapiens/Help/Glossary?id=521,APPRIS,/a, is a system to annotate alternatively spliced transcripts based on a range of computational ...
Tandem splicing events occur at sites less than 12 nucleotides apart. Quantifying ratios of such splice variants is feasible using an...
These little variations endogenous LRTs cause, in protein structure or protein expression, could be a huge driving force behind speciation and diversity! (microRNAs have a role in this too!). Well, weve got a minor problem trying to address the impact of LTRs on gene expression in humans. We do, like, these huge data mining experiments which tell us "OMG LIEK THEIR ALL ACTIVE!"… but then you have to go back by hand to figure out whether the LTR activity is random noise, a minor contributor to gene expression, creating an alternative protein, or the sole promoter for the gene.. A review was just published that consolidates a lot of what we know about ERV LTRs and human genes.. ...
MIT Professor Susan Lee Lindquist, a member and former director of the Whitehead Institute, and one of the nations most lauded scientists, has died of cancer at age 67. She made invaluable contributions to the study of protein folding, demonstrating that alternative protein conformations can have profound and unexpected influences.
Wellness® Super5Mix® Lamb Formula is a complete, balanced blend of thoughtfully chosen ingredients for active, adult dogs that require or prefer an alternative protein sour...
Wellness® Super5Mix® Lamb Formula is a complete, balanced blend of thoughtfully chosen ingredients for active, adult dogs that require or prefer an alternative protein sour...
FUNCTION: This gene encodes a member of a family of proteins that function in the nervous system as receptors and cell adhesion molecules. Extensive alternative splicing and the use of alternative promoters results in multiple transcript variants for this gene, but the full-length nature of many of these variants has not been determined. Transcripts that initiate from an upstream promoter encode alpha isoforms, which contain epidermal growth factor-like (EGF-like) sequences and laminin G domains. Transcripts initiating from the downstream promoter encode beta isoforms, which lack EGF-like sequences. [provided by RefSeq, Dec 2012 ...
As this eMedTV segment explains, there are many different alternatives to Kazano (alogliptin and metformin), including other oral drugs, insulin, and lifestyle changes. This page explains these options in detail with specific examples.
The break has helped Bilbao Athletic recover key players who were dealing with injuries. Iñigo Baqué is the only one ruled out for Saturdays fixture, but the Kumeak will finally have all of the strikers available.. "Aside from Baqué, who is recovering from his ligament injury and had some discomfort this past week, everyone is well. Were very happy to have different alternatives in the attacking positions. Ewan Urain and Andoni Tascón have recovered. Guruzeta will be with us too and Nico Serrano who can give us something different.". On the other hand, both Oihan Sancet and Dani Vivian will be unavailable if the first team is still in the race for Europe this weekend. Etxeberria has no problems losing both because fighting for a top seven finish is the most important goal for the club as a whole right now.. "The coordination between the teams has been very good. The first team is the priority. If Gaizka is going to count on them them we will count on Basconia players. The first team is ...
The European Securities and Markets Authority (ESMA) has published a new Questions and Answers (Q&A) document, comprising six questions, on the implementation of its Guidelines on the Alternative Performance Measures for listed issuers.
The blastp of the GRMZM2G012966 model gives the most complete alignment to lyce1, so that model is likely the most correct model. The lyce1 alignment for Models 1 and 2 are truncated at the 3 end, suggesting that the models have a framshift mutation somewhere in exon 8. Models 1 and 2 do provide some additional information, however. The 3 end of the sequence contains a protein kinase-like (PKc_like superfamily) region, which suggests that both models should in fact be split up into two different genes. This means that the cDNA (gb,BT037027.1; GENE ID: 100216601 LOC100216601 ) is not part of the lcye1 gene, confirming that the gene is confined between coordinates 82,726 and 85,759 (or 138882727 and 138885760 in the Reference Genome).. The blastx results of Model 2 show that exons 8 and 9 (the ones not contained in Model 1 or GRMZM2G012966) aligns to lyce1 (see reading frame +1 between 2000 and 2500 of the query). This supports the idea that an alternative gene model involving alternatively ...
OK....Im into something new. Instead of early morning cable TV infomercials, its now advice columns. And this is a piece on Alternative Advice Columns. Now, whether that means its an alternative to advice columns, or just some alternative advice; Ill let you figure that one out. Heres a little gem, worthy of comment by one…
With just 20,000 genes but more than 100,000 proteins, human beings have become increasingly unique because of alternative RNA splicing in evolution.
Myc-DDK-tagged ORF clone of Homo sapiens RAD52 motif 1 (RDM1), transcript variant 3 as transfection-ready DNA - 10 µg - OriGene - cdna clones
Todays Deals: Save 29% on Alternative Synthetic Magnetic Big Uns Frag Station by The Alternative Reef. Hurry, quantities are limited.
This is perhaps the most difficult part of cognitive restructuring because the practitioner may be able to see the alternatives, but needs to facilitate the individual client to arrive at these alternatives using one or more of the techniques outlined below. The alternative interpretation or constructive idea is phrased as a hypothesis, i.e. a theory or assumption for which we need to come to a conclusion about how accurate it is compared to the initial interpretations and ideas, and/or how helpful it may be in changing the way we feel and behave. At this stage, we may choose not to judge or add value to the alternatives until the next step of cognitive restructuring when we test them for accuracy and helpfulness. Remember, the objective is not to show that we are right and the other person is wrong but to show that there are other options that could be considered. Prompt sheet Using a prompt sheet (Figure 25.4), the client could write down their key thoughts (my interpretations and ideas are ...
Animal testing alternatives fall into three main categories. replacement alternatives, reduction alternatives and refinement alternatives.
I would like to start a discussion on alternative treatments for emphysema. For the most part, all most people know are inhalers of one kind or another and I think.....
It is reasonable to obtain a histological diagnosis before treating patients who have pancreatic masses and are unsuitable or unwilling to undergo surgery.
2020. All rights reserved. All information presented in this website is intended for informational purposes only and not for the purpose of rendering medical advice. Statements made on this website have not been evaluated by the Food and Drug Administration. The information contained herein is not intended to diagnose, treat, cure or prevent any disease. ...
Medical Alternatives Network,This ring site is for holistic and alternative healing websites throughout the world. English only please YOU MUST PUT THE WEBRING CODE ON YOUR INDEX PAGE IN ORDER TO BE ACCEPTED INTO THIS RING.
Alternative to Meds Center focuses on natural solutions and holistic Zyprexa alternatives within a peaceful retreat medical spa-like environment.
This eMedTV segment discusses several Flomax alternatives, such as watchful waiting, surgery, or other medications. This page explains when these alternatives might be useful and lists some of the alternative medications to Flomax.
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Alternative splicing[edit]. Mammalian TNNT3 gene contains 19 exons. Alternative RNA splicing of 8 of them significantly ... Through alternative splicing of the fetal exon and other alternative exons in the N-terminal variable region, the expression of ... Alternative splicing of the two C-terminal mutually exclusive exons 16 and 17 appears also regulated during development.[14] ... 3).[16][17][18] Reflecting the power of combined alternative splicing of multiple exons to generate fsTnT variants, two- ...
Alternative splicingEdit. Main article: Alternative splicing. Alternative splicing (the re-combination of different exons) is a ... Introns typically have a GU nucleotide sequence at the 5' end splice site, and an AG at the 3' end splice site. The 3' splice ... These include the 5' end splice site, the branch point sequence, the polypyrimidine tract, and the 3' end splice site. The ... splice site interaction on a model of substrate oligonucleotide containing a short 5' exon and 5' splice site.[24] Binding of ...
SMN2 alternative splicing modulationEdit. This approach aims at modifying the alternative splicing of the SMN2 gene so that to ... The SMN2 gene, on the other hand - due to a variation in a single nucleotide (840.C→T) - undergoes alternative splicing at the ... Basic research has also identified other compounds which modified SMN2 splicing in vitro, like sodium orthovanadate[48] and ... The following splicing modulators have reached clinical stage development:. *Branaplam (LMI070, NVS-SM1) is a proprietary small ...
"Gene Splicing Mechanism , Alternative Splicing Tutorial , Splice Variant Detection". www.premierbiosoft.com. Retrieved 2016-05- ... believe is a clear sign of the well understood field of gene splicing. "Sars biological weapon?". www.news24.com. 11 April 2003 ...
Roberts's discovery of the alternative splicing of genes, in particular, has had a profound impact on the study and ... or Medicine with Phillip Allen Sharp for the discovery of introns in eukaryotic DNA and the mechanism of gene-splicing. He ...
Are You reelin in the Years? Not without Alternative Splicing. ... alternative splicing, and transcription units of the human ... ApoER2 splice variants can act as a receptor for alpha-2-macroglobulin which can have a role in clearance of alpha-2- ... In ApoER2, there is a proline-rich 59 amino acid insert encoded by the alternatively spliced exon 19. This insert allows for ... Studies with mice have shown that knocking out ApoER2 or just the alternatively spliced exon 19 causes a much greater ...
Alternative splicing produces ∆Elk1. This variant lacks part of the DNA-binding domain that allows interaction with SRF. On the ... Elk1 also interacts with BRCA1 splice variants, namely BRCA1a and BRCA1b. This interaction enhances BRCA1-mediated growth ... "c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth ...
Evidence for alternative splicing". J. Mol. Biol. 207 (3): 491-503. doi:10.1016/0022-2836(89)90459-2. PMID 2760922. Buvoli M, ... Buvoli M, Cobianchi F, Bestagno MG, Mangiarotti A, Bassi MT, Biamonti G, Riva S (1990). "Alternative splicing in the human gene ... and may modulate splice site selection. Multiple alternatively spliced transcript variants have been found for this gene but ... These variants have multiple alternative transcription initiation sites and multiple polyA sites. Heterogeneous nuclear ...
Alternative splicing, polyadenylation, and isoforms". The Journal of Biological Chemistry. 270 (34): 20112-22. doi:10.1074/jbc. ... Multiple alternatively spliced variants, encoding the same protein, have been found for this gene. Cluster of differentiation ...
Alternative splicing, polyadenylation, and isoforms". J. Biol. Chem. 270 (34): 20112-22. doi:10.1074/jbc.270.34.20112. PMID ... 2004). "Activity and tissue distribution of splice variants of alpha6-fucosyltransferase in human embryogenesis". Glycobiology ... large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55-65. ...
"Muscleblind proteins regulate alternative splicing". The EMBO Journal. 23 (15): 3103-12. doi:10.1038/sj.emboj.7600300. PMC ... "Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy". ... CUG-BP1 and hnRNP H proteins in DM1-associated aberrant IR splicing". The EMBO Journal. 25 (18): 4271-83. doi:10.1038/sj.emboj. ... "MBNL1 is the primary determinant of focus formation and aberrant insulin receptor splicing in DM1". The Journal of Biological ...
Alternative splicing of transcription products". The Journal of Biological Chemistry. 272 (28): 17843-50. doi:10.1074/jbc. ... Several alternatively spliced transcript variants, some of which encode distinct isoforms, have been identified. Additional ... "Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism". ...
Alternative splicing, polyadenylation, and isoforms". J. Biol. Chem. 270 (34): 20112-22. doi:10.1074/jbc.270.34.20112. PMID ...
Kim N; Lee C (2008). "Bioinformatics detection of alternative splicing". Methods Mol. Biol. Methods in Molecular Biology™. 452 ... can be aligned to a sequenced genome to find where there are genes and get information about alternative splicing and RNA ... BLAST was developed to provide a faster alternative to FASTA without sacrificing much accuracy; like FASTA, BLAST uses a word ... but does not indicate how much superior a given alignment is to alternative alignments of the same sequences. Measures of ...
Lareau, LF; Green, RE (June 1, 2004). "The evolving roles of alternative splicing". Current Opinion in Structural Biology. 14 ( ...
Woodley L, Valcárcel J (Oct 2002). "Regulation of alternative pre-mRNA splicing". Briefings in Functional Genomics & Proteomics ... the mutant pre-mRNA and the therapeutic pre-trans-splicing molecule carrying the wild-type sequence are spliced together to ... masking exonic splicing enhancer sequences and therefore preventing binding of the splicing machinery and therefore resulting ... Wally V, Murauer EM, Bauer JW (Aug 2012). "Spliceosome-mediated trans-splicing: the therapeutic cut and paste". The Journal of ...
Alternative splicing occurs for this gene; however, the full-length nature of all transcript variants has not yet been ...
This gene undergoes extensive alternative splicing; although ten transcript variants have been described, the full length ... Functional diversity of GIT2 through alternative splicing". The Journal of Biological Chemistry. 275 (29): 22373-80. doi: ...
... is a database of genomic annotations taking alternative splicing events into consideration. Alternative splicing TassDB ... genome annotation for alternative splicing". Nucleic Acids Res. England. 33 (Database issue): D75-9. doi:10.1093/nar/gki118. ...
Alternative splicing results in transcript variants. The LRRs and NTF2-like domains are required for export activity. The ... "Multipotent genetic suppression of retrotransposon-induced mutations by Nxf1 through fine-tuning of alternative splicing". PLoS ... is a component of the splicing-dependent exon-exon junction complex". EMBO J. England. 20 (22): 6424-33. doi:10.1093/emboj/ ...
Alternative splicing generates 2 transcript variants. GRCh38: Ensembl release 89: ENSG00000174233 - Ensembl, May 2017 GRCm38: ...
Alternative splicing occurs in this gene. GRCh38: Ensembl release 89: ENSG00000156453 - Ensembl, May 2017 GRCm38: Ensembl ...
Hollywood is a RNA splicing database containing data for the splicing of orthologous genes in different species. Alternative ... a comparative relational database of alternative splicing". Nucleic Acids Res. England. 34 (Database issue): D56-62. doi: ... splicing EDAS AspicDB Holste, Dirk; Huo George; Tung Vivian; Burge Christopher B (Jan 2006). "HOLLYWOOD: ...
2005). "Muscleblind proteins regulate alternative splicing". EMBO J. 23 (15): 3103-12. doi:10.1038/sj.emboj.7600300. PMC 514918 ...
2005). "Muscleblind proteins regulate alternative splicing". EMBO J. 23 (15): 3103-12. doi:10.1038/sj.emboj.7600300. PMC 514918 ... Several alternatively spliced transcript variants have been described but the full-length natures of only some have been ...
... alternative splicing;將穿插在內含子中的外顯子以選擇性的方
PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and ... PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and ...
Genetics of alternative splicing evolution during sunflower domestication Chris C. R. Smith, Silas Tittes, J. Paul Mendieta, ... Prp8 impacts cryptic but not alternative splicing frequency Megan Mayerle, Samira Yitiz, Cameron Soulette, Lucero E. Rogel, ... Activity-dependent aberrations in gene expression and alternative splicing in a mouse model of Rett syndrome Sivan Osenberg, ... Dysregulation of cotranscriptional alternative splicing underlies CHARGE syndrome Catherine Bélanger, Félix-Antoine Bérubé- ...
Are you looking for more information on alternative splicing modes? If so, read on to learn more about this basic genetics ... In this alternative splicing mode, a sequence may be simply retained or spliced out as an intron. This differs from the exon ... Alternative Donor Site. In this mode, a donor site, an alternative 5 splice junction, is used. This changes the 3 boundary of ... Alternative splicing, also referred to as differential splicing, is a process where the RNA exons of the RNA that is produced ...
Protein for which at least two isoforms exist due to distinct pre-mRNA splicing events. ...
Research Group dealing with alternative Splicing issues and mis-splicing in human diseases Alternative Splicing of ion channels ... Since then, alternative splicing has been found to be ubiquitous in eukaryotes. The "record-holder" for alternative splicing is ... These databases are useful for finding genes having pre-mRNAs undergoing alternative splicing and alternative splicing events. ... A General Definition and Nomenclature for Alternative Splicing Events at SciVee AStalavista (Alternative Splicing landscape ...
Do similar forces act on all types of alternative splicing? Are the products generated by alternative splicing functional? Why ... Alternative splicing: current perspectives.. Kim E1, Goren A, Ast G.. Author information. 1. Department of Human Molecular ... Alternative splicing is a well-characterized mechanism by which multiple transcripts are generated from a single mRNA precursor ... By allowing production of several protein isoforms from one pre-mRNA, alternative splicing contributes to proteomic diversity. ...
Alternative splicing: new insights from global analyses.. Blencowe BJ1.. Author information. 1. Banting and Best Department of ... Recent analyses of sequence and microarray data have suggested that alternative splicing plays a major role in the generation ... and how alternative splicing is coordinated on a global level to achieve cell- and tissue-specific functions. Recent progress ... directed at establishing the full repertoire of functionally relevant transcript variants generated by alternative splicing, ...
Alternative Splicing Annotation Project (ASAP) is a database for alternative splicing data. The purpose of this project was to ... Lee, C., Atanelov, L., Modrek, B., & Xing, Y. (2003). ASAP: the alternative splicing annotation project. Nucleic Acids Research ... analysis and comparative genomics of alternative splicing in 15 animal species". Nucleic Acids Res. England. 35 (Database issue ... AspicDB RNA splicing Kim, Namshin; Alekseyenko Alexander V; Roy Meenakshi; Lee Christopher (Jan 2007). "The ASAP II database: ...
genes undergo alternative splicing, generating multiple mRNAs from each gene (6,7). A large fraction of alternative splicing ... tissue-specific alternative splicing patterns By using a method that normalizes the number of observed alternative splicing ... Alternative splicing is commonly regulated by RNA-binding proteins that bind to sequence motifs located within the alternative ... Variation in alternative splicing across human tissues. (2004) by G Yeo, D Holste, G Kreiman, C B Burge ...
Therefore, the study of alternative splicing opens new doors in the research to cure cancer and may provide new alternatives to ... Alternative splicing, an important mechanism for cancer Scientists discover several alterations in this cellular process with ... "Changes in alternative splicing provide cancer with new ways in which it can escape fine cellular regulation. ... "With this new study, we have discovered that changes in alternative splicing that occur in cancer impact protein functions in a ...
Contribute to HussainAther/awesome-alternative-splicing development by creating an account on GitHub. ... awesome-alternative-splicing. What is this?. This is a resource for software and information about alternative splicing. ... Alternative 5 splice site (A5SS): An alternative 5 splice junction (donor site) is used that changes the 3 boundary of the ... Alternative 3 splice site (A3SS): An alternative 3 splice junction (acceptor site) is used that changes the 5 boundary of ...
This process can lead to transcript diversification through the phenomenon of alternative splicing. Alternative splicing can ... Alternative Spliced Transcripts as Cancer Markers. Otavia L. Caballero,2 Sandro J. de Souza,2 Ricardo R. Brentani,1,2 and ... The effect of alternative splicing in expanding protein repertoire might partially underlie the apparent discrepancy between ... Many cancer-associated genes, such as CD44 and WT1 are alternatively spliced. Variation of the splicing process occurs during ...
RNA alternative splicing was first noticed in adenoviruses in the 1970s. The researchers noticed that adenoviruses produced two ... Find out more about the role of RNA and RNA alternative splicing in protein synthesis and genetic disorders. ... Importance of RNA Alternative Splicing. RNA alternative splicing enables genetic efficiency and genetic diversity. On the ... RNA Alternative Splicing. First let us understand what splicing is. DNA directs the synthesis or production of RNA. This is ...
... such as alternative splicing. We present a methodology for the automated annotation of genes and their alternatively spliced ... and combines the traditionally distinct gene annotation and alternative splicing detection processes in a comprehensive and ... At the core of the method is the splice graph, a compact representation of a gene, its exons, introns, and alternatively ... spliced isoforms. The putative transcripts are enumerated from the graph and assigned confidence scores based on the strength ...
... we will summarize how splicing regulators change and affect alternative splicing in this process. We will also discuss a novel ... we will summarize how splicing regulators change and affect alternative splicing in this process. We will also discuss a novel ... The significance of the dynamic control of alternative splicing in response to changes of calcium levels has been largely ... The significance of the dynamic control of alternative splicing in response to changes of calcium levels has been largely ...
... has shown no evidence for alternative splicing in regions other than what is covered by these two primers (i.e., alternative ... Alternative splicing, muscle calcium sensitivity, and the modulation of dragonfly flight performance. James H. Marden, Gail H. ... Despite the fact that alternative splicing of TnT followed different ontogenetic patterns in the two morphs, they showed the ... In summary, we propose that dragonflies use alternative splicing of TnT to modulate the calcium sensitivity of their flight ...
An estimated 60% of all human genes undergo alternative splicing, a highly regulated process that produces splice variants with ... or force selection of an alternative 5′ splice site (. c. ) by antisense oligonucleotides targeted to appropriate splice sites ... Aberrant splicing in thalassemic β-globin pre-mRNA or in certain splice mutants in CFTR is prevented, and correct splicing is ... describes a promising approach to RNA repair based on the use of antisense oligonucleotides to modulate alternative splicing ...
rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data. Proc Natl Acad Sci U S A ... Alternative splicing resulting in nonsense-mediated mRNA decay: what is the meaning of nonsense? Trends Biochem Sci. 2008;33(8 ... A slow RNA polymerase II affects alternative splicing in vivo. Mol Cell. 2003;12(2):525-532.. View this article via: PubMed ... Histone methyltransferase SETD2 modulates alternative splicing to inhibit intestinal tumorigenesis. Huairui Yuan,1 Ni Li,1 Da ...
Meanwhile some early splicing changes are supplanted by new splicing changes introduced by the up-regulation of ELL2, a ... Some of the ,4000 splicing changes seen at 18 h after LPS stimulation persist into the late stages of antibody secretion, up to ... Inhibition of the mRNA-degradation function of Ire1 is correlated with further differences in the splicing patterns and a ... The mRNA-modifying function of phosphorylated Ire1 non-canonically splices Xbp1 mRNA and yet degrades other cellular mRNAs with ...
English to French translation of alternative splicing, a process that yields different protein products [DNA - Science (general ... alternative splicing, a process that yields different protein products. However, its now believed that the incredible ... alternative splicing, a process that yields different protein products. French translation: épissage alternatif. ... "alternative splicing" (a process that yields different protein products* from the same gene),. ...
... is a co-transcriptional splicing process not only controlled by RNA-binding splicing factors, but also mediated by epigenetic ... alternative 5′-end splice site (A5SS), and alternative 3′-end splice site (A3SS). We attempt to elucidate functional and ... The constitutive splicing isoform is shown in the upper track in yellow and the alternative splicing isoform is shown in the ... Alternative splicing event detection across 34 normal and cancer cell types. a Sashimi plots visualizing a specific splice site ...
... and alcohol consumption also regulates alternative splicing. Thus, investigations of alternative splicing are essential for ... Gene expression is regulated not only at the level of transcription but also through alternative splicing of pre-mRNA. In this ... we discuss some of the evidence suggesting that alternative splicing of candidate genes such as DRD2 (encoding dopamine D2 ... These reports suggest that aberrant expression of splice variants affects alcohol sensitivities, ...
tags: alternative splicing x ecology x evolution x microbiology x The Scientist. » alternative splicing, ecology, evolution and ...
tags: alternative splicing x immunology x culture x The Scientist. » alternative splicing, immunology and culture ...
Neuronal Signaling through Alternative Splicing: Some Exons CaRRE... Message Subject. (Your Name) has forwarded a page to you ...
  • PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and CDC25B. (ox.ac.uk)
  • Also referred to as cassette exon, this mode involves an exon that may be retained or spliced out of the primary transcript. (brighthub.com)
  • In 1981, the first example of alternative splicing in a transcript from a normal, endogenous gene was characterized. (wikipedia.org)
  • Exon skipping or cassette exon: in this case, an exon may be spliced out of the primary transcript or retained. (wikipedia.org)
  • Skipped exon or cassette exon (SE): An exon can be retained or spliced out of the primary transcript. (github.com)
  • rMATS - RNA-Seq Multavariate Analysis of Transcript Splicing. (github.com)
  • This process can lead to transcript diversification through the phenomenon of alternative splicing. (hindawi.com)
  • Two size-distinguishable morphs differ in their maturational pattern of TnT splicing, yet they show the same relationship between TnT transcript mixture and calcium sensitivity and between calcium sensitivity and aerodynamic power output. (pnas.org)
  • This approach allows us to test for associations between TnT transcript variation, muscle calcium sensitivity, and contractile performance that are independent of the developmental and physiological context in which TnT alternative splicing occurs. (pnas.org)
  • PARK2 primary transcript undergoes an extensive alternative splicing, which enhances transcriptomic diversification. (hindawi.com)
  • Splicing of primary RNA transcript is a quasi-systematic step of gene expression in higher organisms. (alibris.com)
  • Cotransfection analyses in which the dsx gene and the female-specific transformer (tra) and transformer-2 (tra-2) complementary DNAs were expressed in Drosophila Kc cells revealed that female-specific splicing of the dsx transcript was positively regulated by the products of the tra and tra-2 genes. (sciencemag.org)
  • Temperature effects on alternative splicing contribute to a decline in LHY transcript abundance on cooling, but LHY promoter strength is not affected. (plantcell.org)
  • In this report, we identify an exon-levelcis-eQTL (rs6471859) that regulates human DRG CA8 alternative splicing, producing a truncated 1,697bp transcript (e.g. (medworm.com)
  • Alternative splicing is a widespread phenomenon (observed in greater than 30% of the loci with transcript support) and we have described nine alternative splicing variations. (biomedcentral.com)
  • In this study, we performed a comprehensive analysis of alternative splicing in rice, a model monocotyledonous species, using the latest set of rice transcript data and the Program to Assemble Spliced Alignments (PASA). (biomedcentral.com)
  • The PASA software [ 5 ] assembles and clusters spliced transcript alignments, providing transcript-based gene structures that are used to automatically improve existing gene annotations by adding untranslated regions (UTRs), adjusting intron and exon boundaries, and adding new models that represent alternative splicing, among its numerous other functions. (biomedcentral.com)
  • However, overlapping transcript alignments that have different introns in their region of overlap, due to a splicing variation, are found incompatible and cannot be assembled together, and hence occupy distinct maximal alignment assemblies. (biomedcentral.com)
  • Furthermore, the SR splicing factor, SC35, was shown to be required for induction of the alternatively spliced KLF6 transcript. (asm.org)
  • A switch in the alternative splicing of MdmX transcript, leading to the inclusion of exon 6, has been identified as the primary mechanism responsible for increased MdmX protein levels in human cancers, including melanoma. (muni.cz)
  • Accumulating evidence suggests alternative splicing (AS) is a co-transcriptional splicing process not only controlled by RNA-binding splicing factors, but also mediated by epigenetic regulators, such as chromatin structure, nucleosome density, and histone modification. (springer.com)
  • Sustained loss of ESRP2 permitted re-emergence of a fetal RNA splicing program that attenuates the Hippo signaling pathway and thus, allows fetal transcriptional regulators to accumulate in adult liver. (jci.org)
  • Recently, alternative splicing of the two most critical regulators of intracellular cholesterol, 3-hydroxy-3-methylglutaryl- coenzyme A reductase (HMGCR), the rate-limiting enzyme of cholesterol biosynthesis, and the LDL receptor (LDLR), responsible for uptake of LDL, have been associated with variation in plasma LDL as well as with the magnitude of LDL reduction by simvastatin. (labome.org)
  • Furthermore, we will look for common targets of AtGRP7 and AtGRP8 with other splicing regulators to identify an alternative splicing network in Arabidopsis thaliana and contribute to unravel the splice code in higher plants. (forschung-sachsen-anhalt.de)
  • We and others have implicated several splicing factors as regulators of lipid metabolism. (ovid.com)
  • Here, we describe how transcriptional regulators and coregulators influence alternative splicing, with a focus on genes that are controlled by steroid hormones. (pasteur.fr)
  • We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. (elifesciences.org)
  • flotilla - reproduce machine learning analysis of gene expression and alternative splicing data. (github.com)
  • Alternative splicing in eukaryotes plays an important role in regulating gene expression by selectively including alternative exons. (frontiersin.org)
  • Here, we show widespread aberrations in gene expression and anomalous patterns of alternative splicing, specifically when neurons of RTT mice are stimulated. (pnas.org)
  • Here we reveal an aberrant global pattern of gene expression, characterized predominantly by higher levels of expression of activity-dependent genes, and anomalous alternative splicing events, specifically in response to neuronal activity in a mouse model for RTT. (pnas.org)
  • Here, we analyzed transcriptome-wide alterations in gene expression and alternative splicing ( AS ) of etiolated seedlings undergoing photomorphogenesis upon exposure to blue, red, or white light. (plantcell.org)
  • Alternative splicing plays crucial roles by influencing the diversity of the transcriptome and proteome and regulating protein structure/function and gene expression. (plantcell.org)
  • One of the goals of this dissertation is to understand how two fundamen- tal biological processes, genome duplication and alternative splicing, factor into the regulation of gene expression. (uni-koeln.de)
  • Citation Query Variation in alternative splicing across human tissues. (psu.edu)
  • Variation in alternative splicing across human tissues. (psu.edu)
  • SingleSplice - detect biological variation in alternative splicing within a population of single cells. (github.com)
  • Variation of the splicing process occurs during tumor progression and may play a major role in tumorigenesis. (hindawi.com)
  • These findings lead to the hypotheses that intracellular cholesterol levels regulate splicing factor(s) to generate coordinated changes in alternative splicing of multiple genes involved in cholesterol synthesis and uptake, and that variation in this process is a determinant of cellular and plasma cholesterol metabolism. (labome.org)
  • Demonstration of the role of alternative splicing in the regulation of cholesterol metabolism and identification of genetic determinants of this process will aid in delineating molecular pathways contributing to inter-individual variation in plasma LDL and thus improve our understanding of cardiovascular disease development and risk. (labome.org)
  • In numerous cases, the potential neurobiological impact of P/Q-type channel splice variation remains uncharted. (jneurosci.org)
  • Analysis of the MCP gene demonstrated that the variation in cDNA structure was a result of alternative splicing. (rupress.org)
  • In this communication, we will summarize the recent advances in calcium signaling-mediated alternative splicing that have provided some insights into the important regulatory mechanisms. (frontiersin.org)
  • Neurons use alternative splicing to produce channels with different sequences and biophysical or regulatory properties. (sciencemag.org)
  • Here, we demonstrated that expression of epithelial splicing regulatory protein-2 (ESRP2), an RNA splicing factor that maintains the non-proliferative, mature phenotype of adult hepatocytes, was suppressed in both human SAH and various mouse models of SAH in parallel with the severity of alcohol consumption and liver damage. (jci.org)
  • We found that the F-domain of zebrafish TRalphaA1 is encoded on a separate exon whose inclusion is regulated by alternative splicing, indicating a regulatory role of the F-domain in vivo. (sigmaaldrich.com)
  • Consensus clustering analysis was conducted to classified glioma samples and correlation analysis was conducted to characterize regulatory network of splicing factors and splicing events. (springer.com)
  • We propose that noncoding exons are functionally modular, with alternative splicing generating an enormous repertoire of potential regulatory RNAs and a rich transcriptional reservoir for gene evolution. (dtu.dk)
  • In this manuscript, we identified several new RNA regulatory elements for alternative splicing of Ron proto-oncogene. (jcancer.org)
  • Genome duplication and alternative splicing have profound implications on gene regulation, as the controlled expression of duplicated genes affects the evolution of genomes, whereas alternative splicing of regulatory genes has enormous ramifications on the functionality of nearly all expressed genes. (uni-koeln.de)
  • Interactions of hnRNPs with silencer elements repress proximal exon recognition by inhibiting the use of adjacent splice sites, either by antagonizing the function of positive regulatory elements or by recruiting factors that directly interfere with the splicing machinery ( 9 , 58 ). (asm.org)
  • The alternative exon, which codes for an in-frame 27 amino acids between the kinase and known regulatory domain of TAK1, contains conserved features in all organisms including potential phosphorylation sites and likely has an important conserved function in TGF beta signaling and development. (cnrs.fr)
  • Background: A systematic examination of prognostic alternative splicing(AS) events in patients with colorectal cancer(CRC) was not well illustrated. (frontiersin.org)
  • Conclusions HNRNPLL is a novel metastasis suppressor of colorectal cancer, and modulates alternative splicing of CD44 during EMT. (bmj.com)
  • Are the products generated by alternative splicing functional? (nih.gov)
  • Recent analyses of sequence and microarray data have suggested that alternative splicing plays a major role in the generation of proteomic and functional diversity in metazoan organisms. (nih.gov)
  • The results of the study show that alternative splicing changes lead to a general loss of functional protein domains, and particularly those domains related to functions that are also affected by genetic mutations in cancer patients. (eurekalert.org)
  • The Functional Impact of Alternative Splicing in Cancer. (eurekalert.org)
  • Designing effective and accurate tools for identifying the functional and structural elements in a genome remains at the frontier of genome annotation owing to incompleteness and inaccuracy of the data, limitations in the computational models, and shifting paradigms in genomics, such as alternative splicing. (jcvi.org)
  • Accordingly, AS of the putative splicing factor REDUCED RED-LIGHT RESPONSES IN CRY1CRY2 BACKGROUND1 , previously identified as a red light signaling component, was shifted to the functional variant under light. (plantcell.org)
  • Although the splicing is highly conserved and the polymorphism that modifies it has been associated with altered AED dosage, the functional impact of the splicing on NaV1.1 is unknown. (ucl.ac.uk)
  • Our functional genomic studies show the "G" allele at rs6471859 produces a cryptic 3'UTR splice site regulating expression of CA8-204. (medworm.com)
  • Functional properties of p54, a novel SR protein active in constitutive and alternative splicing. (asm.org)
  • We report here that p54 is a new member of the SR family of splicing factors, as judged from its structural, antigenic, and functional characteristics. (asm.org)
  • Previous evidence indicates that pituitary and steroid hormones regulate alternative splicing of the Slo gene at the stress axis-regulated exon (STREX), with functional implications for the calcium-activated K+ channels prominent in adrenal medullary and pituitary cells. (ovid.com)
  • We find that both DHP and CRMP are derived from this single gene through alternative splicing of paralogous exons: DHP in nonneuronal tissues throughout the animal and CRMP exclusively in the nervous system. (genetics.org)
  • The human proteome is a highly complex extension of the genome wherein a single gene often produces distinct protein forms due to alternative splicing, RNA editing, polymorphisms, and posttranslational modifications. (mcponline.org)
  • H-DBAS - Human-transcriptome DataBase for Alternative Splicing. (github.com)
  • With the advent of whole-transcriptome sequencing, or RNA-seq, we now know that alternative splicing is a generalized phenomenon, with nearly all multiexonic genes subject to alternative splicing. (ovid.com)
  • Recent global sequencing studies have shown that >95% of the transcriptome undergoes some form of alternative splicing. (upenn.edu)
  • To determine if sterol regulated alternative splicing occurs in a larger number of genes in the cholesterol biosynthesis pathway;changes in alternative splicing will be quantified in HepG2 cells, primary human hepatocytes, and immortalized human lymphocyte cell lines treated with specific inhibitors and products of this pathway (Aim 1). (labome.org)
  • Researchers then applied the same PEGASAS strategy to breast cancer and lung cancer datasets and found the same association between Myc activity and alternative splicing, suggesting Myc activation - and thus disruptions in splicing - occurs in many cancers. (chop.edu)
  • This regulation is at the level of splice site selection, occurs rapidly and reversibly, and is concentration dependent. (asm.org)
  • To better understand the causes and consequences of alternative splicing changes during cancer progression, the team looked at RNA sequences from nearly 900 prostate tissue samples, ranging from healthy prostate tissue to localized or aggressive metastatic tumor tissue. (chop.edu)
  • I need to silence 2 different alternative splicing sequences. (protocol-online.org)
  • Firstly, we demonstrated that RNA sequences from EcoRI cleavage sites regulate alternative splicing of Ron exon 5 and 6. (jcancer.org)
  • We assessed the extent of SR gene AS by generating splice graphs based on multiple alignments of ESTs/cDNAs to SR genomic sequences. (uni-koeln.de)
  • Alternative splicing of the P/Q-type channel (Ca V 2.1) promises customization of the computational repertoire of neurons. (jneurosci.org)
  • Using a combination of in vivo minigene assays, in vitro splicing assays and UV-crosslinking assays I correlate the binding of CELF2 to the function of the USE60 and DSE120. (upenn.edu)
  • They found that Myc, a gene involved in normal cell functions and is amplified in many cancers, was linked to alternative splicing changes in genes that themselves regulate alternative splicing. (chop.edu)
  • Here we examine the role of corticosterone in Slo splicing regulation in pituitary and adrenal tissues during the stress-hyporesponsive period of early rat postnatal life. (ovid.com)
  • Mechanisms of alternative splicing are highly variable, and new examples are constantly being found, particularly through the use of high-throughput techniques. (wikipedia.org)
  • For example, although a number of alternative exons have been shown to be regulated by calcium level alterations, the underlying mechanisms are not well understood. (frontiersin.org)
  • Only a handful of studies have explored the underlying mechanisms by which calcium signaling regulates alternative splicing. (frontiersin.org)
  • Next, he discussed the potential mechanisms of calcium-mediated splicing control using three well-studied examples. (frontiersin.org)
  • In this review, we discuss some of the evidence suggesting that alternative splicing of candidate genes such as DRD2 (encoding dopamine D2 receptor) may form the basis of the mechanisms underlying the pathophysiology of alcoholism. (mdpi.com)
  • DESCRIPTION (provided by applicant): The long-term goal of this project is to understand the mechanisms underlying CD45 alternative splicing and the role of CD45 splicing in lymphocyte and haematopoietic cell biology. (labome.org)
  • These findings provide important new insights into the mechanisms involved in neuronal differentiation, but many questions pertaining to the newly identified miRNA/alternative splicing interface remain to be answered. (harvard.edu)
  • Changes in alternative splicing provide cancer with new ways in which it can escape fine cellular regulation. (eurekalert.org)
  • Recently, we have identified coordinated changes in alternative splicing in multiple genes in response to alterations in cellular sterol content. (ovid.com)
  • Alternative splicing is of importance in various types of genetically influenced dyslipidemias and in the regulation of cellular cholesterol metabolism. (ovid.com)
  • KLF6 is regulated by alternative splicing and we propose that the balance of KLF6 alternative splice forms in different cellular compartments within the liver may influence the rate of NAFLD progression. (bmj.com)
  • Given the pervasive and profound involvement of alternative splicing in multiple cellular processes, it is clear that the choice of splice site can have major phenotypic consequences, and defects in the splicing pathway are associated with a variety of disease states. (asm.org)
  • Recent studies showed that interfering with cellular splicing machinery can result in MdmX downregulation in cancer cells. (muni.cz)
  • In a new study published in the journal Cell Reports , researchers show that alterations in a process known as alternative splicing may also trigger the disease. (eurekalert.org)
  • Once researchers understand how exactly the splicing process is regulated, they may be able to predict alternative splicing products from a given gene, which will be helpful as the outcomes of RNA alternative splicing vary and include turning a gene off and changing the function of a protein. (brighthub.com)
  • This decision is made during the splicing process. (wikidoc.org)
  • An additional DNA code or other regulating process, which regulates the alternative splicing. (wikidoc.org)
  • The process in which eukaryotic RNA is edited prior to protein translation is called splicing. (jove.com)
  • We understand that we can make small unusual structured drugs called oligonucleotides, which is the same material DNA is made out of by and large, and introduce that into cells and shift the splicing process. (dnalc.org)
  • And if we can shift splicing process then we should be able to control some of the changes due to mutations in disease processes. (dnalc.org)
  • Charlotte Sumner: So one very elegant way to treat SMA is to try and alter that process of alternative splicing of exon 7 of these RNAs that arise from SMN2. (dnalc.org)
  • We have previously hypothesized that epithelial mesenchymal transition (EMT) may play a central role in the progression of these adenomas and that epithelial splicing regulator 1 (ESRP1) may function prominently as a master regulator of the EMT process in pituitary adenomas causing acromegaly. (diva-portal.org)
  • Taken together, this research examined the viral life cycle by analyzing the critical steps in alternative splicing involved in a viable MVM infection, and will also give insights into the fundamental biological process of alternative splicing. (umsystem.edu)
  • The importance of splicing and alternative splicing is highlighted by the number of human diseases which are associated with mistakes in the splicing process. (hutton.ac.uk)
  • panel to monitor hundreds of alternative splicing events simultaneously, are developing process-specific alternative splicing panels and other systems to follow alternative splicing. (hutton.ac.uk)
  • Alternative splicing allows organisms to rapidly modulate protein functions to physiological changes and therefore represents a highly versatile adaptive process. (cnrs.fr)
  • In this application we build on our recent discovery that the heterogenous nuclear ribonucleoprotein HNRPLL is the primary regulator of CD45 alternative splicing in stimulated T cells. (labome.org)
  • The splicing factor SRSF1 and its regulator, the kinase SRPK1 , were found to be deregulated upon Wnt inactivation in colorectal carcinoma cells. (mcponline.org)