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Sample records for biochemical pathway adaptability

  1. Simulation of Biochemical Pathway Adaptability Using Evolutionary Algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Bosl, W J

    2005-01-26

    The systems approach to genomics seeks quantitative and predictive descriptions of cells and organisms. However, both the theoretical and experimental methods necessary for such studies still need to be developed. We are far from understanding even the simplest collective behavior of biomolecules, cells or organisms. A key aspect to all biological problems, including environmental microbiology, evolution of infectious diseases, and the adaptation of cancer cells is the evolvability of genomes. This is particularly important for Genomes to Life missions, which tend to focus on the prospect of engineering microorganisms to achieve desired goals in environmental remediation and climate change mitigation, and energy production. All of these will require quantitative tools for understanding the evolvability of organisms. Laboratory biodefense goals will need quantitative tools for predicting complicated host-pathogen interactions and finding counter-measures. In this project, we seek to develop methods to simulate how external and internal signals cause the genetic apparatus to adapt and organize to produce complex biochemical systems to achieve survival. This project is specifically directed toward building a computational methodology for simulating the adaptability of genomes. This project investigated the feasibility of using a novel quantitative approach to studying the adaptability of genomes and biochemical pathways. This effort was intended to be the preliminary part of a larger, long-term effort between key leaders in computational and systems biology at Harvard University and LLNL, with Dr. Bosl as the lead PI. Scientific goals for the long-term project include the development and testing of new hypotheses to explain the observed adaptability of yeast biochemical pathways when the myosin-II gene is deleted and the development of a novel data-driven evolutionary computation as a way to connect exploratory computational simulation with hypothesis

  2. Reconstructing biochemical pathways from time course data.

    Science.gov (United States)

    Srividhya, Jeyaraman; Crampin, Edmund J; McSharry, Patrick E; Schnell, Santiago

    2007-03-01

    Time series data on biochemical reactions reveal transient behavior, away from chemical equilibrium, and contain information on the dynamic interactions among reacting components. However, this information can be difficult to extract using conventional analysis techniques. We present a new method to infer biochemical pathway mechanisms from time course data using a global nonlinear modeling technique to identify the elementary reaction steps which constitute the pathway. The method involves the generation of a complete dictionary of polynomial basis functions based on the law of mass action. Using these basis functions, there are two approaches to model construction, namely the general to specific and the specific to general approach. We demonstrate that our new methodology reconstructs the chemical reaction steps and connectivity of the glycolytic pathway of Lactococcus lactis from time course experimental data. PMID:17370261

  3. Whole blood transcriptomics and urinary metabolomics to define adaptive biochemical pathways of high-intensity exercise in 50-60 year old masters athletes.

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    Kamalika Mukherjee

    Full Text Available Exercise is beneficial for a variety of age-related disorders. However, the molecular mechanisms mediating the beneficial adaptations to exercise in older adults are not well understood. The aim of the current study was to utilize a dual approach to characterize the genetic and metabolic adaptive pathways altered by exercise in veteran athletes and age-matched untrained individuals. Two groups of 50-60 year old males: competitive cyclists (athletes, n = 9; VO2peak 59.1±5.2 ml·kg(-1·min(-1; peak aerobic power 383±39 W and untrained, minimally active individuals (controls, n = 8; VO2peak 35.9±9.7 ml·kg(-1·min(-1; peak aerobic power 230±57 W were examined. All participants completed an acute bout of submaximal endurance exercise, and blood and urine samples pre- and post-exercise were analyzed for gene expression and metabolic changes utilizing genome-wide DNA microarray analysis and NMR spectroscopy-based metabolomics, respectively. Our results indicate distinct differences in gene and metabolite expression involving energy metabolism, lipids, insulin signaling and cardiovascular function between the two groups. These findings may lead to new insights into beneficial signaling pathways of healthy aging and help identify surrogate markers for monitoring exercise and training load.

  4. Adaptative biochemical pathways and regulatory networks in Klebsiella oxytoca BAS-10 producing a biotechnologically relevant exopolysaccharide during Fe(III-citrate fermentation

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    Gallo Giuseppe

    2012-11-01

    Full Text Available Abstract Background A bacterial strain previously isolated from pyrite mine drainage and named BAS-10 was tentatively identified as Klebsiella oxytoca. Unlikely other enterobacteria, BAS-10 is able to grow on Fe(III-citrate as sole carbon and energy source, yielding acetic acid and CO2 coupled with Fe(III reduction to Fe(II and showing unusual physiological characteristics. In fact, under this growth condition, BAS-10 produces an exopolysaccharide (EPS having a high rhamnose content and metal-binding properties, whose biotechnological applications were proven as very relevant. Results Further phylogenetic analysis, based on 16S rDNA sequence, definitively confirmed that BAS-10 belongs to K. oxytoca species. In order to rationalize the biochemical peculiarities of this unusual enterobacteriun, combined 2D-Differential Gel Electrophoresis (2D-DIGE analysis and mass spectrometry procedures were used to investigate its proteomic changes: i under aerobic or anaerobic cultivation with Fe(III-citrate as sole carbon source; ii under anaerobic cultivations using Na(I-citrate or Fe(III-citrate as sole carbon source. Combining data from these differential studies peculiar levels of outer membrane proteins, key regulatory factors of carbon and nitrogen metabolism and enzymes involved in TCA cycle and sugar biosynthesis or required for citrate fermentation and stress response during anaerobic growth on Fe(III-citrate were revealed. The protein differential regulation seems to ensure efficient cell growth coupled with EPS production by adapting metabolic and biochemical processes in order to face iron toxicity and to optimize energy production. Conclusion Differential proteomics provided insights on the molecular mechanisms necessary for anaeorobic utilization of Fe(III-citrate in a biotechnologically promising enterobacteriun, also revealing genes that can be targeted for the rational design of high-yielding EPS producer strains.

  5. Biochemical research elucidating metabolic pathways in Pneumocystis*

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    Kaneshiro E.S.

    2010-12-01

    Full Text Available Advances in sequencing the Pneumocystis carinii genome have helped identify potential metabolic pathways operative in the organism. Also, data from characterizing the biochemical and physiological nature of these organisms now allow elucidation of metabolic pathways as well as pose new challenges and questions that require additional experiments. These experiments are being performed despite the difficulty in doing experiments directly on this pathogen that has yet to be subcultured indefinitely and produce mass numbers of cells in vitro. This article reviews biochemical approaches that have provided insights into several Pneumocystis metabolic pathways. It focuses on 1 S-adenosyl-L-methionine (AdoMet; SAM, which is a ubiquitous participant in numerous cellular reactions; 2 sterols: focusing on oxidosqualene cyclase that forms lanosterol in P. carinii; SAM:sterol C-24 methyltransferase that adds methyl groups at the C-24 position of the sterol side chain; and sterol 14α-demethylase that removes a methyl group at the C-14 position of the sterol nucleus; and 3 synthesis of ubiquinone homologs, which play a pivotal role in mitochondrial inner membrane and other cellular membrane electron transport.

  6. Modeling biochemical pathways in the gene ontology.

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    Hill, David P; D'Eustachio, Peter; Berardini, Tanya Z; Mungall, Christopher J; Renedo, Nikolai; Blake, Judith A

    2016-01-01

    The concept of a biological pathway, an ordered sequence of molecular transformations, is used to collect and represent molecular knowledge for a broad span of organismal biology. Representations of biomedical pathways typically are rich but idiosyncratic presentations of organized knowledge about individual pathways. Meanwhile, biomedical ontologies and associated annotation files are powerful tools that organize molecular information in a logically rigorous form to support computational analysis. The Gene Ontology (GO), representing Molecular Functions, Biological Processes and Cellular Components, incorporates many aspects of biological pathways within its ontological representations. Here we present a methodology for extending and refining the classes in the GO for more comprehensive, consistent and integrated representation of pathways, leveraging knowledge embedded in current pathway representations such as those in the Reactome Knowledgebase and MetaCyc. With carbohydrate metabolic pathways as a use case, we discuss how our representation supports the integration of variant pathway classes into a unified ontological structure that can be used for data comparison and analysis. PMID:27589964

  7. LeishCyc: a biochemical pathways database for Leishmania major

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    Doyle Maria A

    2009-06-01

    Full Text Available Abstract Background Leishmania spp. are sandfly transmitted protozoan parasites that cause a spectrum of diseases in more than 12 million people worldwide. Much research is now focusing on how these parasites adapt to the distinct nutrient environments they encounter in the digestive tract of the sandfly vector and the phagolysosome compartment of mammalian macrophages. While data mining and annotation of the genomes of three Leishmania species has provided an initial inventory of predicted metabolic components and associated pathways, resources for integrating this information into metabolic networks and incorporating data from transcript, protein, and metabolite profiling studies is currently lacking. The development of a reliable, expertly curated, and widely available model of Leishmania metabolic networks is required to facilitate systems analysis, as well as discovery and prioritization of new drug targets for this important human pathogen. Description The LeishCyc database was initially built from the genome sequence of Leishmania major (v5.2, based on the annotation published by the Wellcome Trust Sanger Institute. LeishCyc was manually curated to remove errors, correct automated predictions, and add information from the literature. The ongoing curation is based on public sources, literature searches, and our own experimental and bioinformatics studies. In a number of instances we have improved on the original genome annotation, and, in some ambiguous cases, collected relevant information from the literature in order to help clarify gene or protein annotation in the future. All genes in LeishCyc are linked to the corresponding entry in GeneDB (Wellcome Trust Sanger Institute. Conclusion The LeishCyc database describes Leishmania major genes, gene products, metabolites, their relationships and biochemical organization into metabolic pathways. LeishCyc provides a systematic approach to organizing the evolving information about Leishmania

  8. A case study of evolutionary computation of biochemical adaptation

    International Nuclear Information System (INIS)

    Simulations of evolution have a long history, but their relation to biology is questioned because of the perceived contingency of evolution. Here we provide an example of a biological process, adaptation, where simulations are argued to approach closer to biology. Adaptation is a common feature of sensory systems, and a plausible component of other biochemical networks because it rescales upstream signals to facilitate downstream processing. We create random gene networks numerically, by linking genes with interactions that model transcription, phosphorylation and protein–protein association. We define a fitness function for adaptation in terms of two functional metrics, and show that any reasonable combination of them will yield the same adaptive networks after repeated rounds of mutation and selection. Convergence to these networks is driven by positive selection and thus fast. There is always a path in parameter space of continuously improving fitness that leads to perfect adaptation, implying that the actual mutation rates we use in the simulation do not bias the results. Our results imply a kinetic view of evolution, i.e., it favors gene networks that can be learned quickly from the random examples supplied by mutation. This formulation allows for deductive predictions of the networks realized in nature

  9. The ectodysplasin pathway: from diseases to adaptations.

    Science.gov (United States)

    Sadier, Alexa; Viriot, Laurent; Pantalacci, Sophie; Laudet, Vincent

    2014-01-01

    The ectodysplasin (EDA) pathway, which is active during the development of ectodermal organs, including teeth, hairs, feathers, and mammary glands, and which is crucial for fine-tuning the developmental network controlling the number, size, and density of these structures, was discovered by studying human patients affected by anhidrotic/hypohidrotic ectodermal dysplasia. It comprises three main gene products: EDA, a ligand that belongs to the tumor necrosis factor (TNF)-α family, EDAR, a receptor related to the TNFα receptors, and EDARADD, a specific adaptor. This core pathway relies on downstream NF-κB pathway activation to regulate target genes. The pathway has recently been found to be associated with specific adaptations in natural populations: the magnitude of armor plates in sticklebacks and the hair structure in Asian human populations. Thus, despite its role in human disease, the EDA pathway is a 'hopeful pathway' that could allow adaptive changes in ectodermal appendages which, as specialized interfaces with the environment, are considered hot-spots of morphological evolution. PMID:24070496

  10. Characterization of changes in gene expression and biochemical pathways at low levels of benzene exposure.

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    Reuben Thomas

    Full Text Available Benzene, a ubiquitous environmental pollutant, causes acute myeloid leukemia (AML. Recently, through transcriptome profiling of peripheral blood mononuclear cells (PBMC, we reported dose-dependent effects of benzene exposure on gene expression and biochemical pathways in 83 workers exposed across four airborne concentration ranges (from 10 ppm compared with 42 subjects with non-workplace ambient exposure levels. Here, we further characterize these dose-dependent effects with continuous benzene exposure in all 125 study subjects. We estimated air benzene exposure levels in the 42 environmentally-exposed subjects from their unmetabolized urinary benzene levels. We used a novel non-parametric, data-adaptive model selection method to estimate the change with dose in the expression of each gene. We describe non-parametric approaches to model pathway responses and used these to estimate the dose responses of the AML pathway and 4 other pathways of interest. The response patterns of majority of genes as captured by mean estimates of the first and second principal components of the dose-response for the five pathways and the profiles of 6 AML pathway response-representative genes (identified by clustering exhibited similar apparent supra-linear responses. Responses at or below 0.1 ppm benzene were observed for altered expression of AML pathway genes and CYP2E1. Together, these data show that benzene alters disease-relevant pathways and genes in a dose-dependent manner, with effects apparent at doses as low as 100 ppb in air. Studies with extensive exposure assessment of subjects exposed in the low-dose range between 10 ppb and 1 ppm are needed to confirm these findings.

  11. Biochemical Pathways That Are Important for Cotton Fiber Cell Elongation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The regulatory mechanism that controls the sustained cotton fiber cell elongation is gradually being elucidated by coupling genome-wide transcriptome profiling with systematic biochemical and physiological studies.Very long chain fatty acids(VLCFA),H2O2,and several types of plant hormones

  12. In the light of directed evolution: Pathways of adaptive protein evolution

    OpenAIRE

    Bloom, Jesse D; Arnold, Frances H.

    2009-01-01

    Directed evolution is a widely-used engineering strategy for improving the stabilities or biochemical functions of proteins by repeated rounds of mutation and selection. These experiments offer empirical lessons about how proteins evolve in the face of clearly-defined laboratory selection pressures. Directed evolution has revealed that single amino acid mutations can enhance properties such as catalytic activity or stability and that adaptation can often occur through pathways consisting of s...

  13. Modelling and Analysis of Biochemical Signalling Pathway Cross-talk

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    Robin Donaldson

    2010-02-01

    Full Text Available Signalling pathways are abstractions that help life scientists structure the coordination of cellular activity. Cross-talk between pathways accounts for many of the complex behaviours exhibited by signalling pathways and is often critical in producing the correct signal-response relationship. Formal models of signalling pathways and cross-talk in particular can aid understanding and drive experimentation. We define an approach to modelling based on the concept that a pathway is the (synchronising parallel composition of instances of generic modules (with internal and external labels. Pathways are then composed by (synchronising parallel composition and renaming; different types of cross-talk result from different combinations of synchronisation and renaming. We define a number of generic modules in PRISM and five types of cross-talk: signal flow, substrate availability, receptor function, gene expression and intracellular communication. We show that Continuous Stochastic Logic properties can both detect and distinguish the types of cross-talk. The approach is illustrated with small examples and an analysis of the cross-talk between the TGF-b/BMP, WNT and MAPK pathways.

  14. Nonequilibrium Enhances Adaptation Efficiency of Stochastic Biochemical Systems.

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    Chen Jia

    Full Text Available Adaptation is a crucial biological function possessed by many sensory systems. Early work has shown that some influential equilibrium models can achieve accurate adaptation. However, recent studies indicate that there are close relationships between adaptation and nonequilibrium. In this paper, we provide an explanation of these two seemingly contradictory results based on Markov models with relatively simple networks. We show that as the nonequilibrium driving becomes stronger, the system under consideration will undergo a phase transition along a fixed direction: from non-adaptation to simple adaptation then to oscillatory adaptation, while the transition in the opposite direction is forbidden. This indicates that although adaptation may be observed in equilibrium systems, it tends to occur in systems far away from equilibrium. In addition, we find that nonequilibrium will improve the performance of adaptation by enhancing the adaptation efficiency. All these results provide a deeper insight into the connection between adaptation and nonequilibrium. Finally, we use a more complicated network model of bacterial chemotaxis to validate the main results of this paper.

  15. A coupled mechano-biochemical model for bone adaptation

    Czech Academy of Sciences Publication Activity Database

    Klika, Václav; Pérez, M. A.; García-Aznar, J. M.; Maršík, F.; Doblaré, M.

    2014-01-01

    Roč. 69, 6-7 (2014), s. 1383-1429. ISSN 0303-6812 Institutional support: RVO:61388998 Keywords : mechano-biochemical model * bone remodelling * BMU Subject RIV: BJ - Thermodynamics Impact factor: 1.846, year: 2014 http://link.springer.com/article/10.1007%2Fs00285-013-0736-9

  16. Adaptable Learning Pathway Generation with Ant Colony Optimization

    Science.gov (United States)

    Wong, Lung-Hsiang; Looi, Chee-Kit

    2009-01-01

    One of the new major directions in research on web-based educational systems is the notion of adaptability: the educational system adapts itself to the learning profile, preferences and ability of the student. In this paper, we look into the issues of providing adaptability with respect to learning pathways. We explore the state of the art with…

  17. A structured approach for the engineering of biochemical network models, illustrated for signalling pathways

    OpenAIRE

    Breitling, Rainer; Gilbert, David; Heiner, Monika; Orton, Richard

    2008-01-01

    Quantitative models of biochemical networks (signal transduction cascades, metabolic pathways, gene regulatory circuits) are a central component of modern systems biology. Building and managing these complex models is a major challenge that can benefit from the application of formal methods adopted from theoretical computing science. Here we provide a general introduction to the field of formal modelling, which emphasizes the intuitive biochemical basis of the modelling process, but is also a...

  18. Biochemical Pathways That Are Important for Cotton Fiber Cell Elongation

    Institute of Scientific and Technical Information of China (English)

    ZHU YU-xian

    2008-01-01

    @@ The regulatory mechanism that controls the sustained cotton fiber cell elongation is gradually being elucidated by coupling genome-wide transcriptome profiling with systematic biochemical and physiological studies.Very long chain fatty acids (VLCFA),H2O2,and several types of plant hormones including ethylene,gibberellin,and brassinolide have been reported to be involved in this process.Here we first identified by proteomic analysis a cotton cytosolic APX1 (GhAPX1) that was specifically accumulated during cotton fiber elongation.GhAPX1 expression was up-regulated in response to cellular H2O2 and ethylene,and it was involved in modulating the stead-state level of H2O2.

  19. Biochemical pathways in the antiatherosclerotic effect of berberine

    Institute of Scientific and Technical Information of China (English)

    GUO Yi; WANG Qi-zhang; LI Fang-ming; JIANG Xin; ZUO Yan-fang; WANG Ling

    2008-01-01

    Background This study investigated the inhibitory effect of berberine(BBR)on lipopolysaccharide(LPS)induced cyclooxygenase-2(COX-2)expression via the mitogen activated protein kinase(MAPK)signalling cascade pathways in human peripheral blood monocytes(PBMC).Methods PBMC from whole blood were isolated and cultured for uD 10 24 hours after division into 5 groups treated with LPS,LPS+BBR 25 μmol/L,LPS+BBR 50 μmol/L or LPS+BBR 100 μmol/L and untreated.Monocytes were extracted for RT-PCR and Western blot analyses to examine COX-2 mRNA and protein activated expression of p38 mitogen activated protein kinase(p38MAPK),Jun N-terminal kinase(JNK)and extracellular regulated kinases 1/2(ERK1/2)signalling pathways.Results COX-2 mRNA and protein expression decreased to a minimum at 12 hours after BBR treatment fP<0.05).With the increasing concentration of BBR treatment,the COX-2 expression decreased progressively(P<0.01).With BBR treatment for 6,12 or 24 hours at three doses,ERK1/2 protein expression was significantly inhibited.For the JNK pathway,only with the treatment of BBR at the concentration of 100 μmol/L was JNK protein expression inhibited compared with the LPS stimulation group(P<0.01).Irrespective of the BBR concentration,no difference was shown between the BBR group and the LPS group for p38MAPK protein expression.Human monocytes COX-2 mRNA,by RT-PCR,and protein expression,by Western blot analysis,were inhibited when incubated with PD98059,SP6001 25 and SB203580 (P<0.05).Conclusions Berberine inhibits COX-2 expression via the ERK1/2 signalling pathway and,possibly,at a high dosage via the JNK pathway.P38MAPK may have no relationship with the effect of BBR in PBMC.Berberine inhibited COX-2 mRNA and protein expression in a dose dependent manner and suppressed COX-2 expression to a minimal level after 12 hours of berberine treatment.

  20. Unraveling biochemical pathways affected by mitochondrial dysfunctions using metabolomic approaches.

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    Demine, Stéphane; Reddy, Nagabushana; Renard, Patricia; Raes, Martine; Arnould, Thierry

    2014-01-01

    Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic. PMID:25257998

  1. Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches

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    Stéphane Demine

    2014-09-01

    Full Text Available Mitochondrial dysfunction(s (MDs can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy in the obesity and insulin resistance thematic.

  2. Energetic Metabolism and Biochemical Adaptation: A Bird Flight Muscle Model

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    Rioux, Pierre; Blier, Pierre U.

    2006-01-01

    The main objective of this class experiment is to measure the activity of two metabolic enzymes in crude extract from bird pectoral muscle and to relate the differences to their mode of locomotion and ecology. The laboratory is adapted to stimulate the interest of wildlife management students to biochemistry. The enzymatic activities of cytochrome…

  3. MouseCyc: a curated biochemical pathways database for the laboratory mouse

    OpenAIRE

    Evsikov, Alexei V.; Dolan, Mary E; Genrich, Michael P; Patek, Emily; Bult, Carol J

    2009-01-01

    Linking biochemical genetic data to the reference genome for the laboratory mouse is important for comparative physiology and for developing mouse models of human biology and disease. We describe here a new database of curated metabolic pathways for the laboratory mouse called MouseCyc . MouseCyc has been integrated with genetic and genomic data for the laboratory mouse available from the Mouse Genome Informatics database and with pathway data from other organisms, including human.

  4. Biochemical adaptation of camelids during periods where feed is withheld

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    J. Wensvoort

    2001-03-01

    Full Text Available Biochemical changes during fasting or the withholding of feed for 5 day were studied in serum of camelids (dromedary camel, llama and ruminants (sheep, steers. Camels maintained low levels of 13-hydroxybutyrate (BHB and high levels of glucose but showed some increased levels of non-esterified fatty acid (NEFA and urea when fasting. Sheep and steers showed a rise in serum BHB and much higher increases of NEFA than camels and llamas. Sheep showed decreased serum glucose. The llama showed some increase in BHB but NEFA was lower than the other three species. The results indicate that camelids have a unique ability to control lipolytic and gluconeogenic activity to prevent or postpone the state of ketosis. Understanding and manipulation of these metabolic mechanisms in cattle and sheep could have great benefit to the livestock industry.

  5. Cellular Adaptation Facilitates Sparse and Reliable Coding in Sensory Pathways

    OpenAIRE

    Farkhooi, Farzad; Froese, Anja; Muller, Eilif; Menzel, Randolf; Nawrot, Martin P.

    2013-01-01

    Most neurons in peripheral sensory pathways initially respond vigorously when a preferred stimulus is presented, but adapt as stimulation continues. It is unclear how this phenomenon affects stimulus coding in the later stages of sensory processing. Here, we show that a temporally sparse and reliable stimulus representation develops naturally in sequential stages of a sensory network with adapting neurons. As a modeling framework we employ a mean-field approach together with an adaptive popul...

  6. Unraveling adaptation in eukaryotic pathways: lessons from protocells.

    OpenAIRE

    Giovanna De Palo; Robert G Endres

    2013-01-01

    Eukaryotic adaptation pathways operate within wide-ranging environmental conditions without stimulus saturation. Despite numerous differences in the adaptation mechanisms employed by bacteria and eukaryotes, all require energy consumption. Here, we present two minimal models showing that expenditure of energy by the cell is not essential for adaptation. Both models share important features with large eukaryotic cells: they employ small diffusible molecules and involve receptor subunits resemb...

  7. Lessons and challenges from adaptation pathways planning applications

    Science.gov (United States)

    Haasnoot, M.; Lawrence, J.; Kwakkel, J. H.; Walker, W.; Timmermans, J.; Bloemen, P.; Thissen, W.

    2015-12-01

    Planning for adaptation to dynamic risks (e.g., because of climate change) is a critical need. The concept of 'adaptive policies' is receiving increasing attention as a way of performing strategic planning that is able to address many of the inherent challenges of uncertainty and dynamic change. Several approaches for developing adaptive policies are available in the literature. One approach, for which several applications already exist, is Dynamic Adaptive Policy Pathways (DAPP). Pathway maps enable policy analysts, decision makers, and stakeholders to recognize potential 'locked-in' situations and to assess the flexibility, robustness, and efficacy of decision alternatives. Most of the applications of DAPP have been in deltas, coastal cities, or floodplains, often within the context of climate change adaptation. In this talk, we describe the DAPP approach and present a framework for designing signposts as adaptation signals, together with an illustrative application for the Rhine River in the Netherlands. We also draw lessons and challenges from pathways applications that differ in environment, culture, and institutional context. For example, the Dutch Delta Programme has used pathways to identify short-term decisions and long-term policy options. In Bangladesh, an application is in its early phase. Steps before generating pathways - such as long- term thinking in multiple possible futures and acknowledging uncertainties - are already a big challenge there. In New Zealand, the 'Sustainable Delta Game' has been used as the catalyst for pathways thinking by two local councils. This has led to its application in decision making for coastal and flood risk management and economic analysis of policy options.

  8. Unraveling adaptation in eukaryotic pathways: lessons from protocells.

    Science.gov (United States)

    De Palo, Giovanna; Endres, Robert G

    2013-10-01

    Eukaryotic adaptation pathways operate within wide-ranging environmental conditions without stimulus saturation. Despite numerous differences in the adaptation mechanisms employed by bacteria and eukaryotes, all require energy consumption. Here, we present two minimal models showing that expenditure of energy by the cell is not essential for adaptation. Both models share important features with large eukaryotic cells: they employ small diffusible molecules and involve receptor subunits resembling highly conserved G-protein cascades. Analyzing the drawbacks of these models helps us understand the benefits of energy consumption, in terms of adjustability of response and adaptation times as well as separation of cell-external sensing and cell-internal signaling. Our work thus sheds new light on the evolution of adaptation mechanisms in complex systems. PMID:24204235

  9. Unraveling adaptation in eukaryotic pathways: lessons from protocells.

    Directory of Open Access Journals (Sweden)

    Giovanna De Palo

    2013-10-01

    Full Text Available Eukaryotic adaptation pathways operate within wide-ranging environmental conditions without stimulus saturation. Despite numerous differences in the adaptation mechanisms employed by bacteria and eukaryotes, all require energy consumption. Here, we present two minimal models showing that expenditure of energy by the cell is not essential for adaptation. Both models share important features with large eukaryotic cells: they employ small diffusible molecules and involve receptor subunits resembling highly conserved G-protein cascades. Analyzing the drawbacks of these models helps us understand the benefits of energy consumption, in terms of adjustability of response and adaptation times as well as separation of cell-external sensing and cell-internal signaling. Our work thus sheds new light on the evolution of adaptation mechanisms in complex systems.

  10. Hypoxia Inducible Factor Pathway and Physiological Adaptation: A Cell Survival Pathway?

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    Kumar, Hemant; Choi, Dong-Kug

    2015-01-01

    Oxygen homeostasis reflects the constant body requirement to generate energy. Hypoxia (0.1-1% O2), physioxia or physoxia (∼1-13%), and normoxia (∼20%) are terms used to define oxygen concentration in the cellular environment. A decrease in oxygen (hypoxia) or excess oxygen (hyperoxia) could be deleterious for cellular adaptation and survival. Hypoxia can occur under both physiological (e.g., exercise, embryonic development, underwater diving, or high altitude) and pathological conditions (e.g., inflammation, solid tumor formation, lung disease, or myocardial infarction). Hypoxia plays a key role in the pathophysiology of heart disease, cancers, stroke, and other causes of mortality. Hypoxia inducible factor(s) (HIFs) are key oxygen sensors that mediate the ability of the cell to cope with decreased oxygen tension. These transcription factors regulate cellular adaptation to hypoxia and protect cells by responding acutely and inducing production of endogenous metabolites and proteins to promptly regulate metabolic pathways. Here, we review the role of the HIF pathway as a metabolic adaptation pathway and how this pathway plays a role in cell survival. We emphasize the roles of the HIF pathway in physiological adaptation, cell death, pH regulation, and adaptation during exercise. PMID:26491231

  11. Metabolic control analysis of biochemical pathways based on a thermokinetic description of reaction rates

    DEFF Research Database (Denmark)

    Nielsen, Jens Bredal

    1997-01-01

    of the thermokinetic description of reaction rates to include the influence of effecters. Here the reaction rate is written as a linear function of the logarithm of the metabolite concentrations. With this type of rate function it is shown that the approach of Delgado and Liao [Biochem. J. (1992) 282......, 919-927] can be much more widely applied, although it was originally based on linearized kinetics. The methodology of determining elasticity coefficients directly from pool levels is illustrated with an analysis of the first two steps of the biosynthetic pathway of penicillin. The results compare well...

  12. Design of Adaptive Policy Pathways under Deep Uncertainties

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    Babovic, Vladan

    2013-04-01

    The design of large-scale engineering and infrastructural systems today is growing in complexity. Designers need to consider sociotechnical uncertainties, intricacies, and processes in the long- term strategic deployment and operations of these systems. In this context, water and spatial management is increasingly challenged not only by climate-associated changes such as sea level rise and increased spatio-temporal variability of precipitation, but also by pressures due to population growth and particularly accelerating rate of urbanisation. Furthermore, high investment costs and long term-nature of water-related infrastructure projects requires long-term planning perspective, sometimes extending over many decades. Adaptation to such changes is not only determined by what is known or anticipated at present, but also by what will be experienced and learned as the future unfolds, as well as by policy responses to social and water events. As a result, a pathway emerges. Instead of responding to 'surprises' and making decisions on ad hoc basis, exploring adaptation pathways into the future provide indispensable support in water management decision-making. In this contribution, a structured approach for designing a dynamic adaptive policy based on the concepts of adaptive policy making and adaptation pathways is introduced. Such an approach provides flexibility which allows change over time in response to how the future unfolds, what is learned about the system, and changes in societal preferences. The introduced flexibility provides means for dealing with complexities of adaptation under deep uncertainties. It enables engineering systems to change in the face of uncertainty to reduce impacts from downside scenarios while capitalizing on upside opportunities. This contribution presents comprehensive framework for development and deployment of adaptive policy pathway framework, and demonstrates its performance under deep uncertainties on a case study related to urban

  13. Microfluidics meets metabolomics to reveal the impact of Campylobacter jejuni infection on biochemical pathways.

    Science.gov (United States)

    Mortensen, Ninell P; Mercier, Kelly A; McRitchie, Susan; Cavallo, Tammy B; Pathmasiri, Wimal; Stewart, Delisha; Sumner, Susan J

    2016-06-01

    Microfluidic devices that are currently being used in pharmaceutical research also have a significant potential for utilization in investigating exposure to infectious agents. We have established a microfluidic device cultured with Caco-2 cells, and utilized metabolomics to investigate the biochemical responses to the bacterial pathogen Campylobacter jejuni. In the microfluidic devices, Caco-2 cells polarize at day 5, are uniform, have defined brush borders and tight junctions, and form a mucus layer. Metabolomics analysis of cell culture media collected from both Caco-2 cell culture systems demonstrated a more metabolic homogenous biochemical profile in the media collected from microfluidic devices, compared with media collected from transwells. GeneGo pathway mapping indicated that aminoacyl-tRNA biosynthesis was perturbed by fluid flow, suggesting that fluid dynamics and shear stress impacts the cells translational quality control. Both microfluidic device and transwell culturing systems were used to investigate the impact of Campylobacter jejuni infection on biochemical processes. Caco-2 cells cultured in either system were infected at day 5 with C. jejuni 81-176 for 48 h. Metabolomics analysis clearly differentiated C. jejuni 81-176 infected and non-infected medias collected from the microfluidic devices, and demonstrated that C. jejuni 81-176 infection in microfluidic devices impacts branched-chain amino acid metabolism, glycolysis, and gluconeogenesis. In contrast, no distinction was seen in the biochemical profiles of infected versus non-infected media collected from cells cultured in transwells. Microfluidic culturing conditions demonstrated a more metabolically homogenous cell population, and present the opportunity for studying host-pathogen interactions for extended periods of time. PMID:27231016

  14. Oxidation state, bioavailability & biochemical pathway define the fate of carbon in soil

    Science.gov (United States)

    Kuzyakov, Yakov; Apostel, Carolin; Gunina, Anna; Herrmann, Anke M.; Dippold, Michaela

    2015-04-01

    Numerous experiments under laboratory and field conditions analyzed microbial utilization and mean residence time (MRT) of carbon (C) from plant and microbial residues as well as root exudates in soil. Most of these studies tested the effects of various environmental factors, such as temperature, soil moisture, texture etc. on these parameters. However, only a few studies compared the properties of the substances themselves and there is no conceptual framework based on biochemical pathways. We hypothesize that the fate of C from organic substances in soil strongly depends on the first step of their microbial utilization, specifically, on biochemical pathway and initial C oxidation state, as well as its bioavailability in soils, defined by its hydrophobicity and molecular weight. Here we introduce and evaluate a new conceptual framework based on the following parameters: 1) C oxidation state, 2) molecular weight and hydrophobicity, 3) initial biochemical pathway of a substance class in microbial cells. To assess these parameters, two databases were prepared based on the literature and own studies. The first database included only the studies with 14C or 13C position specific labeled sugars, amino acids, carboxylic acids, phenols and lipids in soil. This database allowed us to analyze microbial utilization and mineralization of organics to CO2 depending on their C oxidation state (OS) and on functional groups. Additionally, we calculated data on the bond electronegativity of all compounds investigated in these studies. The second data base included the results of 14C and 13C studies with uniformly labeled substances of various classes. This database considered the free enthalpie (Delta H) per C unit from a variety of substrates differing in their aromaticity, hydrophobicity/electronegativity and location of the substance on the van Krevelen diagram. In addition, we calculated the hydrophobicity from the electronegativity of the individual bonds and recorded their

  15. 5-Lipoxygenase Pathway, Dendritic Cells, and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Hedi Harizi

    2004-01-01

    Full Text Available 5-lipoxygenase (5-LO pathway is the major source of potent proinflammatory leukotrienes (LTs issued from the metabolism of arachidonic acid (AA, and best known for their roles in the pathogenesis of asthma. These lipid mediators are mainly released from myeloid cells and may act as physiological autocrine and paracrine signalling molecules, and play a central role in regulating the interaction between innate and adaptive immunity. The biological actions of LTs including their immunoregulatory and proinflammatory effects are mediated through extracellular specific G-protein-coupled receptors. Despite their role in inflammatory cells, such as neutrophils and macrophages, LTs may have important effects on dendritic cells (DC-mediated adaptive immunity. Several lines of evidence show that DC not only are important source of LTs, but also become targets of their actions by producing other lipid mediators and proinflammatory molecules. This review focuses on advances in 5-LO pathway biology, the production of LTs from DC and their role on various cells of immune system and in adaptive immunity.

  16. Genomic and Biochemical Analysis of Lipid Biosynthesis in the Unicellular Rhodophyte Cyanidioschyzon merolae: Lack of a Plastidic Desaturation Pathway Results in the Coupled Pathway of Galactolipid Synthesis▿ †

    OpenAIRE

    Sato, Naoki; Moriyama, Takashi

    2007-01-01

    The acyl lipids making up the plastid membranes in plants and algae are highly enriched in polyunsaturated fatty acids and are synthesized by two distinct pathways, known as the prokaryotic and eukaryotic pathways, which are located within the plastids and the endoplasmic reticulum, respectively. Here we report the results of biochemical as well as genomic analyses of lipids and fatty acids in the unicellular rhodophyte Cyanidioschyzon merolae. All of the glycerolipids usually found in photos...

  17. Molecular Biological and Biochemical Studies Reveal New Pathways Important for Cotton Fiber Development

    Institute of Scientific and Technical Information of China (English)

    Yu Xu; Hong-Bin Li; Yu-Xian Zhu

    2007-01-01

    As one of the longest single-celled seed trichomes, fibers provide an excellent model for studying fundamental biological processes such as cell differentiation, cell expansion, and cell wall biosynthesis. In this review, we summarize recent progress in cotton functional genomic studies that characterize the dynamic changes in the transcriptomes of fiber cells. Extensive expression profilings of cotton fiber transcriptomes have provided comprehensive information, as quite a number of transcription factors and enzyme-coding genes have been shown to express preferentially during the fiber elongation period. Biosynthesis of the plant hormone ethylene is found significantly upregulated during the fiber growth period as revealed by both microarray analysis and by biochemical and physiological studies. It is suggested that genetic engineering of the ethylene pathway may improve the quality and the productivity of cotton lint. Many metabolic pathways, such as biosynthesis of celiulose and matrix polysaccharides are preferentially expressed in actively growing fiber cells. Five gene families, including proline-rich proteins (PRP), arabinogalactan proteins (AGP), expansins, tubulins and lipid transfer proteins (LTP) are activated during early fiber development,indicating that they may also be needed for cell elongation. In conclusion, we identify a few areas of future research for cotton functional genomic studies.

  18. Physiological and biochemical characteristics of the ethyl tiglate production pathway in the yeast Saprochaete suaveolens.

    Science.gov (United States)

    Grondin, Eric; Shum Cheong Sing, Alain; Caro, Yanis; de Billerbeck, Gustavo M; François, Jean Marie; Petit, Thomas

    2015-01-01

    A yeast identified as Saprochaete suaveolens was investigated for its capacity to produce a large panel of flavouring molecules. With a production of 32 compounds including 28 esters, S. suaveolens seems to be a good producer of fruity flavours and fragrances and especially of unsaturated esters, such as ethyl tiglate. Physiological and biochemical analyses were performed in this study in an attempt to comprehend the metabolic route to the formation of this compound. We show that the accumulation of ethyl tiglate by S. suaveolens is specifically induced by isoleucine. However, and contrary to S. cerevisiae, which harbours a classical Ehrlich pathway leading to the production of 2-methylbutanol from isoleucine, our results provide phenotypic and enzymological evidence of ethyl tiglate biosynthesis in S. suaveolens through the catabolism of this amino acid by the β-oxidation pathway, which generates tiglyl-CoA as a probable intermediate. A kinetic analysis of this flavour molecule during growth of S. suaveolens on glucose and isoleucine showed a phase of production of ethyl tiglate that culminated concurrently with isoleucine exhaustion, followed by a disappearance of this compound, likely due to reassimilation by the yeast. PMID:25407290

  19. Distinct configurations of protein complexes and biochemical pathways revealed by epistatic interaction network motifs

    LENUS (Irish Health Repository)

    Casey, Fergal

    2011-08-22

    Abstract Background Gene and protein interactions are commonly represented as networks, with the genes or proteins comprising the nodes and the relationship between them as edges. Motifs, or small local configurations of edges and nodes that arise repeatedly, can be used to simplify the interpretation of networks. Results We examined triplet motifs in a network of quantitative epistatic genetic relationships, and found a non-random distribution of particular motif classes. Individual motif classes were found to be associated with different functional properties, suggestive of an underlying biological significance. These associations were apparent not only for motif classes, but for individual positions within the motifs. As expected, NNN (all negative) motifs were strongly associated with previously reported genetic (i.e. synthetic lethal) interactions, while PPP (all positive) motifs were associated with protein complexes. The two other motif classes (NNP: a positive interaction spanned by two negative interactions, and NPP: a negative spanned by two positives) showed very distinct functional associations, with physical interactions dominating for the former but alternative enrichments, typical of biochemical pathways, dominating for the latter. Conclusion We present a model showing how NNP motifs can be used to recognize supportive relationships between protein complexes, while NPP motifs often identify opposing or regulatory behaviour between a gene and an associated pathway. The ability to use motifs to point toward underlying biological organizational themes is likely to be increasingly important as more extensive epistasis mapping projects in higher organisms begin.

  20. Biochemical Pathways: An Atlas of Biochemistry and Molecular Biology (edited by Gerhard Michal)

    Science.gov (United States)

    Voige, Reviewed By William H.

    2000-02-01

    feature to the hyperlinks in an electronic document.) The book's index is comprehensive and useful. Entries for "phenylketonuria" and "sickle cell anemia", for example, lead to commendably concise summaries of these hereditary diseases (and the relevant metabolic pathway, in the former case). Looking up a specific molecule, however, is less helpful. The listing for fumarate hydratase, a citric acid cycle enzyme, directs the reader to the chapter on special bacterial metabolism but not to the section on the citric acid cycle itself. Literature references are included at the end of each section and are mainly from the 1990s, but they could be more useful. A long section on heme proteins, for example, concludes with eight citations, but their titles are not included, so it is impossible to determine what topic each one addresses. This book will be most useful to those with a good understanding of the fundamentals of biochemistry. Some of the information it presents could easily confuse less experienced readers. For example, it classifies selenocysteine as a standard amino acid in a figure but not in the accompanying text. In the diagram of anaerobic glycolysis, a double-headed arrow for the hexokinase reaction reinforces the frustratingly common student misperception that the phosphoryl group of glucose-6-phosphate can be used to phosphorylate ADP. Biochemical Pathways compiles a large amount of information in a single source. Its good index and clear, concise text and diagrams should make it a reliable way of gaining insight into many biochemical topics. With a price similar to that of most textbooks, it merits a place in the libraries of individuals and academic departments that teach biochemistry.

  1. Cooperative Drought Adaptation: Integrating Infrastructure Development, Conservation, and Water Transfers into Adaptive Policy Pathways

    Science.gov (United States)

    Zeff, H. B.; Characklis, G. W.; Reed, P. M.; Herman, J. D.

    2015-12-01

    Water supply policies that integrate portfolios of short-term management decisions with long-term infrastructure development enable utilities to adapt to a range of future scenarios. An effective mix of short-term management actions can augment existing infrastructure, potentially forestalling new development. Likewise, coordinated expansion of infrastructure such as regional interconnections and shared treatment capacity can increase the effectiveness of some management actions like water transfers. Highly adaptable decision pathways that mix long-term infrastructure options and short-term management actions require decision triggers capable of incorporating the impact of these time-evolving decisions on growing water supply needs. Here, we adapt risk-based triggers to sequence a set of potential infrastructure options in combination with utility-specific conservation actions and inter-utility water transfers. Individual infrastructure pathways can be augmented with conservation or water transfers to reduce the cost of meeting utility objectives, but they can also include cooperatively developed, shared infrastructure that expands regional capacity to transfer water. This analysis explores the role of cooperation among four water utilities in the 'Research Triangle' region of North Carolina by formulating three distinct categories of adaptive policy pathways: independent action (utility-specific conservation and supply infrastructure only), weak cooperation (utility-specific conservation and infrastructure development with regional transfers), and strong cooperation (utility specific conservation and jointly developed of regional infrastructure that supports transfers). Results suggest that strong cooperation aids the utilities in meeting their individual objections at substantially lower costs and with fewer irreversible infrastructure options.

  2. Characterization of the biochemical-pathway of uranium (VI) reduction in facultative anaerobic bacteria.

    Science.gov (United States)

    Mtimunye, Phalazane J; Chirwa, Evans M N

    2014-10-01

    Cultures of U(VI) reducing bacteria sourced from abandoned uranium mine tailing dam were evaluated for their ability to reduce U(VI) to U(IV). The species in the cultures reduced U(VI) in solutions with initial U(VI) concentration up to 400mgL(-)(1) under a near neutral pH of 6.5. The electron flow pathway and fate of reduced species was also analysed in the individual species in order to evaluate the potential for control and optimisation of the reduction potential at the biochemical level. The results showed that U(VI) reduction in live cells was completely blocked by the NADH-dehydrogenase inhibitor, rotenone (C23H22O6), and thioredoxin inhibitor, cadmium chloride (CdCl2), showing that U(VI) reduction involves the electron flow through NADH-dehydrogenase, a primary electron donor to the electron transport respiratory (ETR) system. Mass balance analysis of uranium species aided by visual and electron microscopy suggest that most U(VI) reduction occurred on the cell surface of the isolated species. This finding indicates the possibility of easy uranium recovery for beneficial use through biological remediation. Should the U(VI) be reduced inside the cell, recovery would require complete disruption of the cells and therefore would be difficult. The study contributes new knowledge on the underlying mechanisms in the U(VI) reduction in facultative anaerobes. PMID:25065785

  3. Molecular and Biochemical Analysis of Chalcone Synthase from Freesia hybrid in flavonoid biosynthetic pathway.

    Directory of Open Access Journals (Sweden)

    Wei Sun

    Full Text Available Chalcone synthase (CHS catalyzes the first committed step in the flavonoid biosynthetic pathway. In this study, the cDNA (FhCHS1 encoding CHS from Freesia hybrida was successfully isolated and analyzed. Multiple sequence alignments showed that both the conserved CHS active site residues and CHS signature sequence were found in the deduced amino acid sequence of FhCHS1. Meanwhile, crystallographic analysis revealed that protein structure of FhCHS1 is highly similar to that of alfalfa CHS2, and the biochemical analysis results indicated that it has an enzymatic role in naringenin biosynthesis. Moreover, quantitative real-time PCR was performed to detect the transcript levels of FhCHS1 in flowers and different tissues, and patterns of FhCHS1 expression in flowers showed significant correlation to the accumulation patterns of anthocyanin during flower development. To further characterize the functionality of FhCHS1, its ectopic expression in Arabidopsis thaliana tt4 mutants and Petunia hybrida was performed. The results showed that overexpression of FhCHS1 in tt4 mutants fully restored the pigmentation phenotype of the seed coats, cotyledons and hypocotyls, while transgenic petunia expressing FhCHS1 showed flower color alteration from white to pink. In summary, these results suggest that FhCHS1 plays an essential role in the biosynthesis of flavonoid in Freesia hybrida and may be used to modify the components of flavonoids in other plants.

  4. Biochemical Modulation of Lipid Pathway in Microalgae Dunaliella sp. for Biodiesel Production

    Directory of Open Access Journals (Sweden)

    Ahmad Farhad Talebi

    2015-01-01

    Full Text Available Exploitation of renewable sources of energy such as algal biodiesel could turn energy supplies problem around. Studies on a locally isolated strain of Dunaliella sp. showed that the mean lipid content in cultures enriched by 200 mg L−1 myoinositol was raised by around 33% (1.5 times higher than the control. Similarly, higher lipid productivity values were achieved in cultures treated by 100 and 200 mg L−1 myoinositol. Fluorometry analyses (microplate fluorescence and flow cytometry revealed increased oil accumulation in the Nile red-stained algal samples. Moreover, it was predicted that biodiesel produced from myoinositol-treated cells possessed improved oxidative stability, cetane number, and cloud point values. From the genomic point of view, real-time analyses revealed that myoinositol negatively influenced transcript abundance of AccD gene (one of the key genes involved in lipid production pathway due to feedback inhibition and that its positive effect must have been exerted through other genes. The findings of the current research are not to interprete that myoinositol supplementation could answer all the challenges faced in microalgal biodiesel production but instead to show that “there is a there there” for biochemical modulation strategies, which we achieved, increased algal oil quantity and enhanced resultant biodiesel quality.

  5. Metabolomic profiling and genomic analysis of wheat aneuploid lines to identify genes controlling biochemical pathways in mature grain.

    Science.gov (United States)

    Francki, Michael G; Hayton, Sarah; Gummer, Joel P A; Rawlinson, Catherine; Trengove, Robert D

    2016-02-01

    Metabolomics is becoming an increasingly important tool in plant genomics to decipher the function of genes controlling biochemical pathways responsible for trait variation. Although theoretical models can integrate genes and metabolites for trait variation, biological networks require validation using appropriate experimental genetic systems. In this study, we applied an untargeted metabolite analysis to mature grain of wheat homoeologous group 3 ditelosomic lines, selected compounds that showed significant variation between wheat lines Chinese Spring and at least one ditelosomic line, tracked the genes encoding enzymes of their biochemical pathway using the wheat genome survey sequence and determined the genetic components underlying metabolite variation. A total of 412 analytes were resolved in the wheat grain metabolome, and principal component analysis indicated significant differences in metabolite profiles between Chinese Spring and each ditelosomic lines. The grain metabolome identified 55 compounds positively matched against a mass spectral library where the majority showed significant differences between Chinese Spring and at least one ditelosomic line. Trehalose and branched-chain amino acids were selected for detailed investigation, and it was expected that if genes encoding enzymes directly related to their biochemical pathways were located on homoeologous group 3 chromosomes, then corresponding ditelosomic lines would have a significant reduction in metabolites compared with Chinese Spring. Although a proportion showed a reduction, some lines showed significant increases in metabolites, indicating that genes directly and indirectly involved in biosynthetic pathways likely regulate the metabolome. Therefore, this study demonstrated that wheat aneuploid lines are suitable experimental genetic system to validate metabolomics-genomics networks. PMID:26032167

  6. Site-specific isotope fractionation in the characterization of biochemical mechanisms: the glycolytic pathway

    International Nuclear Information System (INIS)

    For a given biochemical transformation, such as the fermentation reaction, the redistribution coefficients, which relate the natural site-specific isotope contents in end products to those of their precursors, are a source of mechanistic information. These coefficients characterize the traceability of specific hydrogens in the products (ethanol and water) to their parent hydrogens in the starting materials (glucose and water). In conditions of complete transformation, they also enable intermolecular exchanges with the water medium to be estimated. Thus it is directly confirmed that hydrogens 1, 2, 6, and 6' of glucose are strongly connected to the methyl site I of ethanol obtained by fermentation by Saccharomyces cerevisiae. However, whereas hydrogens 6 and 6' are transferred to a great extent, transfer is only partial for hydrogen 2, and it is even less for hydrogen 1. Because the two moieties of glucose corresponding to carbons 1-2-3 and 4-5-6 are scrambled by the aldolase and triosephosphate isomerase reactions, additional exchange of hydrogens at positions 1 and 2 must have occurred before these steps. The value of the coefficient that relates site 2 of glucose to site I of ethanol in particular can be used to quantify the contribution of intermolecular exchange occurring in the course of the transfer from site 2 of glucose 6-phosphate to site 1 of fructose 6-phosphate mediated by phosphoglucoisomerase. The average hydrogen isotope effects associated with the transfer of hydrogen from the water pool to the methyl or methylene site of ethanol are estimated. In contrast to conventional experiments carried out in strongly deuterium-enriched media where metabolic switching may occur, the NMR investigation of site-specific natural isotope fractionation, which operates at tracer isotopic abundance, faithfully describes the unperturbed metabolic pathways

  7. Training signaling pathway maps to biochemical data with constrained fuzzy logic: quantitative analysis of liver cell responses to inflammatory stimuli.

    Directory of Open Access Journals (Sweden)

    Melody K Morris

    2011-03-01

    Full Text Available Predictive understanding of cell signaling network operation based on general prior knowledge but consistent with empirical data in a specific environmental context is a current challenge in computational biology. Recent work has demonstrated that Boolean logic can be used to create context-specific network models by training proteomic pathway maps to dedicated biochemical data; however, the Boolean formalism is restricted to characterizing protein species as either fully active or inactive. To advance beyond this limitation, we propose a novel form of fuzzy logic sufficiently flexible to model quantitative data but also sufficiently simple to efficiently construct models by training pathway maps on dedicated experimental measurements. Our new approach, termed constrained fuzzy logic (cFL, converts a prior knowledge network (obtained from literature or interactome databases into a computable model that describes graded values of protein activation across multiple pathways. We train a cFL-converted network to experimental data describing hepatocytic protein activation by inflammatory cytokines and demonstrate the application of the resultant trained models for three important purposes: (a generating experimentally testable biological hypotheses concerning pathway crosstalk, (b establishing capability for quantitative prediction of protein activity, and (c prediction and understanding of the cytokine release phenotypic response. Our methodology systematically and quantitatively trains a protein pathway map summarizing curated literature to context-specific biochemical data. This process generates a computable model yielding successful prediction of new test data and offering biological insight into complex datasets that are difficult to fully analyze by intuition alone.

  8. Unraveling adaptation in eukaryotic pathways: lessons from protocells

    OpenAIRE

    De Palo, Giovanna; Robert G Endres

    2013-01-01

    Author Summary Adaptation is a common feature in sensory systems, well familiar to us from light and dark adaptation of our visual system. Biological cells, ranging from bacteria to complex eukaryotes, including single-cell organisms and human sensory receptors, adopt different strategies to fulfill this property. However, all of them require substantial amounts of energy to adapt. Here, we compare the different biological strategies and design two minimal models which allow adaptation withou...

  9. Adaptation to High Ethanol Reveals Complex Evolutionary Pathways

    Science.gov (United States)

    Das, Anupam; Espinosa-Cantú, Adriana; De Maeyer, Dries; Arslan, Ahmed; Van Pee, Michiel; van der Zande, Elisa; Meert, Wim; Yang, Yudi; Zhu, Bo; Marchal, Kathleen; DeLuna, Alexander; Van Noort, Vera; Jelier, Rob; Verstrepen, Kevin J.

    2015-01-01

    Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to increasing levels of ethanol. Whole-genome sequencing of more than 30 evolved populations and over 100 adapted clones isolated throughout this two-year evolution experiment revealed how a complex interplay of de novo single nucleotide mutations, copy number variation, ploidy changes, mutator phenotypes, and clonal interference led to a significant increase in ethanol tolerance. Although the specific mutations differ between different evolved lineages, application of a novel computational pipeline, PheNetic, revealed that many mutations target functional modules involved in stress response, cell cycle regulation, DNA repair and respiration. Measuring the fitness effects of selected mutations introduced in non-evolved ethanol-sensitive cells revealed several adaptive mutations that had previously not been implicated in ethanol tolerance, including mutations in PRT1, VPS70 and MEX67. Interestingly, variation in VPS70 was recently identified as a QTL for ethanol tolerance in an industrial bio-ethanol strain. Taken together, our results show how, in contrast to adaptation to some other stresses, adaptation to a continuous complex and severe stress involves interplay of different evolutionary mechanisms. In addition, our study reveals functional modules involved in ethanol resistance and identifies several mutations that could help to improve the ethanol tolerance of industrial yeasts. PMID:26545090

  10. Substitutions in woolly mammoth hemoglobin confer biochemical properties adaptive for cold tolerance

    DEFF Research Database (Denmark)

    Campbell, Kevin L.; Roberts, Jason E.E.; Watson, Laura N.;

    2010-01-01

    on the chimeric β/δ-globin subunit of mammoth hemoglobin that provide a unique solution to this problem and thereby minimize energetically costly heat loss. This biochemical specialization may have been involved in the exploitation of high-latitude environments by this African-derived elephantid lineage during...

  11. Glucose pathways adaptation supports acquisition of activated microglia phenotype

    OpenAIRE

    Gimeno-Bayon, Javier; López-López, A.; Rodríguez Allué, Manuel José; Mahy Gehenne, Josette Nicole

    2014-01-01

    With its capacity to survey the environment and phagocyte debris, microglia assume a diversity of phenotypes to respond specifically through neurotrophic and toxic effects. Although these roles are well accepted, the underlying energetic mechanisms associated with microglial activation remain largely unclear. This study investigates microglia metabolic adaptation to ATP, NADPH, H(+) , and reactive oxygen species production. To this end, in vitro studies were performed with BV-2 cells before a...

  12. Improved Differential Evolution Algorithm for Parameter Estimation to Improve the Production of Biochemical Pathway

    Directory of Open Access Journals (Sweden)

    Chuii Khim Chong

    2012-06-01

    Full Text Available This paper introduces an improved Differential Evolution algorithm (IDE which aims at improving its performance in estimating the relevant parameters for metabolic pathway data to simulate glycolysis pathway for yeast. Metabolic pathway data are expected to be of significant help in the development of efficient tools in kinetic modeling and parameter estimation platforms. Many computation algorithms face obstacles due to the noisy data and difficulty of the system in estimating myriad of parameters, and require longer computational time to estimate the relevant parameters. The proposed algorithm (IDE in this paper is a hybrid of a Differential Evolution algorithm (DE and a Kalman Filter (KF. The outcome of IDE is proven to be superior than Genetic Algorithm (GA and DE. The results of IDE from experiments show estimated optimal kinetic parameters values, shorter computation time and increased accuracy for simulated results compared with other estimation algorithms

  13. Drought Adaptation in the Ningxia Hui Autonomous Region, China: Actions, Planning, Pathways and Barriers

    Directory of Open Access Journals (Sweden)

    Jianping Yang

    2015-11-01

    Full Text Available The Ningxia Hui Autonomous Region (NX region of Northwestern China is threatened by increased meteorological drought induced by climate change (CC and constraints on water supply from the Yellow River. Thus, the NX region is representative of attempts to adapt to CC and variability in China’s arid regions. Field visits, a questionnaire and in situ inspections were conducted in 2012–2014 to understand people’s perception and awareness of drought and its impact, particularly with respect to adaptation strategies. We mainly focused on drought adaptation actions and planning implemented at the government level under the double pressures of drought and allocation. We described a suitable adaptation pathway for socio-economic sustainable development and discussed existing adaptation barriers. Construction of modern efficient water-saving agriculture lies at the core of drought adaptation, with socio-economic sustainable development being the ultimate goal. To achieve this, policies and institutional, engineering, technological, structural and social initiatives and measures—classified into macro adaptation strategies and specific coping measures—are implemented. Adaptation often encounters obstacles, e.g., policy issues from household contract responsibility systems, funding difficulties of low-income farmers, traditional behavioral habits and low education and literacy levels among farmers. The adaptation pathway involves the construction of modern efficient water-saving agriculture. Agricultural water savings are then transferred to developed industries, which back-feed socio-economic sustainable development in the NX region.

  14. Biochemical and structural characterization of Klebsiella pneumoniae oxamate amidohydrolase in the uric acid degradation pathway

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, Katherine A.; Ealick, Steven E.

    2016-05-25

    HpxW from the ubiquitous pathogenKlebsiella pneumoniaeis involved in a novel uric acid degradation pathway downstream from the formation of oxalurate. Specifically, HpxW is an oxamate amidohydrolase which catalyzes the conversion of oxamate to oxalate and is a member of the Ntn-hydrolase superfamily. HpxW is autoprocessed from an inactive precursor to form a heterodimer, resulting in a 35.5 kDa α subunit and a 20 kDa β subunit. Here, the structure of HpxW is presented and the substrate complex is modeled. In addition, the steady-state kinetics of this enzyme and two active-site variants were characterized. These structural and biochemical studies provide further insight into this class of enzymes and allow a mechanism for catalysis consistent with other members of the Ntn-hydrolase superfamily to be proposed.

  15. Molecular and biochemical characterization of the tetralin degradation pathway in Rhodococcus sp. strain TFB

    OpenAIRE

    Tomás‐Gallardo, Laura; Santero, Eduardo; Camafeita, Emilio; Calvo, Enrique; Schlömann, Michael; Floriano, Belén

    2009-01-01

    Summary The tetralin biodegradation pathway in Rhodococcus sp. strain TFB, a Gram‐positive bacterium resistant to genetic manipulation, was characterized using a proteomic approach. Relative protein expression in cell free extracts from tetralin‐ and glucose‐grown cells was compared using the 2D‐DIGE technique. Identification of proteins specifically expressed in tetralin‐grown cells was used to characterize a complete set of genes involved in tetralin degradation by reverse genetics. We prop...

  16. The evolution of control and distribution of adaptive mutations in a metabolic pathway.

    Science.gov (United States)

    Wright, Kevin M; Rausher, Mark D

    2010-02-01

    In an attempt to understand whether it should be expected that some genes tend to be used disproportionately often by natural selection, we investigated two related phenomena: the evolution of flux control among enzymes in a metabolic pathway and properties of adaptive substitutions in pathway enzymes. These two phenomena are related by the principle that adaptive substitutions should occur more frequently in enzymes with greater flux control. Predicting which enzymes will be preferentially involved in adaptive evolution thus requires an evolutionary theory of flux control. We investigated the evolution of enzyme control in metabolic pathways with two models of enzyme kinetics: metabolic control theory (MCT) and Michaelis-Menten saturation kinetics (SK). Our models generate two main predictions for pathways in which reactions are moderately to highly irreversible: (1) flux control will evolve to be highly unequal among enzymes in a pathway and (2) upstream enzymes evolve a greater control coefficient then those downstream. This results in upstream enzymes fixing the majority of beneficial mutations during adaptive evolution. Once the population has reached high fitness, the trend is reversed, with the majority of neutral/slightly deleterious mutations occurring in downstream enzymes. These patterns are the result of three factors (the first of these is unique to the MCT simulations while the other two seem to be general properties of the metabolic pathways): (1) the majority of randomly selected, starting combinations of enzyme kinetic rates generate pathways that possess greater control for the upstream enzymes compared to downstream enzymes; (2) selection against large pools of intermediate substrates tends to prevent majority control by downstream enzymes; and (3) equivalent mutations in enzyme kinetic rates have the greatest effect on flux for enzymes with high levels of flux control, and these enzymes will accumulate adaptive substitutions, strengthening their

  17. Complement Activation Pathways: A Bridge between Innate and Adaptive Immune Responses in Asthma

    OpenAIRE

    Wills-Karp, Marsha

    2007-01-01

    Although it is widely accepted that allergic asthma is driven by T helper type 2 (Th2)-polarized immune responses to innocuous environmental allergens, the mechanisms driving these aberrant immune responses remain elusive. Recent recognition of the importance of innate immune pathways in regulating adaptive immune responses have fueled investigation into the role of innate immune pathways in the pathogenesis of asthma. The phylogenetically ancient innate immune system, the complement system, ...

  18. Adaptive Control Model Reveals Systematic Feedback and Key Molecules in Metabolic Pathway Regulation

    OpenAIRE

    Quo, Chang F.; Moffitt, Richard A; Merrill, Alfred H.; Wang, May D.

    2011-01-01

    Robust behavior in metabolic pathways resembles stabilized performance in systems under autonomous control. This suggests we can apply control theory to study existing regulation in these cellular networks. Here, we use model-reference adaptive control (MRAC) to investigate the dynamics of de novo sphingolipid synthesis regulation in a combined theoretical and experimental case study. The effects of serine palmitoyltransferase over-expression on this pathway are studied in vitro using human e...

  19. SISMA: A SOFTWARE FOR DYNAMIC SIMULATION OF METABOLIC PATHWAYS IN BIOCHEMICAL EDUCATION

    Directory of Open Access Journals (Sweden)

    J.A. Macedo

    2008-05-01

    Full Text Available The main purpose of metabolic pathway charts is  clarifying the flow of reactants and products  devised by enzyme  catalytic  reactions . Learning the wealth of information in metabolic pathways , however, is both challenging and overwhelming for students, mainly due to the static nature of printed charts.  In this sense the goal of this work was to develop a software environment for  metabolic chart studies, enhancing both student learning and retention. The system named SISMA (Sistema de Simulações Metabólicas was developed using  the  Unified Modeling Language (UML and Rational Unified Process (RUP tools for specifying, visualizing, constructing, and documenting  the  software system.  SISMA  was modelled with  JAVA programming  language, due to its versatility, efficiency, platform portability, and security. Use Case diagrams were constructing to describe the available functionality of  the software  and  the set of scenarios describing the interactions with the end user, with constraints defined by B usiness  Rules.  In brief, SISMA  can  dynamically  illustrate standard and physiopathological  flow of reactants, create and modifiy compounds, pathways,  and co-factors, and report kinectic data,  among others.  In this way SISMA  can be used as a complementary tool on both conventional full-time as distance learning courses in biochemistry and biotechnology.

  20. Biochemical and Structural Characterization of a Ureidoglycine Aminotransferase in the Klebsiella pneumoniae Uric Acid Catabolic Pathway

    Energy Technology Data Exchange (ETDEWEB)

    French, Jarrod B.; Ealick, Steven E. (Cornell)

    2010-09-03

    Many plants, fungi, and bacteria catabolize allantoin as a mechanism for nitrogen assimilation. Recent reports have shown that in plants and some bacteria the product of hydrolysis of allantoin by allantoinase is the unstable intermediate ureidoglycine. While this molecule can spontaneously decay, genetic analysis of some bacterial genomes indicates that an aminotransferase may be present in the pathway. Here we present evidence that Klebsiella pneumoniae HpxJ is an aminotransferase that preferentially converts ureidoglycine and an {alpha}-keto acid into oxalurate and the corresponding amino acid. We determined the crystal structure of HpxJ, allowing us to present an explanation for substrate specificity.

  1. Transcriptome and biochemical analyses revealed a detailed proanthocyanidin biosynthesis pathway in brown cotton fiber.

    Directory of Open Access Journals (Sweden)

    Yue-Hua Xiao

    Full Text Available Brown cotton fiber is the major raw material for colored cotton industry. Previous studies have showed that the brown pigments in cotton fiber belong to proanthocyanidins (PAs. To clarify the details of PA biosynthesis pathway in brown cotton fiber, gene expression profiles in developing brown and white fibers were compared via digital gene expression profiling and qRT-PCR. Compared to white cotton fiber, all steps from phenylalanine to PA monomers (flavan-3-ols were significantly up-regulated in brown fiber. Liquid chromatography mass spectrometry analyses showed that most of free flavan-3-ols in brown fiber were in 2, 3-trans form (gallocatechin and catechin, and the main units of polymeric PAs were trihydroxylated on B ring. Consistent with monomeric composition, the transcript levels of flavonoid 3', 5'-hydroxylase and leucoanthocyanidin reductase in cotton fiber were much higher than their competing enzymes acting on the same substrates (dihydroflavonol 4-reductase and anthocyanidin synthase, respectively. Taken together, our data revealed a detailed PA biosynthesis pathway wholly activated in brown cotton fiber, and demonstrated that flavonoid 3', 5'-hydroxylase and leucoanthocyanidin reductase represented the primary flow of PA biosynthesis in cotton fiber.

  2. Functional Complementation Analysis (FCA): A Laboratory Exercise Designed and Implemented to Supplement the Teaching of Biochemical Pathways.

    Science.gov (United States)

    Hudson, André O; Harkness, Taylor C M; Savka, Michael A

    2016-01-01

    Functional complementation assay (FCA) is an in vivo assay that is widely used to elucidate the function/role of genes/enzymes. This technique is very common in biochemistry, genetics and many other disciplines. A comprehensive overview of the technique to supplement the teaching of biochemical pathways pertaining to amino acids, peptidoglycan and the bacterial stringent response is reported in this manuscript. Two cDNAs from the model plant organism Arabidopsis thaliana that are involved in the metabolism of lysine (L,L-diaminopimelate aminotransferase (dapL) and tyrosine aminotransferase (tyrB) involved in the metabolism of tyrosine and phenylalanine are highlighted. In addition, the bacterial peptidoglycan anabolic pathway is highlighted through the analysis of the UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-meso-2,6-diaminopimelate ligase (murE) gene from the bacterium Verrucomicrobium spinosum involved in the cross-linking of peptidoglycan. The bacterial stringent response is also reported through the analysis of the rsh (relA/spoT homolog) bifunctional gene responsible for a hyper-mucoid phenotype in the bacterium Novosphingobium sp. Four examples of FCA are presented. The video will focus on three of them, namely lysine, peptidoglycan and the stringent response. PMID:27403640

  3. The cAMP-HMGA1-RBP4 system: a novel biochemical pathway for modulating glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Foti Daniela

    2009-05-01

    Full Text Available Abstract Background We previously showed that mice lacking the high mobility group A1 gene (Hmga1-knockout mice developed a type 2-like diabetic phenotype, in which cell-surface insulin receptors were dramatically reduced (below 10% of those in the controls in the major targets of insulin action, and glucose intolerance was associated with increased peripheral insulin sensitivity. This particular phenotype supports the existence of compensatory mechanisms of insulin resistance that promote glucose uptake and disposal in peripheral tissues by either insulin-dependent or insulin-independent mechanisms. We explored the role of these mechanisms in the regulation of glucose homeostasis by studying the Hmga1-knockout mouse model. Also, the hypothesis that increased insulin sensitivity in Hmga1-deficient mice could be related to the deficit of an insulin resistance factor is discussed. Results We first show that HMGA1 is needed for basal and cAMP-induced retinol-binding protein 4 (RBP4 gene and protein expression in living cells of both human and mouse origin. Then, by employing the Hmga1-knockout mouse model, we provide evidence for the identification of a novel biochemical pathway involving HMGA1 and the RBP4, whose activation by the cAMP-signaling pathway may play an essential role for maintaining glucose metabolism homeostasis in vivo, in certain adverse metabolic conditions in which insulin action is precluded. In comparative studies of normal and mutant mice, glucagon administration caused a considerable upregulation of HMGA1 and RBP4 expression both at the mRNA and protein level in wild-type animals. Conversely, in Hmga1-knockout mice, basal and glucagon-mediated expression of RBP4 was severely attenuated and correlated inversely with increased Glut4 mRNA and protein abundance in skeletal muscle and fat, in which the activation state of the protein kinase Akt, an important downstream mediator of the metabolic effects of insulin on Glut4

  4. Biochemical adaptations in middle-distance runners: an assessment of blood and anthropometric parameters

    OpenAIRE

    Danila Di Majo; Gabriella Schiera; Valentina Contrò; Elena Joana Armeli; Marcello Giaccone; Marco Giammanco; Marcello Traina; Antonio Palma; Patrizia Proia

    2014-01-01

    In order to understand the mechanism underlying the physiological adaptation of purely aerobic workout, we investigated the effect of 2 months of training on nine males (17-22 year-old) middle distance running agonistic athletes. Blood sample was collected in the morning to analyze: hematological parameters, lipid profile, liver function enzymes [glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma-glutamyl transferase (γ-GT)] and skeletal and myocardial markers of musc...

  5. Biochemical characterization of GDP-L-fucose de novo synthesis pathway in fungus Mortierella alpina

    International Nuclear Information System (INIS)

    Mortierella alpina is a filamentous fungus commonly found in soil, which is able to produce large amount of polyunsaturated fatty acids. L-Fucose is an important sugar found in a diverse range of organisms, playing a variety of biological roles. In this study, we characterized the de novo biosynthetic pathway of GDP-L-fucose (the nucleotide-activated form of L-fucose) in M. alpina. Genes encoding GDP-D-mannose 4,6-dehydratase (GMD) and GDP-keto-6-deoxymannose 3,5-epimerase/4-reductase (GMER) were expressed heterologously in Escherichia coli. The recombinant enzymes were produced as His-tagged fusion proteins. Conversion of GDP-mannose to GDP-4-keto-6-deoxy mannose by GMD and GDP-4-keto-6-deoxy mannose to GDP-L-fucose by GMER were analyzed by capillary electrophoresis, electro-spray ionization-mass spectrometry, and nuclear magnetic resonance spectroscopy. The km values of GMD for GDP-mannose and GMER for GDP-4-keto-6-deoxy mannose were determined to be 0.77 mM and 1.047 mM, respectively. Both NADH and NADPH may be used by GMER as the coenzyme. The optimum temperature and pH were determined to be 37 oC and pH 9.0 (GMD) or pH 7.0 (GMER). Divalent cations are not required for GMD and GMER activity, and the activities of both enzymes may be enhanced by DTT. To our knowledge this is the first report on the characterization of GDP-L-fucose biosynthetic pathway in fungi.

  6. Biochemical characterization of GDP-L-fucose de novo synthesis pathway in fungus Mortierella alpina

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Yan [TEDA School of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457 (China); Perepelov, Andrei V. [N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt 47, 119991 Moscow (Russian Federation); Wang, Haiyan [TEDA School of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457 (China); Zhang, Hao [State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122 (China); Knirel, Yuriy A. [N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt 47, 119991 Moscow (Russian Federation); Wang, Lei [TEDA School of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457 (China); Chen, Wei, E-mail: weichen@jiangnan.edu.cn [State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122 (China)

    2010-01-22

    Mortierella alpina is a filamentous fungus commonly found in soil, which is able to produce large amount of polyunsaturated fatty acids. L-Fucose is an important sugar found in a diverse range of organisms, playing a variety of biological roles. In this study, we characterized the de novo biosynthetic pathway of GDP-L-fucose (the nucleotide-activated form of L-fucose) in M. alpina. Genes encoding GDP-D-mannose 4,6-dehydratase (GMD) and GDP-keto-6-deoxymannose 3,5-epimerase/4-reductase (GMER) were expressed heterologously in Escherichia coli. The recombinant enzymes were produced as His-tagged fusion proteins. Conversion of GDP-mannose to GDP-4-keto-6-deoxy mannose by GMD and GDP-4-keto-6-deoxy mannose to GDP-L-fucose by GMER were analyzed by capillary electrophoresis, electro-spray ionization-mass spectrometry, and nuclear magnetic resonance spectroscopy. The k{sub m} values of GMD for GDP-mannose and GMER for GDP-4-keto-6-deoxy mannose were determined to be 0.77 mM and 1.047 mM, respectively. Both NADH and NADPH may be used by GMER as the coenzyme. The optimum temperature and pH were determined to be 37 {sup o}C and pH 9.0 (GMD) or pH 7.0 (GMER). Divalent cations are not required for GMD and GMER activity, and the activities of both enzymes may be enhanced by DTT. To our knowledge this is the first report on the characterization of GDP-L-fucose biosynthetic pathway in fungi.

  7. Biogenesis pathways of RNA guides in archaeal and bacterial CRISPR-Cas adaptive immunity

    NARCIS (Netherlands)

    Charpentier, Emmanuelle; Richter, Hagen; Oost, van der John; White, Malcolm F.

    2015-01-01

    CRISPR-Cas is an RNA-mediated adaptive immune system that defends bacteria and archaea against mobile genetic elements. Short mature CRISPR RNAs (crRNAs) are key elements in the interference step of the immune pathway. A CRISPR array composed of a series of repeats interspaced by spacer sequences

  8. Hurricane Sandy and Adaptation Pathways in New York: Lessons from a First-Responder City

    Science.gov (United States)

    Rosenzweig, Cynthia; Solecki, William

    2014-01-01

    Two central issues of climate change have become increasingly evident: Climate change will significantly affect cities; and rapid global urbanization will increase dramatically the number of individuals, amount of critical infrastructure, and means of economic production that are exposed and vulnerable to dynamic climate risks. Simultaneously, cities in many settings have begun to emerge as early adopters of climate change action strategies including greenhouse gas mitigation and adaptation. The objective of this paper is to examine and analyze how officials of one city - the City of New York - have integrated a flexible adaptation pathways approach into the municipality's climate action strategy. This approach has been connected with the City's ongoing response to Hurricane Sandy, which struck in the October 2012 and resulted in damages worth more than US$19 billion. A case study narrative methodology utilizing the Wise et al. conceptual framework (see this volume) is used to evaluate the effectiveness of the flexible adaptation pathways approach in New York City. The paper finds that Hurricane Sandy serves as a ''tipping point'' leading to transformative adaptation due to the explicit inclusion of increasing climate change risks in the rebuilding effort. The potential for transferability of the approach to cities varying in size and development stage is discussed, with elements useful across cities including the overall concept of flexible adaptation pathways, the inclusion of the full metropolitan region in the planning process, and the co-generation of climate-risk information by stakeholders and scientists.

  9. Hypoxia Inducible Factor Pathway and Physiological Adaptation: A Cell Survival Pathway?

    OpenAIRE

    2015-01-01

    Oxygen homeostasis reflects the constant body requirement to generate energy. Hypoxia (0.1–1% O2), physioxia or physoxia (∼1–13%), and normoxia (∼20%) are terms used to define oxygen concentration in the cellular environment. A decrease in oxygen (hypoxia) or excess oxygen (hyperoxia) could be deleterious for cellular adaptation and survival. Hypoxia can occur under both physiological (e.g., exercise, embryonic development, underwater diving, or high altitude) and pathological conditions (e.g...

  10. Characterization of a novel oxyfluorfen-degrading bacterial strain Chryseobacterium aquifrigidense and its biochemical degradation pathway.

    Science.gov (United States)

    Zhao, Huanhuan; Xu, Jun; Dong, Fengshou; Liu, Xingang; Wu, Yanbing; Wu, Xiaohu; Zheng, Yongquan

    2016-08-01

    Persistent use of the diphenyl ether herbicides oxyfluorfen may seriously increase the health risks and ecological safety problems. A newly bacterium R-21 isolated from active soil was able to degrade and utilize oxyfluorfen as the sole carbon source. R-21 was identified as Chryseobacterium aquifrigidense by morphology, physiobiochemical characteristics, and genetic analysis. Under the optimum cultural conditions (pH 6.9, temperature 33.4 °C, and inoculum size 0.2 g L(-1)), R-21 could degrade 92.1 % of oxyfluorfen at 50 mg L(-1) within 5 days. During oxyfluorfen degradation, six metabolites were detected and identified by atmospheric pressure gas chromatography coupled to quadrupole-time of flight mass spectrometry and ultra-performance liquid chromatography coupled to quadrupole-time of flight mass spectrometry, and a plausible degradation pathway was deduced. Strain R-21 is a promising potential in bioremediation of oxyfluorfen-contaminated environments. PMID:27079576

  11. Formation of soil organic matter via biochemical and physical pathways of litter mass loss

    Science.gov (United States)

    Cotrufo, M. Francesca; Soong, Jennifer L.; Horton, Andrew J.; Campbell, Eleanor E.; Haddix, Michelle L.; Wall, Diana H.; Parton, William J.

    2015-10-01

    Soil organic matter is the largest terrestrial carbon pool. The pool size depends on the balance between formation of soil organic matter from decomposition of plant litter and its mineralization to inorganic carbon. Knowledge of soil organic matter formation remains limited and current C numerical models assume that stable soil organic matter is formed primarily from recalcitrant plant litter. However, labile components of plant litter could also form mineral-stabilized soil organic matter. Here we followed the decomposition of isotopically labelled above-ground litter and its incorporation into soil organic matter over three years in a grassland in Kansas, USA, and used laboratory incubations to determine the decay rates and pool structure of litter-derived organic matter. Early in decomposition, soil organic matter formed when non-structural compounds were lost from litter. Soil organic matter also formed at the end of decomposition, when both non-structural and structural compounds were lost at similar rates. We conclude that two pathways yield soil organic matter efficiently. A dissolved organic matter-microbial path occurs early in decomposition when litter loses mostly non-structural compounds, which are incorporated into microbial biomass at high rates, resulting in efficient soil organic matter formation. An equally efficient physical-transfer path occurs when litter fragments move into soil.

  12. Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

    Directory of Open Access Journals (Sweden)

    Norbert W Lutz

    Full Text Available Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE and adjuvant arthritis (AA in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA and spinal-cord homogenate (SC-H, whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group. Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE or extra-cerebral (AA inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and

  13. Biochemical adaptations to dive-derived hypoxia/reoxygenation in semiaquatic rodents.

    Science.gov (United States)

    Sergina, Svetlana; Antonova, Ekaterina; Ilyukha, Viktor; Łapiński, Stanisław; Lis, Marcin; Niedbała, Piotr; Unzhakov, Alexey; Belkin, Vladimir

    2015-12-01

    To meet the challenges presented by dive-derived hypoxia/reoxygenation transition, the aquatic mammals possess multi-level adaptations. However, the adjustments of the semiaquatic animals as modern analogs of evolutionary intermediates between ancestral terrestrial mammals and their fully aquatic descendants are still not fully elucidated. The aim of this study was to analyze the total lactate dehydrogenase (LDH) activity (in the lactate to pyruvate direction), the LDH patterns and the antioxidant defense in the tissues (heart, kidney, liver, lung, muscle, spleen) of semiaquatic rodents such as Eurasian beaver (Castor fiber), muskrat (Ondatra zibethicus) and nutria (Myocastor coypus). Samples from Wistar rat were used for comparison. Semiaquatic rodents had higher catalase activity compared to rats. The superoxide dismutase activity was higher and the catalase activity was lower in almost all tissues of muskrat than of both beaver and nutria. Comparing beaver and nutria, no significant differences in the antioxidant enzyme activities were found for the heart, kidney and liver. In beaver, most of the examined tissues (heart, kidney, lung and spleen) use lactate as preference to glucose as a substrate but in muskrat the heart, liver and skeletal muscle showed the increased LDH activity. Nutria had the unusual LDH properties that are needed to be further investigated. Our results suggest that beaver, nutria and muskrat have distinct mechanisms of adaptation to diving hypoxia/reoxygenation and support the hypothesis that semiaquatic mammals are the intermediate animals that help to define which potential selection factors and mechanical constraints may have directed the evolution of the aquatic forms. PMID:26341791

  14. Interaction between cAMP and intracellular Ca(2+)-signaling pathways during odor-perception and adaptation in Drosophila.

    Science.gov (United States)

    Murmu, Meena Sriti; Martin, Jean-René

    2016-09-01

    Binding of an odorant to olfactory receptors triggers cascades of second messenger systems in olfactory receptor neurons (ORNs). Biochemical studies indicate that the transduction mechanism at ORNs is mediated by cyclic adenosine monophosphate (cAMP) and/or inositol,1,4,5-triphosphate (InsP3)-signaling pathways in an odorant-dependent manner. However, the interaction between these two second messenger systems during olfactory perception or adaptation processes is much less understood. Here, we used interfering-RNAi to disrupt the level of cAMP alone or in combination with the InsP3-signaling pathway cellular targets, InsP3 receptor (InsP3R) or ryanodine receptor (RyR) in ORNs, and quantify at ORN axon terminals in the antennal lobe, the odor-induced Ca(2+)-response. In-vivo functional bioluminescence Ca(2+)-imaging indicates that a single 5s application of an odor increased Ca(2+)-transients at ORN axon terminals. However, compared to wild-type controls, the magnitude and duration of ORN Ca(2+)-response was significantly diminished in cAMP-defective flies. In a behavioral assay, perception of odorants was defective in flies with a disrupted cAMP level suggesting that the ability of flies to correctly detect an odor depends on cAMP. Simultaneous disruption of cAMP level and InsP3R or RyR further diminished the magnitude and duration of ORN response to odorants and affected the flies' ability to detect an odor. In conclusion, this study provides functional evidence that cAMP and InsP3-signaling pathways act in synergy to mediate odor processing within the ORN axon terminals, which is encoded in the magnitude and duration of ORN response. PMID:27212269

  15. PCOSKB: A KnowledgeBase on genes, diseases, ontology terms and biochemical pathways associated with PolyCystic Ovary Syndrome.

    Science.gov (United States)

    Joseph, Shaini; Barai, Ram Shankar; Bhujbalrao, Rasika; Idicula-Thomas, Susan

    2016-01-01

    Polycystic ovary syndrome (PCOS) is one of the major causes of female subfertility worldwide and ≈ 7-10% of women in reproductive age are affected by it. The affected individuals exhibit varying types and levels of comorbid conditions, along with the classical PCOS symptoms. Extensive studies on PCOS across diverse ethnic populations have resulted in a plethora of information on dysregulated genes, gene polymorphisms and diseases linked to PCOS. However, efforts have not been taken to collate and link these data. Our group, for the first time, has compiled PCOS-related information available through scientific literature; cross-linked it with molecular, biochemical and clinical databases and presented it as a user-friendly, web-based online knowledgebase for the benefit of the scientific and clinical community. Manually curated information on associated genes, single nucleotide polymorphisms, diseases, gene ontology terms and pathways along with supporting reference literature has been collated and included in PCOSKB (http://pcoskb.bicnirrh.res.in). PMID:26578565

  16. Biochemical adaptations in middle-distance runners: an assessment of blood and anthropometric parameters

    Directory of Open Access Journals (Sweden)

    Danila Di Majo

    2014-12-01

    Full Text Available In order to understand the mechanism underlying the physiological adaptation of purely aerobic workout, we investigated the effect of 2 months of training on nine males (17-22 year-old middle distance running agonistic athletes. Blood sample was collected in the morning to analyze: hematological parameters, lipid profile, liver function enzymes [glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, gamma-glutamyl transferase (γ-GT] and skeletal and myocardial markers of muscle damage [creatin kinase (CK and creatin kinase MB (CK-MB]. Endurance training, as it implies high oxygen consumption, should increase reactive oxygen species, but it has been shown that exercise leads to increased activation of antioxidant defenses. In fact, serum levels of γ-GT enzyme and total CK were not increased. On the other hand, a statistical significant reduction of CKMB has been observed. There were not variations in hematological parameters. As far as the anthropometric value is concerned, after two months of training there was a change in weight (P<0.0001. Finally, any oxidative and biological stress was highlighted in the middle distance runners but, since this is a preliminary study, it would be of interest to replicate the study on a larger sample.

  17. Complement activation pathways: a bridge between innate and adaptive immune responses in asthma.

    Science.gov (United States)

    Wills-Karp, Marsha

    2007-07-01

    Although it is widely accepted that allergic asthma is driven by T helper type 2 (Th2)-polarized immune responses to innocuous environmental allergens, the mechanisms driving these aberrant immune responses remain elusive. Recent recognition of the importance of innate immune pathways in regulating adaptive immune responses have fueled investigation into the role of innate immune pathways in the pathogenesis of asthma. The phylogenetically ancient innate immune system, the complement system, is no exception. The emerging paradigm is that C3a production at the airway surface serves as a common pathway for the induction of Th2-mediated inflammatory responses to a variety of environmental triggers of asthma (i.e., allergens, pollutants, viral infections, cigarette smoke). In contrast, C5a plays a dual immunoregulatory role by protecting against the initial development of a Th2-polarized adaptive immune response via its ability to induce tolerogenic dendritic cell subsets. On the other hand, C5a drives type 2-mediated inflammatory responses once inflammation ensues. Thus, alterations in the balance of generation of the various components of the complement pathway either due to environmental exposure changes or genetic alterations in genes of the complement cascade may underlie the recent rise in asthma prevalence in westernized countries. PMID:17607007

  18. From L-dopa to dihydroxyphenylacetaldehyde: a toxic biochemical pathway plays a vital physiological function in insects.

    Directory of Open Access Journals (Sweden)

    Christopher Vavricka

    Full Text Available One protein in Aedes aegypti, classified into the aromatic amino acid decarboxylase (AAAD family based on extremely high sequence homology (∼70% with dopa decarboxylase (Ddc, was biochemically investigated. Our data revealed that this predicted AAAD protein use L-dopa as a substrate, as does Ddc, but it catalyzes the production of 3,4-dihydroxylphenylacetaldehyde (DHPAA directly from L-dopa and apparently has nothing to do with the production of any aromatic amine. The protein is therefore named DHPAA synthase. This subsequently led to the identification of the same enzyme in Drosophila melanogaster, Anopheles gambiae and Culex quinquefasciatus by an initial prediction of putative DHPAA synthase based on sequence homology and subsequent verification of DHPAA synthase identity through protein expression and activity assays. DHPAA is highly toxic because its aldehyde group readily reacts with the primary amino groups of proteins, leading to protein crosslinking and inactivation. It has previously been demonstrated by several research groups that Drosophila DHPAA synthase was expressed in tissues that produce cuticle materials and apparent defects in regions of colorless, flexible cuticular structures have been observed in its gene mutants. The presence of free amino groups in proteins, the high reactivity of DHPAA with the free amino groups, and the genetically ascertained function of the Drosophila DHPAA synthase in the formation of colorless, flexible cuticle, when taken together, suggest that mosquito and Drosophila DHPAA synthases are involved in the formation of flexible cuticle through their reactive DHPAA-mediated protein crosslinking reactions. Our data illustrate how a seemingly highly toxic pathway can serve for an important physiological function in insects.

  19. DMPD: The oxidation of lipoproteins by monocytes-macrophages. Biochemical andbiological mechanisms. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10473535 The oxidation of lipoproteins by monocytes-macrophages. Biochemical andbio.... (.png) (.svg) (.html) (.csml) Show The oxidation of lipoproteins by monocytes-macrophages. Biochemical and...biological mechanisms. PubmedID 10473535 Title The oxidation of lipoproteins by m

  20. Biogenesis pathways of RNA guides in archaeal and bacterial CRISPR-Cas adaptive immunity

    OpenAIRE

    Charpentier, Emmanuelle; Richter, Hagen; van der Oost, John; White, Malcolm F

    2015-01-01

    CRISPR-Cas is an RNA-mediated adaptive immune system that defends bacteria and archaea against mobile genetic elements. Short mature CRISPR RNAs (crRNAs) are key elements in the interference step of the immune pathway. A CRISPR array composed of a series of repeats interspaced by spacer sequences acquired from invading mobile genomes is transcribed as a precursor crRNA (pre-crRNA) molecule. This pre-crRNA undergoes one or two maturation steps to generate the mature crRNAs that guide CRISPR-as...

  1. Systems Analysis of Adaptive Responses to MAP Kinase Pathway Blockade in BRAF Mutant Melanoma.

    Science.gov (United States)

    Capaldo, Brian J; Roller, Devin; Axelrod, Mark J; Koeppel, Alex F; Petricoin, Emanuel F; Slingluff, Craig L; Weber, Michael J; Mackey, Aaron J; Gioeli, Daniel; Bekiranov, Stefan

    2015-01-01

    Fifty percent of cutaneous melanomas are driven by activated BRAFV600E, but tumors treated with RAF inhibitors, even when they respond dramatically, rapidly adapt and develop resistance. Thus, there is a pressing need to identify the major mechanisms of intrinsic and adaptive resistance and develop drug combinations that target these resistance mechanisms. In a combinatorial drug screen on a panel of 12 treatment-naïve BRAFV600E mutant melanoma cell lines of varying levels of resistance to mitogen-activated protein kinase (MAPK) pathway inhibition, we identified the combination of PLX4720, a targeted inhibitor of mutated BRaf, and lapatinib, an inhibitor of the ErbB family of receptor tyrosine kinases, as synergistically cytotoxic in the subset of cell lines that displayed the most resistance to PLX4720. To identify potential mechanisms of resistance to PLX4720 treatment and synergy with lapatinib treatment, we performed a multi-platform functional genomics analysis to profile the genome as well as the transcriptional and proteomic responses of these cell lines to treatment with PLX4720. We found modest levels of resistance correlated with the zygosity of the BRAF V600E allele and receptor tyrosine kinase (RTK) mutational status. Layered over base-line resistance was substantial upregulation of many ErbB pathway genes in response to BRaf inhibition, thus generating the vulnerability to combination with lapatinib. The transcriptional responses of ErbB pathway genes are associated with a number of transcription factors, including ETS2 and its associated cofactors that represent a convergent regulatory mechanism conferring synergistic drug susceptibility in the context of diverse mutational landscapes. PMID:26405815

  2. H. pylori exploits and manipulates innate and adaptive immune cell signaling pathways to establish persistent infection

    Directory of Open Access Journals (Sweden)

    Arnold Isabelle C

    2011-11-01

    Full Text Available Abstract Persistent infection with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes carriers to a high gastric cancer risk, but has also been linked to protection from allergic, chronic inflammatory and autoimmune diseases. In the course of tens of thousands of years of co-existence with its human host, H. pylori has evolved elaborate adaptations that allow it to persist in the hostile environment of the stomach in the face of a vigorous innate and adaptive immune response. For this review, we have identified several key immune cell types and signaling pathways that appear to be preferentially targeted by the bacteria to establish and maintain persistent infection. We explore the mechanisms that allow the bacteria to avoid detection by innate immune cells via their pattern recognition receptors, to escape T-cell mediated adaptive immunity, and to reprogram the immune system towards tolerance rather than immunity. The implications of the immunomodulatory properties of the bacteria for the prevention of allergic and auto-immune diseases in chronically infected individuals are also discussed.

  3. Rod-Driven OFF Pathway Responses in the Distal Retina: Dark-Adapted Flicker Electroretinogram in Mouse

    OpenAIRE

    Lei, Bo

    2012-01-01

    Purpose The rodent retina does not exhibit a positive OFF-response in the electroretinogram (ERG), which makes it difficult to evaluate its OFF-pathway functions in vivo. We studied the rod-driven OFF pathway responses by using a dark-adapted 10-Hz flicker ERG procedure in mouse. Materials and Methods Conventional ERGs and 10-Hz dark-adapted flicker ERGs were obtained in wild-type mice (C57BL/6), in mice with pure rod (cpfl1) or pure cone (rho−/− ) function, and in nob1 mice which have a sele...

  4. Adaptive Image-Guided Radiotherapy (IGRT) Eliminates the Risk of Biochemical Failure Caused by the Bias of Rectal Distension in Prostate Cancer Treatment Planning: Clinical Evidence

    International Nuclear Information System (INIS)

    Purpose: Rectal distension has been shown to decrease the probability of biochemical control. Adaptive image-guided radiotherapy (IGRT) corrects for target position and volume variations, reducing the risk of biochemical failure while yielding acceptable rates of gastrointestinal (GI)/genitourinary (GU) toxicities. Methods and Materials: Between 1998 and 2006, 962 patients were treated with computed tomography (CT)-based offline adaptive IGRT. Patients were stratified into low (n = 400) vs. intermediate/high (n = 562) National Comprehensive Cancer Network (NCCN) risk groups. Target motion was assessed with daily CT during the first week. Electronic portal imaging device (EPID) was used to measure daily setup error. Patient-specific confidence-limited planning target volumes (cl-PTV) were then constructed, reducing the standard PTV and compensating for geometric variation of the target and setup errors. Rectal volume (RV), cross-sectional area (CSA), and rectal volume from the seminal vesicles to the inferior prostate (SVP) were assessed on the planning CT. The impact of these volumetric parameters on 5-year biochemical control (BC) and chronic Grades ≥2 and 3 GU and GI toxicity were examined. Results: Median follow-up was 5.5 years. Median minimum dose covering cl-PTV was 75.6 Gy. Median values for RV, CSA, and SVP were 82.8 cm3, 5.6 cm2, and 53.3 cm3, respectively. The 5-year BC was 89% for the entire group: 96% for low risk and 83% for intermediate/high risk (p < 0.001). No statistically significant differences in BC were seen with stratification by RV, CSA, and SVP in quartiles. Maximum chronic Grades ≥2 and 3 GI toxicities were 21.2% and 2.9%, respectively. Respective values for GU toxicities were 15.5% and 4.3%. No differences in GI or GU toxicities were noted when patients were stratified by RV. Conclusions: Incorporation of adaptive IGRT reduces the risk of geometric miss and results in excellent biochemical control that is independent of rectal volume

  5. Medicine adaptive pathways to patients (MAPPs): using regulatory innovation to defeat Eroom's law.

    Science.gov (United States)

    Schulthess, Duane; Chlebus, Magda; Bergstrӧm, Richard; Baelen, Karin Van

    2014-06-01

    Eroom's Law is, literally, Moore's law in reverse. The pharmaceutical sector invests $50 billion annually in research for new medicines but, "the number of new drugs approved per billion US dollars spent has halved roughly every 9 years since 1950, falling around 80-fold in inflation-adjusted terms". Pharmaceutical companies have invested enormous sums in new molecular entities (NME) in the areas of unmet medical need identified by the World Health Organization (WHO), but the approval rates from phase I are only 7% for cardiovascular disease, dropping to 4% for Alzheimer's disease. The increasing cost of research & development (R&D) is not only a factor of research management quality, but also indicative of an industry trying to address therapeutic areas that have incredibly complex biological mechanisms with budget-crushing failure rates. Medicine adaptive pathways to patients (MAPPs) build on the stratification breakthroughs of personalized medicine to facilitate new types of clinical trials that adapt to a given patient's response. At their core, MAPPs will have a limited commercial marketing authorization for a patient group who has access to new therapeutic agents while validating additional clinical endpoints at the same time. This gives MAPPs a theoretical ability to run trials that fulfil both the efficacy requirements for authorization and the effectiveness needs of national health technology assessments (HTA) simultaneously, providing patients with needed therapies in the most efficient timescale and trial size possible. In order to move science forward and meet these daunting medical challenges for patients, new collaborative approaches to testing the efficacy and effectiveness of new improved medicines such as MAPPs should be embraced by regulators in close partnership with patients, payers, and practitioners. To not do so puts the entire healthcare value chain, and the future health of patients, at risk. PMID:25841417

  6. FK506 binding protein 51 integrates pathways of adaptation: FKBP51 shapes the reactivity to environmental change.

    Science.gov (United States)

    Rein, Theo

    2016-09-01

    This review portraits FK506 binding protein (FKBP) 51 as "reactivity protein" and collates recent publications to develop the concept of FKBP51 as contributor to different levels of adaptation. Adaptation is a fundamental process that enables unicellular and multicellular organisms to adjust their molecular circuits and structural conditions in reaction to environmental changes threatening their homeostasis. FKBP51 is known as chaperone and co-chaperone of heat shock protein (HSP) 90, thus involved in processes ensuring correct protein folding in response to proteotoxic stress. In mammals, FKBP51 both shapes the stress response and is calibrated by the stress levels through an ultrashort molecular feedback loop. More recently, it has been linked to several intracellular pathways related to the reactivity to drug exposure and stress. Through its role in autophagy and DNA methylation in particular it influences adaptive pathways, possibly also in a transgenerational fashion. Also see the video abstract here. PMID:27374865

  7. Enzyme and biochemical producing fungi

    DEFF Research Database (Denmark)

    Lübeck, Peter Stephensen; Lübeck, Mette; Nilsson, Lena;

    2010-01-01

    factories for sustainable production of important molecules. For developing fungi into efficient cell factories, the project includes identification of important factors that control the flux through the pathways using metabolic flux analysis and metabolic engineering of biochemical pathways....

  8. Modification of the biochemical pathways of plants induced by ozone: What are the varied routes to change?

    Energy Technology Data Exchange (ETDEWEB)

    Heath, Robert L. [Department of Botany and Plant Sciences, University of California, 500 Watkins Drive, Riverside, CA 92521 (United States)], E-mail: heath@ucr.edu

    2008-10-15

    When plants are observed under a low dose of ozone, some physiological and metabolic shifts occur. Barring extreme injury such as tissue damage or stomata closure, most of these disruptive changes are likely to have been initiated at the level of gene expression. The belief is oxidative products formed in ozone exposed leaves, e.g. hydrogen peroxide, are responsible for much of the biochemical adjustments. The first line of defense is a range of antioxidants, such as ascorbate and glutathione, but if this defense is overwhelmed, subsequent actions occur, similar to systemic acquired resistance or general wounding. Yet there are seemingly unrelated metabolic responses which are also triggered, such as early senescence. We discuss here the current understanding of gene control and signal transduction/control in order to increase our comprehension of how ozone alters the basic metabolism of plants and how plants counteract or cope with ozone. - A discussion of current concepts of how ozone interactions with plant leaf tissue can trigger a wide variety of injury symptoms, which include antioxidants changes and metabolic shifts.

  9. Modification of the biochemical pathways of plants induced by ozone: What are the varied routes to change?

    International Nuclear Information System (INIS)

    When plants are observed under a low dose of ozone, some physiological and metabolic shifts occur. Barring extreme injury such as tissue damage or stomata closure, most of these disruptive changes are likely to have been initiated at the level of gene expression. The belief is oxidative products formed in ozone exposed leaves, e.g. hydrogen peroxide, are responsible for much of the biochemical adjustments. The first line of defense is a range of antioxidants, such as ascorbate and glutathione, but if this defense is overwhelmed, subsequent actions occur, similar to systemic acquired resistance or general wounding. Yet there are seemingly unrelated metabolic responses which are also triggered, such as early senescence. We discuss here the current understanding of gene control and signal transduction/control in order to increase our comprehension of how ozone alters the basic metabolism of plants and how plants counteract or cope with ozone. - A discussion of current concepts of how ozone interactions with plant leaf tissue can trigger a wide variety of injury symptoms, which include antioxidants changes and metabolic shifts

  10. Identification of Biochemical Pathways Associated with Lead Tolerance and Detoxification in Chrysopogon zizanioides L. Nash (Vetiver) by Metabolic Profiling.

    Science.gov (United States)

    Pidatala, Venkataramana R; Li, Kefeng; Sarkar, Dibyendu; Ramakrishna, Wusirika; Datta, Rupali

    2016-03-01

    Lead (Pb) is a major urban pollutant, due to deteriorating lead-based paint in houses built before 1978. Phytoremediation is an inexpensive and effective technique for remediation of Pb-contaminated homes. Vetiver (Chrysopogon zizanioides), a noninvasive, fast-growing grass with high biomass, can tolerate and accumulate large quantities of Pb in its tissues. Lead is known to induce phytochelatins and antioxidative enzymes in vetiver; however, the overall impact of Pb stress on metabolic pathways of vetiver is unknown. In the current study, vetiver plants were treated with different concentrations of Pb in a hydroponic setup. Metabolites were extracted and analyzed using LC/MS/MS. Multivariate analysis of metabolites in both root and shoot tissue showed tremendous induction in key metabolic pathways including sugar metabolism, amino acid metabolism, and an increase in production of osmoprotectants, such as betaine and polyols, and metal-chelating organic acids. The data obtained provide a comprehensive insight into the overall stress response mechanisms in vetiver. PMID:26843403

  11. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Wu, C-W.; Biggar, K.K.; Storey, K.B. [Carleton University, Department of Biology, Institute of Biochemistry, Ottawa, ON (Canada)

    2013-01-28

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans.

  12. Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

    International Nuclear Information System (INIS)

    An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans

  13. Transcriptome Profiling and Molecular Pathway Analysis of Genes in Association with Salinity Adaptation in Nile Tilapia Oreochromis niloticus.

    Directory of Open Access Journals (Sweden)

    Zhixin Xu

    Full Text Available Nile tilapia Oreochromis niloticus is a freshwater fish but can tolerate a wide range of salinities. The mechanism of salinity adaptation at the molecular level was studied using RNA-Seq to explore the molecular pathways in fish exposed to 0, 8, or 16 (practical salinity unit, psu. Based on the change of gene expressions, the differential genes unions from freshwater to saline water were classified into three categories. In the constant change category (1, steroid biosynthesis, steroid hormone biosynthesis, fat digestion and absorption, complement and coagulation cascades were significantly affected by salinity indicating the pivotal roles of sterol-related pathways in response to salinity stress. In the change-then-stable category (2, ribosomes, oxidative phosphorylation, signaling pathways for peroxisome proliferator activated receptors, and fat digestion and absorption changed significantly with increasing salinity, showing sensitivity to salinity variation in the environment and a responding threshold to salinity change. In the stable-then-change category (3, protein export, protein processing in endoplasmic reticulum, tight junction, thyroid hormone synthesis, antigen processing and presentation, glycolysis/gluconeogenesis and glycosaminoglycan biosynthesis-keratan sulfate were the significantly changed pathways, suggesting that these pathways were less sensitive to salinity variation. This study reveals fundamental mechanism of the molecular response to salinity adaptation in O. niloticus, and provides a general guidance to understand saline acclimation in O. niloticus.

  14. Biochemical, transcriptional and translational evidences of the phenol-meta-degradation pathway by the hyperthermophilic Sulfolobus solfataricus 98/2.

    Directory of Open Access Journals (Sweden)

    Alexia Comte

    Full Text Available Phenol is a widespread pollutant and a model molecule to study the biodegradation of monoaromatic compounds. After a first oxidation step leading to catechol in mesophilic and thermophilic microorganisms, two main routes have been identified depending on the cleavage of the aromatic ring: ortho involving a catechol 1,2 dioxygenase (C12D and meta involving a catechol 2,3 dioxygenase (C23D. Our work aimed at elucidating the phenol-degradation pathway in the hyperthermophilic archaea Sulfolobus solfataricus 98/2. For this purpose, the strain was cultivated in a fermentor under different substrate and oxygenation conditions. Indeed, reducing dissolved-oxygen concentration allowed slowing down phenol catabolism (specific growth and phenol-consumption rates dropped 55% and 39%, respectively and thus, evidencing intermediate accumulations in the broth. HPLC/Diode Array Detector and LC-MS analyses on culture samples at low dissolved-oxygen concentration (DOC  =  0.06 mg x L(-1 suggested, apart for catechol, the presence of 2-hydroxymuconic acid, 4-oxalocrotonate and 4-hydroxy-2-oxovalerate, three intermediates of the meta route. RT-PCR analysis on oxygenase-coding genes of S. solfataricus 98/2 showed that the gene coding for the C23D was expressed only on phenol. In 2D-DIGE/MALDI-TOF analysis, the C23D was found and identified only on phenol. This set of results allowed us concluding that S. solfataricus 98/2 degrade phenol through the meta route.

  15. Characterization of the novel dimethyl sulfide-degrading bacterium Alcaligenes sp. SY1 and its biochemical degradation pathway.

    Science.gov (United States)

    Sun, Yiming; Qiu, Jiguo; Chen, Dongzhi; Ye, Jiexu; Chen, Jianmeng

    2016-03-01

    Recently, the biodegradation of volatile organic sulfur compounds (VOSCs) has become a burgeoning field, with a growing focus on the reduction of VOSCs. The reduction of VOSCs encompasses both organic emission control and odor control. Herein, Alcaligenes sp. SY1 was isolated from active sludge and found to utilize dimethyl sulfide (DMS) as a growth substrate in a mineral salt medium. Response surface methodology (RSM) analysis was applied to optimize the incubation conditions. The following conditions for optimal degradation were identified: temperature 27.03°C; pH 7.80; inoculum salinity 0.84%; and initial DMS concentration 1585.39 μM. Under these conditions, approximately 99% of the DMS was degraded within 30 h of incubation. Two metabolic compounds were detected and identified by gas chromatography-mass spectrometry (GC-MS): dimethyl disulfide (DMDS) and dimethyl trisulfide (DMTS). The DMS degradation kinetics for different concentrations were evaluated using the Haldane-Andrews model and the pseudo first-order model. The maximum specific growth rate and degradation rate of Alcaligenes sp. SY1 were 0.17 h(-1) and 0.63 gs gx(-1)h(-1). A possible degradation pathway is proposed, and the results suggest that Alcaligenes sp. SY1 has the potential to control odor emissions under aerobic conditions. PMID:26623933

  16. Analysis of biochemical compounds and differentially expressed genes of the anthocyanin biosynthetic pathway in variegated peach flowers.

    Science.gov (United States)

    Hassani, D; Liu, H L; Chen, Y N; Wan, Z B; Zhuge, Q; Li, S X

    2015-01-01

    Variegated plants are highly valuable in the floricultural market, yet the genetic mechanism underlying this attractive phenomenon has not been completely elucidated. In this study, we identified and measured different compounds in pink and white flower petals of peach (Prunus persica) by high-performance liquid chromatography and liquid chromatography/mass spectrometry analyses. No cyanidin-based or pelargonidin-based compounds were detected in white petals, but high levels of these compounds were found in pink petals. Additionally, we sequenced and analyzed the expression of six key structural genes in the anthocyanin biosynthesis pathway (CHI, CHS, DFR, F3'H, ANS, and UFGT) in both white and pink petals. Quantitative real-time polymerase chain reaction revealed all six genes to be expressed at greatly reduced levels in white flower petals, relative to pink. No allelic variations were found in the transcribed sequences. However, alignment of transcribed and genomic sequences of the ANS gene detected alternative splicing, resulting in transcripts of 1.071 and 942 bp. Only the longer transcript was observed in white flower petals. Since ANS is the key intermediate enzyme catalyzing the colorless leucopelargonidin and leucocyanidin to substrates required for completion of anthocyanin biosynthesis, the ANS gene is implicated in flower color variegation and should be explored in future studies. This article, together with a previous transcriptome study, elucidates the mechanism underlying peach flower color variegation in terms of the key structural genes involved in anthocyanin biosynthesis. PMID:26535657

  17. Direct evidence of the cyclooxygenase pathway of prostaglandin synthesis in arthropods: genetic and biochemical characterization of two crustacean cyclooxygenases.

    Science.gov (United States)

    Varvas, Külliki; Kurg, Reet; Hansen, Kristella; Järving, Reet; Järving, Ivar; Valmsen, Karin; Lõhelaid, Helike; Samel, Nigulas

    2009-12-01

    Prostaglandins, well-known lipid mediators in vertebrate animals, have also shown to play certain regulatory roles in insects and other arthropods acting on reproduction, immune system and ion transport. However, knowledge of their biosynthetic pathways in arthropods is lacking. In the present study, we report the cloning and expression of cyclooxygenase (COX) from amphipod crustaceans Gammarus spp and Caprella spp. The amphipod COX proteins contain key residues shown to be important for cyclooxygenase and peroxidase activities. Differently from all other known cyclooxygenases the N-terminal signal sequence of amphipod enzymes is not cleaved during protein expression in mammalian cells. The C-terminus of amphipod COX is shorter than that of mammalian isoforms and lacks the KDEL(STEL)-type endoplasmic reticulum retention/retrieval signal. Despite that, amphipod COX proteins are N-glycosylated and locate similarly to the vertebrate COX on the endoplasmic reticulum and nuclear envelope. Both amphipod COX mRNAs encode functional cyclooxygenases that catalyze the transformation of arachidonic acid into prostaglandins. Using bioinformatic analysis we identified a COX-like gene from the human body louse Pediculus humanus corporis genome that encodes a protein with about 30% sequence identity with human COX-1 and COX-2. Although the COX gene is known to be absent from genomes of Drosophila sp., Aedes aegypti, Bombyx mori, and other insects, our studies establish the existence of the COX gene in certain lineages within the insect world. PMID:19854273

  18. Molecular cloning, expression and biochemical characterisation of a cold-adapted novel recombinant chitinase from Glaciozyma antarctica PI12

    Directory of Open Access Journals (Sweden)

    Ramli Aizi

    2011-11-01

    Full Text Available Abstract Background Cold-adapted enzymes are proteins produced by psychrophilic organisms that display a high catalytic efficiency at extremely low temperatures. Chitin consists of the insoluble homopolysaccharide β-(1, 4-linked N-acetylglucosamine, which is the second most abundant biopolymer found in nature. Chitinases (EC 3.2.1.14 play an important role in chitin recycling in nature. Biodegradation of chitin by the action of cold-adapted chitinases offers significant advantages in industrial applications such as the treatment of chitin-rich waste at low temperatures, the biocontrol of phytopathogens in cold environments and the biocontrol of microbial spoilage of refrigerated food. Results A gene encoding a cold-adapted chitinase (CHI II from Glaciozyma antarctica PI12 was isolated using Rapid Amplification of cDNA Ends (RACE and RT-PCR techniques. The isolated gene was successfully expressed in the Pichia pastoris expression system. Analysis of the nucleotide sequence revealed the presence of an open reading frame of 1,215 bp, which encodes a 404 amino acid protein. The recombinant chitinase was secreted into the medium when induced with 1% methanol in BMMY medium at 25°C. The purified recombinant chitinase exhibited two bands, corresponding to the non-glycosylated and glycosylated proteins, by SDS-PAGE with molecular masses of approximately 39 and 50 kDa, respectively. The enzyme displayed an acidic pH characteristic with an optimum pH at 4.0 and an optimum temperature at 15°C. The enzyme was stable between pH 3.0-4.5 and was able to retain its activity from 5 to 25°C. The presence of K+, Mn2+ and Co2+ ions increased the enzyme activity up to 20%. Analysis of the insoluble substrates showed that the purified recombinant chitinase had a strong affinity towards colloidal chitin and little effect on glycol chitosan. CHI II recombinant chitinase exhibited higher Vmax and Kcat values toward colloidal chitin than other substrates at low

  19. DMPD: Innate immunity minireview series: making biochemical sense of nucleic acidsensors that trigger antiviral innate immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17395579 Innate immunity minireview series: making biochemical sense of nucleic acidsensor...007 Mar 29. (.png) (.svg) (.html) (.csml) Show Innate immunity minireview series: making biochemical sense of nucleic acidsensor...itle Innate immunity minireview series: making biochemical sense of nucleic acidsensors that trigger antivir

  20. Adaptability of Indocalamus decorus to climate change based on physiological and biochemical responses to elevated carbon dioxide and ozone

    Directory of Open Access Journals (Sweden)

    Guo Z

    2016-04-01

    Full Text Available Carbon dioxide (CO2 and ozone (O3 are important greenhouse gases that contribute to global climate change. The effects of elevated CO2 and/or O3 on plants remain unclear. Plant responses to mixtures of the two gases at high concentrations are likely to be complex. Previous studies have shown that the ability to tolerate elevated levels of the two gases varies among plant species; physiological adaptability in the face of changing atmospheric composition also differs among taxa. However, the effects of mixtures of the two greenhouse gases on the growth and physiology of bamboo are largely unexplored, even though bamboos are important vegetation elements throughout tropical and subtropical regions of the planet. In this study, we used open-topped chambers (OTCs to double the concentrations of atmospheric CO2 and O3, and examined changes in membrane lipid peroxidation, photosynthetic physiology, and antioxidase activities in Indocalamus decorus leaves. After 103 days of treatment, elevated O3 depressed net photosynthetic rate (Pn without changing stomatal function, but caused no significant oxidative damage in the leaves. High levels of antioxidase activities were maintained in the leaves, indicating that this species had a strong tolerance to elevated O3. Decreases in reactive oxygen content and antioxidase activity in the leaves highlighted the significant positive effects of elevated CO2 on photosynthesis in I. decorus. When a mixture of both gases was supplied at high concentrations, we detected no oxidative damage, although photosynthetic capacity was reduced. Negative effects of O3 were very marked during the early part of the treatment period, but the effects of CO2 were positive. CO2 mitigated the oxidative damage caused by O3 and promoted the growth of I. decorus. Thus, I. decorus tolerated the two greenhouse gases, and was able to adapt to elevated CO2 and O3 levels. These findings contribute to the current knowledge base on the response

  1. Transcriptome analysis of Salicornia europaea under saline conditions revealed the adaptive primary metabolic pathways as early events to facilitate salt adaptation.

    Directory of Open Access Journals (Sweden)

    Pengxiang Fan

    Full Text Available BACKGROUND: Halophytes such as Salicornia europaea have evolved to exhibit unique mechanisms controlled by complex networks and regulated by numerous genes and interactions to adapt to habitats with high salinity. However, these mechanisms remain unknown. METHODS: To investigate the mechanism by which halophytes tolerate salt based on changes in the whole transcriptome, we performed transcriptome sequencing and functional annotation by database search. Using the unigene database, we conducted digital gene expression analysis of S. europaea at various time points after these materials were treated with NaCl. We also quantified ion uptakes. Gene functional enrichment analysis was performed to determine the important pathways involved in this process. RESULTS: A total of 57,151 unigenes with lengths of >300 bp were assembled, in which 57.5% of these unigenes were functionally annotated. Differentially expressed genes indicated that cell wall metabolism and lignin biosynthetic pathways were significantly enriched in S. europaea to promote the development of the xylem under saline conditions. This result is consistent with the increase in sodium uptake as ions pass through the xylem. Given that PSII efficiency remained unaltered, salt treatment activated the expression of electron transfer-related genes encoded by the chloroplast chromosome. Chlorophyll biosynthesis was also inhibited, indicating the energy-efficient state of the electron transfer system of S. europaea. CONCLUSIONS: The key function of adjusting important primary metabolic pathways in salt adaption was identified by analyzing the changes in the transcriptome of S. europaea. These pathways could involve unique salt tolerance mechanisms in halophytes. This study also provided information as the basis of future investigations on salt response genes in S. europaea. Ample gene resources were also provided to improve the genes responsible for the salt tolerance ability of crops.

  2. Gene network inference and biochemical assessment delineates GPCR pathways and CREB targets in small intestinal neuroendocrine neoplasia.

    Directory of Open Access Journals (Sweden)

    Ignat Drozdov

    effects are signaled through the cAMP/PKA/pCREB signaling pathway and that a SI NET cell line was most sensitive to a D(2 and 5-HT(2 receptor agonist BIM-53061.

  3. Influence of cortical descending pathways on neuronal adaptation in the auditory midbrain

    OpenAIRE

    Robinson, B. L.

    2014-01-01

    Adaptation of the spike rate of sensory neurones is associated with alteration in neuronal representation of a wide range of stimuli, including sound level, visual contrast, and whisker vibrissa motion. In the inferior colliculus (IC) of the auditory midbrain, adaptation may allow neurones to adjust their limited representational range to match the current range of sound levels in the environment. Two outstanding questions concern the rapidity of this adaptation in IC, and the mechanisms unde...

  4. Finding novel distinctions between the sAPPα-mediated anabolic biochemical pathways in Autism Spectrum Disorder and Fragile X Syndrome plasma and brain tissue

    Science.gov (United States)

    Ray, Balmiki; Sokol, Deborah K.; Maloney, Bryan; Lahiri, Debomoy K.

    2016-01-01

    Autism spectrum disorder (ASD) and Fragile X syndrome (FXS) are developmental disorders. No validated blood-based biomarkers exist for either, which impedes bench-to-bedside approaches. Amyloid-β (Aβ) precursor protein (APP) and metabolites are usually associated with Alzheimer’s disease (AD). APP cleavage by α-secretase produces potentially neurotrophic secreted APPα (sAPPα) and the P3 peptide fragment. β-site APP cleaving enzyme (BACE1) cleavage produces secreted APPβ (sAPPβ) and intact Aβ. Excess Aβ is potentially neurotoxic and can lead to atrophy of brain regions such as amygdala in AD. By contrast, amygdala is enlarged in ASD but not FXS. We previously reported elevated levels of sAPPα in ASD and FXS vs. controls. We now report elevated plasma Aβ and total APP levels in FXS compared to both ASD and typically developing controls, and elevated levels of sAPPα in ASD and FXS vs. controls. By contrast, plasma and brain sAPPβ and Aβ were lower in ASD vs. controls but elevated in FXS plasma vs. controls. We also detected age-dependent increase in an α-secretase in ASD brains. We report a novel mechanistic difference in APP pathways between ASD (processing) and FXS (expression) leading to distinct APP metabolite profiles in these two disorders. These novel, distinctive biochemical differences between ASD and FXS pave the way for blood-based biomarkers for ASD and FXS. PMID:27212113

  5. Representative Agricultural Pathways and Scenarios for Regional Integrated Assessment of Climate Change Impacts, Vulnerability, and Adaptation. 5; Chapter

    Science.gov (United States)

    Valdivia, Roberto O.; Antle, John M.; Rosenzweig, Cynthia; Ruane, Alexander C.; Vervoort, Joost; Ashfaq, Muhammad; Hathie, Ibrahima; Tui, Sabine Homann-Kee; Mulwa, Richard; Nhemachena, Charles; Ponnusamy, Paramasivam; Rasnayaka, Herath; Singh, Harbir

    2015-01-01

    The global change research community has recognized that new pathway and scenario concepts are needed to implement impact and vulnerability assessment where precise prediction is not possible, and also that these scenarios need to be logically consistent across local, regional, and global scales. For global climate models, representative concentration pathways (RCPs) have been developed that provide a range of time-series of atmospheric greenhouse-gas concentrations into the future. For impact and vulnerability assessment, new socio-economic pathway and scenario concepts have also been developed, with leadership from the Integrated Assessment Modeling Consortium (IAMC).This chapter presents concepts and methods for development of regional representative agricultural pathways (RAOs) and scenarios that can be used for agricultural model intercomparison, improvement, and impact assessment in a manner consistent with the new global pathways and scenarios. The development of agriculture-specific pathways and scenarios is motivated by the need for a protocol-based approach to climate impact, vulnerability, and adaptation assessment. Until now, the various global and regional models used for agricultural-impact assessment have been implemented with individualized scenarios using various data and model structures, often without transparent documentation, public availability, and consistency across disciplines. These practices have reduced the credibility of assessments, and also hampered the advancement of the science through model intercomparison, improvement, and synthesis of model results across studies. The recognition of the need for better coordination among the agricultural modeling community, including the development of standard reference scenarios with adequate agriculture-specific detail led to the creation of the Agricultural Model Intercomparison and Improvement Project (AgMIP) in 2010. The development of RAPs is one of the cross-cutting themes in AgMIP's work

  6. Signaling pathways for stress responses and adaptation in Aspergillus species: stress biology in the post-genomic era.

    Science.gov (United States)

    Hagiwara, Daisuke; Sakamoto, Kazutoshi; Abe, Keietsu; Gomi, Katsuya

    2016-09-01

    Aspergillus species are among the most important filamentous fungi in terms of industrial use and because of their pathogenic or toxin-producing features. The genomes of several Aspergillus species have become publicly available in this decade, and genomic analyses have contributed to an integrated understanding of fungal biology. Stress responses and adaptation mechanisms have been intensively investigated using the accessible genome infrastructure. Mitogen-activated protein kinase (MAPK) cascades have been highlighted as being fundamentally important in fungal adaptation to a wide range of stress conditions. Reverse genetics analyses have uncovered the roles of MAPK pathways in osmotic stress, cell wall stress, development, secondary metabolite production, and conidia stress resistance. This review summarizes the current knowledge on the stress biology of Aspergillus species, illuminating what we have learned from the genomic data in this "post-genomic era." PMID:27007956

  7. A decision analysis approach to climate adaptation: comparing multiple pathways for multi-decadal decision making

    Science.gov (United States)

    Lin, B. B.; Little, L.

    2013-12-01

    Policy planners around the world are required to consider the implications of adapting to climatic change across spatial contexts and decadal timeframes. However, local level information for planning is often poorly defined, even though climate adaptation decision-making is made at this scale. This is especially true when considering sea level rise and coastal impacts of climate change. We present a simple approach using sea level rise simulations paired with adaptation scenarios to assess a range of adaptation options available to local councils dealing with issues of beach recession under present and future sea level rise and storm surge. Erosion and beach recession pose a large socioeconomic risk to coastal communities because of the loss of key coastal infrastructure. We examine the well-known adaptation technique of beach nourishment and assess various timings and amounts of beach nourishment at decadal time spans in relation to beach recession impacts. The objective was to identify an adaptation strategy that would allow for a low frequency of management interventions, the maintenance of beach width, and the ability to minimize variation in beach width over the 2010 to 2100 simulation period. 1000 replications of each adaptation option were produced against the 90 year simulation in order to model the ability each adaptation option to achieve the three key objectives. Three sets of adaptation scenarios were identified. Within each scenario, a number of adaptation options were tested. The three scenarios were: 1) Fixed periodic beach replenishment of specific amounts at 20 and 50 year intervals, 2) Beach replenishment to the initial beach width based on trigger levels of recession (5m, 10m, 20m), and 3) Fixed period beach replenishment of a variable amount at decadal intervals (every 10, 20, 30, 40, 50 years). For each adaptation option, we show the effectiveness of each beach replenishment scenario to maintain beach width and consider the implications of more

  8. DMPD: ITAM-based signaling beyond the adaptive immune response. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available AM-based signaling beyond the adaptive immune response. PubmedID 16332394 Title ITAM-based signaling beyond...16332394 ITAM-based signaling beyond the adaptive immune response. Fodor S, Jakus Z..., Mocsai A. Immunol Lett. 2006 Apr 15;104(1-2):29-37. Epub 2005 Nov 28. (.png) (.svg) (.html) (.csml) Show IT...e (.html) CSML File (.csml) Open .csml file with CIOPlayer Open .csml file with CIOPlayer - ※CIO Playerのご利用上の注意 Open .csml file with CIO Open .csml file with CIO - ※CIOのご利用上の注意 ...

  9. Unveiling the Metabolic Pathways Associated with the Adaptive Reduction of Cell Size During Vibrio harveyi Persistence in Seawater Microcosms.

    Science.gov (United States)

    Kaberdin, Vladimir R; Montánchez, Itxaso; Parada, Claudia; Orruño, Maite; Arana, Inés; Barcina, Isabel

    2015-10-01

    Owing to their ubiquitous presence and ability to act as primary or opportunistic pathogens, Vibrio species greatly contribute to the diversity and evolution of marine ecosystems. This study was aimed at unveiling the cellular strategies enabling the marine gammaproteobacterium Vibrio harveyi to adapt and persist in natural aquatic systems. We found that, although V. harveyi incubation in seawater microcosm at 20 °C for 2 weeks did not change cell viability and culturability, it led to a progressive reduction in the average cell size. Microarray analysis revealed that this morphological change was accompanied by a profound decrease in gene expression affecting the central carbon metabolism, major biosynthetic pathways, and energy production. In contrast, V. harveyi elevated expression of genes closely linked to the composition and function of cell envelope. In addition to triggering lipid degradation via the β-oxidation pathway and apparently promoting the use of endogenous fatty acids as a major energy and carbon source, V. harveyi upregulated genes involved in ancillary mechanisms important for sustaining iron homeostasis, cell resistance to the toxic effect of reactive oxygen species, and recycling of amino acids. The above adaptation mechanisms and morphological changes appear to represent the major hallmarks of the initial V. harveyi response to starvation. PMID:25903990

  10. Pathways to the Future: Community Dialogues on Adaptive Environmental Management Through Scenario Projection in Google Maps

    NARCIS (Netherlands)

    Vervoort, J.M.; Kok, K.; Lammeren, van R.J.A.; Janssen, R.; Veldkamp, A.

    2009-01-01

    This paper presents research on the potential of interactive media for regional community dialogues on future uncertainties and complexities in coupled human and natural systems. More adaptive perspectives on natural resources management are needed to respond to rapid environmental and social change

  11. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway.

    Science.gov (United States)

    Sebastián, David; Sorianello, Eleonora; Segalés, Jessica; Irazoki, Andrea; Ruiz-Bonilla, Vanessa; Sala, David; Planet, Evarist; Berenguer-Llergo, Antoni; Muñoz, Juan Pablo; Sánchez-Feutrie, Manuela; Plana, Natàlia; Hernández-Álvarez, María Isabel; Serrano, Antonio L; Palacín, Manuel; Zorzano, Antonio

    2016-08-01

    Mitochondrial dysfunction and accumulation of damaged mitochondria are considered major contributors to aging. However, the molecular mechanisms responsible for these mitochondrial alterations remain unknown. Here, we demonstrate that mitofusin 2 (Mfn2) plays a key role in the control of muscle mitochondrial damage. We show that aging is characterized by a progressive reduction in Mfn2 in mouse skeletal muscle and that skeletal muscle Mfn2 ablation in mice generates a gene signature linked to aging. Furthermore, analysis of muscle Mfn2-deficient mice revealed that aging-induced Mfn2 decrease underlies the age-related alterations in metabolic homeostasis and sarcopenia. Mfn2 deficiency reduced autophagy and impaired mitochondrial quality, which contributed to an exacerbated age-related mitochondrial dysfunction. Interestingly, aging-induced Mfn2 deficiency triggers a ROS-dependent adaptive signaling pathway through induction of HIF1α transcription factor and BNIP3. This pathway compensates for the loss of mitochondrial autophagy and minimizes mitochondrial damage. Our findings reveal that Mfn2 repression in muscle during aging is a determinant for the inhibition of mitophagy and accumulation of damaged mitochondria and triggers the induction of a mitochondrial quality control pathway. PMID:27334614

  12. Adapt

    Science.gov (United States)

    Bargatze, L. F.

    2015-12-01

    Active Data Archive Product Tracking (ADAPT) is a collection of software routines that permits one to generate XML metadata files to describe and register data products in support of the NASA Heliophysics Virtual Observatory VxO effort. ADAPT is also a philosophy. The ADAPT concept is to use any and all available metadata associated with scientific data to produce XML metadata descriptions in a consistent, uniform, and organized fashion to provide blanket access to the full complement of data stored on a targeted data server. In this poster, we present an application of ADAPT to describe all of the data products that are stored by using the Common Data File (CDF) format served out by the CDAWEB and SPDF data servers hosted at the NASA Goddard Space Flight Center. These data servers are the primary repositories for NASA Heliophysics data. For this purpose, the ADAPT routines have been used to generate data resource descriptions by using an XML schema named Space Physics Archive, Search, and Extract (SPASE). SPASE is the designated standard for documenting Heliophysics data products, as adopted by the Heliophysics Data and Model Consortium. The set of SPASE XML resource descriptions produced by ADAPT includes high-level descriptions of numerical data products, display data products, or catalogs and also includes low-level "Granule" descriptions. A SPASE Granule is effectively a universal access metadata resource; a Granule associates an individual data file (e.g. a CDF file) with a "parent" high-level data resource description, assigns a resource identifier to the file, and lists the corresponding assess URL(s). The CDAWEB and SPDF file systems were queried to provide the input required by the ADAPT software to create an initial set of SPASE metadata resource descriptions. Then, the CDAWEB and SPDF data repositories were queried subsequently on a nightly basis and the CDF file lists were checked for any changes such as the occurrence of new, modified, or deleted

  13. Pathways to the Future: Community Dialogues on Adaptive Environmental Management Through Scenario Projection in Google Maps

    OpenAIRE

    Vervoort, J.M.; Kok, K; Lammeren, van, A.A.M.; Janssen, R.; Veldkamp, A.

    2009-01-01

    This paper presents research on the potential of interactive media for regional community dialogues on future uncertainties and complexities in coupled human and natural systems. More adaptive perspectives on natural resources management are needed to respond to rapid environmental and social change. Scenarios are a useful tool for participatory explorations of future issues that are high on uncertainties and complexities. We explore how scenarios can bank on the communicatory effectiveness o...

  14. Drought Adaptation in the Ningxia Hui Autonomous Region, China: Actions, Planning, Pathways and Barriers

    OpenAIRE

    Jianping Yang; Chunping Tan; Shijin Wang; Shengxia Wang; Yuan Yang; Hongju Chen

    2015-01-01

    The Ningxia Hui Autonomous Region (NX region) of Northwestern China is threatened by increased meteorological drought induced by climate change (CC) and constraints on water supply from the Yellow River. Thus, the NX region is representative of attempts to adapt to CC and variability in China’s arid regions. Field visits, a questionnaire and in situ inspections were conducted in 2012–2014 to understand people’s perception and awareness of drought and its impact, particularly with respect to a...

  15. Genome sequencing of chimpanzee malaria parasites reveals possible pathways of adaptation to human hosts

    KAUST Repository

    Otto, Thomas D.

    2014-09-09

    Plasmodium falciparum causes most human malaria deaths, having prehistorically evolved from parasites of African Great Apes. Here we explore the genomic basis of P. falciparum adaptation to human hosts by fully sequencing the genome of the closely related chimpanzee parasite species P. reichenowi, and obtaining partial sequence data from a more distantly related chimpanzee parasite (P. gaboni). The close relationship between P. reichenowi and P. falciparum is emphasized by almost complete conservation of genomic synteny, but against this strikingly conserved background we observe major differences at loci involved in erythrocyte invasion. The organization of most virulence-associated multigene families, including the hypervariable var genes, is broadly conserved, but P. falciparum has a smaller subset of rif and stevor genes whose products are expressed on the infected erythrocyte surface. Genome-wide analysis identifies other loci under recent positive selection, but a limited number of changes at the host–parasite interface may have mediated host switching.

  16. Multiplexing oscillatory biochemical signals.

    Science.gov (United States)

    de Ronde, Wiet; ten Wolde, Pieter Rein

    2014-04-01

    In recent years it has been increasingly recognized that biochemical signals are not necessarily constant in time and that the temporal dynamics of a signal can be the information carrier. Moreover, it is now well established that the protein signaling network of living cells has a bow-tie structure and that components are often shared between different signaling pathways. Here we show by mathematical modeling that living cells can multiplex a constant and an oscillatory signal: they can transmit these two signals simultaneously through a common signaling pathway, and yet respond to them specifically and reliably. We find that information transmission is reduced not only by noise arising from the intrinsic stochasticity of biochemical reactions, but also by crosstalk between the different channels. Yet, under biologically relevant conditions more than 2 bits of information can be transmitted per channel, even when the two signals are transmitted simultaneously. These observations suggest that oscillatory signals are ideal for multiplexing signals. PMID:24685537

  17. Loss of Niemann-Pick C1 or C2 protein results in similar biochemical changes suggesting that these proteins function in a common lysosomal pathway.

    Directory of Open Access Journals (Sweden)

    Sayali S Dixit

    Full Text Available Niemann-Pick Type C (NPC disease is a lysosomal storage disorder characterized by accumulation of unesterified cholesterol and other lipids in the endolysosomal system. NPC disease results from a defect in either of two distinct cholesterol-binding proteins: a transmembrane protein, NPC1, and a small soluble protein, NPC2. NPC1 and NPC2 are thought to function closely in the export of lysosomal cholesterol with both proteins binding cholesterol in vitro but they may have unrelated lysosomal roles. To investigate this possibility, we compared biochemical consequences of the loss of either protein. Analyses of lysosome-enriched subcellular fractions from brain and liver revealed similar decreases in buoyant densities of lysosomes from NPC1 or NPC2 deficient mice compared to controls. The subcellular distribution of both proteins was similar and paralleled a lysosomal marker. In liver, absence of either NPC1 or NPC2 resulted in similar alterations in the carbohydrate processing of the lysosomal protease, tripeptidyl peptidase I. These results highlight biochemical alterations in the lysosomal system of the NPC-mutant mice that appear secondary to lipid storage. In addition, the similarity in biochemical phenotypes resulting from either NPC1 or NPC2 deficiency supports models in which the function of these two proteins within lysosomes are linked closely.

  18. Genetic and Biochemical Characterization of 4-Carboxy-2-Hydroxymuconate-6-Semialdehyde Dehydrogenase and Its Role in the Protocatechuate 4,5-Cleavage Pathway in Sphingomonas paucimobilis SYK-6

    OpenAIRE

    Masai, Eiji; Momose, Kiyotaka; Hara, Hirofumi; Nishikawa, Seiji; Katayama, Yoshihiro; Fukuda, Masao

    2000-01-01

    Protocatechuate (PCA) is the key intermediate metabolite in the lignin degradation pathway of Sphingomonas paucimobilis SYK-6 and is metabolized to pyruvate and oxaloacetate via the PCA 4,5-cleavage pathway. We characterized the 4-carboxy-2-hydroxymuconate-6-semialdehyde (CHMS) dehydrogenase gene (ligC). CHMS is the 4,5-cleavage product of PCA and is converted into 2-pyrone-4,6-dicarboxylate (PDC) by LigC. We found that ligC was located 295 bp downstream of ligB, which encodes the large subun...

  19. Adaptive immunity alters distinct host feeding pathways during nematode induced inflammation, a novel mechanism in parasite expulsion.

    Directory of Open Access Journals (Sweden)

    John J Worthington

    2013-01-01

    Full Text Available Gastrointestinal infection is often associated with hypophagia and weight loss; however, the precise mechanisms governing these responses remain poorly defined. Furthermore, the possibility that alterations in feeding during infection may be beneficial to the host requires further study. We used the nematode Trichinella spiralis, which transiently inhabits the small intestine before migrating to skeletal muscle, as a biphasic model of infection to determine the cellular and molecular pathways controlling feeding during enteric and peripheral inflammation. Through the infection of genetically modified mice lacking cholecystokinin, Tumor necrosis factor α receptors and T and B-cells, we observed a biphasic hypophagic response to infection resulting from two separate immune-driven mechanisms. The enteroendocrine I-cell derived hormone cholecystokinin is an essential mediator of initial hypophagia and is induced by CD4+ T-cells during enteritis. In contrast, the second hypophagic response is extra-intestinal and due to the anorectic effects of TNFα during peripheral infection of the muscle. Moreover, via maintaining naive levels of the adipose secreted hormone leptin throughout infection we demonstrate a novel feedback loop in the immunoendocrine axis. Immune driven I-cell hyperplasia and resultant weight loss leads to a reduction in the inflammatory adipokine leptin, which in turn heightens protective immunity during infection. These results characterize specific immune mediated mechanisms which reduce feeding during intestinal or peripheral inflammation. Importantly, the molecular mediators of each phase are entirely separate. The data also introduce the first evidence that I-cell hyperplasia is an adaptively driven immune response that directly impinges on the outcome to infection.

  20. Sex Differences in Autism Spectrum Disorders: Does Sex Moderate the Pathway from Clinical Symptoms to Adaptive Behavior?

    OpenAIRE

    Mandic-Maravic, Vanja; Pejovic-Milovancevic, Milica; Mitkovic-Voncina, Marija; Kostic, Milutin; Aleksic-Hil, Olivera; Radosavljev-Kircanski, Jelena; Mincic, Teodora; Lecic-Tosevski, Dusica

    2015-01-01

    We explored sex differences in diagnostic categories, clinical symptoms and adaptive behavior of persons with autism spectrum disorders, as well as sex-specific correlations of clinical and adaptive caracteristics. The study involved 108 patients (83 males, 6.73 ± 4.33 years old) diagnosed with autism spectrum disorders (ASD). Assessment included ADI-R and Vineland Adaptive Behavior Scale II. Males were more often diagnosed with typical autism. There were no sex differences in the autistic sy...

  1. Genetic and Biochemical Characterization of a 2-Pyrone-4,6-Dicarboxylic Acid Hydrolase Involved in the Protocatechuate 4,5-Cleavage Pathway of Sphingomonas paucimobilis SYK-6

    OpenAIRE

    Masai, Eiji; Shinohara, Shouji; Hara, Hirofumi; Nishikawa, Seiji; Katayama, Yoshihiro; Fukuda, Masao

    1999-01-01

    Sphingomonas paucimobilis SYK-6 is able to grow on a wide variety of dimeric lignin compounds with guaiacyl moieties, which are converted into protocatechuate by the actions of lignin degradation enzymes in this strain. Protocatechuate is a key metabolite in the SYK-6 degradation of lignin compounds with guaiacyl moieties, and it is thought that it degrades to pyruvate and oxaloacetate via the protocatechuate 4,5-cleavage pathway. In a 10.5-kb EcoRI fragment carrying the protocatechuate 4,5-d...

  2. Metabolic Engineering of Light and Dark Biochemical Pathways in Wild-Type and Mutant Strains of Synechocystis PCC 6803 for Maximal, 24-Hour Production of Hydrogen Gas

    Energy Technology Data Exchange (ETDEWEB)

    Ely, Roger L.; Chaplen, Frank W.R.

    2014-03-11

    This project used the cyanobacterial species Synechocystis PCC 6803 to pursue two lines of inquiry, with each line addressing one of the two main factors affecting hydrogen (H2) production in Synechocystis PCC 6803: NADPH availability and O2 sensitivity. H2 production in Synechocystis PCC 6803 requires a very high NADPH:NADP+ ratio, that is, the NADP pool must be highly reduced, which can be problematic because several metabolic pathways potentially can act to raise or lower NADPH levels. Also, though the [NiFe]-hydrogenase in PCC 6803 is constitutively expressed, it is reversibly inactivated at very low O2 concentrations. Largely because of this O2 sensitivity and the requirement for high NADPH levels, a major portion of overall H2 production occurs under anoxic conditions in the dark, supported by breakdown of glycogen or other organic substrates accumulated during photosynthesis. Also, other factors, such as N or S limitation, pH changes, presence of other substances, or deletion of particular respiratory components, can affect light or dark H2 production. Therefore, in the first line of inquiry, under a number of culture conditions with wild type (WT) Synechocystis PCC 6803 cells and a mutant with impaired type I NADPH-dehydrogenase (NDH-1) function, we used H2 production profiling and metabolic flux analysis, with and without specific inhibitors, to examine systematically the pathways involved in light and dark H2 production. Results from this work provided rational bases for metabolic engineering to maximize photobiological H2 production on a 24-hour basis. In the second line of inquiry, we used site-directed mutagenesis to create mutants with hydrogenase enzymes exhibiting greater O2 tolerance. The research addressed the following four tasks: 1. Evaluate the effects of various culture conditions (N, S, or P limitation; light/dark; pH; exogenous organic carbon) on H2 production profiles of WT cells and an NDH-1 mutant; 2. Conduct metabolic flux analyses for

  3. HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin–proteasome pathway (Biochemical and Biophysical Research Communications, v. 444 issue 3)

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaozhen [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Institute of Systems Biology, Peking University, Beijing 100191 (China); Lu, Guang; Li, Li; Yi, Juan; Yan, Kaowen; Wang, Yaqing; Zhu, Baili; Kuang, Jingyu; Lin, Ming; Zhang, Sha [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Shao, Genze, E-mail: gzshao@bjmu.edu.cn [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Institute of Systems Biology, Peking University, Beijing 100191 (China)

    2014-02-14

    Highlights: • The 2000–2634 aa region of HUWE1 mediates the interaction with BRCA1 degron. • HUWE1 promotes the degradation of BRCA1 through the ubiquitin–proteasome pathway. • HUWE1 expression is inversely correlated with BRCA1 in breast cancer cells. • RNAi inhibition of HUWE1 confers increased resistance of MCF-10F cells to IR and MMC. - Abstract: The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn–proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin–proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis.

  4. HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin–proteasome pathway (Biochemical and Biophysical Research Communications, v. 444, isse 4)

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaozhen [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Institute of Systems Biology, Peking University, Beijing 100191 (China); Lu, Guang; Li, Li; Yi, Juan; Yan, Kaowen; Wang, Yaqing; Zhu, Baili; Kuang, Jingyu; Lin, Ming; Zhang, Sha [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Shao, Genze, E-mail: gzshao@bjmu.edu.cn [Department of Cell Biology, Peking University Health Science Center, Beijing 100191 (China); Institute of Systems Biology, Peking University, Beijing 100191 (China)

    2014-02-21

    Highlights: • The 2000–2634aa region of HUWE1 mediates the interaction with BRCA1 degron. • HUWE1 promotes the degradation of BRCA1 through the ubiquitin–proteasome pathway. • HUWE1 expression is inversely correlated with BRCA1 in breast cancer cells. • RNAi inhibition of HUWE1 confers increased resistance of MCF-10F cells to IR and MMC. - Abstract: The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn–proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1 binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin–proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis.

  5. HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin–proteasome pathway (Biochemical and Biophysical Research Communications, v. 444, isse 4)

    International Nuclear Information System (INIS)

    Highlights: • The 2000–2634aa region of HUWE1 mediates the interaction with BRCA1 degron. • HUWE1 promotes the degradation of BRCA1 through the ubiquitin–proteasome pathway. • HUWE1 expression is inversely correlated with BRCA1 in breast cancer cells. • RNAi inhibition of HUWE1 confers increased resistance of MCF-10F cells to IR and MMC. - Abstract: The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn–proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1 binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin–proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis

  6. HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin–proteasome pathway (Biochemical and Biophysical Research Communications, v. 444 issue 3)

    International Nuclear Information System (INIS)

    Highlights: • The 2000–2634 aa region of HUWE1 mediates the interaction with BRCA1 degron. • HUWE1 promotes the degradation of BRCA1 through the ubiquitin–proteasome pathway. • HUWE1 expression is inversely correlated with BRCA1 in breast cancer cells. • RNAi inhibition of HUWE1 confers increased resistance of MCF-10F cells to IR and MMC. - Abstract: The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn–proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin–proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis

  7. Adaptive capability as indicated by endocrine and biochemical responses of Malpura ewes subjected to combined stresses (thermal and nutritional) in a semi-arid tropical environment

    Science.gov (United States)

    Sejian, Veerasamy; Maurya, Vijai P.; Naqvi, Sayeed M. K.

    2010-11-01

    A study was conducted to assess the effect of combined stresses (thermal and nutritional) on endocrine and biochemical responses in Malpura ewes. Twenty eight adult Malpura ewes (average body weight 33.56 kg) were used in the present study. The ewes were divided into four groups viz., GI ( n = 7; control), GII ( n = 7; thermal stress), GIII ( n = 7; nutritional stress) and GIV ( n = 7; combined stress). The animals were stall fed with a diet consisting of 60% roughage and 40% concentrate. GI and GII ewes were provided with ad libitum feeding while GIII and GIV ewes were provided with restricted feed (30% intake of GI ewes) to induce nutritional stress. GII and GIV ewes were kept in climatic chamber at 40°C and 55% RH for 6 h a day between 1000 hours and 1600 hours to induce thermal stress. The study was conducted for a period of two estrus cycles. The parameters studied were Hb, PCV, glucose, total protein, total cholesterol, ACP, ALP, cortisol, T4, T3, and insulin. Combined stress significantly ( P sheep.

  8. Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

    Directory of Open Access Journals (Sweden)

    Sorribas Albert

    2009-11-01

    Full Text Available Abstract Background Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements. Results We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA representation. The optimization task is posed as a nonconvex nonlinear programming (NLP problem that is solved by an outer-approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in Saccharomyces cerevisiae. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast Saccharomyces cerevisiae to heat shock Conclusion Our results

  9. Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen Talaromyces marneffei

    Science.gov (United States)

    Cao, Cunwei; Andrianopoulos, Alex

    2016-01-01

    ABSTRACT For successful infection to occur, a pathogen must be able to evade or tolerate the host’s defense systems. This requires the pathogen to first recognize the host environment and then signal this response to elicit a complex adaptive program in order to activate its own defense strategies. In both prokaryotes and eukaryotes, two-component signaling systems are utilized to sense and respond to changes in the external environment. The hybrid histidine kinases (HHKs) at the start of the two-component signaling pathway have been well characterized in human pathogens. However, how these HHKs regulate processes downstream currently remains unclear. This study describes the role of a response regulator downstream of these HHKs, sskA, in Talaromyces marneffei, a dimorphic human pathogen. sskA is required for asexual reproduction, hyphal morphogenesis, cell wall integrity, osmotic adaptation, and the morphogenesis of yeast cells both in vitro at 37°C and during macrophage infection, but not during dimorphic switching. Comparison of the ΔsskA mutant with a strain in which the mitogen-activated protein kinase (MAPK) of the high-osmolarity glycerol pathway (SakA) has been deleted suggests that SskA acts upstream of this pathway in T. marneffei to regulate these morphogenetic processes. This was confirmed by assessing the amount of phosphorylated SakA in the ΔsskA mutant, antifungal resistance due to a lack of SakA activation, and the ability of a constitutively active sakA allele (sakAF316L) to suppress the ΔsskA mutant phenotypes. We conclude that SskA regulates morphogenesis and osmotic stress adaptation in T. marneffei via phosphorylation of the SakA MAPK of the high-osmolarity glycerol pathway. IMPORTANCE This is the first study in a dimorphic fungal pathogen to investigate the role of a response regulator downstream of two-component signaling systems and its connection to the high-osmolarity glycerol pathway. This study will inspire further research into

  10. Systemic Transcriptional Alterations of Innate and Adaptive Immune Signaling Pathways in Atherosclerosis, Ischemia Stroke, and Myocardial Infarction

    OpenAIRE

    Barr, Taura L.; VanGilder, Reynal L.; Seiberg, Ryan; Petrone, Ashely; Chantler, Paul D.; Huang, Chiang-Ching

    2015-01-01

    Background Transcriptional profiles are available for a variety of cardiovascular-related diseases. The goal of this study was to compare blood transcriptional profiles of the Toll-like receptor (TLR), T-cell receptor (TCR), and B-cell receptor (BCR) signaling pathways in asymptomatic atherosclerosis, acute ischemic stroke, and myocardial infarction patients to identify common mechanisms of immune regulation and their association with epigenetic regulation. Methods and results Peripheral bloo...

  11. New Biochemical Pathway May Control Erection

    OpenAIRE

    Mills, Thomas M.

    2001-01-01

    Thirty million men in the U.S. suffer from erectile dysfunction (ED) defined by their inability to achieve or maintain a penile erection sufficient for intercourse. An unestimated number of women also suffer from sexual dysfunction resulting from many of the same causes that lead to ED in men. There are a variety of treatments available for ED including intracavernosal injection, transurethral therapy, surgery, vacuum therapy, and oral medication. Unfortunately, not all patients benefit from ...

  12. Model-Based Design of Biochemical Microreactors.

    Science.gov (United States)

    Elbinger, Tobias; Gahn, Markus; Neuss-Radu, Maria; Hante, Falk M; Voll, Lars M; Leugering, Günter; Knabner, Peter

    2016-01-01

    Mathematical modeling of biochemical pathways is an important resource in Synthetic Biology, as the predictive power of simulating synthetic pathways represents an important step in the design of synthetic metabolons. In this paper, we are concerned with the mathematical modeling, simulation, and optimization of metabolic processes in biochemical microreactors able to carry out enzymatic reactions and to exchange metabolites with their surrounding medium. The results of the reported modeling approach are incorporated in the design of the first microreactor prototypes that are under construction. These microreactors consist of compartments separated by membranes carrying specific transporters for the input of substrates and export of products. Inside the compartments of the reactor multienzyme complexes assembled on nano-beads by peptide adapters are used to carry out metabolic reactions. The spatially resolved mathematical model describing the ongoing processes consists of a system of diffusion equations together with boundary and initial conditions. The boundary conditions model the exchange of metabolites with the neighboring compartments and the reactions at the surface of the nano-beads carrying the multienzyme complexes. Efficient and accurate approaches for numerical simulation of the mathematical model and for optimal design of the microreactor are developed. As a proof-of-concept scenario, a synthetic pathway for the conversion of sucrose to glucose-6-phosphate (G6P) was chosen. In this context, the mathematical model is employed to compute the spatio-temporal distributions of the metabolite concentrations, as well as application relevant quantities like the outflow rate of G6P. These computations are performed for different scenarios, where the number of beads as well as their loading capacity are varied. The computed metabolite distributions show spatial patterns, which differ for different experimental arrangements. Furthermore, the total output of G6P

  13. Complementary processing of haptic information by slowly and rapidly adapting neurons in the trigeminothalamic pathway. Electrophysiology, mathematical modeling and simulations of vibrissae-related neurons.

    Directory of Open Access Journals (Sweden)

    Abel Sanchez-Jimenez

    2013-06-01

    Full Text Available Tonic (slowly adapting and phasic (rapidly adapting primary afferents convey complementary aspects of haptic information to the central nervous system: object location and texture the former, shape the latter. Tonic and phasic neural responses are also recorded in all relay stations of the somatosensory pathway, yet it is unknown their role in both, information processing and information transmission to the cortex: we don’t know if tonic and phasic neurons process complementary aspects of haptic information and/or if these two types constitute two separate channels that convey complementary aspects of tactile information to the cortex. Here we propose to elucidate these two questions in the fast trigeminal pathway of the rat (PrV-VPM: principal trigeminal nucleus-ventroposteromedial thalamic nucleus. We analyze early and global behavior, latencies and stability of the responses of individual cells in PrV and medial lemniscus under 1-40 Hz stimulation of the whiskers in control and decorticated animals and we use stochastic spiking models and extensive simulations. Our results strongly suggest that in the first relay station of the somatosensory system (PrV: 1 tonic and phasic neurons process complementary aspects of whisker-related tactile information 2 tonic and phasic responses are not originated from two different types of neurons 3 the two responses are generated by the differential action of the somatosensory cortex on a unique type of PrV cell 4 tonic and phasic neurons do not belong to two different channels for the transmission of tactile information to the thalamus 5 trigeminothalamic transmission is exclusively performed by tonically firing neurons and 6 all aspects of haptic information are coded into low-pass, band-pass and high-pass filtering profiles of tonically firing neurons. Our results are important for both, basic research on neural circuits and information processing, and development of sensory neuroprostheses.

  14. Rhizobium leguminosarum bv. viciae 3841 Adapts to 2,4-Dichlorophenoxyacetic Acid with "Auxin-Like" Morphological Changes, Cell Envelope Remodeling and Upregulation of Central Metabolic Pathways.

    Directory of Open Access Journals (Sweden)

    Supriya V Bhat

    Full Text Available There is a growing need to characterize the effects of environmental stressors at the molecular level on model organisms with the ever increasing number and variety of anthropogenic chemical pollutants. The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D, as one of the most widely applied pesticides in the world, is one such example. This herbicide is known to have non-targeted undesirable effects on humans, animals and soil microbes, but specific molecular targets at sublethal levels are unknown. In this study, we have used Rhizobium leguminosarum bv. viciae 3841 (Rlv as a nitrogen fixing, beneficial model soil organism to characterize the effects of 2,4-D. Using metabolomics and advanced microscopy we determined specific target pathways in the Rlv metabolic network and consequent changes to its phenotype, surface ultrastructure, and physical properties during sublethal 2,4-D exposure. Auxin and 2,4-D, its structural analogue, showed common morphological changes in vitro which were similar to bacteroids isolated from plant nodules, implying that these changes are related to bacteroid differentiation required for nitrogen fixation. Rlv showed remarkable adaptation capabilities in response to the herbicide, with changes to integral pathways of cellular metabolism and the potential to assimilate 2,4-D with consequent changes to its physical and structural properties. This study identifies biomarkers of 2,4-D in Rlv and offers valuable insights into the mode-of-action of 2,4-D in soil bacteria.

  15. Chemotactic response and adaptation dynamics in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Diana Clausznitzer

    2010-05-01

    Full Text Available Adaptation of the chemotaxis sensory pathway of the bacterium Escherichia coli is integral for detecting chemicals over a wide range of background concentrations, ultimately allowing cells to swim towards sources of attractant and away from repellents. Its biochemical mechanism based on methylation and demethylation of chemoreceptors has long been known. Despite the importance of adaptation for cell memory and behavior, the dynamics of adaptation are difficult to reconcile with current models of precise adaptation. Here, we follow time courses of signaling in response to concentration step changes of attractant using in vivo fluorescence resonance energy transfer measurements. Specifically, we use a condensed representation of adaptation time courses for efficient evaluation of different adaptation models. To quantitatively explain the data, we finally develop a dynamic model for signaling and adaptation based on the attractant flow in the experiment, signaling by cooperative receptor complexes, and multiple layers of feedback regulation for adaptation. We experimentally confirm the predicted effects of changing the enzyme-expression level and bypassing the negative feedback for demethylation. Our data analysis suggests significant imprecision in adaptation for large additions. Furthermore, our model predicts highly regulated, ultrafast adaptation in response to removal of attractant, which may be useful for fast reorientation of the cell and noise reduction in adaptation.

  16. S-system-based analysis of the robust properties common to many biochemical network models.

    Science.gov (United States)

    Matsuoka, Yu; Jahan, Nusrat; Kurata, Hiroyuki

    2016-05-01

    Robustness is a key feature to characterize the adaptation of organisms to changes in their internal and external environments. A broad range of kinetic or dynamic models of biochemical systems have been developed. Robustness analyses are attractive for exploring some common properties of many biochemical models. To reveal such features, we transform different types of mathematical equations into a standard or intelligible formula and use the multiple parameter sensitivity (MPS) to identify some factors critically responsible for the total robustness to many perturbations. The MPS would be determined by the top quarter of the highly sensitive parameters rather than the single parameter with the maximum sensitivity. The MPS did not show any correlation to the network size. The MPS is closely related to the standard deviation of the sensitivity profile. A decrease in the standard deviation enhanced the total robustness, which shows the hallmark of distributed robustness that many factors (pathways) involve the total robustness. PMID:26861555

  17. The Pal pathway required for ambient pH adaptation regulates growth, conidiation, and osmotolerance of Beauveria bassiana in a pH-dependent manner.

    Science.gov (United States)

    Zhu, Jing; Ying, Sheng-Hua; Feng, Ming-Guang

    2016-05-01

    The Pal/Rim pathway essential for fungal adaptation to ambient pH has been unexplored in Beauveria bassiana, a classic fungal entomopathogen. Here, we show the characterized Pal pathway comprising transcription factor PacC and upstream six Pal partners (PalA/B/C/F/H/I) in B. bassiana. Their coding genes were all transcribed most abundantly in standard wild-type culture under the alkaline condition of pH 9. Deletion of pacC or each pal gene resulted in a significant delay of culture acidification in a minimal broth (initial pH = 7.3). This delay concurred with altered accumulation levels of intra/extracellular organic acids and drastically depressed expression of some enzyme genes required for the syntheses of oxalic and lactic acids. Our deletion mutants except ΔpalI showed growth defects and maximal sensitivity to NaCl, KCl, LiCl, or sorbitol at pH 9, an alkaline condition leading to fragmented vacuoles in their hyphal cells exposed to osmotic stress. In these mutants, conidiation was significantly facilitated at pH 3 more than at pH 7 but suppressed slightly at pH 9. Mild virulence defects also occurred in the absence of pacC or any pal gene. These changes were restored by targeted gene complementation. Taken together, PacC and Pal partners regulate the growth, conidiation, and osmotolerance of B. bassiana in a pH-dependent manner, highlighting their vitality for the fungal pH response. PMID:26754817

  18. Reconfigurable neuromorphic computation in biochemical systems.

    Science.gov (United States)

    Chiang, Hui-Ju Katherine; Jiang, Jie-Hong R; Fages, Francois

    2015-08-01

    Implementing application-specific computation and control tasks within a biochemical system has been an important pursuit in synthetic biology. Most synthetic designs to date have focused on realizing systems of fixed functions using specifically engineered components, thus lacking flexibility to adapt to uncertain and dynamically-changing environments. To remedy this limitation, an analog and modularized approach to realize reconfigurable neuromorphic computation with biochemical reactions is presented. We propose a biochemical neural network consisting of neuronal modules and interconnects that are both reconfigurable through external or internal control over the concentrations of certain molecular species. Case studies on classification and machine learning applications using the DNA strain displacement technology demonstrate the effectiveness of our design in both reconfiguration and autonomous adaptation. PMID:26736417

  19. Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria.

    Science.gov (United States)

    Han, Derick; Dara, Lily; Win, Sanda; Than, Tin Aung; Yuan, Liyun; Abbasi, Sadeea Q; Liu, Zhang-Xu; Kaplowitz, Neil

    2013-04-01

    Drugs that cause liver injury often 'stress' mitochondria and activate signal transduction pathways important in determining cell survival or death. In most cases, hepatocytes adapt to the drug-induced stress by activating adaptive signaling pathways, such as mitochondrial adaptive responses and nuclear factor erythroid 2-related factor 2 (Nrf-2), a transcription factor that upregulates antioxidant defenses. Owing to adaptation, drugs alone rarely cause liver injury, with acetaminophen (APAP) being the notable exception. Drug-induced liver injury (DILI) usually involves other extrinsic factors, such as the adaptive immune system, that cause 'stressed' hepatocytes to become injured, leading to idiosyncratic DILI, the rare and unpredictable adverse drug reaction in the liver. Hepatocyte injury, due to drug and extrinsic insult, causes a second wave of signaling changes associated with adaptation, cell death, and repair. If the stress and injury reach a critical threshold, then death signaling pathways such as c-Jun N-terminal kinase (JNK) become dominant and hepatocytes enter a failsafe mode to undergo self-destruction. DILI can be seen as an active process involving recruitment of death signaling pathways that mediate cell death rather than a passive process due to overwhelming biochemical injury. In this review, we highlight the role of signal transduction pathways, which frequently involve mitochondria, in the development of DILI. PMID:23453390

  20. Molecular adaptations of apoptotic pathways and signaling partners in the cerebral cortex of human cocaine addicts and cocaine-treated rats.

    Science.gov (United States)

    Alvaro-Bartolomé, M; La Harpe, R; Callado, L F; Meana, J J; García-Sevilla, J A

    2011-11-24

    Cocaine induces apoptotic effects in cultured cells and in the developing brain, but the aberrant activation of cell death in the adult brain remains inconclusive, especially in humans. This postmortem human brain study examined the status of canonical apoptotic pathways, signaling partners, and the cleavage of poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage, in prefrontal cortex (PFC) of a small but well-characterized cohort of cocaine abusers (n=10). For comparison, the chosen targets were also quantified in the cerebral cortex of cocaine-treated rats. In the PFC of cocaine abusers, FS7-associated cell surface antigen (Fas) receptor aggregates and Fas-associated death domain (FADD) adaptor were reduced (-26% and -66%, respectively) as well as the content of mitochondrial cytochrome c (-61%). In the same brain samples of cocaine abusers, the proteolytic cleavage of PARP-1 was increased (+39%). Nuclear PARP-1 degradation, possibly a consequence of increased mitochondrial oxidative stress, involved the activation of apoptosis-inducing factor (AIF) and not that of caspase-3. In the PFC of cocaine abusers, several signaling molecules associated with cocaine/dopamine and/or apoptotic pathways were not significantly altered, with the exception of anti-apoptotic truncated DARPP-32 (t-DARPP), a truncated isoform of dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), whose content was decreased (-28%). Chronic exposure to cocaine in rats, including withdrawal for 3 days, did not alter Fas-FADD receptor complex, cytochrome c, caspase-3/fragments, AIF, PARP-1 cleavage, and associated signaling in the cerebral cortex. Chronic cocaine and abstinence, however, increased the content of t-DARPP (+39% and +47%) in rat brain cortex. The major findings indicate that cocaine addiction in humans is not associated with abnormal activation of extrinsic and intrinsic apoptotic pathways in PFC. The downregulation of Fas-FADD receptor complex and cytochrome c

  1. Biochemical Aspects of Acclimatization of Man to High Altitude Stress

    Directory of Open Access Journals (Sweden)

    K. K. Srivastava

    1975-07-01

    Full Text Available The paper reviews the biochemical aspects of acclimatization of human body to high altitude with particular reference to the adaptive changes in Skeletal muscles, hepatic function, adrenal function and carbohydrate metabolism.

  2. Genomic encyclopedia of sugar utilization pathways in the Shewanella genus

    Energy Technology Data Exchange (ETDEWEB)

    Rodionov, Dmitry A.; Yang, Chen; Li, Xiaoqing; Rodionova, Irina A.; Wang, Yanbing; Obraztsova, Anna; Zagnitko, Olga P.; Overbeek, Ross; Romine, Margaret F.; Reed, Samantha B.; Fredrickson, Jim K.; Nealson, Kenneth H.; Osterman, Andrei L.

    2010-09-13

    To address a practically and fundamentally important challenge of reconstruction of carbohydrate utilization machinery in any microorganism directly from its genomic sequence, we have established a subsystems-based comparative approach and applied it to 19 genomes from the Shewanella genus. The key stages of our approach include: (i) a homology-based identification of gene candidates using a genomic compilation of ~500 known components of sugar catabolic pathways; (ii) functional assignment of orthologs and prediction of alternative genes and pathway variants based on genomic (operons, regulons) and functional (subsystems, pathways) context analysis; (iii) validation of bioinformatic predictions by a combination of biochemical, genetic and physiological experiments. The obtained genomic encyclopedia of sugar utilization includes ~170 protein families (mostly metabolic enzymes, transporters and transcriptional regulators) spanning 17 distinct pathways with a mosaic distribution across Shewanella species providing insights into their ecophysiology and adaptive evolution. The reconstructed catabolic pathways are significantly enriched by nonorthologous gene replacements and alternative biochemical routes. Phenotypic assays revealed a remarkable consistency between predicted and observed phenotype, an ability to utilize an individual sugar as a sole source of carbon and energy, over the entire matrix of tested strains and sugars. In addition to improving our knowledge of genomics, functional organization and evolution of the sugar catabolome, this study confirmed the efficiency of the established approach, which is scalable and applicable to other groups of microorganisms.

  3. DMPD: TICAM-1 and TICAM-2: toll-like receptor adapters that participate in inductionof type 1 interferons. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15618008 TICAM-1 and TICAM-2: toll-like receptor adapters that participate in induc... Mar;37(3):524-9. (.png) (.svg) (.html) (.csml) Show TICAM-1 and TICAM-2: toll-like receptor adapters that part... TICAM-2: toll-like receptor adapters that participate in inductionof type 1 interferons. Authors Seya T, Os

  4. Biophysical and biochemical constraints imposed by salt stress:Learning from halophyte

    Directory of Open Access Journals (Sweden)

    Bernardo eDuarte

    2014-12-01

    Full Text Available Soil salinization is one of the most important factors impacting plant productivity. About 3.6 billion of the world’s 5.2 billion ha of agricultural dryland have already suffered erosion, degradation and salinization. Halophytes typically are considered as plants able to complete their life cycle in environments where the salt concentration is 200 mM NaCl or higher. Different strategies are known to overcome salt stress, as adaptation mechanisms from this type of plants. Salinity adjustment is a complex phenomenon characterized by both biochemical and biophysical adaptations. As photosynthesis is a prerequisite for biomass production, halophytes adapted their electronic transduction pathways and the entire energetic metabolism to overcome the salt excess. The maintenance of ionic homeostasis is in the basis of all cellular stress in particular in terms of redox potential and energy transduction. In the present work the biophysical mechanisms underlying energy capture and transduction in halophytes are discussed alongside with their relation to biochemical mechanisms, integrating data from photosystem light harvesting complexes, electronic transport chains to the quinone pools, carbon harvesting and energy dissipation metabolism.

  5. Recent abstracts in biochemical technology

    OpenAIRE

    R R Siva Kiran; Brijesh P

    2008-01-01

    “Recent abstracts in biochemical technology” is a collection of interesting research articles published in “List of biochemical technology journals” (Table 1). The abstracts are most likely to report significant results in biochemical technology.

  6. Identifying positive selection candidate loci for high-altitude adaptation in Andean populations

    Directory of Open Access Journals (Sweden)

    Bigham Abigail W

    2009-12-01

    Full Text Available Abstract High-altitude environments (>2,500 m provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach to understanding how life at high altitude has affected human metabolism is to survey genome-wide datasets for signatures of natural selection. In this work, we report on a study to identify selection-nominated candidate genes involved in adaptation to hypoxia in one highland group, Andeans from the South American Altiplano. We analysed dense microarray genotype data using four test statistics that detect departures from neutrality. Using a candidate gene, single nucleotide polymorphism-based approach, we identified genes exhibiting preliminary evidence of recent genetic adaptation in this population. These included genes that are part of the hypoxia-inducible transcription factor (HIF pathway, a biochemical pathway involved in oxygen homeostasis, as well as three other genomic regions previously not known to be associated with high-altitude phenotypes. In addition to identifying selection-nominated candidate genes, we also tested whether the HIF pathway shows evidence of natural selection. Our results indicate that the genes of this biochemical pathway as a group show no evidence of having evolved in response to hypoxia in Andeans. Results from particular HIF-targeted genes, however, suggest that genes in this pathway could play a role in Andean adaptation to high altitude, even if the pathway as a whole does not show higher relative rates of evolution. These data suggest a genetic role in high-altitude adaptation and provide a basis for genotype/phenotype association studies that are necessary to confirm the role of putative natural selection candidate genes and gene regions in adaptation to altitude.

  7. Fit for purpose? Building and evaluating a fast, integrated model for exploring water policy pathways

    NARCIS (Netherlands)

    Haasnoot, M.; Van Deursen, W.P.A.; Guillaume, J.H.A.; Kwakkel, J.H.; Van Beek, E.; Middelkoop, H.

    2014-01-01

    Exploring adaptation pathways is an emerging approach for supporting decision making under uncertain changing conditions. An adaptation pathway is a sequence of policy actions to reach specified objectives. To develop adaptation pathways, interactions between environment and policy response need to

  8. Immunomodulatory Pathways and Metabolism

    OpenAIRE

    Bhargava, Prerna

    2012-01-01

    Energy metabolism plays a vital role in normal physiology, adaptive responses and host defense mechanisms. Research throughout the last decade has shown evidence that immune pathways communicate with metabolic pathways to alter the metabolic status in response to physiological or pathological signals. In this thesis, I will explore how immunomodulatory molecules affect metabolic homeostasis and conversely, how metabolic sensing pathways modulate immune responses. The first part my work utiliz...

  9. Measures of Biochemical Sociology

    Science.gov (United States)

    Snell, Joel; Marsh, Mitchell

    2008-01-01

    In a previous article, the authors introduced a new sub field in sociology that we labeled "biochemical sociology." We introduced the definition of a sociology that encompasses sociological measures, psychological measures, and biological indicators Snell & Marsh (2003). In this article, we want to demonstrate a research strategy that would assess…

  10. Biochemical Education in Brazil.

    Science.gov (United States)

    Vella, F.

    1988-01-01

    Described are discussions held concerning the problems of biochemical education in Brazil at a meeting of the Sociedade Brazileira de Bioquimica in April 1988. Also discussed are other visits that were made to universities in Brazil. Three major recommendations to improve the state of biochemistry education in Brazil are presented. (CW)

  11. Genomic encyclopedia of sugar utilization pathways in the Shewanella genus

    Directory of Open Access Journals (Sweden)

    Overbeek Ross

    2010-09-01

    Full Text Available Abstract Background Carbohydrates are a primary source of carbon and energy for many bacteria. Accurate projection of known carbohydrate catabolic pathways across diverse bacteria with complete genomes constitutes a substantial challenge due to frequent variations in components of these pathways. To address a practically and fundamentally important challenge of reconstruction of carbohydrate utilization machinery in any microorganism directly from its genomic sequence, we combined a subsystems-based comparative genomic approach with experimental validation of selected bioinformatic predictions by a combination of biochemical, genetic and physiological experiments. Results We applied this integrated approach to systematically map carbohydrate utilization pathways in 19 genomes from the Shewanella genus. The obtained genomic encyclopedia of sugar utilization includes ~170 protein families (mostly metabolic enzymes, transporters and transcriptional regulators spanning 17 distinct pathways with a mosaic distribution across Shewanella species providing insights into their ecophysiology and adaptive evolution. Phenotypic assays revealed a remarkable consistency between predicted and observed phenotype, an ability to utilize an individual sugar as a sole source of carbon and energy, over the entire matrix of tested strains and sugars. Comparison of the reconstructed catabolic pathways with E. coli identified multiple differences that are manifested at various levels, from the presence or absence of certain sugar catabolic pathways, nonorthologous gene replacements and alternative biochemical routes to a different organization of transcription regulatory networks. Conclusions The reconstructed sugar catabolome in Shewanella spp includes 62 novel isofunctional families of enzymes, transporters, and regulators. In addition to improving our knowledge of genomics and functional organization of carbohydrate utilization in Shewanella, this study led to a

  12. Biochemical considerations in the design of radiopharmaceuticals

    International Nuclear Information System (INIS)

    The goal of radiopharmaceutical chemistry is to design and develop radiotracers targeted to an organ or function whose activity kinetics in tissue can be detected externally by a gamma or a positron device. Radiopharmaceuticals are divided into the general categories of specific and non-specific agents. The specific radiopharmaceuticals are the tracers that follow a biochemical pathway or are involved in a particular interaction, for example metabolic substrates, drugs or analogs, and antibodies. This paper will focus on trends in the design of specific agents. The best radionuclides for the development of specific tracers are the positron emitting nuclides: carbon-11, nitrogen-13, oxygen-15 and fluorine-18. First the design of radiopharmaceuticals are considered in general (labeling strategies, stereochemical effects, specific activity). Next, a brief summary of the use of several radiopharmaceuticals is presented on the basis of their biochemical rationale. (orig./G.J.P.)

  13. Graded Proteasome Dysfunction in Caenorhabditis elegans Activates an Adaptive Response Involving the Conserved SKN-1 and ELT-2 Transcription Factors and the Autophagy-Lysosome Pathway.

    Science.gov (United States)

    Keith, Scott A; Maddux, Sarah K; Zhong, Yayu; Chinchankar, Meghna N; Ferguson, Annabel A; Ghazi, Arjumand; Fisher, Alfred L

    2016-02-01

    The maintenance of cellular proteins in a biologically active and structurally stable state is a vital endeavor involving multiple cellular pathways. One such pathway is the ubiquitin-proteasome system that represents a major route for protein degradation, and reductions in this pathway usually have adverse effects on the health of cells and tissues. Here, we demonstrate that loss-of-function mutants of the Caenorhabditis elegans proteasome subunit, RPN-10, exhibit moderate proteasome dysfunction and unexpectedly develop both increased longevity and enhanced resistance to multiple threats to the proteome, including heat, oxidative stress, and the presence of aggregation prone proteins. The rpn-10 mutant animals survive through the activation of compensatory mechanisms regulated by the conserved SKN-1/Nrf2 and ELT-2/GATA transcription factors that mediate the increased expression of genes encoding proteasome subunits as well as those mediating oxidative- and heat-stress responses. Additionally, we find that the rpn-10 mutant also shows enhanced activity of the autophagy-lysosome pathway as evidenced by increased expression of the multiple autophagy genes including atg-16.2, lgg-1, and bec-1, and also by an increase in GFP::LGG-1 puncta. Consistent with a critical role for this pathway, the enhanced resistance of the rpn-10 mutant to aggregation prone proteins depends on autophagy genes atg-13, atg-16.2, and prmt-1. Furthermore, the rpn-10 mutant is particularly sensitive to the inhibition of lysosome activity via either RNAi or chemical means. We also find that the rpn-10 mutant shows a reduction in the numbers of intestinal lysosomes, and that the elt-2 gene also plays a novel and vital role in controlling the production of functional lysosomes by the intestine. Overall, these experiments suggest that moderate proteasome dysfunction could be leveraged to improve protein homeostasis and organismal health and longevity, and that the rpn-10 mutant provides a unique

  14. Graded Proteasome Dysfunction in Caenorhabditis elegans Activates an Adaptive Response Involving the Conserved SKN-1 and ELT-2 Transcription Factors and the Autophagy-Lysosome Pathway.

    Directory of Open Access Journals (Sweden)

    Scott A Keith

    2016-02-01

    Full Text Available The maintenance of cellular proteins in a biologically active and structurally stable state is a vital endeavor involving multiple cellular pathways. One such pathway is the ubiquitin-proteasome system that represents a major route for protein degradation, and reductions in this pathway usually have adverse effects on the health of cells and tissues. Here, we demonstrate that loss-of-function mutants of the Caenorhabditis elegans proteasome subunit, RPN-10, exhibit moderate proteasome dysfunction and unexpectedly develop both increased longevity and enhanced resistance to multiple threats to the proteome, including heat, oxidative stress, and the presence of aggregation prone proteins. The rpn-10 mutant animals survive through the activation of compensatory mechanisms regulated by the conserved SKN-1/Nrf2 and ELT-2/GATA transcription factors that mediate the increased expression of genes encoding proteasome subunits as well as those mediating oxidative- and heat-stress responses. Additionally, we find that the rpn-10 mutant also shows enhanced activity of the autophagy-lysosome pathway as evidenced by increased expression of the multiple autophagy genes including atg-16.2, lgg-1, and bec-1, and also by an increase in GFP::LGG-1 puncta. Consistent with a critical role for this pathway, the enhanced resistance of the rpn-10 mutant to aggregation prone proteins depends on autophagy genes atg-13, atg-16.2, and prmt-1. Furthermore, the rpn-10 mutant is particularly sensitive to the inhibition of lysosome activity via either RNAi or chemical means. We also find that the rpn-10 mutant shows a reduction in the numbers of intestinal lysosomes, and that the elt-2 gene also plays a novel and vital role in controlling the production of functional lysosomes by the intestine. Overall, these experiments suggest that moderate proteasome dysfunction could be leveraged to improve protein homeostasis and organismal health and longevity, and that the rpn-10 mutant

  15. Pathways of tau fibrillization.

    Science.gov (United States)

    Kuret, Jeff; Chirita, Carmen N; Congdon, Erin E; Kannanayakal, Theresa; Li, Guibin; Necula, Mihaela; Yin, Haishan; Zhong, Qi

    2005-01-01

    New methods for analyzing tau fibrillization have yielded insights into the biochemical transitions involved in the process. Here we review the parallels between the sequential progression of tau fibrillization observed macroscopically in Alzheimer's disease (AD) lesions and the pathway of tau aggregation observed in vitro with purified tau preparations. In addition, pharmacological agents for further dissection of fibrillization mechanism and lesion formation are discussed. PMID:15615636

  16. Fluctuation preserving coarse graining for biochemical systems

    CERN Document Server

    Altaner, Bernhard

    2011-01-01

    Finite stochastic Markov models play a major role for modelling biochemical pathways. Such models are a coarse-grained description of the underlying microscopic dynamics and can be considered mesoscopic. The level of coarse-graining is to a certain extend arbitrary since it depends on the resolution of accomodating measurements. Here, we present a way to simplify such stochastic descriptions, which preserves both the meso-micro and the meso-macro connection. The former is achieved by demanding locality, the latter by considering cycles on the network of states. Using single- and multicycle examples we demonstrate how our new method preserves fluctuations of observables much better than na\\"ive approaches.

  17. Biochemical Hypermedia: Galactose Metabolism.

    Directory of Open Access Journals (Sweden)

    J.K. Sugai

    2013-05-01

    Full Text Available Introduction: Animations of biochemical processes and virtual laboratory environments lead to true molecular simulations. The use of interactive software’s in education can improve cognitive capacity, better learning and, mainly, it makes information acquisition easier. Material and Methods: This work presents the development of a biochemical hypermedia to understanding of the galactose metabolism. It was developed with the help of concept maps, ISIS Draw, ADOBE Photoshop and FLASH MX Program. Results and Discussion: A step by step animation process shows the enzymatic reactions of galactose conversion to glucose-1-phosphate (to glycogen synthesis, glucose-6-phosphate (glycolysis intermediary, UDP-galactose (substrate to mucopolysaccharides synthesis and collagen’s glycosylation. There are navigation guide that allow scrolling the mouse over the names of the components of enzymatic reactions of via the metabolism of galactose. Thus, explanatory text box, chemical structures and animation of the actions of enzymes appear to navigator. Upon completion of the module, the user’s response to the proposed exercise can be checked immediately through text box with interactive content of the answer. Conclusion: This hypermedia was presented for undergraduate students (UFSC who revealed that it was extremely effective in promoting the understanding of the theme.

  18. Biochemical Network Stochastic Simulator (BioNetS: software for stochastic modeling of biochemical networks

    Directory of Open Access Journals (Sweden)

    Elston Timothy C

    2004-03-01

    Full Text Available Abstract Background Intrinsic fluctuations due to the stochastic nature of biochemical reactions can have large effects on the response of biochemical networks. This is particularly true for pathways that involve transcriptional regulation, where generally there are two copies of each gene and the number of messenger RNA (mRNA molecules can be small. Therefore, there is a need for computational tools for developing and investigating stochastic models of biochemical networks. Results We have developed the software package Biochemical Network Stochastic Simulator (BioNetS for efficientlyand accurately simulating stochastic models of biochemical networks. BioNetS has a graphical user interface that allows models to be entered in a straightforward manner, and allows the user to specify the type of random variable (discrete or continuous for each chemical species in the network. The discrete variables are simulated using an efficient implementation of the Gillespie algorithm. For the continuous random variables, BioNetS constructs and numerically solvesthe appropriate chemical Langevin equations. The software package has been developed to scale efficiently with network size, thereby allowing large systems to be studied. BioNetS runs as a BioSpice agent and can be downloaded from http://www.biospice.org. BioNetS also can be run as a stand alone package. All the required files are accessible from http://x.amath.unc.edu/BioNetS. Conclusions We have developed BioNetS to be a reliable tool for studying the stochastic dynamics of large biochemical networks. Important features of BioNetS are its ability to handle hybrid models that consist of both continuous and discrete random variables and its ability to model cell growth and division. We have verified the accuracy and efficiency of the numerical methods by considering several test systems.

  19. Electronic modulation of biochemical signal generation

    Science.gov (United States)

    Gordonov, Tanya; Kim, Eunkyoung; Cheng, Yi; Ben-Yoav, Hadar; Ghodssi, Reza; Rubloff, Gary; Yin, Jun-Jie; Payne, Gregory F.; Bentley, William E.

    2014-08-01

    Microelectronic devices that contain biological components are typically used to interrogate biology rather than control biological function. Patterned assemblies of proteins and cells have, however, been used for in vitro metabolic engineering, where coordinated biochemical pathways allow cell metabolism to be characterized and potentially controlled on a chip. Such devices form part of technologies that attempt to recreate animal and human physiological functions on a chip and could be used to revolutionize drug development. These ambitious goals will, however, require new biofabrication methodologies that help connect microelectronics and biological systems and yield new approaches to device assembly and communication. Here, we report the electrically mediated assembly, interrogation and control of a multi-domain fusion protein that produces a bacterial signalling molecule. The biological system can be electrically tuned using a natural redox molecule, and its biochemical response is shown to provide the signalling cues to drive bacterial population behaviour. We show that the biochemical output of the system correlates with the electrical input charge, which suggests that electrical inputs could be used to control complex on-chip biological processes.

  20. Ecological adaptation of diverse honey bee (Apis mellifera populations.

    Directory of Open Access Journals (Sweden)

    Robert Parker

    Full Text Available BACKGROUND: Honey bees are complex eusocial insects that provide a critical contribution to human agricultural food production. Their natural migration has selected for traits that increase fitness within geographical areas, but in parallel their domestication has selected for traits that enhance productivity and survival under local conditions. Elucidating the biochemical mechanisms of these local adaptive processes is a key goal of evolutionary biology. Proteomics provides tools unique among the major 'omics disciplines for identifying the mechanisms employed by an organism in adapting to environmental challenges. RESULTS: Through proteome profiling of adult honey bee midgut from geographically dispersed, domesticated populations combined with multiple parallel statistical treatments, the data presented here suggest some of the major cellular processes involved in adapting to different climates. These findings provide insight into the molecular underpinnings that may confer an advantage to honey bee populations. Significantly, the major energy-producing pathways of the mitochondria, the organelle most closely involved in heat production, were consistently higher in bees that had adapted to colder climates. In opposition, up-regulation of protein metabolism capacity, from biosynthesis to degradation, had been selected for in bees from warmer climates. CONCLUSIONS: Overall, our results present a proteomic interpretation of expression polymorphisms between honey bee ecotypes and provide insight into molecular aspects of local adaptation or selection with consequences for honey bee management and breeding. The implications of our findings extend beyond apiculture as they underscore the need to consider the interdependence of animal populations and their agro-ecological context.

  1. Biochemical synthesis with stable isotopes

    International Nuclear Information System (INIS)

    Descriptions of the biochemical synthesis of glucose-13C6 from Agmenellum quadruplication; the biochemical labelling of [13C, 15N] Chlorella and [13C] E. coli, [15N] E. coli, and the production of lactic-13C3 acid utilizing Lactobacillus casei are discussed

  2. EVALUATING BIOCHEMICAL INTERNET RESOURCES

    Directory of Open Access Journals (Sweden)

    R.M. Lima

    2007-05-01

    Full Text Available Many people fail to properly evaluate INTERNET information. This is often due to alack of understanding of the issues, by responsible authorities, and, morespecifically, a lack of understanding of the structure and modis operandi of theINTERNET tool. The aim of this project was to analyze biochemical issuesavailable in WEB pages, evaluating contents quality, coverage, accuracy, authorityand currency. Twenty three sites were analyzed for their contents, presence ofbibliographical references, authorship, titles responsibility and adequacy to targetpublic. The great majority (95% did not mention bibliographic references andtarget public. Less than half divulged names and/or graduation status ofresponsibles. Some sites contained critical conceptual errors, such as: oxygen isessential for anaerobic respiration; presence of H2O in photosynthesis dark phase;yeast is a pluricellular fungal; the overall equation of photosynthesis with errors;NADH2 instead NAD+; etc. None of the analyzed sites was thus consideredexcellent. Although the use of the internet is expanding rapidly on collegecampuses, little is known about students usage; how they perceive the reality ofinternet information and how successful they are in searching through it. Our datastrenghthen the need for rigorous evaluation concerning to educational research ofbiochemical themes on the WEB.

  3. Ouroboros - Playing A Biochemical

    Directory of Open Access Journals (Sweden)

    D. T. Rodrigues

    2014-08-01

    Full Text Available Ouroboros: Playing A Biochemical RODRIGUES,D.T.1,2;GAYER, M.C.1,2; ESCOTO, D.F.1; DENARDIN, E.L.G.2, ROEHRS, R.1,2 1Interdisciplinary Research Group on Teaching Practice, Graduate Program in Biochemistry, Unipampa, RS, Brazil 2Laboratory of Physicochemical Studies and Natural Products, Post Graduate Program in Biochemistry, Unipampa, RS, Brazil Introduction: Currently, teachers seek different alternatives to enhance the teaching-learning process. Innovative teaching methodologies are increasingly common tools in educational routine. The use of games, electronic or conventional, is an effective tool to assist in learning and also to raise the social interaction between students. Objective: In this sense our work aims to evaluate the card game and "Ouroboros" board as a teaching and learning tool in biochemistry for a graduating class in Natural Sciences. Materials and methods: The class gathered 22 students of BSc in Natural Sciences. Each letter contained a question across the board that was drawn to a group to answer within the allotted time. The questions related concepts of metabolism, organic and inorganic chemical reactions, bioenergetics, etc.. Before the game application, students underwent a pre-test with four issues involving the content that was being developed. Soon after, the game was applied. Then again questions were asked. Data analysis was performed from the ratio of the number of correct pre-test and post-test answers. Results and discussion: In the pre-test 18.1% of the students knew all issues, 18.1% got 3 correct answers, 40.9% answered only 2 questions correctly and 22.7% did not hit any. In post-test 45.4% answered all the questions right, 31.8% got 3 questions and 22.7% got 2 correct answers. The results show a significant improvement of the students about the field of content taught through the game. Conclusion: Generally, traditional approaches of chemistry and biochemistry are abstract and complex. Thus, through games

  4. BNDB – The Biochemical Network Database

    Directory of Open Access Journals (Sweden)

    Kaufmann Michael

    2007-10-01

    Full Text Available Abstract Background Technological advances in high-throughput techniques and efficient data acquisition methods have resulted in a massive amount of life science data. The data is stored in numerous databases that have been established over the last decades and are essential resources for scientists nowadays. However, the diversity of the databases and the underlying data models make it difficult to combine this information for solving complex problems in systems biology. Currently, researchers typically have to browse several, often highly focused, databases to obtain the required information. Hence, there is a pressing need for more efficient systems for integrating, analyzing, and interpreting these data. The standardization and virtual consolidation of the databases is a major challenge resulting in a unified access to a variety of data sources. Description We present the Biochemical Network Database (BNDB, a powerful relational database platform, allowing a complete semantic integration of an extensive collection of external databases. BNDB is built upon a comprehensive and extensible object model called BioCore, which is powerful enough to model most known biochemical processes and at the same time easily extensible to be adapted to new biological concepts. Besides a web interface for the search and curation of the data, a Java-based viewer (BiNA provides a powerful platform-independent visualization and navigation of the data. BiNA uses sophisticated graph layout algorithms for an interactive visualization and navigation of BNDB. Conclusion BNDB allows a simple, unified access to a variety of external data sources. Its tight integration with the biochemical network library BN++ offers the possibility for import, integration, analysis, and visualization of the data. BNDB is freely accessible at http://www.bndb.org.

  5. DMPD: Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regulatoryfactor...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of... interferon regulatoryfactor 3. Authors Servant MJ, Grandvaux N, Hiscott J. Publication Biochem Pharmacol. 2

  6. Targeted Proteomics of Metabolic Pathways and Protein Turnover Analysis in Plants

    Institute of Scientific and Technical Information of China (English)

    A.Harvey Millar; Clark Nelson; Lei Li; Nicolas L.Taylor; Ricarda Fenske

    2012-01-01

    Shotgun approaches have dominated proteome studies as discovery tools to find changes in protein abundance.However,they often only provide a mosaic image of the proteome response and they focus mainly on the proteins that are changing in abundance to find biological insights.Using mass spectrometry for targeted identification of changes in whole biochemical pathways and analysing protein synthesis and degradation rates with stable isotope labelling provide an added depth of biological insights.These can help us to uncover the costs of protein production in plants and the role of specific pathways in responding to harsh or nutrient depleted environments.By adapting the selected reaction monitoring and the progressive 15N incorporation stu-dies we have developed in model plants,we are beginning to discover the power of these systems to analyse the response of barley to low nitrogen,rice to low phosphate and wheat to saline conditions.

  7. Biochemical Characterization of Prion Strains in Bank Voles

    Directory of Open Access Journals (Sweden)

    Romolo Nonno

    2013-07-01

    Full Text Available Prions exist as different strains exhibiting distinct disease phenotypes. Currently, the identification of prion strains is still based on biological strain typing in rodents. However, it has been shown that prion strains may be associated with distinct PrPSc biochemical types. Taking advantage of the availability of several prion strains adapted to a novel rodent model, the bank vole, we investigated if any prion strain was actually associated with distinctive PrPSc biochemical characteristics and if it was possible to univocally identify strains through PrPSc biochemical phenotypes. We selected six different vole-adapted strains (three human-derived and three animal-derived and analyzed PrPSc from individual voles by epitope mapping of protease resistant core of PrPSc (PrPres and by conformational stability and solubility assay. Overall, we discriminated five out of six prion strains, while two different scrapie strains showed identical PrPSc types. Our results suggest that the biochemical strain typing approach here proposed was highly discriminative, although by itself it did not allow us to identify all prion strains analyzed.

  8. Biochemical adaptations of antigravity muscle fibers to disuse atrophy

    Science.gov (United States)

    Booth, F. W.

    1978-01-01

    Studies are presented in four parts of this report. The four parts include; (1) studies to gain information on the molecular basis of atrophy by antigravity muscle; (2) studies on the work capacity of antigravity muscles during atrophy and during recovery from atrophy; (3) studies on recovery of degenerated antigravity fibers after removal of hind-limb casts; and (4) studies on the atrophy and recovery of bone. The philosophy of these studies was to identify the time sequence of events in the soleus muscle of the rat following immobilization of the hind limbs, so that the length of the soleus muscle within the fixed limb is less than its resting length. In two separate studies, no decline in the weight of the soleus muscle could be detected during the first 72 hours of limb immobilization.

  9. Training induced adaptation in horse skeletal muscle

    OpenAIRE

    van Dam, K.G.

    2006-01-01

    It appears that the physiological and biochemical adaptation of skeletal muscle to training in equine species shows a lot of similarities with human and rodent physiological adaptation. On the other hand it is becoming increasingly clear that intra-cellular mechanisms of adaptation (substrate transport, enzyme activity, etc) differ considerably between species. The major drawbacks in equine training physiological research are the lack of an appropriate training model and the lack of control o...

  10. Molecular and biochemical analyses of transgenic nicotiana tabacum plants metabolizing glycolate in the chloroplasts

    OpenAIRE

    Thiruveedhi, Krishnaveni

    2006-01-01

    The photorespiratory pathway in C3 plants consumes not only ATP and reducing equivalents but also results in loss of ~ 25% carbon that has been fixed during the process of photosynthesis. In the present study, an alternative biochemical pathway for the metabolism of glycolate was established in the chloroplasts of tobacco (Nicotiana tabacum) plants. The new pathway aims at increasing the refixation of CO2 inside the chloroplasts and thereby at suppressing photorespiration in C3 plants. The pa...

  11. Oxylipin Pathway in Rice and Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    E. Wassim Chehab; John V. Perea; Banu Gopalan; Steve Theg; Katayoon Dehesh

    2007-01-01

    Plants have evolved complex signaling pathways to coordinate responses to developmental and environmental information. The oxylipin pathway is one pivotal lipid-based signaling network, composed of several competing branch pathways, that determines the plant's ability to adapt to various stimuli. Activation of the oxylipin pathway induces the de novo synthesis of biologically active metabolltes called "oxylipins". The relative levels of these metabolltes are a distinct indicator of each plant species and determine the ability of plants to adapt to different stimuli. The two major branches of the oxylipln pathway, allene oxide synthase (AOS) and hydroperoxide lyase (HPL) are responsible for production of the signaling compounds,jasmonates and aldehydes respectively. Here, we compare and contrast the regulation of AOS and HPL branch pathways in rice and Arabidopsis as model monocotyledonous and dicotyledonous systems. These analyses provide new Insights into the evolution of JAs and aldehydes signaling pathways, and the complex network of processes responsible for stress adaptations in monocots and dicots.

  12. Design of a biochemical circuit motif for learning linear functions.

    Science.gov (United States)

    Lakin, Matthew R; Minnich, Amanda; Lane, Terran; Stefanovic, Darko

    2014-12-01

    Learning and adaptive behaviour are fundamental biological processes. A key goal in the field of bioengineering is to develop biochemical circuit architectures with the ability to adapt to dynamic chemical environments. Here, we present a novel design for a biomolecular circuit capable of supervised learning of linear functions, using a model based on chemical reactions catalysed by DNAzymes. To achieve this, we propose a novel mechanism of maintaining and modifying internal state in biochemical systems, thereby advancing the state of the art in biomolecular circuit architecture. We use simulations to demonstrate that the circuit is capable of learning behaviour and assess its asymptotic learning performance, scalability and robustness to noise. Such circuits show great potential for building autonomous in vivo nanomedical devices. While such a biochemical system can tell us a great deal about the fundamentals of learning in living systems and may have broad applications in biomedicine (e.g. autonomous and adaptive drugs), it also offers some intriguing challenges and surprising behaviours from a machine learning perspective. PMID:25401175

  13. Fe-S Cluster Assembly Pathways in Bacteria

    OpenAIRE

    Ayala-Castro, Carla; Saini, Avneesh; Outten, F. Wayne

    2008-01-01

    Summary: Iron-sulfur (Fe-S) clusters are required for critical biochemical pathways, including respiration, photosynthesis, and nitrogen fixation. Assembly of these iron cofactors is a carefully controlled process in cells to avoid toxicity from free iron and sulfide. Multiple Fe-S cluster assembly pathways are present in bacteria to carry out basal cluster assembly, stress-responsive cluster assembly, and enzyme-specific cluster assembly. Although biochemical and genetic characterization is ...

  14. Adaptive Lighting

    OpenAIRE

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive LightingAdaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled i...

  15. Bone Adaptation and Regeneration - New Developments

    Science.gov (United States)

    Klein-Nulend, Jenneke; Bacabac, Rommel Gaud

    Bone is a dynamic tissue that is constantly renewed and adapts to its local loading environment. Mechanical loading results in adaptive changes in bone size and shape that strengthen bone structure. The mechanisms for adaptation involve a multistep process called mechanotransduction, which is the ability of resident bone cells to perceive and translate mechanical energy into a cascade of structural and biochemical changes within the cells. The transduction of a mechanical signal to a biochemical response involves pathways within the cell membrane and cytoskeleton of the osteocytes, the professional mechansensor cells of bone. During the last decade the role of mechanosensitive osteocytes in bone metabolism and turnover, and the lacuno-canalicular porosity as the structure that mediates mechanosensing, is likely to reveal a new paradigm for understanding the bone formation response to mechanical loading, and the bone resorption response to disuse. Strain-derived fluid flow of interstitial fluid through the lacuno-canalicular porosity seems to mechanically activate the osteocytes, as well as ensures transport of cell signaling molecules, nutrients and waste products. Cell-cell signaling from the osteocyte sensor cells to the effector cells (osteoblasts or osteoclasts), and the effector cell response - either bone formation or resorption, allow an explanation of local bone gain and loss as well as remodeling in response to fatigue damage as processes supervised by mechanosensitive osteocytes. The osteogenic activity of cultured bone cells has been quantitatively correlated with varying stress stimulations highlighting the importance of the rate of loading. Theoretically a possible mechanism for the stress response by osteocytes is due to strain amplification at the pericellular matrix. Single cell studies on molecular responses of osteocytes provide insight on local architectural alignment in bone during remodeling. Alignment seems to occur as a result of the

  16. Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis.

    Directory of Open Access Journals (Sweden)

    Jeffrey M Skerker

    2005-10-01

    Full Text Available Two-component signal transduction systems, comprised of histidine kinases and their response regulator substrates, are the predominant means by which bacteria sense and respond to extracellular signals. These systems allow cells to adapt to prevailing conditions by modifying cellular physiology, including initiating programs of gene expression, catalyzing reactions, or modifying protein-protein interactions. These signaling pathways have also been demonstrated to play a role in coordinating bacterial cell cycle progression and development. Here we report a system-level investigation of two-component pathways in the model organism Caulobacter crescentus. First, by a comprehensive deletion analysis we show that at least 39 of the 106 two-component genes are required for cell cycle progression, growth, or morphogenesis. These include nine genes essential for growth or viability of the organism. We then use a systematic biochemical approach, called phosphotransfer profiling, to map the connectivity of histidine kinases and response regulators. Combining these genetic and biochemical approaches, we identify a new, highly conserved essential signaling pathway from the histidine kinase CenK to the response regulator CenR, which plays a critical role in controlling cell envelope biogenesis and structure. Depletion of either cenK or cenR leads to an unusual, severe blebbing of cell envelope material, whereas constitutive activation of the pathway compromises cell envelope integrity, resulting in cell lysis and death. We propose that the CenK-CenR pathway may be a suitable target for new antibiotic development, given previous successes in targeting the bacterial cell wall. Finally, the ability of our in vitro phosphotransfer profiling method to identify signaling pathways that operate in vivo takes advantage of an observation that histidine kinases are endowed with a global kinetic preference for their cognate response regulators. We propose that this

  17. A feedback approach to bifurcation analysis in biochemical networks with many parameters

    OpenAIRE

    Waldherr, Steffen; Allgower, Frank

    2007-01-01

    Feedback circuits in biochemical networks which underly cellular signaling pathways are important elements in creating complex behavior. A specific aspect thereof is how stability of equilibrium points depends on model parameters. For biochemical networks, which are modelled using many parameters, it is typically very difficult to estimate the influence of parameters on stability. Finding parameters which result in a change in stability is a key step for a meaningful bifurcation analysis. We ...

  18. Hematological and biochemical alterations in the fish Prochilodus lineatus caused by the herbicide clomazone.

    Science.gov (United States)

    Pereira, Lindalva; Fernandes, Marisa N; Martinez, Cláudia B R

    2013-07-01

    The indiscriminate use of herbicides has led to the contamination of water bodies, possibly affecting the health of aquatic biota. Therefore, to evaluate the possible effects of the clomazone-based herbicide (Gamit(®) 500) on the fish Prochilodus lineatus, juveniles were exposed for 96h to three concentrations (1, 5 and 10mgL(-1)) of clomazone, and an analysis was made of their hematological parameters: hemoglobin (Hb); hematocrit (Hct); red blood cell (RBC) count; mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH); mean corpuscular hemoglobin concentration (MCHC) and biochemical parameters: glutathione S-transferase (GST); catalase (CAT); glutathione peroxidase (GPx) and acetylcholinesterase (AChE). Hct presented a significant decrease at the concentration of 10mgL(-1), while the parameters Hb, HCM and MCHC presented a significant decrease at the two higher concentrations, indicating an anemic condition. The RBC increased significantly at the lowest concentration, possibly due to the release of new red blood cells into the bloodstream in response to splenic contraction, which may occur as an adaptive response to the stressor agent. P. lineatus presented activation of the biotransformation pathway, indicated by augmented hepatic activity of the enzyme GST and hepatic activation of the antioxidant enzyme CAT at the higher concentrations. Liver GPx was significantly inhibited at the higher concentrations, which may indicate the efficient action of CAT in the elimination of H2O2 or its competition with GST for the same substrate (GSH). AChE activity in brain and muscle was inhibited at the higher concentrations, indicating the neurotoxic effects of the herbicide in the fish. The hematological and biochemical alterations led to the conclusion that the herbicide clomazone has toxic effects on the species P. lineatus, and that its presence in the environment may jeopardize the health of these animals. PMID:23538322

  19. Robust simplifications of multiscale biochemical networks

    Directory of Open Access Journals (Sweden)

    Zinovyev Andrei

    2008-10-01

    Full Text Available Abstract Background Cellular processes such as metabolism, decision making in development and differentiation, signalling, etc., can be modeled as large networks of biochemical reactions. In order to understand the functioning of these systems, there is a strong need for general model reduction techniques allowing to simplify models without loosing their main properties. In systems biology we also need to compare models or to couple them as parts of larger models. In these situations reduction to a common level of complexity is needed. Results We propose a systematic treatment of model reduction of multiscale biochemical networks. First, we consider linear kinetic models, which appear as "pseudo-monomolecular" subsystems of multiscale nonlinear reaction networks. For such linear models, we propose a reduction algorithm which is based on a generalized theory of the limiting step that we have developed in 1. Second, for non-linear systems we develop an algorithm based on dominant solutions of quasi-stationarity equations. For oscillating systems, quasi-stationarity and averaging are combined to eliminate time scales much faster and much slower than the period of the oscillations. In all cases, we obtain robust simplifications and also identify the critical parameters of the model. The methods are demonstrated for simple examples and for a more complex model of NF-κB pathway. Conclusion Our approach allows critical parameter identification and produces hierarchies of models. Hierarchical modeling is important in "middle-out" approaches when there is need to zoom in and out several levels of complexity. Critical parameter identification is an important issue in systems biology with potential applications to biological control and therapeutics. Our approach also deals naturally with the presence of multiple time scales, which is a general property of systems biology models.

  20. Adaptive skills

    OpenAIRE

    Staša Stropnik; Jana Kodrič

    2013-01-01

    Adaptive skills are defined as a collection of conceptual, social and practical skills that are learned by people in order to function in their everyday lives. They include an individual's ability to adapt to and manage her or his surroundings to effectively function and meet social or community expectations. Good adaptive skills promote individual's independence in different environments, whereas poorly developed adaptive skills are connected to individual's dependency and with g...

  1. Morphological, kinetic, membrane biochemical and genetic aspects of intestinal enteroplasticity

    Institute of Scientific and Technical Information of China (English)

    Laurie A Drozdowski; M Tom Clandinin; Alan BR Thomson

    2009-01-01

    The process of intestinal adaptation ("enteroplasticity") is complex and multifaceted. Although a number of trophic nutrients and non-nutritive factors have been identified in animal studies, successful, reproducible clinical trials in humans are awaited. Understanding mechanisms underlying this adaptive process may direct research toward strategies that maximize intestinal function and impart a true clinical benefit to patients with short bowel syndrome, or to persons in whom nutrient absorption needs to be maximized. In this review, we consider the morphological, kinetic and membrane biochemical aspects of enteroplasticity, focus on the importance of nutritional factors, provide an overview of the many hormones that may alter the adaptive process, and consider some of the possible molecular profiles. While most of the data is derived from rodent studies, wherever possible, the results of human studies of intestinal enteroplasticity are provided.

  2. Hyponatraemia: biochemical and clinical perspectives.

    OpenAIRE

    Gill, G; Leese, G

    1998-01-01

    Hyponatraemia is a common bio-chemical abnormality, occurring in about 15% of hospital inpatients. It is often associated with severe illness and relatively poor outcome. Pathophysiologically, hyponatraemia may be spurious, dilutional, depletional or redistributional. Particularly difficult causes and concepts of hyponatraemia are the syndrome of inappropriate antidiuresis and the sick cell syndrome, which are discussed here in detail. Therapy should always be targeted at the underlying disea...

  3. Biochemical markers of bone turnover

    International Nuclear Information System (INIS)

    Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitivity and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone less, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hip fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays

  4. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... distributed differently into an architectural body. We also examine what might occur when light is dynamic and able to change colour, intensity and direction, and when it is adaptive and can be brought into interaction with its surroundings. In short, what happens to an architectural space when artificial...

  5. Imprecision of Adaptation in Escherichia coli Chemotaxis

    OpenAIRE

    Silke Neumann; Nikita Vladimirov; Krembel, Anna K.; Wingreen, Ned S.; Victor Sourjik

    2014-01-01

    Adaptability is an essential property of many sensory systems, enabling maintenance of a sensitive response over a range of background stimulus levels. In bacterial chemotaxis, adaptation to the preset level of pathway activity is achieved through an integral feedback mechanism based on activity-dependent methylation of chemoreceptors. It has been argued that this architecture ensures precise and robust adaptation regardless of the ambient ligand concentration, making perfect adaptation a cel...

  6. Adaptive Lighting

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve; Søndergaard, Karin; Kongshaug, Jesper

    2015-01-01

    Adaptive Lighting Adaptive lighting is based on a partial automation of the possibilities to adjust the colour tone and brightness levels of light in order to adapt to people’s needs and desires. IT support is key to the technical developments that afford adaptive control systems. The possibilities...... offered by adaptive lighting control are created by the ways that the system components, the network and data flow can be coordinated through software so that the dynamic variations are controlled in ways that meaningfully adapt according to people’s situations and design intentions. This book discusses...... the investigations of lighting scenarios carried out in two test installations: White Cube and White Box. The test installations are discussed as large-scale experiential instruments. In these test installations we examine what could potentially occur when light using LED technology is integrated and...

  7. Adaptive skills

    Directory of Open Access Journals (Sweden)

    Staša Stropnik

    2013-02-01

    Full Text Available Adaptive skills are defined as a collection of conceptual, social and practical skills that are learned by people in order to function in their everyday lives. They include an individual's ability to adapt to and manage her or his surroundings to effectively function and meet social or community expectations. Good adaptive skills promote individual's independence in different environments, whereas poorly developed adaptive skills are connected to individual's dependency and with greater need for control and help with everyday tasks. Assessment of adaptive skills is often connected to assessment of intellectual disability, due to the reason that the diagnosis of intellectual disability includes lower levels of achievements on standardized tests of intellectual abilities as well as important deficits in adaptive skills. Assessment of adaptive behavior is a part of standard assessment battery with children and adults with different problems, disorders or disabilities that affect their everyday functioning. This contribution also presents psychometric tools most regularly used for assessment of adaptive skills and characteristics of adaptive skills with individual clinical groups.

  8. ADAPT Dataset

    Data.gov (United States)

    National Aeronautics and Space Administration — Advanced Diagnostics and Prognostics Testbed (ADAPT) Project Lead: Scott Poll Subject Fault diagnosis in electrical power systems Description The Advanced...

  9. Thermodynamically consistent Bayesian analysis of closed biochemical reaction systems

    Directory of Open Access Journals (Sweden)

    Goutsias John

    2010-11-01

    Full Text Available Abstract Background Estimating the rate constants of a biochemical reaction system with known stoichiometry from noisy time series measurements of molecular concentrations is an important step for building predictive models of cellular function. Inference techniques currently available in the literature may produce rate constant values that defy necessary constraints imposed by the fundamental laws of thermodynamics. As a result, these techniques may lead to biochemical reaction systems whose concentration dynamics could not possibly occur in nature. Therefore, development of a thermodynamically consistent approach for estimating the rate constants of a biochemical reaction system is highly desirable. Results We introduce a Bayesian analysis approach for computing thermodynamically consistent estimates of the rate constants of a closed biochemical reaction system with known stoichiometry given experimental data. Our method employs an appropriately designed prior probability density function that effectively integrates fundamental biophysical and thermodynamic knowledge into the inference problem. Moreover, it takes into account experimental strategies for collecting informative observations of molecular concentrations through perturbations. The proposed method employs a maximization-expectation-maximization algorithm that provides thermodynamically feasible estimates of the rate constant values and computes appropriate measures of estimation accuracy. We demonstrate various aspects of the proposed method on synthetic data obtained by simulating a subset of a well-known model of the EGF/ERK signaling pathway, and examine its robustness under conditions that violate key assumptions. Software, coded in MATLAB®, which implements all Bayesian analysis techniques discussed in this paper, is available free of charge at http://www.cis.jhu.edu/~goutsias/CSS%20lab/software.html. Conclusions Our approach provides an attractive statistical methodology for

  10. Total synthesis and biochemical evaluation of azumamides A–E and analogs

    DEFF Research Database (Denmark)

    Villadsen, Jesper

    NMR solution structures we hypothesize that the 2-methyl group, found in the natural products, guides the 3-side chain towards the active site. Judging from the biochemical data on the desmethylated series, this directing feature is important for the activity of this type of inhibitors. Furthermore, a......Histone deacetylases (HDAC) are a family of enzymes, which serve as epigenetic modulators. Their biological function has been related to DNA transcription and regulation of various biochemical pathways. Development of isoform selective HDAC inhibitors could be useful for dissecting the individual...... biochemical pathways associated with each HDAC isoform and these compounds could potentially serve as anti-cancer drugs. Macrocyclic peptides and depsipeptides is an interesting class of HDAC inhibitors, which are found in Nature. These compounds are characterized by being highly potent and moderate selective...

  11. Signaling Pathways in Melanogenesis

    Directory of Open Access Journals (Sweden)

    Stacey A. N. D’Mello

    2016-07-01

    Full Text Available Melanocytes are melanin-producing cells found in skin, hair follicles, eyes, inner ear, bones, heart and brain of humans. They arise from pluripotent neural crest cells and differentiate in response to a complex network of interacting regulatory pathways. Melanins are pigment molecules that are endogenously synthesized by melanocytes. The light absorption of melanin in skin and hair leads to photoreceptor shielding, thermoregulation, photoprotection, camouflage and display coloring. Melanins are also powerful cation chelators and may act as free radical sinks. Melanin formation is a product of complex biochemical events that starts from amino acid tyrosine and its metabolite, dopa. The types and amounts of melanin produced by melanocytes are determined genetically and are influenced by a variety of extrinsic and intrinsic factors such as hormonal changes, inflammation, age and exposure to UV light. These stimuli affect the different pathways in melanogenesis. In this review we will discuss the regulatory mechanisms involved in melanogenesis and explain how intrinsic and extrinsic factors regulate melanin production. We will also explain the regulatory roles of different proteins involved in melanogenesis.

  12. Signaling Pathways in Melanogenesis.

    Science.gov (United States)

    D'Mello, Stacey A N; Finlay, Graeme J; Baguley, Bruce C; Askarian-Amiri, Marjan E

    2016-01-01

    Melanocytes are melanin-producing cells found in skin, hair follicles, eyes, inner ear, bones, heart and brain of humans. They arise from pluripotent neural crest cells and differentiate in response to a complex network of interacting regulatory pathways. Melanins are pigment molecules that are endogenously synthesized by melanocytes. The light absorption of melanin in skin and hair leads to photoreceptor shielding, thermoregulation, photoprotection, camouflage and display coloring. Melanins are also powerful cation chelators and may act as free radical sinks. Melanin formation is a product of complex biochemical events that starts from amino acid tyrosine and its metabolite, dopa. The types and amounts of melanin produced by melanocytes are determined genetically and are influenced by a variety of extrinsic and intrinsic factors such as hormonal changes, inflammation, age and exposure to UV light. These stimuli affect the different pathways in melanogenesis. In this review we will discuss the regulatory mechanisms involved in melanogenesis and explain how intrinsic and extrinsic factors regulate melanin production. We will also explain the regulatory roles of different proteins involved in melanogenesis. PMID:27428965

  13. From the proteomic point of view: Integration of adaptive changes to iron deficiency in plants

    Directory of Open Access Journals (Sweden)

    Hans-Jörg Mai

    2016-04-01

    Full Text Available Knowledge about the proteomic adaptations to iron deficiency in plants may contribute to find possible new research targets in order to generate crop plants that are more tolerant to iron deficiency, to increase the iron content or to enhance the bioavailability of iron in food plants. We provide this update on adaptations to iron deficiency from the proteomic standpoint. We have mined the data and compared ten studies on iron deficiency-related proteomic changes in six different Strategy I plant species. We summarize these results and point out common iron deficiency-induced alterations of important biochemical pathways based on the data provided by these publications, deliver explanations on the possible benefits that arise from these adaptations in iron-deficient plants and present a concluding model of these adaptations. Furthermore, we demonstrate the close interdependence of proteins which were found regulated across multiple studies, and we pinpoint proteins with yet unknown function, which may play important roles in iron homeostasis.

  14. Two pathways for cysteine biosynthesis in Leishmania major

    OpenAIRE

    Williams, Roderick A. M.; Westrop, Gareth D.; Coombs, Graham H.

    2009-01-01

    Abstract Genome mining and biochemical analyses have shown that L. major possesses two pathways for cysteine synthesis - the de novo biosynthesis pathway comprising serine acetyltransferase (SAT) and cysteine synthase (CS) and the reverse transsulfuration (RTS) pathway comprising cystathionine ?-synthase (CBS) and cystathionine gamma-lyase (CGL). The L. major CS (LmjCS) is similar to the type A CSs of bacteria and catalyses the synthesis of cysteine using O-acetyserine and sulfide...

  15. Molecular pathways

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine Terra

    2014-01-01

    45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection of...... fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases. Clin Cancer Res; 20(14); 3637-43. ©2014 AACR....

  16. Endothelial cells and cathepsins: Biochemical and biomechanical regulation.

    Science.gov (United States)

    Platt, Manu O; Shockey, W Andrew

    2016-03-01

    Cathepsins are mechanosensitive proteases that are regulated not only by biochemical factors, but are also responsive to biomechanical forces in the cardiovascular system that regulate their expression and activity to participate in cardiovascular tissue remodeling. Their elastinolytic and collagenolytic activity have been implicated in atherosclerosis, abdominal aortic aneurysms, and in heart valve disease, all of which are lined by endothelial cells that are the mechanosensitive monolayer of cells that sense and respond to fluid shear stress as the blood flows across the surfaces of the arteries and valve leaflets. Inflammatory cytokine signaling is integrated with biomechanical signaling pathways by the endothelial cells to transcribe, translate, and activate either the cysteine cathepsins to remodel the tissue or to express their inhibitors to maintain healthy cardiovascular tissue structure. Other cardiovascular diseases should now be included in the study of the cysteine cathepsin activation because of the additional biochemical cues they provide that merges with the already existing hemodynamics driving cardiovascular disease. Sickle cell disease causes a chronic inflammation including elevated TNFα and increased numbers of circulating monocytes that alter the biochemical stimulation while the more viscous red blood cells due to the sickling of hemoglobin alters the hemodynamics and is associated with accelerated elastin remodeling causing pediatric strokes. HIV-mediated cardiovascular disease also occurs earlier in than the broader population and the influence of HIV-proteins and antiretrovirals on endothelial cells must be considered to understand these accelerated mechanisms in order to identify new therapeutic targets for prevention. PMID:26458976

  17. Biochemical Hypermedia: Glucose as a Central Molecule in Metabolism

    Directory of Open Access Journals (Sweden)

    J.K. Sugai

    2008-05-01

    Full Text Available The technologies of information, together with education resources, have been pointed out as a solution to the improvement of teaching approach, but they still claim for programs to fulfill the demands of didactic materials. So, a biochemical software was developed aiming to contribute for the better understanding of the glycolysis. It was prepared with the help of concept maps, ISIS Draw, ADOBE Photoshop and FLASH MX Program. The introduction screen shows a teacher in a theater presenting glucose as a central molecule in the metabolism of animals, plants and many microorganisms. She invites for a better knowledge of glucose through a view of its discovery and its metabolism. A step by step animation process shows the interaction of glucose in aerobic conditions with the enzymes of the glycolytic pathways and its products. An explanation text of each enzyme catalytic process is provided by links. A static pathway is always available through a link. The fates of pyruvate yielding lactic acid and ethanol under anaerobic conditions are shown as well. The overall reactions of gluconeogenesis and the functional significance of this pathway are presented. The experimental treatment involved the presentation of this hypermedia for Nutrition undergraduate students (UFSC as a tool for better comprehension of the theme. The students revealed that it was extremely effective in promoting the understanding of the enzymatic mechanisms involved in glycolysis. This suggests that there is a significant added value in employing the software as an instructional effort to enhance student’s abilities to understand biochemical pathways.

  18. Stoichiometric estimates of the biochemical conversion efficiencies in tsetse metabolism

    Directory of Open Access Journals (Sweden)

    Custer Adrian V

    2005-08-01

    Full Text Available Abstract Background The time varying flows of biomass and energy in tsetse (Glossina can be examined through the construction of a dynamic mass-energy budget specific to these flies but such a budget depends on efficiencies of metabolic conversion which are unknown. These efficiencies of conversion determine the overall yields when food or storage tissue is converted into body tissue or into metabolic energy. A biochemical approach to the estimation of these efficiencies uses stoichiometry and a simplified description of tsetse metabolism to derive estimates of the yields, for a given amount of each substrate, of conversion product, by-products, and exchanged gases. This biochemical approach improves on estimates obtained through calorimetry because the stoichiometric calculations explicitly include the inefficiencies and costs of the reactions of conversion. However, the biochemical approach still overestimates the actual conversion efficiency because the approach ignores all the biological inefficiencies and costs such as the inefficiencies of leaky membranes and the costs of molecular transport, enzyme production, and cell growth. Results This paper presents estimates of the net amounts of ATP, fat, or protein obtained by tsetse from a starting milligram of blood, and provides estimates of the net amounts of ATP formed from the catabolism of a milligram of fat along two separate pathways, one used for resting metabolism and one for flight. These estimates are derived from stoichiometric calculations constructed based on a detailed quantification of the composition of food and body tissue and on a description of the major metabolic pathways in tsetse simplified to single reaction sequences between substrates and products. The estimates include the expected amounts of uric acid formed, oxygen required, and carbon dioxide released during each conversion. The calculated estimates of uric acid egestion and of oxygen use compare favorably to

  19. Biochemical Analysis of Microbial Rhodopsins.

    Science.gov (United States)

    Maresca, Julia A; Keffer, Jessica L; Miller, Kelsey J

    2016-01-01

    Ion-pumping rhodopsins transfer ions across the microbial cell membrane in a light-dependent fashion. As the rate of biochemical characterization of microbial rhodopsins begins to catch up to the rate of microbial rhodopsin identification in environmental and genomic sequence data sets, in vitro analysis of their light-absorbing properties and in vivo analysis of ion pumping will remain critical to characterizing these proteins. As we learn more about the variety of physiological roles performed by microbial rhodopsins in different cell types and environments, observing the localization patterns of the rhodopsins and/or quantifying the number of rhodopsin-bearing cells in natural environments will become more important. Here, we provide protocols for purification of rhodopsin-containing membranes, detection of ion pumping, and observation of functional rhodopsins in laboratory and environmental samples using total internal reflection fluorescence microscopy. © 2016 by John Wiley & Sons, Inc. PMID:27153387

  20. Improved methods for the mathematically controlled comparison of biochemical systems

    Directory of Open Access Journals (Sweden)

    Schwacke John H

    2004-06-01

    Full Text Available Abstract The method of mathematically controlled comparison provides a structured approach for the comparison of alternative biochemical pathways with respect to selected functional effectiveness measures. Under this approach, alternative implementations of a biochemical pathway are modeled mathematically, forced to be equivalent through the application of selected constraints, and compared with respect to selected functional effectiveness measures. While the method has been applied successfully in a variety of studies, we offer recommendations for improvements to the method that (1 relax requirements for definition of constraints sufficient to remove all degrees of freedom in forming the equivalent alternative, (2 facilitate generalization of the results thus avoiding the need to condition those findings on the selected constraints, and (3 provide additional insights into the effect of selected constraints on the functional effectiveness measures. We present improvements to the method and related statistical models, apply the method to a previously conducted comparison of network regulation in the immune system, and compare our results to those previously reported.

  1. Ambiguous Adaptation

    DEFF Research Database (Denmark)

    Møller Larsen, Marcus; Lyngsie, Jacob

    We investigate why some exchange relationships terminate prematurely. We argue that investments in informal governance structures induce premature termination in relationships already governed by formal contracts. The formalized adaptive behavior of formal governance structures and the flexible and...... reciprocal adaptation of informal governance structure create ambiguity in situations of contingencies, which, subsequently, increases the likelihood of premature relationship termination. Using a large sample of exchange relationships in the global service provider industry, we find support for a hypothesis...

  2. Strategic Adaptation

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    2015-01-01

    This article provides an overview of theoretical contributions that have influenced the discourse around strategic adaptation including contingency perspectives, strategic fit reasoning, decision structure, information processing, corporate entrepreneurship, and strategy process. The related...... concepts of strategic renewal, dynamic managerial capabilities, dynamic capabilities, and strategic response capabilities are discussed and contextualized against strategic responsiveness. The insights derived from this article are used to outline the contours of a dynamic process of strategic adaptation...

  3. 甘蓝型冬油菜在西北不同生态区适应性及生理生化反应%Adaptation and physiological and biochemical characteristics of winter rapeseed (Brassica napus L .) in different eco-regions of northwest China

    Institute of Scientific and Technical Information of China (English)

    王月; 董红业; 杨刚; 侯献飞; 刘林波; 种彦容; 孙万仓; 刘自刚; 杨宁宁; 方彦; 曾秀存; 孔德晶; 鲁美宏; 王丽萍

    2015-01-01

    选用50个国内外甘蓝型冬油菜品种,在兰州和天水两个生态区进行大田种植,苗期进行田间植物学形态特征统计,越冬前降温期对叶片过氧化氢酶(CAT )、过氧化物酶(POD )、超氧化物歧化酶(SOD )活性及丙二醛(MDA )、可溶性蛋白(SP )含量以及相应光合参数进行测定,研究它们在不同生态区的抗寒适应性和生理生化反应。结果显示:由天水北移至兰州后,各参试品种越冬率大幅下降,证明天水是我国冬油菜分布北界;部分品种形态特征发生变化,78%的叶色加深,52%的叶柄变短,大多数品种的侧裂叶对数由1~2对增至3~4对;胞间CO2浓度( Ci )和气孔导度( Gs )下降,平均降幅为1.54%和60.53%,蒸腾速率( Tr )显著升高,平均升幅为44.27%,不同品种的光合速率( Pn )变化存在较大差异;同时,CAT、POD、SOD酶活性、MDA和可溶性蛋白含量都有所升高,其中POD酶活性和MDA含量升高幅度较大,分别为82.59%和48.82%。相关性分析表明,两地的越冬率与POD酶活性和可溶性蛋白含量呈极显著正相关,而与MDA含量呈极显著负相关。%In this research ,filed experiments in Tianshui (original planting area ) and Lanzhou (extending northern area ) ,Gansu province ,with 50 winter varieties of B .napus rapes from domestic and international resources ,were con-ducted to study the adaptation and the physiological and biochemical characteristics of the winter Brassica napus .The fol-lowing indexes were included in this analysis including catalase (CAT ) , peroxidase (POD ) , superoxide dismutase (SOD) activities ,malondialdehyde (MDA) ,soluble protein (SP) contents ,and photosynthetic parameters during the pre-winter cold acclimation stage .The results showed that the wintering rate of varieties (lines ) tested in Lanzhou was decreased largely compared to that in Tianshui

  4. Is adaptation. Truly an adaptation? Is adaptation. Truly an adaptation?

    Directory of Open Access Journals (Sweden)

    Thais Flores Nogueira Diniz

    2008-04-01

    Full Text Available The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition, joined with the study of recycling, remaking, and every form of retelling. The film deals with the attempt by the scriptwriter Charles Kaufman, cast by Nicholas Cage, to adapt/translate a non-fictional book to the cinema, but ends up with a kind of film which is by no means what it intended to be: a film of action in the model of Hollywood productions. During the process of creation, Charles and his twin brother, Donald, undergo a series of adventures involving some real persons from the world of film, the author and the protagonist of the book, all of them turning into fictional characters in the film. In the film, adaptation then signifies something different from itstraditional meaning. The article begins by historicizing film adaptation from the arrival of cinema, pointing out the many theoretical approaches under which the process has been seen: from the concept of “the same story told in a different medium” to a comprehensible definition such as “the process through which works can be transformed, forming an intersection of textual surfaces, quotations, conflations and inversions of other texts”. To illustrate this new concept, the article discusses Spike Jonze’s film Adaptation. according to James Naremore’s proposal which considers the study of adaptation as part of a general theory of repetition

  5. Serum Biochemical Phenotypes in the Domestic Dog

    Science.gov (United States)

    Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A.

    2016-01-01

    The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species. PMID:26919479

  6. Biochemical bases of mineral waters genesis

    Directory of Open Access Journals (Sweden)

    D. D. Zhernosekov

    2005-02-01

    Full Text Available This work directs data about mineral water genesis. The accent on balneological sense is done. We suggest the criteria of biochemical processes estimation which take part in mineral water compounds creation. These criteria can be used for illustration of dependence between waters medical properties and biochemical processes of their genesis.

  7. Metabolic Adaptations of White Lupin Roots and Shoots under Phosphorus Deficiency

    Science.gov (United States)

    Müller, Julia; Gödde, Victoria; Niehaus, Karsten; Zörb, Christian

    2015-01-01

    White lupin (Lupinus albus L.) is highly adapted to phosphorus-diminished soils. P-deficient white lupin plants modify their root architecture and physiology to acquire sparingly available soil phosphorus. We employed gas chromatography–mass spectrometry (GC-MS) for metabolic profiling of P-deficient white lupins, to investigate biochemical pathways involved in the P-acquiring strategy. After 14 days of P-deficiency, plants showed reduced levels of fructose, glucose, and sucrose in shoots. Phosphorylated metabolites such as glucose-6-phosphate, fructose-6-phosphate, myo-inositol-phosphate and glycerol-3-phosphate were reduced in both shoots and roots. After 22 days of P-deficiency, no effect on shoot or root sugar metabolite levels was found, but the levels of phosphorylated metabolites were further reduced. Organic acids, amino acids and several shikimate pathway products showed enhanced levels in 22-day-old P-deficient roots and shoots. These results indicate that P-deficient white lupins adapt their carbohydrate partitioning between shoot and root in order to supply their growing root system as an early response to P-deficiency. Organic acids are released into the rhizosphere to mobilize phosphorus from soil particles. A longer period of P-deficiency leads to scavenging of Pi from P-containing metabolites and reduced protein anabolism, but enhanced formation of secondary metabolites. The latter can serve as stress protection molecules or actively acquire phosphorus from the soil. PMID:26635840

  8. Designing pathways

    DEFF Research Database (Denmark)

    Scheuer, John Damm

    2010-01-01

    The theoretical background in this chapter is organizational studies and especially theories about design and design processes in organizations. The concept of design is defined as a particular kind of work aimed at making arrangements in order to change existing situations into desired ones. The...... illustrative case example is the introduction of clinical pathways in a psychiatric department. The contribution to a general core of design research is the development of the concept of design work and a critical discussion of the role of technological rules in design work....

  9. Adaptive test

    DEFF Research Database (Denmark)

    Kjeldsen, Lars Peter; Eriksen, Mette Rose

    2010-01-01

    Artikelen er en evaluering af de adaptive tests, som blev indført i folkeskolen. Artiklen sætter særligt fokus på evaluering i folkeskolen, herunder bidrager den med vejledning til evaluering, evalueringsværktøjer og fagspecifkt evalueringsmateriale.......Artikelen er en evaluering af de adaptive tests, som blev indført i folkeskolen. Artiklen sætter særligt fokus på evaluering i folkeskolen, herunder bidrager den med vejledning til evaluering, evalueringsværktøjer og fagspecifkt evalueringsmateriale....

  10. Biochemical Characterization of 3-Methyl-4-nitrophenol Degradation in Burkholderia sp. Strain SJ98

    Science.gov (United States)

    Min, Jun; Lu, Yang; Hu, Xiaoke; Zhou, Ning-Yi

    2016-01-01

    Several strains have been reported to grow on 3-methyl-4-nitrophenol (3M4NP), the primary breakdown product of the excessively used insecticide fenitrothion. However, the microbial degradation of 3M4NP at molecular and biochemical levels remains unknown. Here, methyl-1,4-benzoquinone (MBQ) and methylhydroquinone (MHQ), rather than catechol proposed previously, were identified as the intermediates before ring cleavage during 3M4NP degradation by Burkholderia sp. strain SJ98. Real-time quantitative PCR analysis indicated that the pnpABA1CDEF cluster involved in para-nitrophenol (PNP) and 2-chloro-4-nitrophenol (2C4NP) catabolism was also likely responsible for 3M4NP degradation in this strain. Purified PNP 4-monooxygenase (PnpA) is able to catalyze the monooxygenation of 3M4NP to MBQ and exhibited an apparent Km value of 20.3 ± 2.54 μM for 3M4NP, and pnpA is absolutely necessary for the catabolism of 3M4NP by gene knock-out and complementation. PnpB, a 1,4-benzoquinone reductase catalyzes the reduction of MBQ to MHQ, and also found to enhance PnpA activity in vitro in the conversion of 3M4NP to MBQ. By sequential catalysis assays, PnpCD, PnpE, and PnpF were likely involved in the lower pathway of 3M4NP catabolism. Although NpcCD, NpcE, and NpcF are able to catalyze the sequential conversion of MHQ in vitro, these enzymes are unlikely involved in 3M4NP catabolism because their coding genes were not upregulated by 3M4NP induction in vivo. These results revealed that the enzymes involved in PNP and 2C4NP catabolism were also responsible for 3M4NP degradation in strain SJ98. This fills a gap in our understanding of the microbial degradation of 3M4NP at molecular and biochemical levels and also provides another example to illustrate the adaptive flexibility in microbial catabolism for structurally similar compounds. PMID:27252697

  11. BIOCHEMICAL SCREENING OF DIABETIC NEPHROPATHY

    Directory of Open Access Journals (Sweden)

    Vivek

    2016-01-01

    Full Text Available Diabetic nephropathy is a clinical syndrome characterized by the following- Persistent albuminuria (>300mg/d or >200μg/min, that is confirmed on at least 2 occasions 3-6 months apart diabetic, progressive decline in the Glomerular Filtration Rate (GFR, elevated arterial blood pressure. The earliest biochemical criteria for the diagnosis of diabetic nephropathy is the presence of micro-albumin in the urine, which if left untreated will eventually lead to End-Stage Renal Disease (ESRD. Micro-albuminuria refers to the excretion of albumin in the urine at a rate that exceeds normal limits. The current study was conducted to establish the prevalence of micro-albuminuria in a sequential sample of diabetic patients attending hospital and OPD Clinic to determine its relationship with known and putative risk factors to identify micro- and normo-albuminuric patients in their sample for subsequent comparison in different age, sex, weight and creatinine clearance of the micro- and normo-albuminuric patients. This cross-sectional analytical study was conducted in one hundred patients at Saraswathi Institute of Medical Sciences, Anwarpur, Hapur, U. P. Patients having diabetes mellitus in different age group ranging from 30 to 70 years were selected. Data was analysed by SPSS software. Micro-albuminuria was observed in 35% in patients with type 2 diabetes mellitus. It was observed that 65% patients were free from any type of albuminuria. Also micro-albuminuria was present in 10% of the patients less than 50 yrs. of age, while 15% of the patients more than 50 yrs. of age were having micro-albuminuria. There was a statistically significant correlation of micro-albuminuria with duration of diabetes. Incidence of micro-albuminuria increases with age as well as increased duration of diabetes mellitus. Our study shows that only 5% patients developed macro-albuminuria. Glycosylated haemoglobin and fasting plasma glucose was significantly raised among all these

  12. Genetic architecture, biochemical underpinnings and ecological impact of floral UV patterning.

    Science.gov (United States)

    Brock, Marcus T; Lucas, Lauren K; Anderson, Nickolas A; Rubin, Matthew J; Markelz, R J Cody; Covington, Michael F; Devisetty, Upendra K; Chapple, Clint; Maloof, Julin N; Weinig, Cynthia

    2016-03-01

    Floral attraction traits can significantly affect pollinator visitation patterns, but adaptive evolution of these traits may be constrained by correlations with other traits. In some cases, molecular pathways contributing to floral attraction are well characterized, offering the opportunity to explore loci potentially underlying variation among individuals. Here, we quantify the range of variation in floral UV patterning (i.e. UV 'bulls-eye nectar guides) among crop and wild accessions of Brassica rapa. We then use experimental crosses to examine the genetic architecture, candidate loci and biochemical underpinnings of this patterning as well as phenotypic manipulations to test the ecological impact. We find qualitative variation in UV patterning between wild (commonly lacking UV patterns) and crop (commonly exhibiting UV patterns) accessions. Similar to the majority of crops, recombinant inbred lines (RILs) derived from an oilseed crop × WI fast-plant® cross exhibit UV patterns, the size of which varies extensively among genotypes. In RILs, we further observe strong statistical-genetic and QTL correlations within petal morphological traits and within measurements of petal UV patterning; however, correlations between morphology and UV patterning are weak or nonsignificant, suggesting that UV patterning is regulated and may evolve independently of overall petal size. HPLC analyses reveal a high concentration of sinapoyl glucose in UV-absorbing petal regions, which, in concert with physical locations of UV-trait QTLs, suggest a regulatory and structural gene as candidates underlying observed quantitative variation. Finally, insects prefer flowers with UV bulls-eye patterns over those that lack patterns, validating the importance of UV patterning in pollen-limited populations of B. rapa. PMID:26800256

  13. Structural and Biochemical Determinants of Ligand Binding by the c-di-GMP Riboswitch

    International Nuclear Information System (INIS)

    The bacterial second messenger c-di-GMP is used in many species to control essential processes that allow the organism to adapt to its environment. The c-di-GMP riboswitch (GEMM) is an important downstream target in this signaling pathway and alters gene expression in response to changing concentrations of c-di-GMP. The riboswitch selectively recognizes its second messenger ligand primarily through contacts with two critical nucleotides. However, these two nucleotides are not the most highly conserved residues within the riboswitch sequence. Instead, nucleotides that stack with c-di-GMP and that form tertiary RNA contacts are the most invariant. Biochemical and structural evidence reveals that the most common natural variants are able to make alternative pairing interactions with both guanine bases of the ligand. Additionally, a high-resolution (2.3 (angstrom)) crystal structure of the native complex reveals that a single metal coordinates the c-di-GMP backbone. Evidence is also provided that after transcription of the first nucleotide on the 3(prime)-side of the P1 helix, which is predicted to be the molecular switch, the aptamer is functional for ligand binding. Although large energetic effects occur when several residues in the RNA are altered, mutations at the most conserved positions, rather than at positions that base pair with c-di-GMP, have the most detrimental effects on binding. Many mutants retain sufficient c-di-GMP affinity for the RNA to remain biologically relevant, which suggests that this motif is quite resilient to mutation.

  14. Pathway Processor: A Tool for Integrating Whole-Genome Expression Results into Metabolic Networks

    OpenAIRE

    Grosu, Paul; Townsend, Jeffrey P.; Hartl, Daniel L.; Cavalieri, Duccio

    2002-01-01

    We have developed a new tool to visualize expression data on metabolic pathways and to evaluate which metabolic pathways are most affected by transcriptional changes in whole-genome expression experiments. Using the Fisher Exact Test, the method scores biochemical pathways according to the probability that as many or more genes in a pathway would be significantly altered in a given experiment by chance alone. This method has been validated on diauxic shift experiments and reproduces well know...

  15. Pathways to Global Markets

    DEFF Research Database (Denmark)

    Smith, David E.; Mitry, Darryl J.

    2011-01-01

    . An important case study is McDonald‘s corporation, the world‘s largest fast food restaurant chain. This company has employed divergent marketing and economic strategies in both domestic and the international markets to become a leader in the global marketplace. An overview of the company‘s background......, organizational structures, mission and vision illustrate McDonald‘s strategic focus on its proactive evolution from a small drive-through operation to a global fast-food giant. The strategy is based on its ability to adapt to the cultural differences of the markets that McDonald‘s serves while preserving its......For marketing and economic researchers, an important aspect of globalization is the degree to which various consumer behavior dimensions and consumption patterns in different parts of the world are becoming similar, and how multinational companies have identified pathways to global success...

  16. An Inductive Logic Programming Approach to Validate Hexose Binding Biochemical Knowledge

    Science.gov (United States)

    Nassif, Houssam; Al-Ali, Hassan; Khuri, Sawsan; Keirouz, Walid; Page, David

    Hexoses are simple sugars that play a key role in many cellular pathways, and in the regulation of development and disease mechanisms. Current protein-sugar computational models are based, at least partially, on prior biochemical findings and knowledge. They incorporate different parts of these findings in predictive black-box models. We investigate the empirical support for biochemical findings by comparing Inductive Logic Programming (ILP) induced rules to actual biochemical results. We mine the Protein Data Bank for a representative data set of hexose binding sites, non-hexose binding sites and surface grooves. We build an ILP model of hexose-binding sites and evaluate our results against several baseline machine learning classifiers. Our method achieves an accuracy similar to that of other black-box classifiers while providing insight into the discriminating process. In addition, it confirms wet-lab findings and reveals a previously unreported Trp-Glu amino acids dependency.

  17. Modular evolution of glutathione peroxidase genes in association with different biochemical properties of their encoded proteins in invertebrate animals

    Directory of Open Access Journals (Sweden)

    Zo Young-Gun

    2009-04-01

    Full Text Available Abstract Background Phospholipid hydroperoxide glutathione peroxidases (PHGPx, the most abundant isoforms of GPx families, interfere directly with hydroperoxidation of lipids. Biochemical properties of these proteins vary along with their donor organisms, which has complicated the phylogenetic classification of diverse PHGPx-like proteins. Despite efforts for comprehensive analyses, the evolutionary aspects of GPx genes in invertebrates remain largely unknown. Results We isolated GPx homologs via in silico screening of genomic and/or expressed sequence tag databases of eukaryotic organisms including protostomian species. Genes showing strong similarity to the mammalian PHGPx genes were commonly found in all genomes examined. GPx3- and GPx7-like genes were additionally detected from nematodes and platyhelminths, respectively. The overall distribution of the PHGPx-like proteins with different biochemical properties was biased across taxa; selenium- and glutathione (GSH-dependent proteins were exclusively detected in platyhelminth and deuterostomian species, whereas selenium-independent and thioredoxin (Trx-dependent enzymes were isolated in the other taxa. In comparison of genomic organization, the GSH-dependent PHGPx genes showed a conserved architectural pattern, while their Trx-dependent counterparts displayed complex exon-intron structures. A codon for the resolving Cys engaged in reductant binding was found to be substituted in a series of genes. Selection pressure to maintain the selenocysteine codon in GSH-dependent genes also appeared to be relaxed during their evolution. With the dichotomized fashion in genomic organizations, a highly polytomic topology of their phylogenetic trees implied that the GPx genes have multiple evolutionary intermediate forms. Conclusion Comparative analysis of invertebrate GPx genes provides informative evidence to support the modular pathways of GPx evolution, which have been accompanied with sporadic

  18. Biochemical genetics of some Indian fishes

    Digital Repository Service at National Institute of Oceanography (India)

    Menezes, M.R.; Qasim, S.Z.

    Studies on biochemical genetics of fishes, using electrophoretic methods, are relatively of recent origin. Earlier serum and eye lens protein were used to identify marine populations. This technique showed that closely related species have...

  19. Physics and Electro-Biochemical Technology

    Directory of Open Access Journals (Sweden)

    Conrad P Pritscher

    2008-12-01

    Full Text Available Not Available Keywords: Biochemical technology, physics Received: 22 October 2008 / Received in revised form: 23 October 2008, Accepted: 24 October 2008 Published online: 07 January 2009

  20. Free energy simulations of important biochemical processes

    OpenAIRE

    Yang LIU; 刘洋

    2013-01-01

    Free energy simulations have been widely employed to compute the thermodynamic properties of many important biochemical processes. In the first part of this dissertation, two important biochemical processes, protonation/deprotonation of acid in solution and solvation of small organic molecules, are investigated using free energy simulations. Accurate computation of the pKa value of a compound in solution is important and challenging. To efficiently simulate the free energy change associat...

  1. Adaptation Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Huq, Saleemul

    2011-11-15

    Efforts to help the world's poor will face crises in coming decades as climate change radically alters conditions. Action Research for Community Adapation in Bangladesh (ARCAB) is an action-research programme on responding to climate change impacts through community-based adaptation. Set in Bangladesh at 20 sites that are vulnerable to floods, droughts, cyclones and sea level rise, ARCAB will follow impacts and adaptation as they evolve over half a century or more. National and international 'research partners', collaborating with ten NGO 'action partners' with global reach, seek knowledge and solutions applicable worldwide. After a year setting up ARCAB, we share lessons on the programme's design and move into our first research cycle.

  2. Hedonic "adaptation"

    Directory of Open Access Journals (Sweden)

    Paul Rozin

    2008-02-01

    Full Text Available People live in a world in which they are surrounded by potential disgust elicitors such as ``used'' chairs, air, silverware, and money as well as excretory activities. People function in this world by ignoring most of these, by active avoidance, reframing, or adaptation. The issue is particularly striking for professions, such as morticians, surgeons, or sanitation workers, in which there is frequent contact with major disgust elicitors. In this study, we study the ``adaptation'' process to dead bodies as disgust elicitors, by measuring specific types of disgust sensitivity in medical students before and after they have spent a few months dissecting a cadaver. Using the Disgust Scale, we find a significant reduction in disgust responses to death and body envelope violation elicitors, but no significant change in any other specific type of disgust. There is a clear reduction in discomfort at touching a cold dead body, but not in touching a human body which is still warm after death.

  3. Adaptive ethnography

    DEFF Research Database (Denmark)

    Berth, Mette

    2005-01-01

    This paper focuses on the use of an adaptive ethnography when studying such phenomena as young people's use of mobile media in a learning perspective. Mobile media such as PDAs and mobile phones have a number of affordances which make them potential tools for learning. However, before we begin to...... design and develop educational materials for mobile media platforms we must first understand everyday use and behaviour with a medium such as a mobile phone. The paper outlines the research design for a PhD project on mobile learning which focuses on mobile phones as a way to bridge the gap between...... formal and informal learning contexts. The paper also proposes several adaptive methodological techniques for studying young people's interaction with mobiles....

  4. RMBNToolbox: random models for biochemical networks

    Directory of Open Access Journals (Sweden)

    Niemi Jari

    2007-05-01

    Full Text Available Abstract Background There is an increasing interest to model biochemical and cell biological networks, as well as to the computational analysis of these models. The development of analysis methodologies and related software is rapid in the field. However, the number of available models is still relatively small and the model sizes remain limited. The lack of kinetic information is usually the limiting factor for the construction of detailed simulation models. Results We present a computational toolbox for generating random biochemical network models which mimic real biochemical networks. The toolbox is called Random Models for Biochemical Networks. The toolbox works in the Matlab environment, and it makes it possible to generate various network structures, stoichiometries, kinetic laws for reactions, and parameters therein. The generation can be based on statistical rules and distributions, and more detailed information of real biochemical networks can be used in situations where it is known. The toolbox can be easily extended. The resulting network models can be exported in the format of Systems Biology Markup Language. Conclusion While more information is accumulating on biochemical networks, random networks can be used as an intermediate step towards their better understanding. Random networks make it possible to study the effects of various network characteristics to the overall behavior of the network. Moreover, the construction of artificial network models provides the ground truth data needed in the validation of various computational methods in the fields of parameter estimation and data analysis.

  5. Biochemical Models for S-Rnase-Based Self-Incompatibility

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hua Hua; Allison Fields; Teh-hui Kao

    2008-01-01

    S-RNase-based self-incompatibility (SI) is a genetically determined self/non-self-recognition process employed by many flowering plant species to prevent inbreeding and promote outcrosses.For the Plantaginaceae,Rosa-ceae and Solanaceae,it is now known that S-RNase and S-Iocu F-box(two multiple allelic genes at the S-locus)determine the female and male specificity,respectively,during SI interactions.However,how allelic products of these two genes interact inside pollen tubes to result in specific growth inhibition of self-pollen tubes remains to be investigated.Here,we review all the previously proposed biochemical models and discuss whether their predictions are consistent with all SI phenomena,including competitive jnteraction where SI breaks down in pollen that carries two different pollen 5-alleles.We also discuss these models in Iight of the recent findings of compartmentalization of S-RNases in both incompatible and compatible pollen tubes.Lastly,we summarize the results from our recent biochemical studies of PiSLF(Petunia inflata SLF)and S-RNase.and present a new model for the biochemical mechanism of SI in the Solanaceae.The tenet of this model is that a PiSLF preferentially interacts with its non-self S-RNases in the cytoplasm of a pollen tube to result in the assembly of an E3-like complex,which then mediates ubiquitination and degradation of non-self S-RNases through the ubiquitin-26S proteasome pathway.This model can explain all SI phenomena and,at the same time,has raised new questions for further study.

  6. Adaptable positioner

    International Nuclear Information System (INIS)

    This paper describes the circuits and programs in assembly language, developed to control the two DC motors that give mobility to a mechanical arm with two degrees of freedom. As a whole, the system is based in a adaptable regulator designed around a 8 bit microprocessor that, starting from a mode of regulation based in the successive approximation method, evolve to another mode through which, only one approximation is sufficient to get the right position of each motor. (Author) 22 fig. 6 ref

  7. Adaptive positioner

    International Nuclear Information System (INIS)

    This paper describes the circuits and programs in assembly language, developed to control the two DC motors that give mobility to a mechanical arm with two degrees of freedom. As a whole, the system is based in a adaptable regulator designed around a 8 bit microprocessor that, starting from a mode of regulation based in the successive approximation method, evolve to another mode through which, only one approximation is sufficient to get the right position of each motor. (Author) 6 refs

  8. Adaptive noise

    OpenAIRE

    Viney, Mark; Reece, Sarah E.

    2013-01-01

    In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise ...

  9. Insights into the organization of biochemical regulatory networks using graph theory analyses.

    Science.gov (United States)

    Ma'ayan, Avi

    2009-02-27

    Graph theory has been a valuable mathematical modeling tool to gain insights into the topological organization of biochemical networks. There are two types of insights that may be obtained by graph theory analyses. The first provides an overview of the global organization of biochemical networks; the second uses prior knowledge to place results from multivariate experiments, such as microarray data sets, in the context of known pathways and networks to infer regulation. Using graph analyses, biochemical networks are found to be scale-free and small-world, indicating that these networks contain hubs, which are proteins that interact with many other molecules. These hubs may interact with many different types of proteins at the same time and location or at different times and locations, resulting in diverse biological responses. Groups of components in networks are organized in recurring patterns termed network motifs such as feedback and feed-forward loops. Graph analysis revealed that negative feedback loops are less common and are present mostly in proximity to the membrane, whereas positive feedback loops are highly nested in an architecture that promotes dynamical stability. Cell signaling networks have multiple pathways from some input receptors and few from others. Such topology is reminiscent of a classification system. Signaling networks display a bow-tie structure indicative of funneling information from extracellular signals and then dispatching information from a few specific central intracellular signaling nexuses. These insights show that graph theory is a valuable tool for gaining an understanding of global regulatory features of biochemical networks. PMID:18940806

  10. Physiological, Biochemical, and Molecular Mechanisms of Heat Stress Tolerance in Plants

    Directory of Open Access Journals (Sweden)

    Masayuki Fujita

    2013-05-01

    Full Text Available High temperature (HT stress is a major environmental stress that limits plant growth, metabolism, and productivity worldwide. Plant growth and development involve numerous biochemical reactions that are sensitive to temperature. Plant responses to HT vary with the degree and duration of HT and the plant type. HT is now a major concern for crop production and approaches for sustaining high yields of crop plants under HT stress are important agricultural goals. Plants possess a number of adaptive, avoidance, or acclimation mechanisms to cope with HT situations. In addition, major tolerance mechanisms that employ ion transporters, proteins, osmoprotectants, antioxidants, and other factors involved in signaling cascades and transcriptional control are activated to offset stress-induced biochemical and physiological alterations. Plant survival under HT stress depends on the ability to perceive the HT stimulus, generate and transmit the signal, and initiate appropriate physiological and biochemical changes. HT-induced gene expression and metabolite synthesis also substantially improve tolerance. The physiological and biochemical responses to heat stress are active research areas, and the molecular approaches are being adopted for developing HT tolerance in plants. This article reviews the recent findings on responses, adaptation, and tolerance to HT at the cellular, organellar, and whole plant levels and describes various approaches being taken to enhance thermotolerance in plants.

  11. Molecular mechanisms underlying phosphate sensing, signaling, and adaptation in plants

    Institute of Scientific and Technical Information of China (English)

    Zhaoliang Zhang; Hong Liao; William J. Lucas

    2014-01-01

    As an essential plant macronutrient, the low availability of phosphorus (P) in most soils imposes serious limitation on crop production. Plants have evolved complex responsive and adaptive mechanisms for acquisition, remobiliza-tion and recycling of phosphate (Pi) to maintain P homeostasis. Spatio-temporal molecular, physiological, and biochemical Pi deficiency responses developed by plants are the consequence of local and systemic sensing and signaling pathways. Pi deficiency is sensed local y by the root system where hormones serve as important signaling components in terms of develop-mental reprogramming, leading to changes in root system architecture. Root-to-shoot and shoot-to-root signals, delivered through the xylem and phloem, respectively, involving Pi itself, hormones, miRNAs, mRNAs, and sucrose, serve to coordinate Pi deficiency responses at the whole-plant level. A combination of chromatin remodeling, transcriptional and posttranslational events contribute to global y regulating a wide range of Pi deficiency responses. In this review, recent advances are evaluated in terms of progress toward developing a comprehen-sive understanding of the molecular events underlying control over P homeostasis. Application of this knowledge, in terms of developing crop plants having enhanced attributes for P use efficiency, is discussed from the perspective of agricultural sustainability in the face of diminishing global P supplies.

  12. Lysosome: regulator of lipid degradation pathways

    OpenAIRE

    Settembre, Carmine; Ballabio, Andrea

    2014-01-01

    Autophagy is a catabolic pathway that has a fundamental role in the adaptation to fasting and primarily relies on the activity of the endolysosomal system, to which the autophagosome targets substrates for degradation. Recent studies have revealed that the lysosomal–autophagic pathway plays an important part in the early steps of lipid degradation. In this review, we discuss the transcriptional mechanisms underlying co-regulation between lysosome, autophagy, and other steps of lipid catabolis...

  13. Final Technical Report "Multiscale Simulation Algorithms for Biochemical Systems"

    Energy Technology Data Exchange (ETDEWEB)

    Petzold, Linda R.

    2012-10-25

    Biochemical systems are inherently multiscale and stochastic. In microscopic systems formed by living cells, the small numbers of reactant molecules can result in dynamical behavior that is discrete and stochastic rather than continuous and deterministic. An analysis tool that respects these dynamical characteristics is the stochastic simulation algorithm (SSA, Gillespie, 1976), a numerical simulation procedure that is essentially exact for chemical systems that are spatially homogeneous or well stirred. Despite recent improvements, as a procedure that simulates every reaction event, the SSA is necessarily inefficient for most realistic problems. There are two main reasons for this, both arising from the multiscale nature of the underlying problem: (1) stiffness, i.e. the presence of multiple timescales, the fastest of which are stable; and (2) the need to include in the simulation both species that are present in relatively small quantities and should be modeled by a discrete stochastic process, and species that are present in larger quantities and are more efficiently modeled by a deterministic differential equation (or at some scale in between). This project has focused on the development of fast and adaptive algorithms, and the fun- damental theory upon which they must be based, for the multiscale simulation of biochemical systems. Areas addressed by this project include: (1) Theoretical and practical foundations for ac- celerated discrete stochastic simulation (tau-leaping); (2) Dealing with stiffness (fast reactions) in an efficient and well-justified manner in discrete stochastic simulation; (3) Development of adaptive multiscale algorithms for spatially homogeneous discrete stochastic simulation; (4) Development of high-performance SSA algorithms.

  14. Exploring the Genetic Basis of Adaptation to High Elevations in Reptiles: A Comparative Transcriptome Analysis of Two Toad-Headed Agamas (Genus Phrynocephalus)

    Science.gov (United States)

    Yang, Weizhao; Qi, Yin; Fu, Jinzhong

    2014-01-01

    High elevation adaptation offers an excellent study system to understand the genetic basis of adaptive evolution. We acquired transcriptome sequences of two closely related lizards, Phrynocephalus przewalskii from low elevations and P. vlangalii from high elevations. Within a phylogenetic framework, we compared their genomic data along with green anole, chicken and Chinese softshell turtle, and identified candidate genes and functional categories that are potentially linked to adaptation to high elevation environments. More than 100 million sequence reads were generated for each species via Illumina sequencing. A de novo assembly produced 70,919 and 62,118 transcripts for P. przewalskii and P. vlangalii, respectively. Based on a well-established reptile phylogeny, we detected 143 positively selected genes (PSGs) along the P. vlangalii lineage from the 7,012 putative orthologs using a branch-site model. Furthermore, ten GO categories and one KEGG pathway that are over-represented by PSGs were recognized. In addition, 58 GO categories were revealed to have elevated evolutionary rates along the P. vlangalii lineage relative to P. przewalskii. These functional analyses further filter out PSGs that are most likely involved in the adaptation process to high elevations. Among them, ADAM17, MD, and HSP90B1 likely contributed to response to hypoxia, and POLK likely contributed to DNA repair. Many other candidate genes involved in gene expression and metabolism were also identified. Genome-wide scan for candidate genes may serve as the first step to explore the genetic basis of high elevation adaptation. Detailed comparative study and functional verification are needed to solidify any conclusions. High elevation adaptation requires coordinated changes in multiple genes that involve various physiological and biochemical pathways; we hope that our genetic studies will provide useful directions for future physiological or molecular studies in reptiles as well as other

  15. Dysregulation of the mevalonate pathway promotes transformation

    Science.gov (United States)

    Clendening, James W.; Pandyra, Aleks; Boutros, Paul C.; Ghamrasni, Samah El; Khosravi, Fereshteh; Trentin, Grace A.; Martirosyan, Anna; Hakem, Anne; Hakem, Razqallah; Jurisica, Igor; Penn, Linda Z.

    2010-01-01

    The importance of cancer metabolism has been appreciated for many years, but the intricacies of how metabolic pathways interconnect with oncogenic signaling are not fully understood. With a clear understanding of how metabolism contributes to tumorigenesis, we will be better able to integrate the targeting of these fundamental biochemical pathways into patient care. The mevalonate (MVA) pathway, paced by its rate-limiting enzyme, hydroxymethylglutaryl coenzyme A reductase (HMGCR), is required for the generation of several fundamental end-products including cholesterol and isoprenoids. Despite years of extensive research from the perspective of cardiovascular disease, the contribution of a dysregulated MVA pathway to human cancer remains largely unexplored. We address this issue directly by showing that dysregulation of the MVA pathway, achieved by ectopic expression of either full-length HMGCR or its novel splice variant, promotes transformation. Ectopic HMGCR accentuates growth of transformed and nontransformed cells under anchorage-independent conditions or as xenografts in immunocompromised mice and, importantly, cooperates with RAS to drive the transformation of primary mouse embryonic fibroblasts cells. We further explore whether the MVA pathway may play a role in the etiology of human cancers and show that high mRNA levels of HMGCR and additional MVA pathway genes correlate with poor prognosis in a meta-analysis of six microarray datasets of primary breast cancer. Taken together, our results suggest that HMGCR is a candidate metabolic oncogene and provide a molecular rationale for further exploring the statin family of HMGCR inhibitors as anticancer agents. PMID:20696928

  16. A systems biology approach identifies the biochemical mechanisms regulating monoterpenoid essential oil composition in peppermint

    OpenAIRE

    Rios-Estepa, Rigoberto; Turner, Glenn W.; Lee, James M.; Croteau, Rodney B.; Lange, B. Markus

    2008-01-01

    The integration of mathematical modeling and experimental testing is emerging as a powerful approach for improving our understanding of the regulation of metabolic pathways. In this study, we report on the development of a kinetic mathematical model that accurately simulates the developmental patterns of monoterpenoid essential oil accumulation in peppermint (Mentha × piperita). This model was then used to evaluate the biochemical processes underlying experimentally determined changes in the ...

  17. Metabolic rates and biochemical compositions of Apostichopus japonicus (Selenka) tissue during periods of inactivity

    Institute of Scientific and Technical Information of China (English)

    包杰; 董双林; 田相利; 王芳; 高勤峰; 董云伟

    2010-01-01

    Estivation, hibernation, and starvation are indispensable inactive states of sea cucumbers Apostichopus japonicus in nature and in culture ponds. Generally, temperature is the principal factor that induces estivation or hibernation in the sea cucumber. The present study provided insight into the physiological adaptations of A. japonicus during the three types of inactivity (hibernation, estivation, and starvation) by measuring the oxygen consumption rates (Vo2) and biochemical compositions under laboratory ...

  18. Physiological, Biochemical, and Molecular Mechanisms of Heat Stress Tolerance in Plants

    OpenAIRE

    Masayuki Fujita; Md. Mahabub Alam; Rajib Roychowdhury; Mirza Hasanuzzaman; Kamrun Nahar

    2013-01-01

    High temperature (HT) stress is a major environmental stress that limits plant growth, metabolism, and productivity worldwide. Plant growth and development involve numerous biochemical reactions that are sensitive to temperature. Plant responses to HT vary with the degree and duration of HT and the plant type. HT is now a major concern for crop production and approaches for sustaining high yields of crop plants under HT stress are important agricultural goals. Plants possess a number of adapt...

  19. Amphibians biochemical indices from reservoirs of different levels of waste discharge

    Directory of Open Access Journals (Sweden)

    I. N. Zalipuha

    2009-04-01

    Full Text Available Influence of uranium mining and processing wastes on the metabolism of common amphibian species of the Dnieper region – the marsh frog (Pelophylax ridibundus – from differently contaminated reservoirs. The change of protein, lipids and carbohydrates in organs and tissues of frogs with ageing and under influence of the pollution. Considerable increase of energy consumption at the expense of lipids and carbohydrates is one of biochemical adaptations. It promotes partial resistance of amphibians to the influence of uranium mining wastes.

  20. On Robustness Analysis of Stochastic Biochemical Systems by Probabilistic Model Checking

    OpenAIRE

    Brim, Lubos; Ceska, Milan; Drazan, Sven; Safranek, David

    2013-01-01

    This report proposes a novel framework for a rigorous robustness analysis of stochastic biochemical systems. The technique is based on probabilistic model checking. We adapt the general definition of robustness introduced by Kitano to the class of stochastic systems modelled as continuous time Markov Chains in order to extensively analyse and compare robustness of biological models with uncertain parameters. The framework utilises novel computational methods that enable to effectively evaluat...

  1. From the Sugar Platform to biofuels and biochemicals : Final report for the European Commission Directorate-General Energy

    NARCIS (Netherlands)

    Taylor, R.; Nattrass, L.; Alberts, G.; Robson, P.; Chudziak, C.; Bauen, A.; Libelli, I.M.; Lotti, G.; Prussi, M.; Nistri, R.; Chiaramonti, D.; lópez-Contreras, A.M.; Bos, H.H.; Eggink, G.; Springer, J.; Bakker, R.; Ree, van R.

    2015-01-01

    Numerous potential pathways to biofuels and biochemicals exist via the sugar platform1. This study uses literature surveys, market data and stakeholder input to provide a comprehensive evidence base for policymakers and industry – identifying the key benefits and development needs for the sugar plat

  2. 40 CFR 158.2010 - Biochemical pesticides data requirements.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Biochemical pesticides data...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2010 Biochemical pesticides... required to support registration of biochemical pesticides. Sections 158.2080 through 158.2084 identify...

  3. 40 CFR 158.2000 - Biochemical pesticides definition and applicability.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Biochemical pesticides definition and...) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2000 Biochemical pesticides definition and applicability. This subpart applies to all biochemical pesticides as defined in paragraphs...

  4. Evidence of additional excitation energy transfer pathways in the phycobiliprotein antenna system of Acaryochloris marina.

    Science.gov (United States)

    Nganou, A C; David, L; Adir, N; Pouhe, D; Deen, M J; Mkandawire, M

    2015-02-01

    To improve the energy conversion efficiency of solar organic cells, the clue may lie in the development of devices inspired by an efficient light harvesting mechanism of some aquatic photosynthetic microorganisms that are adapted to low light intensity. Consequently, we investigated the pathways of excitation energy transfer (EET) from successive light harvesting pigments to the low energy level inside the phycobiliprotein antenna system of Acaryochloris marina, a cyanobacterium, using a time resolved absorption difference spectroscopy with a resolution time of 200 fs. The objective was to understand the actual biochemical process and pathways that determine the EET mechanism. Anisotropy of the EET pathway was calculated from the absorption change trace in order to determine the contribution of excitonic coupling. The results reveal a new electron energy relaxation pathway of 14 ps inside the phycocyanin component, which runs from phycocyanin to the terminal emitter. The bleaching of the 660 nm band suggests a broader absorption of the terminal emitter between 660 nm and 675 nm. Further, there are trimer depolarization kinetics of 450 fs and 500 fs in high and low ionic strength, respectively, which arise from the relaxation of the β84 and α84 in adjacent monomers of phycocyanin. Under conditions of low ionic strength buffer solution, the evolution of the kinetic amplitude during the depolarization of the trimer is suggestive of trimer conservation within the phycocyanin hexamer. The anisotropy values were 0.38 and 0.40 in high and in low ionic strength, respectively, indicating that there is no excitonic delocalization in the high energy level of phycocyanin hexamers. PMID:25470281

  5. Regulation of drug-induced liver injury by signal transduction pathways: critical role of mitochondria

    OpenAIRE

    Han, Derick; Dara, Lily; Win, Sanda; Than, Tin Aung; Yuan, Liyun; Abbasi, Sadeea Q; Liu, Zhang-Xu; Kaplowitz, Neil

    2013-01-01

    Drugs that cause liver injury often “stress” mitochondria and activate signal transduction pathways important in determining cell survival or death. In most cases, hepatocytes adapt to the drug-induced stress by activating adaptive signaling pathways, such as mitochondrial adaptive responses and erythroid 2-related factor 2 (Nrf-2), a transcription factor that upregulates antioxidant defenses. Due to adaptation, drugs alone rarely cause liver injury, with acetaminophen being the notable excep...

  6. Modeling and analysis of early events in T-lymphocyte antigen-activated intracellular-signaling pathways

    Science.gov (United States)

    Zheng, Yanan; Balakrishnan, Venkataramanan; Buzzard, Greg; Geahlen, Robert; Harrison, Marietta; Rundell, Ann

    2005-12-01

    The T-cell antigen-activated signaling pathway is a highly regulated intracellular biochemical system that is crucial for initiating an appropriate adaptive immune response. To improve the understanding of the complex regulatory mechanisms controlling the early events in T-cell signaling, a detailed mathematical model was developed that utilizes ordinary differential equations to describe chemical reactions of the signaling pathway. The model parameter values were constrained by experimental data on the activation of a specific signaling intermediate and indicated an initial rapid cascade of phosphorylation events followed by a comparatively slow signal downregulation. Nonlinear analysis of the model suggested that thresholding and bistability occur as a result of the embedded positive and negative feedback loops within the model. These nonlinear system properties may enhance the T-cell receptor specificity and provide sub-threshold noise filtering with switch-like behavior to ensure proper cell response. Additional analysis using a reduced second-order model led to further understanding of the observed system behavior. Moreover, the interactions between the positive and negative feedback loops enabled the model to exhibit, among a variety of other feasible dynamics, a sustained oscillation that corresponds to a stable limit cycle in the two-dimensional phase plane. Quantitative analysis in this paper has helped identify potential regulatory mechanisms in the early T-cell signaling events. This integrated approach provides a framework to quantify and discover the ensemble of interconnected T-cell antigen-activated signaling pathways from limited experimental data.

  7. Carbon Assimilation Pathways, Water Relationships and Plant Ecology.

    Science.gov (United States)

    Etherington, John R.

    1988-01-01

    Discusses between-species variation in adaptation of the photosynthetic mechanism to cope with wide fluctuations of environmental water regime. Describes models for water conservation in plants and the role of photorespiration in the evolution of the different pathways. (CW)

  8. Adaptive management

    DEFF Research Database (Denmark)

    Rist, Lucy; Campbell, Bruce Morgan; Frost, Peter

    2013-01-01

    in scientific articles, policy documents and management plans, but both understanding and application of the concept is mixed. This paper reviews recent literature from conservation and natural resource management journals to assess diversity in how the term is used, highlight ambiguities and consider how......Adaptive management (AM) emerged in the literature in the mid-1970s in response both to a realization of the extent of uncertainty involved in management, and a frustration with attempts to use modelling to integrate knowledge and make predictions. The term has since become increasingly widely used...... the concept might be further assessed. AM is currently being used to describe many different management contexts, scales and locations. Few authors define the term explicitly or describe how it offers a means to improve management outcomes in their specific management context. Many do not adhere to the idea...

  9. Protein-protein interactions in the β-oxidation part of the phenylacetate utilization pathway: crystal structure of the PaaF-PaaG hydratase-isomerase complex.

    Science.gov (United States)

    Grishin, Andrey M; Ajamian, Eunice; Zhang, Linhua; Rouiller, Isabelle; Bostina, Mihnea; Cygler, Miroslaw

    2012-11-01

    Microbial anaerobic and so-called hybrid pathways for degradation of aromatic compounds contain β-oxidation-like steps. These reactions convert the product of the opening of the aromatic ring to common metabolites. The hybrid phenylacetate degradation pathway is encoded in Escherichia coli by the paa operon containing genes for 10 enzymes. Previously, we have analyzed protein-protein interactions among the enzymes catalyzing the initial oxidation steps in the paa pathway (Grishin, A. M., Ajamian, E., Tao, L., Zhang, L., Menard, R., and Cygler, M. (2011) J. Biol. Chem. 286, 10735-10743). Here we report characterization of interactions between the remaining enzymes of this pathway and show another stable complex, PaaFG, an enoyl-CoA hydratase and enoyl-Coa isomerase, both belonging to the crotonase superfamily. These steps are biochemically similar to the well studied fatty acid β-oxidation, which can be catalyzed by individual monofunctional enzymes, multifunctional enzymes comprising several domains, or enzymatic complexes such as the bacterial fatty acid β-oxidation complex. We have determined the structure of the PaaFG complex and determined that although individually PaaF and PaaG are similar to enzymes from the fatty acid β-oxidation pathway, the structure of the complex is dissimilar from bacterial fatty acid β-oxidation complexes. The PaaFG complex has a four-layered structure composed of homotrimeric discs of PaaF and PaaG. The active sites of PaaF and PaaG are adapted to accept the intermediary components of the Paa pathway, different from those of the fatty acid β-oxidation. The association of PaaF and PaaG into a stable complex might serve to speed up the steps of the pathway following the conversion of phenylacetyl-CoA to a toxic and unstable epoxide-CoA by PaaABCE monooxygenase. PMID:22961985

  10. Stochastic effects in adaptive reconstruction of body damage: implied the creativity of natural selection.

    Science.gov (United States)

    Xiao, Bo; Cui, Li-Qiang; Chen, Tian-Ming; Lian, Bin

    2015-11-01

    After an injury occurs, mechanical/biochemical loads on muscles influence the composition and structure of recovering muscles; this effect likely occurs in other tissues, cells and biological molecules as well owing to the similarity, interassociation and interaction among biochemical reactions and molecules. The 'damage and reconstruction' model provides an explanation for how an ideal cytoarchitecture is created by reducing components not suitable for bearing loads; in this model, adaptive changes are induced by promoting the stochasticity of biochemical reactions. Biochemical and mechanical loads can direct the stochasticity of biochemical reactions, which can in turn induce cellular changes. Thus, mechanical and biochemical loads, under natural selection pressure, modify the direction of cell- and tissue-level changes and guide the formation of new structures and traits, thereby influencing microevolution. In summary, the 'damage and reconstruction' model accounts for the role of natural selection in the formation of new organisms, helps explain punctuated equilibrium, and illustrates how macroevolution arises from microevolution. PMID:26153081

  11. Predictive biochemical assays for late radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, P.; Finkelstein, J.N.; Siemann, D.W.; Shapiro, D.L.; Van Houtte, P.; Penney, D.P.

    1986-04-01

    Surfactant precursors or other products of Type II pneumocytes have the potential to be the first biochemical marker for late radiation effects. This is particularly clinically important in the combined modality era because of the frequent occurrence of pneumonitis and pulmonary fibrosis secondary to radiation or chemotherapy. Accordingly, correlative studies have been pursued with the Type II pneumocyte as a beginning point to understand the complex pathophysiology of radiation pneumonitis and fibrosis. From our ultrastructural and biochemical studies, it is evident that Type II pneumocytes are an early target of radiation and the release of surfactant into the alveolus shortly after exposure persists for days and weeks. Through the use of lavaging techniques, alveolar surfactant has been elevated after pulmonary irradiation. In three murine strains and in the rabbit, there is a strong correlation with surfactant release at 7 and/or 28 days in vivo with later lethality in months. In vitro studies using cultures of type II pneumocytes also demonstrate dose response and tolerance factors that are comparable to the in vivo small and large animal diagnostic models. New markers are being developed to serve as a predictive index for later lethal pneumonopathies. With the development of these techniques, the search for early biochemical markers in man has been undertaken. Through the use of biochemical, histological, and ultrastructural techniques, a causal relationship between radiation effects on type II pneumocytes, pulmonary cells, endothelial cells of blood vessels, and their roles in the production of pneumonitis and fibrosis will evolve.

  12. Biochemical Applications in the Analytical Chemistry Lab

    Science.gov (United States)

    Strong, Cynthia; Ruttencutter, Jeffrey

    2004-01-01

    An HPLC and a UV-visible spectrophotometer are identified as instruments that helps to incorporate more biologically-relevant experiments into the course, in order to increase the students understanding of selected biochemistry topics and enhances their ability to apply an analytical approach to biochemical problems. The experiment teaches…

  13. Survey of Biochemical Education in Japanese Universities.

    Science.gov (United States)

    Kagawa, Yasuo

    1995-01-01

    Reports findings of questionnaires sent to faculty in charge of biochemical education in medical schools and other programs from dentistry to agriculture. Total class hours have declined since 1984. New trends include bioethics and computer-assisted learning. Tables show trends in lecture hours, lecture content, laboratory hours, core subject…

  14. Predictive biochemical assays for late radiation effects

    International Nuclear Information System (INIS)

    Surfactant precursors or other products of Type II pneumocytes have the potential to be the first biochemical marker for late radiation effects. This is particularly clinically important in the combined modality era because of the frequent occurrence of pneumonitis and pulmonary fibrosis secondary to radiation or chemotherapy. Accordingly, correlative studies have been pursued with the Type II pneumocyte as a beginning point to understand the complex pathophysiology of radiation pneumonitis and fibrosis. From our ultrastructural and biochemical studies, it is evident that Type II pneumocytes are an early target of radiation and the release of surfactant into the alveolus shortly after exposure persists for days and weeks. Through the use of lavaging techniques, alveolar surfactant has been elevated after pulmonary irradiation. In three murine strains and in the rabbit, there is a strong correlation with surfactant release at 7 and/or 28 days in vivo with later lethality in months. In vitro studies using cultures of type II pneumocytes also demonstrate dose response and tolerance factors that are comparable to the in vivo small and large animal diagnostic models. New markers are being developed to serve as a predictive index for later lethal pneumonopathies. With the development of these techniques, the search for early biochemical markers in man has been undertaken. Through the use of biochemical, histological, and ultrastructural techniques, a causal relationship between radiation effects on type II pneumocytes, pulmonary cells, endothelial cells of blood vessels, and their roles in the production of pneumonitis and fibrosis will evolve

  15. 2009 Biochemical Conversion Platform Review Report

    Energy Technology Data Exchange (ETDEWEB)

    Ferrell, John [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States)

    2009-12-01

    This document summarizes the recommendations and evaluations provided by an independent external panel of experts at the U.S. Department of Energy Biomass Program’s Biochemical Conversion platform review meeting, held on April 14-16, 2009, at the Sheraton Denver Downtown, Denver, Colorado.

  16. Biochemical Thermodynamics under near Physiological Conditions

    Science.gov (United States)

    Mendez, Eduardo

    2008-01-01

    The recommendations for nomenclature and tables in Biochemical Thermodynamics approved by IUBMB and IUPAC in 1994 can be easily introduced after the chemical thermodynamic formalism. Substitution of the usual standard thermodynamic properties by the transformed ones in the thermodynamic equations, and the use of appropriate thermodynamic tables…

  17. Combining Flux Balance and Energy Balance Analysis for Large-Scale Metabolic Network: Biochemical Circuit Theory for Analysis of Large-Scale Metabolic Networks

    Science.gov (United States)

    Beard, Daniel A.; Liang, Shou-Dan; Qian, Hong; Biegel, Bryan (Technical Monitor)

    2001-01-01

    Predicting behavior of large-scale biochemical metabolic networks represents one of the greatest challenges of bioinformatics and computational biology. Approaches, such as flux balance analysis (FBA), that account for the known stoichiometry of the reaction network while avoiding implementation of detailed reaction kinetics are perhaps the most promising tools for the analysis of large complex networks. As a step towards building a complete theory of biochemical circuit analysis, we introduce energy balance analysis (EBA), which compliments the FBA approach by introducing fundamental constraints based on the first and second laws of thermodynamics. Fluxes obtained with EBA are thermodynamically feasible and provide valuable insight into the activation and suppression of biochemical pathways.

  18. The Leaf Epidermome of Catharanthus roseus Reveals Its Biochemical Specialization[W][OA

    Science.gov (United States)

    Murata, Jun; Roepke, Jonathon; Gordon, Heather; De Luca, Vincenzo

    2008-01-01

    Catharanthus roseus is the sole commercial source of the monoterpenoid indole alkaloids (MIAs), vindoline and catharanthine, components of the commercially important anticancer dimers, vinblastine and vincristine. Carborundum abrasion technique was used to extract leaf epidermis–enriched mRNA, thus sampling the epidermome, or complement, of proteins expressed in the leaf epidermis. Random sequencing of the derived cDNA library established 3655 unique ESTs, composed of 1142 clusters and 2513 singletons. Virtually all known MIA pathway genes were found in this remarkable set of ESTs, while only four known genes were found in the publicly available Catharanthus EST data set. Several novel MIA pathway candidate genes were identified, as demonstrated by the cloning and functional characterization of loganic acid O-methyltransferase involved in secologanin biosynthesis. The pathways for triterpene biosynthesis were also identified, and metabolite analysis showed that oleanane-type triterpenes were localized exclusively to the cuticular wax layer. The pathways for flavonoid and very-long-chain fatty acid biosynthesis were also located in this cell type. The results illuminate the biochemical specialization of Catharanthus leaf epidermis for the production of multiple classes of metabolites. The value and versatility of this EST data set for biochemical and biological analysis of leaf epidermal cells is also discussed. PMID:18326827

  19. Construction and molecular analysis of genetically modified C 3 plants expressing a glycolate oxidizing pathway inside the chloroplast

    OpenAIRE

    Kebeish, Rashad Mohamed Ahmed

    2006-01-01

    Metabolism of glycolate via the photorespiratory pathway in C3 plants consumes not only ATP and reducing equivalents but results also in approximately 25% loss of the carbon from glycolate. In the present study, a novel biochemical pathway for the metabolism of glycolate was established in the chloroplast of Arabidopsis thaliana plants. The new pathway aims to increase the CO2 concentration in the vicinity of Rubisco thereby suppressing photorespiration in C3 plants. The pathway is derived fr...

  20. Genome Sequencing Reveals Unique Mutations in Characteristic Metabolic Pathways and the Transfer of Virulence Genes between V. mimicus and V. cholerae

    Science.gov (United States)

    Zhou, Yanyan; Zhang, Qiuxiang; Zhang, Fanfei; Du, Pengcheng; Wang, Shujing; Chen, Chen; Kan, Biao

    2011-01-01

    Vibrio mimicus, the species most similar to V. cholerae, is a microbe present in the natural environmental and sometimes causes diarrhea and internal infections in humans. It shows similar phenotypes to V. cholerae but differs in some biochemical characteristics. The molecular mechanisms underlying the differences in biochemical metabolism between V. mimicus and V. cholerae are currently unclear. Several V. mimicus isolates have been found that carry cholera toxin genes (ctxAB) and cause cholera-like diarrhea in humans. Here, the genome of the V. mimicus isolate SX-4, which carries an intact CTX element, was sequenced and annotated. Analysis of its genome, together with those of other Vibrio species, revealed extensive differences within the Vibrionaceae. Common mutations in gene clusters involved in three biochemical metabolism pathways that are used for discrimination between V. mimicus and V. cholerae were found in V. mimicus strains. We also constructed detailed genomic structures and evolution maps for the general types of genomic drift associated with pathogenic characters in polysaccharides, CTX elements and toxin co-regulated pilus (TCP) gene clusters. Overall, the whole-genome sequencing of the V. mimicus strain carrying the cholera toxin gene provides detailed information for understanding genomic differences among Vibrio spp. V. mimicus has a large number of diverse gene and nucleotide differences from its nearest neighbor, V. cholerae. The observed mutations in the characteristic metabolism pathways may indicate different adaptations to different niches for these species and may be caused by ancient events in evolution before the divergence of V. cholerae and V. mimicus. Horizontal transfers of virulence-related genes from an uncommon clone of V. cholerae, rather than the seventh pandemic strains, have generated the pathogenic V. mimicus strain carrying cholera toxin genes. PMID:21731695

  1. Genome sequencing reveals unique mutations in characteristic metabolic pathways and the transfer of virulence genes between V. mimicus and V. cholerae.

    Directory of Open Access Journals (Sweden)

    Duochun Wang

    Full Text Available Vibrio mimicus, the species most similar to V. cholerae, is a microbe present in the natural environmental and sometimes causes diarrhea and internal infections in humans. It shows similar phenotypes to V. cholerae but differs in some biochemical characteristics. The molecular mechanisms underlying the differences in biochemical metabolism between V. mimicus and V. cholerae are currently unclear. Several V. mimicus isolates have been found that carry cholera toxin genes (ctxAB and cause cholera-like diarrhea in humans. Here, the genome of the V. mimicus isolate SX-4, which carries an intact CTX element, was sequenced and annotated. Analysis of its genome, together with those of other Vibrio species, revealed extensive differences within the Vibrionaceae. Common mutations in gene clusters involved in three biochemical metabolism pathways that are used for discrimination between V. mimicus and V. cholerae were found in V. mimicus strains. We also constructed detailed genomic structures and evolution maps for the general types of genomic drift associated with pathogenic characters in polysaccharides, CTX elements and toxin co-regulated pilus (TCP gene clusters. Overall, the whole-genome sequencing of the V. mimicus strain carrying the cholera toxin gene provides detailed information for understanding genomic differences among Vibrio spp. V. mimicus has a large number of diverse gene and nucleotide differences from its nearest neighbor, V. cholerae. The observed mutations in the characteristic metabolism pathways may indicate different adaptations to different niches for these species and may be caused by ancient events in evolution before the divergence of V. cholerae and V. mimicus. Horizontal transfers of virulence-related genes from an uncommon clone of V. cholerae, rather than the seventh pandemic strains, have generated the pathogenic V. mimicus strain carrying cholera toxin genes.

  2. Função bioquímica da via daslipoxigenases em plantas de soja submetidas ao ataque de mosca-branca (Bemisia argentifolii Biochemical function of lipoxygenases pathway of soybean plants submitted to the attack of whitefly (Bemisia argentifolii

    Directory of Open Access Journals (Sweden)

    Francine Barbosa Silva

    2004-04-01

    Full Text Available Neste trabalho, avaliou-se a capacidade da planta de soja de uma cultivar comercial, IAC-100, e de um genótipo IAC-100 TN que apresenta ausência de lipoxigenases nas sementes de responderem ao ataque de mosca-branca (Bemisia argentifolii pela via das Lipoxigenases. Foi realizada a caracterização cinética do pool de lipoxigenases. Os valores de KMapp decresceram nas plantas atacadas, sugerindo uma alteração no pool de lipoxigenases foliares. Valores similares de KMapp, entre os genótipos, indicam que a remoção de lipoxigenases de sementes não interferiram na expressão de lipoxigenases em folhas. Ocorreu aumento significativo na produção de inibidores de proteases. Com esses resultados, infere-se que a produção de inibidores de proteases está envolvida no mecanismo de defesa de soja ao ataque da mosca-branca.This work evaluated the capacity of the soybean plant, from a commercial cultivar IAC-100 and from a genotype IAC-100 TN, with absence of lipoxygenases in their seeds, to respond to the attack by whitefly (sucking insect by lipoxygenases pathway. The kinetic characterization of the “pool” of lipoxygenases was determined. The KMapp values decreased, suggesting a change in the “pool” of lipoxygenases in response to the attack by whitefly. The similar KMapp values suggest that the removal of the lipoxygenases from the seeds does not change the expression of LOX in the leaves. There was a noticeable increase in protease inhibitors. These results suggest that the production of protease inhibitors are involved in the defense mechanism of soybean plant against whitefly injury.

  3. Comparison of conversion pathways for lignocellulosic biomass to biofuel in Mid-Norway

    OpenAIRE

    Berg, Heidi Ødegård

    2013-01-01

    This work investigates one biochemical and one thermochemical biomass-to-liquid biofuel conversion pathway in terms of lignocellulose conversion to liquid Fischer-Tropsch diesel. The focus has been on comparing the two conversion pathways in terms of identifying their energy flows and respective feed to fuel ratios. The conversion pathways investigated comprise two-stage conversion sequences including biomass-to-gas conversion and gas-to-liquid conversion, exerted by anaerobic digestion or ga...

  4. FNV: light-weight flash-based network and pathway viewer

    OpenAIRE

    Dannenfelser, Ruth; Lachmann, Alexander; Szenk, Mariola; Ma'ayan, Avi

    2011-01-01

    Motivation: Network diagrams are commonly used to visualize biochemical pathways by displaying the relationships between genes, proteins, mRNAs, microRNAs, metabolites, regulatory DNA elements, diseases, viruses and drugs. While there are several currently available web-based pathway viewers, there is still room for improvement. To this end, we have developed a flash-based network viewer (FNV) for the visualization of small to moderately sized biological networks and pathways.

  5. Biochemical characterization of the maltokinase from Mycobacterium bovis BCG

    Directory of Open Access Journals (Sweden)

    Lamosa Pedro

    2010-05-01

    Full Text Available Abstract Background Maltose-1-phosphate was detected in Mycobacterium bovis BCG extracts in the 1960's but a maltose-1-phosphate synthetase (maltokinase, Mak was only much later purified from Actinoplanes missouriensis, allowing the identification of the mak gene. Recently, this metabolite was proposed to be the intermediate in a pathway linking trehalose with the synthesis of glycogen in M. smegmatis. Although the M. tuberculosis H37Rv mak gene (Rv0127 was considered essential for growth, no mycobacterial Mak has, to date, been characterized. Results The sequence of the Mak from M. bovis BCG was identical to that from M. tuberculosis strains (99-100% amino acid identity. The enzyme was dependent on maltose and ATP, although GTP and UTP could be used to produce maltose-1-phosphate, which we identified by TLC and characterized by NMR. The Km for maltose was 2.52 ± 0.40 mM and 0.74 ± 0.12 mM for ATP; the Vmax was 21.05 ± 0.89 μmol/min.mg-1. Divalent cations were required for activity and Mg2+ was the best activator. The enzyme was a monomer in solution, had maximal activity at 60°C, between pH 7 and 9 (at 37°C and was unstable on ice and upon freeze/thawing. The addition of 50 mM NaCl markedly enhanced Mak stability. Conclusions The unknown role of maltokinases in mycobacterial metabolism and the lack of biochemical data led us to express the mak gene from M. bovis BCG for biochemical characterization. This is the first mycobacterial Mak to be characterized and its properties represent essential knowledge towards deeper understanding of mycobacterial physiology. Since Mak may be a potential drug target in M. tuberculosis, its high-level production and purification in bioactive form provide important tools for further functional and structural studies.

  6. Walking the C4 pathway: past, present, and future.

    Science.gov (United States)

    Furbank, Robert T

    2016-07-01

    The year 2016 marks 50 years since the publication of the seminal paper by Hatch and Slack describing the biochemical pathway we now know as C4 photosynthesis. This review provides insight into the initial discovery of this pathway, the clues which led Hatch and Slack and others to these definitive experiments, some of the intrigue which surrounds the international activities which led up to the discovery, and personal insights into the future of this research field. While the biochemical understanding of the basic pathways came quickly, the role of the bundle sheath intermediate CO2 pool was not understood for a number of years, and the nature of C4 as a biochemical CO2 pump then linked the unique Kranz anatomy of C4 plants to their biochemical specialization. Decades of "grind and find biochemistry" and leaf physiology fleshed out the regulation of the pathway and the differences in physiological response to the environment between C3 and C4 plants. The more recent advent of plant transformation then high-throughput RNA and DNA sequencing and synthetic biology has allowed us both to carry out biochemical experiments and test hypotheses in planta and to better understand the evolution-driven molecular and genetic changes which occurred in the genomes of plants in the transition from C3 to C4 Now we are using this knowledge in attempts to engineer C4 rice and improve the C4 engine itself for enhanced food security and to provide novel biofuel feedstocks. The next 50 years of photosynthesis will no doubt be challenging, stimulating, and a drawcard for the best young minds in plant biology. PMID:27059273

  7. Simulation methods with extended stability for stiff biochemical Kinetics

    Directory of Open Access Journals (Sweden)

    Rué Pau

    2010-08-01

    Full Text Available Abstract Background With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (biochemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA. The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows. Results In this paper we extend Poisson τ-leap methods to a general class of Runge-Kutta (RK τ-leap methods. We show that with the proper selection of the coefficients, the variance of the extended τ-leap can be well-behaved, leading to significantly larger step sizes. Conclusions The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original τ-leap method. The approach paves the way to explore new multiscale methods to simulate (biochemical systems.

  8. Successful adaptation to climate change across scales

    International Nuclear Information System (INIS)

    Climate change impacts and responses are presently observed in physical and ecological systems. Adaptation to these impacts is increasingly being observed in both physical and ecological systems as well as in human adjustments to resource availability and risk at different spatial and societal scales. We review the nature of adaptation and the implications of different spatial scales for these processes. We outline a set of normative evaluative criteria for judging the success of adaptations at different scales. We argue that elements of effectiveness, efficiency, equity and legitimacy are important in judging success in terms of the sustainability of development pathways into an uncertain future. We further argue that each of these elements of decision-making is implicit within presently formulated scenarios of socio-economic futures of both emission trajectories and adaptation, though with different weighting. The process by which adaptations are to be judged at different scales will involve new and challenging institutional processes. (author)

  9. Kombucha tea fermentation: Microbial and biochemical dynamics.

    Science.gov (United States)

    Chakravorty, Somnath; Bhattacharya, Semantee; Chatzinotas, Antonis; Chakraborty, Writachit; Bhattacharya, Debanjana; Gachhui, Ratan

    2016-03-01

    Kombucha tea, a non-alcoholic beverage, is acquiring significant interest due to its claimed beneficial properties. The microbial community of Kombucha tea consists of bacteria and yeast which thrive in two mutually non-exclusive compartments: the soup or the beverage and the biofilm floating on it. The microbial community and the biochemical properties of the beverage have so far mostly been described in separate studies. This, however, may prevent understanding the causal links between the microbial communities and the beneficial properties of Kombucha tea. Moreover, an extensive study into the microbial and biochemical dynamics has also been missing. In this study, we thus explored the structure and dynamics of the microbial community along with the biochemical properties of Kombucha tea at different time points up to 21 days of fermentation. We hypothesized that several biochemical properties will change during the course of fermentation along with the shifts in the yeast and bacterial communities. The yeast community of the biofilm did not show much variation over time and was dominated by Candida sp. (73.5-83%). The soup however, showed a significant shift in dominance from Candida sp. to Lachancea sp. on the 7th day of fermentation. This is the first report showing Candida as the most dominating yeast genus during Kombucha fermentation. Komagateibacter was identified as the single largest bacterial genus present in both the biofilm and the soup (~50%). The bacterial diversity was higher in the soup than in the biofilm with a peak on the seventh day of fermentation. The biochemical properties changed with the progression of the fermentation, i.e., beneficial properties of the beverage such as the radical scavenging ability increased significantly with a maximum increase at day 7. We further observed a significantly higher D-saccharic acid-1,4-lactone content and caffeine degradation property compared to previously described Kombucha tea fermentations. Our

  10. The Fanconi anaemia pathway: new players and new functions.

    Science.gov (United States)

    Ceccaldi, Raphael; Sarangi, Prabha; D'Andrea, Alan D

    2016-06-01

    The Fanconi anaemia pathway repairs DNA interstrand crosslinks (ICLs) in the genome. Our understanding of this complex pathway is still evolving, as new components continue to be identified and new biochemical systems are used to elucidate the molecular steps of repair. The Fanconi anaemia pathway uses components of other known DNA repair processes to achieve proper repair of ICLs. Moreover, Fanconi anaemia proteins have functions in genome maintenance beyond their canonical roles of repairing ICLs. Such functions include the stabilization of replication forks and the regulation of cytokinesis. Thus, Fanconi anaemia proteins are emerging as master regulators of genomic integrity that coordinate several repair processes. Here, we summarize our current understanding of the functions of the Fanconi anaemia pathway in ICL repair, together with an overview of its connections with other repair pathways and its emerging roles in genome maintenance. PMID:27145721

  11. Addressing uncertainty in adaptation planning for agriculture

    DEFF Research Database (Denmark)

    Vermeulen, Sonja Joy; Challinor, Andrew J.; Thornton, Philip K.;

    2013-01-01

    in specific timeframes and circumstances. The case on coffee in Latin America identifies altitudinal thresholds at which incremental vs. transformative adaptation pathways are robust options. The final case uses three crop-climate simulation studies to demonstrate how uncertainty can be characterized...

  12. Supervised Learning in Adaptive DNA Strand Displacement Networks.

    Science.gov (United States)

    Lakin, Matthew R; Stefanovic, Darko

    2016-08-19

    The development of engineered biochemical circuits that exhibit adaptive behavior is a key goal of synthetic biology and molecular computing. Such circuits could be used for long-term monitoring and control of biochemical systems, for instance, to prevent disease or to enable the development of artificial life. In this article, we present a framework for developing adaptive molecular circuits using buffered DNA strand displacement networks, which extend existing DNA strand displacement circuit architectures to enable straightforward storage and modification of behavioral parameters. As a proof of concept, we use this framework to design and simulate a DNA circuit for supervised learning of a class of linear functions by stochastic gradient descent. This work highlights the potential of buffered DNA strand displacement as a powerful circuit architecture for implementing adaptive molecular systems. PMID:27111037

  13. Use Case Design for AdaptIVe

    OpenAIRE

    Wolter, Stefan; Kelsch, Johann

    2014-01-01

    AdaptIVe is a large scale European project on vehicle automation and the pertaining human-machine interaction. The use case design process is a crucial part of the system design process and a part of the human-vehicle integration subproject. This paper explains the methodology for describing use cases in AdaptIVe. They are primarily based on sequence diagrams with main and alternative flows.

  14. B cell antigen receptor-induced activation of an IRAK4-dependent signaling pathway revealed by a MALT1-IRAK4 double knockout mouse model

    Directory of Open Access Journals (Sweden)

    Dufner Almut

    2011-03-01

    Full Text Available Abstract Background The B cell antigen receptor (BCR and pathogen recognition receptors, such as Toll-like receptor 4 (TLR4, act in concert to control adaptive B cell responses. However, little is known about the signaling pathways that integrate BCR activation with intrinsic TLR4 stimulation. Antigen receptors initialize activation of the inducible transcription factor nuclear factor-κB (NF-κB via recruitment of the membrane-associated guanylate kinase caspase recruitment domain protein 11 (CARD11, the adapter molecule B cell CLL/lymphoma 10 (BCL10, and the "paracaspase" mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1 into lipid rafts. Upon BCR triggering, this activation strictly depends on BCL10, but not on MALT1, leading to the hypothesis that a MALT1-independent NF-κB activation pathway contributes to BCR-induced NF-κB activation downstream of BCL10. The identity of this pathway has remained elusive. Results Using genetic and biochemical approaches, we demonstrate that the IRAK4- and IRAK1-dependent TLR signaling branch is activated upon BCR triggering to induce partial NF-κB activation. BCR-induced MALT1-independent IκB degradation and B cell proliferation were inhibited in MALT1/IRAK4 double knockout B cells. Moreover, IRAK1 was recruited into lipid rafts upon BCR stimulation and activated following transient recruitment of IRAK4. Conclusion We propose that the observed crosstalk between BCR and TLR signaling components may contribute to the discrimination of signals that emanate from single and dual receptor engagement to control adaptive B cell responses.

  15. Linear analysis near a steady-state of biochemical networks: control analysis, correlation metrics and circuit theory

    Directory of Open Access Journals (Sweden)

    Qian Hong

    2008-05-01

    Full Text Available Abstract Background: Several approaches, including metabolic control analysis (MCA, flux balance analysis (FBA, correlation metric construction (CMC, and biochemical circuit theory (BCT, have been developed for the quantitative analysis of complex biochemical networks. Here, we present a comprehensive theory of linear analysis for nonequilibrium steady-state (NESS biochemical reaction networks that unites these disparate approaches in a common mathematical framework and thermodynamic basis. Results: In this theory a number of relationships between key matrices are introduced: the matrix A obtained in the standard, linear-dynamic-stability analysis of the steady-state can be decomposed as A = SRT where R and S are directly related to the elasticity-coefficient matrix for the fluxes and chemical potentials in MCA, respectively; the control-coefficients for the fluxes and chemical potentials can be written in terms of RT BS and ST BS respectively where matrix B is the inverse of A; the matrix S is precisely the stoichiometric matrix in FBA; and the matrix eAt plays a central role in CMC. Conclusion: One key finding that emerges from this analysis is that the well-known summation theorems in MCA take different forms depending on whether metabolic steady-state is maintained by flux injection or concentration clamping. We demonstrate that if rate-limiting steps exist in a biochemical pathway, they are the steps with smallest biochemical conductances and largest flux control-coefficients. We hypothesize that biochemical networks for cellular signaling have a different strategy for minimizing energy waste and being efficient than do biochemical networks for biosynthesis. We also discuss the intimate relationship between MCA and biochemical systems analysis (BSA.

  16. Dynamic analysis of biochemical network using complex network method

    OpenAIRE

    Wang Shuqiang; Shen Yanyan; Hu Jinxing; Li Ning; Zeng Dewei

    2015-01-01

    In this study, the stochastic biochemical reaction model is proposed based on the law of mass action and complex network theory. The dynamics of biochemical reaction system is presented as a set of non-linear differential equations and analyzed at the molecular-scale. Given the initial state and the evolution rules of the biochemical reaction system, the system can achieve homeostasis. Compared with random graph, the biochemical reaction network has larger ...

  17. Adaptively robust filtering with classified adaptive factors

    Institute of Scientific and Technical Information of China (English)

    CUI Xianqiang; YANG Yuanxi

    2006-01-01

    The key problems in applying the adaptively robust filtering to navigation are to establish an equivalent weight matrix for the measurements and a suitable adaptive factor for balancing the contributions of the measurements and the predicted state information to the state parameter estimates. In this paper, an adaptively robust filtering with classified adaptive factors was proposed, based on the principles of the adaptively robust filtering and bi-factor robust estimation for correlated observations. According to the constant velocity model of Kalman filtering, the state parameter vector was divided into two groups, namely position and velocity. The estimator of the adaptively robust filtering with classified adaptive factors was derived, and the calculation expressions of the classified adaptive factors were presented. Test results show that the adaptively robust filtering with classified adaptive factors is not only robust in controlling the measurement outliers and the kinematic state disturbing but also reasonable in balancing the contributions of the predicted position and velocity, respectively, and its filtering accuracy is superior to the adaptively robust filter with single adaptive factor based on the discrepancy of the predicted position or the predicted velocity.

  18. Cytologic-Biochemical Radiation Dosimeters in Man

    International Nuclear Information System (INIS)

    The result of radiation interacting with living tissue is the deposition of energy therein. This energy triggers numerous chemical reactions within the molecules of the target tissues. We have measured in man the results of some of these reactions at doses up to 300 rads: chromosome aberrations; alterations in the kinetics of specific human cell populations; changes in 37 biochemical constituents of serum and/or urine. The utilization of chromosomes as a biological dosimeter is partially perfected but there are numerous discrepancies in data between different laboratories. Etiocholanolone can be used to evaluate marrow injury before the white-cell count falls below 5000/mm3. Most biochemical dosimeters evaluated gave negative or inconsistent results. However, salivary amylase is a promising indicator of human radiation injury from doses as low as 100 rads. (author)

  19. Optical Biochemical Platforms for Nanoparticles Detection

    CERN Document Server

    Campanella, Clarissa Martina

    2014-01-01

    In the biochemical sensing field, a fervent research activity related to the development of real time, low cost, compact and high throughput devices for the detection and characterization of natural or synthetic nanoparticles NPs actually exists. In this research scenario, different platforms for biosensing purposes have been developed according to the huge amount of physical effects involved in the transduction of the biochemical-signal into a measurable output signal. In the present work two different optical platforms for NP detection have been investigated, one based on integrated optics and the other based on microscopy. Both the approaches rely on the study of the interaction of an electromagnetic wave with a small particle in the hypothesis of dealing with a Rayleigh scatterer, i.e. a nanoparticle having a size really smaller than the one of the wavelength of the incident light and scattering light elastically.

  20. Biological dosimetry: biochemical and cellular parameters

    International Nuclear Information System (INIS)

    Early after the beginning of radiobiology studies, biochemistry has led to research of a biological dosimeter. From an extensive literature review, methods were selected that might be suitable for dose assessment via biochemical indicators. By now, research both in laboratory animals and in therapeutic or accidental human exposures, do not allow to retain a biochemical parameter alone for the purpose of diagnosis or prognosis. Several enzymatic activities have been precociously studied after irradiation: from these studies, it seems that analysis of four enzymatic activities in serum (serum glutamic oxaloacetic transaminase, amylase, lactic dehydrogenase, alkaline phosphatase) could be the most useful dosimetry system for mass sorting. Detection of DNA damage or methods for measuring somatic mutations are currently advancing and provide important new opportunities for biological dosimetry of low doses

  1. Advancement in biochemical assays in andrology

    Institute of Scientific and Technical Information of China (English)

    Wolf-BernhardSchill; RaftHenkel

    1999-01-01

    Determination of maikers of sperm function, accessory sex gland secretion and silent male genital tract inflammation is of considerable diagnostic value in the evaluation of male infertility. The introduction of biochemical tests into the analysis of male factor has the advantage that standardized assays with a coefficient of variafion characteristic of clinical chemistry are performed, in contrast to biological test systems with a large variability .Biochemical parameters may be used in clinical practice to evaluate the sperm fertitizing capacity (acrosin, aniline blue,ROS), to characterize male accessory sex gland secretinns (fructose, a-glucosidase, PSA), and to identify men with silent genital tract inflammation (elastase, C'3 complement component, coeruloplasmin, IgA, IgG, ROS). (As/an J Androl 1999 Jun; 1: 45-51)

  2. Biochemical changes in ginger after gamma irradiation

    International Nuclear Information System (INIS)

    Ginger (Zingiber officinate) was irradiated with gamma rays (0.1Kgy, 1.0Kgy). Biochemical changes during storage at room temperature (23-28 degree centigrade), in sand (23-28 degree centigrade) and at cold (8 degree centigrade) temperature were observed. Changes in starch, soluble protein, fixed oil and volatile oil contents showed that treatment of ginger at 0.1Kgy radiation level was most appropriate for storage upto 45 days

  3. Prions: the danger of biochemical weapons

    OpenAIRE

    Eric Almeida Xavier

    2014-01-01

    The knowledge of biotechnology increases the risk of using biochemical weapons for mass destruction. Prions are unprecedented infectious pathogens that cause a group of fatal neurodegenerative diseases by a novel mechanism. They are transmissible particles that are devoid of nucleic acid. Due to their singular characteristics, Prions emerge as potential danger since they can be used in the development of such weapons. Prions cause fatal infectious diseases, and to date there is no therapeutic...

  4. The stochastic dynamics of biochemical systems

    OpenAIRE

    Challenger, Joseph Daniel

    2013-01-01

    The topic of this thesis is the stochastic dynamics of biochemical reaction systems. The importance of the intrinsic fluctuations in these systems has become more widely appreciated in recent years, and should be accounted for when modelling such systems mathematically. These models are described as continuous time Markov processes and their dynamics defined by a master equation. Analytical progress is made possible by the use of the van Kampen system-size expansion, which splits the dynamics...

  5. The Biochemical Anatomy of Cortical Inhibitory Synapses

    OpenAIRE

    Heller, E.A.; Zhang, W.; Selimi, F.; Earnheart, J.C.; Slimak, M.A.; Santos-Torres, J.; Ibanez-Tallon, I.; Aoki, C; Chait, B. T.; Heintz, N

    2012-01-01

    Classical electron microscopic studies of the mammalian brain revealed two major classes of synapses, distinguished by the presence of a large postsynaptic density (PSD) exclusively at type 1, excitatory synapses. Biochemical studies of the PSD have established the paradigm of the synapse as a complex signal-processing machine that controls synaptic plasticity. We report here the results of a proteomic analysis of type 2, inhibitory synaptic complexes isolated by affinity purification from th...

  6. Probabilistic sensitivity analysis of biochemical reaction systems

    OpenAIRE

    Zhang, Hong-Xuan; Dempsey, William P.; Goutsias, John

    2009-01-01

    Sensitivity analysis is an indispensable tool for studying the robustness and fragility properties of biochemical reaction systems as well as for designing optimal approaches for selective perturbation and intervention. Deterministic sensitivity analysis techniques, using derivatives of the system response, have been extensively used in the literature. However, these techniques suffer from several drawbacks, which must be carefully considered before using them in problems of systems biology. ...

  7. Biochemical and functional characterisation of casein and whey protein hydrolysates.

    OpenAIRE

    Ven, van de, P.M.

    2002-01-01

    Whey protein and sodium caseinate were hydrolysed with commercially available enzyme preparations. The resulting hydrolysates were characterised using several analytical characterisation methods and by determination of several functional properties. Subsequently, correlations between the biochemical characteristics themselves and between biochemical and functional properties were studied using multivariate regression analysis.Biochemical characteristics of hydrolysates were determined using u...

  8. [Biochemical antenatal screening for fetal anomalies.].

    Science.gov (United States)

    Torfadóttir, G; Jónsson, J J

    2001-05-01

    Biochemical antenatal screening started 30 years ago. Initially, the goal was to detect neural tube defects by measuring a-fetoprotein in maternal serum (MS-AFP) and amniotic fluid (AF-AFP). The serendipitous discovery of an association between low AFP maternal serum concentration and chromosomal anomalies resulted in increased research interest in biochemical screening in pregnancy. Subsequently double, triple or quadruple tests in 2nd trimester of pregnancy became widely used in combination with fetal chromosome determination in at risk individuals. In Iceland, antenatal screening for chromosomal anomalies has essentially been based on fetal chromosome studies offered to pregnant women 35 years or older. This strategy needs to be revised. Recently first trimester biochemical screening based on maternal serum pregnancy associated plasma protein A (MS-PAPP-A) and free b-human chorionic gonadotropin (MS-free b-hCG) and multivariate risk assessment has been developed. This screening test can be improved if done in conjunction with nuchal translucency measurements in an early sonography scan. PMID:17018982

  9. Hydrogel-based piezoresistive biochemical microsensors

    Science.gov (United States)

    Guenther, Margarita; Schulz, Volker; Gerlach, Gerald; Wallmersperger, Thomas; Solzbacher, Florian; Magda, Jules J.; Tathireddy, Prashant; Lin, Genyao; Orthner, Michael P.

    2010-04-01

    This work is motivated by a demand for inexpensive, robust and reliable biochemical sensors with high signal reproducibility and long-term-stable sensitivity, especially for medical applications. Micro-fabricated sensors can provide continuous monitoring and on-line control of analyte concentrations in ambient aqueous solutions. The piezoresistive biochemical sensor containing a special biocompatible polymer (hydrogel) with a sharp volume phase transition in the neutral physiological pH range near 7.4 can detect a specific analyte, for example glucose. Thereby the hydrogel-based biochemical sensors are useful for the diagnosis and monitoring of diabetes. The response of the glucosesensitive hydrogel was studied at different regimes of the glucose concentration change and of the solution supply. Sensor response time and accuracy with which a sensor can track gradual changes in glucose was estimated. Additionally, the influence of various recommended sterilization methods on the gel swelling properties and on the mechano-electrical transducer of the pH-sensors has been evaluated in order to choose the most optimal sterilization method for the implantable sensors. It has been shown that there is no negative effect of gamma irradiation with a dose of 25.7 kGy on the hydrogel sensitivity. In order to achieve an optimum between sensor signal amplitude and sensor response time, corresponding calibration and measurement procedures have been proposed and evaluated for the chemical sensors.

  10. Molecular mechanism of adaptive response to low dose radiation

    International Nuclear Information System (INIS)

    Adaptive response is a term used to describe the ability of a low, priming dose of ionizing radiation to modify the effects of a subsequent higher, challenge dose. Molecular mechanism of adaptive response to low dose radiation is involved in signal transduction pathway, reactive oxygen species, DNA damage repair

  11. Moorella Strains for the Production of Biochemicals from Syngas

    DEFF Research Database (Denmark)

    Redl, Stephanie; Jensen, Torbjørn Ølshøj; Nielsen, Alex Toftgaard

    In the process of sugar fermentation, a significant portion of lignocellulosic biomass is left unused. Analternative is the gasification into syngas, a carbon-rich gas mixture. Syngas serves as energy andcarbon source for acetogenic bacteria, which can then produce biochemicals. In the syngasferm......In the process of sugar fermentation, a significant portion of lignocellulosic biomass is left unused. Analternative is the gasification into syngas, a carbon-rich gas mixture. Syngas serves as energy andcarbon source for acetogenic bacteria, which can then produce biochemicals. In the...... mainresearch aspect is hereby to determine the acceptance of, and the exact growth rates on different carbonsources (C1 and C6 compounds and gaseous substrates) in different Moorella strains. Genome analysison pathway level is performed to link genotype and phenotype. Differential expression analysis (RNAseq...

  12. Biochemical reasoning for radiation protection and screening methods for radiation sensitivity and potential carcinogenicity

    International Nuclear Information System (INIS)

    Cells of different genetic characteristics respond differently to agents that modify radiation effects. When the modification is a result of chemical repair, reduction of the amount of damage by radical scavenging, production of hypoxia, or any other such mechanism, then the modification of the response will be the same for all types of cells, but not the same when biological or biochemical parameters are involved, because the differences between the cells affect the final outcome, and the genetic traits obviously become affected by chemical modifying agents. Some of these agents directly affect the repair of deoxyribonucleic acid (DNA) by mechanisms not yet understood. Another agent nicotinamide (NA), is directly linked to a repair pathway. Thus, a system that uses NA as a precursor of nicotinamide adenine dinucleotide (NAD)+, and uses NAD+ to produce the polymer polyadenosine diphosphate ribose (PADPR) appears to be an interesting and important factor in the biochemical events that may be linked to improved radioprotection. (author). 36 refs., 5 figs

  13. Plant responses to UV and blue light: biochemical and genetic approaches

    International Nuclear Information System (INIS)

    UV and blue light control many aspects of plant growth and development. It is evident that several different photoreceptors mediate responses to UV and blue light, and there are reports of the functional and biochemical characterisation of a putative photoreceptor for phototropism and of the functional and molecular characterisation of the CRY1 photoreceptor, encoded by the Arabidopsis HY4 gene. The CRY1 photoreceptor mediates extension growth and gene expression responses to UV-A/blue light presumably through different or branching signal transduction pathways. Progress has been made in cell physiological and biochemical studies of UV/blue light signal transduction, but much remains to be done to relate candidate UV/blue signal transduction events to particular photoreceptors and responses. The application of a genetic approach in Arabidopsis has been responsible for many advances in understanding UV/blue responses, but further UV-B, UV-A and blue light response mutants need to be isolated. (author)

  14. A limit cycle oscillator model for cycling mood variations of bipolar disorder patients derived from cellular biochemical reaction equations

    Science.gov (United States)

    Frank, T. D.

    2013-08-01

    We derive a nonlinear limit cycle model for oscillatory mood variations as observed in patients with cycling bipolar disorder. To this end, we consider two signaling pathways leading to the activation of two enzymes that play a key role for cellular and neural processes. We model pathway cross-talk in terms of an inhibitory impact of the first pathway on the second and an excitatory impact of the second on the first. The model also involves a negative feedback loop (inhibitory self-regulation) for the first pathway and a positive feedback loop (excitatory self-regulation) for the second pathway. We demonstrate that due to the cross-talk the biochemical dynamics is described by an oscillator equation. Under disease-free conditions the oscillatory system exhibits a stable fixed point. The breakdown of the self-inhibition of the first pathway at higher concentration levels is studied by means of a scalar control parameter ξ, where ξ equal to zero refers to intact self-inhibition at all concentration levels. Under certain conditions, stable limit cycle solutions emerge at critical parameter values of ξ larger than zero. These oscillations mimic pathological cycling mood variations that emerge due to a disease-induced bifurcation. Consequently, our modeling analysis supports the notion of bipolar disorder as a dynamical disease. In addition, our study establishes a connection between mechanistic biochemical modeling of bipolar disorder and phenomenological nonlinear oscillator approaches to bipolar disorder suggested in the literature.

  15. Structural, biochemical, cellular, and functional changes in skeletal muscle extracellular matrix with aging

    DEFF Research Database (Denmark)

    Kragstrup, T W; Kjaer, M; Mackey, A L

    2011-01-01

    . Structural changes include an increase in the collagen concentration, a change in the elastic fiber system, and an increase in fat infiltration of skeletal muscle. Biochemical changes include a decreased turnover of collagen with potential accumulation of enzymatically mediated collagen cross......The extracellular matrix (ECM) of skeletal muscle is critical for force transmission and for the passive elastic response of skeletal muscle. Structural, biochemical, cellular, and functional changes in skeletal muscle ECM contribute to the deterioration in muscle mechanical properties with aging...... in skeletal muscle ECM contribute to the increased stiffness and impairment in force generated by the contracting muscle fibers seen with aging. The cellular interactions provide and potentially coordinate an adaptation to mechanical loading and ensure successful regeneration after muscle injury. Some...

  16. Adaptive Image Denoising by Mixture Adaptation.

    Science.gov (United States)

    Luo, Enming; Chan, Stanley H; Nguyen, Truong Q

    2016-10-01

    We propose an adaptive learning procedure to learn patch-based image priors for image denoising. The new algorithm, called the expectation-maximization (EM) adaptation, takes a generic prior learned from a generic external database and adapts it to the noisy image to generate a specific prior. Different from existing methods that combine internal and external statistics in ad hoc ways, the proposed algorithm is rigorously derived from a Bayesian hyper-prior perspective. There are two contributions of this paper. First, we provide full derivation of the EM adaptation algorithm and demonstrate methods to improve the computational complexity. Second, in the absence of the latent clean image, we show how EM adaptation can be modified based on pre-filtering. The experimental results show that the proposed adaptation algorithm yields consistently better denoising results than the one without adaptation and is superior to several state-of-the-art algorithms. PMID:27416593

  17. Brain evolution by brain pathway duplication.

    Science.gov (United States)

    Chakraborty, Mukta; Jarvis, Erich D

    2015-12-19

    Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits. PMID:26554045

  18. Mechanisms Underlying Adaptation to Life in Hydrogen Sulfide-Rich Environments.

    Science.gov (United States)

    Kelley, Joanna L; Arias-Rodriguez, Lenin; Patacsil Martin, Dorrelyn; Yee, Muh-Ching; Bustamante, Carlos D; Tobler, Michael

    2016-06-01

    Hydrogen sulfide (H2S) is a potent toxicant interfering with oxidative phosphorylation in mitochondria and creating extreme environmental conditions in aquatic ecosystems. The mechanistic basis of adaptation to perpetual exposure to H2S remains poorly understood. We investigated evolutionarily independent lineages of livebearing fishes that have colonized and adapted to springs rich in H2S and compared their genome-wide gene expression patterns with closely related lineages from adjacent, nonsulfidic streams. Significant differences in gene expression were uncovered between all sulfidic and nonsulfidic population pairs. Variation in the number of differentially expressed genes among population pairs corresponded to differences in divergence times and rates of gene flow, which is consistent with neutral drift driving a substantial portion of gene expression variation among populations. Accordingly, there was little evidence for convergent evolution shaping large-scale gene expression patterns among independent sulfide spring populations. Nonetheless, we identified a small number of genes that was consistently differentially expressed in the same direction in all sulfidic and nonsulfidic population pairs. Functional annotation of shared differentially expressed genes indicated upregulation of genes associated with enzymatic H2S detoxification and transport of oxidized sulfur species, oxidative phosphorylation, energy metabolism, and pathways involved in responses to oxidative stress. Overall, our results suggest that modification of processes associated with H2S detoxification and toxicity likely complement each other to mediate elevated H2S tolerance in sulfide spring fishes. Our analyses allow for the development of novel hypotheses about biochemical and physiological mechanisms of adaptation to extreme environments. PMID:26861137

  19. Mechanisms Underlying Adaptation to Life in Hydrogen Sulfide–Rich Environments

    Science.gov (United States)

    Kelley, Joanna L.; Arias-Rodriguez, Lenin; Patacsil Martin, Dorrelyn; Yee, Muh-Ching; Bustamante, Carlos D.; Tobler, Michael

    2016-01-01

    Hydrogen sulfide (H2S) is a potent toxicant interfering with oxidative phosphorylation in mitochondria and creating extreme environmental conditions in aquatic ecosystems. The mechanistic basis of adaptation to perpetual exposure to H2S remains poorly understood. We investigated evolutionarily independent lineages of livebearing fishes that have colonized and adapted to springs rich in H2S and compared their genome-wide gene expression patterns with closely related lineages from adjacent, nonsulfidic streams. Significant differences in gene expression were uncovered between all sulfidic and nonsulfidic population pairs. Variation in the number of differentially expressed genes among population pairs corresponded to differences in divergence times and rates of gene flow, which is consistent with neutral drift driving a substantial portion of gene expression variation among populations. Accordingly, there was little evidence for convergent evolution shaping large-scale gene expression patterns among independent sulfide spring populations. Nonetheless, we identified a small number of genes that was consistently differentially expressed in the same direction in all sulfidic and nonsulfidic population pairs. Functional annotation of shared differentially expressed genes indicated upregulation of genes associated with enzymatic H2S detoxification and transport of oxidized sulfur species, oxidative phosphorylation, energy metabolism, and pathways involved in responses to oxidative stress. Overall, our results suggest that modification of processes associated with H2S detoxification and toxicity likely complement each other to mediate elevated H2S tolerance in sulfide spring fishes. Our analyses allow for the development of novel hypotheses about biochemical and physiological mechanisms of adaptation to extreme environments. PMID:26861137

  20. Cold adaptation mechanisms in the ghost moth Hepialus xiaojinensis: Metabolic regulation and thermal compensation.

    Science.gov (United States)

    Zhu, Wei; Zhang, Huan; Li, Xuan; Meng, Qian; Shu, Ruihao; Wang, Menglong; Zhou, Guiling; Wang, Hongtuo; Miao, Lin; Zhang, Jihong; Qin, Qilian

    2016-02-01

    Ghost moths (Lepidoptera: Hepialidae) are cold-adapted stenothermal species inhabiting alpine meadows on the Tibetan Plateau. They have an optimal developmental temperature of 12-16°C but can maintain feeding and growth at 0°C. Their survival strategies have received little attention, but these insects are a promising model for environmental adaptation. Here, biochemical adaptations and energy metabolism in response to cold were investigated in larvae of the ghost moth Hepialus xiaojinensis. Metabolic rate and respiratory quotient decreased dramatically with decreasing temperature (15-4°C), suggesting that the energy metabolism of ghost moths, especially glycometabolism, was sensitive to cold. However, the metabolic rate at 4°C increased with the duration of cold exposure, indicating thermal compensation to sustain energy budgets under cold conditions. Underlying regulation strategies were studied by analyzing metabolic differences between cold-acclimated (4°C for 48h) and control larvae (15°C). In cold-acclimated larvae, the energy generating pathways of carbohydrates, instead of the overall consumption of carbohydrates, was compensated in the fat body by improving the transcription of related enzymes. The mobilization of lipids was also promoted, with higher diacylglycerol, monoacylglycerol and free fatty acid content in hemolymph. These results indicated that cold acclimation induced a reorganization on metabolic structure to prioritise energy metabolism. Within the aerobic process, flux throughout the tricarboxylic acid (TCA) cycle was encouraged in the fat body, and the activity of α-ketoglutarate dehydrogenase was the likely compensation target. Increased mitochondrial cristae density was observed in the midgut of cold-acclimated larvae. The thermal compensation strategies in this ghost moth span the entire process of energy metabolism, including degration of metabolic substrate, TCA cycle and oxidative phosphorylation, and from an energy budget

  1. The biochemical basis of antimicrobial responses in Manduca sexta

    Institute of Scientific and Technical Information of China (English)

    Haobo Jiang

    2008-01-01

    Innate immunity is essential for the wellbeing of vertebrates and invertebrates.Key components of this defense system include pattern recognition receptors that bind to infectious agents, extra-and intra-cellular proteins that relay signals, as well as molecules and cells that eliminate pathogens. We have been studying the defense mechanisms in a biochemical model insect, Manduca sexta. In this insect, hemolin, peptidoglycan recognition proteins, β-1,3-glucan recognition proteins and C-type lectins detect microbial surface molecules and induce immune responses such as phagocytosis, nodulation, encapsulation,melanization and production of antimicrobial peptides. Some of these responses are mediated by extracellular serine proteinase pathways. The proteolytic activation of prophenoloxidase (proPO) yields active phenoloxidase (PO) which catalyzes the formation of quinones and melanin for wound healing and microbe killing. M. sexta hemolymph proteinase 14 (HP 14) precursor interacts with peptidoglycan or β- 1,3-glucan, autoactivates,and leads to the activation of other HPs including HP21 and proPO-activating proteinases (PAPs). PAP-1, -2 and -3 cut proPO to generate active PO in the presence of two serine proteinase homologs. Inhibition of the proteinases by serpins and association of the proteinase homologs with bacteria ensure a localized defense reaction. M. sexta HP1, HP6,HP8, HP17 and other proteinases may also participate in proPO activation or processing of sp(a)tzle and plasmatocyte spreading peptide.

  2. Adaptive Modular Playware

    DEFF Research Database (Denmark)

    Lund, Henrik Hautop; Þorsteinsson, Arnar Tumi

    2011-01-01

    In this paper, we describe the concept of adaptive modular playware, where the playware adapts to the interaction of the individual user. We hypothesize that there are individual differences in user interaction capabilities and styles, and that adaptive playware may adapt to the individual user’s...

  3. Biochemical changes in blood under Cr6+

    Directory of Open Access Journals (Sweden)

    Kuzenko E.V.

    2013-01-01

    Full Text Available Background. For the manufacture of dentures many different alloys containing chromium are used. Interaction with oral fluid, organic acids and food, results in formation of Cr3+, Cr6+ ions, but their influence on the whole organism is poorly investigated. Objective. To analyze the biochemical changes in blood plasma during the influence of Cr6+ ions. Methods. 15 animals of experimental group were receiving drinking water with potassium dichromate in a dose of 0,2 mol/l. Rats of control group (5 individuals drank usual drinking water. Animals were led out of experiment on the 20th, 40th and 60th days after the beginning of introduction of potassium dichromate. Results. It was established that at the beginning of experiment the blood biochemical indicators of control and the 1st experimental groups differed by its content. Increase of urea concentration led to suspicion about violation of a glomerular filtration, damage of a kidney parenchyma and tissue disintegration. On the 20th and 40th days of experiment the symptoms of acidosis and increase of potassium ions concentration in blood plasma were defined. Continuous and dynamic increase of creatin-phosphokinase was observed during 60 days of experiment. Conclusion. Biochemical changes in blood under the influence of Cr6+ ions evidence their toxic action on an organism. Especial concern is caused by changes of ionic composition and increase of the atherogenic index of blood plasma on the 40th day of experiment. Substantial increase of the creatin-phosphokinase level indicates general somatic influence of chromium ions.

  4. Modulation, Adaptation, and Control of Orofacial Pathways in Healthy Adults

    Science.gov (United States)

    Estep, Meredith E.

    2009-01-01

    Although the healthy adult possesses a large repertoire of coordinative strategies for oromotor behaviors, a range of nonverbal, speech-like movements can be observed during speech. The extent of overlap among sensorimotor speech and nonspeech neural correlates and the role of neuromodulatory inputs generated during oromotor behaviors are unknown.…

  5. Quantifying environmental adaptation of metabolic pathways in metagenomics

    DEFF Research Database (Denmark)

    Gianoulis, Tara A; Raes, Jeroen; Patel, Prianka V;

    2009-01-01

    Recently, approaches have been developed to sample the genetic content of heterogeneous environments (metagenomics). However, by what means these sequences link distinct environmental conditions with specific biological processes is not well understood. Thus, a major challenge is how the usage...

  6. Moorella Strains for the Production of Biochemicals from Syngas

    DEFF Research Database (Denmark)

    Redl, Stephanie; Jensen, Torbjørn Ølshøj; Nielsen, Alex Toftgaard

    In the process of sugar fermentation, a significant portion of lignocellulosic biomass is left unused. An alternative is the gasification into syngas, a carbon-rich gas mixture. Syngas serves as energy and carbon source for acetogenic bacteria, which can then produce biochemicals. In the syngas...... acetogenic bacteria. The main research aspect is to determine acceptance of, and the exact growth rates on different carbon sources (C1, C6, gaseous substrates) in different Moorella strains. Genome analysis on pathway level is performed to link the genotype to the phenotype. Differential expression analysis...

  7. Biochemical studies on Francisella tularensis RelA in (p)ppGpp biosynthesis

    OpenAIRE

    Wilkinson, Rachael C.; Batten, Laura E.; Wells, Neil J.; Oyston, Petra C. F.; Roach, Peter L.

    2015-01-01

    The bacterial stringent response is induced by nutrient deprivation and is mediated by enzymes of the RSH (RelA/SpoT homologue; RelA, (p)ppGpp synthetase I; SpoT, (p)ppGpp synthetase II) superfamily that control concentrations of the ‘alarmones’ (p)ppGpp (guanosine penta- or tetra-phosphate). This regulatory pathway is present in the vast majority of pathogens and has been proposed as a potential anti-bacterial target. Current understanding of RelA-mediated responses is based on biochemical s...

  8. Adaptive Sticky Generalized Metropolis

    OpenAIRE

    Fabrizio Leisen; Roberto Casarin; David Luengo; Luca Martino

    2013-01-01

    We introduce a new class of adaptive Metropolis algorithms called adaptive sticky algorithms for efficient general-purpose simulation from a target probability distribution. The transition of the Metropolis chain is based on a multiple-try scheme and the different proposals are generated by adaptive nonparametric distributions. Our adaptation strategy uses the interpolation of support points from the past history of the chain as in the adaptive rejection Metropolis. The algorithm efficiency i...

  9. Radiation treatment of drugs, biochemicals and vaccines

    International Nuclear Information System (INIS)

    The concise and tabulated review reports experimental results on the effects of radiation treatment on drugs, vaccines, biochemicals and adjuvants including enzymes as well. Irradiation was mostly performed by γ-radiation using 60Co and to a lesser extent by 137Cs, 182Ta, X-rays and accelerators. Ionizing radiation proved to be a useful tool for sterilization and inactivation in producing drugs, vaccines, and bioactive agents and will contribute to realize procedures difficultly solvable as to engineering and economy, respectively. 124 refs

  10. Induced biochemical conversions of heavy crude oils

    International Nuclear Information System (INIS)

    Products formed during multiple interactions of microorganisms with oils fall into two major categories: those formed due to the action of indigenous microorganisms under reservoir conditions over geological periods of time and those products which are generated by the action of introduced organisms. The extreme end product of the first category is the production of heavy 'biodegraded' crudes. The extreme end product of the second category is the production of reduced sulfates due to the introduction of sulfate-reducing bacteria which may lead to the souring of a field. There is, however, a select group of microorganisms whose action on the crudes is beneficial. The interactions between such microorganisms and different crude oils occur through complex biochemical and chemical reactions. These reactions depend on multiple variables within and at the interface of a multicomponent system consisting of organic, aqueous, and inorganic components. Studies, carried out in this laboratory (BNL) of biochemical and chemical reactions in crude oils which involve extremophilic organisms (organisms which thrive in extreme environments), have shown that the reactions are not random and follow distinct trends. These trends can be categorized. The use of a group of characteristic chemical markers, such as mass spectrometric fragmentation patterns of light and heavy hydrocarbons, heterocyclic and organometallic compounds, as well as total trace metal and heteroatom contents of crude oils before and after the biochemical treatment allows to follow the type and the extent of chemical changes which occur during the biochemical conversion of heavy crude oils by microorganisms. The bioconversion involves multiple, simultaneous, and/or concurrent chemical reactions in which the microorganisms serve as biocatalysts. In this sense, the biocatalysts are active in a reaction medium which depends on the chemical composition of the crude and the selectivity of the biocatalyst. Thus, the

  11. Biochemical Disincentives to Fertilizing Cellulosic Ethanol Crops

    Science.gov (United States)

    Gallagher, M. E.; Hockaday, W. C.; Snapp, S.; McSwiney, C.; Baldock, J.

    2010-12-01

    Corn grain biofuel crops produce the highest yields when the cropping ecosystem is not nitrogen (N)-limited, achieved by application of fertilizer. There are environmental consequences for excessive fertilizer application to crops, including greenhouse gas emissions, hypoxic “dead zones,” and health problems from N runoff into groundwater. The increase in corn acreage in response to demand for alternative fuels (i.e. ethanol) could exacerbate these problems, and divert food supplies to fuel production. A potential substitute for grain ethanol that could reduce some of these impacts is cellulosic ethanol. Cellulosic ethanol feedstocks include grasses (switchgrass), hardwoods, and crop residues (e.g. corn stover, wheat straw). It has been assumed that these feedstocks will require similar N fertilization rates to grain biofuel crops to maximize yields, but carbohydrate yield versus N application has not previously been monitored. We report the biochemical stocks (carbohydrate, protein, and lignin in Mg ha-1) of a corn ecosystem grown under varying N levels. We measured biochemical yield in Mg ha-1 within the grain, leaf and stem, and reproductive parts of corn plants grown at seven N fertilization rates (0-202 kg N ha-1), to evaluate the quantity and quality of these feedstocks across a N fertilization gradient. The N fertilization rate study was performed at the Kellogg Biological Station-Long Term Ecological Research Site (KBS-LTER) in Michigan. Biochemical stocks were measured using 13C nuclear magnetic resonance spectroscopy (NMR), combined with a molecular mixing model (Baldock et al. 2004). Carbohydrate and lignin are the main biochemicals of interest in ethanol production since carbohydrate is the ethanol feedstock, and lignin hinders the carbohydrate to ethanol conversion process. We show that corn residue carbohydrate yields respond only weakly to N fertilization compared to grain. Grain carbohydrate yields plateau in response to fertilization at

  12. Biochemical assessment of physical training: a tool to sports dietitians-nutritionists

    OpenAIRE

    Aritz Urdampilleta; José Miguel Martínez-Sanz; Raúl Lopez-Grueso

    2013-01-01

    The high demand in athletes creates the need to control the process of adaptation to training. The aim of this review is to analyze the biochemical parameters of utility for biological control of the athlete, and provide tools to sports dietitian-nutritionist in the follow-up of the training.Glucose and lipid profile parameters are widely used but insufficient to control training. The lactic acid level in the plasma is the most common tool to assess training load, where values higher than 4 m...

  13. From the Sugar Platform to biofuels and biochemicals : Final report for the European Commission Directorate-General Energy

    OpenAIRE

    Taylor, R.; Nattrass, L.; Alberts, G.; Robson, P; Chudziak, C.; Bauen, A.; Libelli, I.M.; Lotti, G; Prussi, M.; Nistri, R; Chiaramonti, D.; López-Contreras, A.M.; Bos, H.H.; Eggink, G; Springer, J

    2015-01-01

    Numerous potential pathways to biofuels and biochemicals exist via the sugar platform1. This study uses literature surveys, market data and stakeholder input to provide a comprehensive evidence base for policymakers and industry – identifying the key benefits and development needs for the sugar platform. The study created a company database for 94 sugar-based products, with some already commercial, the majority at research/pilot stage, and only a few demonstration plants crossing the “valley ...

  14. Molecular Pathways: Targeting the PI3K Pathway in Cancer-BET Inhibitors to the Rescue.

    Science.gov (United States)

    Stratikopoulos, Elias E; Parsons, Ramon E

    2016-06-01

    The PI3K signaling pathway is a complex and tightly regulated network that is critical for many physiologic processes, such as cell growth, proliferation, metabolism, and survival. Aberrant activation of this pathway can occur through mutation of almost any of its major nodes and has been implicated in a number of human diseases, including cancer. The high frequency of mutations in this pathway in multiple types of cancer has led to the development of small-molecule inhibitors of PI3K, several of which are currently in clinical trials. However, several feedback mechanisms either within the PI3K pathway or in compensatory pathways can render tumor cells resistant to therapy. Recently, targeting proteins of the bromodomain and extraterminal (BET) family of epigenetic readers of histone acetylation has been shown to effectively block adaptive signaling response of cancer cells to inhibitors of the PI3K pathway, which at least in some cases can restore sensitivity. BET inhibitors also enforce blockade of the MAPK, JAK/STAT, and ER pathways, suggesting they may be a rational combinatorial partner for divergent oncogenic signals that are subject to homeostatic regulation. Here, we review the PI3K pathway as a target for cancer therapy and discuss the potential use of BET inhibition to enhance the clinical efficacy of PI3K inhibitors. Clin Cancer Res; 22(11); 2605-10. ©2016 AACR. PMID:27250929

  15. Regulated cell death and adaptive stress responses.

    Science.gov (United States)

    Galluzzi, Lorenzo; Bravo-San Pedro, José Manuel; Kepp, Oliver; Kroemer, Guido

    2016-06-01

    Eukaryotic cells react to potentially dangerous perturbations of the intracellular or extracellular microenvironment by activating rapid (transcription-independent) mechanisms that attempt to restore homeostasis. If such perturbations persist, cells may still try to cope with stress by activating delayed and robust (transcription-dependent) adaptive systems, or they may actively engage in cellular suicide. This regulated form of cell death can manifest with various morphological, biochemical and immunological correlates, and constitutes an ultimate attempt of stressed cells to maintain organismal homeostasis. Here, we dissect the general organization of adaptive cellular responses to stress, their intimate connection with regulated cell death, and how the latter operates for the preservation of organismal homeostasis. PMID:27048813

  16. Brain evolution by brain pathway duplication

    OpenAIRE

    Chakraborty, Mukta; Jarvis, Erich D

    2015-01-01

    Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel ...

  17. Biochemical mechanisms of laser vascular tissue fusion.

    Science.gov (United States)

    Guthrie, C R; Murray, L W; Kopchok, G E; Rosenbaum, D; White, R A

    1991-01-01

    This study examines the biochemical changes that occur in argon laser-fused canine veins compared with control segments of vein. Laser fusions were formed using 0.5 W argon laser energy (1100-1500 J/cm2). Immediately following tissue fusion, blood flow was reestablished to test the integrity of the welds. 1-mm3 sections of the anastomoses and control sections were minced and protein extraction was performed by solubilizing the tissue in hot SDS Laemmli gel sample buffer. The proteins were separated electrophoretically on 5 and 10% polyacylamide SDS gels and silver stained. The analysis demonstrated significant biochemical differences between control and lased veins. We noted increases in several proteins after laser welding: the putative beta chain of type V collagen (5/5 gels), the putative gamma chain of type I collagen (4/5 gels), a 156-kDa protein (based on collagen molecular weight standards) 7/7 gels), an 82-kDa protein (8/9 gels), and several proteins of lower molecular weight (3/8 gels). The increases may be due to crosslinking of lower molecular weight proteins, degradation of higher molecular weight proteins, or increased solubility of certain proteins. These findings suggest that laser welding may occur by formation of crosslinks or by denaturation and reannealment of structural proteins. PMID:1863584

  18. BIOCHEMICAL PROCESSES FOR GEOTHERMAL BRINE TREATMENT

    Energy Technology Data Exchange (ETDEWEB)

    PREMUZIC,E.T.; LIN,M.S.; BOHENEK,M.; JOSHI-TOPE,G.; ZHOU,W.; SHELENKOVA,L.; WILKE,R.

    1998-09-20

    As part of the DOE Geothermal Energy Program, BNL's Advanced Biochemical Processes for Geothermal Brines (ABPGB) project is aimed at the development of cost-efficient and environmentally acceptable technologies for the disposal of geothermal wastes. Extensive chemical studies of high and low salinity brines and precipitates have indicated that in addition to trace quantities of regulated substances, e.g., toxic metals such as arsenic and mercury, there are significant concentrations of valuable metals, including gold, silver and platinum. Further chemical and physical studies of the silica product have also shown that the produced silica is a valuable material with commercial potential. A combined biochemical and chemical technology is being developed which (1) solubilizes, separates, and removes environmentally regulated constituents in geothermal precipitates and brines (2) generates an amorphous silica product which may be used as feedstock for the production of revenue generating materials, (3) recover economically valuable trace metals and salts. Geothermal power resources which utilize low salinity brines and use the Stretford process for hydrogen sulfide abatement generate a contaminated sulfur cake. Combined technology converts such sulfur to a commercial grade sulfur, suitable for agricultural use. The R and D activities at BNL are conducted jointly with industrial parties in an effort focused on field applications.

  19. Biochemical processes for geothermal brine treatment

    Energy Technology Data Exchange (ETDEWEB)

    Premuzic, E.T.; Lin, M.S.; Bohenek, M.; Joshi-Tope, G.; Zhou, W.; Shelenkova, L.; Wilke, R.

    1998-08-01

    As part of the DOE Geothermal Energy Program, BNL`s Advanced Biochemical Processes for Geothermal Brines (ABPGB) project is aimed at the development of cost-efficient and environmentally acceptable technologies for the disposal of geothermal wastes. Extensive chemical studies of high and low salinity brines and precipitates have indicated that in addition to trace quantities of regulated substances, e.g., toxic metals such as arsenic and mercury, there are significant concentrations of valuable metals, including gold, silver and platinum. Further chemical and physical studies of the silica product have also shown that the produced silica is a valuable material with commercial potential. A combined biochemical and chemical technology is being developed which (1) solubilizes, separates, and removes environmentally regulated constituents in geothermal precipitates and brines, (2) generates an amorphous silica product which may be used as feedstock for the production of revenue generating materials, (3) recover economically valuable trace metals and salts. Geothermal power resources which utilize low salinity brines and use the Stretford process for hydrogen sulfide abatement generate a contaminated sulfur cake. Combined technology converts such sulfur to a commercial grade sulfur, suitable for agricultural use. The R and D activities at BNL are conducted jointly with industrial parties in an effort focused on field applications.

  20. Serum biochemical markers in carcinoma breast.

    Directory of Open Access Journals (Sweden)

    Seth R

    2003-08-01

    Full Text Available BACKGROUND: Despite the extensive research for many years throughout the world, the etiopathogenesis of cancer still remains obscure. For the early detection of carcinoma of various origins, a number of biochemical markers have been studied to evaluate the malignancy. AIM: To analyse serum gamma glutamyl transpeptidase (GGTP, lactate dehydrogenase (LDH and superoxide dismutase (SOD in carcinoma breast patients. SETTINGS & DESIGN: The serum biochemical markers were estimated in twenty five histopathologically confirmed patients with carcinoma breast and equal number of healthy age- matched individuals served as control. MATERIAL & METHODS: Serum gamma glutamyl transpeptidase (GGTP, lactate dehydrogenase (LDH and superoxide dismutase (SOD were estimated and their sensitivity determined. Statistics: Data was analysed with student′s ′t′-test and sensitivity score of these markers was determined. RESULTS & CONCLUSIONS: The mean serum GGTP, LDH and SOD activities in patients with carcinoma breast were tremendously increased as compared to controls, and a steady increase was observed in their activities from stage I through stage IV as well as following distant metastasis. Serum GGTP, LDH and SOD might prove to be most sensitive biomarkers in carcinoma breast in early detection of the disease.

  1. Roadmap towards justice in urban climate adaptation research

    Science.gov (United States)

    Shi, Linda; Chu, Eric; Anguelovski, Isabelle; Aylett, Alexander; Debats, Jessica; Goh, Kian; Schenk, Todd; Seto, Karen C.; Dodman, David; Roberts, Debra; Roberts, J. Timmons; Vandeveer, Stacy D.

    2016-02-01

    The 2015 United Nations Climate Change Conference in Paris (COP21) highlighted the importance of cities to climate action, as well as the unjust burdens borne by the world's most disadvantaged peoples in addressing climate impacts. Few studies have documented the barriers to redressing the drivers of social vulnerability as part of urban local climate change adaptation efforts, or evaluated how emerging adaptation plans impact marginalized groups. Here, we present a roadmap to reorient research on the social dimensions of urban climate adaptation around four issues of equity and justice: (1) broadening participation in adaptation planning; (2) expanding adaptation to rapidly growing cities and those with low financial or institutional capacity; (3) adopting a multilevel and multi-scalar approach to adaptation planning; and (4) integrating justice into infrastructure and urban design processes. Responding to these empirical and theoretical research needs is the first step towards identifying pathways to more transformative adaptation policies.

  2. Molecular and Biochemical Effects of a Kola Nut Extract on Androgen Receptor-Mediated Pathways

    International Nuclear Information System (INIS)

    The low incidence of prostate cancer in Asians has been attributed to chemo preventative properties of certain chemicals found in their diet. This study characterized the androgenic and chemo preventative properties of the Jamaican bush tea Bizzy using androgen receptor positive and negative cell lines. Exposure of prostate cells to Biz-2 resulted in a growth inhibition (GI50) of 15 ppm in LNCaP cells and 3.6 ppm in DU145 cells. Biz-2 elicited a 2-fold increase in the mRNA of the anti-apoptotic gene Bcl2, with a 10-fold increase in that of the pro apoptotic gene Bax. We observed a 2.4- to 7.5-fold change in apoptotic cells in both cell lines. Biz-2 at 10 ppm elicited a time- and dose-dependent stimulation of both the protein and mRNA levels of several androgen-regulated genes. Biz-2 caused a 36% decrease in PSA secretion and a significant increase in PSA mRNA. The relative binding affinity (IC50) of Biz-2 for AR was 2- to 5-fold lower than that of the synthetic androgen R1881. Biz-2 was found to be a specific ligand for the AR in that the natural ligand, DHT, and the anti-androgen, flutamide, displaced Biz-2 bound to AR and inhibited Biz-2-induced transcription and PSA secretion. This study provided evidence that Biz-2 extract possesses the ability to modulate prostate cancer cell biology in an AR-dependent manner.

  3. Molecular and Biochemical Effects of a Kola Nut Extract on Androgen Receptor-Mediated Pathways

    Directory of Open Access Journals (Sweden)

    Rajasree Solipuram

    2009-01-01

    Full Text Available The low incidence of prostate cancer in Asians has been attributed to chemopreventative properties of certain chemicals found in their diet. This study characterized the androgenic and chemopreventative properties of the Jamaican bush tea “Bizzy,” using androgen receptor positive and negative cell lines. Exposure of prostate cells to Biz-2 resulted in a growth inhibition (GI50 of 15 ppm in LNCaP cells and 3.6 ppm in DU145 cells. Biz-2 elicited a 2-fold increase in the mRNA of the anti-apoptotic gene Bcl2, with a 10-fold increase in that of the proapoptotic gene Bax. We observed a 2.4- to 7.5-fold change in apoptotic cells in both cell lines. Biz-2 at 10 ppm elicited a time- and dose-dependent stimulation of both the protein and mRNA levels of several androgen-regulated genes. Biz-2 caused a 36% decrease in PSA secretion and a significant increase in PSA mRNA. The relative binding affinity (IC50 of Biz-2 for AR was 2- to 5-fold lower than that of the synthetic androgen R1881. Biz-2 was found to be a specific ligand for the AR in that the natural ligand, DHT, and the anti-androgen, flutamide, displaced Biz-2 bound to AR and inhibited Biz-2-induced transcription and PSA secretion. This study provided evidence that Biz-2 extract possesses the ability to modulate prostate cancer cell biology in an AR-dependent manner.

  4. Microbial degradation of fluorinated drugs: biochemical pathways, impacts on the environment and potential applications.

    Science.gov (United States)

    Murphy, Cormac D

    2016-03-01

    Since the discovery over 60 years ago of fluorocortisone's biological properties (9-α-Fluoro derivatives of cortisone and hydrocortisone; Fried J and Sabo EF, J Am Chem Soc 76: 1455-1456, 1954), the number of fluorinated drugs has steadily increased. With the improvement in synthetic methodologies, this trend is likely to continue and will lead to the introduction of new fluorinated substituents into pharmaceutical compounds. Although the biotransformation of organofluorine compounds by microorganisms has been well studied, specific investigations on fluorinated drugs are relatively few, despite the increase in the number and variety of fluorinated drugs that are available. The strength of the carbon-fluorine bond conveys stability to fluorinated drugs; thus, they are likely to be recalcitrant in the environment or may be partially metabolized to a more toxic metabolite. This review examines the research done on microbial biotransformation and biodegradation of fluorinated drugs and highlights the importance of understanding how microorganisms interact with this class of compound from environmental, clinical and biotechnological perspectives. PMID:26830103

  5. Biochemical Modulation of Lipid Pathway in Microalgae Dunaliella sp. for Biodiesel Production

    OpenAIRE

    Ahmad Farhad Talebi; Masoud Tohidfar; Seyedeh Mahsa Mousavi Derazmahalleh; Alawi Sulaiman; Azhari Samsu Baharuddin,; Meisam Tabatabaei

    2015-01-01

    Exploitation of renewable sources of energy such as algal biodiesel could turn energy supplies problem around. Studies on a locally isolated strain of Dunaliella sp. showed that the mean lipid content in cultures enriched by 200 mg L−1 myoinositol was raised by around 33% (1.5 times higher than the control). Similarly, higher lipid productivity values were achieved in cultures treated by 100 and 200 mg L−1 myoinositol. Fluorometry analyses (microplate fluorescence and flow cytometry) revealed...

  6. Biochemical and molecular analyses of the biosynthesis pathway of the indole derivatives in Piriformospora indica

    OpenAIRE

    Hilbert, Magdalena

    2013-01-01

    The mutualistic root endophyte Piriformospora indica has the ability to colonize a wide range of plants including the monocot barley (Hordeum vulgare) and the dicot model plant Arabidopsis thaliana. The colonization of both, Arabidopsis and barley is characterized by a biphasic colonization strategy with an initial biotrophic interaction followed by a cell death associated phase. During both phases fungal inter- and intracellular ...

  7. TrypanoCyc: A community-led biochemical pathways database for Trypanosoma brucei

    NARCIS (Netherlands)

    S. Shameer (Sanu); F.J. Logan-Klumpler (Flora J.); F. Vinson (Florence); L. Cottret (Ludovic); B. Merlet (Benjamin); F. Achcar (Fiona); M. Boshart (Michael); M. Berriman (Matthew); R. Breitling (Rainer); F. Bringaud (Frédéric); P. Bütikofer (Peter); A.M. Cattanach (Amy M.); B. Bannerman-Chukualim (Bridget); D.J. Creek (Darren J.); K. Crouch (Kathryn); H.P. De Koning (Harry P.); H. Denise (Hubert); C. Ebikeme (Charles); A.H. Fairlamb (Alan H.); M.A.J. Ferguson (Michael A. J.); M.L. Ginger (Michael L.); C. Hertz-Fowler (Christiane); E.J. Kerkhoven (Eduard); P. Mäser (Pascal); P.A.M. Michels (Paul); A. Nayak (Archana); D. Nes (DavidW.); D.P. Nolan (Derek P.); C. Olsen (Christian); F. Silva-Franco (Fatima); T.K. Smith (Terry K.); M.C. Taylor (Martin C.); A.G.M. Tielens (Aloysius); M.D. Urbaniak (Michael D.); J.J. van Hellemond (Jaap); I.M. Vincent (Isabel M.); S.R. Wilkinson (Shane R.); S. Wyllie (Susan); F.R. Opperdoes (Fred); M.P. Barrett (Michael P.); F. Jourdan (Fabien)

    2015-01-01

    textabstractThe metabolic network of a cell represents the catabolic and anabolic reactions that interconvert small molecules (metabolites) through the activity of enzymes, transporters and non-catalyzed chemical reactions. Our understanding of individualmetabolic networks is increasing as we learn

  8. TrypanoCyc : a community-led biochemical pathways database for Trypanosoma brucei

    NARCIS (Netherlands)

    Shameer, Sanu; Logan-Klumpler, Flora J; Vinson, Florence; Cottret, Ludovic; Merlet, Benjamin; Achcar, Fiona; Boshart, Michael; Berriman, Matthew; Breitling, Rainer; Bringaud, Frédéric; Bütikofer, Peter; Cattanach, Amy M; Bannerman-Chukualim, Bridget; Creek, Darren J; Crouch, Kathryn; de Koning, Harry P; Denise, Hubert; Ebikeme, Charles; Fairlamb, Alan H; Ferguson, Michael A J; Ginger, Michael L; Hertz-Fowler, Christiane; Kerkhoven, Eduard J; Mäser, Pascal; Michels, Paul A M; Nayak, Archana; Nes, David W; Nolan, Derek P; Olsen, Christian; Silva-Franco, Fatima; Smith, Terry K; Taylor, Martin C; Tielens, Aloysius G M; Urbaniak, Michael D; van Hellemond, Jaap J; Vincent, Isabel M; Wilkinson, Shane R; Wyllie, Susan; Opperdoes, Fred R; Barrett, Michael P; Jourdan, Fabien

    2015-01-01

    The metabolic network of a cell represents the catabolic and anabolic reactions that interconvert small molecules (metabolites) through the activity of enzymes, transporters and non-catalyzed chemical reactions. Our understanding of individual metabolic networks is increasing as we learn more about

  9. Expressing Adaptation Strategies Using Adaptation Patterns

    Science.gov (United States)

    Zemirline, N.; Bourda, Y.; Reynaud, C.

    2012-01-01

    Today, there is a real challenge to enable personalized access to information. Several systems have been proposed to address this challenge including Adaptive Hypermedia Systems (AHSs). However, the specification of adaptation strategies remains a difficult task for creators of such systems. In this paper, we consider the problem of the definition…

  10. Mutual information in time-varying biochemical systems

    OpenAIRE

    Tostevin, Filipe; Wolde, Pieter Rein ten

    2010-01-01

    Cells must continuously sense and respond to time-varying environmental stimuli. These signals are transmitted and processed by biochemical signalling networks. However, the biochemical reactions making up these networks are intrinsically noisy, which limits the reliability of intracellular signalling. Here we use information theory to characterise the reliability of transmission of time-varying signals through elementary biochemical reactions in the presence of noise. We calculate the mutual...

  11. Possibilities and methods for biochemical assessment of radiation injury

    International Nuclear Information System (INIS)

    An extensitive review (77 references) is made of the application of biochemical diagnostic methods for assessment of radiation diseases. A brief characteristics of several biochemical indicators is given: deoxycytidine, thymidine, ρ-aminoisocarboxylic acid, DNA-ase, nucleic acids. Influence of such factors as age, sex, season etc. is studied by means of functional biochemical indicators as: creatine, triptophanic metabolites, 5-hydroxy-indolacetic acid, biogenic amines, serum proteins, enzymes, etc

  12. Conceptual Aspects of Theory Appraisal: Some Biochemical Examples

    Directory of Open Access Journals (Sweden)

    F. Michael Akeroyd

    1997-11-01

    Full Text Available This paper considers papers on conceptual analysis by Laudan (1981 and Whitt (1989 and relates them to three biochemical episodes: (1 the modern 'biochemical explanation' of acupuncture; (2 the chemio-osmotic hypothesis of oxidative phosphorylation; (3 the theory of the complete digestion of proteins in the gut. The advantages of including philosophical debate in chemical/biochemical undergraduate courses is then discussed.

  13. Study regarding magnetospirillum griphyswaldenses bacteria biochemical changes using FTIR and Raman spectroscopy

    International Nuclear Information System (INIS)

    Complete text of publication follows. Spectroscopy using Fourier transform and Raman spectroscopy can be used to enlighten functional groups that belong to different biomolecules that are specific to cells (proteins, lipids, carbohydrates, nucleic acids), thus obtaining valuable information regarding bacteria's biochemical composition. Since microorganisms react very promptly to the culture medium changes, the apparition of a stress agent produces a modification of the cellular enzymatic print in order to compensate for the effect of those factors, thus the bacteria self adapting to those changes. These methods can be used to highlight the metabolically modifications in cells which respond to stress factors. The biochemical modification are important in bioremediation processes like biosorption of metal contaminated waste water from metallurgical baths or even from irradiator pool, heavy water from nuclear power plant. The main targets are to analyze the biochemical modification appeared in presence or absence of two metals, Fe and Co. The presence of Fe is benefit for bacteria because she can absorb iron and deposit as magnetic inside the cell. The presence of Co determines changes in metabolism with the loss of many polar bindings but the growth was not inhibited even in concentration like 100 mM.

  14. Discrimination, mental problems and social adaptation in young refugees

    DEFF Research Database (Denmark)

    Montgomery, Edith; Foldspang, Anders

    2008-01-01

    mean of 1.8 experiences of discrimination, and the prevalence of five indicators of positive social adaptation was 47–92%. Discrimination, mental problems and social adaptation were strongly mutually associated, without gender difference. Discrimination predicted internalizing behaviour. Improved...... externalizing behaviour. The direction of other pathways is ambiguous, suggesting a certain amount of recursive interaction between mental health, discrimination and social adaptation.......Background: Mental problems have been hypothesized to impede social adaptation and vice versa, and discrimination is assumed to interact with both. The available empirical documentation is, however, limited. The objective of this study is to contribute to a more comprehensive understanding of...

  15. Dynamic analysis of biochemical network using complex network method

    Directory of Open Access Journals (Sweden)

    Wang Shuqiang

    2015-01-01

    Full Text Available In this study, the stochastic biochemical reaction model is proposed based on the law of mass action and complex network theory. The dynamics of biochemical reaction system is presented as a set of non-linear differential equations and analyzed at the molecular-scale. Given the initial state and the evolution rules of the biochemical reaction system, the system can achieve homeostasis. Compared with random graph, the biochemical reaction network has larger information capacity and is more efficient in information transmission. This is consistent with theory of evolution.

  16. Uncertainty in adaptive capacity

    International Nuclear Information System (INIS)

    The capacity to adapt is a critical element of the process of adaptation: it is the vector of resources that represent the asset base from which adaptation actions can be made. Adaptive capacity can in theory be identified and measured at various scales, from the individual to the nation. The assessment of uncertainty within such measures comes from the contested knowledge domain and theories surrounding the nature of the determinants of adaptive capacity and the human action of adaptation. While generic adaptive capacity at the national level, for example, is often postulated as being dependent on health, governance and political rights, and literacy, and economic well-being, the determinants of these variables at national levels are not widely understood. We outline the nature of this uncertainty for the major elements of adaptive capacity and illustrate these issues with the example of a social vulnerability index for countries in Africa. (authors)

  17. Adaptive Rationality, Adaptive Behavior and Institutions

    Directory of Open Access Journals (Sweden)

    Volchik Vyacheslav, V.

    2015-12-01

    Full Text Available The economic literature focused on understanding decision-making and choice processes reveals a vast collection of approaches to human rationality. Theorists’ attention has moved from absolutely rational, utility-maximizing individuals to boundedly rational and adaptive ones. A number of economists have criticized the concepts of adaptive rationality and adaptive behavior. One of the recent trends in the economic literature is to consider humans irrational. This paper offers an approach which examines adaptive behavior in the context of existing institutions and constantly changing institutional environment. It is assumed that adaptive behavior is a process of evolutionary adjustment to fundamental uncertainty. We emphasize the importance of actors’ engagement in trial and error learning, since if they are involved in this process, they obtain experience and are able to adapt to existing and new institutions. The paper aims at identifying relevant institutions, adaptive mechanisms, informal working rules and practices that influence actors’ behavior in the field of Higher Education in Russia (Rostov Region education services market has been taken as an example. The paper emphasizes the application of qualitative interpretative methods (interviews and discourse analysis in examining actors’ behavior.

  18. The role of nitrogen oxides in human adaptation to hypoxia

    OpenAIRE

    Levett, Denny Z; Fernandez, Bernadette O.; Riley, Heather L.; Martin, Daniel S; Kay Mitchell; Leckstrom, Carl A.; Can Ince; Brian J. Whipp; Mythen, Monty G; Montgomery, Hugh E.; Grocott, Mike P.; Martin Feelisch

    2011-01-01

    Lowland residents adapt to the reduced oxygen availability at high altitude through a process known as acclimatisation, but the molecular changes underpinning these functional alterations are not well understood. Using an integrated biochemical/whole-body physiology approach we here show that plasma biomarkers of NO production (nitrite, nitrate) and activity (cGMP) are elevated on acclimatisation to high altitude while S-nitrosothiols are initially consumed, suggesting multiple nitrogen oxide...

  19. Ecological Adaptation of Diverse Honey Bee (Apis mellifera) Populations

    OpenAIRE

    Parker, Robert; Melathopoulos, Andony P; White, Rick; Pernal, Stephen F; Guarna, M. Marta; Leonard J Foster

    2010-01-01

    Background Honey bees are complex eusocial insects that provide a critical contribution to human agricultural food production. Their natural migration has selected for traits that increase fitness within geographical areas, but in parallel their domestication has selected for traits that enhance productivity and survival under local conditions. Elucidating the biochemical mechanisms of these local adaptive processes is a key goal of evolutionary biology. Proteomics provides tools unique among...

  20. Category analysis: from biochemical mechanics to astrophysics

    International Nuclear Information System (INIS)

    Full text: One of the main goals of this report is to bridge the gap between computer modelling and group analysis of nonlinear partial differential equations. But we can work with a category of groups rather than a Lie group. In view of the experience of the past development of the relation between mathematics, mechanics and physics, the categorical extension may be justified that one day categoric structures will be as important as groups are today. Also our aim is the application of the same category-theoretic methods in biochemical mechanics and astrophysics. As examples we consider the category analysis of material models for concrete, wood and reinforcing or prestressing steel, on the one hand, and process of the linear and circular polarization of the cosmic microwave background radiation due to the quantum effects of electromagnetic field in anisotropic Bianchi-type cosmological models, on the other hand. (author)

  1. Prions: the danger of biochemical weapons

    Directory of Open Access Journals (Sweden)

    Eric Almeida Xavier

    2014-09-01

    Full Text Available The knowledge of biotechnology increases the risk of using biochemical weapons for mass destruction. Prions are unprecedented infectious pathogens that cause a group of fatal neurodegenerative diseases by a novel mechanism. They are transmissible particles that are devoid of nucleic acid. Due to their singular characteristics, Prions emerge as potential danger since they can be used in the development of such weapons. Prions cause fatal infectious diseases, and to date there is no therapeutic or prophylactic approach against these diseases. Furthermore, Prions are resistant to food-preparation treatments such as high heat and can find their way from the digestive system into the nervous system; recombinant Prions are infectious either bound to soil particles or in aerosols. Therefore, lethal Prions can be developed by malicious researchers who could use it to attack political enemies since such weapons cause diseases that could be above suspicion.

  2. Biochemically enhanced methane production from coal

    Science.gov (United States)

    Opara, Aleksandra

    For many years, biogas was connected mostly with the organic matter decomposition in shallow sediments (e.g., wetlands, landfill gas, etc.). Recently, it has been realized that biogenic methane production is ongoing in many hydrocarbon reservoirs. This research examined microbial methane and carbon dioxide generation from coal. As original contributions methane production from various coal materials was examined in classical and electro-biochemical bench-scale reactors using unique, developed facultative microbial consortia that generate methane under anaerobic conditions. Facultative methanogenic populations are important as all known methanogens are strict anaerobes and their application outside laboratory would be problematic. Additional testing examined the influence of environmental conditions, such as pH, salinity, and nutrient amendments on methane and carbon dioxide generation. In 44-day ex-situ bench-scale batch bioreactor tests, up to 300,000 and 250,000 ppm methane was generated from bituminous coal and bituminous coal waste respectively, a significant improvement over 20-40 ppm methane generated from control samples. Chemical degradation of complex hydrocarbons using environmentally benign reagents, prior to microbial biodegradation and methanogenesis, resulted in dissolution of up to 5% bituminous coal and bituminous coal waste and up to 25% lignite in samples tested. Research results confirm that coal waste may be a significant underutilized resource that could be converted to useful fuel. Rapid acidification of lignite samples resulted in low pH (below 4.0), regardless of chemical pretreatment applied, and did not generate significant methane amounts. These results confirmed the importance of monitoring and adjusting in situ and ex situ environmental conditions during methane production. A patented Electro-Biochemical Reactor technology was used to supply electrons and electron acceptor environments, but appeared to influence methane generation in a

  3. Biochemical Pharmacology of the Sigma-1 Receptor.

    Science.gov (United States)

    Chu, Uyen B; Ruoho, Arnold E

    2016-01-01

    The sigma-1 receptor (S1R) is a 223 amino acid two transmembrane (TM) pass protein. It is a non-ATP-binding nonglycosylated ligand-regulated molecular chaperone of unknown three-dimensional structure. The S1R is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes with broad functions that regulate cellular calcium homeostasis and reduce oxidative stress. Several multitasking functions of the S1R are underwritten by chaperone-mediated direct (and indirect) interactions with ion channels, G-protein coupled receptors and cell-signaling molecules involved in the regulation of cell growth. The S1R is a promising drug target for the treatment of several neurodegenerative diseases related to cellular stress. In vitro and in vivo functional and molecular characteristics of the S1R and its interactions with endogenous and synthetic small molecules have been discovered by the use of pharmacologic, biochemical, biophysical, and molecular biology approaches. The S1R exists in monomer, dimer, tetramer, hexamer/octamer, and higher oligomeric forms that may be important determinants in defining the pharmacology and mechanism(s) of action of the S1R. A canonical GXXXG in putative TM2 is important for S1R oligomerization. The ligand-binding regions of S1R have been identified and include portions of TM2 and the TM proximal regions of the C terminus. Some client protein chaperone functions and interactions with the cochaperone 78-kDa glucose-regulated protein (binding immunoglobulin protein) involve the C terminus. Based on its biochemical features and mechanisms of chaperone action the possibility that the S1R is a member of the small heat shock protein family is discussed. PMID:26560551

  4. Adaptive Coordinate Descent

    OpenAIRE

    Loshchilov, Ilya; Schoenauer, Marc; Sebag, Michèle

    2011-01-01

    Independence from the coordinate system is one source of efficiency and robustness for the Covariance Matrix Adaptation Evolution Strategy (CMA-ES). The recently proposed Adaptive Encoding (AE) procedure generalizes CMA-ES adaptive mechanism, and can be used together with any optimization algorithm. Adaptive Encoding gradually builds a transformation of the coordinate system such that the new coordinates are as decorrelated as possible with respect to the objective function. But any optimizat...

  5. Mammalian O-Mannosylation Pathway: Glycan Structures, Enzymes, and Protein Substrates

    OpenAIRE

    Praissman, Jeremy L; Wells, Lance

    2014-01-01

    The mammalian O-mannosylation pathway for protein post-translational modification is intricately involved in modulating cell–matrix interactions in the musculature and nervous system. Defects in enzymes of this biosynthetic pathway are causative for multiple forms of congenital muscular dystophy. The application of advanced genetic and biochemical technologies has resulted in remarkable progress in this field over the past few years, culminating with the publication of three landmark papers i...

  6. Metabolic Pathway Confirmation and Discovery Through 13C-labeling of Proteinogenic Amino Acids

    OpenAIRE

    You, Le; Page, Lawrence; Feng, Xueyang; Berla, Bert; Pakrasi, Himadri B; Yinjie J. Tang

    2012-01-01

    Microbes have complex metabolic pathways that can be investigated using biochemistry and functional genomics methods. One important technique to examine cell central metabolism and discover new enzymes is 13C-assisted metabolism analysis 1. This technique is based on isotopic labeling, whereby microbes are fed with a 13C labeled substrates. By tracing the atom transition paths between metabolites in the biochemical network, we can determine functional pathways and discover new ...

  7. Simulation of a Petri net-based Model of the Terpenoid Biosynthesis Pathway

    OpenAIRE

    Hawari Aliah; Mohamed-Hussein Zeti-Azura

    2010-01-01

    Abstract Background The development and simulation of dynamic models of terpenoid biosynthesis has yielded a systems perspective that provides new insights into how the structure of this biochemical pathway affects compound synthesis. These insights may eventually help identify reactions that could be experimentally manipulated to amplify terpenoid production. In this study, a dynamic model of the terpenoid biosynthesis pathway was constructed based on the Hybrid Functional Petri Net (HFPN) t...

  8. The role of the Akt/mTOR pathway in tobacco-carcinogen induced lung tumorigenesis

    OpenAIRE

    Memmott, Regan M.; Dennis, Phillip A.

    2009-01-01

    Lung cancer is the leading cause of cancer-related death in the United States, and 85–90% of lung cancer cases are associated with tobacco use. Tobacco components promote lung tumorigenesis through genotoxic effects, as well as through biochemical modulation of signaling pathways such as the Akt/mTOR pathway that regulate cell proliferation and survival. This review will describe cell surface receptors and other upstream components required for tobacco-carcinogen induced activation of Akt and...

  9. Adaptation to climate change

    NARCIS (Netherlands)

    J. Carmin; K. Tierney; E. Chu; L.M. Hunter; J.T. Roberts; L. Shi

    2015-01-01

    Climate change adaptation involves major global and societal challenges such as finding adequate and equitable adaptation funding and integrating adaptation and development programs. Current funding is insufficient. Debates between the Global North and South center on how best to allocate the financ

  10. Biochemical Mechanisms for Geographical Adaptations to Novel Toxin Exposures in Butterflyfish

    Science.gov (United States)

    Knuston, Sean; Slattery, Marc; Ankisetty, Sridevi; Goldstone, Jared V.; Watanabe, Kayo; Hoh, Eunha; Gadepalli, Rama S.; Rimoldi, John M.; Ostrander, Gary K.

    2016-01-01

    Some species of butterflyfish have had preyed upon corals for millions of years, yet the mechanism of butterflyfish specialized coral feeding strategy remains poorly understood. Certain butterflyfish have the ability to feed on allelochemically rich soft corals, e.g. Sinularia maxima. Cytochrome P450 (CYP) is the predominant enzyme system responsible for the detoxification of dietary allelochemicals. CYP2-like and CYP3A-like content have been associated with butterflyfish that preferentially consumes allelochemically rich soft corals. To investigate the role of butterflyfish CYP2 and CYP3A enzymes in dietary preference, we conducted oral feeding experiments using homogenates of S. maxima and a toxin isolated from the coral in four species of butterflyfish with different feeding strategies. After oral exposure to the S. maxima toxin 5-episinulaptolide (5ESL), which is not normally encountered in the Hawaiian butterflyfish diet, an endemic specialist, Chaetodon multicinctus experienced 100% mortality compared to a generalist, Chaetodon auriga, which had significantly more (3–6 fold higher) CYP3A-like basal content and catalytic activity. The specialist, Chaetodon unimaculatus, which preferentially feed on S. maxima in Guam, but not in Hawaii, had 100% survival, a significant induction of 8–12 fold CYP3A-like content, and an increased ability (2-fold) to metabolize 5ESL over other species. Computer modeling data of CYP3A4 with 5ESL were consistent with microsomal transformation of 5ESL to a C15-16 epoxide from livers of C. unimaculatus. Epoxide formation correlated with CYP3A-like content, catalytic activity, induction, and NADPH-dependent metabolism of 5ESL. These results suggest a potentially important role for the CYP3A family in butterflyfish-coral diet selection through allelochemical detoxification. PMID:27136924

  11. Climate variability and the energetic pathways of evolution: the origin of endothermy in mammals and birds.

    Science.gov (United States)

    Portner, Hans O

    2004-01-01

    Large-scale climate oscillations in earth's history have influenced the directions of evolution, last but not least, through mass extinction events. This analysis tries to identify some unifying forces behind the course of evolution that favored an increase in organismic complexity and performance, paralleled by an increase in energy turnover, and finally led to endothermy. The analysis builds on the recent concept of oxygen-limited thermal tolerance and on the hypothesis that unifying principles exist in the temperature-dependent biochemical design of the eukaryotic cell in animals. The comparison of extant water-breathing and air-breathing animal species from various climates provides a cause-and-effect understanding of the trade-offs and constraints in thermal adaptation and their energetic consequences. It is hypothesized that the high costs of functional adaptation to fluctuating temperatures, especially in the cold (cold eurythermy), cause an increase in energy turnover and, at the same time, mobility and agility. These costs are associated with elevated mitochondrial capacities at minimized levels of activation enthalpies for proton leakage. Cold eurythermy is seen as a precondition for the survival of evolutionary crises elicited by repeated cooling events during extreme climate fluctuations. The costs of cold eurythermy appear as the single most important reason why metazoan evolution led to life forms with high energy turnover. They also explain why dinosaurs were able to live in subpolar climates. Finally, they give insight into the pathways, benefits, and trade-offs involved in the evolution of constant, elevated body temperature maintained by endothermy. Eurythermy, which encompasses cold tolerance, is thus hypothesized to be the "missing link" between ectothermy and endothermy. Body temperatures between 32 degrees and 42 degrees C in mammals and birds then result from trade-offs between the limiting capacities of ventilation and circulation and the

  12. Synthesizing Configurable Biochemical Implementation of Linear Systems from Their Transfer Function Specifications.

    Directory of Open Access Journals (Sweden)

    Tai-Yin Chiu

    Full Text Available The ability to engineer synthetic systems in the biochemical context is constantly being improved and has a profound societal impact. Linear system design is one of the most pervasive methods applied in control tasks, and its biochemical realization has been proposed by Oishi and Klavins and advanced further in recent years. However, several technical issues remain unsolved. Specifically, the design process is not fully automated from specification at the transfer function level, systems once designed often lack dynamic adaptivity to environmental changes, matching rate constants of reactions is not always possible, and implementation may be approximative and greatly deviate from the specifications. Building upon the work of Oishi and Klavins, this paper overcomes these issues by introducing a design flow that transforms a transfer-function specification of a linear system into a set of chemical reactions, whose input-output response precisely conforms to the specification. This system is implementable using the DNA strand displacement technique. The underlying configurability is embedded into primitive components and template modules, and thus the entire system is adaptive. Simulation of DNA strand displacement implementation confirmed the feasibility and superiority of the proposed synthesis flow.

  13. Salinity influences the biochemical response of Crassostrea angulata to Arsenic.

    Science.gov (United States)

    Moreira, Anthony; Figueira, Etelvina; Soares, Amadeu M V M; Freitas, Rosa

    2016-07-01

    The increasing rate of occurrence and persistence of climatic events causing salinity shifts, in combination with contamination, may further challenge organisms response to environmental stress. Hence, we studied the effects of different salinity levels (10, 20, 30 and 40) on the response of the oyster Crassostrea angulata to Arsenic (As) exposure (4 mg L(-1)). Total As, Na(+) and K(+) concentrations in oyster tissues were determined. Biochemical analysis were performed to assess osmotic regulation (CA), metabolism (ETS), enzymatic (SOD, CAT and GSTs) and non-enzymatic (GSH/GSSG and LPO) markers of oxidative stress. Results obtained showed significantly higher metabolic activities in oysters maintained in low salinity (10) exposure, coupled with higher As accumulation, as well as higher SOD and CAT activities, compared to higher salinities (30 and 40). GSTs activity and LPO levels were higher in oysters exposed to As at salinities 20, 30 and 40, compared to the same conditions without As. From our findings we concluded that the response of C. angulata to As is influenced by salinity. At the lowest salinity (10) oysters accumulated higher As concentrations, here attributed to higher metabolic rate involved in physiological osmoregulation, also stimulating antioxidant related enzymes activity (SOD and CAT) and thus preventing increased LPO (higher ETS activity also observed without As). On the contrary, at salinities 30 and 40 with As, antioxidant SOD and CAT were inhibited, enabling for LPO generation. Given our results, the effects of As on the oysters antioxidant capacity appears to be more deleterious under higher salinities (20, 30 and 40), comparing to salinity 10. The differentiated responses demonstrated in the present study in C. angulata oysters exposed to As under different salinities, bring new insights on the mechanisms of environmental adaptability of this species, namely to salinity shifts, and the interactions between such alterations and As

  14. Structural and Biochemical Advances in Mammalian RNAi

    OpenAIRE

    Collins, Robert E.; Cheng, Xiaodong

    2006-01-01

    RNAi is a collection of processes mediated by small RNAs that silence gene expression in a sequence-specific manner. Studies of processes as divergent as post-transcriptional gene silencing, transcriptional silencing through RNA-directed DNA methylation, or heterochromatin formation, and even RNA-guided DNA elimination have converged on a core pathway. This review will highlight recent structural and mechanistic studies illustrating siRNA and miRNA processing, RISC formation, the execution of...

  15. Chronic daily headache: biochemical and neurotransmitter abnormalities

    OpenAIRE

    Gallai, Virgilio; Sarchielli, Paola; Genco, Sergio; Alberti, Andrea; D'Andrea, Giovanni

    2000-01-01

    Although chronic daily headache (CDH) represents one of the most relevant complaints of patients in headache centers, the mechanisms underlying the chronicization of head pain are poorly understood. Experimental animal models of chronic pain suggest the involvement of a functional disturbance of several neuronal pathways. The disturbances include an abnormal excitability of nociceptive fibers supplying pain-sensitive structures in the brain responsible for peripheral sensitization (chronic ne...

  16. Essential pathway identification: from in silico analysis to potential antifungal targets in Aspergillus fumigatus

    DEFF Research Database (Denmark)

    Thykær, Jette; Andersen, Mikael Rørdam; Baker, S. E.

    2009-01-01

    Computational metabolic flux modeling has been a great aid for both understanding and manipulating microbial metabolism. A previously developed metabolic flux model for Aspergillus niger, an economically important biotechnology fungus known for protein and organic acid production, is comprised of...... 1190 biochemically unique reactions that are associated with 871 open reading frames. Through a systematic in silico deletion of single metabolic reactions using this model, several essential metabolic pathways were identified for A. niger. A total of 138 reactions were identified as being essential...... biochemical reactions during growth on a minimal glucose medium. The majority of the reactions grouped into essential biochemical pathways covering cell wall biosynthesis, amino acid biosynthesis, energy metabolism and purine and pyrimidine metabolism. Based on the A. niger open reading frames associated with...

  17. The sensory transduction pathways in bacterial chemotaxis

    Science.gov (United States)

    Taylor, Barry L.

    1989-01-01

    Bacterial chemotaxis is a useful model for investigating in molecular detail the behavioral response of cells to changes in their environment. Peritrichously flagellated bacteria such as coli and typhimurium swim by rotating helical flagella in a counterclockwise direction. If flagellar rotation is briefly reversed, the bacteria tumble and change the direction of swimming. The bacteria continuously sample the environment and use a temporal sensing mechanism to compare the present and immediate past environments. Bacteria respond to a broad range of stimuli including changes in temperature, oxygen concentration, pH and osmotic strength. Bacteria are attracted to potential sources of nutrition such as sugars and amino acids and are repelled by other chemicals. In the methylation-dependent pathways for sensory transduction and adaptation in E. coli and S. typhimurium, chemoeffectors bind to transducing proteins that span the plasma membrane. The transducing proteins are postulated to control the rate of autophosphorylation of the CheA protein, which in turn phosphorylates the CheY protein. The phospho-CheY protein binds to the switch on the flagellar motor and is the signal for clockwise rotation of the motor. Adaptation to an attractant is achieved by increasing methylation of the transducing protein until the attractant stimulus is cancelled. Responses to oxygen and certain sugars involve methylation-independent pathways in which adaption occurs without methylation of a transducing protein. Taxis toward oxygen is mediated by the electron transport system and changes in the proton motive force. Recent studies have shown that the methylation-independent pathway converges with the methylation-dependent pathway at or before the CheA protein.

  18. Local biochemical and morphological differences in human Achilles tendinopathy

    DEFF Research Database (Denmark)

    J, Pingel; Fredberg, Ulrich; K, Qvortrup;

    2012-01-01

    The incidence of Achilles tendinopathy is high and underlying etiology as well as biochemical and morphological pathology associated with the disease is largely unknown. The aim of the present study was to describe biochemical and morphological differences in chronic Achilles tendinopathy. The...

  19. Regulation of the Cyanide-Resistant Alternative Respiratory Pathway in the Fungus Acremonium chrysogenum

    OpenAIRE

    Sándor, Erzsébet; Fekete, Erzsébet; Karaffa, Levente

    2003-01-01

    This review summarises the current knowledge on the biochemical and physiological events that directly or indirectly alter the engagement of the cyanide-resistant alternative respiratory pathway in the cephalosporin C producer filamentous fungus Acremonium chrysogenum. Particular emphasis is placed on the role this activity plays in the overproduction of antibiotic, and also on the critical fermentation technology background that supports its operation.

  20. Definitions of biochemical failure in prostate cancer following radiation therapy

    International Nuclear Information System (INIS)

    Purpose: The American Society for Therapeutic Radiology and Oncology (ASTRO) published a consensus panel definition of biochemical failure following radiation therapy for prostate cancer. In this paper, we develop a series of alternative definitions of biochemical failure. Using data from 688 patients, we evaluated the sensitivity and specificity of the various definitions, with respect to a defined 'clinically meaningful' outcome. Methods and Materials: The ASTRO definition of biochemical failure requires 3 consecutive rises in prostate-specific antigen (PSA). We considered several modifications to the standard definition: to require PSA rises of a certain magnitude, to consider 2 instead of 3 rises, to require the final PSA value to be greater than a fixed cutoff level, and to define biochemical failure based on the slope of PSA over 1, 1.5, or 2 years. A clinically meaningful failure is defined as local recurrence, distant metastases, initiation of unplanned hormonal therapy, unplanned radical prostatectomy, or a PSA>25 later than 6 months after radiation. Results: Requiring the final PSA in a series of consecutive rises to be larger than 1.5 ng/mL increased the specificity of biochemical failure. For a fixed specificity, defining biochemical failure based on 2 consecutive rises, or the slope over the last year, could increase the sensitivity by up to approximately 20%, compared to the ASTRO definition. Using a rule based on the slope over the previous year or 2 rises leads to a slightly earlier detection of biochemical failure than does the ASTRO definition. Even with the best rule, only approximately 20% of true failures are biochemically detected more than 1 year before the clinically meaningful event time. Conclusion: There is potential for improvement in the ASTRO consensus definition of biochemical failure. Further research is needed, in studies with long follow-up times, to evaluate the relationship between various definitions of biochemical failure and

  1. Migration pathways in soils

    International Nuclear Information System (INIS)

    This study looked at diffusive migration through three types of deformation; the projectile pathways, hydraulic fractures of the sediments and faults, and was divided into three experimental areas: autoradiography, the determination of diffusion coefficients and electron microscopy of model projectile pathways in clay. For the autoradiography, unstressed samples were exposed to two separate isotopes, Pm-147 (a possible model for Am behaviour) and the poorly sorbed iodide-125. The results indicated that there was no enhanced migration through deformed kaolin samples nor through fractured Great Meteor East (GME) sediment, although some was evident through the projectile pathways in GME and possibly through the GME sheared samples. The scanning electron microscopy of projectile pathways in clay showed that emplacement of a projectile appeared to have no effect on the orientation of particles at distances greater than two projectile radii from the centre of a projectile pathway. It showed that the particles were not simply aligned with the direction of motion of the projectile but that, the closer to the surface of a particular pathway, the closer the particles lay to their original orientation. This finding was of interest from two points of view: i) the ease of migration of a pollutant along the pathway, and ii) possible mechanisms of hole closure. It was concluded that, provided that there is no advective migration, the transport of radionuclides through sediments containing these defects would not be significantly more rapid than in undeformed sediments. (author)

  2. Microarray and Biochemical Analysis of Lovastatin-induced Apoptosis of Squamous Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    Jim Dimitroulakos

    2002-01-01

    Full Text Available We recently identified 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, as a potential therapeutic target of the head and neck squamous cell carcinomas (HNSCC and cervical carcinomas (CC. The products of this complex biochemical pathway, including de novo cholesterol, are vital for a variety of key cellular functions affecting membrane integrity, cell signaling, protein synthesis, and cell cycle progression. Lovastatin, a specific inhibitor of HMG-CoA reductase, induces a pronounced apoptotic response in a specific subset of tumor types, including HNSCC and CC. The mediators of this response are not well established. Identification of differentially expressed genes represents a feasible approach to delineate these mediators as lovastatin has the potential to modulate transcription indirectly by perturbing levels of sterols and other mevalonate metabolites. Expression analysis following treatment of the HNSCC cell lines SCC9 or SCC25 with 10 μM lovastatin for 1 day showed that less than 2% (9 cDNAs of the 588 cDNAs on this microarray were affected in both cell lines. These included diazepam-binding inhibitor/acyl-CoA-binding protein, the activated transcription factor 4 and rhoA. Because the biosynthesis of mevalonate leads to its incorporation into more than a dozen classes of end products, their role in lovastatin-induced apoptosis was also evaluated. Addition of the metabolites of all the major branches of the mevalonate pathway indicated that only the nonsterol moiety, geranylgeranyl pyrophosphate (GGPP, significantly inhibited the apoptotic effects of lovastatin in HNSCC and CC cells. Because rhoA requires GGPP for its function, this links the microarray and biochemical data and identifies rhoA as a potential mediator of the anticancer properties of lovastatin. Our data suggest that the depletion of nonsterol mevalonate metabolites, particularly GGPP, can be potential mediators of

  3. DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl

  4. BALL - biochemical algorithms library 1.3

    Directory of Open Access Journals (Sweden)

    Stöckel Daniel

    2010-10-01

    Full Text Available Abstract Background The Biochemical Algorithms Library (BALL is a comprehensive rapid application development framework for structural bioinformatics. It provides an extensive C++ class library of data structures and algorithms for molecular modeling and structural bioinformatics. Using BALL as a programming toolbox does not only allow to greatly reduce application development times but also helps in ensuring stability and correctness by avoiding the error-prone reimplementation of complex algorithms and replacing them with calls into the library that has been well-tested by a large number of developers. In the ten years since its original publication, BALL has seen a substantial increase in functionality and numerous other improvements. Results Here, we discuss BALL's current functionality and highlight the key additions and improvements: support for additional file formats, molecular edit-functionality, new molecular mechanics force fields, novel energy minimization techniques, docking algorithms, and support for cheminformatics. Conclusions BALL is available for all major operating systems, including Linux, Windows, and MacOS X. It is available free of charge under the Lesser GNU Public License (LPGL. Parts of the code are distributed under the GNU Public License (GPL. BALL is available as source code and binary packages from the project web site at http://www.ball-project.org. Recently, it has been accepted into the debian project; integration into further distributions is currently pursued.

  5. PHA bioplastics, biochemicals, and energy from crops.

    Science.gov (United States)

    Somleva, Maria N; Peoples, Oliver P; Snell, Kristi D

    2013-02-01

    Large scale production of polyhydroxyalkanoates (PHAs) in plants can provide a sustainable supply of bioplastics, biochemicals, and energy from sunlight and atmospheric CO(2). PHAs are a class of polymers with various chain lengths that are naturally produced by some microorganisms as storage materials. The properties of these polyesters make them functionally equivalent to many of the petroleum-based plastics that are currently in the market place. However, unlike most petroleum-derived plastics, PHAs can be produced from renewable feedstocks and easily degrade in most biologically active environments. This review highlights research efforts over the last 20 years to engineer the production of PHAs in plants with a focus on polyhydroxybutryrate (PHB) production in bioenergy crops with C(4) photosynthesis. PHB has the potential to be a high volume commercial product with uses not only in the plastics and materials markets, but also in renewable chemicals and feed. The major challenges of improving product yield and plant fitness in high biomass yielding C(4) crops are discussed in detail. PMID:23294864

  6. NUTRITION AND SPORTS: A BIOCHEMICAL APPROACH

    Directory of Open Access Journals (Sweden)

    A.A.G. Bianco

    2004-05-01

    Full Text Available This work presents a course dedicated to the pedagogical instruction of graduate students (Ensino deBioqumica - QBQ 5711 in which they have to plan and teach a 30 hour-discipline for undergraduatestudents. The graduate students have to choose a subject for the discipline and, in 2003, the cho-sen subject was Nutrition and Sports: a Biochemical Approach, which is not specically broached inregular disciplines. The discipline was structured in the basis of collaborative learning, thus, the 75 en-rolled undergraduate students (from dierent courses as Nutrition, Sports, Pharmacy, Chemistry andBiology were organized in small working groups. The students were given a study guide produced bythe graduate teachers (available in Portuguese at http://www.sbbq.org.br/revista/mtdidaticos.php,in which the following contents were covered: muscle contraction, O2 up-take, oxidative stress andanti-oxidant response, cramp, hydration, doping and nutritional supplies. In the nal activity thestudents had to evaluate critically myths and true facts in 80 statements usually associated to physi-cal activities and sports. The discipline was evaluated through questionnaires. From the analysis ofthe answers of both undergraduate and graduate/teachers students it is possible to conclude that thediscipline was well conduced and succeeded. These results emphasize the relevance and contribution ofthis kind of discipline to the pedagogical instruction of the graduate students and also to the increaseof undergraduate students interests in Biochemistry.

  7. Biochemical and proteomic characterization of alkaptonuric chondrocytes.

    Science.gov (United States)

    Braconi, Daniela; Bernardini, Giulia; Bianchini, Claretta; Laschi, Marcella; Millucci, Lia; Amato, Loredana; Tinti, Laura; Serchi, Tommaso; Chellini, Federico; Spreafico, Adriano; Santucci, Annalisa

    2012-09-01

    Alkaptonuria (AKU) is a rare genetic disease associated with the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products which leads to the deposition of melanin-like pigments (ochronosis) in connective tissues. Although numerous case reports have described ochronosis in joints, little is known on the molecular mechanisms leading to such a phenomenon. For this reason, we characterized biochemically chondrocytes isolated from the ochronotic cartilage of AKU patients. Based on the macroscopic appearance of the ochronotic cartilage, two sub-populations were identified: cells coming from the black portion of the cartilage were referred to as "black" AKU chondrocytes, while those coming from the white portion were referred to as "white" AKU chondrocytes. Notably, both AKU chondrocytic types were characterized by increased apoptosis, NO release, and levels of pro-inflammatory cytokines. Transmission electron microscopy also revealed that intracellular ochronotic pigment deposition was common to both "white" and "black" AKU cells. We then undertook a proteomic and redox-proteomic analysis of AKU chondrocytes which revealed profound alterations in the levels of proteins involved in cell defence, protein folding, and cell organization. An increased post-translational oxidation of proteins, which also involved high molecular weight protein aggregates, was found to be particularly relevant in "black" AKU chondrocytes. PMID:22213341

  8. Skin biochemical composition analysis by Raman spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Patricia Karen; Tosato, Maira Gaspar; Alves, Rani de Souza; Martin, Airton Abrahao; Favero, Priscila Pereira; Raniero, Leandro, E-mail: amartin@univap.br [Laboratorio de Espectroscopia Vibracional Biomedica, Instituto de Pesquisa e Desenvolvimento - IP e D, Universidade do Vale do Paraiba - UniVap, Sao Jose dos Campos, SP (Brazil)

    2012-09-15

    Skin aging is characterized by cellular and molecular alterations. In this context, Confocal Raman spectroscopy was used in vivo to measure these biochemical changes as function of the skin depth. In this study we have tried to correlate spectra from pure amino acids to in vivo spectra from volunteers with different ages. This study was performed on 32 volunteers: 11 from Group A (20-23 years), 11 from Group B (39-42 years) and 10 from Group C (59-62 years). For each group, the Raman spectra were measured on the surface (0 mm), 30 +- 3 mm and 60 +- 3 {mu}m below the surface. The results from intergroup comparisons showed that the oldest group had a prevalence of the tyrosine band, but it also presented a decrease in the band centered at 875 cm{sup -1} of pyrrolidone acid. The amide I band centered at 1637 cm{sup -1} that is attributed to collagen, as well as other proteins and lipid, showed a smaller amount of these biomolecules for Group C, which can be explained by the decrease in collagen concentration as a function of age. (author)

  9. [Blood biochemical indices of female red-crowned crane (Grus japonensis) in Zhalong Nature Reserve of Heilongjiang Province, Northeast China].

    Science.gov (United States)

    Wang, Hong-Wei; Sun, Zhong-Wu; Zou, Hong-Fei; Jin, Guang-Yao

    2009-10-01

    From November 2004 to October 2005, twenty blood biochemical indices, i. e., total protein, serum albumin, serum globulin, total bilirubin, direct bilirubin, indirect bilirubin, blood glucose, serum urea nitrogen, serum creatine, total cholesterol, triglyceride, aspartate amino transferase, alanine amino transferase, alkaline phosphatase, serum creatine kinase, hydroxybutyrate dehydrogenase, lactic dehydrogenase, serum calcium ion, inorganic phosphate, and magnesium ion, of 10 female Grus japonensis adults in their wintering, reproduction, and migration periods in Zhalong Nature Reserve were analyzed by automatic biochemical analyzer. Significant differences (P < 0.05 or P < 0.01) were observed in the test indices except serum total protein, serum globulin, and blood glucose among the three life periods, which suggested that the serum total protein, serum globulin, and blood glucose could be used as the reliable references of blood biochemical indices of female G. japonensis, while the year-round dynamics of the other 17 indices reflected the physiological characteristics and ecological adaptability of female G. japonensis in its different periods in one year. When using these 17 indices as the references of the blood biochemical indices of female G. japonensis, the physiological period should be considered. PMID:20077721

  10. Modular and Stochastic Approaches to Molecular Pathway Models of ATM, TGF beta, and WNT Signaling

    Science.gov (United States)

    Cucinotta, Francis A.; O'Neill, Peter; Ponomarev, Artem; Carra, Claudio; Whalen, Mary; Pluth, Janice M.

    2009-01-01

    Deterministic pathway models that describe the biochemical interactions of a group of related proteins, their complexes, activation through kinase, etc. are often the basis for many systems biology models. Low dose radiation effects present a unique set of challenges to these models including the importance of stochastic effects due to the nature of radiation tracks and small number of molecules activated, and the search for infrequent events that contribute to cancer risks. We have been studying models of the ATM, TGF -Smad and WNT signaling pathways with the goal of applying pathway models to the investigation of low dose radiation cancer risks. Modeling challenges include introduction of stochastic models of radiation tracks, their relationships to more than one substrate species that perturb pathways, and the identification of a representative set of enzymes that act on the dominant substrates. Because several pathways are activated concurrently by radiation the development of modular pathway approach is of interest.

  11. Origins of adaptive immunity.

    Science.gov (United States)

    Liongue, Clifford; John, Liza B; Ward, Alister

    2011-01-01

    Adaptive immunity, involving distinctive antibody- and cell-mediated responses to specific antigens based on "memory" of previous exposure, is a hallmark of higher vertebrates. It has been argued that adaptive immunity arose rapidly, as articulated in the "big bang theory" surrounding its origins, which stresses the importance of coincident whole-genome duplications. Through a close examination of the key molecules and molecular processes underpinning adaptive immunity, this review suggests a less-extreme model, in which adaptive immunity emerged as part of longer evolutionary journey. Clearly, whole-genome duplications provided additional raw genetic materials that were vital to the emergence of adaptive immunity, but a variety of other genetic events were also required to generate some of the key molecules, whereas others were preexisting and simply co-opted into adaptive immunity. PMID:21395512

  12. Technology transfer for adaptation

    Science.gov (United States)

    Biagini, Bonizella; Kuhl, Laura; Gallagher, Kelly Sims; Ortiz, Claudia

    2014-09-01

    Technology alone will not be able to solve adaptation challenges, but it is likely to play an important role. As a result of the role of technology in adaptation and the importance of international collaboration for climate change, technology transfer for adaptation is a critical but understudied issue. Through an analysis of Global Environment Facility-managed adaptation projects, we find there is significantly more technology transfer occurring in adaptation projects than might be expected given the pessimistic rhetoric surrounding technology transfer for adaptation. Most projects focused on demonstration and early deployment/niche formation for existing technologies rather than earlier stages of innovation, which is understandable considering the pilot nature of the projects. Key challenges for the transfer process, including technology selection and appropriateness under climate change, markets and access to technology, and diffusion strategies are discussed in more detail.

  13. Diffusion Adaptation over Networks

    CERN Document Server

    Sayed, Ali H

    2012-01-01

    Adaptive networks are well-suited to perform decentralized information processing and optimization tasks and to model various types of self organized and complex behavior encountered in nature. Adaptive networks consist of a collection of agents with processing and learning abilities. The agents are linked together through a connection topology, and they cooperate with each other through local interactions to solve distributed inference problems in real-time. The continuous diffusion of information across the network enables agents to adapt their performance in relation to changing data and network conditions; it also results in improved adaptation and learning performance relative to non-cooperative networks. This article provides an overview of diffusion strategies for adaptation and learning over networks. The article is divided into several sections: 1. Motivation; 2. Mean-Square-Error Estimation; 3. Distributed Optimization via Diffusion Strategies; 4. Adaptive Diffusion Strategies; 5. Performance of Ste...

  14. Stimulus-specific adaptation at the synapse level in vitro

    OpenAIRE

    Haitao Wang; Yi-Fan Han; Ying-Shing Chan; Jufang He

    2014-01-01

    Stimulus-specific adaptation (SSA) is observed in many brain regions in humans and animals. SSA of cortical neurons has been proposed to accumulate through relays in ascending pathways. Here, we examined SSA at the synapse level using whole-cell patch-clamp recordings of primary cultured cortical neurons of the rat. First, we found that cultured neurons had high firing capability with 100-Hz current injection. However, neuron firing started to adapt to repeated electrically activated synaptic...

  15. Exercise, PGC-1α and metabolic adaptation in skeletal muscle

    OpenAIRE

    Yan, Zhen

    2009-01-01

    Endurance exercise promotes skeletal muscle adaptation, and exercise-induced peroxisome proliferator-activated receptor γ co-activator-1α (Pgc-1α) gene expression may play a pivotal role in the adaptive processes. Recent applications of mouse genetic models and in vivo imaging in exercise studies started to delineate the signaling-transcription pathways that are involved in the regulation of the Pgc-1α gene. These studies revealed the importance of p38 mitogen-activated protein kinase (MAPK)/...

  16. Connecting the Sun to Flowering in Sunflower Adaptation

    OpenAIRE

    Blackman, Benjamin K.; Michaels, Scott D.; Rieseberg, Loren H.

    2011-01-01

    Species living in seasonal environments often adaptively time their reproduction in response to photoperiod cues. We characterized the expression of genes in the flowering-time regulatory network across wild populations of the common sunflower, Helianthus annuus, that we found to be adaptively differentiated for photoperiod response. The observed clinal variation was associated with changes at multiple hierarchical levels in multiple pathways. Paralog-specific changes in FT homolog expression...

  17. Consciousness And Adaptive Behavior

    OpenAIRE

    Sieb, Richard/A.

    2005-01-01

    Consciousness has resisted scientific explanation for centuries. The main problem in explaining consciousness is its subjectivity. Subjective systems may be adaptive. Humans can produce voluntary new or novel intentional (adaptive) action and such action is always accompanied by consciousness. Action normally arises from perception. Perception must be rerepresented in order to produce new or novel adaptive action. The internal explicit states produced by a widespread nonlinear emergen...

  18. Human Adaptations: Free divers

    OpenAIRE

    Tournat, Troy Z.

    2014-01-01

    Freediving has been around for thousands of years and was only way to dive until the inventionof oxygen tanks in the 19th century. Around the world, people dove for goods such as pearls, andtoday people freedive for sport. Divers stretch the limit of their body and mind’s capabilitiesthrough psychological adaptations from thermal, respiratory, and cardiovascular responses.Findings conclude that thermal adaptations are a similar process to cold adaptive response. Withthe implementation of wets...

  19. Adaptive Multimedia Retrieval: Semantics, Context, and Adaptation

    DEFF Research Database (Denmark)

    This book constitutes the thoroughly refereed post-conference proceedings of the 10th International Conference on Adaptive Multimedia Retrieval, AMR 2012, held in Copenhagen, Denmark, in October 2012. The 17 revised full papers presented were carefully reviewed and selected from numerous submissi......This book constitutes the thoroughly refereed post-conference proceedings of the 10th International Conference on Adaptive Multimedia Retrieval, AMR 2012, held in Copenhagen, Denmark, in October 2012. The 17 revised full papers presented were carefully reviewed and selected from numerous...

  20. Decentralized adaptive control

    Science.gov (United States)

    Oh, B. J.; Jamshidi, M.; Seraji, H.

    1988-01-01

    A decentralized adaptive control is proposed to stabilize and track the nonlinear, interconnected subsystems with unknown parameters. The adaptation of the controller gain is derived by using model reference adaptive control theory based on Lyapunov's direct method. The adaptive gains consist of sigma, proportional, and integral combination of the measured and reference values of the corresponding subsystem. The proposed control is applied to the joint control of a two-link robot manipulator, and the performance in computer simulation corresponds with what is expected in theoretical development.

  1. Adaptive Wireless Transceiver Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Wireless technologies are an increasingly attractive means for spatial data, input, manipulation, and distribution. Mobitrum is proposing an innovative Adaptive...

  2. Light harvesting complexes and chromatic adaptation of Eustigmatophyte alga \\kur{Trachydiscus minutus}

    OpenAIRE

    PAZDERNÍK, Marek

    2015-01-01

    The chromatic adaptation of Trachydiscus minutus was investigated by separation of light harvesting complexes (antennae and photosystems) on a sucrose gradient using variety of detergents and their concentrations, further complex purification and characterization was done using biochemical separation and spectroscopic techniques.

  3. Growth rate regulates membrane fluidity and membrane cold adaptation in .i.Bacillus subtilis./i

    Czech Academy of Sciences Publication Activity Database

    Beranová, J.; Jemiola-Rzeminska, M.; Elhottová, Dana; Strzalka, K.; Konopásek, I.

    2007-01-01

    Roč. 274, Suppl. 1 (2007), s. 362. ISSN 1742-464X. [Congress of the Federation-of-European-Biochemical-Societies /32./. 07.07.2007-12.07.2007, Vienna] Institutional research plan: CEZ:AV0Z60660521 Keywords : membrane fluidity * membrane cold adaptation * Bacillus subtilis Subject RIV: EH - Ecology, Behaviour

  4. 40 CFR 158.2080 - Experimental use permit data requirements-biochemical pesticides.

    Science.gov (United States)

    2010-07-01

    ... requirements-biochemical pesticides. 158.2080 Section 158.2080 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR PESTICIDES Biochemical Pesticides § 158.2080 Experimental use permit data requirements—biochemical pesticides. (a) Sections...

  5. Using Bioinformatic Approaches to Identify Pathways Targeted by Human Leukemogens

    Directory of Open Access Journals (Sweden)

    Luoping Zhang

    2012-07-01

    Full Text Available We have applied bioinformatic approaches to identify pathways common to chemical leukemogens and to determine whether leukemogens could be distinguished from non-leukemogenic carcinogens. From all known and probable carcinogens classified by IARC and NTP, we identified 35 carcinogens that were associated with leukemia risk in human studies and 16 non-leukemogenic carcinogens. Using data on gene/protein targets available in the Comparative Toxicogenomics Database (CTD for 29 of the leukemogens and 11 of the non-leukemogenic carcinogens, we analyzed for enrichment of all 250 human biochemical pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG database. The top pathways targeted by the leukemogens included metabolism of xenobiotics by cytochrome P450, glutathione metabolism, neurotrophin signaling pathway, apoptosis, MAPK signaling, Toll-like receptor signaling and various cancer pathways. The 29 leukemogens formed 18 distinct clusters comprising 1 to 3 chemicals that did not correlate with known mechanism of action or with structural similarity as determined by 2D Tanimoto coefficients in the PubChem database. Unsupervised clustering and one-class support vector machines, based on the pathway data, were unable to distinguish the 29 leukemogens from 11 non-leukemogenic known and probable IARC carcinogens. However, using two-class random forests to estimate leukemogen and non-leukemogen patterns, we estimated a 76% chance of distinguishing a random leukemogen/non-leukemogen pair from each other.

  6. Vitamin B12 transport from food to the body's cells--a sophisticated, multistep pathway

    DEFF Research Database (Denmark)

    Nielsen, Marianne J; Rasmussen, Mie R; Andersen, Christian B F;

    2012-01-01

    Vitamin B(12) (B(12); also known as cobalamin) is a cofactor in many metabolic processes; deficiency of this vitamin is associated with megaloblastic anaemia and various neurological disorders. In contrast to many prokaryotes, humans and other mammals are unable to synthesize B(12). Instead, a...... transport pathway are also known culprits of functional B(12) deficiency. Biochemical and genetic approaches have identified novel proteins in the B(12) transport pathway--now known to involve more than 15 gene products--delineating a coherent pathway for B(12) trafficking from food to the body's cells...

  7. Electron transfer pathways induced in photosynthetic chain upon intensive illumination

    International Nuclear Information System (INIS)

    The changes in the redox state of cytochromes f, b559 and b0 from isolated pean cloroplasts upon intensive (200 Wt/m2) illuminatioon of dark- or light-adapted plastids (pH 6.0) were studied. In the latter case, the illuminating light was switched on 2 min after 1 min illumination with intensive light. It was found that in preilluminated chloroplasts a steady redox state of the cytochromes was induced earlier than in dark-adapted ones. The kinetics of the cytochrome b6 transition during intensive illumination of dark-adapted plastids is suggestive of a slow formation of an oxidation pathway, whereas upon illumination of light-adapted plastids, this pathway comes into operation very quickly. Upon weak illumination, such an oxidation takes place in preliminary plastids. The kinetics of cytochrome b559 transition in preilluminated plastids suggest that upon intensive illumination the oxidation pathway of cytochrome b559 is formed in the photosystem II reaction center. It is assumed that the formation of specific pathways of oxidation and reduction of the cytochomes under effects of intensive illumination is a result of conformational changes in tylakoid memebranes and their slow recovery in the dark at weakly acidic values of pH

  8. Predicting the pathway involved in post-translational modification of Elongation factor P in a subset of bacterial species

    Directory of Open Access Journals (Sweden)

    de Crécy-Lagard Valérie

    2010-01-01

    Full Text Available Abstract Background The bacterial elongation factor P (EF-P is strictly conserved in bacteria and essential for protein synthesis. It is homologous to the eukaryotic translation initiation factor 5A (eIF5A. A highly conserved eIF5A lysine is modified into an unusual amino acid derived from spermidine, hypusine. Hypusine is absolutely required for eIF5A's role in translation in Saccharomyces cerevisiae. The homologous lysine of EF-P is also modified to a spermidine derivative in Escherichia coli. However, the biosynthesis pathway of this modification in the bacterial EF-P is yet to be elucidated. Presentation of the Hypothesis Here we propose a potential mechanism for the post-translational modification of EF-P. By using comparative genomic methods based on physical clustering and phylogenetic pattern analysis, we identified two protein families of unknown function, encoded by yjeA and yjeK genes in E. coli, as candidates for this missing pathway. Based on the analysis of the structural and biochemical properties of both protein families, we propose two potential mechanisms for the modification of EF-P. Testing the hypothesis This hypothesis could be tested genetically by constructing a bacterial strain with a tagged efp gene. The tag would allow the purification of EF-P by affinity chromatography and the analysis of the purified protein by mass spectrometry. yjeA or yjeK could then be deleted in the efp tagged strain and the EF-P protein purified from each mutant analyzed by mass spectrometry for the presence or the absence of the modification. This hypothesis can also be tested by purifying the different components (YjeK, YjeA and EF-P and reconstituting the pathway in vitro. Implication of the hypothesis The requirement for a fully modified EF-P for protein synthesis in certain bacteria implies the presence of specific post-translational modification mechanism in these organisms. All of the 725 bacterial genomes analyzed, possess an efp gene

  9. Behavioral Adaptation and Acceptance

    NARCIS (Netherlands)

    Martens, M.H.; Jenssen, G.D.

    2012-01-01

    One purpose of Intelligent Vehicles is to improve road safety, throughput, and emissions. However, the predicted effects are not always as large as aimed for. Part of this is due to indirect behavioral changes of drivers, also called behavioral adaptation. Behavioral adaptation (BA) refers to uninte

  10. Behavioural adaptation and acceptance

    NARCIS (Netherlands)

    Martens, M.H.; Jenssen, G.D.; Eskandarian, A.

    2012-01-01

    One purpose of Intelligent Vehicles is to improve road safety, throughput, and emissions. However, the predicted effects are not always as large as aimed for. Part of this is due to indirect behavioral changes of drivers, also called behavioral adaptation. Behavioral adaptation (BA) refers to uninte

  11. Adaptive Capacity and Traps

    Directory of Open Access Journals (Sweden)

    William A. Brock

    2008-12-01

    Full Text Available Adaptive capacity is the ability of a living system, such as a social–ecological system, to adjust responses to changing internal demands and external drivers. Although adaptive capacity is a frequent topic of study in the resilience literature, there are few formal models. This paper introduces such a model and uses it to explore adaptive capacity by contrast with the opposite condition, or traps. In a social–ecological rigidity trap, strong self-reinforcing controls prevent the flexibility needed for adaptation. In the model, too much control erodes adaptive capacity and thereby increases the risk of catastrophic breakdown. In a social–ecological poverty trap, loose connections prevent the mobilization of ideas and resources to solve problems. In the model, too little control impedes the focus needed for adaptation. Fluctuations of internal demand or external shocks generate pulses of adaptive capacity, which may gain traction and pull the system out of the poverty trap. The model suggests some general properties of traps in social–ecological systems. It is general and flexible, so it can be used as a building block in more specific and detailed models of adaptive capacity for a particular region.

  12. Biocatalytic Pathway Selection in Transient Tripeptide Nanostructures.

    Science.gov (United States)

    Pappas, Charalampos G; Sasselli, Ivan R; Ulijn, Rein V

    2015-07-01

    Structural adaption in living systems is achieved by competing catalytic pathways that drive assembly and disassembly of molecular components under the influence of chemical fuels. We report on a simple mimic of such a system that displays transient, sequence-dependent formation of supramolecular nanostructures based on biocatalytic formation and hydrolysis of self-assembling tripeptides. The systems are catalyzed by α-chymotrypsin and driven by hydrolysis of dipeptide aspartyl-phenylalanine-methyl ester (the sweetener aspartame, DF-OMe). We observed switch-like pathway selection, with the kinetics and consequent lifetime of transient nanostructures controlled by the peptide sequence. In direct competition, kinetic (rather than thermodynamic) component selection is observed. PMID:26014441

  13. Impact on biochemical research of the discovery of stable isotopes: the outcome of the serendipic meeting of a refugee with the discoverer of heavy isotopes at Columbia University

    International Nuclear Information System (INIS)

    As late as the 1930s, approaches to biochemical research not only were rather primitive, but a certain amount of mysticism still surrounded the biochemical events that occur in the living cell. To a great extent, this was due to the lack of techniques needed to uncover the subtle reactions in the living cell. In the early 1930s, an accidental meeting of two scientists revolutionized approaches in biochemical studies and led to the scientific explosion in molecular biology that has occurred during the last few decades. The dark political storm in Germany deposited Dr. Rudolf Schoenheimer on the New York shore, where he met Professor Urey, who recently had discovered ''heavy'' hydrogen. Schoenheimer suggested that biological compounds tagged with heavy atoms of hydrogen would enable investigators to follow their metabolic pathways. This intellectual leap revolutionized the thinking and design of experiments and made it possible to uncover the myriad reactions that occur in the living cell

  14. Adapt or Become Extinct!

    DEFF Research Database (Denmark)

    Goumas, Georgios; McKee, Sally A.; Själander, Magnus;

    2011-01-01

    boundaries (walls) for applications which limit software development (parallel programming wall), performance (memory wall, communication wall) and viability (power wall). The only way to survive in such a demanding environment is by adaptation. In this paper we discuss how dynamic information collected...... during the execution of an application can be utilized to adapt the execution context and may lead to performance gains beyond those provided by static information and compile-time adaptation. We consider specialization based on dynamic information like user input, architectural characteristics such as...... from static analysis (either during ahead-of-time or just-in-time) compilation. We extend the notion of information-driven adaptation and outline the architecture of an infrastructure designed to enable information ow and adaptation throughout the life-cycle of an application....

  15. Appraising Adaptive Management

    Directory of Open Access Journals (Sweden)

    Kai N. Lee

    1999-12-01

    Full Text Available Adaptive management is appraised as a policy implementation approach by examining its conceptual, technical, equity, and practical strengths and limitations. Three conclusions are drawn: (1 Adaptive management has been more influential, so far, as an idea than as a practical means of gaining insight into the behavior of ecosystems utilized and inhabited by humans. (2 Adaptive management should be used only after disputing parties have agreed to an agenda of questions to be answered using the adaptive approach; this is not how the approach has been used. (3 Efficient, effective social learning, of the kind facilitated by adaptive management, is likely to be of strategic importance in governing ecosystems as humanity searches for a sustainable economy.

  16. Adaptive noise cancellation

    International Nuclear Information System (INIS)

    In this report we describe the concept of adaptive noise canceling, an alternative method of estimating signals corrupted by additive noise of interference. The method uses 'primary' input containing the corrupted signal and a 'reference' input containing noise correlated in some unknown way with the primary noise, the reference input is adaptively filtered and subtracted from the primary input to obtain the signal estimate. Adaptive filtering before subtraction allows the treatment of inputs that are deterministic or stochastic, stationary or time variable. When the reference input is free of signal and certain other conditions are met then noise in the primary input can be essentially eliminated without signal distortion. It is further shown that the adaptive filter also acts as notch filter. Simulated results illustrate the usefulness of the adaptive noise canceling technique. (author)

  17. Adaptive signal processor

    International Nuclear Information System (INIS)

    An experimental, general purpose adaptive signal processor system has been developed, utilizing a quantized (clipped) version of the Widrow-Hoff least-mean-square adaptive algorithm developed by Moschner. The system accommodates 64 adaptive weight channels with 8-bit resolution for each weight. Internal weight update arithmetic is performed with 16-bit resolution, and the system error signal is measured with 12-bit resolution. An adapt cycle of adjusting all 64 weight channels is accomplished in 8 μsec. Hardware of the signal processor utilizes primarily Schottky-TTL type integrated circuits. A prototype system with 24 weight channels has been constructed and tested. This report presents details of the system design and describes basic experiments performed with the prototype signal processor. Finally some system configurations and applications for this adaptive signal processor are discussed

  18. Assessment of biochemical concentrations of vegetation using remote sensing technology

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The main biochemicals (such as lignin, protein, cellulose, sugar, starch, chlorophyll and water) of vegetation are directly or indirectly involved in major ecological processes, such as the functions of terrestrial ecosystems (i.e., nutrient-cycling processes, primary production, and decomposition). Remote sensing techniques provide a very convenient way of data acquisition capable of covering a large area several times during one season, so it can play a unique and essential role provided that we can relate remote sensing measurements to the biochemical characteristics of the Earth surface in a reliable and operational way. The application of remote sensing techniques for the estimation of canopy biochemicals was reviewed. Three methods of estimating biochemical concentrations of vegetation were included in this paper: index, stepwise multiple linear regression, and stepwise multiple linear regression based on a model of the forest crown. In addition, the vitality and potential applying value are stressed.

  19. NERVOUS-SYSTEM SPECIFIC PROTEINS AS BIOCHEMICAL INDICATORS OF NEUROTOXICITY

    Science.gov (United States)

    Recent advances in neuroimmunology and protein purification methodology have led to the identification of nervous-system specific proteins. Their intimate relationship to the cellular and functional heterogeneity of the nervous system, makes these proteins ideal biochemical marke...

  20. 2011 Biomass Program Platform Peer Review: Biochemical Conversion

    Energy Technology Data Exchange (ETDEWEB)

    Pezzullo, Leslie [Office of Energy Efficiency and Renewable Energy (EERE), Washington, DC (United States)

    2012-02-01

    This document summarizes the recommendations and evaluations provided by an independent external panel of experts at the 2011 U.S. Department of Energy Biomass Program’s Biochemical Conversion Platform Review meeting.

  1. Effects of dopaminergic therapy on locomotor adaptation and adaptive learning in persons with Parkinson's disease.

    Science.gov (United States)

    Roemmich, Ryan T; Hack, Nawaz; Akbar, Umer; Hass, Chris J

    2014-07-15

    Persons with Parkinson's disease (PD) are characterized by multifactorial gait deficits, though the factors which influence the abilities of persons with PD to adapt and store new gait patterns are unclear. The purpose of this study was to investigate the effects of dopaminergic therapy on the abilities of persons with PD to adapt and store gait parameters during split-belt treadmill (SBT) walking. Ten participants with idiopathic PD who were being treated with stable doses of orally-administered dopaminergic therapy participated. All participants performed two randomized testing sessions on separate days: once while optimally-medicated (ON meds) and once after 12-h withdrawal from dopaminergic medication (OFF meds). During each session, locomotor adaptation was investigated as the participants walked on a SBT for 10 min while the belts moved at a 2:1 speed ratio. We assessed locomotor adaptive learning by quantifying: (1) aftereffects during de-adaptation (once the belts returned to tied speeds immediately following SBT walking) and (2) savings during re-adaptation (as the participants repeated the same SBT walking task after washout of aftereffects following the initial SBT task). The withholding of dopaminergic medication diminished step length aftereffects significantly during de-adaptation. However, both locomotor adaptation and savings were unaffected by levodopa. These findings suggest that dopaminergic pathways influence aftereffect storage but do not influence locomotor adaptation or savings within a single session of SBT walking. It appears important that persons with PD should be optimally-medicated if walking on the SBT as gait rehabilitation. PMID:24698798

  2. Signaling Pathways Involved in Cardiac Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    Tao Zewei; Li Longgui

    2006-01-01

    Cardiac hypertrophy is the heart's response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress.Traditionally, it has been considered a beneficial mechanism; however, sustained hypertrophy has been associated with a significant increase in the risk of cardiovascular disease and mortality. Delineating intracellular signaling pathways involved in the different aspects of cardiac hypertrophy will permit future improvements in potential targets for therapeutic intervention. Generally, there are two types of cardiac hypertrophies, adaptive hypertrophy, including eutrophy (normal growth) and physiological hypertrophy (growth induced by physical conditioning), and maladaptive hypertrophy, including pathologic or reactive hypertrophy (growth induced by pathologic stimuli) and hypertrophic growth caused by genetic mutations affecting sarcomeric or cytoskeletal proteins. Accumulating observations from animal models and human patients have identified a number of intracellular signaling pathways that characterized as important transducers of the hypertrophic response,including calcineurin/nuclear factor of activated Tcells, phosphoinositide 3-kinases/Akt (PI3Ks/Akt),G protein-coupled receptors, small G proteins,MAPK, PKCs, Gp130/STAT'3, Na+/H+ exchanger,peroxisome proliferator-activated receptors, myocyte enhancer factor 2/histone deacetylases, and many others. Furthermore, recent evidence suggests that adaptive cardiac hypertrophy is regulated in large part by the growth hormone/insulin-like growth factors axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive hypertrophy is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phosphorlipase C pathway, leading to an increase in cytosolic calcium and activation of PKC.

  3. Anatomical and biochemical investigation of primary brain tumours

    International Nuclear Information System (INIS)

    Cancerous transformation entails major biochemical changes including modifications of the energy metabolism of the cell, e.g. utilisation of glucose and other substrates, protein synthesis, and expression of receptors and antigens. Tumour growth also leads to heterogeneity in blood flow owing to focal necrosis, angiogenesis and metabolic demands, as well as disruption of transport mechanisms of substrates across cell membranes and other physiological boundaries such as the blood-brain barrier. All these biochemical, histological and anatomical changes can be assessed with emission tomography, X-ray computed tomography (CT), magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Whereas anatomical imaging is aimed at the diagnosis of brain tumours, biochemical imaging is better suited for tissue characterisation. The identification of a tumoural mass and the assessment of its size and vascularisation are best achieved with X-ray CT and MRI, while biochemical imaging can provide additional information that is crucial for tumour classification, differential diagnosis and follow-up. As the assessment of variables such as water content, appearance of cystic lesions and location of the tumour are largely irrelevant for tissue characterisation, a number of probes have been employed for the assessment of the biochemical features of tumours. Since biochemical changes may be related to the growth rate of cancer cells, they can be thought of as markers of tumour cell proliferation. Biochemical imaging with radionuclides of processes that occur at a cellular level provides information that complements findings obtained by anatomical imaging aimed at depicting structural, vascular and histological changes. This review focusses on the clinical application of anatomical brain imaging and biochemical assessment with positron emission tomography, single-photon emission tomography and MRS in the diagnosis of primary brain tumours, as well as in follow-up. (orig.)

  4. Click Chemistry-Mediated Nanosensors for Biochemical Assays

    OpenAIRE

    Chen, Yiping; Xianyu, Yunlei; Wu, Jing; Yin, Binfeng; Jiang, Xingyu

    2016-01-01

    Click chemistry combined with functional nanoparticles have drawn increasing attention in biochemical assays because they are promising in developing biosensors with effective signal transformation/amplification and straightforward signal readout for clinical diagnostic assays. In this review, we focus on the latest advances of biochemical assays based on Cu (I)-catalyzed 1, 3-dipolar cycloaddition of azides and alkynes (CuAAC)-mediated nanosensors, as well as the functionalization of nanopro...

  5. Biomphalaria prona (Gastropoda: Planorbidae): a morphological and biochemical study

    OpenAIRE

    W. Lobato Paraense; Pointier, J.P.; Delay, B.; A. F. Pernot; Incani, R N; C. Balzan; P. Chrosciechowski

    1992-01-01

    Two samples of Biomphalaria prona (Martens, 1873) from Lake Valencia (type locality) and seven from other Venezuelan localities were studied morphologically (shell and reproductive system) and biochemically (allozyme electrophoresis). In spite of marked differences in shell characters, all of them proved indistinguishable under the anatomic and biochemical criteria. So far B. prona has been considered an endemic species, restricted to Lake Valencia. It is now demonstrated that the extralacust...

  6. Correlations between female breast density and biochemical markers

    OpenAIRE

    Kim, Ji-Hye; Lee, Hae-Kag; Cho, Jae-Hwan; Park, Hyong-Keun; Yang, Han-Jun

    2015-01-01

    [Purpose] The aim of this study was to identify biochemical markers related to breast density. The study was performed with 200 patients who received mammography and biochemical marker testing between March 1, 2014 to October 1, 2014. [Subjects and Methods] Following the American College of Radiology, Breast Imaging Reporting and Data System (ACR BI-RADS), breast parenchymal pattern density from mammography was categorized into four grades: grade 1, almost entirely fat; grade 2, fibroglandula...

  7. Serum Biochemical Profile of Post Partum Metritic Cow

    OpenAIRE

    Magnus P. K.; Lali F. A.

    2009-01-01

    Present study was conducted to find out the relationship between serum biochemical profile and postpartum metritis. Mainly serum glucose, total protein, albumin, albumin globulin ratio, blood urea nitrogen (BUN), creatinine and calcium were studied. Colorimetric method was used for quantitative estimation of biochemical profile. Twenty-seven animals with recent history of calving and subsequent metritis were included in the study. On analysis, serum glucose was found to be 22.3 ± 2.1...

  8. A useful routine for biochemical detection and diagnosis of mucopolysaccharidoses

    Directory of Open Access Journals (Sweden)

    Sandra Leistner

    1998-03-01

    Full Text Available Mucopolysaccharidoses (MPS constitute, owing to their biochemical, genetical and clinical characteristics, a large and heterogeneous subgroup among the lysosomal storage diseases (LSD. They are caused by deficiency of specific enzymes, which are responsible for glycosaminoglycan (GAG breakdown during different steps of its degradation pathway. MPS are responsible for about 32% of inborn errors of metabolism (IEM and 54% of LSD identified in our laboratory (Regional Laboratory of Inborn Errors of Metabolism (RLIEM, Medical Genetics Unit, Hospital de Clínicas in Porto Alegre, which is a reference center for LSD diagnosis in Brazil. Therefore, we decided to set up a specific laboratory routine for detection and differential diagnosis of MPS in patients with clinical features suggestive of this group of disordersAs mucopolissacaridoses (MPS constituem, devido às suas características bioquímicas, genéticas e clínicas, um grupo grande e heterogêneo dentro das doenças lisossômicas de depósito (LSD, e são causadas pela deficiência de enzimas específicas que são responsáveis pela quebra de glicosaminoglicanos (GAGs em passos diferentes da sua rota de degradação. Sendo as MPS responsáveis por aproximadamente 32% dos erros inatos do metabolismo (EIM e 54% das LSD identificadas em nosso laboratório (Laboratório Regional dos Erros Inatos do Metabolismo (RLIEM, Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, que é um centro de referência para o diagnóstico de LSD no Brasil, nós decidimos implantar uma rotina para a detecção e o diagnóstico diferencial de MPS em pacientes com características clínicas sugestivas deste grupo de doenças.

  9. Modeling biochemical transformation processes and information processing with Narrator

    Directory of Open Access Journals (Sweden)

    Palfreyman Niall M

    2007-03-01

    Full Text Available Abstract Background Software tools that model and simulate the dynamics of biological processes and systems are becoming increasingly important. Some of these tools offer sophisticated graphical user interfaces (GUIs, which greatly enhance their acceptance by users. Such GUIs are based on symbolic or graphical notations used to describe, interact and communicate the developed models. Typically, these graphical notations are geared towards conventional biochemical pathway diagrams. They permit the user to represent the transport and transformation of chemical species and to define inhibitory and stimulatory dependencies. A critical weakness of existing tools is their lack of supporting an integrative representation of transport, transformation as well as biological information processing. Results Narrator is a software tool facilitating the development and simulation of biological systems as Co-dependence models. The Co-dependence Methodology complements the representation of species transport and transformation together with an explicit mechanism to express biological information processing. Thus, Co-dependence models explicitly capture, for instance, signal processing structures and the influence of exogenous factors or events affecting certain parts of a biological system or process. This combined set of features provides the system biologist with a powerful tool to describe and explore the dynamics of life phenomena. Narrator's GUI is based on an expressive graphical notation which forms an integral part of the Co-dependence Methodology. Behind the user-friendly GUI, Narrator hides a flexible feature which makes it relatively easy to map models defined via the graphical notation to mathematical formalisms and languages such as ordinary differential equations, the Systems Biology Markup Language or Gillespie's direct method. This powerful feature facilitates reuse, interoperability and conceptual model development. Conclusion Narrator is a

  10. Murine interleukin 2 receptor. IV. Biochemical characterization

    International Nuclear Information System (INIS)

    The IL 2 receptor isolated from the IL 2-dependent CTL-L cell line was subjected to biochemical analysis. Pulse-chase and tunicamycin studies, as well as digestion with the endoglycosidases, Endo-F and Endo-H, of 35S-methionine-labeled IL 2 receptors suggested a single protein pecursor of 32,000 (p32) daltons. The p32 precursor was rapidly processed by addition of high-mannose-containing core N-linked sugars to intracytoplasmic precursor intermediates of 38,000 (p38) and 40,000 (p40) daltons, which undergo further processing to yield a mature surface receptor with heterogeneous apparent m.w. of 52,000 to 65,000 (p58). Two-dimensional gel studies indicated that p58 exhibited broad charge heterogeneity between pH 4.6 and 6.3. Endo-F digestions of p58 shifted the isoelectric focus point to a more basic 5.5 to 7.4. This considerable charge heterogeneity is consistent with the possibility that other post-translational modifications to the mouse IL 2 receptor occur besides addition of complex N-linked glycans. Immunoprecipitations of the IL 2 receptor from surface iodinated cells also revealed an additional band at 110,000 (p110) daltons. IEF vs SDS-PAGE two-dimensional gel studies demonstrated that p110 also had an isoelectric focus point identical to p58. Western blot studies with an anti-IL 2 receptor monoclonal antibody (7D4) demonstrates that p38, p40, p58, and p110 each expressed the epitope recognized by this antibody. Thus, it is likely that p110 is not a unique molecule that coprecipitates with IL 2 receptor. Western blot analysis of mitogen-stimulated T and B lymphocytes also revealed bands similar to p58 and p110, although these bands had an average apparent m.w. 3000 and 6000 less than those seen for CTL-L cells

  11. Clinical, endocrinological and biochemical effects of zinc deficiency.

    Science.gov (United States)

    Prasad, A S

    1985-08-01

    The essentiality of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, chronic renal disease, certain diuretics, the use of chelating agents such as penicillamine for Wilson's disease, and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during the growing age period. The clinical manifestations in severe cases of zinc deficiency included bullous-pustular dermatitis, alopecia, diarrhoea, emotional disorder, weight loss, intercurrent infections, hypogonadism in males and it is fatal if untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss and hyperammonaemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and in man. Inasmuch as zinc is needed for protein and DNA synthesis and cell division, it is believed that the growth effect of zinc is related to its effect on protein synthesis. Testicular functions are affected adversely as a result of zinc deficiency in both humans and experimental animals. This effect of zinc is at the end organ level and the hypothalamic--pituitary axis is intact in zinc-deficient subjects. Inasmuch as zinc is intimately involved in a cell division, its deficiency may adversely affect testicular size and thus its function. In mice, the incidence of degenerate oocytes, and hypohaploidy and hyperhaploidy in metaphase II oocytes were increased due to zinc deficiency. Zinc at physiological concentrations reduced prolactin secretion from the pituitary in vitro and it has been

  12. Modularized study of human calcium signalling pathway

    Indian Academy of Sciences (India)

    Losiana Nayak; Rajat K De

    2007-08-01

    Signalling pathways are complex biochemical networks responsible for reg ulation of numerous cellular functions. These networks function by serial and successive interactions among a large number of vital biomolecules and chemical compounds. For deciphering and analysing the underlying mechanism of such networks, a modularized study is quite helpful. Here we propose an algorithm for modularization of calcium signalling pathway of H. sapiens. The idea that ``a node whose function is dependant on maximum number of other nodes tends to be the center of a sub network” is used to divide a large signalling network into smaller sub networks. Inclusion of node(s) into sub networks(s) is dependant on the outdegree of the node(s). Here outdegree of a node refers to the number of re lations of the considered node lying outside the constructed sub network. Node(s) having more than c relations lying outside the expanding subnetwork have to be excluded from it. Here is a specified variable based on user preference, which is finally fixed during adjustments of created subnetworks, so that certain biological significance can be conferred on them.

  13. Metabolomics analysis reveals insights into biochemical mechanisms of mental stress-induced left ventricular dysfunction

    Science.gov (United States)

    Boyle, Stephen H.; Matson, Wayne R.; Velazquez, Eric J.; Samad, Zainab; Williams, Redford B.; Sharma, Swati; Thomas, Beena; Wilson, Jennifer L.; O'Connor, Christopher

    2014-01-01

    Mental stress induced left ventricular dysfunction (LVD) has been associated with a greater risk of adverse events in coronary heart disease (CHD) patients independent of conventional risk indicators. The underlying biochemical mechanisms of this cardiovascular condition are poorly understood. Our objective was to use metabolomics technology to identify biochemical changes that co-occur with mental stress-induced LVD in patients with clinically stable CHD. Participants were adult CHD patients who were recruited for mental stress-induced myocardial ischemia screening. For this study, we randomly selected 30 patients representing the extremes of the mental stress-induced left ventricular ejection fraction (LVEF) change distribution; 15 who showed LVD (i.e. LVEF reduction ≥5) and 15 who showed a normal left ventricular response (NLVR; i.e. a LVEF increase of ≥5) to three mental stressors. An electrochemistry based metabolomics platform was used to profile pre- and post-stress serum samples yielding data for 22 known compounds, primarily within the tyrosine, tryptophan, purine and methionine pathways. There were significant stress-induced changes in several compounds. A comparison between the NLVR and LVD groups showed significant effects for kynurenine (p = .036, N-acetylserotonin (p = .054), uric acid (p = .015), tyrosine (p = .019) and a trend for methionine (p = .065); the NLVR group showed a significantly greater stress-induced reduction in all of those compounds compared to the LVD group. Many of these biochemicals have been implicated in other stress-related phenomena and are plausible candidates for mechanisms underlying LVD in response to mental stress. PMID:25983674

  14. Biochemical characterization of plant Rad52 protein from rice (Oryza sativa).

    Science.gov (United States)

    Nair, Anuradha; Agarwal, Rachna; Chittela, Rajani Kant

    2016-09-01

    DNA damage in living cells is repaired by two main pathways, homologous recombination (HR) and non-homologous end joining (NHEJ). Of all the genes promoting HR, Rad52 (Radiation sensitive 52) is an important gene which is found to be highly conserved across different species. It was believed that RAD52 is absent in plant systems until lately. However, recent genetic studies have shown the presence of RAD52 homologues in plants. Rad52 homologues in plant systems have not yet been characterized biochemically. In the current study, we bring out the biochemical properties of rice Rad52-2a protein. OsRad52-2a was over-expressed in Escherichia coli BL21 (DE3) cells and the protein was purified. The identity of purified OsRad52-2a protein was confirmed via peptide mass fingerprinting. Gel filtration and native PAGE analysis indicated that the OsRad52-2a protein in its native state probably formed an undecameric structure. Purified OsRad52-2a protein showed binding to single stranded DNA, double stranded DNA. Protein also mediated the renaturation of complementary single strands into duplex DNA in both agarose gel and FRET based assays. Put together, OsRad52-2a forms oligomeric structures and binds to ssDNA/dsDNA for mediating an important function like renaturation during homologous recombination. This study represents the first report on biochemical properties of OsRad52-2a protein from important crop like rice. This information will help in dissecting the recombination and repair machinery in plant systems. PMID:27156135

  15. Intraspecific variation in cellular and biochemical heat response strategies of Mediterranean Xeropicta derbentina [Pulmonata, Hygromiidae].

    Directory of Open Access Journals (Sweden)

    Sandra Troschinski

    Full Text Available Dry and hot environments challenge the survival of terrestrial snails. To minimize overheating and desiccation, physiological and biochemical adaptations are of high importance for these animals. In the present study, seven populations of the Mediterranean land snail species Xeropicta derbentina were sampled from their natural habitat in order to investigate the intraspecific variation of cellular and biochemical mechanisms, which are assigned to contribute to heat resistance. Furthermore, we tested whether genetic parameters are correlated with these physiological heat stress response patterns. Specimens of each population were individually exposed to elevated temperatures (25 to 52°C for 8 h in the laboratory. After exposure, the health condition of the snails' hepatopancreas was examined by means of qualitative description and semi-quantitative assessment of histopathological effects. In addition, the heat-shock protein 70 level (Hsp70 was determined. Generally, calcium cells of the hepatopancreas were more heat resistant than digestive cells - this phenomenon was associated with elevated Hsp70 levels at 40°C.We observed considerable variation in the snails' heat response strategy: Individuals from three populations invested much energy in producing a highly elevated Hsp70 level, whereas three other populations invested energy in moderate stress protein levels - both strategies were in association with cellular functionality. Furthermore, one population kept cellular condition stable despite a low Hsp70 level until 40°C exposure, whereas prominent cellular reactions were observed above this thermal limit. Genetic diversity (mitochondrial cytochrome c oxidase subunit I gene within populations was low. Nevertheless, when using genetic indices as explanatory variables in a multivariate regression tree (MRT analysis, population structure explained mean differences in cellular and biochemical heat stress responses, especially in the group

  16. Activity profiles of 309 ToxCastTM chemicals evaluated across 292 biochemical targets

    International Nuclear Information System (INIS)

    Understanding the potential health risks posed by environmental chemicals is a significant challenge elevated by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms, and toxicities. The present study is a performance evaluation and critical analysis of assay results for an array of 292 high-throughput cell-free assays aimed at preliminary toxicity evaluation of 320 environmental chemicals in EPA's ToxCastTM project (Phase I). The chemicals (309 unique, 11 replicates) were mainly precursors or the active agent of commercial pesticides, for which a wealth of in vivo toxicity data is available. Biochemical HTS (high-throughput screening) profiled cell and tissue extracts using semi-automated biochemical and pharmacological methodologies to evaluate a subset of G-protein coupled receptors (GPCRs), CYP450 enzymes (CYPs), kinases, phosphatases, proteases, HDACs, nuclear receptors, ion channels, and transporters. The primary screen tested all chemicals at a relatively high concentration 25 μM concentration (or 10 μM for CYP assays), and a secondary screen re-tested 9132 chemical-assay pairs in 8-point concentration series from 0.023 to 50 μM (or 0.009-20 μM for CYPs). Mapping relationships across 93,440 chemical-assay pairs based on half-maximal activity concentration (AC50) revealed both known and novel targets in signaling and metabolic pathways. The primary dataset, summary data and details on quality control checks are available for download at (http://www.epa.gov/ncct/toxcast/).

  17. Biochemical studies on gamma irradiated male rats fed on whey protein concentrate

    International Nuclear Information System (INIS)

    This study carried out to investigate the possible role of whey protein protein concentrate in ameliorating some biochemical disorders induced in gamma irradiated male rats. Forty eight male albino rats were divided into four equal groups: Group 1 fed on normal diet during experimental period. Group 2 where the diet contain 15 % whey protein concentrate instead of soybean protein . Group 3 rats were exposed to whole body gamma radiation with single dose of 5 Gy and fed on the normal diet. Group 4 rate exposed to 5 Gy then fed on diet contain 15 % whey protein concentrate, the rats were decapitated after two and four weeks post irradiation. Exposure to whole body irradiation caused significant elevation of serum ALT, AST, glucose, urea, creatinine and total triiodothyronine with significant decrease in total protein, albumin and thyroxin. Irradiated rats fed on whey protein concentrate revealed significant improvement of some biochemical parameters. It could be conclude that whey protein concentrate may be considered as a useful protein source for reducing radiation injury via metabolic pathway.

  18. Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.

    Directory of Open Access Journals (Sweden)

    Mary Cloud B Ammons

    Full Text Available Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.

  19. Engineering the iron-oxidizing chemolithoautotroph Acidithiobacillus ferrooxidans for biochemical production.

    Science.gov (United States)

    Kernan, Timothy; Majumdar, Sudipta; Li, Xiaozheng; Guan, Jingyang; West, Alan C; Banta, Scott

    2016-01-01

    There is growing interest in developing non-photosynthetic routes for the conversion of CO2 to fuels and chemicals. One underexplored approach is the transfer of energy to the metabolism of genetically modified chemolithoautotrophic bacteria. Acidithiobacillus ferrooxidans is an obligate chemolithoautotroph that derives its metabolic energy from the oxidation of iron or sulfur at low pH. Two heterologous biosynthetic pathways have been expressed in A. ferrooxidans to produce either isobutyric acid or heptadecane from CO2 and the oxidation of Fe(2+). A sevenfold improvement in productivity of isobutyric acid was obtained through improved media formulations in batch cultures. Steady-state efficiencies were lower in continuous cultures, likely due to ferric inhibition. If coupled to solar panels, the photon-to-fuel efficiency of this proof-of-principle process approaches estimates for agriculture-derived biofuels. These efforts lay the foundation for the utilization of this organism in the exploitation of electrical energy for biochemical synthesis. PMID:26174759

  20. Biochemical and Structural Insights of the Early Glycosylation Steps in Calicheamicin Biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Changsheng; Bitto, Eduard; Goff, Randal D.; Singh, Shanteri; Bingman, Craig A.; Griffith, Byron R.; Albermann, Christoph; Phillips, Jr., George N.; Thorson, Jon S. (UW); (Chinese Aca. Sci.)

    2008-09-17

    The enediyne antibiotic calicheamicin (CLM) {gamma}{sub 1}{sup I} is a prominent antitumor agent that is targeted to DNA by a novel aryltetrasaccharide comprised of an aromatic unit and four unusual carbohydrates. Herein we report the heterologous expression and the biochemical characterization of the two 'internal' glycosyltransferases CalG3 and CalG2 and the structural elucidation of an enediyne glycosyltransferase (CalG3). In conjunction with the previous characterization of the 'external' CLM GTs CalG1 and CalG4, this study completes the functional assignment of all four CLM GTs, extends the utility of enediyne GT-catalyzed reaction reversibility, and presents conclusive evidence of a sequential glycosylation pathway in CLM biosynthesis. This work also reveals the common GT-B structural fold can now be extended to include enediyne GTs.

  1. High-field MR imaging of craniopharyngiomas: Correlations with biochemical data

    International Nuclear Information System (INIS)

    Seventeen patients with craniopharyngiomas underwent MR imaging performed with a 1.5-unit. Correlations were made with CT and pathologic findings in all cases. Cystic collections were analyzed in seven cases (proteins, lactic dehydrogenase [LDH], lipid and ferrous content). Three-dimensional spin-echo sequences were performed with T1 and T2 weighting. Fast imaging was done in nine cases. Contrast medium (Gd-DTPA or Gd-DOTA) was intravenously injected in five patients. MR imaging clearly depicted the cystic and solid portions of the tumor; moreover, the solid vascularized parts and the cylic tumoral walls enhanced after contrast agent injection. Analysis of the cystic collections allowed correlation of the variable MR signals and the biochemical data: high concentrations of proteins and LDH, various lipid and iron contents. Calcifications were visualized in only seven cases. Relationships with the optic pathways, the hypothalmus, and the cisterns were precisely established

  2. Conserved features and evolutionary shifts of the EDA signaling pathway involved in vertebrate skin appendage development.

    OpenAIRE

    2008-01-01

    It is widely accepted that evolutionary changes in conserved developmental signaling pathways play an important role in morphological evolution. However, few in silico studies were interested in tracking such changes in a signaling pathway. The Ectodysplasin (EDA) pathway provides an opportunity to fill this gap because it is involved in vertebrate skin appendage development such as scales, teeth, hair, and feathers that take an obvious part in the adaptation of species to their environment. ...

  3. Biochemical Composition Suggests Different Roles of Leaf Litter and Fine Roots in Soil Carbon Formation

    Science.gov (United States)

    Xia, M.; Pregitzer, K. S.; Talhelm, A. F.

    2012-12-01

    Plant litter is a major source of soil organic carbon (C). This litter is not homogenous, but instead primarily composed of fine root and leaf litter that adapted to different physiological functions. These unique functions suggest that root and leaf litter likely have different biochemical traits, and thus different decomposition patterns. However, few studies have compared their substrate quality and contributions to soil C. Also, much less attention has been given to fine roots although they can represent a substantial litter production. Here we hypothesize that 1) leaf litter and fine roots have different substrate quality as they are highly different in biochemical composition; 2) the biochemical composition of leaf litter and fine roots responds differently to the simulated nitrogen (N) deposition. To test these hypotheses, we collected leaf litter and fine roots of Acer saccharum (the dominant species in the northern temperate ecosystems we studied) in both ambient and N addition treatment plots at four sites of Michigan N deposition gradient study. We quantified ten biochemical components thought to be important on decomposition. Strikingly, we found a consistently three-fold higher lignin concentration in fine roots than that in leaf litter (Ptannin (CT) concentration in fine roots (13.13±0.51%) was also substantially higher than that in leaf litter (P< 0.01, 4.63±0.42 %). Tissue CT can inhibit litter decay by both precipitating proteins and by having antimicrobial properties. In contrast, fine roots exhibited lower concentrations of non-structural carbohydrates (NSC), soluble phenolics, and holocellulose (hemicelluloses & cellulose) than leaf litter (P< 0.01). These components are considered more easily accessible, and may stimulate the decay of lignin by providing required energy. Therefore, fine roots of Acer saccharum have a relatively recalcitrant nature based on their distinct biochemical composition, suggesting fine roots may be the major driver

  4. EU-wide economic valuation of adaptation to climate change

    DEFF Research Database (Denmark)

    Jeuken, Ad; Bouwer, Laurens; Burzel, Andreas;

    2016-01-01

    . Costs and benefits are explored for present and future climates, for different socio-economic developments paths and different adaptation strategies. For all models the SSP (Shared Socio-economic Pathways) 2 (‘middle of the road’), 3 (‘fragmented world’) and 5 (‘market driven development’) have been...

  5. The process of organisational adaptation through innovations, and organisational adaptability

    OpenAIRE

    Tikka, Tommi

    2010-01-01

    This study is about the process of organisational adaptation and organisational adaptability. The study generates a theoretical framework about organisational adaptation behaviour and conditions that have influence on success of organisational adaptation. The research questions of the study are: How does an organisation adapt through innovations, and which conditions enhance or impede organisational adaptation through innovations? The data were gathered from five case organisations withi...

  6. Adaptive network countermeasures.

    Energy Technology Data Exchange (ETDEWEB)

    McClelland-Bane, Randy; Van Randwyk, Jamie A.; Carathimas, Anthony G.; Thomas, Eric D.

    2003-10-01

    This report describes the results of a two-year LDRD funded by the Differentiating Technologies investment area. The project investigated the use of countermeasures in protecting computer networks as well as how current countermeasures could be changed in order to adapt with both evolving networks and evolving attackers. The work involved collaboration between Sandia employees and students in the Sandia - California Center for Cyber Defenders (CCD) program. We include an explanation of the need for adaptive countermeasures, a description of the architecture we designed to provide adaptive countermeasures, and evaluations of the system.

  7. Introduction to adaptive arrays

    CERN Document Server

    Monzingo, Bob; Haupt, Randy

    2011-01-01

    This second edition is an extensive modernization of the bestselling introduction to the subject of adaptive array sensor systems. With the number of applications of adaptive array sensor systems growing each year, this look at the principles and fundamental techniques that are critical to these systems is more important than ever before. Introduction to Adaptive Arrays, 2nd Edition is organized as a tutorial, taking the reader by the hand and leading them through the maze of jargon that often surrounds this highly technical subject. It is easy to read and easy to follow as fundamental concept

  8. [Adaptive optics for ophthalmology].

    Science.gov (United States)

    Saleh, M

    2016-04-01

    Adaptive optics is a technology enhancing the visual performance of an optical system by correcting its optical aberrations. Adaptive optics have already enabled several breakthroughs in the field of visual sciences, such as improvement of visual acuity in normal and diseased eyes beyond physiologic limits, and the correction of presbyopia. Adaptive optics technology also provides high-resolution, in vivo imaging of the retina that may eventually help to detect the onset of retinal conditions at an early stage and provide better assessment of treatment efficacy. PMID:27019970

  9. Theory of adaptive adjustment

    Directory of Open Access Journals (Sweden)

    Weihong Huang

    2000-01-01

    Full Text Available Conventional adaptive expectation as a mechanism of stabilizing an unstable economic process is reexamined through a generalization to an adaptive adjustment framework. The generic structures of equilibria that can be stabilized through an adaptive adjustment mechanism are identified. The generalization can be applied to a broad class of discrete economic processes where the variables interested can be adjusted or controlled directly by economic agents such as in cobweb dynamics, Cournot games, Oligopoly markets, tatonnement price adjustment, tariff games, population control through immigration etc.

  10. Symmetry Adapted Basis Sets

    DEFF Research Database (Denmark)

    Avery, John Scales; Rettrup, Sten; Avery, James Emil

    In theoretical physics, theoretical chemistry and engineering, one often wishes to solve partial differential equations subject to a set of boundary conditions. This gives rise to eigenvalue problems of which some solutions may be very difficult to find. For example, the problem of finding...... such problems can be much reduced by making use of symmetry-adapted basis functions. The conventional method for generating symmetry-adapted basis sets is through the application of group theory, but this can be difficult. This book describes an easier method for generating symmetry-adapted basis sets...

  11. Biochemical Methods to Analyze Wnt Protein Secretion.

    Science.gov (United States)

    Glaeser, Kathrin; Boutros, Michael; Gross, Julia Christina

    2016-01-01

    Wnt proteins act as potent morphogens in various aspects of embryonic development and adult tissue homeostasis. However, in addition to its physiological importance, aberrant Wnt signaling has been linked to the onset and progression of different types of cancer. On the cellular level, the secretion of Wnt proteins involves trafficking of lipid-modified Wnts from the endoplasmic reticulum (ER) to Golgi and further compartments via the Wnt cargo receptor evenness interrupted. Others and we have recently shown that Wnt proteins are secreted on extracellular vesicles (EVs) such as microvesicles and exosomes. Although more details about specific regulation of Wnt secretion steps are emerging, it remains largely unknown how Wnt proteins are channeled into different release pathways such as lipoprotein particles, EVs and cytonemes. Here, we describe protocols to purify and quantify Wnts from the supernatant of cells by either assessing total Wnt proteins in the supernatant or monitoring Wnt proteins on EVs. Purified Wnts from the supernatant as well as total cellular protein content can be investigated by immunoblotting. Additionally, the relative activity of canonical Wnts in the supernatant can be assessed by a dual-luciferase Wnt reporter assay. Quantifying the amount of secreted Wnt proteins and their activity in the supernatant of cells allows the investigation of intracellular trafficking events that regulate Wnt secretion and the role of extracellular modulators of Wnt spreading. PMID:27590148

  12. comparative transcriptomics between Synechococcus PCC 7942 and Synechocystis PCC 6803 provide insights into mechanisms of adaptation to stress.

    Energy Technology Data Exchange (ETDEWEB)

    Konstantinos, Billis [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); European Bioinformatics Inst., Hinxton, Cambridge (United Kingdom). European Molecular Biology Lab.; Aristotle Univ., Thessaloniki (Greece). Dept. of Genetics; Billini, Maria [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Max Planck Inst. for Terrestrial Microbiology, Marburg (Germany); Tripp, Harry J. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Kyrpides, Nikos C. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Mavrommatis, Konstantinos [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Celgene Corp, San Francisco, CA (United States)

    2014-03-21

    Background: Synechococcus sp. PCC 7942 and Synechocystis sp. PCC 6803 are model cyanobacteria from which the metabolism and adaptive responses of other cyanobacteria are inferred. Here we report the gene expression response of these two strains to a variety of nutrient and environmental stresses of varying duration, using transcriptomics. Our data comprise both stranded and 5? enriched libraries in order to elucidate many aspects of the transcriptome. Results: Both organisms were exposed to stress conditions due to nutrient deficiency (inorganic carbon) or change of environmental conditions (salinity, temperature, pH, light) sampled at 1 and 24 hours after the application of stress. The transcriptome profile of each strain revealed similarities and differences in gene expression for photosynthetic and respiratory electron transport chains and carbon fixation. Transcriptome profiles also helped us improve the structural annotation of the genome and identify possible missed genes (including anti-sense) and determine transcriptional units (operons). Finally, we predicted association of proteins of unknown function biochemical pathways by associating them to well-characterized ones based on their transcript levels correlation. Conclusions: Overall, this study results an informative annotation of those species and the comparative analysis of the response of the two organisms revealed similarities but also significant changes in the way they respond to external stress and the duration of the response

  13. A chloroplast pathway for the de novo biosynthesis of triacylglycerol in Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Fan, J.; Xu, C.; Andre, C.

    2011-06-23

    Neutral lipid metabolism has been extensively studied in yeast, plants and mammals. In contrast, little information is available regarding the biochemical pathway, enzymes and regulatory factors involved in the biosynthesis of triacylglycerol (TAG) in microalgae. In the conventional TAG biosynthetic pathway widely accepted for yeast, plants and mammals, TAG is assembled in the endoplasmic reticulum (ER) from its immediate precursor diacylglycerol (DAG) made by ER-specific acyltransferases, and is deposited exclusively in lipid droplets in the cytosol. Here, we demonstrated that the unicellular microalga Chlamydomonas reinhardtii employs a distinct pathway that uses DAG derived almost exclusively from the chloroplast to produce TAG. This unique TAG biosynthesis pathway is largely dependent on de novo fatty acid synthesis, and the TAG formed in this pathway is stored in lipid droplets in both the chloroplast and the cytosol. These findings have wide implications for understanding TAG biosynthesis and storage and other areas of lipid metabolism in microalgae and other organisms.

  14. Protein coalitions in a core mammalian biochemical network linked by rapidly evolving proteins

    Directory of Open Access Journals (Sweden)

    Tsoka Sophia

    2011-05-01

    Full Text Available Abstract Background Cellular ATP levels are generated by glucose-stimulated mitochondrial metabolism and determine metabolic responses, such as glucose-stimulated insulin secretion (GSIS from the β-cells of pancreatic islets. We describe an analysis of the evolutionary processes affecting the core enzymes involved in glucose-stimulated insulin secretion in mammals. The proteins involved in this system belong to ancient enzymatic pathways: glycolysis, the TCA cycle and oxidative phosphorylation. Results We identify two sets of proteins, or protein coalitions, in this group of 77 enzymes with distinct evolutionary patterns. Members of the glycolysis, TCA cycle, metabolite transport, pyruvate and NADH shuttles have low rates of protein sequence evolution, as inferred from a human-mouse comparison, and relatively high rates of evolutionary gene duplication. Respiratory chain and glutathione pathway proteins evolve faster, exhibiting lower rates of gene duplication. A small number of proteins in the system evolve significantly faster than co-pathway members and may serve as rapidly evolving adapters, linking groups of co-evolving genes. Conclusions Our results provide insights into the evolution of the involved proteins. We find evidence for two coalitions of proteins and the role of co-adaptation in protein evolution is identified and could be used in future research within a functional context.

  15. BIOCHEMICAL STUDIES ON NIGERIAN MONODORA TENUIFOLIA SEED

    Directory of Open Access Journals (Sweden)

    Ekeanyanwu Raphael Chukwuma

    2013-01-01

    Full Text Available The nutritive constituents of the seeds of Monodora tenuifolia were analyzed to augment the available information on Monodora tenuifolia research. Blood glucose and lipid profile were investigated on the flavonoid rich fraction of M. tenuifolia in rats. The composition (gkg-1 of alkaloids, cyanogenic glycosides, tannins and flavonoids were 13.3±0.1, 21.2×10-2±0.6, 1.3±0.1, 1.7±0.1 and 11.7±1.1 respectively. The proximate composition (gkg-1 of M. tenuifolia seed were crude fibre (262.3±1.2, crude protein (82.6±1.0, crude fat (349.9±1.9, ash (49.9±0.6, moisture (190.0±0.00 and carbohydrate (65.5±4.7. Analysis of the minerals content (gkg-1 yielded calcium (864.0±29.38, sodium (2752.0±140.35, iron (3.34±0.06, zinc (5.26±0.08, potassium (326.4±13.06, magnesium (342.9±13.71 and phosphorus (9.52±0.17, while vitamin analysis yielded vitamin A (10.05±0.17 iu/100 g, C (56.40±0.14 gkg-1 and E (11.71±0.87 iu /100 g, thiamine (0.11±0.01 gkg-1, niacin (0.46±0.32 gkg-1 and riboflavin (0.04±0.01 gkg-1. The results of amino acid analysis showed the total amino acid of M. tenuifolia seed was 71.78 of crude protein. The total essential amino acid with Histidine was calculated to be 29.24 of the crude protein. The antinutrient analysis of M. tenuifolia shows it contained total phenol (0.8±0.0 gkg-1, oxalates (4.09±1.17 gkg-1, phytates (0.012±0.42 gkg-1 and trypsin inhibitor (0.230±0.42 iu/g. The main fatty acids of the seed oil are linoleic acid (401.7 g kg-1, oleic acid (346.1 g kg-1 and palmitic acid (122.61 g kg-1. The LD50 of the flavonoid-rich fraction was found to be above 5000 mg kg-1 b.w. After the day 14 study, biochemical markers such as triacylglycerol, very low density lipoprotein increased significantly (p0.05 effect was observed on the blood glucose and lipid profile of wistar albino rats compared with the control. The result shows that M. tenuifolia seed is rich

  16. Biochemical and histological characterization of tomato mutants

    Directory of Open Access Journals (Sweden)

    Carolina C. Monteiro

    2012-06-01

    Full Text Available Biochemical responses inherent to antioxidant systems as well morphological and anatomical properties of photomorphogenic, hormonal and developmental tomato mutants were investigated. Compared to the non-mutant Micro-Tom (MT, we observed that the malondialdehyde (MDA content was enhanced in the diageotropica (dgt and lutescent (l mutants, whilst the highest levels of hydrogen peroxide (H2O2 were observed in high pigment 1 (hp1 and aurea (au mutants. The analyses of antioxidant enzymes revealed that all mutants exhibited reduced catalase (CAT activity when compared to MT. Guaiacol peroxidase (GPOX was enhanced in both sitiens (sit and notabilis (not mutants, whereas in not mutant there was an increase in ascorbate peroxidase (APX. Based on PAGE analysis, the activities of glutathione reductase (GR isoforms III, IV, V and VI were increased in l leaves, while the activity of superoxide dismutase (SOD isoform III was reduced in leaves of sit, epi, Never ripe (Nr and green flesh (gf mutants. Microscopic analyses revealed that hp1 and au showed an increase in leaf intercellular spaces, whereas sit exhibited a decrease. The au and hp1 mutants also exhibited a decreased in the number of leaf trichomes. The characterization of these mutants is essential for their future use in plant development and ecophysiology studies, such as abiotic and biotic stresses on the oxidative metabolism.Neste trabalho, analisamos as respostas bioquímicas inerentes ao sistema antioxidante, assim como propriedades morfológicas e anatômicas de mutantes fotomorfogenéticos e hormonais de tomateiro. Comparados ao não mutante Micro-Tom (MT, observamos que o conteúdo de malondialdeído (MDA aumentou nos mutantes diageotropica (dgt e lutescent (l, enquanto os maiores níveis de H2O2 foram encontrados nos mutantes high pigment 1 (hp1 e aurea (au. Análises de enzimas antioxidantes mostraram que todos os mutantes reduziram a atividade de catalase (CAT quando comparado a MT. A

  17. Pharmacological evidence for connection of nitric oxide-mediated pathways in neuroprotective mechanism of ischemic postconditioning in mice

    Directory of Open Access Journals (Sweden)

    Puja Gulati

    2014-01-01

    Full Text Available Introduction: Postconditioning (PoCo is an adaptive phenomenon whereby brief repetitive cycles of ischemia with intermittent reperfusion instituted immediately after prolonged ischemia at the onset of prolonged reperfusion elicit tissue protection. PoCo is noted to exert a protective effect in various organs like heart, liver, kidney and brain. Various triggers, mediators and end effectors are suggested to contribute to the protective effect of PoCo. However, the neuroprotective mechanism of PoCo is poorly understood. Objectives: The present study has been designed to investigate the role of nitric oxide pathway in the neuroprotective mechanism of ischemic postconditioning (iPoCo employing a mouse model of global cerebral ischemia and reperfusion-induced injury. Materials and Methods: Bilateral carotid artery occlusion (BCAO of 12 min followed by reperfusion for 24 h was employed to produce ischemia and reperfusion (I/R-induced cerebral injury in mice. Cerebral injury was assessed in the terms of cerebral infarct, memory impairment and motor in-coordination. Brain nitrite/nitrate; acetylcholinesterase activity, thiobarbituric acid reactive species (TBARS and glutathione level were also estimated. Results: BCAO followed by reperfusion produced a significant rise in cerebral infarct size, memory impairment and motor incoordination. Further a rise in acetylcholinesterase activity and TBARS level along with fall in brain nitrite/nitrate and glutathione levels was also noted. iPoCo consisting of three episodes of 10 s carotid artery occlusion and reperfusion (instituted immediately after BCAO significantly attenuated infarct size, memory impairment, motor incoordination as well as altered biochemicals. iPoCo-induced neuroprotective effects were significantly abolished by pretreatment of L-NAME, a nonselective NOS inhibitor. Conclusion: It may be concluded that the nitric oxide pathway probably plays a vital role in the neuroprotective mechanism of iPoCo.

  18. Glucose Metabolism in Legionella pneumophila: Dependence on the Entner-Doudoroff Pathway and Connection with Intracellular Bacterial Growth† ▿

    OpenAIRE

    Harada, Eiji; Iida, Ken-ichiro; Shiota, Susumu; Nakayama, Hiroaki; Yoshida, Shin-ichi

    2010-01-01

    Glucose metabolism in Legionella pneumophila was studied by focusing on the Entner-Doudoroff (ED) pathway with a combined genetic and biochemical approach. The bacterium utilized exogenous glucose for synthesis of acid-insoluble cell components but manifested no discernible increase in the growth rate. Assays with permeabilized cell preparations revealed the activities of three enzymes involved in the pathway, i.e., glucokinase, phosphogluconate dehydratase, and 2-dehydro-3-deoxy-phosphogluco...

  19. Dexter energy transfer pathways.

    Science.gov (United States)

    Skourtis, Spiros S; Liu, Chaoren; Antoniou, Panayiotis; Virshup, Aaron M; Beratan, David N

    2016-07-19

    Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor-acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways. PMID:27382185

  20. A Bioinformatics Resource for TWEAK-Fn14 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Mitali Bhattacharjee

    2012-01-01

    Full Text Available TNF-related weak inducer of apoptosis (TWEAK is a new member of the TNF superfamily. It signals through TNFRSF12A, commonly known as Fn14. The TWEAK-Fn14 interaction regulates cellular activities including proliferation, migration, differentiation, apoptosis, angiogenesis, tissue remodeling and inflammation. Although TWEAK has been reported to be associated with autoimmune diseases, cancers, stroke, and kidney-related disorders, the downstream molecular events of TWEAK-Fn14 signaling are yet not available in any signaling pathway repository. In this paper, we manually compiled from the literature, in particular those reported in human systems, the downstream reactions stimulated by TWEAK-Fn14 interactions. Our manual amassment of the TWEAK-Fn14 pathway has resulted in cataloging of 46 proteins involved in various biochemical reactions and TWEAK-Fn14 induced expression of 28 genes. We have enabled the availability of data in various standard exchange formats from NetPath, a repository for signaling pathways. We believe that this composite molecular interaction pathway will enable identification of new signaling components in TWEAK signaling pathway. This in turn may lead to the identification of potential therapeutic targets in TWEAK-associated disorders.

  1. Asimovian Adaptive Agents

    CERN Document Server

    Gordon, D F

    2011-01-01

    The goal of this research is to develop agents that are adaptive and predictable and timely. At first blush, these three requirements seem contradictory. For example, adaptation risks introducing undesirable side effects, thereby making agents' behavior less predictable. Furthermore, although formal verification can assist in ensuring behavioral predictability, it is known to be time-consuming. Our solution to the challenge of satisfying all three requirements is the following. Agents have finite-state automaton plans, which are adapted online via evolutionary learning (perturbation) operators. To ensure that critical behavioral constraints are always satisfied, agents' plans are first formally verified. They are then reverified after every adaptation. If reverification concludes that constraints are violated, the plans are repaired. The main objective of this paper is to improve the efficiency of reverification after learning, so that agents have a sufficiently rapid response time. We present two solutions: ...

  2. Limits to adaptation

    Science.gov (United States)

    Dow, Kirstin; Berkhout, Frans; Preston, Benjamin L.; Klein, Richard J. T.; Midgley, Guy; Shaw, M. Rebecca

    2013-04-01

    An actor-centered, risk-based approach to defining limits to social adaptation provides a useful analytic framing for identifying and anticipating these limits and informing debates over society's responses to climate change.

  3. The genomics of adaptation.

    Science.gov (United States)

    Radwan, Jacek; Babik, Wiesław

    2012-12-22

    The amount and nature of genetic variation available to natural selection affect the rate, course and outcome of evolution. Consequently, the study of the genetic basis of adaptive evolutionary change has occupied biologists for decades, but progress has been hampered by the lack of resolution and the absence of a genome-level perspective. Technological advances in recent years should now allow us to answer many long-standing questions about the nature of adaptation. The data gathered so far are beginning to challenge some widespread views of the way in which natural selection operates at the genomic level. Papers in this Special Feature of Proceedings of the Royal Society B illustrate various aspects of the broad field of adaptation genomics. This introductory article sets up a context and, on the basis of a few selected examples, discusses how genomic data can advance our understanding of the process of adaptation. PMID:23097510

  4. Adaptive shared control system

    OpenAIRE

    Sanders, David

    2009-01-01

    A control system to aid mobility is presented that is intended to assist living independently and that provides physical guidance. The system has two levels: a human machine interface and an adaptive shared controller.

  5. Adaptations, exaptations, and spandrels.

    Science.gov (United States)

    Buss, D M; Haselton, M G; Shackelford, T K; Bleske, A L; Wakefield, J C

    1998-05-01

    Adaptation and natural selection are central concepts in the emerging science of evolutionary psychology. Natural selection is the only known causal process capable of producing complex functional organic mechanisms. These adaptations, along with their incidental by-products and a residue of noise, comprise all forms of life. Recently, S. J. Gould (1991) proposed that exaptations and spandrels may be more important than adaptations for evolutionary psychology. These refer to features that did not originally arise for their current use but rather were co-opted for new purposes. He suggested that many important phenomena--such as art, language, commerce, and war--although evolutionary in origin, are incidental spandrels of the large human brain. The authors outline the conceptual and evidentiary standards that apply to adaptations, exaptations, and spandrels and discuss the relative utility of these concepts for psychological science. PMID:9612136

  6. Adapt or Die

    DEFF Research Database (Denmark)

    Brody, Joshua Eric; Larsen, Kasper Green

    2015-01-01

    In this paper, we study the role non-adaptivity plays in maintaining dynamic data structures. Roughly speaking, a data structure is non-adaptive if the memory locations it reads and/or writes when processing a query or update depend only on the query or update and not on the contents of previously...... read cells. We study such non-adaptive data structures in the cell probe model. This model is one of the least restrictive lower bound models and in particular, cell probe lower bounds apply to data structures developed in the popular word-RAM model. Unfortunately, this generality comes at a high cost......: the highest lower bound proved for any data structure problem is only polylogarithmic. Our main result is to demonstrate that one can in fact obtain polynomial cell probe lower bounds for non-adaptive data structures. To shed more light on the seemingly inherent polylogarithmic lower bound barrier, we...

  7. Adaptive Space Structures

    Science.gov (United States)

    Wada, B.

    1993-01-01

    The term adaptive structures refers to a structural control approach in which sensors, actuators, electronics, materials, structures, structural concepts, and system-performance-validation strategies are integrated to achieve specific objectives.

  8. Adaptive Spectral Doppler Estimation

    DEFF Research Database (Denmark)

    Gran, Fredrik; Jakobsson, Andreas; Jensen, Jørgen Arendt

    2009-01-01

    In this paper, 2 adaptive spectral estimation techniques are analyzed for spectral Doppler ultrasound. The purpose is to minimize the observation window needed to estimate the spectrogram to provide a better temporal resolution and gain more flexibility when designing the data acquisition sequence....... The methods can also provide better quality of the estimated power spectral density (PSD) of the blood signal. Adaptive spectral estimation techniques are known to pro- vide good spectral resolution and contrast even when the ob- servation window is very short. The 2 adaptive techniques are tested and...... compared with the averaged periodogram (Welch’s method). The blood power spectral capon (BPC) method is based on a standard minimum variance technique adapted to account for both averaging over slow-time and depth. The blood amplitude and phase estimation technique (BAPES) is based on finding a set of...

  9. Adaptive multiresolution methods

    Directory of Open Access Journals (Sweden)

    Schneider Kai

    2011-12-01

    Full Text Available These lecture notes present adaptive multiresolution schemes for evolutionary PDEs in Cartesian geometries. The discretization schemes are based either on finite volume or finite difference schemes. The concept of multiresolution analyses, including Harten’s approach for point and cell averages, is described in some detail. Then the sparse point representation method is discussed. Different strategies for adaptive time-stepping, like local scale dependent time stepping and time step control, are presented. Numerous numerical examples in one, two and three space dimensions validate the adaptive schemes and illustrate the accuracy and the gain in computational efficiency in terms of CPU time and memory requirements. Another aspect, modeling of turbulent flows using multiresolution decompositions, the so-called Coherent Vortex Simulation approach is also described and examples are given for computations of three-dimensional weakly compressible mixing layers. Most of the material concerning applications to PDEs is assembled and adapted from previous publications [27, 31, 32, 34, 67, 69].

  10. Adaptive Heat Engine

    Science.gov (United States)

    Allahverdyan, A. E.; Babajanyan, S. G.; Martirosyan, N. H.; Melkikh, A. V.

    2016-07-01

    A major limitation of many heat engines is that their functioning demands on-line control and/or an external fitting between the environmental parameters (e.g., temperatures of thermal baths) and internal parameters of the engine. We study a model for an adaptive heat engine, where—due to feedback from the functional part—the engine's structure adapts to given thermal baths. Hence, no on-line control and no external fitting are needed. The engine can employ unknown resources; it can also adapt to results of its own functioning that make the bath temperatures closer. We determine resources of adaptation and relate them to the prior information available about the environment.

  11. Adaptive Architectural Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Kirkegaard, Poul Henning

    2010-01-01

    Recent years have seen an increasing variety of applications of adaptive architectural structures for improvement of structural performance by recognizing changes in their environments and loads, adapting to meet goals, and using past events to improve future performance or maintain serviceability....... The general scopes of this paper are to develop a new adaptive kinetic architectural structure, particularly a reconfigurable architectural structure which can transform body shape from planar geometries to hyper-surfaces using different control strategies, i.e. a transformation into more than one or...... two different shape alternatives. The adaptive structure is a proposal for a responsive building envelope which is an idea of a first level operational framework for present and future investigations towards performance based responsive architectures through a set of responsive typologies. A mock- up...

  12. Statistical Physics of Adaptation

    CERN Document Server

    Perunov, Nikolai; England, Jeremy

    2014-01-01

    All living things exhibit adaptations that enable them to survive and reproduce in the natural environment that they inhabit. From a biological standpoint, it has long been understood that adaptation comes from natural selection, whereby maladapted individuals do not pass their traits effectively to future generations. However, we may also consider the phenomenon of adaptation from the standpoint of physics, and ask whether it is possible to delineate what the difference is in terms of physical properties between something that is well-adapted to its surrounding environment, and something that is not. In this work, we undertake to address this question from a theoretical standpoint. Building on past fundamental results in far-from-equilibrium statistical mechanics, we demonstrate a generalization of the Helmholtz free energy for the finite-time stochastic evolution of driven Newtonian matter. By analyzing this expression term by term, we are able to argue for a general tendency in driven many-particle systems...

  13. Adaptive trial designs.

    Science.gov (United States)

    Lai, Tze Leung; Lavori, Philip William; Shih, Mei-Chiung

    2012-01-01

    We review adaptive designs for clinical trials, giving special attention to the control of the Type I error in late-phase confirmatory trials, when the trial planner wishes to adjust the final sample size of the study in response to an unblinded analysis of interim estimates of treatment effects. We point out that there is considerable inefficiency in using the adaptive designs that employ conditional power calculations to reestimate the sample size and that maintain the Type I error by using certain weighted test statistics. Although these adaptive designs have little advantage over familiar group-sequential designs, our review also describes recent developments in adaptive designs that are both flexible and efficient. We also discuss the use of Bayesian designs, when the context of use demands control over operating characteristics (Type I and II errors) and correction of the bias of estimated treatment effects. PMID:21838549

  14. Leak test adapter for containers

    Science.gov (United States)

    Hallett, Brian H.; Hartley, Michael S.

    1996-01-01

    An adapter is provided for facilitating the charging of containers and leak testing penetration areas. The adapter comprises an adapter body and stem which are secured to the container's penetration areas. The container is then pressurized with a tracer gas. Manipulating the adapter stem installs a penetration plug allowing the adapter to be removed and the penetration to be leak tested with a mass spectrometer. Additionally, a method is provided for using the adapter.

  15. Frustratingly Easy Domain Adaptation

    CERN Document Server

    Daumé, Hal

    2009-01-01

    We describe an approach to domain adaptation that is appropriate exactly in the case when one has enough ``target'' data to do slightly better than just using only ``source'' data. Our approach is incredibly simple, easy to implement as a preprocessing step (10 lines of Perl!) and outperforms state-of-the-art approaches on a range of datasets. Moreover, it is trivially extended to a multi-domain adaptation problem, where one has data from a variety of different domains.

  16. Adaptive quantum teleportation

    OpenAIRE

    Modlawska, Joanna; Grudka, Andrzej

    2008-01-01

    We consider multiple teleportation in the Knill-Laflamme-Milburn (KLM) scheme. We introduce adaptive teleportation, i.e., such that the choice of entangled state used in the next teleportation depends on the results of the measurements performed during the previous teleportations. We show that adaptive teleportation enables an increase in the probability of faithful multiple teleportation in the KLM scheme. In particular if a qubit is to be teleported more than once then it is better to use n...

  17. The Adaptive Automation Design

    OpenAIRE

    Calefato, Caterina; Montanari, Roberto; TESAURI, Francesco

    2008-01-01

    After considering the positive effects of adaptive automation implementation, this chapter focuses on two partly overlapping phenomena: on the one hand, the role of trust in automation is considered, particularly as to the effects of overtrust and mistrust in automation's reliability; on the other hand, long-term lack of exercise on specific operation may lead users to skill deterioration. As a future work, it will be interesting and challenging to explore the conjunction of adaptive automati...

  18. The genomics of adaptation

    OpenAIRE

    Radwan, Jacek; Babik, Wiesław

    2012-01-01

    The amount and nature of genetic variation available to natural selection affect the rate, course and outcome of evolution. Consequently, the study of the genetic basis of adaptive evolutionary change has occupied biologists for decades, but progress has been hampered by the lack of resolution and the absence of a genome-level perspective. Technological advances in recent years should now allow us to answer many long-standing questions about the nature of adaptation. The data gathered so far ...

  19. Facilitation of CRISPR adaptation

    OpenAIRE

    Abedon, Stephen T.

    2011-01-01

    CRISPR systems, as bacterial defenses against phages, logically must display in their functioning a sequence of at least three major steps. These, in order of occurrence, are “facilitation,” adaptation and interference, where the facilitation step is the main issue considered in this commentary. Interference is the blocking of phage infections as mediated in part by CRISPR spacer sequences. Adaptation, at least as narrowly defined, is the acquisition of these spacer sequences by CRISPR loci. ...

  20. Robust Adaptive Control

    Science.gov (United States)

    Narendra, K. S.; Annaswamy, A. M.

    1985-01-01

    Several concepts and results in robust adaptive control are are discussed and is organized in three parts. The first part surveys existing algorithms. Different formulations of the problem and theoretical solutions that have been suggested are reviewed here. The second part contains new results related to the role of persistent excitation in robust adaptive systems and the use of hybrid control to improve robustness. In the third part promising new areas for future research are suggested which combine different approaches currently known.

  1. Climate Adaptation in Europe

    International Nuclear Information System (INIS)

    At the Conference of Parties in Copenhagen, Denmark, December 7-18, 2009 Change Magazine will present a special issue on 'Climate Adaptation in Europe'. The magazine contains articles on climate policy strategies in European countries and cross-border studies on climate change, articles on climate adaptation in the Alps, on water quality as a bottleneck for the agricultural sector, and drought in the mediterranean countries. How will member countries in the European Union tackle the climate crisis?.

  2. Network and adaptive sampling

    CERN Document Server

    Chaudhuri, Arijit

    2014-01-01

    Combining the two statistical techniques of network sampling and adaptive sampling, this book illustrates the advantages of using them in tandem to effectively capture sparsely located elements in unknown pockets. It shows how network sampling is a reliable guide in capturing inaccessible entities through linked auxiliaries. The text also explores how adaptive sampling is strengthened in information content through subsidiary sampling with devices to mitigate unmanageable expanding sample sizes. Empirical data illustrates the applicability of both methods.

  3. Opportunistic Adaptation Knowledge Discovery

    OpenAIRE

    Badra, Fadi; Cordier, Amélie; Lieber, Jean

    2009-01-01

    The original publication is available at www.springerlink.com International audience Adaptation has long been considered as the Achilles' heel of case-based reasoning since it requires some domain-specific knowledge that is difficult to acquire. In this paper, two strategies are combined in order to reduce the knowledge engineering cost induced by the adaptation knowledge (CA) acquisition task: CA is learned from the case base by the means of knowledge discovery techniques, and the CA a...

  4. Learning to Adapt. Organisational Adaptation to Climate Change Impacts

    International Nuclear Information System (INIS)

    Analysis of human adaptation to climate change should be based on realistic models of adaptive behaviour at the level of organisations and individuals. The paper sets out a framework for analysing adaptation to the direct and indirect impacts of climate change in business organisations with new evidence presented from empirical research into adaptation in nine case-study companies. It argues that adaptation to climate change has many similarities with processes of organisational learning. The paper suggests that business organisations face a number of obstacles in learning how to adapt to climate change impacts, especially in relation to the weakness and ambiguity of signals about climate change and the uncertainty about benefits flowing from adaptation measures. Organisations rarely adapt 'autonomously', since their adaptive behaviour is influenced by policy and market conditions, and draws on resources external to the organisation. The paper identifies four adaptation strategies that pattern organisational adaptive behaviour

  5. Adaptation and perceptual norms

    Science.gov (United States)

    Webster, Michael A.; Yasuda, Maiko; Haber, Sara; Leonard, Deanne; Ballardini, Nicole

    2007-02-01

    We used adaptation to examine the relationship between perceptual norms--the stimuli observers describe as psychologically neutral, and response norms--the stimulus levels that leave visual sensitivity in a neutral or balanced state. Adapting to stimuli on opposite sides of a neutral point (e.g. redder or greener than white) biases appearance in opposite ways. Thus the adapting stimulus can be titrated to find the unique adapting level that does not bias appearance. We compared these response norms to subjectively defined neutral points both within the same observer (at different retinal eccentricities) and between observers. These comparisons were made for visual judgments of color, image focus, and human faces, stimuli that are very different and may depend on very different levels of processing, yet which share the property that for each there is a well defined and perceptually salient norm. In each case the adaptation aftereffects were consistent with an underlying sensitivity basis for the perceptual norm. Specifically, response norms were similar to and thus covaried with the perceptual norm, and under common adaptation differences between subjectively defined norms were reduced. These results are consistent with models of norm-based codes and suggest that these codes underlie an important link between visual coding and visual experience.

  6. Adaptation of teleosts to very high salinity

    DEFF Research Database (Denmark)

    Laverty, Gary; Skadhauge, Erik

    2012-01-01

    with intestinal water absorption and with the properties of the gill epithelium. While there is much that is still not completely understood, recent work has begun to look at these adaptations at the cellular and molecular level. As with seawater osmoregulation, fish adapting to hypersaline conditions generally...... increase drinking rates and water absorption across the intestine by solute-linked transport. This process requires increased activity, expression levels and possibly changes in subunit isoforms of Na(+)/K(+)-ATPase pumps, along with increases in other components of the NaCl absorptive pathway......(-), which ultimately drives the overall process of NaCl secretion. Balance studies of intake and output clearly indicate that a decrease in the osmotic permeability of the gill epithelium must also occur. The molecular correlates of this effect are not known, although decreased expression of one or more...

  7. Biochemical diversification through foreign gene expression in bdelloid rotifers.

    Directory of Open Access Journals (Sweden)

    Chiara Boschetti

    Full Text Available Bdelloid rotifers are microinvertebrates with unique characteristics: they have survived tens of millions of years without sexual reproduction; they withstand extreme desiccation by undergoing anhydrobiosis; and they tolerate very high levels of ionizing radiation. Recent evidence suggests that subtelomeric regions of the bdelloid genome contain sequences originating from other organisms by horizontal gene transfer (HGT, of which some are known to be transcribed. However, the extent to which foreign gene expression plays a role in bdelloid physiology is unknown. We address this in the first large scale analysis of the transcriptome of the bdelloid Adineta ricciae: cDNA libraries from hydrated and desiccated bdelloids were subjected to massively parallel sequencing and assembled transcripts compared against the UniProtKB database by blastx to identify their putative products. Of ~29,000 matched transcripts, ~10% were inferred from blastx matches to be horizontally acquired, mainly from eubacteria but also from fungi, protists, and algae. After allowing for possible sources of error, the rate of HGT is at least 8%-9%, a level significantly higher than other invertebrates. We verified their foreign nature by phylogenetic analysis and by demonstrating linkage of foreign genes with metazoan genes in the bdelloid genome. Approximately 80% of horizontally acquired genes expressed in bdelloids code for enzymes, and these represent 39% of enzymes in identified pathways. Many enzymes encoded by foreign genes enhance biochemistry in bdelloids compared to other metazoans, for example, by potentiating toxin degradation or generation of antioxidants and key metabolites. They also supplement, and occasionally potentially replace, existing metazoan functions. Bdelloid rotifers therefore express horizontally acquired genes on a scale unprecedented in animals, and foreign genes make a profound contribution to their metabolism. This represents a potential

  8. Migratory behaviour of a dominant detritivorous fish Prochilodus lineatus evaluated by multivariate biochemical and pollutant data.

    Science.gov (United States)

    Speranza, E D; Cappelletti, N; Migoya, M C; Tatone, L M; Colombo, J C

    2012-07-01

    This paper studies the migration pathways and ranges of a dominant detritivorous fish Prochilodus lineatus along pollution gradients in the Río de la Plata basin using multivariate analysis of biochemical and pollutant data. Biochemical composition (water, ash, lipids, proteins, carbohydrates, neutral lipids classes and fatty acids), aliphatic hydrocarbons (ALI), polychlorinated biphenyls (PCB), linear alkylbenzenes (LAB) and organochlorine pesticides (OClP) were determined in muscle samples of P. lineatus collected in Metropolitan Buenos Aires, the lower Paraná River (Paraná: 200-1000 km from Buenos Aires) and the middle Paraná and Paraguay Rivers (North: 1000-1400 km north). Biochemical variables and pollutants exhibited large variability [Lipids 1.1-89.5% wet mass; ALI 1.4-413; LABs not detectable (n.d.)-115.2; PCBs n.d.-27.9; OClPs n.d.-11.8 µg g(-1) dry mass], due to the contrast of Buenos Aires with North fish. Fish from Buenos Aires were fatty (lipids 24.7 ± 12.3% wet mass), enriched in 18 carbon fatty acids and severely contaminated (ALI 152.4 ± 72.3; LABs 65.1 ± 26.4; PCBs 15.2 ± 6.8; OClPs 1.8 ± 1.9 µg g(-1) dry mass mean ±S.D.). In contrast, fish from North were lean (4.1 ± 3.1% wet mass), enriched in long chain (>20 carbons) polyunsaturated fatty acids, with average one to two orders of magnitude lower pollutant levels (ALI 41.2 ± 51.9; PCBs 2.2 ± 3.5; LABs 8.8 ± 21.1; OClPs 0.67 ± 0.75 µg g(-1) dry mass mean ±S.D.). Paraná showed intermediate values in all variables, denoting the mixing of different fish stocks. Based on principal component analysis, 14 outliers from 60 North and Paraná samples (representing 26 from 108 individual fish) were identified as pertaining to the Buenos Aires group with very similar lipid and pollutant levels. Data suggest that P. lineatus migrates a highly variable distance, exceeding 800-1000 km in multiple spatial and temporal overlapping ranges. Chemometric analysis of biochemical and pollutant data

  9. Determining the gross biochemical composition of cells and tissue with Raman spectrosocpy

    Science.gov (United States)

    Mourant, Judith R.; Dominguez, Jorge; Carpenter, Susan; Powers, Tamara M.; Guerra, Anabel; Short, Kurt W.; Kunapareddy, Nagapratima; Freyer, James P.

    2006-02-01

    The biochemical composition of mammalian cells has been estimated by Raman spectroscopy and the results compared with other biochemical methods. The Raman spectroscopy estimates were performed by fitting measured Raman and infrared spectra of dense cell suspensions to a linear combination of basis components (RNA, DNA, protein, lipid, glycoen). The Raman spectroscopy results are compared to biochemical analyses performed by extraction and quantfication of the biochemical components. Both absolute and relative measurements of biochemical composition are compared. Both the Raman and biochemical results indicate that there are signficant differences in gross biochemical composition dependent on growth stage and tumorigneicity.

  10. Right Ventricular Adaptation in Congenital Heart Diseases

    Directory of Open Access Journals (Sweden)

    Beatrijs Bartelds

    2014-05-01

    Full Text Available In the last four decades, enormous progress has been made in the treatment of congenital heart diseases (CHD; most patients now survive into adulthood, albeit with residual lesions. As a consequence, the focus has shifted from initial treatment to long-term morbidity and mortality. An important predictor for long-term outcome is right ventricular (RV dysfunction, but knowledge on the mechanisms of RV adaptation and dysfunction is still scarce. This review will summarize the main features of RV adaptation to CHD, focusing on recent knowledge obtained in experimental models of the most prevalent abnormal loading conditions, i.e., pressure load and volume load. Models of increased pressure load for the RV have shown a similar pattern of responses, i.e., increased contractility, RV dilatation and hypertrophy. Evidence is accumulating that RV failure in response to increased pressure load is marked by progressive diastolic dysfunction. The mechanisms of this progressive dysfunction are insufficiently known. The RV response to pressure load shares similarities with that of the LV, but also has specific features, e.g., capillary rarefaction, oxidative stress and inflammation. The contribution of these pathways to the development of failure needs further exploration. The RV adaptation to increased volume load is an understudied area, but becomes increasingly important in the growing groups of survivors of CHD, especially with tetralogy of Fallot. Recently developed animal models may add to the investigation of the mechanisms of RV adaptation and failure, leading to the development of new RV-specific therapies.

  11. Biochemical characterisation during seed development of oil palm (Elaeis guineensis).

    Science.gov (United States)

    Kok, Sau-Yee; Namasivayam, Parameswari; Ee, Gwendoline Cheng-Lian; Ong-Abdullah, Meilina

    2013-07-01

    Developmental biochemical information is a vital base for the elucidation of seed physiology and metabolism. However, no data regarding the biochemical profile of oil palm (Elaeis guineensis Jacq.) seed development has been reported thus far. In this study, the biochemical changes in the developing oil palm seed were investigated to study their developmental pattern. The biochemical composition found in the seed differed significantly among the developmental stages. During early seed development, the water, hexose (glucose and fructose), calcium and manganese contents were present in significantly high levels compared to the late developmental stage. Remarkable changes in the biochemical composition were observed at 10 weeks after anthesis (WAA): the dry weight and sucrose content increased significantly, whereas the water content and hexose content declined. The switch from a high to low hexose/sucrose ratio could be used to identify the onset of the maturation phase. At the late stage, dramatic water loss occurred, whereas the content of storage reserves increased progressively. Lauric acid was the most abundant fatty acid found in oil palm seed starting from 10 WAA. PMID:23575803

  12. Microstereolithography and its application to biochemical IC chip

    Science.gov (United States)

    Ikuta, Koji; Maruo, Shoji; Hasegawa, Tadahiro; Adachi, Takao

    2001-06-01

    The world's first micro stereo lithography, named IH process, was proposed and developed by the speaker in 1992. By now, several types of micro stereo lithography systems have been developed. Three-dimensional resolution of solidification has reached to 0.2 micron at present. These 3D micro fabrication processes using UV curable polymer gave a big impact on not only MEMS but also optics. The latest version of IH process enables us to make a movable micro mechanism without assemble process or sacrificial layer technique often used in silicon process. It is well known that the IH process is the mother of two-photon micro stereo lithography and its applications. Recently new micro chemical device named Biochemical IC Chip was proposed and developed by the speaker. This chip is based on the module IC chip-set like today's TTL family. IH process enable to make the biochemical IC including real three-dimensional micro fluid channels. Various kinds of Biochemical IC chips such as micro pump, switching valve, reactor, concentrator and detector have already been fabricated successfully. Basic performance of micro chemical devices constructed by the biochemical IC chips were demonstrated. The biochemical IC chips will open new bioscience and medicine based on innovative technology.

  13. The role of the sphingosine-1-phosphate signaling pathway in osteocyte mechanotransduction.

    Science.gov (United States)

    Zhang, Jia-Ning; Zhao, Yan; Liu, Chao; Han, Elizabeth S; Yu, Xue; Lidington, Darcy; Bolz, Steffen-Sebastian; You, Lidan

    2015-10-01

    Osteocytes are proposed to be the mechanosensory cells that translate mechanical loading into biochemical signals during the process of bone adaptation. The lipid mediator sphingosine-1-phosphate (S1P) has been reported to play a role in the mechanotransduction process of blood vessels and also in the dynamic control of bone mineral homeostasis. Nevertheless, the potential role of S1P in bone mechanotransduction has yet to be elucidated. In this study, we hypothesized that a S1P cascade is involved in the activation of osteocytes in response to loading-induced oscillatory fluid flow (OFF) in bone. MLO-Y4 osteocyte-like cells express the necessary components of a functional S1P cascade. To examine the involvement of S1P signaling in osteocyte mechanotransduction, we applied OFF (1 Pa, 1 Hz) to osteocyte-like MLO-Y4 cells under conditions where the S1P signaling pathway was modulated. We found that decreased endogenous S1P levels significantly suppressed the OFF-induced intracellular calcium response. Addition of extracellular S1P to MLO-Y4 cells enhanced the synthesis and release of prostaglandin E2 (PGE2) under static cells and amplified OFF-induced PGE2 release. The stimulatory effect of OFF on the gene expression levels of osteoprotegerin (OPG) and receptor activator for nuclear factor κB ligand (RANKL) was S1P dependent. Furthermore, the S1P2 receptor subtype was shown to be involved in OFF-induced PGE2 synthesis and release, as well as down-regulation of RANKL/OPG gene expression ratio. In summary, our data suggest that S1P cascade is involved in OFF-induced mechanotransduction in MLO-Y4 cells and that extracellular S1P exerts its effect partly through S1P2 receptors. PMID:25988659

  14. Adaptation of the symbiotic Mesorhizobium-chickpea relationship to phosphate deficiency relies on reprogramming of whole-plant metabolism.

    Science.gov (United States)

    Nasr Esfahani, Maryam; Kusano, Miyako; Nguyen, Kien Huu; Watanabe, Yasuko; Ha, Chien Van; Saito, Kazuki; Sulieman, Saad; Herrera-Estrella, Luis; Tran, L S

    2016-08-01

    Low inorganic phosphate (Pi) availability is a major constraint for efficient nitrogen fixation in legumes, including chickpea. To elucidate the mechanisms involved in nodule acclimation to low Pi availability, two Mesorhizobium-chickpea associations exhibiting differential symbiotic performances, Mesorhizobium ciceri CP-31 (McCP-31)-chickpea and Mesorhizobium mediterranum SWRI9 (MmSWRI9)-chickpea, were comprehensively studied under both control and low Pi conditions. MmSWRI9-chickpea showed a lower symbiotic efficiency under low Pi availability than McCP-31-chickpea as evidenced by reduced growth parameters and down-regulation of nifD and nifK These differences can be attributed to decline in Pi level in MmSWRI9-induced nodules under low Pi stress, which coincided with up-regulation of several key Pi starvation-responsive genes, and accumulation of asparagine in nodules and the levels of identified amino acids in Pi-deficient leaves of MmSWRI9-inoculated plants exceeding the shoot nitrogen requirement during Pi starvation, indicative of nitrogen feedback inhibition. Conversely, Pi levels increased in nodules of Pi-stressed McCP-31-inoculated plants, because these plants evolved various metabolic and biochemical strategies to maintain nodular Pi homeostasis under Pi deficiency. These adaptations involve the activation of alternative pathways of carbon metabolism, enhanced production and exudation of organic acids from roots into the rhizosphere, and the ability to protect nodule metabolism against Pi deficiency-induced oxidative stress. Collectively, the adaptation of symbiotic efficiency under Pi deficiency resulted from highly coordinated processes with an extensive reprogramming of whole-plant metabolism. The findings of this study will enable us to design effective breeding and genetic engineering strategies to enhance symbiotic efficiency in legume crops. PMID:27450089

  15. On Adaptive vs. Non-adaptive Security of Multiparty Protocols

    DEFF Research Database (Denmark)

    Canetti, Ran; Damgård, Ivan Bjerre; Dziembowski, Stefan; Ishai, Yuval; Malkin, Tal

    course of the computation. We study the relations between adaptive security (i.e., security in the adaptive setting) and non-adaptive security, according to two definitions and in several models of computation. While affirming some prevailing beliefs, we also obtain some unexpected results. Some...... definition of Canetti, for honest-but-curious adversaries, adaptive security is equivalent to non-adaptive security when the number of parties is logarithmic, and is strictly stronger than non-adaptive security when the number of parties is super-logarithmic. For Byzantine adversaries, adaptive security is...

  16. BIOCHEMICAL AND PHYSIOLOGICAL CHARACTERIZATION OF OIL PALM INTERSPECIFIC HYBRIDS (Elaeis oleifera x Elaeis guineensis GROWN IN HYDROPONICS

    Directory of Open Access Journals (Sweden)

    Yurany Dayana Rivera

    2013-09-01

    Full Text Available The interspecific hybrid, Elaeis oleifera x Elaeis guineensis (OxG is an alternative for improving the competitiveness and sustainability of the Latin American oil palm agro-industry, because of its partial resistance to some lethal diseases and also because of the high quality of its oil. A comparative characterization was conducted of the physiological and biochemical performance of seedlings of six OxG hybrids grown in hydroponics. Gas exchange, vegetative growth, protein, sugar and photosynthetic pigment content, and antioxidant system activity were determined. With the exception of gas exchange, the other variables showed significant differences between materials. The ‘U1273’ and ‘U1737’ materials showed greater vegetative growth with no expression of biochemical traits, while the ‘U1914’and ‘U1990’ materials showed high levels of reducing and total sugars, photosynthetic pigments, and antioxidant system activities, characteristics that could confer them adaptation to stress conditions. With the standardized hydroponics technique, the optimal conditions for the growth of seedlings were ensured, the differences between materials and hybrid crosses were established, so those with promising features from the physiological and biochemical standpoint were identified. Finally, it could be used to study in a simple, fast, clean and inexpensive way, the effect of levels and sources of mineral nutrients on the growth and development of oil palm.

  17. Carbamates toxicity in farmers and its assesment through biochemical parameters

    International Nuclear Information System (INIS)

    Prevalent environmental toxicity of various chemical group of pesticides and their effects leading towards increasing morbidity and mortality in the farmers is of great concerned. In this situation the biochemical biomarkers are regarded as meaningful tools for monitoring toxic end points. This work was aimed to assess the toxic impacts of carbamates through some biochemical parameters and useful validity of these biomarkers was also observed. Present results reveal inhibition of cholinesterase activity by 46% whereas bilirubin, urea and creatinine levels in serum were increased and sugar values was decreased at highly significant level (p<0.001). Urine urobilinogen concentration found raised significantly at high level (p<0.001) while protein, urea creatinine and sugar values in urine of the farmers seen non-significant. This study concluded that the selected biochemical parameters can be used as biomarkers to assess the significant toxic effects in the exposed populations. (author)

  18. Click Chemistry-Mediated Nanosensors for Biochemical Assays

    Science.gov (United States)

    Chen, Yiping; Xianyu, Yunlei; Wu, Jing; Yin, Binfeng; Jiang, Xingyu

    2016-01-01

    Click chemistry combined with functional nanoparticles have drawn increasing attention in biochemical assays because they are promising in developing biosensors with effective signal transformation/amplification and straightforward signal readout for clinical diagnostic assays. In this review, we focus on the latest advances of biochemical assays based on Cu (I)-catalyzed 1, 3-dipolar cycloaddition of azides and alkynes (CuAAC)-mediated nanosensors, as well as the functionalization of nanoprobes based on click chemistry. Nanoprobes including gold nanoparticles, quantum dots, magnetic nanoparticles and carbon nanomaterials are covered. We discuss the advantages of click chemistry-mediated nanosensors for biochemical assays, and give perspectives on the development of click chemistry-mediated approaches for clinical diagnosis and other biomedical applications. PMID:27217831

  19. Hematologic and plasma biochemical values of hyacinth macaws (Anodorhynchus hyacinthinus).

    Science.gov (United States)

    Kolesnikovas, Cristiane K M; Niemeyer, Claudia; Teixeira, Rodrigo H F; Nunes, Adauto L V; Rameh-de-Albuquerque, Luciana C; Sant'Anna, Sávio S; Catão-Dias, José L

    2012-09-01

    The hyacinth macaw (Anodorhyncus hyacinthinus), considered the largest psittacine bird species in the world, is an endangered species, with a remaining population of approximately 6500 birds in the wild. To establish hematologic and plasma biochemical reference ranges and to verify differences related to sex, samples from 29 hyacinth macaws (14 males, 15 females) were obtained from birds apprehended from illegal wildlife trade and subsequently housed at the Sorocaba Zoo, Brazil. No significant differences in hematologic or plasma biochemical values were found between females and males. Compared with published reference values, differences were found in mean concentrations of total red blood cell count, corpuscular volume, corpuscular hemoglobin level, total white blood cell count, aspartate aminotransferase level, creatine kinase concentration, alkaline phosphatase concentration, and phosphorus level. Baseline hematologic and plasma biochemical ranges were established, which may be useful as reference values for clinicians working with this endangered species in captivity or rehabilitation centers. PMID:23156973

  20. Hematologic and plasma biochemical values of Spix's macaws (Cyanopsitta spixii).

    Science.gov (United States)

    Foldenauer, Ulrike; Borjal, Raffy Jim; Deb, Amrita; Arif, Abdi; Taha, Abid Sharif; Watson, Ryan William; Steinmetz, Hanspeter; Bürkle, Marcellus; Hammer, Sven

    2007-12-01

    The Spix's macaw (Cyanopsitta spixii) is considered the world's most endangered parrot, with the last wild bird disappearing in 2001 and only 74 birds in captivity. To establish hematologic and plasma biochemical reference ranges and to look for differences relative to sex, age, and season, we obtained blood samples from 46 captive Spix's macaws (23 male, 23 female) housed in aviaries at the Al Wabra Wildlife Preservation in the State of Qatar. No significant differences in hematologic or plasma biochemical values were found between females and males. Adult and juvenile birds differed in mean concentrations of glucose, total protein, amylase, cholesterol, and phosphorus; in percentages of heterophils and lymphocytes; and in the absolute lymphocyte count. Total protein, cholesterol, and phosphorus concentrations; hematocrit; and heterophil and lymphocyte counts differed significantly by season. Baseline hematologic and plasma biochemical ranges were established, which may be useful as reference values for clinicians working with this highly endangered species. PMID:18351006

  1. New pathways into headship?

    OpenAIRE

    Higham, Rob; Early, Peter; Coldwell, Michael; Stevens, Anna; Brown, Chris

    2015-01-01

    There continues to be something of a conundrum in the recruitment of headteachers in England. While “a very large majority of headteachers report being satisfied with their jobs” (Micklewright et al 2014: 17), headteacher recruitment and retention remain major challenges for school governors and policy makers. In this context, the New Pathways into Headship project was commissioned by the National College for Teaching and Leadership (NCTL) in January 2013. Tasked with considering new or a...

  2. Pathway analysis of IMC

    DEFF Research Database (Denmark)

    Skrypnyuk, Nataliya; Nielson, Flemming; Pilegaard, Henrik

    We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced into the...... syntax of IMC in order to make our analysis feasible. Finally we describe the analysis itself together with several theoretical results that we have proved for it....

  3. Solar Adaptive Optics

    Directory of Open Access Journals (Sweden)

    Thomas R. Rimmele

    2011-06-01

    Full Text Available Adaptive optics (AO has become an indispensable tool at ground-based solar telescopes. AO enables the ground-based observer to overcome the adverse effects of atmospheric seeing and obtain diffraction limited observations. Over the last decade adaptive optics systems have been deployed at major ground-based solar telescopes and revitalized ground-based solar astronomy. The relatively small aperture of solar telescopes and the bright source make solar AO possible for visible wavelengths where the majority of solar observations are still performed. Solar AO systems enable diffraction limited observations of the Sun for a significant fraction of the available observing time at ground-based solar telescopes, which often have a larger aperture than equivalent space based observatories, such as HINODE. New ground breaking scientific results have been achieved with solar adaptive optics and this trend continues. New large aperture telescopes are currently being deployed or are under construction. With the aid of solar AO these telescopes will obtain observations of the highly structured and dynamic solar atmosphere with unprecedented resolution. This paper reviews solar adaptive optics techniques and summarizes the recent progress in the field of solar adaptive optics. An outlook to future solar AO developments, including a discussion of Multi-Conjugate AO (MCAO and Ground-Layer AO (GLAO will be given.

  4. Adaptation and risk management

    Energy Technology Data Exchange (ETDEWEB)

    Preston, Benjamin L [ORNL

    2011-01-01

    Adaptation assessment methods are compatible with the international risk management standard ISO:31000. Risk management approaches are increasingly being recommended for adaptation assessments at both national and local levels. Two orientations to assessments can commonly be identified: top-down and bottom-up, and prescriptive and diagnostic. Combinations of these orientations favor different types of assessments. The choice of orientation can be related to uncertainties in prediction and taking action, in the type of adaptation and in the degree of system stress. Adopting multiple viewpoints is to be encouraged, especially in complex situations. The bulk of current guidance material is consistent with top-down and predictive approaches, thus is most suitable for risk scoping and identification. Abroad range ofmaterial fromwithin and beyond the climate change literature can be used to select methods to be used in assessing and implementing adaptation. The framing of risk, correct formulation of the questions being investigated and assessment methodology are critical aspects of the scoping phase. Only when these issues have been addressed should be issue of specific methods and tools be addressed. The reorientation of adaptation from an assessment focused solely on anthropogenic climate change to broader issues of vulnerability/resilience, sustainable development and disaster risk, especially through a risk management framework, can draw from existing policy and management understanding in communities, professions and agencies, incorporating existing agendas, knowledge, risks, and issues they already face.

  5. Occurrence of bacteria and biochemical markers on public surfaces.

    Science.gov (United States)

    Reynolds, Kelly A; Watt, Pamela M; Boone, Stephanie A; Gerba, Charles P

    2005-06-01

    From 1999-2003, the hygiene of 1061 environmental surfaces from shopping, daycare, and office environments, personal items, and miscellaneous activities (i.e., gymnasiums, airports, movie theaters, restaurants, etc.), in four US cities, was monitored. Samples were analyzed for fecal and total coliform bacteria, protein, and biochemical markers. Biochemical markers, i.e., hemoglobin (blood marker), amylase (mucus, saliva, sweat, and urine marker), and urea (urine and sweat marker) were detected on 3% (26/801); 15% (120/801), and 6% (48/801) of the surfaces, respectively. Protein (general hygiene marker) levels > or = 200 microg/10 cm2 were present on 26% (200/801) of the surfaces tested. Surfaces from children's playground equipment and daycare centers were the most frequently contaminated (biochemical markers on 36%; 15/42 and 46%; 25/54, respectively). Surfaces from the shopping, miscellaneous activities, and office environments were positive for biochemical markers with a frequency of 21% (69/333), 21% (66/308), and 11% (12/105), respectively). Sixty samples were analyzed for biochemical markers and bacteria. Total and fecal coliforms were detected on 20% (12/60) and 7% (4/ 60) of the surfaces, respectively. Half and one-third of the sites positive for biochemical markers were also positive for total and fecal coliforms, respectively. Artificial contamination of public surfaces with an invisible fluorescent tracer showed that contamination from outside surfaces was transferred to 86% (30/ 35) of exposed individual's hands and 82% (29/35) tracked the tracer to their home or personal belongings hours later. Results provide information on the relative hygiene of commonly encountered public surfaces and aid in the identification of priority environments where contaminant occurrence and risk of exposure may be greatest. Children's playground equipment is identified as a priority surface for additional research on the occurrence of and potential exposure to infectious

  6. Decoupled Adapt-then-Combine diffusion networks with adaptive combiners

    OpenAIRE

    Fernandez-Bes, Jesus; Arenas-García, Jerónimo; Silva, Magno T. M.; Azpicueta-Ruiz, Luis A.

    2015-01-01

    In this paper we analyze a novel diffusion strategy for adaptive networks called Decoupled Adapt-then-Combine, which keeps a fully local estimate of the solution for the adaptation step. Our strategy, which is specially convenient for heterogeneous networks, is compared with the standard Adapt-then-Combine scheme and theoretically analyzed using energy conservation arguments. Such comparison shows the need of implementing adaptive combiners for both schemes to obtain a good performance in cas...

  7. The Development of a Biochemical Profile of Acacia Honey by Identifying Biochemical Determinants of its Quality

    Directory of Open Access Journals (Sweden)

    Liviu Alexandru MARGHITAS

    2010-09-01

    Full Text Available Codex Alimentarius Standard, EU Legislation and National Standards state honey authenticity. Authenticity in respect of production (to prevent adulteration and authenticity in respect of geographical and botanical origin are the two main aspects of general honey authenticity. Quality of honey depends on the plant source, the chemical composition of these plants as well, as on the climatic conditions and soil mineral composition. Romanian acacia (Robinia pseudoacacia honey that came from the most important Transylvanian massif (Valea lui Mihai, Bihor County, Romania was evaluated for authenticity by pollen-analysis, several physico-chemical analyses, including sugar profile and mineral content. As polyphenolic content could be also an important factor for botanical authentification, HPLC-DAD-MS analyses were performed to assess the fingerprint of this important secondary plant metabolite. Statistical data were processed in order to develop a biochemical profile of this type of honey and the main quality categories identification. The results of physico-chemical analysis demonstrated that the tested honey samples could be framed into monofloral type of acacia honeys. The analysis of acacia honeys originating from Valea lui Mihai, Romania, showed that polyphenolic profile (phenolic acids and flavonoids could be used as a complementary method for authenticity determination together with pollen analysis and other physico-chemical analysis.

  8. Physiological and biochemical basis of salmon young ifshes migratory behavior

    Institute of Scientific and Technical Information of China (English)

    Vladimir Ivanovich Martemyanov

    2016-01-01

    The review presents data on structural changes, physiological and biochemical reactions occurring at salmon young fishes during smoltification. It is shown, that young salmon fishes located in fresh water, in the process of smoltification undergo a complex of structural, physiological and biochemical changes directed on preparation of the organism for living in the sea. These changes cause stress reaction which excites young fishes to migrate down the river towards the sea. Measures to improve reproduction of young salmon fishes at fish farms are offered.

  9. Biochemical response and the effects of bariatric surgeries on type 2 diabetes

    Science.gov (United States)

    Allen, Roland; Hughes, Tyler; Lerd Ng, Jia; Ortiz, Roberto; Abou Ghantous, Michel; Bouhali, Othmane; Arredouani, Abdelilah

    2013-03-01

    A general method is introduced for calculating the biochemical response to pharmaceuticals, surgeries, or other medical interventions. This method is then applied in a simple model of the response to Roux-en-Y gastric bypass (RYGB) surgery in obese diabetic patients. We specifically address the amazing fact that glycemia correction is usually achieved immediately after RYGB surgery, long before there is any appreciable weight loss. Many studies indicate that this result is not due merely to caloric restriction, and it is usually attributed to an increase in glucagon-like peptide 1 (GLP-1) levels observed after the surgery. However, our model indicates that this mechanism alone is not sufficient to explain either the largest declines in glucose levels or the measured declines in the homeostatic model assessment insulin resistance (HOMA-IR). The most robust additional mechanism would be production of a factor which opens an insulin-independent pathway for glucose transport into cells, perhaps related to the well-established insulin-independent pathway associated with exercise. Potential candidates include bradykinin, a 9 amino acid peptide. If such a substance were found to exist, it would offer hope for medications which mimic the immediate beneficial effect of RYGB surgery. Supported by Qatar Biomedical Research Institute and Science Program at Texas A&M University at Qatar

  10. Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to psychopathology.

    Directory of Open Access Journals (Sweden)

    Anna Kubesova

    Full Text Available Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson's disease and Alzheimer's disease. The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin, their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases--glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders.

  11. Evolution of adaptation mechanisms: Adaptation energy, stress, and oscillating death.

    Science.gov (United States)

    Gorban, Alexander N; Tyukina, Tatiana A; Smirnova, Elena V; Pokidysheva, Lyudmila I

    2016-09-21

    In 1938, Selye proposed the notion of adaptation energy and published 'Experimental evidence supporting the conception of adaptation energy.' Adaptation of an animal to different factors appears as the spending of one resource. Adaptation energy is a hypothetical extensive quantity spent for adaptation. This term causes much debate when one takes it literally, as a physical quantity, i.e. a sort of energy. The controversial points of view impede the systematic use of the notion of adaptation energy despite experimental evidence. Nevertheless, the response to many harmful factors often has general non-specific form and we suggest that the mechanisms of physiological adaptation admit a very general and nonspecific description. We aim to demonstrate that Selye׳s adaptation energy is the cornerstone of the top-down approach to modelling of non-specific adaptation processes. We analyze Selye׳s axioms of adaptation energy together with Goldstone׳s modifications and propose a series of models for interpretation of these axioms. Adaptation energy is considered as an internal coordinate on the 'dominant path' in the model of adaptation. The phenomena of 'oscillating death' and 'oscillating remission' are predicted on the base of the dynamical models of adaptation. Natural selection plays a key role in the evolution of mechanisms of physiological adaptation. We use the fitness optimization approach to study of the distribution of resources for neutralization of harmful factors, during adaptation to a multifactor environment, and analyze the optimal strategies for different systems of factors. PMID:26801872

  12. Adaptive cancellation techniques

    Science.gov (United States)

    1983-11-01

    An adaptive signal canceller has been evaluated for the enhancement of pulse signal reception during the transmission of a high power ECM jamming signal. The canceller design is based on the use of DRFM(Digital RF Memory) technology as part of an adaptive multiple tapped delay line. The study includes analysis of relationship of tap spacing and waveform bandwidth, survey of related documents in areas of sidelobe cancellers, transversal equalizers, and adaptive filters, and derivation of control equations and corresponding control processes. The simulation of overall processes included geometric analysis of the multibeam transmitting antenna, multiple reflection sources and the receiving antenna; waveforms, tap spacings and bandwidths; and alternate control algorithms. Conclusions are provided regarding practical system control algorithms, design characteristics and limitations.

  13. Adaptable Embedded Systems

    CERN Document Server

    Lisbôa, Carlos; Carro, Luigi

    2013-01-01

    As embedded systems become more complex, designers face a number of challenges at different levels: they need to boost performance, while keeping energy consumption as low as possible, they need to reuse existent software code, and at the same time they need to take advantage of the extra logic available in the chip, represented by multiple processors working together.  This book describes several strategies to achieve such different and interrelated goals, by the use of adaptability. Coverage includes reconfigurable systems, dynamic optimization techniques such as binary translation and trace reuse, new memory architectures including homogeneous and heterogeneous multiprocessor systems, communication issues and NOCs, fault tolerance against fabrication defects and soft errors, and finally, how one can combine several of these techniques together to achieve higher levels of performance and adaptability.  The discussion also includes how to employ specialized software to improve this new adaptive system, and...

  14. Engineering Adaptive Web Applications

    DEFF Research Database (Denmark)

    Dolog, Peter

    2007-01-01

    Information and services on the web are accessible for everyone. Users of the web differ in their background, culture, political and social environment, interests and so on. Ambient intelligence was envisioned as a concept for systems which are able to adapt to user actions and needs....... With the growing amount of information and services, the web applications become natural candidates to adopt the concepts of ambient intelligence. Such applications can deal with divers user intentions and actions based on the user profile and can suggest the combination of information content and services which...... suit the user profile the most. This paper summarizes the domain engineering framework for such adaptive web applications. The framework provides guidelines to develop adaptive web applications as members of a family. It suggests how to utilize the design artifacts as knowledge which can be used...

  15. Robust adaptive control of nonlinearly parameterized systems with unmodeled dynamics

    Institute of Scientific and Technical Information of China (English)

    LIU Yu-sheng; CHEN Jiang; LI Xing-yuan

    2006-01-01

    Many physical systems such as biochemical processes and machines with friction are of nonlinearly parameterized systems with uncertainties.How to control such systems effectively is one of the most challenging problems.This paper presents a robust adaptive controller for a significant class of nonlinearly parameterized systems.The controller can be used in cases where there exist parameter and nonlinear uncertainties,unmodeled dynamics and unknown bounded disturbances.The design of the controller is based on the control Lyapunov function method.A dynamic signal is introduced and adaptive nonlinear damping terms are used to restrain the effects of unmodeled dynamics,nonlinear uncertainties and unknown bounded disturbances.The backstepping procedure is employed to overcome the complexity in the design.With the proposed method,the estimation of the unknown parameters of the system is not required and there is only one adaptive parameter no matter how high the order of the system is and how many unknown parameters.there are.It is proved theoretically that the proposed robust adaptive control scheme guarantees the stability of nonlinearly parameterized system.Furthermore,all the states approach the equilibrium in arbitrary precision by choosing some design constants appropriately.Simulation results illustrate the effectiveness of the proposed robust adaptive controller.

  16. Pathways with PathWhiz.

    Science.gov (United States)

    Pon, Allison; Jewison, Timothy; Su, Yilu; Liang, Yongjie; Knox, Craig; Maciejewski, Adam; Wilson, Michael; Wishart, David S

    2015-07-01

    PathWhiz (http://smpdb.ca/pathwhiz) is a web server designed to create colourful, visually pleasing and biologically accurate pathway diagrams that are both machine-readable and interactive. As a web server, PathWhiz is accessible from almost any place and compatible with essentially any operating system. It also houses a public library of pathways and pathway components that can be easily viewed and expanded upon by its users. PathWhiz allows users to readily generate biologically complex pathways by using a specially designed drawing palette to quickly render metabolites (including automated structure generation), proteins (including quaternary structures, covalent modifications and cofactors), nucleic acids, membranes, subcellular structures, cells, tissues and organs. Both small-molecule and protein/gene pathways can be constructed by combining multiple pathway processes such as reactions, interactions, binding events and transport activities. PathWhiz's pathway replication and propagation functions allow for existing pathways to be used to create new pathways or for existing pathways to be automatically propagated across species. PathWhiz pathways can be saved in BioPAX, SBGN-ML and SBML data exchange formats, as well as PNG, PWML, HTML image map or SVG images that can be viewed offline or explored using PathWhiz's interactive viewer. PathWhiz has been used to generate over 700 pathway diagrams for a number of popular databases including HMDB, DrugBank and SMPDB. PMID:25934797

  17. Adaptive Metric Kernel Regression

    DEFF Research Database (Denmark)

    Goutte, Cyril; Larsen, Jan

    1998-01-01

    Kernel smoothing is a widely used nonparametric pattern recognition technique. By nature, it suffers from the curse of dimensionality and is usually difficult to apply to high input dimensions. In this paper, we propose an algorithm that adapts the input metric used in multivariate regression by...... minimising a cross-validation estimate of the generalisation error. This allows one to automatically adjust the importance of different dimensions. The improvement in terms of modelling performance is illustrated on a variable selection task where the adaptive metric kernel clearly outperforms the standard...

  18. STUDYING COMPLEX ADAPTIVE SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    John H. Holland

    2006-01-01

    Complex adaptive systems (cas) - systems that involve many components that adapt or learn as they interact - are at the heart of important contemporary problems. The study of cas poses unique challenges: Some of our most powerful mathematical tools, particularly methods involving fixed points, attractors, and the like, are of limited help in understanding the development of cas. This paper suggests ways to modify research methods and tools, with an emphasis on the role of computer-based models, to increase our understanding of cas.

  19. Adaptive metric kernel regression

    DEFF Research Database (Denmark)

    Goutte, Cyril; Larsen, Jan

    2000-01-01

    Kernel smoothing is a widely used non-parametric pattern recognition technique. By nature, it suffers from the curse of dimensionality and is usually difficult to apply to high input dimensions. In this contribution, we propose an algorithm that adapts the input metric used in multivariate...... regression by minimising a cross-validation estimate of the generalisation error. This allows to automatically adjust the importance of different dimensions. The improvement in terms of modelling performance is illustrated on a variable selection task where the adaptive metric kernel clearly outperforms the...

  20. Adaptive radar resource management

    CERN Document Server

    Moo, Peter

    2015-01-01

    Radar Resource Management (RRM) is vital for optimizing the performance of modern phased array radars, which are the primary sensor for aircraft, ships, and land platforms. Adaptive Radar Resource Management gives an introduction to radar resource management (RRM), presenting a clear overview of different approaches and techniques, making it very suitable for radar practitioners and researchers in industry and universities. Coverage includes: RRM's role in optimizing the performance of modern phased array radars The advantages of adaptivity in implementing RRMThe role that modelling and