Metabolic Networks and Pathways: Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites.Metabolism: The chemical reactions that occur within the cells, tissues, or an organism. These processes include both the biosynthesis (ANABOLISM) and the breakdown (CATABOLISM) of organic materials utilized by the living organism.Systems Biology: Comprehensive, methodical analysis of complex biological systems by monitoring responses to perturbations of biological processes. Large scale, computerized collection and analysis of the data are used to develop and test models of biological systems.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.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Gene Regulatory Networks: Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations.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.Metabolome: The dynamic collection of metabolites which represent a cell's or organism's net metabolic response to current conditions.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Enzymes: Biological molecules that possess catalytic activity. They may occur naturally or be synthetically created. Enzymes are usually proteins, however CATALYTIC RNA and CATALYTIC DNA molecules have also been identified.Cell Physiological Phenomena: Cellular processes, properties, and characteristics.Neural Networks (Computer): A computer architecture, implementable in either hardware or software, modeled after biological neural networks. Like the biological system in which the processing capability is a result of the interconnection strengths between arrays of nonlinear processing nodes, computerized neural networks, often called perceptrons or multilayer connectionist models, consist of neuron-like units. A homogeneous group of units makes up a layer. These networks are good at pattern recognition. They are adaptive, performing tasks by example, and thus are better for decision-making than are linear learning machines or cluster analysis. They do not require explicit programming.Biomass: Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop.Metabolomics: The systematic identification and quantitation of all the metabolic products of a cell, tissue, organ, or organism under varying conditions. The METABOLOME of a cell or organism is a dynamic collection of metabolites which represent its net response to current conditions.Genome, Bacterial: The genetic complement of a BACTERIA as represented in its DNA.Metabolic Engineering: Methods and techniques used to genetically modify cells' biosynthetic product output and develop conditions for growing the cells as BIOREACTORS.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Autotrophic Processes: The processes by which organisms use simple inorganic substances such as gaseous or dissolved carbon dioxide and inorganic nitrogen as nutrient sources. Contrasts with heterotrophic processes which make use of organic materials as the nutrient supply source. Autotrophs can be either chemoautotrophs (or chemolithotrophs), largely ARCHAEA and BACTERIA, which also use simple inorganic substances for their metabolic energy reguirements; or photoautotrophs (or photolithotrophs), such as PLANTS and CYANOBACTERIA, which derive their energy from light. Depending on environmental conditions some organisms can switch between different nutritional modes (autotrophy; HETEROTROPHY; chemotrophy; or PHOTOTROPHY) to utilize different sources to meet their nutrient and energy requirements.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.Proteome: The protein complement of an organism coded for by its genome.Citric Acid Cycle: A series of oxidative reactions in the breakdown of acetyl units derived from GLUCOSE; FATTY ACIDS; or AMINO ACIDS by means of tricarboxylic acid intermediates. The end products are CARBON DIOXIDE, water, and energy in the form of phosphate bonds.Protein Interaction Mapping: Methods for determining interaction between PROTEINS.Carbon: A nonmetallic element with atomic symbol C, atomic number 6, and atomic weight [12.0096; 12.0116]. It may occur as several different allotropes including DIAMOND; CHARCOAL; and GRAPHITE; and as SOOT from incompletely burned fuel.Computer Graphics: The process of pictorial communication, between human and computers, in which the computer input and output have the form of charts, drawings, or other appropriate pictorial representation.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.Substrate Cycling: A set of opposing, nonequilibrium reactions catalyzed by different enzymes which act simultaneously, with at least one of the reactions driven by ATP hydrolysis. The results of the cycle are that ATP energy is depleted, heat is produced and no net substrate-to-product conversion is achieved. Examples of substrate cycling are cycling of gluconeogenesis and glycolysis pathways and cycling of the triglycerides and fatty acid pathways. Rates of substrate cycling may be increased many-fold in association with hypermetabolic states resulting from severe burns, cold exposure, hyperthyroidism, or acute exercise.Biochemical Processes: Chemical reactions or functions, enzymatic activities, and metabolic pathways of living things.Escherichia coli K12: A species of gram-negative, rod-shaped bacteria belonging to the K serogroup of ESCHERICHIA COLI. It lives as a harmless inhabitant of the human LARGE INTESTINE and is widely used in medical and GENETIC RESEARCH.Glycolysis: A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH.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.Genomics: The systematic study of the complete DNA sequences (GENOME) of organisms.User-Computer Interface: The portion of an interactive computer program that issues messages to and receives commands from a user.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Pentose Phosphate Pathway: An oxidative decarboxylation process that converts GLUCOSE-6-PHOSPHATE to D-ribose-5-phosphate via 6-phosphogluconate. The pentose product is used in the biosynthesis of NUCLEIC ACIDS. The generated energy is stored in the form of NADPH. This pathway is prominent in tissues which are active in the synthesis of FATTY ACIDS and STEROIDS.Heterotrophic Processes: The processes by which organisms utilize organic substances as their nutrient sources. Contrasts with AUTOTROPHIC PROCESSES which make use of simple inorganic substances as the nutrient supply source. Heterotrophs can be either chemoheterotrophs (or chemoorganotrophs) which also require organic substances such as glucose for their primary metabolic energy requirements, or photoheterotrophs (or photoorganotrophs) which derive their primary energy requirements from light. Depending on environmental conditions some organisms can switch between different nutritional modes (AUTOTROPHY; heterotrophy; chemotrophy; or PHOTOTROPHY) to utilize different sources to meet their nutrients and energy requirements.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.Databases, Genetic: Databases devoted to knowledge about specific genes and gene products.Software Design: Specifications and instructions applied to the software.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.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.Databases, Factual: Extensive collections, reputedly complete, of facts and data garnered from material of a specialized subject area and made available for analysis and application. The collection can be automated by various contemporary methods for retrieval. The concept should be differentiated from DATABASES, BIBLIOGRAPHIC which is restricted to collections of bibliographic references.Genome: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.Biological Evolution: The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Phototrophic Processes: Processes by which phototrophic organisms use sunlight as their primary energy source. Contrasts with chemotrophic processes which do not depend on light and function in deriving energy from exogenous chemical sources. Photoautotrophy (or photolithotrophy) is the ability to use sunlight as energy to fix inorganic nutrients to be used for other organic requirements. Photoautotrophs include all GREEN PLANTS; GREEN ALGAE; CYANOBACTERIA; and green and PURPLE SULFUR BACTERIA. Photoheterotrophs or photoorganotrophs require a supply of organic nutrients for their organic requirements but use sunlight as their primary energy source; examples include certain PURPLE NONSULFUR BACTERIA. Depending on environmental conditions some organisms can switch between different nutritional modes (AUTOTROPHY; HETEROTROPHY; chemotrophy; or phototrophy) to utilize different sources to meet their nutrients and energy requirements.Amino Acids, Aromatic: Amino acids containing an aromatic side chain.Cells: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.Genome, Fungal: The complete gene complement contained in a set of chromosomes in a fungus.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.Bacteria: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Archaea: One of the three domains of life (the others being BACTERIA and Eukarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: (1) the presence of characteristic tRNAs and ribosomal RNAs; (2) the absence of peptidoglycan cell walls; (3) the presence of ether-linked lipids built from branched-chain subunits; and (4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least four kingdoms: CRENARCHAEOTA; EURYARCHAEOTA; NANOARCHAEOTA; and KORARCHAEOTA.Biochemistry: The study of the composition, chemical structures, and chemical reactions of living things.Nerve Net: A meshlike structure composed of interconnecting nerve cells that are separated at the synaptic junction or joined to one another by cytoplasmic processes. In invertebrates, for example, the nerve net allows nerve impulses to spread over a wide area of the net because synapses can pass information in any direction.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Clostridium acetobutylicum: A species of gram-positive bacteria in the family Clostridiaceae, used for the industrial production of SOLVENTS.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.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.GlyoxylatesMethylobacterium extorquens: A species of METHYLOBACTERIUM which can utilize acetate, ethanol, or methylamine as a sole carbon source. (From Bergey's Manual of Determinative Bacteriology, 9th ed)Systems Theory: Principles, models, and laws that apply to complex interrelationships and interdependencies of sets of linked components which form a functioning whole, a system. Any system may be composed of components which are systems in their own right (sub-systems), such as several organs within an individual organism.Gene Knockout Techniques: Techniques to alter a gene sequence that result in an inactivated gene, or one in which the expression can be inactivated at a chosen time during development to study the loss of function of a gene.Photobioreactors: Devices for generating biological products that use light as the energy source. They are used for controlled BIOMASS production such as growing cyanobacteria, mosses, or algae.Genes, Essential: Those genes found in an organism which are necessary for its viability and normal function.Databases, Chemical: Databases devoted to knowledge about specific chemicals.Methanosarcina barkeri: A species of halophilic archaea whose organisms are nonmotile. Habitats include freshwater and marine mud, animal-waste lagoons, and the rumens of ungulates.Buchnera: A genus of gram-negative bacteria which are obligately intracellular endosymbionts of APHIDS. The bacteria are found within specialized cells in the aphid body cavity.Systems Integration: The procedures involved in combining separately developed modules, components, or subsystems so that they work together as a complete system. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Proteomics: The systematic study of the complete complement of proteins (PROTEOME) of organisms.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Molecular Sequence Annotation: The addition of descriptive information about the function or structure of a molecular sequence to its MOLECULAR SEQUENCE DATA record.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.Gene Expression Regulation, Fungal: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.Multienzyme Complexes: Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.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.Computer Communication Networks: A system containing any combination of computers, computer terminals, printers, audio or visual display devices, or telephones interconnected by telecommunications equipment or cables: used to transmit or receive information. (Random House Unabridged Dictionary, 2d ed)Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Carbon Cycle: The cycle by which the element carbon is exchanged between organic matter and the earth's physical environment.Thermoanaerobacterium: A genus of gram-positive, anaerobic bacteria in the family Thermoanaerobacteriaceae. They are thermophilic and saccharolytic.Environment: The external elements and conditions which surround, influence, and affect the life and development of an organism or population.Carbon Isotopes: Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.Plants: Multicellular, eukaryotic life forms of kingdom Plantae (sensu lato), comprising the VIRIDIPLANTAE; RHODOPHYTA; and GLAUCOPHYTA; all of which acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations.Fermentation: Anaerobic degradation of GLUCOSE or other organic nutrients to gain energy in the form of ATP. End products vary depending on organisms, substrates, and enzymatic pathways. Common fermentation products include ETHANOL and LACTIC ACID.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)Corynebacterium glutamicum: A species of gram-positive, asporogenous, non-pathogenic, soil bacteria that produces GLUTAMIC ACID.Community Networks: Organizations and individuals cooperating together toward a common goal at the local or grassroots level.Adaptation, Biological: Changes in biological features that help an organism cope with its ENVIRONMENT. These changes include physiological (ADAPTATION, PHYSIOLOGICAL), phenotypic and genetic changes.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.Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc.Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Bacterial Physiological Phenomena: Physiological processes and properties of BACTERIA.Data Compression: Information application based on a variety of coding methods to minimize the amount of data to be stored, retrieved, or transmitted. Data compression can be applied to various forms of data, such as images and signals. It is used to reduce costs and increase efficiency in the maintenance of large volumes of data.Genome, Plant: The genetic complement of a plant (PLANTS) as represented in its DNA.Genes, Fungal: The functional hereditary units of FUNGI.Vitamin K 3: A synthetic naphthoquinone without the isoprenoid side chain and biological activity, but can be converted to active vitamin K2, menaquinone, after alkylation in vivo.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.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.Principal Component Analysis: Mathematical procedure that transforms a number of possibly correlated variables into a smaller number of uncorrelated variables called principal components.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.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.NADP: Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed)Adaptation, Physiological: The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT.trans-Golgi Network: A network of membrane compartments, located at the cytoplasmic side of the GOLGI APPARATUS, where proteins and lipids are sorted for transport to various locations in the cell or cell membrane.Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Chemistry, Organic: The study of the structure, preparation, properties, and reactions of carbon compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Prokaryotic Cells: Cells lacking a nuclear membrane so that the nuclear material is either scattered in the cytoplasm or collected in a nucleoid region.Bacterial Proteins: Proteins found in any species of bacterium.Photosynthesis: The synthesis by organisms of organic chemical compounds, especially carbohydrates, from carbon dioxide using energy obtained from light rather than from the oxidation of chemical compounds. Photosynthesis comprises two separate processes: the light reactions and the dark reactions. In higher plants; GREEN ALGAE; and CYANOBACTERIA; NADPH and ATP formed by the light reactions drive the dark reactions which result in the fixation of carbon dioxide. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)Kinetics: The rate dynamics in chemical or physical systems.Databases, Protein: Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.Artificial Intelligence: Theory and development of COMPUTER SYSTEMS which perform tasks that normally require human intelligence. Such tasks may include speech recognition, LEARNING; VISUAL PERCEPTION; MATHEMATICAL COMPUTING; reasoning, PROBLEM SOLVING, DECISION-MAKING, and translation of language.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.Fuzzy Logic: Approximate, quantitative reasoning that is concerned with the linguistic ambiguity which exists in natural or synthetic language. At its core are variables such as good, bad, and young as well as modifiers such as more, less, and very. These ordinary terms represent fuzzy sets in a particular problem. Fuzzy logic plays a key role in many medical expert systems.Software Validation: The act of testing the software for compliance with a standard.Lactobacillus plantarum: A species of rod-shaped, LACTIC ACID bacteria used in PROBIOTICS and SILAGE production.Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., GENETIC ENGINEERING) is a central focus; laboratory methods used include TRANSFECTION and CLONING technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction.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.Information Storage and Retrieval: Organized activities related to the storage, location, search, and retrieval of information.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.Protein Interaction Maps: Graphs representing sets of measurable, non-covalent physical contacts with specific PROTEINS in living organisms or in cells.Drug Discovery: The process of finding chemicals for potential therapeutic use.Industrial Microbiology: The study, utilization, and manipulation of those microorganisms capable of economically producing desirable substances or changes in substances, and the control of undesirable microorganisms.Gene Expression Regulation, Plant: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.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.Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

*  In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development | Nature...

While some of them use detailed kinetic models of several particular metabolic networks to derive importance factors17, in ... According to DART usage guidelines, we evaluated gene network consistency and pruned each network. We next predicted pathway ... In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development. *Ivan V. Ozerov1. ... How to cite this article: Ozerov, I. V. et al. In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method ...

*  Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response...

... signaling networks.18,​. 19,​. 20,​. 21 In addition, consensus maps detailing the cell cycle processes and metabolic pathways ... b) Network motifs specific to stimuli response pathways. Among 30 motifs common to the six yeast stress response pathways, 12 ... it is interesting to compare these features with the bow-tie structures observed in metabolic networks. In metabolic processes ... Pathway connectivity and signaling coordination in the yeast stress‐activated signaling network. . Mol. Syst. Biol. 10: 759 ( ...

*  Herniarin | C10H8O3 | ChemSpider

Metabolic Pathways. Molecular Libraries Screening Center Network. Natural Products. NIH Substance Repository. Physical ...

*  2-Methyl-2-propanyl 3-bromopropanoate | C7H13BrO2 | ChemSpider

Metabolic Pathways. Molecular Libraries Screening Center Network. Natural Products. NIH Substance Repository. Physical ...

*  benzene; carbon monoxide; chromium | C9H6CrO3 | ChemSpider

Metabolic Pathways. Molecular Libraries Screening Center Network. Natural Products. NIH Substance Repository. Physical ...

*  4-(1H-Benzimidazol-1-ylmethyl)benzoic acid | C15H12N2O2 | ChemSpider

Metabolic Pathways. Molecular Libraries Screening Center Network. Natural Products. NIH Substance Repository. Physical ...

*  8ξ,12ξ,16ξ)-Strychnidin-10-one | C21H22N2O2 | ChemSpider

Metabolic Pathways. Molecular Libraries Screening Center Network. Natural Products. NIH Substance Repository. Physical ...

*  3,5,6,7-Tetrahydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one | C15H10O7 | ChemSpider

Metabolic Pathways. Molecular Libraries Screening Center Network. Natural Products. NIH Substance Repository. Physical ...

*  2</sup>H<sub>5</sub>)Aniline |...

Metabolic Pathways. Molecular Libraries Screening Center Network. Natural Products. NIH Substance Repository. Physical ...

*  9,11-Octadecadienoic acid | C18H32O2 | ChemSpider

Metabolic Pathways. Molecular Libraries Screening Center Network. Natural Products. NIH Substance Repository. Physical ...

*  Genome-Scale Metabolic Network Validation of Shewanella oneidensis Using Transposon Insertion Frequency Analysis

Author Summary Metabolic modeling techniques play a central role in rational design of industrial strains, personalized medicine, and automated network reconstruction. However, due to the large size of models, very few have been comprehensively tested using single gene knockout mutants for every gene in the model. Such a genetic test could evaluate whether genes that for a given condition are predicted to be essential by a model, are indeed essential in reality (and vice versa). We developed a new probability-based technology that identifies the essentiality of genes from observed transposon insertion data. This data was acquired by pooling tens of thousands of transposon mutants, and localizing the insertion locations all at once by using massive parallel sequencing. We utilized this gene essentiality data for the genome-scale genetic validation of a metabolic model. For instance: our work identified nonessential genes that were predicted to be essential for growth by an ...

*  Where Tuberculosis Meets Computation: 10 Points of Intersection | Biomedical Computation Review

Researchers would like to understand how TB survives its veiled existence in the lung. "If we can better understand latency, it might change our minds about how to treat latency," Galagan says.. To understand latency, researchers must combine gene regulatory models with metabolic network models. "There are probably 1,000 papers on how to model regulatory networks and probably 1,000 on metabolic networks" says Nathan Price, PhD, of the Institute for Systems Biology in Seattle. "But there are very few that do them together in an integrated way.". In a paper published in PLoS Computational Biology in June 2011, McFadden's team explored changes in metabolites when Mtb is grown inside a host cell (a macrophage). Their method, called differential producibility analysis (DPA), uses a metabolic network to extract metabolic signals from transcriptome data, allowing a glimpse at which pathways Mtb is ...

*  Plant Metabolic Pathway Databases | Plant Metabolic Network

We are pleased to announce the PMN12 release. In this release we introduce 54 new species-specific metabolic pathway databases, which brings the total number of species-specific databases to 76. The 76 species cover the green plant lineage widely, including green algae, a moss, a club moss, a basal flowering plant, and higher plants of monocots and eudicots. They include major crops from grains to vegetables and fruits. ...

*  The Tree of Life: Lake arrowhead notes - UPDATED

Not sure exactly how to say this, but here goes. There was one talk in the AM I was not overly fond of. This was a talk by Bernard Palsson. Now I confess, I am not overly familiar with much of his work but what I know of it suggests he does some really solid, interesting and important work on metabolic network modeling and analysis. But his talk at this meeting was disappointing. His talk was about his use of genome sequencing to characterize "adaptive evolution" in E. coli. And the results he presented seemed solid enough. The problem I had was that it was a prime example of "overselling genomics". Why? Here is what they did. They took E. coli mutants. And the then took them through cycles of growth and then dilution. And then they looked at the populations after a certain number of generations and did a variety of analyses. Included in this was some whole genome sequencing that helped identify mutations arising in the cultures. And then they did some characterization of these ...

Flux (metabolism): Flux, or metabolic flux is the rate of turnover of molecules through a metabolic pathway. Flux is regulated by the enzymes involved in a pathway.List of systems biology conferences: Systems biology is a biological study field that focuses on the systematic study of complex interactions in biological systems, thus using a new perspective (integration instead of reduction) to study them. Particularly from year 2000 onwards, the term is used widely in the biosciences.Matrix model: == Mathematics and physics ==Interval boundary element method: Interval boundary element method is classical boundary element method with the interval parameters.
Biological network: A biological network is any network that applies to biological systems. A network is any system with sub-units that are linked into a whole, such as species units linked into a whole food web.PSI Protein Classifier: PSI Protein Classifier is a program generalizing the results of both successive and independent iterations of the PSI-BLAST program. PSI Protein Classifier determines belonging of the found by PSI-BLAST proteins to the known families.Metabolome: The metabolome refers to the complete set of small-molecule chemicals found within a biological sample. The biological sample can be a cell, a cellular organelle, an organ, a tissue, a tissue extract, a biofluid or an entire organism.Clonal Selection Algorithm: In artificial immune systems, Clonal selection algorithms are a class of algorithms inspired by the clonal selection theory of acquired immunity that explains how B and T lymphocytes improve their response to antigens over time called affinity maturation. These algorithms focus on the Darwinian attributes of the theory where selection is inspired by the affinity of antigen-antibody interactions, reproduction is inspired by cell division, and variation is inspired by somatic hypermutation.Enzyme Commission number: The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze.Physical neural network: A physical neural network is a type of artificial neural network in which an electrically adjustable resistance material is used to emulate the function of a neural synapse. "Physical" neural network is used to emphasize the reliance on physical hardware used to emulate neurons as opposed to software-based approaches which simulate neural networks.Metabolomics: Metabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles.Global microbial identifier: The genomic epidemiological database for global identification of microorganisms or global microbial identifier (GMI) is a platform for storing whole genome sequencing (WGS) data of microorganisms, for the identification of relevant genes and for the comparison of genomes to detect and track-and-trace infectious disease outbreaks and emerging pathogens. The database holds two types of information: 1) genomic information of microorganisms, linked to, 2) metadata of those microorganism such as epidemiological details.Tank chassis: Tank container chassis, also referred to as tank chassis, drop frame chassis or tank trailers, are a form of intermodal transportation for portable bulk liquid containers or ISO tank containers. They are characteristically longer and have lower deck height ideal for transporting constantly shifting payloads.Mac OS X Server 1.0List of strains of Escherichia coli: Escherichia coli is a well studied bacterium that was first identified by Theodor Escherich, after whom it was later named.Plant Proteome Database: The Plant Proteome Database is a National Science Foundation-funded project to determine the biological function of each protein in plants.Sun Q, Zybailov B, Majeran W, Friso G, Olinares PD, van Wijk KJ.Reverse Krebs cycle: The reverse Krebs cycle (also known as the reverse tricarboxylic acid cycle, the reverse TCA cycle, or the reverse citric acid cycle)Protein–protein interactionCarbon–carbon bond: A carbon–carbon bond is a covalent bond between two carbon atoms. The most common form is the single bond: a bond composed of two electrons, one from each of the two atoms.List of molecular graphics systems: This is a list of software systems that are used for visualizing macromolecules.Futile cycle: A futile cycle, also known as a substrate cycle, occurs when two metabolic pathways run simultaneously in opposite directions and have no overall effect other than to dissipate energy in the form of heat. For example, if glycolysis and gluconeogenesis were to be active at the same time, glucose would be converted to pyruvate by glycolysis and then converted back to glucose by gluconeogenesis, with an overall consumption of ATP.Shirley du Boulay: Shirley du Boulay (born 1933BnF notice d'autorité personne (in French) and similar sources) is a British author and biographer, resident in Oxford.Anaerobic glycolysis: Anaerobic glycolysis is the transformation of glucose to pyruvate when limited amounts of oxygen (O2) are available. Anaerobic glycolysis is only an effective means of energy production during short, intense exercise, providing energy for a period ranging from 10 seconds to 2 minutes.Gene signature: A gene signature is a group of genes in a cell whose combined expression patternItadani H, Mizuarai S, Kotani H. Can systems biology understand pathway activation?Ontario Genomics Institute: The Ontario Genomics Institute (OGI) is a not-for-profit organization that manages cutting-edge genomics research projects and platforms.The Ontario Genomics Institute OGI also helps scientists find paths to the marketplace for their discoveries and the products to which they lead, and it works through diverse outreach and educational activities to raise awareness and facilitate informed public dialogue about genomics and its social impacts.Immersive technologyZuotin: Z-DNA binding protein 1, also known as Zuotin, is a Saccharomyces cerevisiae yeast gene.Pentose phosphate pathwayLacandonia: Lacandonia is a mycoheterotrophic plant that contains no chlorophyll and has the unusual characteristic of inverted positions of the male (androecium) and female (gynoecium) floral parts, something that had not been seen in any other plants with the occasional exception of some individuals of the related 'Esteban Martinez and Clara Hilda Ramos Lacandoniaceae (Triuridales): Una Nueva Familia de Mexico. Ann.Extracellular: In cell biology, molecular biology and related fields, the word extracellular (or sometimes extracellular space) means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid.List of software development philosophies: This is a list of approaches, styles, and philosophies in software development not included in the category tree of software development philosophies. It contains also software development processes, software development methodologies and single practices, principles and laws.Index of energy articles: This is an index of energy articles.List of sequenced eukaryotic genomesMolecular evolution: Molecular evolution is a change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes.Aerobic anoxygenic photoheterotroph bacteria: Aerobic anoxygenic photoheterotrophic bacteria (AAPB), also named aerobic anoxygenic photoheterotrophs (AAPs), is a group of bacteria that are primarily heterotrophic but can utilize light energy through bacterial chlorophyll a.Nianzhi Jiao, Gerhard J.Biopterin-dependent aromatic amino acid hydroxylase: In molecular biology, the biopterin-dependent aromatic amino acid hydroxylases (abbreviated AAAH) constitute a family of aromatic amino acid hydroxylases, including phenylalanine 4-hydroxylase (), tyrosine 3-hydroxylase (), and tryptophan 5-hydroxylase (). These enzymes primarily hydroxylate phenylalanine, tyrosine, and tryptophan, respectively.Inverse probability weighting: Inverse probability weighting is a statistical technique for calculating statistics standardized to a population different from that in which the data was collected. Study designs with a disparate sampling population and population of target inference (target population) are common in application.Exogenous bacteria: Exogenous bacteria are microorganisms introduced to closed biological systems from the external world. They exist in aquatic and terrestrial environments, as well as the atmosphere.Phenotype microarray: The phenotype microarray approach is a technology for high-throughput phenotyping of cells.Domain (biology): In biological taxonomy, a domain (also superregnum, superkingdom, empire, or regio) is the highest taxonomic rank of organisms in the three-domain system of taxonomy designed by Carl Woese, an American microbiologist and biophysicist. According to the Woese system, introduced in 1990, the tree of life consists of three domains: Archaea (a term which Woese created), Bacteria, and Eukaryota.Frank Dickens (biochemist): Frank Dickens FRS (15 December 1899 - 15 June 1986) was a biochemist, best known for his work at the Courtauld Institute of Biochemistry with Edward Charles Dodds on the pentose phosphate pathway which generates NADPH.Peter N.Clostridium acetobutylicum: Clostridium acetobutylicum, ATCC 824, is a commercially valuable bacterium sometimes called the "Weizmann Organism", after Jewish-Russian-born Chaim Weizmann. A senior lecturer at the University of Manchester, England, he used them in 1916 as a bio-chemical tool to produce at the same time, jointly, acetone, ethanol, and butanol from starch.Von Neumann regular ring: In mathematics, a von Neumann regular ring is a ring R such that for every a in R there exists an x in R such that . To avoid the possible confusion with the regular rings and regular local rings of commutative algebra (which are unrelated notions), von Neumann regular rings are also called absolutely flat rings, because these rings are characterized by the fact that every left module is flat.Internet organizations: This is a list of Internet organizations, or organizations that play or played a key role in the evolution of the Internet by developing recommendations, standards, and technology; deploying infrastructure and services; and addressing other major issues.Glyoxylic acidCritical systems thinking: Critical systems thinking is a systems thinking framework, that wants to bring unity to the diversity of different systems approaches and advises managers how best to use them.Werner Ulrich (2003).Photobioreactor: A photobioreactor is a bioreactor that utilizes a light source to cultivate phototrophic microorganisms. These organisms use photosynthesis to generate biomass from light and carbon dioxide and include plants, mosses, macroalgae, microalgae, cyanobacteria and purple bacteria.InvitrogenMethylated-thiol-coenzyme M methyltransferase: Methylated-thiol-coenzyme M methyltransferase (, mtsA (gene)) is an enzyme with system name methylated-thiol:coenzyme M methyltransferase. This enzyme catalyses the following chemical reactionBuchnera (bacterium): Buchnera aphidicola, a member of the Proteobacteria, is the primary endosymbiont of aphids, and has been studied in the pea aphid, Acyrthosiphon pisum. Buchnera is believed to have had a free-living, Gram-negative ancestor similar to a modern Enterobacteriaceae, such as Escherichia coli.Proteomics Standards Initiative: The Proteomics Standards Initiative (PSI) is a working group of Human Proteome Organization. It aims to define data standards for proteomics in order to facilitate data comparison, exchange and verification.Branching order of bacterial phyla (Gupta, 2001): There are several models of the Branching order of bacterial phyla, one of these was proposed in 2001 by Gupta based on conserved indels or protein, termed "protein signatures", an alternative approach to molecular phylogeny. Some problematic exceptions and conflicts are present to these conserved indels, however, they are in agreement with several groupings of classes and phyla.GAI (Arabidopsis thaliana gene)Deletion (genetics)Acknowledgement (data networks): In data networking, an acknowledgement (or acknowledgment) is a signal passed between communicating processes or computers to signify acknowledgement, or receipt of response, as part of a communications protocol. For instance, ACK packets are used in the Transmission Control Protocol (TCP) to acknowledge the receipt of SYN packets when establishing a connection, data packets while a connection is being used, and FIN packets when terminating a connection.Escherichia coli (molecular biology): Escherichia coli (; commonly abbreviated E. coli) is a gammaproteobacterium commonly found in the lower intestine of warm-blooded organisms (endotherms).Glucose transporterCarbon fixation: Carbon fixation or сarbon assimilation refers to the conversion process of inorganic carbon (carbon dioxide) to organic compounds by living organisms. The most prominent example is photosynthesis, although chemosynthesis is another form of carbon fixation that can take place in the absence of sunlight.Evolution in Variable EnvironmentSteptoean positive carbon isotope excursion: The Steptoean Positive Carbon Isotope Excursion (SPICE) was a geological event which occurred about 500 million years ago at the end of the Cambrian Period. The SPICE event was a sudden reversal of the anoxia (lack of oxygen) that had steadily spread throughout the oceans during the Cambrian which also affected the atmosphere.Lactic acid fermentationStandard enthalpy of formation: The standard enthalpy of formation or standard heat of formation of a compound is the change of enthalpy during the formation of 1 mole of the compound from its constituent elements, with all substances in their standard states at 1 atmosphere (1 atm or 101.3 kPa).Generalizability theory: Generalizability theory, or G Theory, is a statistical framework for conceptualizing, investigating, and designing reliable observations. It is used to determine the reliability (i.Chromosome engineering: Chromosome engineering is "the controlled generation of chromosomal deletions, inversions, or translocations with defined endpoints." For: By combining chromosomal translocation, chromosomal inversion,and chromosomal deletion, chromosome engineering has been shown to identify the underlying genes that cause certain diseases in mice.Gas chromatography–mass spectrometry: right|300 px|Example of a GC-MS instrument|thumbLempel–Ziv–Oberhumer: Lempel–Ziv–Oberhumer (LZO) is a lossless data compression algorithm that is focused on decompression speed.No Mend No RepairRV coefficient: In statistics, the RV coefficient

(1/3529) Where are we in genomics?

Genomic studies provide scientists with methods to quickly analyse genes and their products en masse. The first high-throughput techniques to be developed were sequencing methods. A great number of genomes from different organisms have thus been sequenced. Genomics is now shifting to the study of gene expression and function. In the past 5-10 years genomics, proteomics and high-throughput microarray technologies have fundamentally changed our ability to study the molecular basis of cells and tissues in health and diseases, giving a new comprehensive view. For example, in cancer research we have seen new diagnostic opportunities for tumour classification, and prognostication. A new exciting development is metabolomics and lab-on-a-chip techniques (which combine miniaturization and automation) for metabolic studies. However, to interpret the large amount of data, extensive computational development is required. In the coming years, we will see the study of biological networks dominating the scene in Physiology. The great accumulation of genomics information will be used in computer programs to simulate biologic processes. Originally developed for genome analysis, bioinformatics now encompasses a wide range of fields in biology from gene studies to integrated biology (i.e. combination of different data sets from genes to metabolites). This is systems biology which aims to study biological organisms as a whole. In medicine, scientific results and applied biotechnologies arising from genomics will be used for effective prediction of diseases and risk associated with drugs. Preventive medicine and medical therapy will be personalized. Widespread applications of genomics for personalized medicine will require associations of gene expression pattern with diagnoses, treatment and clinical data. This will help in the discovery and development of drugs. In agriculture and animal science, the outcomes of genomics will include improvement in food safety, in crop yield, in traceability and in quality of animal products (dairy products and meat) through increased efficiency in breeding and better knowledge of animal physiology. Genomics and integrated biology are huge tasks and no single lab can pursue this alone. We are probably at the end of the beginning rather than at the beginning of the end because Genomics will probably change Biology to a greater extent than previously forecasted. In addition, there is a great need for more information and better understanding of genomics before complete public acceptance.  (+info)

(2/3529) Identification of metabolic system parameters using global optimization methods.

BACKGROUND: The problem of estimating the parameters of dynamic models of complex biological systems from time series data is becoming increasingly important. METHODS AND RESULTS: Particular consideration is given to metabolic systems that are formulated as Generalized Mass Action (GMA) models. The estimation problem is posed as a global optimization task, for which novel techniques can be applied to determine the best set of parameter values given the measured responses of the biological system. The challenge is that this task is nonconvex. Nonetheless, deterministic optimization techniques can be used to find a global solution that best reconciles the model parameters and measurements. Specifically, the paper employs branch-and-bound principles to identify the best set of model parameters from observed time course data and illustrates this method with an existing model of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively simple yet representative system with five dependent states and a total of 19 unknown parameters of which the values are to be determined. CONCLUSION: The efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae example. The method described in this paper is likely to be widely applicable in the dynamic modeling of metabolic networks.  (+info)

(3/3529) Metabolic complementarity and genomics of the dual bacterial symbiosis of sharpshooters.

Mutualistic intracellular symbiosis between bacteria and insects is a widespread phenomenon that has contributed to the global success of insects. The symbionts, by provisioning nutrients lacking from diets, allow various insects to occupy or dominate ecological niches that might otherwise be unavailable. One such insect is the glassy-winged sharpshooter (Homalodisca coagulata), which feeds on xylem fluid, a diet exceptionally poor in organic nutrients. Phylogenetic studies based on rRNA have shown two types of bacterial symbionts to be coevolving with sharpshooters: the gamma-proteobacterium Baumannia cicadellinicola and the Bacteroidetes species Sulcia muelleri. We report here the sequencing and analysis of the 686,192-base pair genome of B. cicadellinicola and approximately 150 kilobase pairs of the small genome of S. muelleri, both isolated from H. coagulata. Our study, which to our knowledge is the first genomic analysis of an obligate symbiosis involving multiple partners, suggests striking complementarity in the biosynthetic capabilities of the two symbionts: B. cicadellinicola devotes a substantial portion of its genome to the biosynthesis of vitamins and cofactors required by animals and lacks most amino acid biosynthetic pathways, whereas S. muelleri apparently produces most or all of the essential amino acids needed by its host. This finding, along with other results of our genome analysis, suggests the existence of metabolic codependency among the two unrelated endosymbionts and their insect host. This dual symbiosis provides a model case for studying correlated genome evolution and genome reduction involving multiple organisms in an intimate, obligate mutualistic relationship. In addition, our analysis provides insight for the first time into the differences in symbionts between insects (e.g., aphids) that feed on phloem versus those like H. coagulata that feed on xylem. Finally, the genomes of these two symbionts provide potential targets for controlling plant pathogens such as Xylella fastidiosa, a major agroeconomic problem, for which H. coagulata and other sharpshooters serve as vectors of transmission.  (+info)

(4/3529) Potential compensatory responses through autophagic/lysosomal pathways in neurodegenerative diseases.

Intracellular protein degradation decreases with age, altering the important balance between protein synthesis and breakdown. Slowly, protein accumulation events increase causing axonopathy, synaptic deterioration, and subsequent cell death. As toxic species accumulate, autophagy-lysosomal protein degradation pathways are activated. Responses include autophagic vacuoles that degrade damaged cellular components and long-lived proteins, as well as enhanced levels of lysosomal hydrolases. Although such changes correlate with neuronal atrophy in age-related neurodegenerative disorders and in related models of protein accumulation, the autophagic/lysosomal responses appear to be compensatory reactions. Recent studies indicate that protein oligomerization/ aggregation induces autophagy and activates lysosomal protein degradation in an attempt to clear toxic accumulations. Such compensatory responses may delay cell death and account for the gradual nature of protein deposition pathology that can extend over months/years in model systems and years/decades in the human diseases. Correspondingly, enhancement of compensatory pathways shifts the balance from pathogenesis to protection. Positive modulation of protein degradation processes represents a strategy to promote clearance of toxic accumulations and to slow the synaptopathogenesis and associated cognitive decline in aging-related dementias.  (+info)

(5/3529) Transcriptome kinetics of arsenic-induced adaptive response in zebrafish liver.

Arsenic is a prominent environmental toxicant and carcinogen; however, its molecular mechanism of toxicity and carcinogenicity remains poorly understood. In this study, we performed microarray-based expression profiling on liver of zebrafish exposed to 15 parts/million (ppm) arsenic [As(V)] for 8-96 h to identify global transcriptional changes and biological networks involved in arsenic-induced adaptive responses in vivo. We found that there was an increase of transcriptional activity associated with metabolism, especially for biosyntheses, membrane transporter activities, cytoplasm, and endoplasmic reticulum in the 96 h of arsenic treatment, while transcriptional programs for proteins in catabolism, energy derivation, and stress response remained active throughout the arsenic treatment. Many differentially expressed genes encoding proteins involved in heat shock proteins, DNA damage/repair, antioxidant activity, hypoxia induction, iron homeostasis, arsenic metabolism, and ubiquitin-dependent protein degradation were identified, suggesting strongly that DNA and protein damage as a result of arsenic metabolism and oxidative stress caused major cellular injury. These findings were comparable with those reported in mammalian systems, suggesting that the zebrafish liver coupled with the available microarray technology present an excellent in vivo toxicogenomic model for investigating arsenic toxicity. We proposed an in vivo, acute arsenic-induced adaptive response model of the zebrafish liver illustrating the relevance of many transcriptional activities that provide both global and specific information of a coordinated adaptive response to arsenic in the liver.  (+info)

(6/3529) Dietary electrolyte-driven responses in the renal WNK kinase pathway in vivo.

WNK1 and WNK4 are unusual serine/threonine kinases with atypical positioning of the catalytic active-site lysine (WNK: With-No-K[lysine]). Mutations in these WNK kinase genes can cause familial hyperkalemic hypertension (FHHt), an autosomal dominant, hypertensive, hyperkalemic disorder, implicating this novel WNK pathway in normal regulation of BP and electrolyte balance. Full-length (WNK1-L) and short (WNK1-S) kinase-deficient WNK1 isoforms previously have been identified. Importantly, WNK1-S is overwhelmingly predominant in kidney. Recent Xenopus oocyte studies implicate WNK4 in inhibition of both thiazide-sensitive co-transporter-mediated Na+ reabsorption and K+ secretion via renal outer medullary K+ channel and now suggest that WNK4 is inhibited by WNK1-L, itself inhibited by WNK1-S. This study examined WNK pathway gene expression in mouse kidney and its regulation in vivo. Expression of WNK1-S and WNK4 is strongest in distal tubule, dropping sharply in collecting duct and with WNK4 also expressed in thick ascending limb and the macula densa. These nephron segments that express WNK1-S and WNK4 mRNA have major influence on long-term NaCl reabsorption, BP, K+, and acid-base balance, processes that all are disrupted in FHHt. In vivo, this novel WNK pathway responds with significant upregulation of WNK1-S and WNK4 with high K+ intake and reduction in WNK1-S on chronic lowering of K+ or Na+ intake. A two-compartment distal nephron model explains these in vivo findings and the pathophysiology of FHHt well, with WNK and classic aldosterone pathways responding to drivers from K+ balance, extracellular volume, and aldosterone and cross-talk through distal Na+ delivery regulating electrolyte balance and BP.  (+info)

(7/3529) Reconstructing the regulatory kinase pathways of myogenesis from phosphopeptide data.

Multiple kinase activities are required for skeletal muscle differentiation. However, the mechanisms by which these kinase pathways converge to coordinate the myogenic process are unknown. Using multiple phosphoprotein and phosphopeptide enrichment techniques we obtained phosphopeptides from growing and differentiating C2C12 muscle cells and determined specific peptide sequences using LC-MS/MS. To place these phosphopeptides into a rational context, a bioinformatics approach was used. Phosphorylation sites were matched to known site-specific and to site non-specific kinase-substrate interactions, and then other substrates and upstream regulators of the implicated kinases were incorporated into a model network of protein-protein interactions. The model network implicated several kinases of known relevance to myogenesis including AKT, GSK3, CDK5, p38, DYRK, and MAPKAPK2 kinases. This combination of proteomics and bioinformatics technologies should offer great utility as the volume of protein-protein and kinase-substrate information continues to increase.  (+info)

(8/3529) A network-based analysis of polyanion-binding proteins utilizing yeast protein arrays.

The high affinity of certain cellular polyanions for many proteins (polyanion-binding proteins (PABPs)) has been demonstrated previously. It has been hypothesized that such polyanions may be involved in protein structure stabilization, stimulation of folding through chaperone-like activity, and intra- and extracellular protein transport as well as intracellular organization. The purpose of the proteomics studies reported here was to seek evidence for the idea that the nonspecific but high affinity interactions of PABPs with polyanions have a functional role in intracellular processes. Utilizing yeast protein arrays and five biotinylated cellular polyanion probes (actin, tubulin, heparin, heparan sulfate, and DNA), we identified proteins that interact with these probes and analyzed their structural and amino acid sequence requirements as well as their predicted functions in the yeast proteome. We also provide evidence for the existence of a network-like system for PABPs and their potential roles as critical hubs in intracellular behavior. This investigation takes a first step toward achieving a better understanding of the nature of polyanion-protein interactions within cells and introduces an alternative way of thinking about intracellular organization.  (+info)

biological networks

  • However, despite significant advancements, current pathway-based methods are still imperfect in extrapolating the functional states of transcriptomes into the biological networks. (
  • 1 From the perspective of global network architectures, it has been argued that a bow-tie structure, where diverse stimuli sensing upstream signals converge into a limited number of 'core' molecules, which then trigger diverse effector molecules or genes, is an evolutionarily conserved core architecture of biological networks, a version of which can be observed in signaling networks. (


  • Although this can lead to the identification of prospective genetic biomarkers and expression signature patterns of the process under study, it fails to capture subtle differences between samples that arise from dynamic interactions between genes at the level of signalling networks. (
  • Many popular pathway-based algorithms, such as Gene Set Enrichment Analysis (GSEA) and its extensions, rely solely on gene enrichment statistics, treating pathways as unstructured sets of genes 8 . (


  • In the present study, we introduce the in silico Pathway Activation Network Decomposition Analysis (iPANDA) as a scalable robust method for biomarker identification using gene expression data. (
  • Using Microarray Analysis Quality Control (MAQC) data sets and pretreatment data on Taxol-based neoadjuvant breast cancer therapy from multiple sources, we demonstrate that iPANDA provides significant noise reduction in transcriptomic data and identifies highly robust sets of biologically relevant pathway signatures. (
  • Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. (
  • A series of network analyses revealed that yeast stress response pathways are organized in bow-tie structures, which have been proposed as universal sub-systems for robust biological regulation. (


  • To circumvent these limitations, a number of computational scoring platforms that can project gene expression data into a molecular signalling network have been proposed for integrative pathway analysis 7 . (
  • We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker's or budding yeast). (
  • Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. (
  • To understand the overall picture of molecular stress responses, we chose to investigate stress response pathways in Saccharomyces cerevisiae (baker's or budding yeast). (


  • Signalling pathway activation analysis is a powerful approach for extracting biologically relevant features from large-scale transcriptomic and proteomic data. (


  • One of the most relevant challenges in transcriptomic data analysis is the inherent complexity of gene network interactions, which remains a significant obstacle in building comprehensive predictive models. (
  • However, such approaches are not scalable when networks contain more than a thousand states and interactions. (


  • The major advantage of pathway-based methods is their capability to perform biologically relevant dimension reduction as a result of the analysis. (


  • Network analyses serve as powerful alternative tools to extract fundamental features from complex networks. (


  • However, modern pathway-based methods often fail to provide stable pathway signatures of a specific phenotype or reliable disease biomarkers. (