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Sample records for metabolism functional polarization

  1. Metabolic Reprograming in Macrophage Polarization

    PubMed Central

    Galván-Peña, Silvia; O’Neill, Luke A. J.

    2014-01-01

    Studying the metabolism of immune cells in recent years has emphasized the tight link existing between the metabolic state and the phenotype of these cells. Macrophages in particular are a good example of this phenomenon. Whether the macrophage obtains its energy through glycolysis or through oxidative metabolism can give rise to different phenotypes. Classically activated or M1 macrophages are key players of the first line of defense against bacterial infections and are known to obtain energy through glycolysis. Alternatively activated or M2 macrophages on the other hand are involved in tissue repair and wound healing and use oxidative metabolism to fuel their longer-term functions. Metabolic intermediates, however, are not just a source of energy but can be directly implicated in a particular macrophage phenotype. In M1 macrophages, the Krebs cycle intermediate succinate regulates HIF1α, which is responsible for driving the sustained production of the pro-inflammatory cytokine IL1β. In M2 macrophages, the sedoheptulose kinase carbohydrate kinase-like protein is critical for regulating the pentose phosphate pathway. The potential to target these events and impact on disease is an exciting prospect. PMID:25228902

  2. Sleep and metabolic function

    PubMed Central

    Morselli, Lisa L.; Guyon, Aurore; Spiegel, Karine

    2012-01-01

    Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper airway obstruction leading to intermittent hypoxemia and sleep fragmentation, has also become highly prevalent as a consequence of the epidemic of obesity and has been shown to contribute, in a vicious circle, to the metabolic disturbances observed in obese patients. In this article, we summarize the current data supporting the role of sleep in the regulation of glucose homeostasis and the hormones involved in the regulation of appetite. We also review the results of the epidemiologic and laboratory studies that investigated the impact of sleep duration and quality on the risk of developing diabetes and obesity, as well as the mechanisms underlying this increased risk. Finally, we discuss how obstructive sleep apnea affects glucose metabolism and the beneficial impact of its treatment, the continuous positive airway pressure. In conclusion, the data available in the literature highlight the importance of getting enough good sleep for metabolic health. PMID:22101912

  3. Mammalian Polyamine Metabolism and Function

    PubMed Central

    Pegg, Anthony E.

    2009-01-01

    Summary Polyamines are ubiquitous small basic molecules that play multiple essential roles in mammalian physiology. Their cellular content is highly regulated and there is convincing evidence that altered metabolism is involvement in many disease states. Drugs altering polyamine levels may therefore have a variety of important targets. This review will summarize the current state of understanding of polyamine metabolism and function, the regulation of polyamine content, and heritable pathological conditions that may be derived from altered polyamine metabolism. PMID:19603518

  4. The Metabolic Prospective and Redox Regulation of Macrophage Polarization

    PubMed Central

    He, Chao; Carter, A Brent

    2016-01-01

    Macrophage plasticity is an important feature of these innate immune cells. Macrophage phenotypes are divided into two categories, the classically activated macrophages (CAM, M1 phenotype) and the alternatively activated macrophages (AAM, M2 phenotype). M1 macrophages are commonly associated with the generation of proinflammatory cytokines, whereas M2 macrophages are anti-inflammatory and often associated with tumor progression and fibrosis development. Macrophages produce high levels of reactive oxygen species (ROS). Recent evidence suggests ROS can potentially regulate macrophage phenotype. In addition, macrophages phenotypes are closely related to their metabolic patterns, particularly fatty acid/cholesterol metabolism. In this review, we briefly summarize recent advances in macrophage polarization with special attention to their relevance to specific disease conditions and metabolic regulation of polarization. Understanding these metabolic switches can facilitate the development of targeted therapies for various diseases. PMID:26962470

  5. Kupffer Cell Metabolism and Function

    PubMed Central

    Nguyen-Lefebvre, Anh Thu; Horuzsko, Anatolij

    2015-01-01

    Kupffer cells are resident liver macrophages and play a critical role in maintaining liver functions. Under physiological conditions, they are the first innate immune cells and protect the liver from bacterial infections. Under pathological conditions, they are activated by different components and can differentiate into M1-like (classical) or M2-like (alternative) macrophages. The metabolism of classical or alternative activated Kupffer cells will determine their functions in liver damage. Special functions and metabolism of Kupffer cells suggest that they are an attractive target for therapy of liver inflammation and related diseases, including cancer and infectious diseases. Here we review the different types of Kupffer cells and their metabolism and functions in physiological and pathological conditions. PMID:26937490

  6. Polarization measurement analysis. III. Analysis of the polarization angle dispersion function with high precision polarization data

    NASA Astrophysics Data System (ADS)

    Alina, D.; Montier, L.; Ristorcelli, I.; Bernard, J.-P.; Levrier, F.; Abdikamalov, E.

    2016-10-01

    High precision polarization measurements, such as those from the Planck satellite, open new opportunities for the study of the magnetic field structure as traced by polarimetric measurements of the interstellar dust emission. The polarization parameters suffer from bias in the presence of measurement noise. It is critical to take into account all the information available in the data in order to accurately derive these parameters. In our previous work, we studied the bias on polarization fraction and angle, various estimators of these quantities, and their associated uncertainties. The goal of this paper is to characterize the bias on the polarization angle dispersion function that is used to study the spatial coherence of the polarization angle. We characterize for the first time the bias on the conventional estimator of the polarization angle dispersion function and show that it can be positive or negative depending on the true value. Monte Carlo simulations were performed to explore the impact of the noise properties of the polarization data, as well as the impact of the distribution of the true polarization angles on the bias. We show that in the case where the ellipticity of the noise in (Q,U) varies by less than 10%, one can use simplified, diagonal approximation of the noise covariance matrix. In other cases, the shape of the noise covariance matrix should be taken into account in the estimation of the polarization angle dispersion function. We also study new estimators such as the dichotomic and the polynomial estimators. Though the dichotomic estimator cannot be directly used to estimate the polarization angle dispersion function, we show that, on the one hand, it can serve as an indicator of the accuracy of the conventional estimator and, on the other hand, it can be used for deriving the polynomial estimator. We propose a method for determining the upper limit of the bias on the conventional estimator of the polarization angle dispersion function. The

  7. The stress polarity pathway: AMPK ‘GIV’-es protection against metabolic insults

    PubMed Central

    Ghosh, Pradipta

    2017-01-01

    Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis. How AMPK protects the epithelium remained unknown until recently Aznar et al. identified GIV/Girdin as a novel effector of AMPK at the cell-cell junctions; phosphorylation of GIV at a single site by AMPK appears to be both necessary and sufficient for strengthening tight junctions and preserving cell polarity and epithelial barrier function in the face of energetic stress. Here we review the fundamentals of this specialized signaling pathway that buttresses cell-cell junctions against stress-induced collapse and discuss its pathophysiologic relevance in the context of a variety of diseases, including cancers, diabetes, aging, and the growing list of beneficial effects of the AMPK-activator, Metformin. PMID:28209925

  8. Metabolism Is Central to Tolerogenic Dendritic Cell Function

    PubMed Central

    Sim, Wen Jing; Ahl, Patricia Jennifer; Connolly, John Edward

    2016-01-01

    Immunological tolerance is a fundamental tenant of immune homeostasis and overall health. Self-tolerance is a critical component of the immune system that allows for the recognition of self, resulting in hyporeactivity instead of immunogenicity. Dendritic cells are central to the establishment of dominant immune tolerance through the secretion of immunosuppressive cytokines and regulatory polarization of T cells. Cellular metabolism holds the key to determining DC immunogenic or tolerogenic cell fate. Recent studies have demonstrated that dendritic cell maturation leads to a shift toward a glycolytic metabolic state and preferred use of glucose as a carbon source. In contrast, tolerogenic dendritic cells favor oxidative phosphorylation and fatty acid oxidation. This dichotomous metabolic reprogramming of dendritic cells drives differential cellular function and plays a role in pathologies, such as autoimmune disease. Pharmacological alterations in metabolism have promising therapeutic potential. PMID:26980944

  9. Persistence, entrainment, and function of circadian rhythms in polar vertebrates.

    PubMed

    Williams, Cory T; Barnes, Brian M; Buck, C Loren

    2015-03-01

    Polar organisms must cope with an environment that periodically lacks the strongest time-giver, or zeitgeber, of circadian organization-robust, cyclical oscillations between light and darkness. We review the factors influencing the persistence of circadian rhythms in polar vertebrates when the light-dark cycle is absent, the likely mechanisms of entrainment that allow some polar vertebrates to remain synchronized with geophysical time, and the adaptive function of maintaining circadian rhythms in such environments.

  10. Polar accumulation of the metabolic sensory histidine kinases DcuS and CitA in Escherichia coli.

    PubMed

    Scheu, Patrick; Sdorra, Sven; Liao, Yun-Feng; Wegner, Maria; Basché, Thomas; Unden, Gottfried; Erker, Wolfgang

    2008-08-01

    Signal transduction in prokaryotes is frequently accomplished by two-component regulatory systems in which a histidine protein kinase is the sensory component. Many of these sensory kinases control metabolic processes that do not show an obvious requirement for inhomogeneous distribution within bacterial cells. Here, the sensory kinases DcuS and CitA, two histidine kinases of Escherichia coli, were investigated. Both are membrane-integral and involved in the regulation of carboxylate metabolism. The two-component sensors were fused with yellow fluorescent protein (YFP) and live images of immobilized cells were obtained by confocal laser fluorescence microscopy. The fluorescence of the fusion proteins was concentrated at the poles of the cells, indicating polar accumulation of the sensory kinases. For quantitative evaluation, line profiles of the imaged fluorescence intensities were generated; these revealed that the fluorescence intensity of the polar bright spots was 2.3-8.5 times higher than that of the cytoplasm. With respect to the cylindrical part of the membrane, the values were lower by about 40 %. The polar accumulation was comparable to that of methyl-accepting chemotaxis proteins (MCPs) and MCP-related proteins. The degree of DcuS-YFP localization was independent of the presence of MCP and the expression level of dcuS-yfp (or DcuS concentration). The presence of effector (fumarate or citrate, respectively) increased the polar accumulation by more than 20 %. Cell fractionation demonstrated that polar accumulation was not related to inclusion body formation. Therefore, sensory kinases DcuS and CitA, which regulate metabolic processes without obvious polar function, exhibit polar accumulation.

  11. Computing the hadronic vacuum polarization function by analytic continuation

    DOE PAGES

    Feng, Xu; Hashimoto, Shoji; Hotzel, Grit; ...

    2013-08-29

    We propose a method to compute the hadronic vacuum polarization function on the lattice at continuous values of photon momenta bridging between the spacelike and timelike regions. We provide two independent demonstrations to show that this method leads to the desired hadronic vacuum polarization function in Minkowski spacetime. We present with the example of the leading-order QCD correction to the muon anomalous magnetic moment that this approach can provide a valuable alternative method for calculations of physical quantities where the hadronic vacuum polarization function enters.

  12. Functions for diverse metabolic activities in heterochromatin

    PubMed Central

    Su, Xue Bessie; Pillus, Lorraine

    2016-01-01

    Growing evidence demonstrates that metabolism and chromatin dynamics are not separate processes but that they functionally intersect in many ways. For example, the lysine biosynthetic enzyme homocitrate synthase was recently shown to have unexpected functions in DNA damage repair, raising the question of whether other amino acid metabolic enzymes participate in chromatin regulation. Using an in silico screen combined with reporter assays, we discovered that a diverse range of metabolic enzymes function in heterochromatin regulation. Extended analysis of the glutamate dehydrogenase 1 (Gdh1) revealed that it regulates silent information regulator complex recruitment to telomeres and ribosomal DNA. Enhanced N-terminal histone H3 proteolysis is observed in GDH1 mutants, consistent with telomeric silencing defects. A conserved catalytic Asp residue is required for Gdh1’s functions in telomeric silencing and H3 clipping. Genetic modulation of α-ketoglutarate levels demonstrates a key regulatory role for this metabolite in telomeric silencing. The metabolic activity of glutamate dehydrogenase thus has important and previously unsuspected roles in regulating chromatin-related processes. PMID:26936955

  13. Metabolic hormones in saliva: origins and functions

    PubMed Central

    Zolotukhin, S.

    2012-01-01

    The salivary proteome consists of thousands of proteins, which include, among others, hormonal modulators of energy intake and output. Although the functions of this prominent category of hormones in whole body energy metabolism are well characterized, their functions in the oral cavity, whether as a salivary component, or when expressed in taste cells, are less studied and poorly understood. The respective receptors for the majority of salivary metabolic hormones have been also shown to be expressed in salivary glands, taste cells, or other cells in the oral mucosa. This review provides a comprehensive account of the gastrointestinal hormones, adipokines, and neuropeptides identified in saliva, salivary glands, or lingual epithelium, as well as their respective cognate receptors expressed in the oral cavity. Surprisingly, few functions are assigned to salivary metabolic hormones, and these functions are mostly associated with the modulation of taste perception. Because of the well-characterized correlation between impaired oral nutrient sensing and increased energy intake and body mass index, a conceptually provocative point of view is introduced, whereupon it is argued that targeted changes in the composition of saliva could affect whole body metabolism in response to the activation of cognate receptors expressed locally in the oral mucosa. PMID:22994880

  14. Functions for diverse metabolic activities in heterochromatin.

    PubMed

    Su, Xue Bessie; Pillus, Lorraine

    2016-03-15

    Growing evidence demonstrates that metabolism and chromatin dynamics are not separate processes but that they functionally intersect in many ways. For example, the lysine biosynthetic enzyme homocitrate synthase was recently shown to have unexpected functions in DNA damage repair, raising the question of whether other amino acid metabolic enzymes participate in chromatin regulation. Using an in silico screen combined with reporter assays, we discovered that a diverse range of metabolic enzymes function in heterochromatin regulation. Extended analysis of the glutamate dehydrogenase 1 (Gdh1) revealed that it regulates silent information regulator complex recruitment to telomeres and ribosomal DNA. Enhanced N-terminal histone H3 proteolysis is observed in GDH1 mutants, consistent with telomeric silencing defects. A conserved catalytic Asp residue is required for Gdh1's functions in telomeric silencing and H3 clipping. Genetic modulation of α-ketoglutarate levels demonstrates a key regulatory role for this metabolite in telomeric silencing. The metabolic activity of glutamate dehydrogenase thus has important and previously unsuspected roles in regulating chromatin-related processes.

  15. Three-dimensional polarization aberration functions in optical system based on three-dimensional polarization ray-tracing calculus

    NASA Astrophysics Data System (ADS)

    He, Wenjun; Fu, Yuegang; Liu, Zhiying; Zhang, Lei; Wang, Jiake; Zheng, Yang; Li, Yahong

    2017-03-01

    The polarization aberrations of a complex optical system with multi-element lens have been investigated using a 3D polarization aberration function. The 3D polarization ray-tracing matrix has been combined with the optical path difference to obtain a 3D polarization aberration function, which avoids the need for a complicated phase unwrapping process. The polarization aberrations of a microscope objective have been analyzed to include, the distributions of 3D polarization aberration functions, diattenuation aberration, retardance aberration, and polarization-dependent intensity on the exit pupil. Further, the aberrations created by the field of view and the coating on the distribution rules of 3D polarization aberration functions are discussed in detail. Finally a novel appropriate field of view and wavelength correction is proposed for a polarization aberration function which optimizes the image quality of a multi-element optical system.

  16. Comment on elimination of polarization dependence from optical excitation functions

    SciTech Connect

    Maseberg, Jack W.

    2008-05-15

    The measurement of optical excitation functions excited by electron impact is typically accomplished by recording atomic fluorescence emitted into a small solid angle perpendicular to the incident electron beam. This measured intensity is not proportional to the emission cross section because the fluorescence exhibits an angular distribution and polarization that varies with the energy of the exciting electrons. Typically, a polarizer is set at the ''magic angle'' (54.7 degree sign ) with respect to the electron beam axis to remove this polarization dependence. The literature for the derivation of the magic angle value assumes the polarizing element is perfect. An expression for the angle that accounts for the use of a partial polarizer is presented.

  17. The Sedoheptulose Kinase CARKL Directs Macrophage Polarization through Control of Glucose Metabolism

    PubMed Central

    Haschemi, Arvand; Kosma, Paul; Gille, Lars; Evans, Charles R.; Burant, Charles F.; Starkl, Philipp; Knapp, Bernhard; Haas, Robert; Schmid, Johannes A.; Jandl, Christoph; Amir, Shahzada; Lubec, Gert; Park, Jaehong; Esterbauer, Harald; Bilban, Martin; Brizuela, Leonardo; Pospisilik, J. Andrew; Otterbein, Leo E.; Wagner, Oswald

    2012-01-01

    Summary Immune cells are somewhat unique in that activation responses can alter quantitative phenotypes upwards of 100,000-fold. To date little is known about the metabolic adaptations necessary to mount such dramatic phenotypic shifts. Screening for novel regulators of macrophage activation, we found nonprotein kinases of glucose metabolism among the most enriched classes of candidate immune modulators. We find that one of these, the carbohydrate kinase-like protein CARKL, is rapidly downregulated in vitro and in vivo upon LPS stimulation in both mice and humans. Interestingly, CARKL catalyzes an orphan reaction in the pentose phosphate pathway, refocusing cellular metabolism to a high-redox state upon physiological or artificial downregulation. We find that CARKL-dependent metabolic reprogramming is required for proper M1- and M2-like macrophage polarization and uncover a rate-limiting requirement for appropriate glucose flux in macrophage polarization. PMID:22682222

  18. Amino acids: metabolism, functions, and nutrition.

    PubMed

    Wu, Guoyao

    2009-05-01

    Recent years have witnessed the discovery that amino acids (AA) are not only cell signaling molecules but are also regulators of gene expression and the protein phosphorylation cascade. Additionally, AA are key precursors for syntheses of hormones and low-molecular weight nitrogenous substances with each having enormous biological importance. Physiological concentrations of AA and their metabolites (e.g., nitric oxide, polyamines, glutathione, taurine, thyroid hormones, and serotonin) are required for the functions. However, elevated levels of AA and their products (e.g., ammonia, homocysteine, and asymmetric dimethylarginine) are pathogenic factors for neurological disorders, oxidative stress, and cardiovascular disease. Thus, an optimal balance among AA in the diet and circulation is crucial for whole body homeostasis. There is growing recognition that besides their role as building blocks of proteins and polypeptides, some AA regulate key metabolic pathways that are necessary for maintenance, growth, reproduction, and immunity. They are called functional AA, which include arginine, cysteine, glutamine, leucine, proline, and tryptophan. Dietary supplementation with one or a mixture of these AA may be beneficial for (1) ameliorating health problems at various stages of the life cycle (e.g., fetal growth restriction, neonatal morbidity and mortality, weaning-associated intestinal dysfunction and wasting syndrome, obesity, diabetes, cardiovascular disease, the metabolic syndrome, and infertility); (2) optimizing efficiency of metabolic transformations to enhance muscle growth, milk production, egg and meat quality and athletic performance, while preventing excess fat deposition and reducing adiposity. Thus, AA have important functions in both nutrition and health.

  19. Interaction corrections to the polarization function of graphene

    NASA Astrophysics Data System (ADS)

    Sodemann, I.; Fogler, M. M.

    2012-09-01

    The first-order interaction correction to the irreducible polarization function of pristine graphene is studied at arbitrary relation between momentum and frequency. The results are used to calculate the dielectric function and the dynamical conductivity of graphene beyond the standard random-phase approximation. The computed static dielectric constant compares favorably with recent experiments.

  20. Drug-metabolizing enzymes: mechanisms and functions.

    PubMed

    Sheweita, S A

    2000-09-01

    Drug-metabolizing enzymes are called mixed-function oxidase or monooxygenase and containing many enzymes including cytochrome P450, cytochrome b5, and NADPH-cytochrome P450 reductase and other components. The hepatic cytochrome P450s (Cyp) are a multigene family of enzymes that play a critical role in the metabolism of many drugs and xenobiotics with each cytochrome isozyme responding differently to exogenous chemicals in terms of its induction and inhibition. For example, Cyp 1A1 is particularly active towards polycyclic aromatic hydrocarbons (PAHs), activating them into reactive intermediates those covalently bind to DNA, a key event in the initiation of carcinogenesis. Likewise, Cyp 1A2 activates a variety of bladder carcinogens, such as aromatic amines and amides. Also, some forms of cytochrome P450 isozymes such as Cyp 3A and 2E1 activate the naturally occurring carcinogens (e.g. aflatoxin B1) and N-nitrosamines respectively into highly mutagenic and carcinogenic agents. The carcinogenic potency of PAHs, and other carcinogens and the extent of binding of their ultimate metabolites to DNA and proteins are correlated with the induction of cytochrome P450 isozymes. Phase II drug-metabolizing enzymes such as glutathione S-transferase, aryl sulfatase and UDP-glucuronyl transferase inactivate chemical carcinogens into less toxic or inactive metabolites. Many drugs change the rate of activation or detoxification of carcinogens by changing the activities of phases I and II drug-metabolizing enzymes. The balance of detoxification and activation reactions depends on the chemical structure of the agents, and is subjected to many variables that are a function of this structure, or genetic background, sex, endocrine status, age, diet, and the presence of other chemicals. It is important to realize that the enzymes involved in carcinogen metabolism are also involved in the metabolism of a variety of substrates, and thus the introduction of specific xenobiotics may change

  1. Structural and functional hepatocyte polarity and liver disease

    PubMed Central

    Gissen, Paul; Arias, Irwin M.

    2015-01-01

    Summary Hepatocytes form a crucially important cell layer that separates sinusoidal blood from the canalicular bile. They have a uniquely organized polarity with a basal membrane facing liver sinusoidal endothelial cells, while one or more apical poles can contribute to several bile canaliculi jointly with the directly opposing hepatocytes. Establishment and maintenance of hepatocyte polarity is essential for many functions of hepatocytes and requires carefully orchestrated cooperation between cell adhesion molecules, cell junctions, cytoskeleton, extracellular matrix and intracellular trafficking machinery. The process of hepatocyte polarization requires energy and, if abnormal, may result in severe liver disease. A number of inherited disorders affecting tight junction and intracellular trafficking proteins have been described and demonstrate clinical and pathophysiological features overlapping those of the genetic cholestatic liver diseases caused by defects in canalicular ABC transporters. Thus both structural and functional components contribute to the final hepatocyte polarity phenotype. Many acquired liver diseases target factors that determine hepatocyte polarity, such as junctional proteins. Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus. However, the molecular mechanisms underlying these defects are not well understood. Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases. PMID:26116792

  2. Extractions of polarized and unpolarized parton distribution functions

    SciTech Connect

    Jimenez-Delgado, Pedro

    2014-01-01

    An overview of our ongoing extractions of parton distribution functions of the nucleon is given. First JAM results on the determination of spin-dependent parton distribution functions from world data on polarized deep-inelastic scattering are presented first, and followed by a short report on the status of the JR unpolarized parton distributions. Different aspects of PDF analysis are briefly discussed, including effects of the nuclear structure of targets, target-mass corrections and higher twist contributions to the structure functions.

  3. Conservation of Planar Polarity Pathway Function Across the Animal Kingdom.

    PubMed

    Hale, Rosalind; Strutt, David

    2015-01-01

    Planar polarity is a well-studied phenomenon resulting in the directional coordination of cells in the plane of a tissue. In invertebrates and vertebrates, planar polarity is established and maintained by the largely independent core and Fat/Dachsous/Four-jointed (Ft-Ds-Fj) pathways. Loss of function of these pathways can result in a wide range of developmental or cellular defects, including failure of gastrulation and problems with placement and function of cilia. This review discusses the conservation of these pathways across the animal kingdom. The lack of vital core pathway components in basal metazoans suggests that the core planar polarity pathway evolved shortly after, but not necessarily alongside, the emergence of multicellularity.

  4. Chiral dynamics of the polarizing fracture functions for baryon production

    NASA Astrophysics Data System (ADS)

    Sivers, Dennis

    2009-04-01

    The concept of spin-directed momentum provides a useful and restrictive framework for describing dynamical mechanisms that can lead to single-spin observables. The value of this framework can be demonstrated by consideration of the polarizing fracture functions, ΔNMB↑/pq(x,z,kTN;Q2), that characterize the production of polarized baryons in the target fragmentation region of semi-inclusive deep-inelastic scattering from an unpolarized target. When Bjorken x is chosen large enough to indicate a hard scattering from a valence quark, the fracture function formalism dynamically selects a quark-diquark basis for baryon structure. Attention to constituent orbital angular momentum in the formation process and its role in contributing to the transverse momentum of the produced baryon illustrates important aspects of the generation of polarization observables.

  5. The polarization function of a finite number of confined spin polarized fermions

    NASA Astrophysics Data System (ADS)

    Lemmens, Lucien F.; Saeys, Dirk; Brosens, Fons; Devreese, Jozef T.

    2001-03-01

    The Fourier transform of an inhomogeneous two-point correlation function, in space and Euclidean time, is derived for a limited number of spin polarized fermions in an external potential. The formulation is based on the many-body generalization of the Feynman-Kac functional. Special attention is given to the finite number aspects and the implications thereof for the fugacity. An analysis of the correlation function in terms of single particle propagators is obtained, leading to an occupation function representation. For the harmonic model, the temporal Fourier components of the two-point correlation matrix are worked out in the low temperature limit.

  6. The polarization function of a finite number of confined spin polarized fermions

    NASA Astrophysics Data System (ADS)

    Lemmens, L. F.; Saeys, D.; Brosens, F.; Devreese, J. T.

    2001-01-01

    The Fourier transform of an inhomogeneous two-point correlation function, in space and Euclidean time, is derived for a limited number of spin polarized fermions in an external potential. The formulation is based on the many-body generalization of the Feynman-Kac functional. Special attention is given to the finite number aspects and the implications thereof for the fugacity. An analysis of the correlation function in terms of single-particle propagators is obtained, leading to an occupation function representation. For the harmonic model, the temporal Fourier components of the two-point correlation matrix are worked out in the low-temperature limit.

  7. The polarization response function and electrostatic modes of focused beams

    SciTech Connect

    Gnavi, G.; Gratton, F.T.

    1986-02-01

    It is shown that the method of percussion for obtaining the spatial-temporal representation of the polarization response function directly can also be used to study stability problems in nonuniform plasmas, thus providing a physical and mathematical alternative to the traditional approach. As an example, the stability analysis of particle beams is given, focused with cylindrical symmetry through an axis. The integral equation for electrostatic modes is set up with the polarization response, and solved with a technique that provides both the characteristic values and an integral representation for the field. The instability of this model, which is the cylindrical counterpart of the plane symmetric counterstreaming configuration, is then discussed.

  8. Frequency redistribution function for the polarized two-term atom

    SciTech Connect

    Casini, R.; Landi Degl'Innocenti, M.; Manso Sainz, R.; Landolfi, M.

    2014-08-20

    We present a generalized frequency redistribution function for the polarized two-term atom in an arbitrary magnetic field. This result is derived within a new formulation of the quantum problem of coherent scattering of polarized radiation by atoms in the collisionless regime. The general theory, which is based on a diagrammatic treatment of the atom-photon interaction, is still a work in progress. However, the results anticipated here are relevant enough for the study of the magnetism of the solar chromosphere and of interest for astrophysics in general.

  9. Metabolism and functions of copper in brain.

    PubMed

    Scheiber, Ivo F; Mercer, Julian F B; Dringen, Ralf

    2014-05-01

    Copper is an important trace element that is required for essential enzymes. However, due to its redox activity, copper can also lead to the generation of toxic reactive oxygen species. Therefore, cellular uptake, storage as well as export of copper have to be tightly regulated in order to guarantee sufficient copper supply for the synthesis of copper-containing enzymes but also to prevent copper-induced oxidative stress. In brain, copper is of importance for normal development. In addition, both copper deficiency as well as excess of copper can seriously affect brain functions. Therefore, this organ possesses ample mechanisms to regulate its copper metabolism. In brain, astrocytes are considered as important regulators of copper homeostasis. Impairments of homeostatic mechanisms in brain copper metabolism have been associated with neurodegeneration in human disorders such as Menkes disease, Wilson's disease and Alzheimer's disease. This review article will summarize the biological functions of copper in the brain and will describe the current knowledge on the mechanisms involved in copper transport, storage and export of brain cells. The role of copper in diseases that have been connected with disturbances in brain copper homeostasis will also be discussed.

  10. Pure amnesia after unilateral left polar thalamic infarct: topographic and sequential neuropsychological and metabolic (PET) correlations.

    PubMed Central

    Clarke, S; Assal, G; Bogousslavsky, J; Regli, F; Townsend, D W; Leenders, K L; Blecic, S

    1994-01-01

    A 54-year-old patient who had an isolated small polar thalamic infarct and acute global amnesia with slight frontal type dysfunction but without other neurological dysfunction was studied. Memory improved partially within 8 months. At all stages the impairment was more severe for verbal than non-verbal memory. Autobiographic recollections and newly acquired information tended to be disorganised with respect to temporal order. Procedural memory was unaffected. Both emotional involvement and pleasure in reading were lost. On MRI, the infarct was limited to the left anterior thalamic nuclei and the adjacent mamillothalamic tract. The regional cerebral metabolic rate of glucose (measured with PET) was decreased on the left in the thalamus, amygdala, and posterior cingulate cortex 2 weeks after the infarct, and in the thalamus and posterior cingulate cortex 9 months later. These findings stress the specific role of the left anterior thalamic region in memory and confirm that longlasting amnesia from a thalamic lesion can occur without significant structural damage to the dorsomedial nucleus. Furthermore, they suggest that the anterior thalamic nuclei and possibly their connections with the posterior cingulate cortex play a role in emotional involvement linked to ipsilateral hemispheric functions. Images PMID:8301301

  11. Modular community structure suggests metabolic plasticity during the transition to polar night in ice-covered Antarctic lakes.

    PubMed

    Vick-Majors, Trista J; Priscu, John C; Amaral-Zettler, Linda A

    2014-04-01

    High-latitude environments, such as the Antarctic McMurdo Dry Valley lakes, are subject to seasonally segregated light-dark cycles, which have important consequences for microbial diversity and function on an annual basis. Owing largely to the logistical difficulties of sampling polar environments during the darkness of winter, little is known about planktonic microbial community responses to the cessation of photosynthetic primary production during the austral sunset, which lingers from approximately February to April. Here, we hypothesized that changes in bacterial, archaeal and eukaryotic community structure, particularly shifts in favor of chemolithotrophs and mixotrophs, would manifest during the transition to polar night. Our work represents the first concurrent molecular characterization, using 454 pyrosequencing of hypervariable regions of the small-subunit ribosomal RNA gene, of bacterial, archaeal and eukaryotic communities in permanently ice-covered lakes Fryxell and Bonney, before and during the polar night transition. We found vertically stratified populations that varied at the community and/or operational taxonomic unit-level between lakes and seasons. Network analysis based on operational taxonomic unit level interactions revealed nonrandomly structured microbial communities organized into modules (groups of taxa) containing key metabolic potential capacities, including photoheterotrophy, mixotrophy and chemolithotrophy, which are likely to be differentially favored during the transition to polar night.

  12. Comparative analysis of fecal microbiota and intestinal microbial metabolic activity in captive polar bears.

    PubMed

    Schwab, Clarissa; Gänzle, Michael

    2011-03-01

    The composition of the intestinal microbiota depends on gut physiology and diet. Ursidae possess a simple gastrointestinal system composed of a stomach, small intestine, and indistinct hindgut. This study determined the composition and stability of fecal microbiota of 3 captive polar bears by group-specific quantitative PCR and PCR-DGGE (denaturing gradient gel electrophoresis) using the 16S rRNA gene as target. Intestinal metabolic activity was determined by analysis of short-chain fatty acids in feces. For comparison, other Carnivora and mammals were included in this study. Total bacterial abundance was approximately log 8.5 DNA gene copies·(g feces)-1 in all 3 polar bears. Fecal polar bear microbiota was dominated by the facultative anaerobes Enterobacteriaceae and enterococci, and the Clostridium cluster I. The detection of the Clostridium perfringens α-toxin gene verified the presence of C. perfringens. Composition of the fecal bacterial population was stable on a genus level; according to results obtained by PCR-DGGE, dominant bacterial species fluctuated. The total short-chain fatty acid content of Carnivora and other mammals analysed was comparable; lactate was detected in feces of all carnivora but present only in trace amounts in other mammals. In comparison, the fecal microbiota and metabolic activity of captive polar bears mostly resembled the closely related grizzly and black bears.

  13. Matched and Mismatched Metabolic Fuels in Lymphocyte Function

    PubMed Central

    Caro-Maldonado, Alfredo; Gerriets, Valerie A.; Rathmell, Jeffrey C.

    2012-01-01

    Immunological function requires metabolic support to suit the needs of lymphocytes at a variety of distinct differentiation and activation states. It is now evident that the signaling pathways that drive lymphocyte survival and activity can directly control cellular metabolism. This linkage provides a mechanism by which activation and specific signaling pathways provide a supply of appropriate and required nutrients to support cell functions in a pro-active supply rather than consumption-based metabolic model. In this way, the metabolism and fuel choices of lymphocytes are guided to specifically match the anticipated needs. If the fuel choice or metabolic pathways of lymphocytes are dysregulated, however, metabolic checkpoints can become activated to disrupt immunological function. These changes are now shown in several immunological diseases and may open new opportunities to selectively enhance or suppress specific immune functions through targeting of glucose, lipid, or amino acid metabolism. PMID:23290889

  14. Maternal metabolic stress may affect oviduct gatekeeper function.

    PubMed

    Jordaens, Lies; Van Hoeck, Veerle; Maillo, Veronica; Gutierrez-Adan, Alfonso; Marei, Waleed Fawzy A; Vlaeminck, Bruno; Thys, Sofie; Sturmey, Roger G S; Bols, Peter; Leroy, Jo

    2017-03-03

    We hypothesized that elevated non-esterified fatty acids (NEFA) modify in vitro bovine oviduct epithelial cell (BOEC) metabolism and barrier function. Hereto, BOECs were studied in a polarized system with 24h-treatments at day 9: 1) CONTROL (0µM NEFA + 0%EtOH), 2) SOLVENT CONTROL (0µM NEFA + 0.45%EtOH), 3) BASAL NEFA (720µM NEFA + 0.45%EtOH in the basal compartment), 4) APICAL NEFA (720µM NEFA + 0.45%EtOH in the apical compartment). FITC-albumin was used for monolayer permeability assessment, and related to Transepithelial Electric Resistance (TER). Fatty acid (FA), glucose, lactate and pyruvate concentrations were measured in spent medium. Intracellular lipid droplets (LD) and FA-uptake were studied using Bodipy 493/503 and immunolabelling of FA-transporters (FAT/CD36, FABP3 and caveolin1). BOEC-mRNA was retrieved for qRT-PCR. Results revealed that APICAL NEFA reduced relative TER-increase (46.85%) during treatment, and increased FITC-albumin flux (27.59%) compared to other treatments. In BASAL NEFA, FAs were transferred to the apical compartment as free FAs: mostly palmitic and oleic acid increased, respectively 56.0 % and 33.5% of initial FA-concentrations. APICAL NEFA allowed no FA-transfer, but induced LD-accumulation and upregulated FA-transporter expression (↑CD36, ↑FABP3, ↑CAV1-protein-expression). Gene expression in APICAL NEFA indicated increased anti-apoptotic (↑BCL2) and anti-oxidative (↑SOD1) capacity, upregulated lipid metabolism (↑CPT1, ↑ACSL1 and ↓ACACA), and FA-uptake (↑CAV1). All treatments had similar carbohydrate metabolism and oviduct function specific gene expression (=OVGP1, ESR1, FOXJ1). Overall, elevated NEFAs affected BOEC-metabolism and barrier function differently depending on NEFA-exposure side. Data substantiate the concept of the oviduct as a gatekeeper that may actively alter early embryonic developmental conditions.

  15. Self-consistent polarization density functional theory: Application to Argon

    SciTech Connect

    Maerzke, Katie A.; Murdachaew, Garold; Mundy, Christopher J.; Schenter, Gregory K.; Siepmann, J. I.

    2009-03-12

    We present a comprehensive set of results for argon, a case study in weak interactions, using the selfconsistent polarization density functional theory (SCP-DFT). With minimal parameterization, SCPDFT is found is give excellent results for the dimer interaction energy, the second virial coefficient, the liquid structure, and the lattice constant and cohesion energy of the face-centered cubic (fcc) crystal compared to both accurate theoretical and experimental benchmarks. Thus, SCP-DFT holds promise as a fast, efficient, and accurate method for performing ab initio dynamics that include additional polarization and dispersion interactions for large, complex systems involving solvation and bond breaking. This work was supported by the U.S. Department of Energy's (DOE) Office of Basic Energy Sciences, Chemical Sciences program. The Pacific Northwest National Laboratory is operated by Battelle for DOE.

  16. Field metabolic rate and PCB adipose tissue deposition efficiency in East Greenland polar bears derived from contaminant monitoring data.

    PubMed

    Pavlova, Viola; Nabe-Nielsen, Jacob; Dietz, Rune; Svenning, Jens-Christian; Vorkamp, Katrin; Rigét, Frank Farsø; Sonne, Christian; Letcher, Robert J; Grimm, Volker

    2014-01-01

    Climate change will increasingly affect the natural habitat and diet of polar bears (Ursus maritimus). Understanding the energetic needs of polar bears is therefore important. We developed a theoretical method for estimating polar bear food consumption based on using the highly recalcitrant polychlorinated biphenyl (PCB) congener, 2,2',4,4',55-hexaCB (CB153) in bear adipose tissue as an indicator of food intake. By comparing the CB153 tissue concentrations in wild polar bears with estimates from a purposely designed individual-based model, we identified the possible combinations of field metabolic rates (FMR) and CB153 deposition efficiencies in East Greenland polar bears. Our simulations indicate that if 30% of the CB153 consumed by polar bear individuals were deposited into their adipose tissue, the corresponding FMR would be only two times the basal metabolic rate. In contrast, if the modelled CB153 deposition efficiency were 10%, adult polar bears would require six times more energy than that needed to cover basal metabolism. This is considerably higher than what has been assumed for polar bears in previous studies though it is similar to FMRs found in other marine mammals. An implication of this result is that even relatively small reductions in future feeding opportunities could impact the survival of East Greenland polar bears.

  17. Field Metabolic Rate and PCB Adipose Tissue Deposition Efficiency in East Greenland Polar Bears Derived from Contaminant Monitoring Data

    PubMed Central

    Pavlova, Viola; Nabe-Nielsen, Jacob; Dietz, Rune; Svenning, Jens-Christian; Vorkamp, Katrin; Rigét, Frank Farsø; Sonne, Christian; Letcher, Robert J.; Grimm, Volker

    2014-01-01

    Climate change will increasingly affect the natural habitat and diet of polar bears (Ursus maritimus). Understanding the energetic needs of polar bears is therefore important. We developed a theoretical method for estimating polar bear food consumption based on using the highly recalcitrant polychlorinated biphenyl (PCB) congener, 2,2′,4,4′,55-hexaCB (CB153) in bear adipose tissue as an indicator of food intake. By comparing the CB153 tissue concentrations in wild polar bears with estimates from a purposely designed individual-based model, we identified the possible combinations of field metabolic rates (FMR) and CB153 deposition efficiencies in East Greenland polar bears. Our simulations indicate that if 30% of the CB153 consumed by polar bear individuals were deposited into their adipose tissue, the corresponding FMR would be only two times the basal metabolic rate. In contrast, if the modelled CB153 deposition efficiency were 10%, adult polar bears would require six times more energy than that needed to cover basal metabolism. This is considerably higher than what has been assumed for polar bears in previous studies though it is similar to FMRs found in other marine mammals. An implication of this result is that even relatively small reductions in future feeding opportunities could impact the survival of East Greenland polar bears. PMID:25101837

  18. Free energy functionals for polarization fluctuations: Pekar factor revisited

    NASA Astrophysics Data System (ADS)

    Dinpajooh, Mohammadhasan; Newton, Marshall D.; Matyushov, Dmitry V.

    2017-02-01

    The separation of slow nuclear and fast electronic polarization in problems related to electron mobility in polarizable media was considered by Pekar 70 years ago. Within dielectric continuum models, this separation leads to the Pekar factor in the free energy of solvation by the nuclear degrees of freedom. The main qualitative prediction of Pekar's perspective is a significant, by about a factor of two, drop of the nuclear solvation free energy compared to the total (electronic plus nuclear) free energy of solvation. The Pekar factor enters the solvent reorganization energy of electron transfer reactions and is a significant mechanistic parameter accounting for the solvent effect on electron transfer. Here, we study the separation of the fast and slow polarization modes in polar molecular liquids (polarizable dipolar liquids and polarizable water force fields) without relying on the continuum approximation. We derive the nonlocal free energy functional and use atomistic numerical simulations to obtain nonlocal, reciprocal space electronic and nuclear susceptibilities. A consistent transition to the continuum limit is introduced by extrapolating the results of finite-size numerical simulation to zero wavevector. The continuum nuclear susceptibility extracted from the simulations is numerically close to the Pekar factor. However, we derive a new functionality involving the static and high-frequency dielectric constants. The main distinction of our approach from the traditional theories is found in the solvation free energy due to the nuclear polarization: the anticipated significant drop of its magnitude with increasing liquid polarizability does not occur. The reorganization energy of electron transfer is either nearly constant with increasing the solvent polarizability and the corresponding high-frequency dielectric constant (polarizable dipolar liquids) or actually noticeably increases (polarizable force fields of water).

  19. Free energy functionals for polarization fluctuations: Pekar factor revisited.

    PubMed

    Dinpajooh, Mohammadhasan; Newton, Marshall D; Matyushov, Dmitry V

    2017-02-14

    The separation of slow nuclear and fast electronic polarization in problems related to electron mobility in polarizable media was considered by Pekar 70 years ago. Within dielectric continuum models, this separation leads to the Pekar factor in the free energy of solvation by the nuclear degrees of freedom. The main qualitative prediction of Pekar's perspective is a significant, by about a factor of two, drop of the nuclear solvation free energy compared to the total (electronic plus nuclear) free energy of solvation. The Pekar factor enters the solvent reorganization energy of electron transfer reactions and is a significant mechanistic parameter accounting for the solvent effect on electron transfer. Here, we study the separation of the fast and slow polarization modes in polar molecular liquids (polarizable dipolar liquids and polarizable water force fields) without relying on the continuum approximation. We derive the nonlocal free energy functional and use atomistic numerical simulations to obtain nonlocal, reciprocal space electronic and nuclear susceptibilities. A consistent transition to the continuum limit is introduced by extrapolating the results of finite-size numerical simulation to zero wavevector. The continuum nuclear susceptibility extracted from the simulations is numerically close to the Pekar factor. However, we derive a new functionality involving the static and high-frequency dielectric constants. The main distinction of our approach from the traditional theories is found in the solvation free energy due to the nuclear polarization: the anticipated significant drop of its magnitude with increasing liquid polarizability does not occur. The reorganization energy of electron transfer is either nearly constant with increasing the solvent polarizability and the corresponding high-frequency dielectric constant (polarizable dipolar liquids) or actually noticeably increases (polarizable force fields of water).

  20. Free energy functionals for polarization fluctuations: Pekar factor revisited

    DOE PAGES

    Dinpajooh, Mohammadhasan; Newton, Marshall D.; Matyushov, Dmitry V.

    2017-02-13

    The separation of slow nuclear and fast electronic polarization in problems related to electron mobility in polarizable media was considered by Pekar 70 years ago. This separation leads to the Pekar factor in the free energy of solvation by the nuclear degrees of freedom, within dielectric continuum models. The main qualitative prediction of Pekar’s perspective is a significant, by about a factor of two, drop of the nuclear solvation free energy compared to the total (electronic plus nuclear) free energy of solvation. The Pekar factor enters the solvent reorganization energy of electron transfer reactions and is a significant mechanistic parametermore » accounting for the solvent effect on electron transfer. We study the separation of the fast and slow polarization modes in polar molecular liquids (polarizable dipolar liquids and polarizable water force fields) without relying on the continuum approximation. We derive the nonlocal free energy functional and use atomistic numerical simulations to obtain nonlocal, reciprocal space electronic and nuclear susceptibilities. A consistent transition to the continuum limit is introduced by extrapolating the results of finite-size numerical simulation to zero wavevector. The continuum nuclear susceptibility extracted from the simulations is numerically close to the Pekar factor. But, we derive a new functionality involving the static and high-frequency dielectric constants. The main distinction of our approach from the traditional theories is found in the solvation free energy due to the nuclear polarization: the anticipated significant drop of its magnitude with increasing liquid polarizability does not occur. The reorganization energy of electron transfer is either nearly constant with increasing the solvent polarizability and the corresponding high-frequency dielectric constant (polarizable dipolar liquids) or actually noticeably increases (polarizable force fields of water).« less

  1. Students' Challenges with Polar Functions: Covariational Reasoning and Plotting in the Polar Coordinate System

    ERIC Educational Resources Information Center

    Habre, Samer

    2017-01-01

    Covariational reasoning has been the focus of many studies but only a few looked into this reasoning in the polar coordinate system. In fact, research on student's familiarity with polar coordinates and graphing in the polar coordinate system is scarce. This paper examines the challenges that students face when plotting polar curves using the…

  2. Does taurine deficiency cause metabolic bone disease and rickets in polar bear cubs raised in captivity?

    PubMed

    Chesney, Russell W; Hedberg, Gail E; Rogers, Quinton R; Dierenfeld, Ellen S; Hollis, Bruce E; Derocher, Andrew; Andersen, Magnus

    2009-01-01

    Rickets and fractures have been reported in captive polar bears. Taurine (TAU) is key for the conjugation of ursodeoxycholic acid (UDCA), a bile acid unique to bears. Since TAU-conjugated UDCA optimizes fat and fat-soluble vitamin absorption, we asked if TAU deficiency could cause vitamin D malabsorption and lead to metabolic bone disease in captive polar bears. We measured TAU levels in plasma (P) and whole blood (WB) from captive and free-ranging cubs and adults, and vitamin D3 and TAU concentrations in milk samples from lactating sows. Plasma and WB TAU levels were significantly higher in cubs vs captive and free-ranging adult bears. Vitamin D in polar bear milk was 649.2 +/- 569.2 IU/L, similar to that found in formula. The amount of TAU in polar bear milk is 3166.4 +/- 771 nmol/ml, 26-fold higher than in formula. Levels of vitamin D in bear milk and formula as well as in plasma do not indicate classical nutritional vitamin D deficiency. Higher dietary intake of TAU by free-ranging cubs may influence bile acid conjugation and improve vitamin D absorption.

  3. Star-type polarizer with equal-power splitting function for each polarization based on polarization-dependent defects in two-dimensional photonic-crystal waveguides.

    PubMed

    Lin, Mi; Xi, Xiang; Qiu, Wenbiao; Ai, Yuexia; Wang, Qiong; Liu, Qiang; Ouyang, Zhengbiao

    2016-10-17

    We propose a star-type polarizer with equal-power splitting function for each polarization based on polarization-dependent defects (PDDs) in two-dimensional photonic-crystal waveguides (PCWs). The structure is designed by combining two Y-type PCWs, and two types of PDDs are introduced into the PCWs respectively to provide polarization functions. By using finite-element method and optimizing the parameters of the PDDs, it is demonstrated that different polarizations can only transmit through their own PCWs and output with identical power distributions, i.e., the structure can function as polarizer and equal-power splitter for each polarization at the same time. In addition, by scanning the wavelength of the structure, it is proved that the proposed splitter can work in a wide range of wavelength while keeping high output transmission for both the TE and TM polarizations. Such a structure is useful for polarization-relative multi-channel signal processing for optical communications in the mid- and far-infrared wavelength regions.

  4. MicroRNA-33–dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis

    PubMed Central

    Ouimet, Mireille; Ediriweera, Hasini N.; Gundra, U. Mahesh; Sheedy, Frederick J.; Ramkhelawon, Bhama; Hutchison, Susan B.; Rinehold, Kaitlyn; van Solingen, Coen; Fullerton, Morgan D.; Cecchini, Katharine; Rayner, Katey J.; Steinberg, Gregory R.; Zamore, Phillip D.; Fisher, Edward A.; Loke, P’ng; Moore, Kathryn J.

    2015-01-01

    Cellular metabolism is increasingly recognized as a controller of immune cell fate and function. MicroRNA-33 (miR-33) regulates cellular lipid metabolism and represses genes involved in cholesterol efflux, HDL biogenesis, and fatty acid oxidation. Here, we determined that miR-33–mediated disruption of the balance of aerobic glycolysis and mitochondrial oxidative phosphorylation instructs macrophage inflammatory polarization and shapes innate and adaptive immune responses. Macrophage-specific Mir33 deletion increased oxidative respiration, enhanced spare respiratory capacity, and induced an M2 macrophage polarization–associated gene profile. Furthermore, miR-33–mediated M2 polarization required miR-33 targeting of the energy sensor AMP-activated protein kinase (AMPK), but not cholesterol efflux. Notably, miR-33 inhibition increased macrophage expression of the retinoic acid–producing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1A2) and retinal dehydrogenase activity both in vitro and in a mouse model. Consistent with the ability of retinoic acid to foster inducible Tregs, miR-33–depleted macrophages had an enhanced capacity to induce forkhead box P3 (FOXP3) expression in naive CD4+ T cells. Finally, treatment of hypercholesterolemic mice with miR-33 inhibitors for 8 weeks resulted in accumulation of inflammation-suppressing M2 macrophages and FOXP3+ Tregs in plaques and reduced atherosclerosis progression. Collectively, these results reveal that miR-33 regulates macrophage inflammation and demonstrate that miR-33 antagonism is atheroprotective, in part, by reducing plaque inflammation by promoting M2 macrophage polarization and Treg induction. PMID:26517695

  5. Functional modelling of planar cell polarity: an approach for identifying molecular function

    PubMed Central

    2013-01-01

    Background Cells in some tissues acquire a polarisation in the plane of the tissue in addition to apical-basal polarity. This polarisation is commonly known as planar cell polarity and has been found to be important in developmental processes, as planar polarity is required to define the in-plane tissue coordinate system at the cellular level. Results We have built an in-silico functional model of cellular polarisation that includes cellular asymmetry, cell-cell signalling and a response to a global cue. The model has been validated and parameterised against domineering non-autonomous wing hair phenotypes in Drosophila. Conclusions We have carried out a systematic comparison of in-silico polarity phenotypes with patterns observed in vivo under different genetic manipulations in the wing. This has allowed us to classify the specific functional roles of proteins involved in generating cell polarity, providing new hypotheses about their specific functions, in particular for Pk and Dsh. The predictions from the model allow direct assignment of functional roles of genes from genetic mosaic analysis of Drosophila wings. PMID:23672397

  6. Estrogen and Mitochondria Function in Cardiorenal Metabolic Syndrome

    PubMed Central

    Jia, Guanghong; Aroor, Annayya R.; Sowers, James R.

    2015-01-01

    The cardiorenal metabolic syndrome (CRS) consists of a constellation of cardiac, renal, and metabolic disorders including insulin resistance (IR), obesity, metabolic dyslipidemia, high-blood pressure, and evidence of early cardiac and renal disease. Mitochondria dysfunction often occurs in the CRS, and this dysfunction is promoted by excess reactive oxygen species, genetic factors, IR, aging, and altered mitochondrial biogenesis. Recently, it has been shown that there are important sex-related differences in mitochondria function and metabolic, cardiovascular, and renal components. Sex differences in the CRS have mainly been attributed to the estrogen’s effects that are mainly mediated by estrogen receptor (ER) α, ERβ, and G-protein coupled receptor 30. In this review, we discuss the effects of estrogen on the mitochondrial function, insulin metabolic signaling, glucose transport, lipid metabolism, and inflammatory responses from liver, pancreatic β cells, adipocytes, skeletal muscle, and cardiovascular tissue. PMID:25149220

  7. Fueling Immunity: Insights into Metabolism and Lymphocyte Function

    PubMed Central

    Pearce, Erika L.; Poffenberger, Maya C.; Chang, Chih-Hao; Jones, Russell G.

    2015-01-01

    Lymphocytes face major metabolic challenges upon activation. They must meet the bioenergetic and biosynthetic demands of increased cell proliferation and also adapt to changing environmental conditions, in which nutrients and oxygen may be limiting. An emerging theme in immunology is that metabolic reprogramming and lymphocyte activation are intricately linked. However, why T cells adopt specific metabolic programs and the impact that these programs have on T cell function and, ultimately, immunological outcome remain unclear. Research on tumor cell metabolism has provided valuable insight into metabolic pathways important for cell proliferation and the influence of metabolites themselves on signal transduction and epigenetic programming. In this Review, we highlight emerging concepts regarding metabolic reprogramming in proliferating cells and discuss their potential impact on T cell fate and function. PMID:24115444

  8. 2011 Plant Lipids: Structure, Metabolism, & Function Gordon Research Conference

    SciTech Connect

    Christopher Benning

    2011-02-04

    This is the second Gordon Research Conference on 'Plant Lipids: Structure, Metabolism & Function'. It covers current topics in lipid structure, metabolism and function in eukaryotic photosynthetic organisms including seed plants, algae, mosses and ferns. Work in photosynthetic bacteria is considered as well as it serves the understanding of specific aspects of lipid metabolism in plants. Breakthroughs are discussed in research on plant lipids as diverse as glycerolipids, sphingolipids, lipids of the cell surface, isoprenoids, fatty acids and their derivatives. The program covers nine concepts at the forefront of research under which afore mentioned plant lipid classes are discussed. The goal is to integrate areas such as lipid signaling, basic lipid metabolism, membrane function, lipid analysis, and lipid engineering to achieve a high level of stimulating interaction among diverse researchers with interests in plant lipids. One Emphasis is on the dynamics and regulation of lipid metabolism during plant cell development and in response to environmental factors.

  9. Cell-selective metabolic labeling of biomolecules with bioorthogonal functionalities.

    PubMed

    Xie, Ran; Hong, Senlian; Chen, Xing

    2013-10-01

    Metabolic labeling of biomolecules with bioorthogonal functionalities enables visualization, enrichment, and analysis of the biomolecules of interest in their physiological environments. This versatile strategy has found utility in probing various classes of biomolecules in a broad range of biological processes. On the other hand, metabolic labeling is nonselective with respect to cell type, which imposes limitations for studies performed in complex biological systems. Herein, we review the recent methodological developments aiming to endow metabolic labeling strategies with cell-type selectivity. The cell-selective metabolic labeling strategies have emerged from protein and glycan labeling. We envision that these strategies can be readily extended to labeling of other classes of biomolecules.

  10. Regulatory functions of PPARbeta in metabolism: implications for the treatment of metabolic syndrome.

    PubMed

    Grimaldi, Paul A

    2007-08-01

    The prevalence of metabolic disturbances, collectively known as metabolic syndrome, has reached an epidemic proportion in industrialized countries. Lifestyle interventions and pharmacological treatments of such pathologies are only partially efficient and new therapeutic approaches are urgently needed. This review focuses on the recent findings describing the regulatory functions of peroxisome proliferator-activated receptor beta (PPARbeta) on lipid metabolism in several tissues and on the implications of such findings on the therapeutic usefulness of PPARbeta agonists in the treatment of particular features of the metabolic syndrome, such as insulin resistance, obesity, dyslipidemia and cardiac dysfunctions.

  11. Steviol glycosides: chemical diversity, metabolism, and function.

    PubMed

    Ceunen, Stijn; Geuns, Jan M C

    2013-06-28

    Steviol glycosides are a group of highly sweet diterpene glycosides discovered in only a few plant species, most notably the Paraguayan shrub Stevia rebaudiana. During the past few decades, the nutritional and pharmacological benefits of these secondary metabolites have become increasingly apparent. While these properties are now widely recognized, many aspects related to their in vivo biochemistry and metabolism and their relationship to the overall plant physiology of S. rebaudiana are not yet understood. Furthermore, the large size of the steviol glycoside pool commonly found within S. rebaudiana leaves implies a significant metabolic investment and poses questions regarding the benefits S. rebaudiana might gain from their accumulation. The current review intends to thoroughly discuss the available knowledge on these issues.

  12. Calcium metabolism and cardiovascular function after spaceflight

    NASA Technical Reports Server (NTRS)

    Hatton, Daniel C.; Yue, Qi; Dierickx, Jacqueline; Roullet, Chantal; Otsuka, Keiichi; Watanabe, Mitsuaki; Coste, Sarah; Roullet, Jean Baptiste; Phanouvang, Thongchan; Orwoll, Eric; Orwoll, Shiela; McCarron, David A.

    2002-01-01

    To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P < 0.001), elevated parathyroid hormone levels (P < 0.001), reduced calcitonin levels (P < 0.05), unchanged 1,25(OH)(2)D(3) levels, and elevated skull (P < 0.01) and reduced femur bone mineral density. Basal and thrombin-stimulated platelet free calcium (intracellular calcium concentration) were also reduced (P < 0.05). There was a tendency for indirect systolic BP to be reduced in conscious flight animals (P = 0.057). However, mean arterial pressure was elevated (P < 0.001) after anesthesia. Dietary calcium altered all aspects of calcium metabolism (P < 0.001), as well as BP (P < 0.001), but the only interaction with flight was a relatively greater increase in ionized calcium in flight animals fed low- compared with high-calcium diets (P < 0.05). The results indicate that 1) flight-induced disruptions of calcium metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

  13. A cellular perspective on brain energy metabolism and functional imaging.

    PubMed

    Magistretti, Pierre J; Allaman, Igor

    2015-05-20

    The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and point at a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales.

  14. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

    PubMed Central

    Park, Hyeong-Kyu; Ahima, Rexford S.

    2014-01-01

    Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in patients with congenital leptin deficiency or generalized lipodystrophy. However, further research on molecular mediators of leptin resistance is needed for the development of targeted leptin sensitizing therapies for obesity and related metabolic diseases. PMID:25199978

  15. Metabolic function of the CTRP family of hormones

    PubMed Central

    Seldin, Marcus M.; Tan, Stefanie Y.; Wong, G. William

    2013-01-01

    Maintaining proper energy balance in mammals entails intimate crosstalk between various tissues and organs. These inter-organ communications are mediated, to a great extent, by secreted hormones that circulate in blood. Regulation of the complex metabolic networks by secreted hormones (e.g., insulin, glucagon, leptin, adiponectin, FGF21) constitutes an important mechanism governing the integrated control of whole-body metabolism. Disruption of hormone-mediated metabolic circuits frequently results in dysregulated energy metabolism and pathology. As part of an effort to identify novel metabolic hormones, we recently characterized a highly conserved family of fifteen secreted proteins, the C1q/TNF-related proteins (CTRP1–15). While related to adiponectin in sequence and structural organization, each CTRP has its own unique tissue expression profile and non-redundant function in regulating sugar and/or fat metabolism. Here, we summarize the current understanding of the physiological functions of CTRPs, emphasizing their metabolic roles. Future studies using gain-of-function and loss-of-function mouse models will provide greater mechanistic insights into the critical role CTRPs play in regulating systemic energy homeostasis. PMID:23963681

  16. Functional modules, structural topology, and optimal activity in metabolic networks.

    PubMed

    Resendis-Antonio, Osbaldo; Hernández, Magdalena; Mora, Yolanda; Encarnación, Sergio

    2012-01-01

    Modular organization in biological networks has been suggested as a natural mechanism by which a cell coordinates its metabolic strategies for evolving and responding to environmental perturbations. To understand how this occurs, there is a need for developing computational schemes that contribute to integration of genomic-scale information and assist investigators in formulating biological hypotheses in a quantitative and systematic fashion. In this work, we combined metabolome data and constraint-based modeling to elucidate the relationships among structural modules, functional organization, and the optimal metabolic phenotype of Rhizobium etli, a bacterium that fixes nitrogen in symbiosis with Phaseolus vulgaris. To experimentally characterize the metabolic phenotype of this microorganism, we obtained the metabolic profile of 220 metabolites at two physiological stages: under free-living conditions, and during nitrogen fixation with P. vulgaris. By integrating these data into a constraint-based model, we built a refined computational platform with the capability to survey the metabolic activity underlying nitrogen fixation in R. etli. Topological analysis of the metabolic reconstruction led us to identify modular structures with functional activities. Consistent with modular activity in metabolism, we found that most of the metabolites experimentally detected in each module simultaneously increased their relative abundances during nitrogen fixation. In this work, we explore the relationships among topology, biological function, and optimal activity in the metabolism of R. etli through an integrative analysis based on modeling and metabolome data. Our findings suggest that the metabolic activity during nitrogen fixation is supported by interacting structural modules that correlate with three functional classifications: nucleic acids, peptides, and lipids. More fundamentally, we supply evidence that such modular organization during functional nitrogen fixation is

  17. Rhinovirus Disrupts the Barrier Function of Polarized Airway Epithelial Cells

    PubMed Central

    Sajjan, Umadevi; Wang, Qiong; Zhao, Ying; Gruenert, Dieter C.; Hershenson, Marc B.

    2008-01-01

    Rationale: Secondary bacterial infection following rhinovirus (RV) infection has been recognized in chronic obstructive pulmonary disease. Objectives: We sought to understand mechanisms by which RV infection facilitates secondary bacterial infection. Methods: Primary human airway epithelial cells grown at air–liquid interface and human bronchial epithelial (16HBE14o-) cells grown as polarized monolayers were infected apically with RV. Transmigration of bacteria (nontypeable Haemophilus influenzae and others) was assessed by colony counting and transmission electron microscopy. Transepithelial resistance (RT) was measured by using a voltmeter. The distribution of zona occludins (ZO)-1 was determined by immunohistochemistry and immunoblotting. Measurements and Main Results: Epithelial cells infected with RV showed 2-log more bound bacteria than sham-infected cultures, and bacteria were recovered from the basolateral media of RV- but not sham-infected cells. Infection of polarized airway epithelial cell cultures with RV for 24 hours caused a significant decrease in RT without causing cell death or apoptosis. Ultraviolet-treated RV did not decrease RT, suggesting a requirement for viral replication. Reduced RT was associated with increased paracellular permeability, as determined by flux of fluorescein isothiocyanate (FITC)-inulin. Neutralizing antibodies to tumor necrosis factor (TNF)-α, IFN-γ and IL-1β reversed corresponding cytokine-induced reductions in RT but not that induced by RV, indicating that the RV effect is independent of these proinflammatory cytokines. Confocal microscopy and immunoblotting revealed the loss of ZO-1 from tight junction complexes in RV-infected cells. Intranasal inoculation of mice with RV1B also caused the loss of ZO-1 from the bronchial epithelium tight junctions in vivo. Conclusions: RV facilitates binding, translocation, and persistence of bacteria by disrupting airway epithelial barrier function. PMID:18787220

  18. Thiamine in plants: aspects of its metabolism and functions.

    PubMed

    Goyer, Aymeric

    2010-10-01

    Thiamine diphosphate (vitamin B(1)) plays a fundamental role as an enzymatic cofactor in universal metabolic pathways including glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle. In addition, thiamine diphosphate has recently been shown to have functions other than as a cofactor in response to abiotic and biotic stress in plants. Recently, several steps of the plant thiamine biosynthetic pathway have been characterized, and a mechanism of feedback regulation of thiamine biosynthesis via riboswitch has been unraveled. This review focuses on these most recent advances made in our understanding of thiamine metabolism and functions in plants. Phenotypes of plant mutants affected in thiamine biosynthesis are described, and genomics, proteomics, and metabolomics data that have increased further our knowledge of plant thiamine metabolic pathways and functions are summarized. Aspects of thiamine metabolism such as catabolism, salvage, and transport in plants are discussed.

  19. Functional crosstalk of CAR-LXR and ROR-LXR in drug metabolism and lipid metabolism.

    PubMed

    Xiao, Lei; Xie, Xinni; Zhai, Yonggong

    2010-10-30

    Nuclear receptor crosstalk represents an important mechanism to expand the functions of individual receptors. The liver X receptors (LXR, NR1H2/3), both the α and β isoforms, are nuclear receptors that can be activated by the endogenous oxysterols and other synthetic agonists. LXRs function as cholesterol sensors, which protect mammals from cholesterol overload. LXRs have been shown to regulate the expression of a battery of metabolic genes, especially those involved in lipid metabolism. LXRs have recently been suggested to play a novel role in the regulation of drug metabolism. The constitutive androstane receptor (CAR, NR1I3) is a xenobiotic receptor that regulates the expression of drug-metabolizing enzymes and transporters. Disruption of CAR alters sensitivity to toxins, increasing or decreasing it depending on the compounds. More recently, additional roles for CAR have been discovered. These include the involvement of CAR in lipid metabolism. Mechanistically, CAR forms an intricate regulatory network with other members of the nuclear receptor superfamily, foremost the LXRs, in exerting its effect on lipid metabolism. Retinoid-related orphan receptors (RORs, NR1F1/2/3) have three isoforms, α, β and γ. Recent reports have shown that loss of RORα and/or RORγ can positively or negatively influence the expression of multiple drug-metabolizing enzymes and transporters in the liver. The effects of RORs on expression of drug-metabolizing enzymes were reasoned to be, at least in part, due to the crosstalk with LXR. This review focuses on the CAR-LXR and ROR-LXR crosstalk, and the implications of this crosstalk in drug metabolism and lipid metabolism.

  20. Insulin action in brain regulates systemic metabolism and brain function.

    PubMed

    Kleinridders, André; Ferris, Heather A; Cai, Weikang; Kahn, C Ronald

    2014-07-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases.

  1. Metabolic Assessment of Suited Mobility Using Functional Tasks

    NASA Technical Reports Server (NTRS)

    Norcross, J. R.; McFarland, S. M.; Ploutz-Snyder, Robert

    2016-01-01

    Existing methods for evaluating extravehicular activity (EVA) suit mobility have typically focused on isolated joint range of motion or torque, but these techniques have little to do with how well a crewmember functionally performs in an EVA suit. To evaluate suited mobility at the system level through measuring metabolic cost (MC) of functional tasks.

  2. Functional genomics in the study of yeast cell polarity: moving in the right direction.

    PubMed

    Styles, Erin; Youn, Ji-Young; Mattiazzi Usaj, Mojca; Andrews, Brenda

    2013-01-01

    The budding yeast Saccharomyces cerevisiae has been used extensively for the study of cell polarity, owing to both its experimental tractability and the high conservation of cell polarity and other basic biological processes among eukaryotes. The budding yeast has also served as a pioneer model organism for virtually all genome-scale approaches, including functional genomics, which aims to define gene function and biological pathways systematically through the analysis of high-throughput experimental data. Here, we outline the contributions of functional genomics and high-throughput methodologies to the study of cell polarity in the budding yeast. We integrate data from published genetic screens that use a variety of functional genomics approaches to query different aspects of polarity. Our integrated dataset is enriched for polarity processes, as well as some processes that are not intrinsically linked to cell polarity, and may provide new areas for future study.

  3. Underwater linear polarization: physical limitations to biological functions

    PubMed Central

    Shashar, Nadav; Johnsen, Sönke; Lerner, Amit; Sabbah, Shai; Chiao, Chuan-Chin; Mäthger, Lydia M.; Hanlon, Roger T.

    2011-01-01

    Polarization sensitivity is documented in a range of marine animals. The variety of tasks for which animals can use this sensitivity, and the range over which they do so, are confined by the visual systems of these animals and by the propagation of the polarization information in the aquatic environment. We examine the environmental physical constraints in an attempt to reveal the depth, range and other limitations to the use of polarization sensitivity by marine animals. In clear oceanic waters, navigation that is based on the polarization pattern of the sky appears to be limited to shallow waters, while solar-based navigation is possible down to 200–400 m. When combined with intensity difference, polarization sensitivity allows an increase in target detection range by 70–80% with an upper limit of 15 m for large-eyed animals. This distance will be significantly smaller for small animals, such as plankton, and in turbid waters. Polarization-contrast detection, which is relevant to object detection and communication, is strongly affected by water conditions and in clear waters its range limit may reach 15 m as well. We show that polarization sensitivity may also serve for target distance estimation, when examining point source bioluminescent objects in the photic mesopelagic depth range. PMID:21282168

  4. Circadian rhythms in myocardial metabolism and function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circadian rhythms in myocardial function and dysfunction are firmly established in both animal models and humans. For example, the incidence of arrhythmias and sudden cardiac death increases when organisms awaken. Such observations have classically been explained by circadian rhythms in neurohumoral...

  5. Strabismus requires Flamingo and Prickle function to regulate tissue polarity in the Drosophila eye.

    PubMed

    Rawls, Amy S; Wolff, Tanya

    2003-05-01

    Tissue polarity in Drosophila is regulated by a number of genes that are thought to function in a complex, many of which interact genetically and/or physically, co-localize, and require other tissue polarity proteins for their localization. We report the enhancement of the strabismus tissue polarity phenotype by mutations in two other tissue polarity genes, flamingo and prickle. Flamingo is autonomously required for the establishment of ommatidial polarity. Its localization is dynamic throughout ommatidial development and is dependent on Frizzled and Notch. Flamingo and Strabismus co-localize for several rows posterior to the morphogenetic furrow and subsequently diverge. While neither of these proteins is required for the other's localization, Prickle localization is influenced by Strabismus function. Our data suggest that Strabismus, Flamingo and Prickle function together to regulate the establishment of tissue polarity in the Drosophila eye.

  6. A balance of form and function: planar polarity and development of the vestibular maculae.

    PubMed

    Deans, Michael R

    2013-05-01

    The mechanosensory hair cells of the inner ear have emerged as one of the primary models for studying the development of planar polarity in vertebrates. Planar polarity is the polarized organization of cells or cellular structures in the plane of an epithelium. For hair cells, planar polarity is manifest at the subcellular level in the polarized organization of the stereociliary bundle and at the cellular level in the coordinated orientation of stereociliary bundles between adjacent cells. This latter organization is commonly called Planar Cell Polarity and has been described in the greatest detail for auditory hair cells of the cochlea. A third level of planar polarity, referred to as tissue polarity, occurs in the utricular and saccular maculae; two inner ear sensory organs that use hair cells to detect linear acceleration and gravity. In the utricle and saccule hair cells are divided between two groups that have opposite stereociliary bundle polarities and, as a result, are able to detect movements in opposite directions. Thus vestibular hair cells are a unique model system for studying planar polarity because polarization develops at three different anatomical scales in the same sensory organ. Moreover the system has the potential to be used to dissect functional interactions between molecules regulating planar polarity at each of the three levels. Here the significance of planar polarity on vestibular system function will be discussed, and the molecular mechanisms associated with development of planar polarity at each anatomical level will be reviewed. Additional aspects of planar polarity that are unique to the vestibular maculae will also be introduced.

  7. [Basic mechanisms: structure, function and metabolism of plasma lipoproteins].

    PubMed

    Errico, Teresa L; Chen, Xiangyu; Martin Campos, Jesús M; Julve, Josep; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2013-01-01

    The aim of this work is to present basic information on the lipoprotein physiology. The protein fraction of lipoproteins consists of several apolipoproteins and enzymes whose functions are lipid transport and metabolism. Classification of lipoproteins is based on their density. Chylomicrons, VLDL, IDL, LDL and HDL can be isolated by ultracentrifugation. Both chylomicrons- and VLDL-triglycerides are transported from the intestine and liver, respectively, to the peripheral tissues. The metabolism of VLDL originates IDL and LDL. LDL is the main transporter of cholesterol to extrahepatic tissues. HDL mobilizes cholesterol from peripheral tissues to the liver where it is secreted to bile as free cholesterol or bile salts, a process termed reverse cholesterol transport. Lipoprotein metabolism can be regulated by nuclear receptors that regulate the expression of genes involved in triglyceride and apolipoprotein metabolism.

  8. Phosphatidylserine in the brain: metabolism and function.

    PubMed

    Kim, Hee-Yong; Huang, Bill X; Spector, Arthur A

    2014-10-01

    Phosphatidylserine (PS) is the major anionic phospholipid class particularly enriched in the inner leaflet of the plasma membrane in neural tissues. PS is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine, and this reaction is catalyzed by phosphatidylserine synthase 1 and phosphatidylserine synthase 2 located in the endoplasmic reticulum. Activation of Akt, Raf-1 and protein kinase C signaling, which supports neuronal survival and differentiation, requires interaction of these proteins with PS localized in the cytoplasmic leaflet of the plasma membrane. Furthermore, neurotransmitter release by exocytosis and a number of synaptic receptors and proteins are modulated by PS present in the neuronal membranes. Brain is highly enriched with docosahexaenoic acid (DHA), and brain PS has a high DHA content. By promoting PS synthesis, DHA can uniquely expand the PS pool in neuronal membranes and thereby influence PS-dependent signaling and protein function. Ethanol decreases DHA-promoted PS synthesis and accumulation in neurons, which may contribute to the deleterious effects of ethanol intake. Improvement of some memory functions has been observed in cognitively impaired subjects as a result of PS supplementation, but the mechanism is unclear.

  9. Vitamin D metabolism, sex hormones, and male reproductive function.

    PubMed

    Blomberg Jensen, Martin

    2012-08-01

    The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

  10. Microbial metabolite butyrate facilitates M2 macrophage polarization and function.

    PubMed

    Ji, Jian; Shu, Dingming; Zheng, Mingzhu; Wang, Jie; Luo, Chenglong; Wang, Yan; Guo, Fuyou; Zou, Xian; Lv, Xiaohui; Li, Ying; Liu, Tianfei; Qu, Hao

    2016-04-20

    Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

  11. Biological Polarized-Light Signaling: Environment, Structure, and Function

    DTIC Science & Technology

    2006-02-27

    crustaceans (mantis shrimps), cephalopod mollusks (squids and cuttlefish ), and of the wings of butterflies (in collaboration with a visiting undergraduate...Rutgers University, New Jersey, working on polarization reflectors in the skin of several species of cephalopod mollusks (squid, cuttlefish ). This

  12. Metabolic Functions of the Lung, Disorders and Associated Pathologies

    PubMed Central

    Alvarado, Alcibey; Arce, Isabel

    2016-01-01

    The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth’s atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration. PMID:27635172

  13. Metabolic Functions of the Lung, Disorders and Associated Pathologies.

    PubMed

    Alvarado, Alcibey; Arce, Isabel

    2016-10-01

    The primary function of the lungs is gas exchange. Approximately 400 million years ago, the Earth's atmosphere gained enough oxygen in the gas phase for the animals that emerged from the sea to breathe air. The first lungs were merely primitive air sacs with a few vessels in the walls that served as accessory organs of gas exchange to supplement the gills. Eons later, as animals grew accustomed to a solely terrestrial life, the lungs became highly compartmentalized to provide the vast air-blood surface necessary for O2 uptake and CO2 elimination, and a respiratory control system was developed to regulate breathing in accordance with metabolic demands and other needs. With the evolution and phylogenetic development, lungs were taking a variety of other specialized functions to maintain homeostasis, which we will call the non-respiratory functions of the lung and that often, and by mistake, are believed to have little or no connection with the replacement gas. In this review, we focus on the metabolic functions of the lung, perhaps the least known, and mainly, in the lipid metabolism and blood-adult lung vascular endothelium interaction. When these functions are altered, respiratory disorders or diseases appear, which are discussed concisely, emphasizing how they impact the most important function of the lungs: external respiration.

  14. Metagenomic analysis reveals that modern microbialites and polar microbial mats have similar taxonomic and functional potential

    PubMed Central

    White, Richard Allen; Power, Ian M.; Dipple, Gregory M.; Southam, Gordon; Suttle, Curtis A.

    2015-01-01

    Within the subarctic climate of Clinton Creek, Yukon, Canada, lies an abandoned and flooded open-pit asbestos mine that harbors rapidly growing microbialites. To understand their formation we completed a metagenomic community profile of the microbialites and their surrounding sediments. Assembled metagenomic data revealed that bacteria within the phylum Proteobacteria numerically dominated this system, although the relative abundances of taxa within the phylum varied among environments. Bacteria belonging to Alphaproteobacteria and Gammaproteobacteria were dominant in the microbialites and sediments, respectively. The microbialites were also home to many other groups associated with microbialite formation including filamentous cyanobacteria and dissimilatory sulfate-reducing Deltaproteobacteria, consistent with the idea of a shared global microbialite microbiome. Other members were present that are typically not associated with microbialites including Gemmatimonadetes and iron-oxidizing Betaproteobacteria, which participate in carbon metabolism and iron cycling. Compared to the sediments, the microbialite microbiome has significantly more genes associated with photosynthetic processes (e.g., photosystem II reaction centers, carotenoid, and chlorophyll biosynthesis) and carbon fixation (e.g., CO dehydrogenase). The Clinton Creek microbialite communities had strikingly similar functional potentials to non-lithifying microbial mats from the Canadian High Arctic and Antarctica, but are functionally distinct, from non-lithifying mats or biofilms from Yellowstone. Clinton Creek microbialites also share metabolic genes (R2 < 0.750) with freshwater microbial mats from Cuatro Ciénegas, Mexico, but are more similar to polar Arctic mats (R2 > 0.900). These metagenomic profiles from an anthropogenic microbialite-forming ecosystem provide context to microbialite formation on a human-relevant timescale. PMID:26441900

  15. Metabolic functions of FABPs— mechanisms and therapeutic implications

    PubMed Central

    Hotamisligil, Gökhan S.; Bernlohr, David A.

    2015-01-01

    Intracellular and extracellular interactions with proteins enables the functional and mechanistic diversity of lipids. Fatty acid-binding proteins (FABPs) were originally described as intracellular proteins that can affect lipid fluxes, metabolism and signalling within cells. As the functions of this protein family have been further elucidated, it has become evident that they are critical mediators of metabolism and inflammatory processes, both locally and systemically, and therefore are potential therapeutic targets for immunometabolic diseases. In particular, genetic deficiency and small molecule-mediated inhibition of FABP4 (also known as aP2) and FABP5 can potently improve glucose homeostasis and reduce atherosclerosis in mouse models. Further research has shown that in addition to their intracellular roles, some FABPs are found outside the cells, and FABP4 undergoes regulated, vesicular secretion. The circulating form of FABP4 has crucial hormonal functions in systemic metabolism. In this Review we discuss the roles and regulation of both intracellular and extracellular FABP actions, highlighting new insights that might direct drug discovery efforts and opportunities for management of chronic metabolic diseases. PMID:26260145

  16. Optical polarization based logic functions (XOR or XNOR) with nonlinear Gallium nitride nanoslab.

    PubMed

    Bovino, F A; Larciprete, M C; Giardina, M; Belardini, A; Centini, M; Sibilia, C; Bertolotti, M; Passaseo, A; Tasco, V

    2009-10-26

    We present a scheme of XOR/XNOR logic gate, based on non phase-matched noncollinear second harmonic generation from a medium of suitable crystalline symmetry, Gallium nitride. The polarization of the noncollinear generated beam is a function of the polarization of both pump beams, thus we experimentally investigated all possible polarization combinations, evidencing that only some of them are allowed and that the nonlinear interaction of optical signals behaves as a polarization based XOR. The experimental results show the peculiarity of the nonlinear optical response associated with noncollinear excitation, and are explained using the expression for the effective second order optical nonlinearity in noncollinear scheme.

  17. Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

    PubMed Central

    Kleinridders, André; Ferris, Heather A.; Cai, Weikang

    2014-01-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. PMID:24931034

  18. The skin function: a factor of anti-metabolic syndrome

    PubMed Central

    2012-01-01

    The body’s total antioxidant capacity represents a sum of the antioxidant capacity of various tissues/organs. A decrease in the body’s antioxidant capacity may induce oxidative stress and subsequent metabolic syndrome, a clustering of risk factors for type 2 diabetes and cardiovascular disease. The skin, the largest organ of the body, is one of the major components of the body’s total antioxidant defense system, primarily through its xenobiotic/drug biotransformation system, reactive oxygen species-scavenging system, and sweat glands- and sebaceous glands-mediated excretion system. Notably, unlike other contributors, the skin contribution is variable, depending on lifestyles and ambient temperature or seasonal variations. Emerging evidence suggests that decreased skin’s antioxidant and excretory functions (e.g., due to sedentary lifestyles and low ambient temperature) may increase the risk for metabolic syndrome. This review focuses on the relationship between the variability of skin-mediated detoxification and elimination of exogenous and endogenous toxic substances and the development of metabolic syndrome. The potential role of sebum secretion in lipid and cholesterol homeostasis and its impact on metabolic syndrome, and the association between skin disorders (acanthosis nigricans, acne, and burn) and metabolic syndrome are also discussed. PMID:22537765

  19. Functional fixedness and functional reduction as common sense reasonings in chemical equilibrium and in geometry and polarity of molecules

    NASA Astrophysics Data System (ADS)

    Furió, C.; Calatayud, M. L.; Bárcenas, S. L.; Padilla, O. M.

    2000-09-01

    Many of the learning difficulties in the specific domain of chemistry are found not only in the ideas already possessed by students but in the strategic and procedural knowledge that is characteristic of everyday thinking. These defects in procedural knowledge have been described as functional fixedness and functional reduction. This article assesses the procedural difficulties of students (grade 12 and first and third year of university) based on common sense reasoning in two areas of chemistry: chemical equilibrium and geometry and polarity of molecules. In the first area, the theme of external factors affecting equilibria (temperature and concentration change) was selected because the explanations given by the students could be analyzed easily. The existence of a functional fixedness where Le Chatelier's principle was almost exclusively applied by rote could be observed, with this being the cause of the incorrect responses given to the proposed items. Functional fixedness of the Lewis structure also led to an incorrect prediction of molecular geometry. When molecular geometry was correctly determined by the students, it seemed that other methodological or procedural difficulties appeared when the task was to determine molecular polarity. The students showed a tendency, in many cases, to reduce the factors affecting molecular polarity in two possible ways: (a) assuming that polarity depends only on shape (geometric functional reduction) or (b) assuming that molecular polarity depends only on the polarity of bonds (bonding functional reduction).

  20. Spin-polarized 3He in a density-functional frame

    NASA Astrophysics Data System (ADS)

    Gatica, S. M.; Hernández, E. S.; Navarro, J.

    1998-11-01

    The properties of spin-polarized liquid helium are analyzed in a density-functional framework. It is shown that the BHN functional [M. Barranco et al., Phys. Rev. B 54, 7394 (1996)] designed to describe the thermodynamics and the response of the unpolarized liquid also reproduces reasonably well recent experimental results at low magnetization. In particular, the present description reproduces the magnetic field data for the weakly polarized liquid, and is also consistent with the existence of a near-metamagnetic transition at a polarization close to 0.2. We indicate the various difficulties associated with the extension of the current scenario to highly and fully magnetized systems.

  1. Atomic and electronic structure of polar oxide interfaces: Electron microscopy and density functional theory study

    NASA Astrophysics Data System (ADS)

    Lazarov, Vlado

    Polar oxide interfaces are formed when two polar oxide surfaces join. The apparent presence of an electric dipole moment in the repeat unit parallel to the surface/interface closely relate the polar oxide interfaces instability to that of the of polar oxide surfaces. In this thesis, we combined Electron Microscopy and Density Functional Theory to study how the interface polarity affects the atomic and electronic structure of polar oxide interfaces, by using Fe3O4(111)/MgO(111) as a model system. The formation of Fe nanoinclusions found at the interface and within the polar Fe3 O4(111) film is proposed to be new stabilization mechanism for the magnetite film. High-resolution electron microscopy imaging of the interface together with first principle calculations suggest an atomically abrupt substrate-film interface determined with Fe monolayer in octahedral position (FeB). This interface stacking (O/Mg/O/3FeB/O) provides lowest total interface (system) energy and the most effectively screening of the MgO(111) substrate surface polarity. The results of our study suggest that surface polarity could be used as an additional growth parameter in creating novel material structures, such as metals in oxide matrices.

  2. The spin polarized linear response from density functional theory: Theory and application to atoms

    SciTech Connect

    Fias, Stijn Boisdenghien, Zino; De Proft, Frank; Geerlings, Paul

    2014-11-14

    Within the context of spin polarized conceptual density functional theory, the spin polarized linear response functions are introduced both in the [N, N{sub s}] and [N{sub α}, N{sub β}] representations. The mathematical relations between the spin polarized linear response functions in both representations are examined and an analytical expression for the spin polarized linear response functions in the [N{sub α}, N{sub β}] representation is derived. The spin polarized linear response functions were calculated for all atoms up to and including argon. To simplify the plotting of our results, we integrated χ(r, r′) to a quantity χ(r, r{sup ′}), circumventing the θ and ϕ dependence. This allows us to plot and to investigate the periodicity throughout the first three rows in the periodic table within the two different representations. For the first time, χ{sub αβ}(r, r{sup ′}), χ{sub βα}(r, r{sup ′}), and χ{sub SS}(r, r{sup ′}) plots have been calculated and discussed. By integration of the spin polarized linear response functions, different components to the polarisability, α{sub αα}, α{sub αβ}, α{sub βα}, and α{sub ββ} have been calculated.

  3. Functional analysis of colonic bacterial metabolism: relevant to health?

    PubMed

    Hamer, Henrike M; De Preter, Vicky; Windey, Karen; Verbeke, Kristin

    2012-01-01

    With the use of molecular techniques, numerous studies have evaluated the composition of the intestinal microbiota in health and disease. However, it is of major interest to supplement this with a functional analysis of the microbiota. In this review, the different approaches that have been used to characterize microbial metabolites, yielding information on the functional end products of microbial metabolism, have been summarized. To analyze colonic microbial metabolites, the most conventional way is by application of a hypothesis-driven targeted approach, through quantification of selected metabolites from carbohydrate (e.g., short-chain fatty acids) and protein fermentation (e.g., p-cresol, phenol, ammonia, or H(2)S), secondary bile acids, or colonic enzymes. The application of stable isotope-labeled substrates can provide an elegant solution to study these metabolic pathways in vivo. On the other hand, a top-down approach can be followed by applying metabolite fingerprinting techniques based on (1)H-NMR or mass spectrometric analysis. Quantification of known metabolites and characterization of metabolite patterns in urine, breath, plasma, and fecal samples can reveal new pathways and give insight into physiological regulatory processes of the colonic microbiota. In addition, specific metabolic profiles can function as a diagnostic tool for the identification of several gastrointestinal diseases, such as ulcerative colitis and Crohn's disease. Nevertheless, future research will have to evaluate the relevance of associations between metabolites and different disease states.

  4. Hypothalamic inflammation in the control of metabolic function.

    PubMed

    Valdearcos, Martin; Xu, Allison W; Koliwad, Suneil K

    2015-01-01

    Diet-induced obesity leads to devastating and common chronic diseases, fueling ongoing interest in determining new mechanisms underlying both obesity and its consequences. It is now well known that chronic overnutrition produces a unique form of inflammation in peripheral insulin target tissues, and efforts to limit this inflammation have met with some success in preserving insulin sensitivity in obese individuals. Recently, the activation of inflammatory pathways by dietary excess has also been observed among cells located in the mediobasal hypothalamus, a brain area that exerts central control over peripheral glucose, fat, and energy metabolism. Here we review progress in the field of diet-induced hypothalamic inflammation, drawing key distinctions between metabolic inflammation in the hypothalamus and that occurring in peripheral tissues. We focus on specific stimuli of the inflammatory response, the roles of individual hypothalamic cell types, and the links between hypothalamic inflammation and metabolic function under normal and pathophysiological circumstances. Finally, we explore the concept of controlling hypothalamic inflammation to mitigate metabolic disease.

  5. Metabolic functions of glucocorticoid receptor in skeletal muscle.

    PubMed

    Kuo, Taiyi; Harris, Charles A; Wang, Jen-Chywan

    2013-11-05

    Glucocorticoids (GCs) exert key metabolic influences on skeletal muscle. GCs increase protein degradation and decrease protein synthesis. The released amino acids are mobilized from skeletal muscle to liver, where they serve as substrates for hepatic gluconeogenesis. This metabolic response is critical for mammals' survival under stressful conditions, such as fasting and starvation. GCs suppress insulin-stimulated glucose uptake and utilization and glycogen synthesis, and play a permissive role for catecholamine-induced glycogenolysis, thus preserving the level of circulating glucose, the major energy source for the brain. However, chronic or excess exposure of GCs can induce muscle atrophy and insulin resistance. GCs convey their signal mainly through the intracellular glucocorticoid receptor (GR). While GR can act through different mechanisms, one of its major actions is to regulate the transcription of its primary target genes through genomic glucocorticoid response elements (GREs) by directly binding to DNA or tethering onto other DNA-binding transcription factors. These GR primary targets trigger physiological and pathological responses of GCs. Much progress has been made to understand how GCs regulate protein and glucose metabolism. In this review, we will discuss how GR primary target genes confer metabolic functions of GCs, and the mechanisms governing the transcriptional regulation of these targets. Comprehending these processes not only contributes to the fundamental understanding of mammalian physiology, but also will provide invaluable insight for improved GC therapeutics.

  6. Irisin levels in relation to metabolic and liver functions in Egyptian patients with metabolic syndrome.

    PubMed

    Rizk, Fatma H; Elshweikh, Samah A; Abd El-Naby, Amira Y

    2016-04-01

    Irisin is a new myokine that is suspected to influence metabolic syndrome (MetS). However, there is a great controversy with respect to its level in cases of MetS and its correlation with different metabolic parameters. The present study assesses irisin levels in MetS patients and studies its relationship to metabolic and liver functions to evaluate the possible role of the liver in regulation of this level. Sixty subjects were included in this experiment, who were divided into 3 groups: group I (normal control), group II (MetS patients with normal liver enzymes), and group III (MetS with elevated liver enzymes and fatty liver disease). Serum irisin levels showed significant increases in groups II and III compared with group I, and significant increases in group III compared with group II. Also, irisin levels were positively correlated with body mass index, serum triglycerides, homeostatic model assessment of insulin resistance index (HOMA-IR), and liver enzymes. We concluded that serum irisin levels increased in patients with MetS, especially those with elevated liver enzymes, and had a positive correlation with parameters of lipid metabolism and glucose homeostasis with the possibility of hepatic clearance to irisin.

  7. Analytical polarization transfer functions for four coupled spins 12 under isotropic mixing conditions

    PubMed

    Luy; Schedletzky; Glaser

    1999-05-01

    Analytical polarization transfer functions are presented for spin systems consisting of four spins 12 with arbitrary coupling constants under isotropic mixing conditions. In addition, simplified transfer functions were derived for symmetric coupling topologies. Based on these transfer functions optimal durations for the mixing period can be determined for correlations of interest. Copyright 1999 Academic Press.

  8. Functional Imaging of Tissue Morphology with Polarized Light Scattering Spectroscopy

    NASA Astrophysics Data System (ADS)

    Backman, Vadim

    2001-03-01

    We report a new imaging technique to study the morphology of living epithelial cells in vivo. The method is based on light scattering spectroscopy with polarized light (PLSS) and makes it possible to distinguish between single backscattering from epithelial cell nuclei and multiply scattered light. The spectrum of the single backscattering component is further analyzed to provide quantitative histological information about the epithelial cells such as the size distribution, refractive index, and chromatin content of the cell nuclei. The measurement of cell nuclear morphology is crucial for detection and diagnosis of cancerous and precancerous conditions in many human tissues. The method was successfully applied to image precancerous regions of several tissues. Clinical studies in five organs (esophagus, colon, bladder, oral cavity, and uterine cervix) showed the generality and efficacy of the technique.

  9. Identifying functional microRNAs in macrophages with polarized phenotypes.

    PubMed

    Graff, Joel W; Dickson, Anne M; Clay, Gwendolyn; McCaffrey, Anton P; Wilson, Mary E

    2012-06-22

    Macrophages respond to external stimuli with rapid changes in expression of many genes. Different combinations of external stimuli lead to distinct polarized activation patterns, resulting in a spectrum of possible macrophage activation phenotypes. MicroRNAs (miRNAs) are small, noncoding RNAs that can repress the expression of many target genes. We hypothesized that miRNAs play a role in macrophage polarization. miRNA expression profiles were determined in monocyte-derived macrophages (MDMs) incubated in conditions causing activation toward M1, M2a, M2b, or M2c phenotypes. One miRNA guide strand and seven miRNA passenger strands were significantly altered. Changes were confirmed in MDMs from six separate donors. The amplitude of miRNA expression changes in MDMs was smaller than described studies of monocytes responding to inflammatory stimuli. Further investigation revealed this correlated with higher basal miRNA expression in MDMs compared with monocytes. The regulation of M1- and M2b-responsive miRNAs (miR-27a, miR-29b, miR-125a, miR-146a, miR-155, and miR-222) was similar in differentiated THP-1 cells and primary MDMs. Studies in this model revealed cross-talk between IFNγ- and LPS-associated pathways regulating miRNA expression. Furthermore, expression of M1-associated transcripts was increased in THP-1 cells transfected with mimics of miR-29b, miR-125a-5p, or miR-155. The apparent inflammatory property of miR-29b and miR-125a-5p can be at least partially explained by repression of TNFAIP3, a negative regulator of NF-κB signaling. Overall, these data suggest miRNAs can contribute to changes in macrophage gene expression that occur in different exogenous activating conditions.

  10. Identifying Functional MicroRNAs in Macrophages with Polarized Phenotypes*

    PubMed Central

    Graff, Joel W.; Dickson, Anne M.; Clay, Gwendolyn; McCaffrey, Anton P.; Wilson, Mary E.

    2012-01-01

    Macrophages respond to external stimuli with rapid changes in expression of many genes. Different combinations of external stimuli lead to distinct polarized activation patterns, resulting in a spectrum of possible macrophage activation phenotypes. MicroRNAs (miRNAs) are small, noncoding RNAs that can repress the expression of many target genes. We hypothesized that miRNAs play a role in macrophage polarization. miRNA expression profiles were determined in monocyte-derived macrophages (MDMs) incubated in conditions causing activation toward M1, M2a, M2b, or M2c phenotypes. One miRNA guide strand and seven miRNA passenger strands were significantly altered. Changes were confirmed in MDMs from six separate donors. The amplitude of miRNA expression changes in MDMs was smaller than described studies of monocytes responding to inflammatory stimuli. Further investigation revealed this correlated with higher basal miRNA expression in MDMs compared with monocytes. The regulation of M1- and M2b-responsive miRNAs (miR-27a, miR-29b, miR-125a, miR-146a, miR-155, and miR-222) was similar in differentiated THP-1 cells and primary MDMs. Studies in this model revealed cross-talk between IFNγ- and LPS-associated pathways regulating miRNA expression. Furthermore, expression of M1-associated transcripts was increased in THP-1 cells transfected with mimics of miR-29b, miR-125a-5p, or miR-155. The apparent inflammatory property of miR-29b and miR-125a-5p can be at least partially explained by repression of TNFAIP3, a negative regulator of NF-κB signaling. Overall, these data suggest miRNAs can contribute to changes in macrophage gene expression that occur in different exogenous activating conditions. PMID:22549785

  11. Sialic acid metabolism and sialyltransferases: natural functions and applications

    PubMed Central

    Li, Yanhong

    2012-01-01

    Sialic acids are a family of negatively charged monosaccharides which are commonly presented as the terminal residues in glycans of the glycoconjugates on eukaryotic cell surface or as components of capsular polysaccharides or lipooligosaccharides of some pathogenic bacteria. Due to their important biological and pathological functions, the biosynthesis, activation, transfer, breaking down, and recycle of sialic acids are attracting increasing attention. The understanding of the sialic acid metabolism in eukaryotes and bacteria leads to the development of metabolic engineering approaches for elucidating the important functions of sialic acid in mammalian systems and for large-scale production of sialosides using engineered bacterial cells. As the key enzymes in biosynthesis of sialylated structures, sialyltransferases have been continuously identified from various sources and characterized. Protein crystal structures of seven sialyltransferases have been reported. Wild-type sialyltransferases and their mutants have been applied with or without other sialoside biosynthetic enzymes for producing complex sialic acid-containing oligosaccharides and glycoconjugates. This mini-review focuses on current understanding and applications of sialic acid metabolism and sialyltransferases. PMID:22526796

  12. Analysis of polar urinary metabolites for metabolic phenotyping using supercritical fluid chromatography and mass spectrometry.

    PubMed

    Sen, Arundhuti; Knappy, Christopher; Lewis, Matthew R; Plumb, Robert S; Wilson, Ian D; Nicholson, Jeremy K; Smith, Norman W

    2016-06-03

    Supercritical fluid chromatography (SFC) is frequently used for the analysis and separation of non-polar metabolites, but remains relatively underutilised for the study of polar molecules, even those which pose difficulties with established reversed-phase (RP) or hydrophilic interaction liquid chromatographic (HILIC) methodologies. Here, we present a fast SFC-MS method for the analysis of medium and high-polarity (-7≤cLogP≤2) compounds, designed for implementation in a high-throughput metabonomics setting. Sixty polar analytes were first screened to identify those most suitable for inclusion in chromatographic test mixtures; then, a multi-dimensional method development study was conducted to determine the optimal choice of stationary phase, modifier additive and temperature for the separation of such analytes using SFC. The test mixtures were separated on a total of twelve different column chemistries at three different temperatures, using CO2-methanol-based mobile phases containing a variety of polar additives. Chromatographic performance was evaluated with a particular emphasis on peak capacity, overall resolution, peak distribution and repeatability. The results suggest that a new generation of stationary phases, specifically designed for improved robustness in mixed CO2-methanol mobile phases, can improve peak shape, peak capacity and resolution for all classes of polar analytes. A significant enhancement in chromatographic performance was observed for these urinary metabolites on the majority of the stationary phases when polar additives such as ammonium salts (formate, acetate and hydroxide) were included in the organic modifier, and the use of water or alkylamine additives was found to be beneficial for specific subsets of polar analytes. The utility of these findings was confirmed by the separation of a mixture of polar metabolites in human urine using an optimised 7min gradient SFC method, where the use of the recommended column and co

  13. The evolution, metabolism and functions of the apicoplast

    PubMed Central

    Lim, Liting; McFadden, Geoffrey Ian

    2010-01-01

    The malaria parasite, Plasmodium falciparum, harbours a relict plastid known as the ‘apicoplast’. The discovery of the apicoplast ushered in an exciting new prospect for drug development against the parasite. The eubacterial ancestry of the organelle offers a wealth of opportunities for the development of therapeutic interventions. Morphological, biochemical and bioinformatic studies of the apicoplast have further reinforced its ‘plant-like’ characteristics and potential as a drug target. However, we are still not sure why the apicoplast is essential for the parasite's survival. This review explores the origins and metabolic functions of the apicoplast. In an attempt to decipher the role of the organelle within the parasite we also take a closer look at the transporters decorating the plastid to better understand the metabolic exchanges between the apicoplast and the rest of the parasite cell. PMID:20124342

  14. Triacylglycerol Metabolism, Function, and Accumulation in Plant Vegetative Tissues

    DOE PAGES

    Xu, Changcheng; Shanklin, John

    2016-02-03

    One of the most abundant energy-dense storage compounds in eukaryotes are oils in the form of triacylglycerols , and their metabolism plays a key role in cellular energy balance, lipid homeostasis, growth, and maintenance. Plants accumulate oils primarily in seeds and fruits. Moreover, plant oils are used for food and feed and, increasingly, as feedstocks for biodiesel and industrial chemicals. Although plant vegetative tissues do not accumulate significant levels of triacylglycerols, they possess a high capacity for their synthesis, storage, and metabolism. The development of plants that accumulate oil in vegetative tissues presents an opportunity for expanded production of triacylglycerolsmore » as a renewable and sustainable bioenergy source. We review recent progress in the understanding of triacylglycerol synthesis, turnover, storage, and function in leaves and discuss emerging genetic engineering strategies targeted at enhancing triacylglycerol accumulation in biomass crops. Such plants could potentially be modified to produce oleochemical feedstocks or nutraceuticals.« less

  15. Triacylglycerol Metabolism, Function, and Accumulation in Plant Vegetative Tissues

    SciTech Connect

    Xu, Changcheng; Shanklin, John

    2016-02-03

    One of the most abundant energy-dense storage compounds in eukaryotes are oils in the form of triacylglycerols , and their metabolism plays a key role in cellular energy balance, lipid homeostasis, growth, and maintenance. Plants accumulate oils primarily in seeds and fruits. Moreover, plant oils are used for food and feed and, increasingly, as feedstocks for biodiesel and industrial chemicals. Although plant vegetative tissues do not accumulate significant levels of triacylglycerols, they possess a high capacity for their synthesis, storage, and metabolism. The development of plants that accumulate oil in vegetative tissues presents an opportunity for expanded production of triacylglycerols as a renewable and sustainable bioenergy source. We review recent progress in the understanding of triacylglycerol synthesis, turnover, storage, and function in leaves and discuss emerging genetic engineering strategies targeted at enhancing triacylglycerol accumulation in biomass crops. Such plants could potentially be modified to produce oleochemical feedstocks or nutraceuticals.

  16. Polarization of an electroactive functional film on titanium for inducing osteogenic differentiation

    PubMed Central

    Zhou, Zhengnan; Li, Weiping; He, Tianrui; Qian, Lei; Tan, Guoxin; Ning, Chengyun

    2016-01-01

    To enhance the surface bioactivity of titanium (Ti) prostheses, an electroactive polyvinylidene fluoride (PVDF) film was prepared on a Ti substrate to provide a mimetic of the electrical microenvironment, which facilitated the performance of cell functions. The results of cell proliferation and differentiation assays indicated that polarization of the PVDF-Ti (PTi) altered its surface charge, thus inducing adhesion, proliferation and osteogenic differentiation of cells. The polarized PVDF-Ti (PPTi) may therefore find applications in bone regeneration. PMID:27762318

  17. Polarization of an electroactive functional film on titanium for inducing osteogenic differentiation

    NASA Astrophysics Data System (ADS)

    Zhou, Zhengnan; Li, Weiping; He, Tianrui; Qian, Lei; Tan, Guoxin; Ning, Chengyun

    2016-10-01

    To enhance the surface bioactivity of titanium (Ti) prostheses, an electroactive polyvinylidene fluoride (PVDF) film was prepared on a Ti substrate to provide a mimetic of the electrical microenvironment, which facilitated the performance of cell functions. The results of cell proliferation and differentiation assays indicated that polarization of the PVDF-Ti (PTi) altered its surface charge, thus inducing adhesion, proliferation and osteogenic differentiation of cells. The polarized PVDF-Ti (PPTi) may therefore find applications in bone regeneration.

  18. The polarized structure function of the nucleons with a non-extensive statistical quark model

    SciTech Connect

    Trevisan, Luis A.; Mirez, Carlos

    2013-05-06

    We studied an application of nonextensive thermodynamics to describe the polarized structure function of nucleon, in a model where the usual Fermi-Dirac and Bose-Einstein energy distribution, often used in the statistical models, were replaced by the equivalent functions of the q-statistical. The parameters of the model are given by an effective temperature T, the q parameter (from Tsallis statistics), and the chemical potentials given by the corresponding up (u) and down (d) quark normalization in the nucleon and by {Delta}u and {Delta}d of the polarized functions.

  19. Linking community size structure and ecosystem functioning using metabolic theory.

    PubMed

    Yvon-Durocher, Gabriel; Allen, Andrew P

    2012-11-05

    Understanding how biogeochemical cycles relate to the structure of ecological communities is a central research question in ecology. Here we approach this problem by focusing on body size, which is an easily measured species trait that has a pervasive influence on multiple aspects of community structure and ecosystem functioning. We test the predictions of a model derived from metabolic theory using data on ecosystem metabolism and community size structure. These data were collected as part of an aquatic mesocosm experiment that was designed to simulate future environmental warming. Our analyses demonstrate significant linkages between community size structure and ecosystem functioning, and the effects of warming on these links. Specifically, we show that carbon fluxes were significantly influenced by seasonal variation in temperature, and yielded activation energies remarkably similar to those predicted based on the temperature dependencies of individual-level photosynthesis and respiration. We also show that community size structure significantly influenced fluxes of ecosystem respiration and gross primary production, particularly at the annual time-scale. Assessing size structure and the factors that control it, both empirically and theoretically, therefore promises to aid in understanding links between individual organisms and biogeochemical cycles, and in predicting the responses of key ecosystem functions to future environmental change.

  20. The role of metabolic reprogramming in T cell fate and function

    PubMed Central

    Patsoukis, Nikolaos; Bardhan, Kankana; Weaver, Jessica; Herbel, Christoph; Seth, Pankaj; Li, Lequn; Boussiotis, Vassiliki A.

    2016-01-01

    T lymphocytes undergo extensive changes in their metabolic properties during their transition through various differentiation states, from naïve to effector to memory or regulatory roles. The cause and effect relationship between metabolism and differentiation is a field of intense investigation. Many recent studies demonstrate the dependency of T cell functional outcomes on metabolic pathways and the possibility of metabolic intervention to modify these functions. In this review, we describe the basic metabolic features of T cells and new findings on how these correlate with various differentiation fates and functions. We also highlight the latest information regarding the main factors that affect T cell metabolic reprogramming. PMID:28356677

  1. Formation and function of the polar body contractile ring in Spisula.

    PubMed

    Pielak, Rafal M; Gaysinskaya, Valeriya A; Cohen, William D

    2004-05-15

    Initial studies suggested that spatial organization of the putative polar body contractile ring was determined by the peripheral aster in Spisula [Biol. Bull. 205 (2003) 192]. Here we report detailed supporting observations, including testing of aster and ring function with inhibitors. The metaphase peripheral aster was confirmed to spread cortically in an umbrella-like pattern, with microtubule-poor center. The aster disassembled during anaphase, leaving the spindle docked at the F-actin-poor center of a newly generated cortical F-actin ring that closely approximated the aster in location, measured diameter range, and pattern. Cytochalasin D and latrunculin-B permitted all events except ring and polar body formation. Nocodazole disassembly or taxol stabilization of the peripheral aster produced poorly defined rings or bulging anaphase asters within the ring center, respectively, inhibiting polar body formation. Polar body extrusion occurred at the ring center, the diameter of which diminished. Ring contractility-previously assumed-was verified using blebbistatin, a myosin-II ATPase inhibitor that permitted ring assembly but blocked polar body extrusion. The data support the hypothesis that peripheral aster spreading, perhaps dynein-driven, is causally related to polar body contractile ring formation, with anaphase entry and aster disassembly also required for polar body biogenesis. Previously reported astral spreading during embryonic micromere formation suggests that related mechanisms are involved in asymmetric somatic cytokinesis.

  2. Linear polarization of binaries II. Phase function : wQ~(?)Q~? (??)

    NASA Astrophysics Data System (ADS)

    Barman, S. K.

    2000-12-01

    This paper presents a method of calculating linear polarizations in close binaries whose surfaces are distorted due to tidal and rotational forces. Limb-darkening effect has been taken into account. Particles of different sizes are embedded in the outer atmosphere. The law of differential rotation of the primary is considered in analytic form: ??=3D b1 + b2 w2 + b3 w4, where b1, b2 and b3 are constants and w is the distance of a point P (r,?,?) from the axis of rotation of the primary. The atmosphere is assumed to be non-grey, plane-parallel and the phase function is wQ~(?)Q~? (??). Calculations are done with respect to rest frame fixed at the centre of the primary star for several functions as : mass-ratio (q) between the secondary and the primary, polar radius (rp) of the primary, wave-length (?) of the incident light, radius of a particle (1) and angle of inclination (?) with respect to the line of sight. It is noticed that polarization increases with an increase of the radius rp steadily; polarization increases with an increase of the radius of the particle (1), polarization increases with an increase of the mass-ratio q. The method of solution has been applied to several late type binaries to calculate disk integrated linear polarization of light emitted by them. When the mass-ratio q = 0, the general problem reduces to the calculation for a rotationally distorted single (primary) star.

  3. Light-emitting liquid-crystal cells with polarization switching function: Electrochemiluminescent method

    NASA Astrophysics Data System (ADS)

    Honma, Michinori; Horiuchi, Takao; Nose, Toshiaki

    2009-07-01

    A unique light-emitting liquid-crystal (LC) cell that emits polarized light is developed by an electrochemiluminescent (ECL) method; sandwich-type LC cells filled with a nematic LC doped with an organic fluorescent dye are constructed. Luminance and current density characteristics as a function of an applied voltage are investigated under different sample preparation conditions such as mixing temperature and time. It is shown that luminance strongly depends on the abovementioned conditions. From the results of ECL and photoluminescent measurements, we conclude that a significant increase in luminance by heating is attributed to an increase in the molecularly dissolved rubrene concentration. Furthermore, attempts were made to develop a dynamic polarization switch by introducing a pair of crossed interdigitated electrodes. As a result, although a not so high polarization ratio smaller than 2 was obtained, the polarization direction of the emitted light was switched by changing the direction of the in-plane electric field.

  4. Impact of dispersed fuel oil on cardiac mitochondrial function in polar cod Boreogadus saida.

    PubMed

    Dussauze, Matthieu; Camus, Lionel; Le Floch, Stéphane; Pichavant-Rafini, Karine; Geraudie, Perrine; Coquillé, Nathalie; Amérand, Aline; Lemaire, Philippe; Theron, Michael

    2014-12-01

    In this study, impact of dispersed oil on cardiac mitochondrial function was assessed in a key species of Arctic marine ecosystem, the polar cod Boreogadus saida. Mature polar cod were exposed during 48 h to dispersed oil (mechanically and chemically) and dispersants alone. The increase observed in ethoxyresorufin-O-deethylase activity and polycyclic aromatic hydrocarbon metabolites in bile indicated no difference in contamination level between fish exposed to chemical or mechanical dispersion of oil. Oil induced alterations of O2 consumption of permeabilised cardiac fibres showing inhibitions of complexes I and IV of the respiratory chain. Oil did not induce any modification of mitochondrial proton leak. Dispersants did not induce alteration of mitochondrial activity and did not increase oil toxicity. These data suggest that oil exposure may limit the fitness of polar cod and consequently could lead to major disruption in the energy flow of polar ecosystem.

  5. Vitamin D Metabolism and Function in the Skin

    PubMed Central

    Bikle, Daniel D

    2011-01-01

    The keratinocytes of the skin are unique in being not only the primary source of vitamin D for the body, but in possessing the enzymatic machinery to metabolize vitamin D to its active metabolite 1,25(OH)2D. Furthermore, these cells also express the vitamin D receptor (VDR) that enables them to respond to the 1,25(OH)2D they produce. Numerous functions of the skin are regulated by 1,25(OH)2D and/or its receptor. These include inhibition of proliferation, stimulation of differentiation including formation of the permeability barrier, promotion of innate immunity, and promotion of the hair follicle cycle. Regulation of these actions is exerted by a number of different coregulators including the coactivators DRIP and SRC, the cosuppressor hairless (Hr), and β-catenin. This review will examine the regulation of vitamin D production and metabolism in the skin, and explore the various functions regulated by 1,25(OH)2D and its receptor. PMID:21664236

  6. Sucrose metabolism gene families and their biological functions

    PubMed Central

    Jiang, Shu-Ye; Chi, Yun-Hua; Wang, Ji-Zhou; Zhou, Jun-Xia; Cheng, Yan-Song; Zhang, Bao-Lan; Ma, Ali; Vanitha, Jeevanandam; Ramachandran, Srinivasan

    2015-01-01

    Sucrose, as the main product of photosynthesis, plays crucial roles in plant development. Although studies on general metabolism pathway were well documented, less information is available on the genome-wide identification of these genes, their expansion and evolutionary history as well as their biological functions. We focused on four sucrose metabolism related gene families including sucrose synthase, sucrose phosphate synthase, sucrose phosphate phosphatase and UDP-glucose pyrophosphorylase. These gene families exhibited different expansion and evolutionary history as their host genomes experienced differentiated rates of the whole genome duplication, tandem and segmental duplication, or mobile element mediated gene gain and loss. They were evolutionarily conserved under purifying selection among species and expression divergence played important roles for gene survival after expansion. However, we have detected recent positive selection during intra-species divergence. Overexpression of 15 sorghum genes in Arabidopsis revealed their roles in biomass accumulation, flowering time control, seed germination and response to high salinity and sugar stresses. Our studies uncovered the molecular mechanisms of gene expansion and evolution and also provided new insight into the role of positive selection in intra-species divergence. Overexpression data revealed novel biological functions of these genes in flowering time control and seed germination under normal and stress conditions. PMID:26616172

  7. Metabolic profile and biological activities of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco: studies on the essential oil and polar extracts.

    PubMed

    Costa, Patrícia; Gonçalves, Sandra; Valentão, Patrícia; Andrade, Paula B; Almeida, Carlos; Nogueira, José M F; Romano, Anabela

    2013-12-01

    We investigated the metabolic profile and biological activities of the essential oil and polar extracts of Lavandula pedunculata subsp. lusitanica (Chaytor) Franco collected in south Portugal. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that oxygen-containing monoterpenes was the principal group of compounds identified in the essential oil. Camphor (40.6%) and fenchone (38.0%) were found as the major constituents. High-performance liquid chromatography with diode array detection (HPLC-DAD) analysis allowed the identification of hydroxycinnamic acids (3-O-caffeoylquinic, 4-O-caffeoylquinic, 5-O-caffeoylquinic and rosmarinic acids) and flavones (luteolin and apigenin) in the polar extracts, with rosmarinic acid being the main compound in most of them. The bioactive compounds from L. pedunculata polar extracts were the most efficient free-radical scavengers, Fe(2+) chelators and inhibitors of malondialdehyde production, while the essential oil was the most active against acetylcholinesterase. Our results reveal that the subspecies of L. pedunculata studied is a potential source of active metabolites with a positive effect on human health.

  8. Metabolism and biological functions of human milk oligosaccharides.

    PubMed

    Bertino, E; Peila, C; Giuliani, F; Martano, C; Cresi, F; Di Nicola, P; Occhi, L; Sabatino, G; Fabris, C

    2012-01-01

    It is well known that breastfeeding is beneficial both for its nutritional properties and for the presence of biologically active compounds. Among these, human milk oligosaccharides (HMOs), representing the third largest fraction of human milk, have been assigned important biological functions, such as prebiotic and immunomodulatory and antimicrobial effects. HMOs are synthesized in the mammary gland by glycosyltransferase enzymes and can be divided in core-oligosaccharides, sialo-oligosaccharides, fucosyl-oligosaccharides and sialo-fucosyl-oligosaccharides on the basis of their chemical structure. Glycosyltransferases enzymes are partially regulated by genetic mechanisms; according to the expression of secretory and Lewis' genes, it is possible to classify human milk in 4 different secretory groups. We hereby present a review of the current knowledge concerning HMOs, their metabolism and main biological functions.

  9. microRNA control of HDL Metabolism and Function

    PubMed Central

    Rayner, Katey J; Moore, Kathryn J.

    2015-01-01

    Recent discoveries of microRNAs (miRNAs) that control HDL abundance and function have expanded our knowledge of the mechanisms regulating this important lipoprotein subclass. miRNAs have been shown to regulate gene networks that control HDL biogenesis and uptake, as well as discrete steps in the reverse cholesterol transport pathway. Furthermore, HDL itself has been shown to selectively transport miRNAs in health and disease, offering new possibilities of how this lipoprotein may alter gene expression in distal target cells and tissues. Collectively, these discoveries offer new insights into the mechanisms governing HDL metabolism and function, and open new avenues for the development of therapeutics for the treatment of cardiovascular disease. PMID:24385511

  10. Physical, metabolic and developmental functions of the seed coat

    PubMed Central

    Radchuk, Volodymyr; Borisjuk, Ljudmilla

    2014-01-01

    The conventional understanding of the role of the seed coat is that it provides a protective layer for the developing zygote. Recent data show that the picture is more nuanced. The seed coat certainly represents a first line of defense against adverse external factors, but it also acts as channel for transmitting environmental cues to the interior of the seed. The latter function primes the seed to adjust its metabolism in response to changes in its external environment. The purpose of this review is to provide the reader with a comprehensive view of the structure and functionality of the seed coat, and to expose its hidden interaction with both the endosperm and embryo. Any breeding and/or biotechnology intervention seeking to increase seed size or modify seed features will have to consider the implications on this tripartite interaction. PMID:25346737

  11. Density-functional theory for polar fluids at functionalized surfaces. I. Fluid-wall association

    NASA Astrophysics Data System (ADS)

    Tripathi, Sandeep; Chapman, Walter G.

    2003-12-01

    We present a novel perturbation density-functional theory (DFT) to describe adsorption of associating fluids on surfaces activated with polar sites to which fluid molecules can bond or associate, such as water adsorbing on activated carbon, silica, clay minerals, etc. Association is modeled within the framework of first order thermodynamic perturbation theory (TPT1). In this first of two papers, we explore in detail the changes brought about in a system due to fluid-wall (FW) association. Hence fluid-fluid association is not considered here. However, the theory can be coupled with existing DF theories of associating fluids to study the interplay between the wall-fluid and fluid-fluid association as is shown in a future paper by S. Tripathi. The proposed theory, in excellent agreement with simulations, shows that FW association significantly changes the fluid structure and adsorption behavior. The theory accurately predicts the distribution of bonded and nonbonded species away from the surface, adsorption characteristics and surface coverage over a range of conditions commonly found in several real systems. The most striking feature of the theory is that in addition to properties away from the wall, it also estimates the distribution of the fluid along the surface, or the three-dimensional (3D) structure, despite being one-dimensional (1D) in form.

  12. Muscle metabolic function and free-living physical activity.

    PubMed

    Hunter, Gary R; Larson-Meyer, D Enette; Sirikul, Bovorn; Newcomer, Bradley R

    2006-11-01

    We have previously shown that muscle metabolic function measured during exercise is related to exercise performance and subsequent 1-yr weight gain. Because it is well established that physical activity is important in weight maintenance, we examined muscle function relationships with free-living energy expenditure and physical activity. Subjects were 71 premenopausal black and white women. Muscle metabolism was evaluated by (31)P magnetic resonance spectroscopy during 90-s isometric plantar flexion contractions (45% maximum). Free-living energy expenditure (TEE) was measured using doubly labeled water, activity-related energy expenditure (AEE) was calculated as 0.9 x TEE - sleeping energy expenditure from room calorimetry, and free-living physical activity (ARTE) was calculated by dividing AEE by energy cost of standard physical activities. At the end of exercise, anaerobic glycolytic rate (ANGLY) and muscle concentration of phosphomonoesters (PME) were negatively related to TEE, AEE, and ARTE (P < 0.05). Multiple regression analysis showed that both PME (partial r = -0.29, <0.02) and ANGLY (partial r = -0.24, P < 0.04) were independently related to ARTE. PME, primarily glucose-6-phosphate and fructose-6-phosphate, was significantly related to ratings of perceived exertion (r = 0.21, P < or = 0.05) during a maximal treadmill test. PME was not related to ARTE after inclusion of RPE in the multiple regression model, suggesting that PME may be obtaining its relationship with ARTE through an increased perception of effort during physical activity. In conclusion, physically inactive individuals tend to be more dependent on anaerobic glycolysis during exercise while relying on a glycolytic pathway that may not be functioning optimally.

  13. Experimental nonalcoholic steatohepatitis compromises ureagenesis, an essential hepatic metabolic function.

    PubMed

    Thomsen, Karen Louise; Grønbæk, Henning; Glavind, Emilie; Hebbard, Lionel; Jessen, Niels; Clouston, Andrew; George, Jacob; Vilstrup, Hendrik

    2014-08-01

    Nonalcoholic steatohepatitis (NASH) is increasing in prevalence, yet its consequences for liver function are unknown. We studied ureagenesis, an essential metabolic liver function of importance for whole body nitrogen homeostasis, in a rodent model of diet-induced NASH. Rats were fed a high-fat, high-cholesterol diet for 4 and 16 wk, resulting in early and advanced experimental NASH, respectively. We examined the urea cycle enzyme mRNAs in liver tissue, the hepatocyte urea cycle enzyme proteins, and the in vivo capacity of urea-nitrogen synthesis (CUNS). Early NASH decreased all of the urea cycle mRNAs to an average of 60% and the ornithine transcarbamylase protein to 10%, whereas the CUNS remained unchanged. Advanced NASH further decreased the carbamoyl phosphate synthetase protein to 63% and, in addition, decreased the CUNS by 20% [from 5.65 ± 0.23 to 4.58 ± 0.30 μmol × (min × 100 g)(-1); P = 0.01]. Early NASH compromised the genes and enzyme proteins involved in ureagenesis, whereas advanced NASH resulted in a functional reduction in the capacity for ureagenesis. The pattern of urea cycle perturbations suggests a prevailing mitochondrial impairment by NASH. The decrease in CUNS has consequences for the ability of the body to adjust to changes in the requirements for nitrogen homeostasis e.g., at stressful events. NASH, thus, in terms of metabolic consequences, is not an innocuous lesion, and the manifestations of the damage seem to be a continuum with increasing disease severity.

  14. Exploring metabolic pathways and regulation through functional chemoproteomic and metabolomic platforms.

    PubMed

    Medina-Cleghorn, Daniel; Nomura, Daniel K

    2014-09-18

    Genome sequencing efforts have revealed a strikingly large number of uncharacterized genes, including poorly or uncharacterized metabolic enzymes, metabolites, and metabolic networks that operate in normal physiology, and those enzymes and pathways that may be rewired under pathological conditions. Although deciphering the functions of the uncharacterized metabolic genome is a challenging prospect, it also presents an opportunity for identifying novel metabolic nodes that may be important in disease therapy. In this review, we will discuss the chemoproteomic and metabolomic platforms used in identifying, characterizing, and targeting nodal metabolic pathways important in physiology and disease, describing an integrated workflow for functional mapping of metabolic enzymes.

  15. Retinol Dehydrogenases Regulate Vitamin A Metabolism for Visual Function

    PubMed Central

    Sahu, Bhubanananda; Maeda, Akiko

    2016-01-01

    The visual system produces visual chromophore, 11-cis-retinal from dietary vitamin A, all-trans-retinol making this vitamin essential for retinal health and function. These metabolic events are mediated by a sequential biochemical process called the visual cycle. Retinol dehydrogenases (RDHs) are responsible for two reactions in the visual cycle performed in retinal pigmented epithelial (RPE) cells, photoreceptor cells and Müller cells in the retina. RDHs in the RPE function as 11-cis-RDHs, which oxidize 11-cis-retinol to 11-cis-retinal in vivo. RDHs in rod photoreceptor cells in the retina work as all-trans-RDHs, which reduce all-trans-retinal to all-trans-retinol. Dysfunction of RDHs can cause inherited retinal diseases in humans. To facilitate further understanding of human diseases, mouse models of RDHs-related diseases have been carefully examined and have revealed the physiological contribution of specific RDHs to visual cycle function and overall retinal health. Herein we describe the function of RDHs in the RPE and the retina, particularly in rod photoreceptor cells, their regulatory properties for retinoid homeostasis and future therapeutic strategy for treatment of retinal diseases. PMID:27879662

  16. Comprehension of the Electric Polarization as a Function of Low Temperature

    NASA Astrophysics Data System (ADS)

    Liu, Changshi

    2017-01-01

    Polarization response to warming plays an increasingly important role in a number of ferroelectric memory devices. This paper reports on the theoretical explanation of the relationship between polarization and temperature. According to the Fermi-Dirac distribution, the basic property of electric polarization response to temperature in magnetoelectric multiferroic materials is theoretically analyzed. The polarization in magnetoelectric multiferroic materials can be calculated by low temperature using a phenomenological theory suggested in this paper. Simulation results revealed that the numerically calculated results are in good agreement with experimental results of some inhomogeneous multiferroic materials. Numerical simulations have been performed to investigate the influences of both electric and magnetic fields on the polarization in magnetoelectric multiferroic materials. Furthermore, polarization behavior of magnetoelectric multiferroic materials can be predicted by low temperature, electric field and magnetic induction using only one function. The calculations offer an insight into the understanding of the effects of heating and magnetoelectric field on electrical properties of multiferroic materials and offer a potential to use similar methods to analyze electrical properties of other memory devices.

  17. Is there more to learn about functional vitamin D metabolism?

    PubMed

    DeLuca, Hector F

    2015-04-01

    The state of information on the enzymes responsible for the conversion of vitamin D3 to 1α,25-dhydroxyvitamin D3 (1,25-(OH)2D3), the metabolic active form responsible for the well-known function of vitamin D on calcium metabolism and bone mineralization has been briefly reviewed. There remains an unidentified enzyme responsible for 25% of the 25-hydroxylation of vitamin D3, while 75% of serum 25-hydroxyvitamin D3 (25-OH-D3) arises from CYP2R1. The well-established suppression of multiple sclerosis (MS) by sunlight has been confirmed using the mouse model, experimental autoimmune encephalomyelitis (EAE). This suppression results from a narrow band of ultraviolet light (300-315nm) that does not increase serum 25-OH-D3. Thus, UV light suppresses EAE by a mechanism not involving vitamin D. Vitamin D deficiency unexpectedly suppresses the development of EAE. Further, vitamin D receptor knockout in susceptible mice also prevents the development of EAE. On the other hand, deletion of CYP2R1 and the 1α-hydroxylase, CYP27B1, does not impair the development of EAE. Thus, either vitamin D itself or a heretofore-unknown metabolite is needed for the development of a component of the immune system necessary for development of EAE. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  18. Effects of metabolic syndrome on language functions in aging.

    PubMed

    Cahana-Amitay, Dalia; Spiro, Avron; Cohen, Jason A; Oveis, Abigail C; Ojo, Emmanuel A; Sayers, Jesse T; Obler, Loraine K; Albert, Martin L

    2015-02-01

    This study explored effects of the metabolic syndrome (MetS) on language in aging. MetS is a constellation of five vascular and metabolic risk factors associated with the development of chronic diseases and increased risk of mortality, as well as brain and cognitive impairments. We tested 281 English-speaking older adults aged 55-84, free of stroke and dementia. Presence of MetS was based on the harmonized criteria (Alberti et al., 2009). Language performance was assessed by measures of accuracy and reaction time on two tasks of lexical retrieval and two tasks of sentence processing. Regression analyses, adjusted for age, education, gender, diabetes, hypertension, and heart disease, demonstrated that participants with MetS had significantly lower accuracy on measures of lexical retrieval (action naming) and sentence processing (embedded sentences, both subject and object relative clauses). Reaction time was slightly faster on the test of embedded sentences among those with MetS. MetS adversely affects the language performance of older adults, impairing accuracy of both lexical retrieval and sentence processing. This finding reinforces and extends results of earlier research documenting the negative influence of potentially treatable medical conditions (diabetes, hypertension) on language performance in aging. The unanticipated finding that persons with MetS were faster in processing embedded sentences may represent an impairment of timing functions among older individuals with MetS.

  19. Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme

    PubMed Central

    Levati, Elisabetta; Sartini, Sara; Bolchi, Angelo; Ottonello, Simone; Montanini, Barbara

    2016-01-01

    Moonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies, and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant. PMID:27121330

  20. Lipid Droplet Accumulation and Impaired Fat Efflux in Polarized Hepatic Cells: Consequences of Ethanol Metabolism

    PubMed Central

    McVicker, Benita L.; Rasineni, Karuna; Tuma, Dean J.; McNiven, Mark A.; Casey, Carol A.

    2012-01-01

    Steatosis, an early manifestation in alcoholic liver disease, is associated with the accumulation of hepatocellular lipid droplets (LDs). However, the role ethanol metabolism has in LD formation and turnover remains undefined. Here, we assessed LD dynamics following ethanol and oleic acid treatment to ethanol-metabolizing WIF-B cells (a hybrid of human fibroblasts (WI 38) and Fao rat hepatoma cells). An OA dose-dependent increase in triglyceride and stained lipids was identified which doubled (P < 0.05) in the presence of ethanol. This effect was blunted with the inclusion of an alcohol metabolism inhibitor. The ethanol/ OA combination also induced adipophilin, LD coat protein involved in the attenuation of lipolysis. Additionally, ethanol treatment resulted in a significant reduction in lipid efflux. These data demonstrate that the metabolism of ethanol in hepatic cells is related to LD accumulation, impaired fat efflux, and enhancements in LD-associated proteins. These alterations in LD dynamics may contribute to ethanol-mediated defects in hepatocellular LD regulation and the formation of steatosis. PMID:22506128

  1. Anatomical Reconstruction and Functional Imaging Reveal an Ordered Array of Skylight Polarization Detectors in Drosophila

    PubMed Central

    Bleul, Christiane; Baumann-Klausener, Franziska; Labhart, Thomas; Dickinson, Michael H.

    2016-01-01

    Many insects exploit skylight polarization as a compass cue for orientation and navigation. In the fruit fly, Drosophila melanogaster, photoreceptors R7 and R8 in the dorsal rim area (DRA) of the compound eye are specialized to detect the electric vector (e-vector) of linearly polarized light. These photoreceptors are arranged in stacked pairs with identical fields of view and spectral sensitivities, but mutually orthogonal microvillar orientations. As in larger flies, we found that the microvillar orientation of the distal photoreceptor R7 changes in a fan-like fashion along the DRA. This anatomical arrangement suggests that the DRA constitutes a detector for skylight polarization, in which different e-vectors maximally excite different positions in the array. To test our hypothesis, we measured responses to polarized light of varying e-vector angles in the terminals of R7/8 cells using genetically encoded calcium indicators. Our data confirm a progression of preferred e-vector angles from anterior to posterior in the DRA, and a strict orthogonality between the e-vector preferences of paired R7/8 cells. We observed decreased activity in photoreceptors in response to flashes of light polarized orthogonally to their preferred e-vector angle, suggesting reciprocal inhibition between photoreceptors in the same medullar column, which may serve to increase polarization contrast. Together, our results indicate that the polarization-vision system relies on a spatial map of preferred e-vector angles at the earliest stage of sensory processing. SIGNIFICANCE STATEMENT The fly's visual system is an influential model system for studying neural computation, and much is known about its anatomy, physiology, and development. The circuits underlying motion processing have received the most attention, but researchers are increasingly investigating other functions, such as color perception and object recognition. In this work, we investigate the early neural processing of a somewhat

  2. Understanding the structure and functioning of polar pelagic ecosystems to predict the impacts of change

    PubMed Central

    Drinkwater, K. F.; Grant, S. M.; Heymans, J. J.; Hofmann, E. E.; Hunt, G. L.; Johnston, N. M.

    2016-01-01

    The determinants of the structure, functioning and resilience of pelagic ecosystems across most of the polar regions are not well known. Improved understanding is essential for assessing the value of biodiversity and predicting the effects of change (including in biodiversity) on these ecosystems and the services they maintain. Here we focus on the trophic interactions that underpin ecosystem structure, developing comparative analyses of how polar pelagic food webs vary in relation to the environment. We highlight that there is not a singular, generic Arctic or Antarctic pelagic food web, and, although there are characteristic pathways of energy flow dominated by a small number of species, alternative routes are important for maintaining energy transfer and resilience. These more complex routes cannot, however, provide the same rate of energy flow to highest trophic-level species. Food-web structure may be similar in different regions, but the individual species that dominate mid-trophic levels vary across polar regions. The characteristics (traits) of these species are also different and these differences influence a range of food-web processes. Low functional redundancy at key trophic levels makes these ecosystems particularly sensitive to change. To develop models for projecting responses of polar ecosystems to future environmental change, we propose a conceptual framework that links the life histories of pelagic species and the structure of polar food webs. PMID:27928038

  3. Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?

    PubMed

    Cartocci, Veronica; Servadio, Michela; Trezza, Viviana; Pallottini, Valentina

    2017-02-01

    Cholesterol is an important component for cell physiology. It regulates the fluidity of cell membranes and determines the physical and biochemical properties of proteins. In the central nervous system, cholesterol controls synapse formation and function and supports the saltatory conduction of action potential. In recent years, the role of cholesterol in the brain has caught the attention of several research groups since a breakdown of cholesterol metabolism has been associated with different neurodevelopmental and neurodegenerative diseases, and interestingly also with psychiatric conditions. The aim of this review is to summarize the current knowledge about the connection between cholesterol dysregulation and various neurologic and psychiatric disorders based on clinical and preclinical studies. J. Cell. Physiol. 232: 281-286, 2017. © 2016 Wiley Periodicals, Inc.

  4. Metabolically active functional food ingredients for weight control.

    PubMed

    Kovacs, E M R; Mela, D J

    2006-02-01

    The scale of the obesity epidemic creates a pressing consumer need as well as an enormous business opportunity for successful development and marketing of food products with added benefits for weight control. A number of proposed functional food ingredients have been shown to act post-absorptively to influence substrate utilization or thermogenesis. Characteristics and supporting data on conjugated linoleic acid, diglycerides, medium-chain triglycerides, green tea, ephedrine, caffeine, capsaicin and calcium, are reviewed here, giving examples of how these could act to alter energy expenditure or appetite control. Consideration is also given to other factors, in addition to efficacy, which must be satisfied to get such ingredients into foods. We conclude that, for each of the safe, putatively metabolically active agents, there remain gaps in clinical evidence or knowledge of mechanisms, which need to be addressed in order to specify the dietary conditions and food product compositions where these ingredients could be of most benefit for weight control.

  5. APUM23, a PUF family protein, functions in leaf development and organ polarity in Arabidopsis

    PubMed Central

    Huang, Tengbo

    2014-01-01

    The normal biological function of leaves, such as intercepting light and exchanging gasses, relies on proper differentiation of adaxial and abaxial polarity. KANADI (KAN) genes, members of the GARP family, are key regulators of abaxial identity in leaf morphogenesis. This study identified a mutant allele (apum23-3) of APUM23, which encodes a Pumilio/PUF domain protein and acts as an enhancer of the kan mutant. Arabidopsis APUM23 has been shown to function in pre-rRNA processing and play pleiotropic roles in plant development. The apum23-3 mutant also synergistically interacts with other leaf polarity mutants, affects proliferation of division-competent cells, and alters the expression of important leaf polarity genes. These phenotypes show that APUM23 has critical functions in plant development, particularly in polarity formation. The PUF gene family is conserved across kingdoms yet it has not been well characterized in plants. These results illuminating the functions of APUM23 suggest a novel role for PUF genes in Arabidopsis leaf development. PMID:24449383

  6. Gravimetric excitation function of polar motion from the GRACE RL05 solution

    NASA Astrophysics Data System (ADS)

    Nastula, Y.

    2014-12-01

    Impact of land hydrosphere on polar motion excitation is still not as well known as the impact of the angular momentum of the atmosphere and ocean. Satellite mission Gravity Recovery and Climate Experiment (GRACE) from 2002 provides additional information about mass distribution of the land hydrosphere. However, despite the use of similar computational procedures, the differences between GRACE data series made available by the various centers of computations are still considerable. In the paper we compare three series of gravimetric excitation functions of polar motion determined from Rl05 GRACE solution from the Center for Space Research (CSR), the Jet Propulsion Laboratory (JPL) and the GeoForschungsZentrum (GFZ). These data are used to determine the gravimetric polar motion excitation function. Gravimetric signal is compared also with the geodetic residuals computed by subtracting atmospheric and oceanic signals from geodetic excitation functions of polar motion. Gravimetric excitation functions obtained on the basis of JPL data differ significantly from the geodetic residuals while and the series obtained from CSR and GFZ are more compatible.

  7. APUM23, a PUF family protein, functions in leaf development and organ polarity in Arabidopsis.

    PubMed

    Huang, Tengbo; Kerstetter, Randall A; Irish, Vivian F

    2014-03-01

    The normal biological function of leaves, such as intercepting light and exchanging gases, relies on proper differentiation of adaxial and abaxial polarity. KANADI (KAN) genes, members of the GARP family, are key regulators of abaxial identity in leaf morphogenesis. This study identified a mutant allele (apum23-3) of APUM23, which encodes a Pumilio/PUF domain protein and acts as an enhancer of the kan mutant. Arabidopsis APUM23 has been shown to function in pre-rRNA processing and play pleiotropic roles in plant development. The apum23-3 mutant also synergistically interacts with other leaf polarity mutants, affects proliferation of division-competent cells, and alters the expression of important leaf polarity genes. These phenotypes show that APUM23 has critical functions in plant development, particularly in polarity formation. The PUF gene family is conserved across kingdoms yet it has not been well characterized in plants. These results illuminating the functions of APUM23 suggest a novel role for PUF genes in Arabidopsis leaf development.

  8. Relationship between Students' Understanding of Functions in Cartesian and Polar Coordinate Systems

    ERIC Educational Resources Information Center

    Montiel, Mariana; Vidakovic, Draga; Kabael, Tangul

    2009-01-01

    The present study was implemented as a prelude to a study on the generalization of the single variable function concept to multivariate calculus. In the present study we analyze students' mental processes and adjustments, as they are being exposed to single variable calculus with polar coordinates. The results show that there appears to be a…

  9. Maternal blood metal levels and fetal markers of metabolic function

    SciTech Connect

    Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E.; Ettinger, Adrienne S.; Shapiro, Gabriel D.; Fisher, Mandy; Taback, Shayne; Bouchard, Maryse F.; Monnier, Patricia; Dallaire, Renee; Fraser, William D.

    2015-01-15

    Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between metals and

  10. Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation.

    PubMed

    Holmes, Andrew P; Turner, Philip J; Carter, Paul; Leadbeater, Wendy; Ray, Clare J; Hauton, David; Buckler, Keith J; Kumar, Prem

    2014-10-15

    The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate PO2 led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run-down by ∼33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge.

  11. Executive Functioning and the Metabolic Syndrome: A Project FRONTIER Study

    PubMed Central

    Falkowski, Jed; Atchison, Timothy; DeButte-Smith, Maxine; Weiner, Myron F.; O'Bryant, Sid

    2014-01-01

    Decrements in cognitive functioning have been linked to the metabolic syndrome (MetS), a risk factor for cardiovascular disease defined by the presence of three of the following: elevated blood pressure, increased waist circumference, elevated blood glucose, elevated triglycerides, and low high-density lipoprotein cholesterol. We examined the relationship between four measures of executive functioning (EF) and MetS as diagnosed by National Heart, Lung, and Blood Institute-American Heart Association criteria. MetS was examined in a rural population of 395 persons with a mean age of 61.3 years, 71.4% women, 37.0% Hispanic, 53.7% White non-Hispanic. There was a 61.0% prevalence of MetS. We derived a factor score from the four executive function measures which was used to compare those with and without the syndrome, as well as any additive effects of components of the syndrome. Those with MetS exhibited significantly poorer performance than those without the syndrome. However, there was no additive effect, having more components of the syndrome was not related to lower performance. The presence of MetS was associated with poorer EF in this rural cohort of community dwelling volunteers. PMID:24152591

  12. Sphingolipid Metabolism, Oxidant Signaling, and Contractile Function of Skeletal Muscle

    PubMed Central

    Nikolova-Karakashian, Mariana N.

    2011-01-01

    Abstract Significance Sphingolipids are a class of bioactive lipids that regulate diverse cell functions. Ceramide, sphingosine, and sphingosine-1-phosphate accumulate in tissues such as liver, brain, and lung under conditions of cellular stress, including oxidative stress. The activity of some sphingolipid metabolizing enzymes, chiefly the sphingomyelinases, is stimulated during inflammation and in response to oxidative stress. Ceramide, the sphingomyelinase product, as well as the ceramide metabolite, sphingosine-1-phosphate, can induce the generation of more reactive oxygen species, propagating further inflammation. Recent Advances This review article summarizes information on sphingolipid biochemistry and signaling pertinent to skeletal muscle and describes the potential influence of sphingolipids on contractile function. Critical Issues It encompasses topics related to (1) the pathways for complex sphingolipid biosynthesis and degradation, emphasizing sphingolipid regulation in various muscle fiber types and subcellular compartments; (2) the emerging evidence that implicates ceramide, sphingosine, and sphingosine-1-phosphate as regulators of muscle oxidant activity, and (3) sphingolipid effects on contractile function and fatigue. Future Directions We propose that prolonged inflammatory conditions alter ceramide, sphingosine, and sphingosine-1-phosphate levels in skeletal muscle and that these changes promote the weakness, premature fatigue, and cachexia that plague individuals with heart failure, cancer, diabetes, and other chronic inflammatory diseases. Antioxid. Redox Signal. 15, 2501–2517. PMID:21453197

  13. Time-dependent density functional theory for strong-field ionization by circularly polarized pulses

    NASA Astrophysics Data System (ADS)

    Chirilă, Ciprian C.; Lein, Manfred

    2017-03-01

    By applying time-dependent density functional theory to a two-dimensional multielectron atom subject to strong circularly polarized light pulses, we confirm that the ionization of p orbitals with defined angular momentum depends on the sense of rotation of the applied field. A simple ad-hoc modification of the adiabatic local-density exchange-correlation functional is proposed to remedy its unphysical behavior under orbital depletion.

  14. Analytical polarization and coherence transfer functions for three dipolar coupled spins 12.

    PubMed

    Luy, B; Glaser, S J

    2000-02-01

    Analytical polarization and coherence transfer functions are presented for a spin system consisting of three dipolar coupled homonuclear spins 12 under energy matched conditions. Based on these transfer functions, optimal durations of Hartmann-Hahn mixing periods can be determined for arbitrary dipolar coupling constants D(12), D(13), and D(23). In addition, the dependence of the transfer efficiency on the relative size of the dipolar coupling constants is illustrated.

  15. Impact of dietary dairy polar lipids on lipid metabolism of mice fed a high-fat diet.

    PubMed

    Reis, Mariza G; Roy, Nicole C; Bermingham, Emma N; Ryan, Leigh; Bibiloni, Rodrigo; Young, Wayne; Krause, Lutz; Berger, Bernard; North, Mike; Stelwagen, Kerst; Reis, Marlon M

    2013-03-20

    The effect of milk polar lipids on lipid metabolism of liver, adipose tissue, and brain and on composition of intestinal microbiota was investigated. C57BL/6J mice were fed a high-fat diet (HFD) for 5 weeks, followed by 5 weeks with HFD without (control) or supplemented with total polar lipids (TPL), phospholipids (PL), or sphingolipids (SPL). Animals fed SPL showed a tendency for lower triglyceride synthesis (P = 0.058) in the liver, but not in adipose tissue. PL and TPL reduced de novo hepatic fatty acid biosynthesis. The ratio of palmitoleic to palmitic acid in the liver was lower for animals fed SPL or TPL compared to control. There was little effect of the supplementation on the cecal microbiota composition. In the brain, DHA (C22:6) content correlated negatively with tetracosanoic acid (C24:0) after TPL supplementation (-0.71, P = 0.02) but not in control (0.26, P = 0.44). Arachidonic acid (C20:4) was negatively correlated with C24:0 in both groups (TPL, -0.77, P = 0.008; control, -0.81, P = 0.003).

  16. Metabolism Supports Macrophage Activation

    PubMed Central

    Langston, P. Kent; Shibata, Munehiko; Horng, Tiffany

    2017-01-01

    Macrophages are found in most tissues of the body, where they have tissue- and context-dependent roles in maintaining homeostasis as well as coordinating adaptive responses to various stresses. Their capacity for specialized functions is controlled by polarizing signals, which activate macrophages by upregulating transcriptional programs that encode distinct effector functions. An important conceptual advance in the field of macrophage biology, emerging from recent studies, is that macrophage activation is critically supported by metabolic shifts. Metabolic shifts fuel multiple aspects of macrophage activation, and preventing these shifts impairs appropriate activation. These findings raise the exciting possibility that macrophage functions in various contexts could be regulated by manipulating their metabolism. Here, we review the rapidly evolving field of macrophage metabolism, discussing how polarizing signals trigger metabolic shifts and how these shifts enable appropriate activation and sustain effector activities. We also discuss recent studies indicating that the mitochondria are central hubs in inflammatory macrophage activation. PMID:28197151

  17. Yeast diversity of sourdoughs and associated metabolic properties and functionalities.

    PubMed

    De Vuyst, Luc; Harth, Henning; Van Kerrebroeck, Simon; Leroy, Frédéric

    2016-12-19

    Together with acidifying lactic acid bacteria, yeasts play a key role in the production process of sourdough, where they are either naturally present or added as a starter culture. Worldwide, a diversity of yeast species is encountered, with Saccharomyces cerevisiae, Candida humilis, Kazachstania exigua, Pichia kudriavzevii, Wickerhamomyces anomalus, and Torulaspora delbrueckii among the most common ones. Sourdough-adapted yeasts are able to withstand the stress conditions encountered during their growth, including nutrient starvation as well as the effects of acidic, oxidative, thermal, and osmotic stresses. From a technological point of view, their metabolism primarily contributes to the leavening and flavour of sourdough products. Besides ethanol and carbon dioxide, yeasts can produce metabolites that specifically affect flavour, such as organic acids, diacetyl, higher alcohols from branched-chain amino acids, and esters derived thereof. Additionally, several yeast strains possess functional properties that can potentially lead to nutritional and safety advantages. These properties encompass the production of vitamins, an improvement of the bioavailability of phenolic compounds, the dephosphorylation of phytic acid, the presence of probiotic potential, and the inhibition of fungi and their mycotoxin production. Strains of diverse species are new candidate functional starter cultures, offering opportunities beyond the conventional use of baker's yeast.

  18. Effect of metabolic syndrome on sexual function in pre- and postmenopausal women.

    PubMed

    Otunctemur, Alper; Dursun, Murat; Ozbek, Emin; Sahin, Suleyman; Besiroglu, Huseyin; Koklu, Ismail; Polat, Emre Can; Erkoc, Mustafa; Danis, Eyyup; Bozkurt, Muammer

    2015-01-01

    Female sexual dysfunction is a prevalent and multidimensional disorder related to many biological, psychological, and social determinants. The authors assessed the effect of one of the many factors affect sexual function-metabolic syndrome-on female sexual function. They equally divided 400 women participants among 4 groups: (a) premenopausal with metabolic syndrome, (b) premenopausal without metabolic syndrome, (c) postmenopausal with metabolic syndrome, and (d) postmenopausal without metabolic syndrome. The authors used the Female Sexual Function Index to assess women's sexual function. Female sexual dysfunction was found more often in both pre- and postmenopausal women with metabolic syndrome (p =.001). Overall Female Sexual Function Index score and satisfaction, pain, and desire domain scores independently of the menopause status showed statistically significant differences across women with metabolic syndrome in comparison with participants with no metabolic syndrome (p <.05). The authors also evaluated the associations among 5 components of metabolic syndrome and Female Sexual Function Index scores. Higher fasting glucose levels were significantly associated with the Female Sexual Function Index score (p <.05). This study shows that sexual dysfunction is more prevalent in pre- and postmenopausal women with the metabolic syndrome.

  19. Investigation of Carbohydrate Metabolism and Transport in Castor Bean Seedlings by Cyclic JCross Polarization Imaging and Spectroscopy

    NASA Astrophysics Data System (ADS)

    Heidenreich, M.; Köckenberger, W.; Kimmich, R.; Chandrakumar, N.; Bowtell, R.

    1998-05-01

    NMR experiments using13C-labeled compounds offer the possibility of noninvasive monitoring of carbohydrate transport and metabolism in living plants, but are usually hampered by the low sensitivity of the13C nucleus. The problem of low sensitivity can be overcome by using the cyclicJcross polarization (CYCLCROP) technique, which allows the indirect detection of13C nuclei coupled to1H nuclei with the high NMR sensitivity of protons. We report here on methods for imaging and spectroscopy based on the CYCLCROP technique, and their use in the firstin vivoNMR study of carbohydrate transport and metabolism in castor bean seedlings (Ricinus communis L.). Comprehensive acquisition strategies for the various NMR methods are given, including the procedure for setting up the experiments. In addition, a full analysis of the effect of relaxation on the signals generated from smallJ-coupled spin systems by the CYCLCROP sequence is given, and the high sensitivity of the sequence is demonstrated. In thein vivostudy of six-day-old castor bean seedlings, we were able to measure the uptake of labeled hexoses, supplied in solution to the cotyledons, and their conversion to sucrose, as well as the transport of this sucrose in the vascular bundles. Images of the actual distribution of labeled sucrose in the hypocotyl of the seedling have also been obtained. The resulting data show some evidence for a preferential incorporation of labeled fructose in the process of sucrose synthesis, which decreases with the time of incubation.

  20. Metabolic footprinting in microbiology: methods and applications in functional genomics and biotechnology.

    PubMed

    Mapelli, Valeria; Olsson, Lisbeth; Nielsen, Jens

    2008-09-01

    Metabolomics embraces several strategies that aim to quantify cell metabolites in order to increase our understanding of how metabolite levels and interactions influence phenotypes. Metabolic footprinting represents a niche within metabolomics, because it focuses on the analysis of extracellular metabolites. Although metabolic footprinting represents only a fraction of the entire metabolome, it provides important information for functional genomics and strain characterization, and it can also provide scientists with a key understanding of cell communication mechanisms, metabolic engineering and industrial biotechnological processes. Due to the tight and convoluted relationship between intracellular metabolism and metabolic footprinting, metabolic footprinting can provide precious information about the intracellular metabolic status. Hereby, we state that integrative information from metabolic footprinting can assist in further interpretation of metabolic networks.

  1. Structure-Function Study of Tertiary Amines as Switchable Polarity Solvents

    SciTech Connect

    Aaron D. Wilson; Frederick F. Stewart

    2014-02-01

    A series of tertiary amines have been screened for their function as switchable polarity solvents (SPS). The relative ratios of tertiary amine and carbonate species as well as maximum possible concentration were determined through quantitative 1H and 13C NMR spectroscopy. The viscosities of the polar SPS solutions were measured and ranged from near water in dilute systems through to gel formation at high concentrations. The van't Hoff indices for SPS solutions were measured through freezing point depression studies as a proxy for osmotic pressures. A new form of SPS with an amine : carbonate ratio significantly greater than unity has been identified. Tertiary amines that function as SPS at ambient pressures appear to be limited to molecules with fewer than 12 carbons. The N,N-dimethyl-n-alkylamine structure has been identified as important to the function of an SPS.

  2. Metabolic profiling of Lolium perenne shows functional integration of metabolic responses to diverse subtoxic conditions of chemical stress.

    PubMed

    Serra, Anne-Antonella; Couée, Ivan; Renault, David; Gouesbet, Gwenola; Sulmon, Cécile

    2015-04-01

    Plant communities are confronted with a great variety of environmental chemical stresses. Characterization of chemical stress in higher plants has often been focused on single or closely related stressors under acute exposure, or restricted to a selective number of molecular targets. In order to understand plant functioning under chemical stress conditions close to environmental pollution conditions, the C3 grass Lolium perenne was subjected to a panel of different chemical stressors (pesticide, pesticide degradation compound, polycyclic aromatic hydrocarbon, and heavy metal) under conditions of seed-level or root-level subtoxic exposure. Physiological and metabolic profiling analysis on roots and shoots revealed that all of these subtoxic chemical stresses resulted in discrete physiological perturbations and complex metabolic shifts. These metabolic shifts involved stressor-specific effects, indicating multilevel mechanisms of action, such as the effects of glyphosate and its degradation product aminomethylphosphonic acid on quinate levels. They also involved major generic effects that linked all of the subtoxic chemical stresses with major modifications of nitrogen metabolism, especially affecting asparagine, and of photorespiration, especially affecting alanine and glycerate. Stress-related physiological effects and metabolic adjustments were shown to be integrated through a complex network of metabolic correlations converging on Asn, Leu, Ser, and glucose-6-phosphate, which could potentially be modulated by differential dynamics and interconversion of soluble sugars (sucrose, trehalose, fructose, and glucose). Underlying metabolic, regulatory, and signalling mechanisms linking these subtoxic chemical stresses with a generic impact on nitrogen metabolism and photorespiration are discussed in relation to carbohydrate and low-energy sensing.

  3. Vibrational frequency scale factors for density functional theory and the polarization consistent basis sets.

    PubMed

    Laury, Marie L; Carlson, Matthew J; Wilson, Angela K

    2012-11-15

    Calculated harmonic vibrational frequencies systematically deviate from experimental vibrational frequencies. The observed deviation can be corrected by applying a scale factor. Scale factors for: (i) harmonic vibrational frequencies [categorized into low (<1000 cm(-1)) and high (>1000 cm(-1))], (ii) vibrational contributions to enthalpy and entropy, and (iii) zero-point vibrational energies (ZPVEs) have been determined for widely used density functionals in combination with polarization consistent basis sets (pc-n, n = 0,1,2,3,4). The density functionals include pure functionals (BP86, BPW91, BLYP, HCTH93, PBEPBE), hybrid functionals with Hartree-Fock exchange (B3LYP, B3P86, B3PW91, PBE1PBE, mPW1K, BH&HLYP), hybrid meta functionals with the kinetic energy density gradient (M05, M06, M05-2X, M06-2X), a double hybrid functional with Møller-Plesset correlation (B2GP-PLYP), and a dispersion corrected functional (B97-D). The experimental frequencies for calibration were from 41 organic molecules and the ZPVEs for comparison were from 24 small molecules (diatomics, triatomics). For this family of basis sets, the scale factors for each property are more dependent on the functional selection than on basis set level, and thus allow for a suggested scale factor for each density functional when employing polarization consistent basis sets (pc-n, n = 1,2,3,4). A separate scale factor is recommended when the un-polarized basis set, pc-0, is used in combination with the density functionals.

  4. The Effects of Instrumental Elliptical Polarization on Stellar Point Spread Function Fine Structure

    NASA Technical Reports Server (NTRS)

    Carson, Joseph C.; Kern, Brian D.; Breckinridge, James B.; Trauger, John T.

    2005-01-01

    We present procedures and preliminary results from a study on the effects of instrumental polarization on the fine structure of the stellar point spread function (PSF). These effects are important to understand because the the aberration caused by instrumental polarization on an otherwise diffraction-limited will likely have have severe consequences for extreme high contrast imaging systems such as NASA's planned Terrestrial Planet Finder (TPF) mission and the proposed NASA Eclipse mission. The report here, describing our efforts to examine these effects, includes two parts: 1) a numerical analysis of the effect of metallic reflection, with some polarization-specific retardation, on a spherical wavefront; 2) an experimental approach for observing this effect, along with some preliminary laboratory results. While the experimental phase of this study requires more fine-tuning to produce meaningful results, the numerical analysis indicates that the inclusion of polarization-specific phase effects (retardation) results in a point spread function (PSF) aberration more severe than the amplitude (reflectivity) effects previously recorded in the literature.

  5. Polar-solvation classical density-functional theory for electrolyte aqueous solutions near a wall

    NASA Astrophysics Data System (ADS)

    Warshavsky, Vadim; Marucho, Marcelo

    2016-04-01

    A precise description of the structural and dielectric properties of liquid water is critical to understanding the physicochemical properties of solutes in electrolyte solutions. In this article, a mixture of ionic and dipolar hard spheres is considered to account for water crowding and polarization effects on ionic electrical double layers near a uniformly charged hard wall. As a unique feature, solvent hard spheres carrying a dipole at their centers were used to model water molecules at experimentally known concentration, molecule size, and dipolar moment. The equilibrium ionic and dipole density profiles of this electrolyte aqueous model were calculated using a polar-solvation classical density-functional theory (PSCDFT). These profiles were used to calculate the charge density distribution, water polarization, dielectric permittivity function, and mean electric potential profiles as well as differential capacitance, excess adsorptions, and wall-fluid surface tension. These results were compared with those corresponding to the pure dipolar model and unpolar primitive solvent model of electrolyte aqueous solutions to understand the role that water crowding and polarization effects play on the structural and thermodynamic properties of these systems. Overall, PSCDFT predictions are in agreement with available experimental data.

  6. Metabolic gatekeeper function of B-lymphoid transcription factors.

    PubMed

    Chan, Lai N; Chen, Zhengshan; Braas, Daniel; Lee, Jae-Woong; Xiao, Gang; Geng, Huimin; Cosgun, Kadriye Nehir; Hurtz, Christian; Shojaee, Seyedmehdi; Cazzaniga, Valeria; Schjerven, Hilde; Ernst, Thomas; Hochhaus, Andreas; Kornblau, Steven M; Konopleva, Marina; Pufall, Miles A; Cazzaniga, Giovanni; Liu, Grace J; Milne, Thomas A; Koeffler, H Phillip; Ross, Theodora S; Sánchez-García, Isidro; Borkhardt, Arndt; Yamamoto, Keith R; Dickins, Ross A; Graeber, Thomas G; Müschen, Markus

    2017-02-23

    B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply. Our metabolic analyses revealed that PAX5 and IKZF1 enforce a state of chronic energy deprivation, resulting in constitutive activation of the energy-stress sensor AMPK. Dominant-negative mutants of PAX5 and IKZF1, however, relieved this glucose and energy restriction. In a transgenic pre-B ALL mouse model, the heterozygous deletion of Pax5 increased glucose uptake and ATP levels by more than 25-fold. Reconstitution of PAX5 and IKZF1 in samples from patients with pre-B ALL restored a non-permissive state and induced energy crisis and cell death. A CRISPR/Cas9-based screen of PAX5 and IKZF1 transcriptional targets identified the products of NR3C1 (encoding the glucocorticoid receptor), TXNIP (encoding a glucose-feedback sensor) and CNR2 (encoding a cannabinoid receptor) as central effectors of B-lymphoid restriction of glucose and energy supply. Notably, transport-independent lipophilic methyl-conjugates of pyruvate and tricarboxylic acid cycle metabolites bypassed the gatekeeper function of PAX5 and IKZF1 and readily enabled leukaemic transformation. Conversely, pharmacological TXNIP and CNR2 agonists and a small-molecule AMPK inhibitor strongly synergized with glucocorticoids, identifying TXNIP, CNR2 and AMPK as potential therapeutic targets. Furthermore, our results provide a mechanistic explanation for the empirical finding that glucocorticoids are effective in the treatment of B-lymphoid but not myeloid malignancies. Thus, B-lymphoid transcription factors

  7. Mitochondrial metabolism, reactive oxygen species, and macrophage function-fishing for insights.

    PubMed

    Hall, Christopher J; Sanderson, Leslie E; Crosier, Kathryn E; Crosier, Philip S

    2014-11-01

    Metabolism and defense mechanisms that protect against pathogens are two fundamental requirements for the survival of multicellular organisms. Research into metabolic disease has revealed these core mechanisms are highly co-dependent. This emerging field of research, termed immunometabolism, focuses on understanding how metabolism influences immunological processes and vice versa. It is now accepted that obesity influences the immune system and that obesity-driven inflammation contributes to many diseases including type 2 diabetes, cardiovascular disease and Alzheimer's disease. The immune response requires the reallocation of nutrients within immune cells to different metabolic pathways to satisfy energy demands and the production of necessary macromolecules. One aspect of immunometabolic research is understanding how these metabolic changes help regulate specific immune cell functions. It is hoped that further understanding of the pathways involved in managing this immunological-metabolic interface will reveal new ways to treat metabolic disease. Given their growing status as principle drivers of obesity-associated inflammation, monocytes/macrophages have received much attention when studying the consequences of inflammation within adipose tissue. Less is known regarding how metabolic changes within macrophages (metabolic reprogramming) influence their immune cell function. In this review, we focus on our current understanding of how monocytes/macrophages alter their intracellular metabolism during the immune response and how these changes dictate specific effector functions. In particular, the immunomodulatory functions of mitochondrial metabolism and mitochondrial reactive oxygen species. We also highlight how the attributes of the zebrafish model system can be exploited to reveal new mechanistic insights into immunometabolic processes.

  8. (13)C-labeled biochemical probes for the study of cancer metabolism with dynamic nuclear polarization-enhanced magnetic resonance imaging.

    PubMed

    Salamanca-Cardona, Lucia; Keshari, Kayvan R

    2015-01-01

    In recent years, advances in metabolic imaging have become dependable tools for the diagnosis and treatment assessment in cancer. Dynamic nuclear polarization (DNP) has recently emerged as a promising technology in hyperpolarized (HP) magnetic resonance imaging (MRI) and has reached clinical relevance with the successful visualization of [1-(13)C] pyruvate as a molecular imaging probe in human prostate cancer. This review focuses on introducing representative compounds relevant to metabolism that are characteristic of cancer tissue: aerobic glycolysis and pyruvate metabolism, glutamine addiction and glutamine/glutamate metabolism, and the redox state and ascorbate/dehydroascorbate metabolism. In addition, a brief introduction of probes that can be used to trace necrosis, pH changes, and other pathways relevant to cancer is presented to demonstrate the potential that HP MRI has to revolutionize the use of molecular imaging for diagnosis and assessment of treatments in cancer.

  9. Tensor-polarized structure functions: Tensor structure of deuteron in 2020's

    NASA Astrophysics Data System (ADS)

    Kumano, S.

    2014-10-01

    We explain spin structure for a spin-one hadron, in which there are new structure functions, in addition to the ones (F1, F2, g1, g2) which exist for the spin-1/2 nucleon, associated with its tensor structure. The new structure functions are b1, b2, b3, and b4 in deep inelastic scattering of a charged-lepton from a spin-one hadron such as the deuteron. Among them, twist- two functions are related by the Callan-Gross type relation b2 = 2xb1 in the Bjorken scaling limit. First, these new structure functions are introduced, and useful formulae are derived for projection operators of b1-4 from a hadron tensor Wμν. Second, a sum rule is explained for b1, and possible tensor-polarized distributions are discussed by using HERMES data in order to propose future experimental measurements and to compare them with theoretical models. A proposal was approved to measure b1 at the Thomas Jefferson National Accelerator Facility (JLab), so that much progress is expected for b1 in the near future. Third, formalisms of polarized proton-deuteron Drell-Yan processes are explained for probing especially tensor- polarized antiquark distributions, which were suggested by the HERMES data. The studies of the tensor-polarized structure functions will open a new era in 2020's for tensor-structure studies in terms of quark and gluon degrees of freedom, which are very different from ordinary descriptions in terms of nucleons and mesons.

  10. Enhanced preconcentration of selected chlorofluorocarbons on multiwalled carbon nanotubes with polar functionalities.

    PubMed

    Saridara, Chutarat; Hussain, Chaudhery Mustansar; Ragunath, Smruti; Mitra, Somenath

    2015-02-01

    Chromatographic monitoring of chlorofluorocarbons in air requires the preconcentration of these highly volatile species. In this paper, we present functionalized multiwalled carbon nanotubes as effective sorbents for a microtrap designed for chlorofluorocarbons preconcentration. Among the commercial carbons and carbon nanotubes studied, functionalization via carboxylation and propyl amine was most effective for dichlorofluoromethane and trichlorofluoromethane (Freon 11), which were selected as representative chlorofluorocarbons. The results show that carbon nanotubes functionalized with a polar groups led to as much as a 300% increase in breakthrough volume and the desorption bandwidth was reduced by 2.5 times.

  11. Functional interactions between Fat family cadherins in tissue morphogenesis and planar polarity

    PubMed Central

    Saburi, Sakura; Hester, Ian; Goodrich, Lisa; McNeill, Helen

    2012-01-01

    The atypical cadherin fat (ft) was originally discovered as a tumor suppressor in Drosophila and later shown to regulate a form of tissue patterning known as planar polarity. In mammals, four ft homologs have been identified (Fat1-4). Recently, we demonstrated that Fat4 plays a role in vertebrate planar polarity. Fat4 has the highest homology to ft, whereas other Fat family members are homologous to the second ft-like gene, ft2. Genetic studies in flies and mice imply significant functional differences between the two groups of Fat cadherins. Here, we demonstrate that Fat family proteins act both synergistically and antagonistically to influence multiple aspects of tissue morphogenesis. We find that Fat1 and Fat4 cooperate during mouse development to control renal tubular elongation, cochlear extension, cranial neural tube formation and patterning of outer hair cells in the cochlea. Similarly, Fat3 and Fat4 synergize to drive vertebral arch fusion at the dorsal midline during caudal vertebra morphogenesis. We provide evidence that these effects depend on conserved interactions with planar polarity signaling components. In flies, the transcriptional co-repressor Atrophin (Atro) physically interacts with Ft and acts as a component of Fat signaling for planar polarity. We find that the mammalian orthologs of atro, Atn1 and Atn2l, modulate Fat4 activity during vertebral arch fusion and renal tubular elongation, respectively. Moreover, Fat4 morphogenetic defects are enhanced by mutations in Vangl2, a ‘core’ planar cell polarity gene. These studies highlight the wide range and complexity of Fat activities and suggest that a Fat-Atrophin interaction is a conserved element of planar polarity signaling. PMID:22510986

  12. Cutting Edge: Murine Mast Cells Rapidly Modulate Metabolic Pathways Essential for Distinct Effector Functions.

    PubMed

    Phong, Binh; Avery, Lyndsay; Menk, Ashley V; Delgoffe, Greg M; Kane, Lawrence P

    2017-01-15

    There is growing appreciation that cellular metabolic and bioenergetic pathways do not play merely passive roles in activated leukocytes. Rather, metabolism has important roles in controlling cellular activation, differentiation, survival, and effector function. Much of this work has been performed in T cells; however, there is still very little information regarding mast cell metabolic reprogramming and its effect on cellular function. Mast cells perform important barrier functions and help control type 2 immune responses. In this study we show that murine bone marrow-derived mast cells rapidly alter their metabolism in response to stimulation through the FcεRI. We also demonstrate that specific metabolic pathways appear to be differentially required for the control of mast cell function. Manipulation of metabolic pathways may represent a novel point for the manipulation of mast cell activation.

  13. Updated knowledge about polyphenols: functions, bioavailability, metabolism, and health.

    PubMed

    Landete, J M

    2012-01-01

    Polyphenols are important constituents of food products of plant origin. Fruits, vegetables, and beverages are the main sources of phenolic compounds in the human diet. These compounds are directly related to sensory characteristics of foods such as flavor, astringency and color. Polyphenols are extensively metabolized both in tissues and by the colonic microbiota. Normally, the circulating polyphenols are glucuronidated and/or sulphated and no free aglycones are found in plasma. The presence of phenolic compounds in the diet is beneficial to health due to their antioxidant, anti-inflammatory, and vasodilating properties. The health effects of polyphenols depend on the amount consumed and their bioavailability. Moreover, polyphenols are able to kill or inhibit the growth of microorganisms such as bacteria, fungi, or protozoans. Some dietary polyphenols may have significant effects on the colonic flora providing a type of prebiotic effect. The anti-nutrient properties of polyphenols are also discussed in this paper. The antioxidant, anti-inflammatory, vasodilating, and prebiotic properties of polyphenols make them potential functional foods.

  14. Functional compartmentalization of oxidative and glycolytic metabolism in frog skin

    SciTech Connect

    Skul'skii, I.A.; Lapin, A.V.

    1985-07-01

    One of the basic functions of the epithelial cells of the skin of amphibians is unidirectional transport of Na/sup +/ from the environment into the blood. This transport is carried out in two stages. First, Na/sup +/ is absorbed from the environment by the epithelial cells through their apical membranes. Next, Na/sup +/ is actively drawn into the blood stream with the help of Na-K pumps which are located on the basolateral membranes. Huf, as early as 1957, proposed that ionic homeostasis of Na-transporting epithelial cells may be maintained at the expense of glycolysis, whereas the unidirectional transport of Na/sup +/ requires exclusively energy from oxidative metabolism. At that time, however, little was known about the nature of the Na-K pump and there were no isotopic data on permeability of epithelial cells to Na/sup +/ and K/sup +/. The authors confirm and update Huf's hypothesis in accordance with current knowledge. It was shown that anaerobic conditions (argon atmosphere) and various respiration inhibitors (rotenone, thallium) selectively inhibit unidirectional transport of Na/sup +/, as measured with the help of /sup 22/Na or short-circuit current, without influencing the concentration of sodium and potassium in the cells. The rate of penetration of Na/sup +/ through the apical membrane decrease by at least twice, but, irrespective of a significant flow of Na/sup +/ through the epithelial layer disappears.

  15. β-cell function is associated with metabolic syndrome in Mexican subjects

    PubMed Central

    Baez-Duarte, Blanca G; Sánchez-Guillén, María Del Carmen; Pérez-Fuentes, Ricardo; Zamora-Ginez, Irma; Leon-Chavez, Bertha Alicia; Revilla-Monsalve, Cristina; Islas-Andrade, Sergio

    2010-01-01

    Aims The clinical diagnosis of metabolic syndrome does not find any parameters to evaluate the insulin sensitivity (IS) or β-cell function. The evaluation of these parameters would detect early risk of developing metabolic syndrome. The aim of this study is to determine the relationship between β-cell function and presence of metabolic syndrome in Mexican subjects. Material and methods This study is part of the Mexican Survey on the Prevention of Diabetes (MexDiab Study) with headquarters in the city of Puebla, Mexico. The study comprised of 444 subjects of both genders, aged between 18 and 60 years and allocated into two study groups: (1) control group of individuals at metabolic balance without metabolic syndrome and (2) group composed of subjects with metabolic syndrome and diagnosed according to the criteria of the Third Report of the National Cholesterol Education Program Expert Panel on Defection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Anthropometric, biochemical, and clinical assessments were carried out. Results Average age of the subjects in the control group (n = 254) was 35.7 ± 11.5 years and 42.0 ± 10.7 years for subjects in the metabolic syndrome group (n = 190). Subjects at metabolic balance without metabolic syndrome showed decreased IS, increased insulin resistance (IR), and altered β-cell function. Individuals with metabolic syndrome showed a high prevalence (P ≤ 0.05) of family history of type 2 diabetes (T2D). This group also showed a significant metabolic imbalance with glucose and insulin levels and lipid profile outside the ranges considered safe to prevent the development of cardiovascular disease and T2D. Conclusion The main finding in this study was the detection of altered β-cell function, decreased IS, an increased IR in subjects at metabolic balance, and the progressive deterioration of β-cell function and IS in subjects with metabolic syndrome as the number of features of metabolic syndrome increases

  16. Myocardial Function and Lipid Metabolism in the Chronic Alcoholic Animal

    PubMed Central

    Regan, Timothy J.; Khan, Mohammad I.; Ettinger, Philip O.; Haider, Bunyad; Lyons, Michael M.; Oldewurtel, Henry A.; Weber, Marilyn

    1974-01-01

    In view of the variables that obscure the pathogenesis of cardiomyopathy, a study was undertaken in mongrel dogs fed ethanol as 36% of calories for up to 22 mo. Both the experimental and control groups maintained body weight, hematocrit, plasma vitamin, and protein levels. Left ventricular function was evaluated in the intact anesthetized dog using indicator dilution for end-diastolic and stroke volume determinations. During increased afterload with angiotensin, the ethanol group exhibited a larger rise of end-diastolic pressure (P<0.01), whereas end-diastolic and stroke volume responses were significantly less than in controls. Preload increments with saline elicited a significantly higher end-diastolic pressure rise in the ethanol group (P<0.01). No hypertrophy, inflammation, or fibrosis was present and it was postulated that the enhanced diastolic stiffness was related to accumulation of Alcian Blue-positive material in the ventricular interstitium. To evaluate myocardial lipid metabolism, [1-14C]oleic acid was infused systemically. Plasma specific activity and myocardial lipid uptake were similar in both groups. There was a significantly increased incorporation of label into triglyceride, associated with a reduced 14CO2 production, considered the basis for a twofold increment of triglyceride content. In addition, diminished incorporation of [14C]oleic acid into phospholipid was observed accompanied by morphologic abnormalities of cardiac cell membranes. Potassium loss and sodium gain, like the lipid alteration, was more prominent in the subendocardium. Thus, chronic ethanol ingestion in this animal model is associated with abnormalities of ventricular function without evident malnutrition, analogous to the preclinical malfunction described in the human alcoholic. Images PMID:4368946

  17. Density functional perturbational orbital theory of spin polarization in electronic systems. I. Formalism.

    PubMed

    Seo, Dong-Kyun

    2006-10-21

    A perturbational approach is presented for the general analysis of spin-polarization effect on electronic structures and energies within spin-density functional formalism. Explicit expressions for the changes in Kohn-Sham [Phys. Rev. 140, 1133 (1965)] orbital energies and coefficients as well as for the change in total electronic energy are derived upon using the local spin density and self-interaction-corrected exchange-correlation functionals. The application of the method for atoms provides analytical expressions for the exchange splitting energy and spin-polarization energy. The atomic exchange parameters are obtained from the expressions for the elements with Z=1-92 and they match well with Stoner exchange parameters for 3d metal elements.

  18. Serrano (sano) functions with the planar cell polarity genes to control tracheal tube length.

    PubMed

    Chung, SeYeon; Vining, Melissa S; Bradley, Pamela L; Chan, Chih-Chiang; Wharton, Keith A; Andrew, Deborah J

    2009-11-01

    Epithelial tubes are the functional units of many organs, and proper tube geometry is crucial for organ function. Here, we characterize serrano (sano), a novel cytoplasmic protein that is apically enriched in several tube-forming epithelia in Drosophila, including the tracheal system. Loss of sano results in elongated tracheae, whereas Sano overexpression causes shortened tracheae with reduced apical boundaries. Sano overexpression during larval and pupal stages causes planar cell polarity (PCP) defects in several adult tissues. In Sano-overexpressing pupal wing cells, core PCP proteins are mislocalized and prehairs are misoriented; sano loss or overexpression in the eye disrupts ommatidial polarity and rotation. Importantly, Sano binds the PCP regulator Dishevelled (Dsh), and loss or ectopic expression of many known PCP proteins in the trachea gives rise to similar defects observed with loss or gain of sano, revealing a previously unrecognized role for PCP pathway components in tube size control.

  19. Polarity functions' characterization and the mechanism of starch modification by DC glow discharge plasma.

    PubMed

    Khorram, S; Zakerhamidi, M S; Karimzadeh, Z

    2015-01-01

    The wheat starch was investigated, before and after exposure to the argon and oxygen glow discharge plasma, without any added chemical reagents, using a novel media polarity functions method. The mechanisms of modification of starch in plasma discharge irradiation were explained using some methods such as; NMR, IR spectroscopy, Kamlet-Abboud-Taft polarity functions (specific and nonspecific interaction) of modified starch. The starch modification, by plasma treatment, shows valuable changes with plasma gas and relative ionized or active species. Characterizations indicate that argon glow discharge plasma increases crosslink in C-2 site of starch. Also, oxygen plasma discharge irradiation tends to oxidize the OH group in C-6 site of carbonyl group. Furthermore, the reported mechanisms show the highest efficiency, because of the stereo-chemical orientation of active sites of starch and plasma potential of wall in plasma media.

  20. Direct determination of multipole moments of Cartesian Gaussian functions in spherical polar coordinates.

    PubMed

    Choi, Cheol Ho

    2004-02-22

    A new way of generating the multipole moments of Cartesian Gaussian functions in spherical polar coordinates has been established, bypassing the intermediary of Cartesian moment tensors. A new set of recurrence relations have also been derived for the resulting analytic integral values. The new method furnishes a conceptually simple and numerically efficient evaluation procedure for the multipole moments. The advantages over existing methods are documented. The results are relevant for the linear scaling quantum theories based on the fast multipole method.

  1. Mitochondrial metabolism in hematopoietic stem cells requires functional FOXO3

    PubMed Central

    Rimmelé, Pauline; Liang, Raymond; Bigarella, Carolina L; Kocabas, Fatih; Xie, Jingjing; Serasinghe, Madhavika N; Chipuk, Jerry; Sadek, Hesham; Zhang, Cheng Cheng; Ghaffari, Saghi

    2015-01-01

    Hematopoietic stem cells (HSC) are primarily dormant but have the potential to become highly active on demand to reconstitute blood. This requires a swift metabolic switch from glycolysis to mitochondrial oxidative phosphorylation. Maintenance of low levels of reactive oxygen species (ROS), a by-product of mitochondrial metabolism, is also necessary for sustaining HSC dormancy. Little is known about mechanisms that integrate energy metabolism with hematopoietic stem cell homeostasis. Here, we identify the transcription factor FOXO3 as a new regulator of metabolic adaptation of HSC. ROS are elevated in Foxo3−/− HSC that are defective in their activity. We show that Foxo3−/− HSC are impaired in mitochondrial metabolism independent of ROS levels. These defects are associated with altered expression of mitochondrial/metabolic genes in Foxo3−/− hematopoietic stem and progenitor cells (HSPC). We further show that defects of Foxo3−/− HSC long-term repopulation activity are independent of ROS or mTOR signaling. Our results point to FOXO3 as a potential node that couples mitochondrial metabolism with HSC homeostasis. These findings have critical implications for mechanisms that promote malignant transformation and aging of blood stem and progenitor cells. PMID:26209246

  2. Genome-Scale Metabolic Modeling of Archaea Lends Insight into Diversity of Metabolic Function

    PubMed Central

    2017-01-01

    Decades of biochemical, bioinformatic, and sequencing data are currently being systematically compiled into genome-scale metabolic reconstructions (GEMs). Such reconstructions are knowledge-bases useful for engineering, modeling, and comparative analysis. Here we review the fifteen GEMs of archaeal species that have been constructed to date. They represent primarily members of the Euryarchaeota with three-quarters comprising representative of methanogens. Unlike other reviews on GEMs, we specially focus on archaea. We briefly review the GEM construction process and the genealogy of the archaeal models. The major insights gained during the construction of these models are then reviewed with specific focus on novel metabolic pathway predictions and growth characteristics. Metabolic pathway usage is discussed in the context of the composition of each organism's biomass and their specific energy and growth requirements. We show how the metabolic models can be used to study the evolution of metabolism in archaea. Conservation of particular metabolic pathways can be studied by comparing reactions using the genes associated with their enzymes. This demonstrates the utility of GEMs to evolutionary studies, far beyond their original purpose of metabolic modeling; however, much needs to be done before archaeal models are as extensively complete as those for bacteria. PMID:28133437

  3. Metabolism

    MedlinePlus

    Metabolism refers to all the physical and chemical processes in the body that convert or use energy, ... Tortora GJ, Derrickson BH. Metabolism. In: Tortora GJ, Derrickson ... Physiology . 14th ed. Hoboken, NJ: John Wiley & Sons; 2014:chap ...

  4. Metabolism

    MedlinePlus

    ... El metabolismo Metabolism Basics Our bodies get the energy they need from food through metabolism, the chemical ... that convert the fuel from food into the energy needed to do everything from moving to thinking ...

  5. Jigsaw puzzle metasurface for multiple functions: polarization conversion, anomalous reflection and diffusion.

    PubMed

    Zhao, Yi; Cao, Xiangyu; Gao, Jun; Liu, Xiao; Li, Sijia

    2016-05-16

    We demonstrate a simple reconfigurable metasurface with multiple functions. Anisotropic tiles are investigated and manufactured as fundamental elements. Then, the tiles are combined in a certain sequence to construct a metasurface. Each of the tiles can be adjusted independently which is like a jigsaw puzzle and the whole metasurface can achieve diverse functions by different layouts. For demonstration purposes, we realize polarization conversion, anomalous reflection and diffusion by a jigsaw puzzle metasurface with 6 × 6 pieces of anisotropic tile. Simulated and measured results prove that our method offers a simple and effective strategy for metasurface design.

  6. The function of oxalic acid in the human metabolism.

    PubMed

    Robertson, Daniel Stewart

    2011-09-01

    Biochemical reactions in cells which involve oxalic acid are described. It is shown that this compound is required for the formation of uracil and orotic acid. The former is a component of RNA which is common to all cells in the human metabolism. On the basis of the biochemical reactions described a possible treatment to relieve the effects of calcium oxalate renal calculi whose origin is related to the metabolic concentration of oxalic acid is proposed.

  7. Comparative activity and functional ecology of permafrost soils and lithic niches in a hyper-arid polar desert.

    PubMed

    Goordial, Jacqueline; Davila, Alfonso; Greer, Charles W; Cannam, Rebecca; DiRuggiero, Jocelyne; McKay, Christopher P; Whyte, Lyle G

    2017-02-01

    Permafrost in the high elevation McMurdo Dry Valleys of Antarctica ranks among the driest and coldest on Earth. Permafrost soils appear to be largely inhospitable to active microbial life, but sandstone lithic microhabitats contain a trophically simple but functional cryptoendolithic community. We used metagenomic sequencing and activity assays to examine the functional capacity of permafrost soils and cryptoendolithic communities in University Valley, one of the most extreme regions in the Dry Valleys. We found metagenomic evidence that cryptoendolithic microorganisms are adapted to the harsh environment and capable of metabolic activity at in situ temperatures, possessing a suite of stress response and nutrient cycling genes to fix carbon under the fluctuating conditions that the sandstone rock would experience during the summer months. We additionally identified genes involved in microbial competition and cooperation within the cryptoendolithic habitat. In contrast, permafrost soils have a lower richness of stress response genes, and instead the metagenome is enriched in genes involved with dormancy and sporulation. The permafrost soils also have a large presence of phage genes and genes involved in the recycling of cellular material. Our results underlie two different habitability conditions under extreme cold and dryness: the permafrost soil which is enriched in traits which emphasize survival and dormancy, rather than growth and activity; and the cryptoendolithic environment that selects for organisms capable of growth under extremely oligotrophic, arid and cold conditions. This study represents the first metagenomic interrogation of Antarctic permafrost and polar cryptoendolithic microbial communities.

  8. Determination of the exchange interaction energy from the polarization expansion of the wave function

    NASA Astrophysics Data System (ADS)

    Gniewek, Piotr; Jeziorski, Bogumił

    2016-10-01

    The exchange contribution to the energy of the hydrogen atom interacting with a proton is calculated from the polarization expansion of the wave function using the conventional surface-integral formula and two formulas involving volume integrals: the formula of the symmetry-adapted perturbation theory (SAPT) and the variational formula recommended by us. At large internuclear distances R , all three formulas yield the correct expression -(2 /e ) R e-R , but they approximate it with very different convergence rates. In the case of the SAPT formula, the convergence is geometric with the error falling as 3-K, where K is the order of the applied polarization expansion. The error of the surface-integral formula decreases exponentially as aK/(K +1 ) , where a =ln2 - 1/2. The variational formula performs best, its error decays as K1 /2[aK/(K+1 ) ] 2 . These convergence rates are much faster than those resulting from approximating the wave function through the multipole expansion. This shows the efficiency of the partial resummation of the multipole series effected by the polarization expansion. Our results demonstrate also the benefits of incorporating the variational principle into the perturbation theory of molecular interactions.

  9. Finite element analysis of the dynamic behavior of radially polarized Functionally Graded Piezoelectric (FGP) structures

    NASA Astrophysics Data System (ADS)

    Kandasamy, Ramkumar; Cui, Fangsen

    2016-04-01

    In the traditional layered piezoelectric structures, high stress concentrations could cause the structural failure in interlayer surfaces due to repeated strain reversals. To overcome the performance limitations of these structures, the concept of Functionally Graded Materials (FGMs) has been introduced to improve the lifetime, integrity, and reliability of these structures. In this paper, the free and forced vibration of radially polarized Functionally Graded Piezoelectric (FGP) cylinders under different sets of loading are studied. Material properties such as piezoelectric, elastic and permittivity are assumed to change along its thickness, based on a specific gradation function. Four-parameter power law distribution is used to grade the volume fraction of the constituents comprising of PZT-5A and PZT-5H. Material property is assumed to be temperature dependent for a few numerical studies. The present modeling approach is validated by comparing the free and forced vibration of radially polarized Functionally Graded Piezoelectric (FGP) cylinders with those reported in the literature. The effects of material composition, loading and boundary conditions on the dynamic behavior of FGP cylinder are described. Since the modeling of functionally graded piezoelectric systems is challenging, the present study can help in the design and analysis of FGP cylinders.

  10. Nonuniqueness of magnetic fields and energy derivatives in spin-polarized density functional theory.

    PubMed

    Gál, T; Ayers, P W; De Proft, F; Geerlings, P

    2009-10-21

    The effect of the recently uncovered nonuniqueness of the external magnetic field B(r) corresponding to a given pair of density n(r) and spin density n(s)(r) on the derivative of the energy functional of spin-polarized density functional theory, and its implications for the definition of chemical reactivity descriptors, is examined. For ground states, the nonuniqueness of B(r) implies the nondifferentiability of the energy functional E(v,B)[n,n(s)] with respect to n(s)(r). It is shown, on the other hand, that this nonuniqueness allows the existence of the one-sided derivatives of E(v,B)[n,n(s)] with respect to n(s)(r). Although the N-electron ground state can always be obtained from the minimization of E(v,B)[n,n(s)] without any constraint on the spin number N(s)=integraln(s)(r)dr, the Lagrange multiplier mu(s) associated with the fixation of N(s) does not vanish even for ground states. Mu(s) is identified as the left- or right-side derivative of the total energy with respect to N(s), which justifies the interpretation of mu(s) as a (spin) chemical potential. This is relevant not only for the spin-polarized generalization of conceptual density functional theory, the spin chemical potential being one of the elementary reactivity descriptors, but also for the extension of the thermodynamical analogy of density functional theory for the spin-polarized case. For higher-order reactivity indices, B(r)'s nonuniqueness has similar implications as for mu(s), leading to a split of the indices with respect to N(s) into one-sided reactivity descriptors.

  11. Adaptive robust image registration approach based on adequately sampling polar transform and weighted angular projection function

    NASA Astrophysics Data System (ADS)

    Wei, Zhao; Tao, Feng; Jun, Wang

    2013-10-01

    An efficient, robust, and accurate approach is developed for image registration, which is especially suitable for large-scale change and arbitrary rotation. It is named the adequately sampling polar transform and weighted angular projection function (ASPT-WAPF). The proposed ASPT model overcomes the oversampling problem of conventional log-polar transform. Additionally, the WAPF presented as the feature descriptor is robust to the alteration in the fovea area of an image, and reduces the computational cost of the following registration process. The experimental results show two major advantages of the proposed method. First, it can register images with high accuracy even when the scale factor is up to 10 and the rotation angle is arbitrary. However, the maximum scaling estimated by the state-of-the-art algorithms is 6. Second, our algorithm is more robust to the size of the sampling region while not decreasing the accuracy of the registration.

  12. Work function mediated by deposition of ultrathin polar FeO on Pt(111)

    NASA Astrophysics Data System (ADS)

    Lu, Shuangzan; Qin, Zhihui; Guo, Qinmin; Cao, Gengyu

    2017-01-01

    Significant work function changes from bare Pt(111) surface to 1 monolayer and 2 monolayers of ultrathin iron oxide (FeO) films on it are investigated by means of scanning tunneling microscopy/spectroscopy (STM/STS). With FeO layer-by-layer growth, a continuous reduction of the work function along with the surface vacuum level (VL) shifting is observed. We found that the compression of the electron spill-out at the metal-oxide interface and the substantial reconstruction of 2 ML FeO film, respectively, make major contributions to the first and the second reductions of the work function. The rectifying effect in FeO films is also observed, which is attributed to the downward shift of band alignment imposed by the total change in surface dipole. Our work shows that the polar oxide films play an important role to adjust surface electronic structures for enhancing device functionality.

  13. Identification of Functional Differences in Metabolic Networks Using Comparative Genomics and Constraint-Based Models

    PubMed Central

    Hamilton, Joshua J.; Reed, Jennifer L.

    2012-01-01

    Genome-scale network reconstructions are useful tools for understanding cellular metabolism, and comparisons of such reconstructions can provide insight into metabolic differences between organisms. Recent efforts toward comparing genome-scale models have focused primarily on aligning metabolic networks at the reaction level and then looking at differences and similarities in reaction and gene content. However, these reaction comparison approaches are time-consuming and do not identify the effect network differences have on the functional states of the network. We have developed a bilevel mixed-integer programming approach, CONGA, to identify functional differences between metabolic networks by comparing network reconstructions aligned at the gene level. We first identify orthologous genes across two reconstructions and then use CONGA to identify conditions under which differences in gene content give rise to differences in metabolic capabilities. By seeking genes whose deletion in one or both models disproportionately changes flux through a selected reaction (e.g., growth or by-product secretion) in one model over another, we are able to identify structural metabolic network differences enabling unique metabolic capabilities. Using CONGA, we explore functional differences between two metabolic reconstructions of Escherichia coli and identify a set of reactions responsible for chemical production differences between the two models. We also use this approach to aid in the development of a genome-scale model of Synechococcus sp. PCC 7002. Finally, we propose potential antimicrobial targets in Mycobacterium tuberculosis and Staphylococcus aureus based on differences in their metabolic capabilities. Through these examples, we demonstrate that a gene-centric approach to comparing metabolic networks allows for a rapid comparison of metabolic models at a functional level. Using CONGA, we can identify differences in reaction and gene content which give rise to different

  14. A set of d-polarization functions for pseudo-potential basis sets of the main group elements AlBi and f-type polarization functions for Zn, Cd, Hg

    NASA Astrophysics Data System (ADS)

    Höllwarth, A.; Böhme, M.; Dapprich, S.; Ehlers, A. W.; Gobbi, A.; Jonas, V.; Köhler, K. F.; Stegmann, R.; Veldkamp, A.; Frenking, G.

    1993-06-01

    A set of five-component d-type polarization functions has been optimized for the main group elements AlBi at the energetically lowest lying s 2p n electronic states for use with the effective core potentials of Hay and Wadt at the CISD level of theory. Also a set of f-type polarization functions is suggested for the elements Zn, Cd and Hg.

  15. Analyzing the function of small GTPases by microinjection of plasmids into polarized epithelial cells.

    PubMed

    Cook, Rita Nokes; Ang, Su Fen; Kang, Richard Seung-on; Fölsch, Heike

    2011-05-31

    Epithelial cells polarize their plasma membrane into biochemically and functionally distinct apical and basolateral domains where the apical domain faces the 'free' surfaces and the basolateral membrane is in contact with the substrate and neighboring cells. Both membrane domains are separated by tight junctions, which form a diffusion barrier. Apical-basolateral polarization can be recapitulated successfully in culture when epithelial cells such as Madin-Darby Canine Kidney (MDCK) cells are seeded at high density on polycarbonate filters and cultured for several days. Establishment and maintenance of cell polarity is regulated by an array of small GTPases of the Ras superfamily such as RalA, Cdc42, Rab8, Rab10 and Rab13. Like all GTPases these proteins cycle between an inactive GDP-bound state and an active GTP-bound state. Specific mutations in the nucleotide binding regions interfere with this cycling. For example, Rab13T22N is permanently locked in the GDP-form and thus dubbed 'dominant negative', whereas Rab13Q67L can no longer hydrolyze GTP and is thus locked in a 'dominant active' state. To analyze their function in cells both dominant negative and dominant active alleles of GTPases are typically expressed at high levels to interfere with the function of the endogenous proteins. An elegant way to achieve high levels of overexpression in a short amount of time is to introduce the plasmids encoding the relevant proteins directly into the nuclei of polarized cells grown on filter supports using microinjection technique. This is often combined with the co-injection of reporter plasmids that encode plasma membrane receptors that are specifically sorted to the apical or basolateral domain. A cargo frequently used to analyze cargo sorting to the basolateral domain is a temperature sensitive allele of the vesicular stomatitis virus glycoprotein (VSVGts045). This protein cannot fold properly at 39°C and will thus be retained in the endoplasmic reticulum (ER) while

  16. A Strategy for Functional Interpretation of Metabolomic Time Series Data in Context of Metabolic Network Information

    PubMed Central

    Nägele, Thomas; Fürtauer, Lisa; Nagler, Matthias; Weiszmann, Jakob; Weckwerth, Wolfram

    2016-01-01

    The functional connection of experimental metabolic time series data with biochemical network information is an important, yet complex, issue in systems biology. Frequently, experimental analysis of diurnal, circadian, or developmental dynamics of metabolism results in a comprehensive and multidimensional data matrix comprising information about metabolite concentrations, protein levels, and/or enzyme activities. While, irrespective of the type of organism, the experimental high-throughput analysis of the transcriptome, proteome, and metabolome has become a common part of many systems biological studies, functional data integration in a biochemical and physiological context is still challenging. Here, an approach is presented which addresses the functional connection of experimental time series data with biochemical network information which can be inferred, for example, from a metabolic network reconstruction. Based on a time-continuous and variance-weighted regression analysis of experimental data, metabolic functions, i.e., first-order derivatives of metabolite concentrations, were related to time-dependent changes in other biochemically relevant metabolic functions, i.e., second-order derivatives of metabolite concentrations. This finally revealed time points of perturbed dependencies in metabolic functions indicating a modified biochemical interaction. The approach was validated using previously published experimental data on a diurnal time course of metabolite levels, enzyme activities, and metabolic flux simulations. To support and ease the presented approach of functional time series analysis, a graphical user interface including a test data set and a manual is provided which can be run within the numerical software environment Matlab®. PMID:27014700

  17. A Strategy for Functional Interpretation of Metabolomic Time Series Data in Context of Metabolic Network Information.

    PubMed

    Nägele, Thomas; Fürtauer, Lisa; Nagler, Matthias; Weiszmann, Jakob; Weckwerth, Wolfram

    2016-01-01

    The functional connection of experimental metabolic time series data with biochemical network information is an important, yet complex, issue in systems biology. Frequently, experimental analysis of diurnal, circadian, or developmental dynamics of metabolism results in a comprehensive and multidimensional data matrix comprising information about metabolite concentrations, protein levels, and/or enzyme activities. While, irrespective of the type of organism, the experimental high-throughput analysis of the transcriptome, proteome, and metabolome has become a common part of many systems biological studies, functional data integration in a biochemical and physiological context is still challenging. Here, an approach is presented which addresses the functional connection of experimental time series data with biochemical network information which can be inferred, for example, from a metabolic network reconstruction. Based on a time-continuous and variance-weighted regression analysis of experimental data, metabolic functions, i.e., first-order derivatives of metabolite concentrations, were related to time-dependent changes in other biochemically relevant metabolic functions, i.e., second-order derivatives of metabolite concentrations. This finally revealed time points of perturbed dependencies in metabolic functions indicating a modified biochemical interaction. The approach was validated using previously published experimental data on a diurnal time course of metabolite levels, enzyme activities, and metabolic flux simulations. To support and ease the presented approach of functional time series analysis, a graphical user interface including a test data set and a manual is provided which can be run within the numerical software environment Matlab®.

  18. Blind polarization demultiplexing by constructing a cost function for coherent optical PDM-OFDM.

    PubMed

    Yu, Zhenming; Chen, Minghua; Chen, Hongwei; Yi, Xingwen; Yang, Sigang; Xie, Shizhong

    2015-07-13

    We propose a training symbols-free polarization demultiplexing method by constructing a cost function (CCF-PDM) for coherent optical PDM-OFDM. This method is applicable for high-speed, wide-bandwidth OFDM signals, different subcarrier modulation formats and long-haul transmission. It shows comparable performance with that of conventional method but without overhead and converges fast. Since the neighboring subcarriers experience similar polarization effects, we set the initial matrix parameters by the neighboring subcarrier to reduce the number of iteration for the gradient algorithm and prevent swapping the data of the two orthogonal polarizations. We verify this method in experiment by transmitting 66.6-Gb/s PDM-OFDM signal with 4QAM subcarrier modulation over 5440 km SSMF and 133.3-Gb/s PDM-OFDM signal with 16QAM subcarrier modulation over 960 km SSMF respectively. We compare its performance with that of training symbols. We also analyze the convergence speed of this method.

  19. Cross-polarization microwave radar return at severe wind conditions: laboratory model and geophysical model function.

    NASA Astrophysics Data System (ADS)

    Troitskaya, Yuliya; Abramov, Victor; Ermoshkin, Alexey; Zuikova, Emma; Kazakov, Vassily; Sergeev, Daniil; Kandaurov, Alexandr

    2014-05-01

    Satellite remote sensing is one of the main techniques of monitoring severe weather conditions over the ocean. The principal difficulty of the existing algorithms of retrieving wind based on dependence of microwave backscattering cross-section on wind speed (Geophysical Model Function, GMF) is due to its saturation at winds exceeding 25 - 30 m/s. Recently analysis of dual- and quad-polarization C-band radar return measured from satellite Radarsat-2 suggested that the cross-polarized radar return has much higher sensitivity to the wind speed than co-polarized back scattering [1] and conserved sensitivity to wind speed at hurricane conditions [2]. Since complete collocation of these data was not possible and time difference in flight legs and SAR images acquisition was up to 3 hours, these two sets of data were compared in [2] only statistically. The main purpose of this paper is investigation of the functional dependence of cross-polarized radar cross-section on the wind speed in laboratory experiment. Since cross-polarized radar return is formed due to scattering at small-scale structures of the air-sea interface (short-crested waves, foam, sprays, etc), which are well reproduced in laboratory conditions, then the approach based on laboratory experiment on radar scattering of microwaves at the water surface under hurricane wind looks feasible. The experiments were performed in the Wind-wave flume located on top of the Large Thermostratified Tank of the Institute of Applied Physics, where the airflow was produced in the flume with the straight working part of 10 m and operating cross section 0.40?0.40 sq. m, the axis velocity can be varied from 5 to 25 m/s. Microwave measurements were carried out by a coherent Doppler X-band (3.2 cm) scatterometer with the consequent receive of linear polarizations. Experiments confirmed higher sensitivity to the wind speed of the cross-polarized radar return. Simultaneously parameters of the air flow in the turbulent boundary layer

  20. Regulated Synthesis and Functions of Laminin 5 in Polarized Madin-Darby Canine Kidney Epithelial Cells

    PubMed Central

    Mak, Grace Z.; Kavanaugh, Gina M.; Buschmann, Mary M.; Stickley, Shaun M.; Koch, Manuel; Goss, Kathleen Heppner; Waechter, Holly; Zuk, Anna

    2006-01-01

    Renal tubular epithelial cells synthesize laminin (LN)5 during regeneration of the epithelium after ischemic injury. LN5 is a truncated laminin isoform of particular importance in the epidermis, but it is also constitutively expressed in a number of other epithelia. To investigate the role of LN5 in morphogenesis of a simple renal epithelium, we examined the synthesis and function of LN5 in the spreading, proliferation, wound-edge migration, and apical–basal polarization of Madin-Darby canine kidney (MDCK) cells. MDCK cells synthesize LN5 only when subconfluent, and they degrade the existing LN5 matrix when confluent. Through the use of small-interfering RNA to knockdown the LN5 α3 subunit, we were able to demonstrate that LN5 is necessary for cell proliferation and efficient wound-edge migration, but not apical–basal polarization. Surprisingly, suppression of LN5 production caused cells to spread much more extensively than normal on uncoated surfaces, and exogenous keratinocyte LN5 was unable to rescue this phenotype. MDCK cells also synthesized laminin α5, a component of LN10, that independent studies suggest may form an assembled basal lamina important for polarization. Overall, our findings indicate that LN5 is likely to play an important role in regulating cell spreading, migration, and proliferation during reconstitution of a continuous epithelium. PMID:16775009

  1. MIRAGE: a functional genomics-based approach for metabolic network model reconstruction and its application to cyanobacteria networks.

    PubMed

    Vitkin, Edward; Shlomi, Tomer

    2012-11-29

    Genome-scale metabolic network reconstructions are considered a key step in quantifying the genotype-phenotype relationship. We present a novel gap-filling approach, MetabolIc Reconstruction via functionAl GEnomics (MIRAGE), which identifies missing network reactions by integrating metabolic flux analysis and functional genomics data. MIRAGE's performance is demonstrated on the reconstruction of metabolic network models of E. coli and Synechocystis sp. and validated via existing networks for these species. Then, it is applied to reconstruct genome-scale metabolic network models for 36 sequenced cyanobacteria amenable for constraint-based modeling analysis and specifically for metabolic engineering. The reconstructed network models are supplied via standard SBML files.

  2. Thyroid function in childhood obesity and metabolic comorbidity.

    PubMed

    Pacifico, Lucia; Anania, Caterina; Ferraro, Flavia; Andreoli, Gian Marco; Chiesa, Claudio

    2012-02-18

    Childhood obesity is a worldwide health problem and its prevalence is increasing steadily and dramatically all over the world. Obese subjects have a much greater likelihood than normal-weight children of acquiring dyslipidemia, elevated blood pressure, and impaired glucose metabolism, which significantly increase their risk of cardiovascular and metabolic diseases. Elevated TSH concentrations in association with normal or slightly elevated free T4 and/or free T3 levels have been consistently found in obese subjects, but the mechanisms underlying these thyroid hormonal changes are still unclear. Whether higher TSH in childhood obesity is adaptive, increasing metabolic rate in an attempt to reduce further weight gain, or indicates subclinical hypothyroidism or resistance and thereby contributes to lipid and/or glucose dysmetabolism, remains controversial. This review highlights current evidence on thyroid involvement in obese children and discusses the current controversy regarding the relationship between thyroid hormonal derangements and obesity-related metabolic changes (hypertension, dyslipidemia, hyperglycemia and insulin resistance, nonalcoholic fatty liver disease) in such population. Moreover, the possible mechanisms linking thyroid dysfunction and pediatric obesity are reviewed. Finally, the potential role of lifestyle intervention as well as of therapy with thyroid hormone in the treatment of thyroid abnormalities in childhood obesity is discussed.

  3. Metabolic fate and function of dietary glutamate in the gut

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glutamate is a major constituent of dietary protein and is also consumed in many prepared foods as an additive in the form of monosodium glutamate. Evidence from human and animal studies indicates that glutamate is a major oxidative fuel for the gut and that dietary glutamate is extensively metabol...

  4. Impact of Metabolism on T-Cell Differentiation and Function and Cross Talk with Tumor Microenvironment

    PubMed Central

    Kouidhi, Soumaya; Elgaaied, Amel Benammar; Chouaib, Salem

    2017-01-01

    The immune system and metabolism are highly integrated and multilevel interactions between metabolic system and T lymphocyte signaling and fate exist. Accumulating evidence indicates that the regulation of nutrient uptake and utilization in T cells is critically important for the control of their differentiation and manipulating metabolic pathways in these cells can shape their function and survival. This review will discuss some potential cell metabolism pathways involved in shaping T lymphocyte function and differentiation. It will also describe show subsets of T cells have specific metabolic requirements and signaling pathways that contribute to their respective function. Examples showing the apparent similarity between cancer cell metabolism and T cells during activation are illustrated and finally some mechanisms being used by tumor microenvironment to orchestrate T-cell metabolic dysregulation and the subsequent emergence of immune suppression are discussed. We believe that targeting T-cell metabolism may provide an additional opportunity to manipulate T-cell function in the development of novel therapeutics. PMID:28348562

  5. Dissection of Arabidopsis ADP-RIBOSYLATION FACTOR 1 Function in Epidermal Cell PolarityW⃞

    PubMed Central

    Xu, Jian; Scheres, Ben

    2005-01-01

    Vesicle trafficking is essential for the generation of asymmetries, which are central to multicellular development. Core components of the vesicle transport machinery, such as ADP-ribosylation factor (ARF) GTPases, have been studied primarily at the single-cell level. Here, we analyze developmental functions of the ARF1 subclass of the Arabidopsis thaliana multigene ARF family. Six virtually identical ARF1 genes are ubiquitously expressed, and single loss-of-function mutants in these genes reveal no obvious developmental phenotypes. Fluorescence colocalization studies reveal that ARF1 is localized to the Golgi apparatus and endocytic organelles in both onion (Allium cepa) and Arabidopsis cells. Apical-basal polarity of epidermal cells, reflected by the position of root hair outgrowth, is affected when ARF1 mutants are expressed at early stages of cell differentiation but after they exit mitosis. Genetic interactions during root hair tip growth and localization suggest that the ROP2 protein is a target of ARF1 action, but its localization is slowly affected upon ARF1 manipulation when compared with that of Golgi and endocytic markers. Localization of a second potential target of ARF1 action, PIN2, is also affected with slow kinetics. Although extreme redundancy precludes conventional genetic dissection of ARF1 functions, our approach separates different ARF1 downstream networks involved in local and specific aspects of cell polarity. PMID:15659621

  6. Molecular density functional theory: application to solvation and electron-transfer thermodynamics in polar solvents.

    PubMed

    Borgis, Daniel; Gendre, Lionel; Ramirez, Rosa

    2012-03-01

    A molecular density functional theory of solvation is presented. The solvation properties of an arbitrary solute in a given solvent, both described by a molecular force field, can be obtained by minimization of a position- and orientation-dependent free-energy density functional. In the homogeneous reference fluid approximation, the unknown excess term of the functional can be approximated by the angular-dependent direct correlation function of the pure solvent. This function can be extracted from a preliminary MD simulation of the pure solvent by computing the angular-dependent pair distribution function and solving subsequently the molecular Ornstein-Zernike equation. The corresponding functional can then be minimized on a three-dimensional cubic grid for positions and a Gauss-Legendre angular grid for orientations to provide the solvation free energy of embedded molecules at the same time as the solvent three-dimensional microscopic structure. This functional minimization procedure is much more efficient than direct molecular dynamics simulations combined with thermodynamic integration schemes. The approach is shown to be also pertinent to the molecular-level determination of electron-transfer properties such as reaction free energy and reorganization energy. It is illustrated for molecular solvation and photochemical electron-transfer reactions in acetonitrile, a prototypical polar aprotic solvent.

  7. A body composition model to estimate mammalian energy stores and metabolic rates from body mass and body length, with application to polar bears.

    PubMed

    Molnár, Péter K; Klanjscek, Tin; Derocher, Andrew E; Obbard, Martyn E; Lewis, Mark A

    2009-08-01

    Many species experience large fluctuations in food availability and depend on energy from fat and protein stores for survival, reproduction and growth. Body condition and, more specifically, energy stores thus constitute key variables in the life history of many species. Several indices exist to quantify body condition but none can provide the amount of stored energy. To estimate energy stores in mammals, we propose a body composition model that differentiates between structure and storage of an animal. We develop and parameterize the model specifically for polar bears (Ursus maritimus Phipps) but all concepts are general and the model could be easily adapted to other mammals. The model provides predictive equations to estimate structural mass, storage mass and storage energy from an appropriately chosen measure of body length and total body mass. The model also provides a means to estimate basal metabolic rates from body length and consecutive measurements of total body mass. Model estimates of body composition, structural mass, storage mass and energy density of 970 polar bears from Hudson Bay were consistent with the life history and physiology of polar bears. Metabolic rate estimates of fasting adult males derived from the body composition model corresponded closely to theoretically expected and experimentally measured metabolic rates. Our method is simple, non-invasive and provides considerably more information on the energetic status of individuals than currently available methods.

  8. Plasma phospholipid transfer protein (PLTP) modulates adaptive immune functions through alternation of T helper cell polarization

    PubMed Central

    Desrumaux, Catherine; Lemaire-Ewing, Stéphanie; Ogier, Nicolas; Yessoufou, Akadiri; Hammann, Arlette; Sequeira-Le Grand, Anabelle; Deckert, Valérie; Pais de Barros, Jean-Paul; Le Guern, Naïg; Guy, Julien; Khan, Naim A; Lagrost, Laurent

    2016-01-01

    Objective: Plasma phospholipid transfer protein (PLTP) is a key determinant of lipoprotein metabolism, and both animal and human studies converge to indicate that PLTP promotes atherogenesis and its thromboembolic complications. Moreover, it has recently been reported that PLTP modulates inflammation and immune responses. Although earlier studies from our group demonstrated that PLTP can modify macrophage activation, the implication of PLTP in the modulation of T-cell-mediated immune responses has never been investigated and was therefore addressed in the present study. Approach and results: In the present study, we demonstrated that PLTP deficiency in mice has a profound effect on CD4+ Th0 cell polarization, with a shift towards the anti-inflammatory Th2 phenotype under both normal and pathological conditions. In a model of contact hypersensitivity, a significantly impaired response to skin sensitization with the hapten-2,4-dinitrofluorobenzene (DNFB) was observed in PLTP-deficient mice compared to wild-type (WT) mice. Interestingly, PLTP deficiency in mice exerted no effect on the counts of total white blood cells, lymphocytes, granulocytes, or monocytes in the peripheral blood. Moreover, PLTP deficiency did not modify the amounts of CD4+ and CD8+ T lymphocyte subsets. However, PLTP-deficiency, associated with upregulation of the Th2 phenotype, was accompanied by a significant decrease in the production of the pro-Th1 cytokine interleukin 18 by accessory cells. Conclusions: For the first time, this work reports a physiological role for PLTP in the polarization of CD4+ T cells toward the pro-inflammatory Th1 phenotype. PMID:26320740

  9. Metabolic network structure and function in bacteria goes beyond conserved enzyme components

    PubMed Central

    Bazurto, Jannell V.; Downs, Diana M.

    2016-01-01

    For decades, experimental work has laid the foundation for our understanding of the linear and branched pathways that are integrated to form the metabolic networks on which life is built. Genetic and biochemical approaches applied in model organisms generate empirical data that correlate genes, gene products and their biological activities. In the post-genomic era, these results have served as the basis for the genome annotation that is routinely used to infer the metabolic capabilities of an organism and mathematically model the presumed metabolic network structure. At large, genome annotation and metabolic network reconstructions have demystified genomic content of non-culturable microorganisms and allowed researchers to explore the breadth of metabolisms in silico. Mis-annotation aside, it is unclear whether in silico reconstructions of metabolic structure from component parts accurately captures the higher levels of network organization and flux distribution. For this approach to provide accurate predictions, one must assume that the conservation of metabolic components leads to conservation of metabolic network architecture and function. This assumption has not been rigorously tested. Here we describe the implications of a recent study (MBio 5;7(1): e01840-15), which demonstrated that conservation of metabolic components was not sufficient to predict network structure and function. PMID:28357363

  10. The human NAD metabolome: Functions, metabolism and compartmentalization

    PubMed Central

    Nikiforov, Andrey; Kulikova, Veronika; Ziegler, Mathias

    2015-01-01

    Abstract The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD+ and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools. PMID:25837229

  11. Complex pectin metabolism by gut bacteria reveals novel catalytic functions.

    PubMed

    Ndeh, Didier; Rogowski, Artur; Cartmell, Alan; Luis, Ana S; Baslé, Arnaud; Gray, Joseph; Venditto, Immacolata; Briggs, Jonathon; Zhang, Xiaoyang; Labourel, Aurore; Terrapon, Nicolas; Buffetto, Fanny; Nepogodiev, Sergey; Xiao, Yao; Field, Robert A; Zhu, Yanping; O'Neill, Malcolm A; Urbanowicz, Breeanna R; York, William S; Davies, Gideon J; Abbott, D Wade; Ralet, Marie-Christine; Martens, Eric C; Henrissat, Bernard; Gilbert, Harry J

    2017-03-22

    The metabolism of carbohydrate polymers drives microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron uses the most structurally complex glycan known: the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but 1 of its 21 distinct glycosidic linkages. The deconstruction of rhamnogalacturonan-II side chains and backbone are coordinated to overcome steric constraints, and the degradation involves previously undiscovered enzyme families and catalytic activities. The degradation system informs revision of the current structural model of rhamnogalacturonan-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycan in the human diet.

  12. The human NAD metabolome: Functions, metabolism and compartmentalization.

    PubMed

    Nikiforov, Andrey; Kulikova, Veronika; Ziegler, Mathias

    2015-01-01

    The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD(+) and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools.

  13. Planar Cell Polarity Effector Fritz Interacts with Dishevelled and Has Multiple Functions in Regulating PCP.

    PubMed

    Wang, Ying; Naturale, Victor F; Adler, Paul N

    2017-03-03

    The Planar cell Polarity Effector (PPE) genes inturned, fuzzy and fritz are downstream components in the frizzled/starry night signaling pathway, and their function is instructed by upstream Planar Cell Polarity (PCP) core genes such as frizzled and disheveled PPE proteins accumulate asymmetrically in wing cells and function in a protein complex mediated by direct interactions between In and Frtz and In and Fy. How the PCP proteins instruct the accumulation of PPE protein is unknown. We found a likely direct interaction between Dishevelled and Fritz and Dishevelled and Fuzzy that could play a role in this. We previously found that mild over expression of frtz rescued a weak in allele. To determine if this was due to extra Frtz stabilizing mutant In or due to Frtz being able to bypass the need for In we generate a precise deletion of the inturned gene (in(PD) ). We found that mild overexpression of Fritz partially rescued in(PD) , indicating that fritz has In independent activity in PCP. Previous studies of PPE proteins used fixed tissues, and did not provide any insights into the dynamic properties of PPE proteins. We used CRISPR/Cas9 genome editing technology to edit the fritz gene to add a green fluorescent protein tag. fritz(m)(NeonGreen) provides complete rescue activity and works well for in vivo imaging. Our data showed that Fritz is very dynamic in epidermal cells and preferentially distributed to discrete membrane subdomains ("puncta"). Surprisingly, we found it in stripes in developing bristles.

  14. The polarization response function and the dielectric permittivity of a plasma

    SciTech Connect

    Gnavi, G.; Gratton, F.

    1984-09-01

    We give a simple direct derivation of the polarization response function h for linear electrostatic excitations of a plasma (without magnetic field) considering the effect of a percussion on the electrons. The physical meaning of the procedure is discussed, thus bringing into light basic facts of the plasma dielectric behavior. The result h = S/sub p/ fo(x/t) (where f/sub o/ is the electron distribution function in velocity space and /sub p/ the plasma frequency) is obtained without passing through the Vlasov-Poisson equations as in the standard theory. We show that the equivalence between the present method and the classic Landau analysis rests on properties of the Fourier transform applied on velocity space.

  15. Integrating the Kuramoto-Sivashinsky equation in polar coordinates: Application of the distributed approximating functional approach

    SciTech Connect

    Zhang, D.S.; Wei, G.W.; Kouri, D.J. ); Hoffman, D.K. ); Gorman, M.; Palacios, A. ); Gunaratne, G.H. The Institute of Fundamental Studies, Kandy )

    1999-09-01

    An algorithm is presented to integrate nonlinear partial differential equations, which is particularly useful when accurate estimation of spatial derivatives is required. It is based on an analytic approximation method, referred to as distributed approximating functionals (DAF[close quote]s), which can be used to estimate a function and a finite number of derivatives with a specified accuracy. As an application, the Kuramoto-Sivashinsky (KS) equation is integrated in polar coordinates. Its integration requires accurate estimation of spatial derivatives, particularly close to the origin. Several stationary and nonstationary solutions of the KS equation are presented, and compared with analogous states observed in the combustion front of a circular burner. A two-ring, nonuniform counter-rotating state has been obtained in a KS model simulation of such a burner. [copyright] [ital 1999] [ital The American Physical Society

  16. Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases.

    PubMed

    Casero, Robert A; Marton, Laurence J

    2007-05-01

    The polyamines spermidine and spermine and their diamine precursor putrescine are naturally occurring, polycationic alkylamines that are essential for eukaryotic cell growth. The requirement for and the metabolism of polyamines are frequently dysregulated in cancer and other hyperproliferative diseases, thus making polyamine function and metabolism attractive targets for therapeutic intervention. Recent advances in our understanding of polyamine function, metabolic regulation, and differences between normal cells and tumour cells with respect to polyamine biology, have reinforced the interest in this target-rich pathway for drug development.

  17. Polarization Ray Tracing Calculation of Polarized Bidirectional Reflectance Distribution Function (pBRDF) of Microfaceted Surfaces to Investigate Multiple Reflection Effects

    NASA Astrophysics Data System (ADS)

    Bradley, C. L.; Kupinski, M.; Xu, F.; Diner, D. J.; Chipman, R. A.

    2015-12-01

    Remote sensing algorithms for aerosol retrieval rely on surface reflectance models for the extraction of path radiance of aerosol scattering in top of atmosphere measurements. A well-defined surface boundary condition is necessary due to the variability in the surface albedo and bidirectional reflectance distribution function. Polarization measurements can help constrain the surface model. Prior work features polarization measurements taken by Jet Propulsion Laboratory's Ground-based Multiangle SpectroPolarimetric Imager (GroundMSPI). This work has shown that an analytical model that assumes singly reflected light from a rough surface comprised of microfacets sufficiently represents the polarized reflectance of natural surfaces (such as grass), but is less successful for manmade objects. For the linear Stokes parameters (I, Q, U), a single reflection of unpolarized light will result in a null U Stokes parameter relative to the scattering plane. However, some GroundMSPI measurements exhibit a non-zero U Stokes parameter. We show that multiple reflections may be a cause for this discrepancy by using a polarization ray trace (PRT) routine to calculate the polarized Bidirectional Reflectance Distribution Function (pBRDF) for a microfaceted surface. While the effect of multiple reflections, particularly for double reflections, is an order of magnitude smaller compared to single reflections, we show non-zero U Stokes parameters generated from multiple reflections. Furthermore, we have found that for illumination-view geometries with scattering angles less than ~45 degrees, Q and U parameters can have similar magnitude. We report on the magnitude of this effect and compare the PRT simulations to non-zero U measurements from GroundMSPI.

  18. Density functional theory analysis of the impact of steric interaction on the function of switchable polarity solvents

    SciTech Connect

    McNally, Joshua S.; Noll, Bruce; Orme, Christopher J.; Wilson, Aaron D.

    2015-05-04

    Here, a density functional theory (DFT) analysis has been performed to explore the impact of steric interactions on the function of switchable polarity solvents (SPS) and their implications on a quantitative structure-activity relationship (QSAR) model previously proposed for SPS. An x-ray crystal structure of the N,N-dimethylcyclohexylammonium bicarbonate (Hdmcha) salt has been solved as an asymmetric unit containing two cation/anion pairs, with a hydrogen bonding interaction observed between the bicarbonate anions, as well as between the cation and anion in each pair. DFT calculations provide an optimized structure of Hdmcha that closely resembles experimental data and reproduces the cation/anion interaction with the inclusion of a dielectric field. Relaxed potential energy surface (PES) scans have been performed on Hdmcha-based computational model compounds, differing in the size of functional group bonded to the nitrogen center, to assess the steric impact of the group on the relative energy and structural properties of the compound. Results suggest that both the length and amount of branching associated with the substituent impact the energetic limitations on rotation of the group along the N-R bond and NC-R bond, and disrupt the energy minimized position of the hydrogen bonded bicarbonate group. The largest interaction resulted from functional groups that featured five bonds between the ammonium proton and a proton on a functional group with the freedom of rotation to form a pseudo-six membered ring which included both protons.

  19. Density functional theory analysis of the impact of steric interaction on the function of switchable polarity solvents

    DOE PAGES

    McNally, Joshua S.; Noll, Bruce; Orme, Christopher J.; ...

    2015-05-04

    Here, a density functional theory (DFT) analysis has been performed to explore the impact of steric interactions on the function of switchable polarity solvents (SPS) and their implications on a quantitative structure-activity relationship (QSAR) model previously proposed for SPS. An x-ray crystal structure of the N,N-dimethylcyclohexylammonium bicarbonate (Hdmcha) salt has been solved as an asymmetric unit containing two cation/anion pairs, with a hydrogen bonding interaction observed between the bicarbonate anions, as well as between the cation and anion in each pair. DFT calculations provide an optimized structure of Hdmcha that closely resembles experimental data and reproduces the cation/anion interaction withmore » the inclusion of a dielectric field. Relaxed potential energy surface (PES) scans have been performed on Hdmcha-based computational model compounds, differing in the size of functional group bonded to the nitrogen center, to assess the steric impact of the group on the relative energy and structural properties of the compound. Results suggest that both the length and amount of branching associated with the substituent impact the energetic limitations on rotation of the group along the N-R bond and NC-R bond, and disrupt the energy minimized position of the hydrogen bonded bicarbonate group. The largest interaction resulted from functional groups that featured five bonds between the ammonium proton and a proton on a functional group with the freedom of rotation to form a pseudo-six membered ring which included both protons.« less

  20. Metabolism

    MedlinePlus

    ... and intestines. Several of the hormones of the endocrine system are involved in controlling the rate and direction ... For Kids For Parents MORE ON THIS TOPIC Endocrine System What Can I Do About My High Metabolism? ...

  1. Metabolism

    MedlinePlus

    ... symptoms. Metabolic diseases and conditions include: Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism is caused ... or through surgery or radiation treatments. Hypothyroidism (pronounced: hi-po-THIGH-roy-dih-zum). Hypothyroidism is caused ...

  2. Preserved pontine glucose metabolism in Alzheimer disease: A reference region for functional brain image (PET) analysis

    SciTech Connect

    Minoshima, Satoshi; Frey, K.A.; Foster, N.L.; Kuhl, D.W.

    1995-07-01

    Our goal was to examine regional preservation of energy metabolism in Alzheimer disease (AD) and to evaluate effects of PET data normalization to reference regions. Regional metabolic rates in the pons, thalamus, putamen, sensorimotor cortex, visual cortex, and cerebellum (reference regions) were determined stereotaxically and examined in 37 patients with probable AD and 22 normal controls based on quantitative {sup 18}FDG-PET measurements. Following normalization of metabolic rates of the parietotemporal association cortex and whole brain to each reference region, distinctions of the two groups were assessed. The pons showed the best preservation of glucose metabolism in AD. Other reference regions showed relatively preserved metabolism compared with the parietotemporal association cortex and whole brain, but had significant metabolic reduction. Data normalization to the pons not only enhanced statistical significance of metabolic reduction in the parietotemporal association cortex, but also preserved the presence of global cerebral metabolic reduction indicated in analysis of the quantitative data. Energy metabolism in the pons in probable AD is well preserved. The pons is a reliable reference for data normalization and will enhance diagnostic accuracy and efficiency of quantitative and nonquantitative functional brain imaging. 39 refs., 2 figs., 3 tabs.

  3. High density lipoprotein and metabolic disease: Potential benefits of restoring its functional properties

    PubMed Central

    Klancic, Teja; Woodward, Lavinia; Hofmann, Susanna M.; Fisher, Edward A.

    2016-01-01

    Background High density lipoproteins (HDLs) are thought to be atheroprotective and to reduce the risk of cardiovascular disease (CVD). Besides their antioxidant, antithrombotic, anti-inflammatory, anti-apoptotic properties in the vasculature, HDLs also improve glucose metabolism in skeletal muscle. Scope of the review Herein, we review the functional role of HDLs to improve metabolic disorders, especially those involving insulin resistance and to induce regression of CVD with a particular focus on current pharmacological treatment options as well as lifestyle interventions, particularly exercise. Major conclusions Functional properties of HDLs continue to be considered important mediators to reverse metabolic dysfunction and to regress atherosclerotic cardiovascular disease. Lifestyle changes are often recommended to reduce the risk of CVD, with exercise being one of the most important of these. Understanding how exercise improves HDL function will likely lead to new approaches to battle the expanding burden of obesity and the metabolic syndrome. PMID:27110484

  4. Rodent Models for the Analysis of Tissue Clock Function in Metabolic Rhythms Research

    PubMed Central

    Tsang, Anthony H.; Astiz, Mariana; Leinweber, Brinja; Oster, Henrik

    2017-01-01

    The circadian timing system consists on a distributed network of cellular clocks that together coordinate 24-h rhythms of physiology and behavior. Clock function and metabolism are tightly coupled, from the cellular to the organismal level. Genetic and non-genetic approaches in rodents have been employed to study circadian clock function in the living organism. Due to the ubiquitous expression of clock genes and the intricate interaction between the circadian system and energy metabolism, genetic approaches targeting specific tissue clocks have been used to assess their contribution in systemic metabolic processes. However, special requirements regarding specificity and efficiency have to be met to allow for valid conclusions from such studies. In this review, we provide a brief summary of different approaches developed for dissecting tissue clock function in the metabolic context in rodents, compare their strengths and weaknesses, and suggest new strategies in assessing tissue clock output and the consequences of circadian clock disruption in vivo. PMID:28243224

  5. Functional ESCRT machinery is required for constitutive recycling of claudin-1 and maintenance of polarity in vertebrate epithelial cells.

    PubMed

    Dukes, Joseph D; Fish, Laura; Richardson, Judith D; Blaikley, Elizabeth; Burns, Samir; Caunt, Christopher J; Chalmers, Andrew D; Whitley, Paul

    2011-09-01

    Genetic screens in Drosophila have identified regulators of endocytic trafficking as neoplastic tumor suppressor genes. For example, Drosophila endosomal sorting complex required for transport (ESCRT) mutants lose epithelial polarity and show increased cell proliferation, suggesting that ESCRT proteins could function as tumor suppressors. In this study, we show for the for the first time to our knowledge that ESCRT proteins are required to maintain polarity in mammalian epithelial cells. Inhibition of ESCRT function caused the tight junction protein claudin-1 to accumulate in intracellular vesicles. In contrast E-cadherin and occludin localization was unaffected. We investigated the cause of this accumulation and show that claudin-1 is constitutively recycled in kidney, colon, and lung epithelial cells, identifying claudin-1 recycling as a newly described feature of diverse epithelial cell types. This recycling requires ESCRT function, explaining the accumulation of intracellular claudin-1 when ESCRT function is inhibited. We further demonstrate that small interfering RNA knockdown of the ESCRT protein Tsg101 causes epithelial monolayers to lose their polarized organization and interferes with the establishment of a normal epithelial permeability barrier. ESCRT knockdown also reduces the formation of correctly polarized three-dimensional cysts. Thus, in mammalian epithelial cells, ESCRT function is required for claudin-1 trafficking and for epithelial cell polarity, supporting the hypothesis that ESCRT proteins function as tumor suppressors.

  6. Metabolic and Demographic Feedbacks Shape the Emergent Spatial Structure and Function of Microbial Communities

    PubMed Central

    Estrela, Sylvie; Brown, Sam P.

    2013-01-01

    Microbes are predominantly found in surface-attached and spatially structured polymicrobial communities. Within these communities, microbial cells excrete a wide range of metabolites, setting the stage for interspecific metabolic interactions. The links, however, between metabolic and ecological interactions (functional relationships), and species spatial organization (structural relationships) are still poorly understood. Here, we use an individual-based modelling framework to simulate the growth of a two-species surface-attached community where food (resource) is traded for detoxification (service) and investigate how metabolic constraints of individual species shape the emergent structural and functional relationships of the community. We show that strong metabolic interdependence drives the emergence of mutualism, robust interspecific mixing, and increased community productivity. Specifically, we observed a striking and highly stable emergent lineage branching pattern, generating a persistent lineage mixing that was absent when the metabolic exchange was removed. These emergent community properties are driven by demographic feedbacks, such that aid from neighbouring cells directly enhances focal cell growth, which in turn feeds back to neighbour fecundity. In contrast, weak metabolic interdependence drives conflict (exploitation or competition), and in turn greater interspecific segregation. Together, these results support the idea that species structural and functional relationships represent the net balance of metabolic interdependencies. PMID:24385891

  7. Contrast sensitivity functions to stimuli defined in Cartesian, polar and hyperbolic coordinates.

    PubMed

    Zana, Y; Cavalcanti, A C G T

    2005-01-01

    Recent electrophysiological studies indicate that cells in the LGN, V1, V2, and V4 areas in monkeys are specifically sensitive to Cartesian, polar and hyperbolic stimuli. We have characterized the contrast sensitivity functions (CSF) to stimuli defined in these coordinates with the two-alternatives forced-choice paradigm. CSFs to Cartesian, concentric, and hyperbolic stimuli have had similar shapes, with peak sensitivity at approximately 3 c/deg. However, the Cartesian CSF peak sensitivity has been at least 0.1 log units higher than that to stimuli in any other coordinate system. The concentric-Bessel CSF has a low-pass shape, peaking at 1.5 c/deg or below. The radial CSF has a bell shape with maximum sensitivity at 8 c/360 degrees. Only the concentric-Bessel CSF could be explained in terms of the components of maximum amplitude of the Fourier transform. Neural models, which in previous studies predicted the responses to Cartesian and polar Glass patterns, failed to account for the full CSFs data.

  8. Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier function

    PubMed Central

    Alves, Marco G.; Martins, Ana D.; Cavaco, José E.; Socorro, Sílvia; Oliveira, Pedro F.

    2013-01-01

    Blood testis barrier (BTB) is one of the tightest blood-barriers controlling the entry of substances into the intratubular fluid. Diabetes Mellitus (DM) is an epidemic metabolic disease concurrent with falling fertility rates, which provokes severe detrimental BTB alterations. It induces testicular alterations, disrupting the metabolic cooperation between the cellular constituents of BTB, with dramatic consequences on sperm quality and fertility. As Sertoli cells are involved in the regulation of spermatogenesis, providing nutritional support for germ cells, any metabolic alteration in these cells derived from DM may be responsible for spermatogenesis disruption, playing a crucial role in fertility/subfertility associated with this pathology. These cells have a glucose sensing machinery that reacts to hormonal fluctuations and several mechanisms to counteract hyper/hypoglycemic events. The role of DM on Sertoli/BTB glucose metabolism dynamics and the metabolic molecular mechanisms through which DM and insulin deregulation alter its functioning, affecting male reproductive potential will be discussed. PMID:24665384

  9. The enhanced spin-polarized transport behaviors through cobalt benzene-porphyrin-benzene molecular junctions: the effect of functional groups.

    PubMed

    Cheng, Jue-Fei; Zhou, Liping; Wen, Zhongqian; Yan, Qiang; Han, Qin; Gao, Lei

    2017-05-04

    The modification effects of the groups amino (NH2) and nitro (NO2) on the spin polarized transport properties of the cobalt benzene-porphyrin-benzene (Co-BPB) molecule coupled to gold (Au) nanowire electrodes are investigated by the nonequilibrium Green's function method combined with the density functional theory. The calculation results show that functional groups can lead to the significant spin-filter effect, enhanced low-bias negative differential resistance (NDR) behavior and novel reverse rectifying effect in Co-BPB molecular junction. The locations and types of functional groups have distinct influences on spin-polarized transport performances. The configuration with NH2 group substituting H atom in central porphyrin ring has larger spin-down current compared to that with NO2 substitution. And Co-BPB molecule junction with NH2 group substituting H atom in side benzene ring shows reverse rectifying effect. Detailed analyses confirm that NH2 and NO2 group substitution change the spin-polarized transferred charge, which makes the highest occupied molecular orbitals (HOMO) of spin-down channel of Co-BPB closer to the Fermi level. And the shift of HOMO strengthens the spin-polarized coupling between the molecular orbitals and the electrodes, leading to the enhanced spin-polarized behavior. Our findings might be useful in the design of multi-functional molecular devices in the future.

  10. Microbial community assembly and metabolic function during mammalian corpse decomposition.

    PubMed

    Metcalf, Jessica L; Xu, Zhenjiang Zech; Weiss, Sophie; Lax, Simon; Van Treuren, Will; Hyde, Embriette R; Song, Se Jin; Amir, Amnon; Larsen, Peter; Sangwan, Naseer; Haarmann, Daniel; Humphrey, Greg C; Ackermann, Gail; Thompson, Luke R; Lauber, Christian; Bibat, Alexander; Nicholas, Catherine; Gebert, Matthew J; Petrosino, Joseph F; Reed, Sasha C; Gilbert, Jack A; Lynne, Aaron M; Bucheli, Sibyl R; Carter, David O; Knight, Rob

    2016-01-08

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

  11. Biosynthesis, function and metabolic engineering of plant volatile organic compounds.

    PubMed

    Dudareva, Natalia; Klempien, Antje; Muhlemann, Joëlle K; Kaplan, Ian

    2013-04-01

    Plants synthesize an amazing diversity of volatile organic compounds (VOCs) that facilitate interactions with their environment, from attracting pollinators and seed dispersers to protecting themselves from pathogens, parasites and herbivores. Recent progress in -omics technologies resulted in the isolation of genes encoding enzymes responsible for the biosynthesis of many volatiles and contributed to our understanding of regulatory mechanisms involved in VOC formation. In this review, we largely focus on the biosynthesis and regulation of plant volatiles, the involvement of floral volatiles in plant reproduction as well as their contribution to plant biodiversity and applications in agriculture via crop-pollinator interactions. In addition, metabolic engineering approaches for both the improvement of plant defense and pollinator attraction are discussed in light of methodological constraints and ecological complications that limit the transition of crops with modified volatile profiles from research laboratories to real-world implementation.

  12. Microbial community assembly and metabolic function during mammalian corpse decomposition

    USGS Publications Warehouse

    Metcalf, Jessica L; Xu, Zhenjiang Zech; Weiss, Sophie; Lax, Simon; Van Treuren, Will; Hyde, Embriette R.; Song, Se Jin; Amir, Amnon; Larsen, Peter; Sangwan, Naseer; Haarmann, Daniel; Humphrey, Greg C; Ackermann, Gail; Thompson, Luke R; Lauber, Christian; Bibat, Alexander; Nicholas, Catherine; Gebert, Matthew J; Petrosino, Joseph F; Reed, Sasha C.; Gilbert, Jack A; Lynne, Aaron M; Bucheli, Sibyl R; Carter, David O; Knight, Rob

    2016-01-01

    Vertebrate corpse decomposition provides an important stage in nutrient cycling in most terrestrial habitats, yet microbially mediated processes are poorly understood. Here we combine deep microbial community characterization, community-level metabolic reconstruction, and soil biogeochemical assessment to understand the principles governing microbial community assembly during decomposition of mouse and human corpses on different soil substrates. We find a suite of bacterial and fungal groups that contribute to nitrogen cycling and a reproducible network of decomposers that emerge on predictable time scales. Our results show that this decomposer community is derived primarily from bulk soil, but key decomposers are ubiquitous in low abundance. Soil type was not a dominant factor driving community development, and the process of decomposition is sufficiently reproducible to offer new opportunities for forensic investigations.

  13. Psychosocial and metabolic function by smoking status in individuals with binge eating disorder and obesity.

    PubMed

    Udo, Tomoko; White, Marney A; Barnes, Rachel D; Ivezaj, Valentina; Morgan, Peter; Masheb, Robin M; Grilo, Carlos M

    2016-02-01

    Individuals with binge eating disorder (BED) report smoking to control appetite and weight. Smoking in BED is associated with increased risk for comorbid psychiatric disorders, but its impact on psychosocial functioning and metabolic function has not been evaluated. Participants were 429 treatment-seeking adults (72.4% women; mean age 46.2±11.0years old) with BED comorbid with obesity. Participants were categorized into current smokers (n=66), former smokers (n=145), and never smokers (n=218). Smoking status was unrelated to most historical eating/weight variables and to current eating disorder psychopathology. Smoking status was associated with psychiatric, psychosocial, and metabolic functioning. Compared with never smokers, current smokers were more likely to meet lifetime diagnostic criteria for alcohol (OR=5.51 [95% CI=2.46-12.33]) and substance use disorders (OR=7.05 [95% CI=3.37-14.72]), poorer current physical quality of life, and increased risk for metabolic syndrome (OR=1.80 [95% CI=0.97-3.35]) and related metabolic risks (reduced HDL, elevated total cholesterol). On the other hand, the odds of meeting criteria for lifetime psychiatric comorbidity or metabolic abnormalities were not significantly greater in former smokers, relative to never smokers. Our findings suggest the importance of promoting smoking cessation in treatment-seeking patients with BED and obesity for its potential long-term implications for psychiatric and metabolic functioning.

  14. Enlarging the color gamut of liquid crystal displays with a functional reflective polarizer.

    PubMed

    Chen, Haiwei; Zhu, Ruidong; Tan, Guanjun; Li, Ming-Chun; Lee, Seok-Lyul; Wu, Shin-Tson

    2017-01-09

    We propose to add a functional reflective polarizer (FRP) in the backlight unit to suppress the crosstalk between red, green and blue color filters of a liquid crystal display (LCD) panel. When incorporated with a commercial two-phosphor-converted white light-emitting diode (2pc-WLED), the color gamut of the LCD can be improved from 92% to 115% NTSC standard, which is comparable to the cadmium-based quantum dot (QD) backlight. If a narrow-band color filter is employed, the color gamut can be further enhanced to 135% NTSC. Our design offers an alternative approach to QDs, while keeping low cost and long lifetime. Such a simple yet efficient approach would find widespread applications for enlarging the color gamut of LCDs.

  15. Chronic Alcohol Ingestion in Rats Alters Lung Metabolism, Promotes Lipid Accumulation, and Impairs Alveolar Macrophage Functions

    PubMed Central

    Romero, Freddy; Shah, Dilip; Duong, Michelle; Stafstrom, William; Hoek, Jan B.; Kallen, Caleb B.; Lang, Charles H.

    2014-01-01

    Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and

  16. Planar Cell Polarity Effector Fritz Interacts with Dishevelled and Has Multiple Functions in Regulating PCP

    PubMed Central

    Wang, Ying; Naturale, Victor F.; Adler, Paul N.

    2017-01-01

    The Planar cell Polarity Effector (PPE) genes inturned, fuzzy, and fritz are downstream components in the frizzled/starry night signaling pathway, and their function is instructed by upstream Planar Cell Polarity (PCP) core genes such as frizzled and dishevelled. PPE proteins accumulate asymmetrically in wing cells and function in a protein complex mediated by direct interactions between In and Frtz and In and Fy. How the PCP proteins instruct the accumulation of PPE protein is unknown. We found a likely direct interaction between Dishevelled and Fritz and Dishevelled and Fuzzy that could play a role in this. We previously found that mild overexpression of frtz rescued a weak in allele. To determine if this was due to extra Frtz stabilizing mutant In or due to Frtz being able to bypass the need for In we generate a precise deletion of the inturned gene (inPD). We found that mild overexpression of Fritz partially rescued inPD, indicating that fritz has In independent activity in PCP. Previous studies of PPE proteins used fixed tissues, and did not provide any insights into the dynamic properties of PPE proteins. We used CRISPR/Cas9 genome editing technology to edit the fritz gene to add a green fluorescent protein tag. fritzmNeonGreen provides complete rescue activity and works well for in vivo imaging. Our data showed that Fritz is very dynamic in epidermal cells and preferentially distributed to discrete membrane subdomains (“puncta”). Surprisingly, we found it in stripes in developing bristles. PMID:28258110

  17. Intestinal microbiota in metabolic diseases: from bacterial community structure and functions to species of pathophysiological relevance.

    PubMed

    Clavel, Thomas; Desmarchelier, Charles; Haller, Dirk; Gérard, Philippe; Rohn, Sascha; Lepage, Patricia; Daniel, Hannelore

    2014-07-01

    The trillions of bacterial cells that colonize the mammalian digestive tract influence both host physiology and the fate of dietary compounds. Gnotobionts and fecal transplantation have been instrumental in revealing the causal role of intestinal bacteria in energy homeostasis and metabolic dysfunctions such as type-2 diabetes. However, the exact contribution of gut bacterial metabolism to host energy balance is still unclear and knowledge about underlying molecular mechanisms is scant. We have previously characterized cecal bacterial community functions and host responses in diet-induced obese mice using omics approaches. Based on these studies, we here discuss issues on the relevance of mouse models, give evidence that the metabolism of cholesterol-derived compounds by gut bacteria is of particular importance in the context of metabolic disorders and that dominant species of the family Coriobacteriaceae are good models to study these functions.

  18. Macrophages and Mitochondria: A Critical Interplay Between Metabolism, Signaling, and the Functional Activity.

    PubMed

    Tur, J; Vico, T; Lloberas, J; Zorzano, A; Celada, A

    2017-01-01

    Macrophages are phagocytic cells that participate in a broad range of cellular functions and they are key regulators of innate immune responses and inflammation. Mitochondria are highly dynamic endosymbiotic organelles that play key roles in cellular metabolism and apoptosis. Mounting evidence suggests that mitochondria are involved in the interplay between metabolism and innate immune responses. The ability of these organelles to alter the metabolic profile of a cell, thereby allowing an appropriate response to each situation, is crucial for the correct establishment of immune responses. Furthermore, mitochondria act as scaffolds for many proteins involved in immune signaling pathways and as such they are able to modulate the function of these proteins. Finally, mitochondria release molecules, such as reactive oxygen species, which directly regulate the immune response. In summary, mitochondria can be considered as core components in the regulation of innate immune signaling. Here we discuss the intricate relationship between mitochondria, metabolism, intracellular signaling, and innate immune responses in macrophages.

  19. A worm of one's own: how helminths modulate host adipose tissue function and metabolism.

    PubMed

    Guigas, Bruno; Molofsky, Ari B

    2015-09-01

    Parasitic helminths have coexisted with human beings throughout time. Success in eradicating helminths has limited helminth-induced morbidity and mortality but is also correlated with increasing rates of 'western' diseases, including metabolic syndrome and type 2 diabetes. Recent studies in mice describe how type 2 immune cells, traditionally associated with helminth infection, maintain adipose tissue homeostasis and promote adipose tissue beiging, protecting against obesity and metabolic dysfunction. Here, we review these studies and discuss how helminths and helminth-derived molecules may modulate these physiologic pathways to improve metabolic functions in specific tissues, such as adipose and liver, as well as at the whole-organism level.

  20. Circadian rhythms and the regulation of metabolic tissue function and energy homeostasis.

    PubMed

    Zvonic, Sanjin; Floyd, Z Elizabeth; Mynatt, Randall L; Gimble, Jeffrey M

    2007-03-01

    Circadian oscillators play an indispensable role in the coordination of physiological processes with the cyclic changes in the physical environment. A significant number of recent clinical and molecular studies suggest that circadian biology may play an important role in the regulation of adipose and other metabolic tissue functions. In this discussion, we present the hypothesis that circadian dysfunction may be involved in the pathogenesis of obesity, type 2 diabetes, and the metabolic syndrome.

  1. Beyond polarity: functional membrane domains in astrocytes and Müller cells.

    PubMed

    Derouiche, Amin; Pannicke, Thomas; Haseleu, Julia; Blaess, Sandra; Grosche, Jens; Reichenbach, Andreas

    2012-11-01

    Various ependymoglial cells display varying degrees of process specialization, in particular processes contacting mesenchymal borders (pia, blood vessels, vitreous body), or those lining the ventricular surface. Within the neuropil, glial morphology, cellular contacts, and interaction partners are complex. It appears that glial processes contacting neurons, specific parts of neurons, or mesenchymal or ventricular borders are characterized by specialized membranes. We propose a concept of membrane domains in addition to the existing concept of ependymoglial polarity. Such membrane domains are equipped with certain membrane-bound proteins, enabling them to function in their specific environment. This review focuses on Müller cells and astrocytes and discusses exemplary the localization of established glial markers in membrane domains. We distinguish three functional glial membrane domains based on their typical molecular arrangement. The domain of the endfoot specifically displays the complex of dystrophin-associated proteins, aquaporin 4 and the potassium channel Kir4.1. We show that the domain of microvilli and the peripheral glial process in the Müller cell share the presence of ezrin, as do peripheral astrocyte processes. As a third domain, the Müller cell has peripheral glial processes related to a specific subtype of synapse. Although many details remain to be studied, the idea of glial membrane domains may permit new insights into glial function and pathology.

  2. Plasma protein regulation of platelet function and metabolism.

    PubMed

    Hansen, M S; Bang, N U

    1979-04-02

    This reviews summarizes our evidence suggesting that the plasma protein enviroment influences platelet aggregation potential and metabolic activity. Cationic proteins are capable of restoring the aggreation potential of washed human platelets. The aggregation restoring effect of gamma globulin is inhibited by more anionic proteins in subfractions of Cohn fraction IV and fractions V and VI. Artificial enhancement of the net negative charge of plasma proteins through acylation produces derivatives capable of inhibiting platelet rich plasma. The oxygen consumption of washed human platelets is lower than in platelet rich plasma while the lactate production is identical. Autologus plasma, albumin or IgG immunoglobulin restores the oxygen consumption of washed platelets to values comparable to those obtained for platelet rich plasma, while the lactate production is unaffected. Fibrinogen on IgA myeloma protein increases the lactate production, but not the oxygen consumption. Cyclic AMP levels are considerably lower in washed platelets than in platelet rich plasma. Gamma globulin and albumin causes a futher decrease, which is progressive with time. Fibrinogen causes no change in platelet cyclic AMP content. It is suggested that these observations may in part be explained by the equilibriun between anionic and cationic proteins in the platelet microenvironment. This hypothesis appears applicable in certain situations.

  3. Metabolic classification of microbial genomes using functional probes

    PubMed Central

    2012-01-01

    Background Microorganisms able to grow under artificial culture conditions comprise only a small proportion of the biosphere's total microbial community. Until recently, scientists have been unable to perform thorough analyses of difficult-to-culture microorganisms due to limitations in sequencing technology. As modern techniques have dramatically increased sequencing rates and rapidly expanded the number of sequenced genomes, in addition to traditional taxonomic classifications which focus on the evolutionary relationships of organisms, classifications of the genomes based on alternative points of view may help advance our understanding of the delicate relationships of organisms. Results We have developed a proteome-based method for classifying microbial species. This classification method uses a set of probes comprising short, highly conserved amino acid sequences. For each genome, in silico translation is performed to obtained its proteome, based on which a probe-set frequency pattern is generated. Then, the probe-set frequency patterns are used to cluster the proteomes/genomes. Conclusions Features of the proposed method include a high running speed in challenge of a large number of genomes, and high applicability for classifying organisms with incomplete genome sequences. Moreover, the probe-set clustering method is sensitive to the metabolic phenotypic similarities/differences among species and is thus supposed potential for the classification or differentiation of closely-related organisms. PMID:22537274

  4. L-carnitine--metabolic functions and meaning in humans life.

    PubMed

    Pekala, Jolanta; Patkowska-Sokoła, Bozena; Bodkowski, Robert; Jamroz, Dorota; Nowakowski, Piotr; Lochyński, Stanisław; Librowski, Tadeusz

    2011-09-01

    L-Carnitine is an endogenous molecule involved in fatty acid metabolism, biosynthesized within the human body using amino acids: L-lysine and L-methionine, as substrates. L-Carnitine can also be found in many foods, but red meats, such as beef and lamb, are the best choices for adding carnitine into the diet. Good carnitine sources also include fish, poultry and milk. Essentially, L-carnitine transports the chains of fatty acids into the mitochondrial matrix, thus allowing the cells to break down fat and get energy from the stored fat reserves. Recent studies have started to shed light on the beneficial effects of L-carnitine when used in various clinical therapies. Because L-carnitine and its esters help reduce oxidative stress, they have been proposed as a treatment for many conditions, i.e. heart failure, angina and weight loss. For other conditions, such as fatigue or improving exercise performance, L-carnitine appears safe but does not seem to have a significant effect. The presented review of the literature suggests that continued studies are required before L-carnitine administration could be recommended as a routine procedure in the noted disorders. Further research is warranted in order to evaluate the biochemical, pharmacological, and physiological determinants of the response to carnitine supplementation, as well as to determine the potential benefits of carnitine supplements in selected categories of individuals who do not have fatty acid oxidation defects.

  5. Simulated microgravity enhances oligodendrocyte mitochondrial function and lipid metabolism.

    PubMed

    Espinosa-Jeffrey, Araceli; Nguyen, Kevin; Kumar, Shalini; Toshimasa, Ochiai; Hirose, Ryuji; Reue, Karen; Vergnes, Laurent; Kinchen, Jason; Vellis, Jean de

    2016-12-01

    The primary energy sources of mammalian cells are proteins, fats, and sugars that are processed by well-known biochemical mechanisms that have been discovered and studied in 1G (terrestrial gravity). Here we sought to determine how simulated microgravity (sim-µG) impacts both energy and lipid metabolism in oligodendrocytes (OLs), the myelin-forming cells in the central nervous system. We report increased mitochondrial respiration and increased glycolysis 24 hr after exposure to sim-µG. Moreover, examination of the secretome after 3 days' exposure of OLs to sim-µG increased the Krebs cycle (Krebs and Weitzman, ) flux in sim-µG. The secretome study also revealed a significant increase in the synthesis of fatty acids and complex lipids such as 1,2-dipalmitoyl-GPC (5.67); lysolipids like 1-oleoyl-GPE (4.48) were also increased by microgravity. Although longer-chain lipids were not observed in this study, it is possible that at longer time points OLs would have continued moving forward toward the synthesis of lipids that constitute myelin. For centuries, basic developmental biology research has been the pillar of an array of discoveries that have led to clinical applications; we believe that studies using microgravity will open new avenues to our understanding of the brain in health and disease-in particular, to the discovery of new molecules and mechanisms impossible to unveil while in 1G. © 2016 Wiley Periodicals, Inc.

  6. Molecular changes in hepatic metabolism and transport in cirrhosis and their functional importance

    PubMed Central

    Dietrich, Christoph G; Götze, Oliver; Geier, Andreas

    2016-01-01

    Liver cirrhosis is the common endpoint of many hepatic diseases and represents a relevant risk for liver failure and hepatocellular carcinoma. The progress of liver fibrosis and cirrhosis is accompanied by deteriorating liver function. This review summarizes the regulatory and functional changes in phase I and phase II metabolic enzymes as well as transport proteins and provides an overview regarding lipid and glucose metabolism in cirrhotic patients. Interestingly, phase I enzymes are generally downregulated transcriptionally, while phase II enzymes are mostly preserved transcriptionally but are reduced in their function. Transport proteins are regulated in a specific way that resembles the molecular changes observed in obstructive cholestasis. Lipid and glucose metabolism are characterized by insulin resistance and catabolism, leading to the disturbance of energy expenditure and wasting. Possible non-invasive tests, especially breath tests, for components of liver metabolism are discussed. The heterogeneity and complexity of changes in hepatic metabolism complicate the assessment of liver function in individual patients. Additionally, studies in humans are rare, and species differences preclude the transferability of data from rodents to humans. In clinical practice, some established global scores or criteria form the basis for the functional evaluation of patients with liver cirrhosis, but difficult treatment decisions such as selection for transplantation or resection require further research regarding the application of existing non-invasive tests and the development of more specific tests. PMID:26755861

  7. Polarized Imaging Nephelometer for Field and Aircraft Measurements of Aerosol Phase Function

    NASA Astrophysics Data System (ADS)

    Dolgos, G.; Martins, J.

    2012-12-01

    Aerosols have a significant impact on the radiative balance and water cycle of our planet through influencing atmospheric radiation. Remote sensing of aerosols relies on scattering phase matrix information to retrieve aerosol properties with frequent global coverage. At the Laboratory for Aerosols, Clouds and Optics (LACO) at the University of Maryland, Baltimore County we developed a new technique to directly measure the aerosol phase function and the degree of linear polarization of the scattered light (two elements of the phase matrix). We designed and built a portable instrument called the Polarized Imaging Nephelometer (PI-Neph). The PI-Neph successfully participated in dozens of flights of the NASA Development and Evaluation of satellite ValidatiOn Tools by Experimenters (DEVOTE) project and the Deep Convective Clouds and Chemistry (DC3) project. The ambient aerosol enters the PI-Neph through an inlet and the sample is illuminated by laser light (wavelength of 532 nm); the scattered light is imaged by a stationary wide field of view camera in the scattering angle range of 2° to 178°. (In some cases stray light limited the scattering angle range to 3° to 176°). The PI-Neph measurement of phase function and the AERONET (AErosol RObotic NETwork) retrievals have already been compared in some cases when the aircraft spiraled over AERONET sites, for example at NASA's Wallops Flight Facility, on October 18 2011, as shown in Figure 1. The differences between the PI-Neph and the AERONET retrievals can be attributed to differences between the ambient size distribution and the one sampled inside the aircraft. The data that is resolved with respect to scattering angle is used to compute the volume scattering coefficient. The above mentioned October 18 flight data showed good agreement between the PI-Neph measurements of volume scattering coefficient and the parallel TSI integrating nephelometer measurements. On average the TSI measurements were 1.02 times the PI

  8. Emergence of Complexity in Protein Functions and Metabolic Networks

    NASA Technical Reports Server (NTRS)

    Pohorille, Andzej

    2009-01-01

    In modern organisms proteins perform a majority of cellular functions, such as chemical catalysis, energy transduction and transport of material across cell walls. Although great strides have been made towards understanding protein evolution, a meaningful extrapolation from contemporary proteins to their earliest ancestors is virtually impossible. In an alternative approach, the origin of water-soluble proteins was probed through the synthesis of very large libraries of random amino acid sequences and subsequently subjecting them to in vitro evolution. In combination with computer modeling and simulations, these experiments allow us to address a number of fundamental questions about the origins of proteins. Can functionality emerge from random sequences of proteins? How did the initial repertoire of functional proteins diversify to facilitate new functions? Did this diversification proceed primarily through drawing novel functionalities from random sequences or through evolution of already existing proto-enzymes? Did protein evolution start from a pool of proteins defined by a frozen accident and other collections of proteins could start a different evolutionary pathway? Although we do not have definitive answers to these questions, important clues have been uncovered. Considerable progress has been also achieved in understanding the origins of membrane proteins. We will address this issue in the example of ion channels - proteins that mediate transport of ions across cell walls. Remarkably, despite overall complexity of these proteins in contemporary cells, their structural motifs are quite simple, with -helices being most common. By combining results of experimental and computer simulation studies on synthetic models and simple, natural channels, I will show that, even though architectures of membrane proteins are not nearly as diverse as those of water-soluble proteins, they are sufficiently flexible to adapt readily to the functional demands arising during

  9. Functional role of polar amino acid residues in Na+/H+ exchangers.

    PubMed Central

    Wiebe, C A; Dibattista, E R; Fliegel, L

    2001-01-01

    Na(+)/H(+) exchangers are a family of ubiquitous membrane proteins. In higher eukaryotes they regulate cytosolic pH by removing an intracellular H(+) in exchange for an extracellular Na(+). In yeast and Escherichia coli, Na(+)/H(+) exchangers function in the opposite direction to remove intracellular Na(+) in exchange for extracellular H(+). Na(+)/H(+) exchangers display an internal pH-sensitivity that varies with the different antiporter types. Only recently have investigations examined the amino acids involved in pH-sensitivity and in cation binding and transport. Histidine residues are good candidates for H(+)-sensing amino acids, since they can ionize within the physiological pH range. Histidine residues have been shown to be important in the function of the E. coli Na(+)/H(+) exchanger NhaA and in the yeast Na(+)/H(+) exchanger sod2. In E. coli, His(225) of NhaA may function to interact with, or regulate, the pH-sensory region of NhaA. In sod2, His(367) is also critical to transport and may be a functional analogue of His(225) of NhaA. Histidine residues are not critical for the function of the mammalian Na(+)/H(+) exchanger, although an unusual histidine-rich sequence of the C-terminal tail has some influence on activity. Other amino acids involved in cation binding and transport by Na(+)/H(+) exchangers are only beginning to be studied. Amino acids with polar side chains such as aspartate and glutamate have been implicated in transport activity of NhaA and sod2, but have not been studied in the mammalian Na(+)/H(+) exchanger. Further studies are needed to elucidate the mechanisms involved in pH-sensitivity and cation binding and transport by Na(+)/H(+) exchangers. PMID:11415429

  10. Single-walled carbon nanotubes disturbed the immune and metabolic regulation function 13-weeks after a single intratracheal instillation.

    PubMed

    Park, Eun-Jung; Hong, Young-Shick; Lee, Byoung-Seok; Yoon, Cheolho; Jeong, Uiseok; Kim, Younghun

    2016-07-01

    Due to their unique physicochemical properties, the potential health effects of single-walled carbon nanotubes (SWCNTs) have attracted continuous attention together with their extensive application. In this study, we aimed to identify local and systemic health effects following pulmonary persistence of SWCNTs. As expected, SWCNTs remained in the lung for 13 weeks after a single intratracheal instillation (50, 100, and 200μg/kg). In the lung, the total number of cells and the percentages of lymphocytes and neutrophils significantly increased at 200μg/kg compared to the control, and the Th1-polarized immune response was induced accompanying enhanced expression of tissue damage-related genes and increased release of chemokines. Additionally, SWCNTs enhanced the expression of antigen presentation-related proteins on the surface of antigen-presenting cells, however, maturation of dendritic cells was inhibited by their persistence. As compared to the control, a significant increase in the percentage of neutrophils and a remarkable decrease of BUN and potassium level were observed in the blood of mice treated with the highest dose. This was accompanied by the down-regulation of the expression of antigen presentation-related proteins on splenocytes. Moreover, protein and glucose metabolism were disturbed with an up-regulation of fatty acid β-oxidation. Taken together, we conclude that SWCNTs may induce adverse health effects by disturbing immune and metabolic regulation functions in the body. Therefore, careful application of SWCNTs is necessary for the enforcement of safety in nano-industries.

  11. Polarized cells, polar actions.

    PubMed

    Maddock, J R; Alley, M R; Shapiro, L

    1993-11-01

    The recognition of polar bacterial organization is just emerging. The examples of polar localization given here are from a variety of bacterial species and concern a disparate array of cellular functions. A number of well-characterized instances of polar localization of bacterial proteins, including the chemoreceptor complex in both C. crescentus and E. coli, the maltose-binding protein in E. coli, the B. japonicum surface attachment proteins, and the actin tail of L. monocytogenes within a mammalian cell, involve proteins or protein complexes that facilitate bacterial interaction with the environment, either the extracellular milieux or that within a plant or mammalian host. The significance of this observation remains unclear. Polarity in bacteria poses many problems, including the necessity for a mechanism for asymmetrically distributing proteins as well as a mechanism by which polar localization is maintained. Large structures, such as a flagellum, are anchored at the pole by means of the basal body that traverses the peptidoglycan wall. But for proteins and small complexes, whether in the periplasm or the membrane, one must invoke a mechanism that prevents the diffusion of these proteins away from the cell pole. Perhaps the periplasmic proteins are retained at the pole by the presence of the periseptal annulus (35). The constraining features for membrane components are not known. For large aggregates, such as the clusters of MCP, CheA, and CheW complexes, perhaps the size of the aggregate alone prevents displacement. In most cases of cellular asymmetry, bacteria are able to discriminate between the new pole and the old pole and to utilize this information for localization specificity. The maturation of new pole to old pole appears to be a common theme as well. Given numerous examples reported thus far, we propose that bacterial polarity displays specific rules and is a more general phenomenon than has been previously recognized.

  12. Structure and function relationships of proteins based on polar profile: a review.

    PubMed

    Polanco, Carlos; Buhse, Thomas; Uversky, Vladimir N

    2016-01-01

    Proteins in the post-genome era impose diverse research challenges, the main are the understanding of their structure-function mechanism, and the growing need for new pharmaceutical drugs, particularly antibiotics that help clinicians treat the ever- increasing number of Multidrug-Resistant Organisms (MDROs). Although, there is a wide range of mathematical-computational algorithms to satisfy the demand, among them the Quantitative Structure-Activity Relationship algorithms that have shown better performance using a characteristic training data of the property searched; their performance has stagnated regardless of the number of metrics they evaluate and their complexity. This article reviews the characteristics of these metrics, and the need to reconsider the mathematical structure that expresses them, directing their design to a more comprehensive algebraic structure. It also shows how the main function of a protein can be determined by measuring the polarity of its linear sequence, with a high level of accuracy, and how such exhaustive metric stands as a "fingerprint" that can be applied to scan the protein regions to obtain new pharmaceutical drugs, and thus to establish how the singularities led to the specialization of the protein groups known today.

  13. Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine.

    PubMed

    Marcovina, Santica M; Sirtori, Cesare; Peracino, Andrea; Gheorghiade, Mihai; Borum, Peggy; Remuzzi, Giuseppe; Ardehali, Hossein

    2013-02-01

    Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of insulin resistance, and abnormalities in fatty acid metabolism. As a consequence, mitochondrial dysfunction contributes to the pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and chronic heart failure. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted therapies. We review the current knowledge of the contribution of mitochondrial dysfunction to chronic diseases, the outcomes of experimental studies on mitochondrial-targeted therapies, and explore the potential of metabolic modulators in the treatment of selected chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of L-carnitine and its analogues acetyl and propionyl L-carnitine in several chronic diseases. L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in fatty acid oxidation and energy metabolism. In addition to the transportation of free fatty acids across the inner mitochondrial membrane, L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment of chronic conditions and diseases associated with mitochondrial dysfunction but further translational studies are needed to fully explore their potential.

  14. Medium-chain fatty acids: functional lipids for the prevention and treatment of the metabolic syndrome.

    PubMed

    Nagao, Koji; Yanagita, Teruyoshi

    2010-03-01

    Metabolic syndrome is a cluster of metabolic disorders, such as abdominal obesity, dyslipidemia, hypertension and impaired fasting glucose, that contribute to increased cardiovascular morbidity and mortality. Although the pathogenesis of metabolic syndrome is complicated and the precise mechanisms have not been elucidated, dietary lipids have been recognized as contributory factors in the development and the prevention of cardiovascular risk clustering. This review explores the physiological functions and molecular actions of medium-chain fatty acids (MCFAs) and medium-chain triglycerides (MCTs) in the development of metabolic syndrome. Experimental studies demonstrate that dietary MCFAs/MCTs suppress fat deposition through enhanced thermogenesis and fat oxidation in animal and human subjects. Additionally, several reports suggest that MCFAs/MCTs offer the therapeutic advantage of preserving insulin sensitivity in animal models and patients with type 2 diabetes.

  15. Retinoic Acid-Related Orphan Receptors (RORs): Regulatory Functions in Immunity, Development, Circadian Rhythm, and Metabolism

    PubMed Central

    Cook, Donald N.; Kang, Hong Soon; Jetten, Anton M.

    2015-01-01

    In this overview, we provide an update on recent progress made in understanding the mechanisms of action, physiological functions, and roles in disease of retinoic acid related orphan receptors (RORs). We are particularly focusing on their roles in the regulation of adaptive and innate immunity, brain function, retinal development, cancer, glucose and lipid metabolism, circadian rhythm, metabolic and inflammatory diseases and neuropsychiatric disorders. We also summarize the current status of ROR agonists and inverse agonists, including their regulation of ROR activity and their therapeutic potential for management of various diseases in which RORs have been implicated. PMID:26878025

  16. Brain glycogen—new perspectives on its metabolic function and regulation at the subcellular level

    PubMed Central

    Obel, Linea F.; Müller, Margit S.; Walls, Anne B.; Sickmann, Helle M.; Bak, Lasse K.; Waagepetersen, Helle S.; Schousboe, Arne

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia. In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies—it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms underlying glycogen metabolism. Based on (1) the compartmentation of the interconnected second messenger pathways controlling glycogen metabolism (calcium and cAMP), (2) alterations in the subcellular location of glycogen-associated enzymes and proteins induced by the metabolic status and (3) a sequential component in the intermolecular mechanisms of glycogen metabolism, we suggest that glycogen metabolism in astrocytes is compartmentalized at the subcellular level. As a consequence, the meaning and importance of conventional terms used to describe glycogen metabolism (e.g., turnover) is challenged. Overall, this review represents an overview of contemporary knowledge about brain glycogen and its metabolism and function. However, it also has a sharp focus on what we do not know, which is perhaps even more important for the future quest of uncovering the roles of glycogen in brain physiology and pathology. PMID:22403540

  17. Oral administration of nano-titanium dioxide particle disrupts hepatic metabolic functions in a mouse model.

    PubMed

    Yang, Julin; Luo, Min; Tan, Zhen; Dai, Manyun; Xie, Minzhu; Lin, Jiao; Hua, Huiying; Ma, Qing; Zhao, Jinshun; Liu, Aiming

    2017-01-01

    TiO2 nano-particle (TiO2 NP) is widely used in industrial, household necessities, as well as medicinal products. However, the effect of TiO2 NP on liver metabolic function has not been reported. In this study, after mice were orally administered TiO2 NP (21nm) for 14days, the serum and liver tissues were assayed by biochemical analysis, real time quantitative polymerase chain reaction, western blot and transmission electron microscopy. The serum bilirubin was increased in a dose dependent manner. Deposition of TiO2 NP in hepatocytes and the abnormality of microstructures was observed. Expression of metabolic genes involved in the endogenous and exogenous metabolism was modified, supporting the toxic phenotype. Collectively, oral administration of TiO2 NP (21nm) led to deposition of particles in hepatocytes, mitochondrial edema, and the disturbance of liver metabolism function. These data suggested oral administration disrupts liver metabolic functions, which was more sensitive than regular approaches to detect material hepatotoxicity. This study provided useful information for risk analysis and regulation of TiO2 NPs by administration agencies.

  18. Non-invasive evaluation of vasomotor and metabolic functions of microvascular endothelium in human skin.

    PubMed

    Fedorovich, Andrey A

    2012-07-01

    Correlation between metabolic and microhemodynamic processes in skin was assessed through acute pharmacological test with metabolically active Actovegin in 28 healthy volunteers. Laser Doppler flowmetry in combination with wavelet analysis of blood flow oscillations was used to identify functional state of arteriolar-venular areas of microvascular bed in the right forearm skin; capillary blood flow parameters were assessed through computer capillaroscopy in the nail bed of the right hand on the 4th finger. The metabolic effect (improved oxygen uptake and glucose disposal by tissues) was accompanied by significant increase in endothelial rhythm amplitude by 98% (p<0.00006), neurogenic rhythm amplitude by 50% (p<0.003) and myogenic rhythm amplitude by 54% (p<0.03), with capillary blood flow rate increasing by 90μm/s (p<0.04), pericapillary zone reducing by 15μm (p<0.0001) and diastolic blood pressure dropping by 4mm Hg (p<0.02). These results show close correlation between metabolic and microhemodynamic processes, which suggests that the amplitude activity within the range of endothelial rhythm (0.0095-0.021Hz) during laser Doppler flowmetry reflects not only solely vasomotor function but also metabolic function of microvascular endothelium.

  19. Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets.

    PubMed

    Fuchs, Ann-Kathrin; Syrovets, Tatiana; Haas, Karina A; Loos, Cornelia; Musyanovych, Anna; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

    2016-04-01

    Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironmental stimuli determines their polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. M1 exhibit high expression of proinflammatory TNF-α and IL-1β, and M2 promote tissue repair, but likewise support tumor growth and cause immune suppression by expressing IL-10. Thus, the M1/M2 balance critically determines tissue homeostasis. By using carboxyl- (PS-COOH) and amino-functionalized (PS-NH2) polystyrene nanoparticles, the effects of surface decoration on the polarization of human macrophages were investigated. The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-α, and IL-1β. By contrast, in M2, both nanoparticles impaired expression of scavenger receptor CD163 and CD200R, and the release of IL-10. PS-NH2 also inhibited phagocytosis of Escherichia coli by both, M1 and M2. PS-COOH did not impair phagocytosis by M2, but increased protein mass in M1 and M2, TGF-β1 release by M1, and ATP levels in M2. Thus, nanoparticles skew the M2 macrophage polarization without affecting M1 markers. Given the critical role of the M1 and M2 polarization for the immunological balance in patients with cancer or chronic inflammation, functionalized nanoparticles might serve as tools for reprogramming the M1/M2 polarization.

  20. Absorption, metabolism, and functions of β-cryptoxanthin

    PubMed Central

    La Frano, Michael R.; Zhu, Chenghao

    2016-01-01

    β-Cryptoxanthin, a carotenoid found in fruits and vegetables such as tangerines, red peppers, and pumpkin, has several functions important for human health. Most evidence from observational, in vitro, animal model, and human studies suggests that β-cryptoxanthin has relatively high bioavailability from its common food sources, to the extent that some β-cryptoxanthin–rich foods might be equivalent to β-carotene–rich foods as sources of retinol. β-Cryptoxanthin is an antioxidant in vitro and appears to be associated with decreased risk of some cancers and degenerative diseases. In addition, many in vitro, animal model, and human studies suggest that β-cryptoxanthin–rich foods may have an anabolic effect on bone and, thus, may help delay osteoporosis. PMID:26747887

  1. Intrinsic and Tumor Microenvironment-Induced Metabolism Adaptations of T Cells and Impact on Their Differentiation and Function

    PubMed Central

    Kouidhi, Soumaya; Noman, Muhammad Zaeem; Kieda, Claudine; Elgaaied, Amel Benammar; Chouaib, Salem

    2016-01-01

    It is well recognized that the immune system and metabolism are highly integrated. In this context, multilevel interactions between metabolic system and T lymphocyte signaling and fate exist. This review will discuss different potential cell metabolism pathways involved in shaping T lymphocyte function and differentiation. We will also provide a general framework for understanding how tumor microenvironmental metabolism, associated with hypoxic stress, interferes with T-cell priming and expansion. How T-cell metabolism drives T-cell-mediated immunity and how the manipulation of metabolic programing for therapeutic purposes will be also discussed. PMID:27066006

  2. Dietary Proteins as Determinants of Metabolic and Physiologic Functions of the Gastrointestinal Tract

    PubMed Central

    Jahan-Mihan, Alireza; Luhovyy, Bohdan L.; Khoury, Dalia El; Anderson, G. Harvey

    2011-01-01

    Dietary proteins elicit a wide range of nutritional and biological functions. Beyond their nutritional role as the source of amino acids for protein synthesis, they are instrumental in the regulation of food intake, glucose and lipid metabolism, blood pressure, bone metabolism and immune function. The interaction of dietary proteins and their products of digestion with the regulatory functions of the gastrointestinal (GI) tract plays a dominant role in determining the physiological properties of proteins. The site of interaction is widespread, from the oral cavity to the colon. The characteristics of proteins that influence their interaction with the GI tract in a source-dependent manner include their physico-chemical properties, their amino acid composition and sequence, their bioactive peptides, their digestion kinetics and also the non-protein bioactive components conjugated with them. Within the GI tract, these products affect several regulatory functions by interacting with receptors releasing hormones, affecting stomach emptying and GI transport and absorption, transmitting neural signals to the brain, and modifying the microflora. This review discusses the interaction of dietary proteins during digestion and absorption with the physiological and metabolic functions of the GI tract, and illustrates the importance of this interaction in the regulation of amino acid, glucose, lipid metabolism, and food intake. PMID:22254112

  3. Dietary proteins as determinants of metabolic and physiologic functions of the gastrointestinal tract.

    PubMed

    Jahan-Mihan, Alireza; Luhovyy, Bohdan L; El Khoury, Dalia; Anderson, G Harvey

    2011-05-01

    Dietary proteins elicit a wide range of nutritional and biological functions. Beyond their nutritional role as the source of amino acids for protein synthesis, they are instrumental in the regulation of food intake, glucose and lipid metabolism, blood pressure, bone metabolism and immune function. The interaction of dietary proteins and their products of digestion with the regulatory functions of the gastrointestinal (GI) tract plays a dominant role in determining the physiological properties of proteins. The site of interaction is widespread, from the oral cavity to the colon. The characteristics of proteins that influence their interaction with the GI tract in a source-dependent manner include their physico-chemical properties, their amino acid composition and sequence, their bioactive peptides, their digestion kinetics and also the non-protein bioactive components conjugated with them. Within the GI tract, these products affect several regulatory functions by interacting with receptors releasing hormones, affecting stomach emptying and GI transport and absorption, transmitting neural signals to the brain, and modifying the microflora. This review discusses the interaction of dietary proteins during digestion and absorption with the physiological and metabolic functions of the GI tract, and illustrates the importance of this interaction in the regulation of amino acid, glucose, lipid metabolism, and food intake.

  4. Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions

    PubMed Central

    Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

    2016-01-01

    Background: There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome–gut–brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity. Objectives: We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. Methods: We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry–based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome. Results: 16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice. Conclusions: Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects. Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198–206; http://dx.doi.org/10

  5. Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass†

    PubMed Central

    Aass, Terje; Stangeland, Lodve; Moen, Christian Arvei; Salminen, Pirjo-Riitta; Dahle, Geir Olav; Chambers, David J.; Markou, Thomais; Eliassen, Finn; Urban, Malte; Haaverstad, Rune; Matre, Knut; Grong, Ketil

    2016-01-01

    OBJECTIVES Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable myocardial protection in a clinically relevant animal model. METHODS Twenty anaesthetized young pigs, 42 ± 2 (standard deviation) kg on standardized tepid cardiopulmonary bypass (CPB) were randomized (10 per group) to depolarizing or polarizing cardiac arrest for 60 min with cardioplegia administered in the aortic root every 20 min as freshly mixed cold, intermittent, oxygenated blood. Global and local baseline and postoperative cardiac function 60, 120 and 180 min after myocardial reperfusion was evaluated with pressure–conductance catheter and strain by Tissue Doppler Imaging. Regional tissue blood flow, cleaved caspase-3 activity, GRK2 phosphorylation and mitochondrial function and ultrastructure were evaluated in myocardial tissue samples. RESULTS Left ventricular function and general haemodynamics did not differ between groups before CPB. Cardiac asystole was obtained and maintained during aortic cross-clamping. Compared with baseline, heart rate was increased and left ventricular end-systolic and end-diastolic pressures decreased in both groups after weaning. Cardiac index, systolic pressure and radial peak systolic strain did not differ between groups. Contractility, evaluated as dP/dtmax, gradually increased from 120 to 180 min after declamping in animals with polarizing cardioplegia and was significantly higher, 1871 ± 160 (standard error) mmHg/s, compared with standard potassium-based cardioplegic arrest, 1351 ± 70 mmHg/s, after 180 min of reperfusion (P = 0

  6. Divergent Expression and Metabolic Functions of Human Glucuronosyltransferases through Alternative Splicing.

    PubMed

    Rouleau, Michèle; Tourancheau, Alan; Girard-Bock, Camille; Villeneuve, Lyne; Vaucher, Jonathan; Duperré, Anne-Marie; Audet-Delage, Yannick; Gilbert, Isabelle; Popa, Ion; Droit, Arnaud; Guillemette, Chantal

    2016-09-27

    Maintenance of cellular homeostasis and xenobiotic detoxification is mediated by 19 human UDP-glucuronosyltransferase enzymes (UGTs) encoded by ten genes that comprise the glucuronidation pathway. Deep RNA sequencing of major metabolic organs exposes a substantial expansion of the UGT transcriptome by alternative splicing, with variants representing 20% to 60% of canonical transcript expression. Nearly a fifth of expressed variants comprise in-frame sequences that may create distinct structural and functional features. Follow-up cell-based assays reveal biological functions for these alternative UGT proteins. Some isoforms were found to inhibit or induce inactivation of drugs and steroids in addition to perturbing global cell metabolism (energy, amino acids, nucleotides), cell adhesion, and proliferation. This work highlights the biological relevance of alternative UGT expression, which we propose increases protein diversity through the evolution of metabolic regulators from specific enzymes.

  7. Estimating Fiber Orientation Distribution Functions in 3D-Polarized Light Imaging

    PubMed Central

    Axer, Markus; Strohmer, Sven; Gräßel, David; Bücker, Oliver; Dohmen, Melanie; Reckfort, Julia; Zilles, Karl; Amunts, Katrin

    2016-01-01

    Research of the human brain connectome requires multiscale approaches derived from independent imaging methods ideally applied to the same object. Hence, comprehensible strategies for data integration across modalities and across scales are essential. We have successfully established a concept to bridge the spatial scales from microscopic fiber orientation measurements based on 3D-Polarized Light Imaging (3D-PLI) to meso- or macroscopic dimensions. By creating orientation distribution functions (pliODFs) from high-resolution vector data via series expansion with spherical harmonics utilizing high performance computing and supercomputing technologies, data fusion with Diffusion Magnetic Resonance Imaging has become feasible, even for a large-scale dataset such as the human brain. Validation of our approach was done effectively by means of two types of datasets that were transferred from fiber orientation maps into pliODFs: simulated 3D-PLI data showing artificial, but clearly defined fiber patterns and real 3D-PLI data derived from sections through the human brain and the brain of a hooded seal. PMID:27147981

  8. Loss of GSNOR1 Function Leads to Compromised Auxin Signaling and Polar Auxin Transport.

    PubMed

    Shi, Ya-Fei; Wang, Da-Li; Wang, Chao; Culler, Angela Hendrickson; Kreiser, Molly A; Suresh, Jayanti; Cohen, Jerry D; Pan, Jianwei; Baker, Barbara; Liu, Jian-Zhong

    2015-09-01

    Cross talk between phytohormones, nitric oxide (NO), and auxin has been implicated in the control of plant growth and development. Two recent reports indicate that NO promoted auxin signaling but inhibited auxin transport probably through S-nitrosylation. However, genetic evidence for the effect of S-nitrosylation on auxin physiology has been lacking. In this study, we used a genetic approach to understand the broader role of S-nitrosylation in auxin physiology in Arabidopsis. We compared auxin signaling and transport in Col-0 and gsnor1-3, a loss-of-function GSNOR1 mutant defective in protein de-nitrosylation. Our results showed that auxin signaling was impaired in the gsnor1-3 mutant as revealed by significantly reduced DR5-GUS/DR5-GFP accumulation and compromised degradation of AXR3NT-GUS, a useful reporter in interrogating auxin-mediated degradation of Aux/IAA by auxin receptors. In addition, polar auxin transport was compromised in gsnor1-3, which was correlated with universally reduced levels of PIN or GFP-PIN proteins in the roots of the mutant in a manner independent of transcription and 26S proteasome degradation. Our results suggest that S-nitrosylation and GSNOR1-mediated de-nitrosylation contribute to auxin physiology, and impaired auxin signaling and compromised auxin transport are responsible for the auxin-related morphological phenotypes displayed by the gsnor1-3 mutant.

  9. Estimation of boiling points using density functional theory with polarized continuum model solvent corrections.

    PubMed

    Chan, Poh Yin; Tong, Chi Ming; Durrant, Marcus C

    2011-09-01

    An empirical method for estimation of the boiling points of organic molecules based on density functional theory (DFT) calculations with polarized continuum model (PCM) solvent corrections has been developed. The boiling points are calculated as the sum of three contributions. The first term is calculated directly from the structural formula of the molecule, and is related to its effective surface area. The second is a measure of the electronic interactions between molecules, based on the DFT-PCM solvation energy, and the third is employed only for planar aromatic molecules. The method is applicable to a very diverse range of organic molecules, with normal boiling points in the range of -50 to 500 °C, and includes ten different elements (C, H, Br, Cl, F, N, O, P, S and Si). Plots of observed versus calculated boiling points gave R²=0.980 for a training set of 317 molecules, and R²=0.979 for a test set of 74 molecules. The role of intramolecular hydrogen bonding in lowering the boiling points of certain molecules is quantitatively discussed.

  10. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression.

    PubMed

    Nantasanti, Sathidpak; Toussaint, Mathilda J M; Youssef, Sameh A; Tooten, Peter C J; de Bruin, Alain

    2016-01-01

    The tumor suppressors Retinoblastoma (Rb) and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC) or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). DDC is metabolized mainly by cytochrome P450 (Cyp)3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC.

  11. A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro.

    PubMed

    Zhang, Xiaoqian; Lu, Juan; He, Bin; Tang, Lingling; Liu, Xiaoli; Zhu, Danhua; Cao, Hongcui; Wang, Yingjie; Li, Lanjuan

    2017-01-01

    Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotra-nsformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two‑dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases.

  12. A tryptophan derivative, ITE, enhances liver cell metabolic functions in vitro

    PubMed Central

    Zhang, Xiaoqian; Lu, Juan; He, Bin; Tang, Lingling; Liu, Xiaoli; Zhu, Danhua; Cao, Hongcui; Wang, Yingjie; Li, Lanjuan

    2017-01-01

    Cell encapsulation provides a three-dimensional support by incorporating isolated cells into microcapsules with the goal of simultaneously maintaining cell survival and function, as well as providing active transport for a bioreactor in vitro similarly to that observed in vivo. However, the biotransformation and metabolic functions of the encapsulated cells are not satisfactory for clinical applications. For this purpose, in this study, hepatoma-derived Huh7 cells/C3A cells were treated with 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous non-toxic ligand for aryl hydrocarbon receptor, in monolayer cultures and on microspheres. The mRNA and protein levels, as well as the metabolic activities of drug metabolizing enzymes, albumin secretion and urea synthesis were determined. When the Huh7 and C3A cells cultured in a monolayer on two-dimensional surfaces, ITE enhanced the protein levels and the metabolic activities of the major cytochrome P450 (CYP450) enzymes, CYP1A1, CYP1A2, CYP3A4 and CYP1B1, and slightly increased albumin secretion and urea synthesis. Moreover, when cultured on microspheres, ITE also substantially increased the protein levels and metabolic activities of CYP1A1, CYP1A2, CYP3A4 and CYP1B1 in both liver cell lines. On the whole, our findings indicate that ITE enhances the enzymatic activities of major CYP450 enzymes and the metabolic functions of liver cells cultured in monolayer or on microspheres, indicating that it may be utilized to improve the functions of hepatocytes. Thus, it may be used in the future for the treatment of liver diseases. PMID:27959388

  13. Towards stable kinetics of large metabolic networks: Nonequilibrium potential function approach

    NASA Astrophysics Data System (ADS)

    Chen, Yong-Cong; Yuan, Ruo-Shi; Ao, Ping; Xu, Min-Juan; Zhu, Xiao-Mei

    2016-06-01

    While the biochemistry of metabolism in many organisms is well studied, details of the metabolic dynamics are not fully explored yet. Acquiring adequate in vivo kinetic parameters experimentally has always been an obstacle. Unless the parameters of a vast number of enzyme-catalyzed reactions happened to fall into very special ranges, a kinetic model for a large metabolic network would fail to reach a steady state. In this work we show that a stable metabolic network can be systematically established via a biologically motivated regulatory process. The regulation is constructed in terms of a potential landscape description of stochastic and nongradient systems. The constructed process draws enzymatic parameters towards stable metabolism by reducing the change in the Lyapunov function tied to the stochastic fluctuations. Biologically it can be viewed as interplay between the flux balance and the spread of workloads on the network. Our approach allows further constraints such as thermodynamics and optimal efficiency. We choose the central metabolism of Methylobacterium extorquens AM1 as a case study to demonstrate the effectiveness of the approach. Growth efficiency on carbon conversion rate versus cell viability and futile cycles is investigated in depth.

  14. Bidirectional reflectance distribution function of thermal control coatings and heat-shielding materials illuminated by polarized light

    NASA Astrophysics Data System (ADS)

    Voschula, I. V.; Dlugunovich, V. A.; Zhumar, A. Yu.

    2013-05-01

    Stokes parameters were measured for radiation reflected in the range 5° to 80° by silver-colored, white, and black thermal control coatings deposited on an aluminum alloy substrate, by green paint on a phenolic plastic surface, and by uncoated carbon-fiber reinforced plastic illuminated by linearly polarized He-Ne laser radiation at an incident angle of -5°. The bidirectional reflectance distribution function of the investigated samples was determined as a function of the view zenith angle.

  15. Genomic islands link secondary metabolism to functional adaptation in marine Actinobacteria

    PubMed Central

    Penn, Kevin; Jenkins, Caroline; Nett, Markus; Udwary, Daniel W.; Gontang, Erin A.; McGlinchey, Ryan P.; Foster, Brian; Lapidus, Alla; Podell, Sheila; Allen, Eric E.; Moore, Bradley S.; Jensen, Paul R.

    2009-01-01

    Genomic islands have been shown to harbor functional traits that differentiate ecologically distinct populations of environmental bacteria. A comparative analysis of the complete genome sequences of the marine Actinobacteria Salinispora tropica and S. arenicola reveals that 75% of the species-specific genes are located in 21 genomic islands. These islands are enriched in genes associated with secondary metabolite biosynthesis providing evidence that secondary metabolism is linked to functional adaptation. Secondary metabolism accounts for 8.8% and 10.9% of the genes in the S. tropica and S. arenicola genomes, respectively, and represents the major functional category of annotated genes that differentiates the two species. Genomic islands harbor all 25 of the species-specific biosynthetic pathways, the majority of which occur in S. arenicola and may contribute to the cosmopolitan distribution of this species. Genome evolution is dominated by gene duplication and acquisition, which in the case of secondary metabolism provide immediate opportunities for the production of new bioactive products. Evidence that secondary metabolic pathways are exchanged horizontally, coupled with prior evidence for fixation among globally distributed populations, supports a functional role and suggests that the acquisition of natural product biosynthetic gene clusters represents a previously unrecognized force driving bacterial diversification. Species-specific differences observed in CRISPR (clustered regularly interspaced short palindromic repeat) sequences suggest that S. arenicola may possess a higher level of phage immunity, while a highly duplicated family of polymorphic membrane proteins provides evidence of a new mechanism of marine adaptation in Gram-positive bacteria. PMID:19474814

  16. Beyond Leptin: Emerging Candidates for the Integration of Metabolic and Reproductive Function during Negative Energy Balance.

    PubMed

    True, Cadence; Grove, Kevin L; Smith, M Susan

    2011-01-01

    Reproductive status is tightly coupled to metabolic state in females, and ovarian cycling in mammals is halted when energy output exceeds energy input, a metabolic condition known as negative energy balance. This inhibition of reproductive function during negative energy balance occurs due to suppression of gonadotropin-releasing hormone (GnRH) release in the hypothalamus. The GnRH secretagogue kisspeptin is also inhibited during negative energy balance, indicating that inhibition of reproductive neuroendocrine circuits may occur upstream of GnRH itself. Understanding the metabolic signals responsible for the inhibition of reproductive pathways has been a compelling research focus for many years. A predominant theory in the field is that the status of energy balance is conveyed to reproductive neuroendocrine circuits via the adipocyte hormone leptin. Leptin is stimulatory for GnRH release and lower levels of leptin during negative energy balance are believed to result in decreased stimulatory drive for GnRH cells. However, recent evidence found that restoring leptin to physiological levels did not restore GnRH function in three different models of negative energy balance. This suggests that although leptin may be an important permissive signal for reproductive function as indicated by many years of research, factors other than leptin must critically contribute to negative energy balance-induced reproductive inhibition. This review will focus on emerging candidates for the integration of metabolic status and reproductive function during negative energy balance.

  17. Metabolic status, gonadotropin secretion, and ovarian function during acute nutrient restriction of beef heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of acute nutritional restriction on metabolic status, gonadotropin secretion, and ovarian function of heifers was determined in 2 experiments. In Exp. 1, 14-mo-old heifers were fed a diet supplying 1.2 × maintenance energy requirements (1.2M). After 10 d, heifers were fed 1.2M or were res...

  18. Beyond Leptin: Emerging Candidates for the Integration of Metabolic and Reproductive Function during Negative Energy Balance

    PubMed Central

    True, Cadence; Grove, Kevin L.; Smith, M. Susan

    2011-01-01

    Reproductive status is tightly coupled to metabolic state in females, and ovarian cycling in mammals is halted when energy output exceeds energy input, a metabolic condition known as negative energy balance. This inhibition of reproductive function during negative energy balance occurs due to suppression of gonadotropin-releasing hormone (GnRH) release in the hypothalamus. The GnRH secretagogue kisspeptin is also inhibited during negative energy balance, indicating that inhibition of reproductive neuroendocrine circuits may occur upstream of GnRH itself. Understanding the metabolic signals responsible for the inhibition of reproductive pathways has been a compelling research focus for many years. A predominant theory in the field is that the status of energy balance is conveyed to reproductive neuroendocrine circuits via the adipocyte hormone leptin. Leptin is stimulatory for GnRH release and lower levels of leptin during negative energy balance are believed to result in decreased stimulatory drive for GnRH cells. However, recent evidence found that restoring leptin to physiological levels did not restore GnRH function in three different models of negative energy balance. This suggests that although leptin may be an important permissive signal for reproductive function as indicated by many years of research, factors other than leptin must critically contribute to negative energy balance-induced reproductive inhibition. This review will focus on emerging candidates for the integration of metabolic status and reproductive function during negative energy balance. PMID:22645510

  19. Plastoglobuli: Plastid Microcompartments with Integrated Functions in Metabolism, Plastid Developmental Transitions, and Environmental Adaptation.

    PubMed

    van Wijk, Klaas J; Kessler, Felix

    2017-01-25

    Plastoglobuli (PGs) are plastid lipoprotein particles surrounded by a membrane lipid monolayer. PGs contain small specialized proteomes and metabolomes. They are present in different plastid types (e.g., chloroplasts, chromoplasts, and elaioplasts) and are dynamic in size and shape in response to abiotic stress or developmental transitions. PGs in chromoplasts are highly enriched in carotenoid esters and enzymes involved in carotenoid metabolism. PGs in chloroplasts are associated with thylakoids and contain ∼30 core proteins (including six ABC1 kinases) as well as additional proteins recruited under specific conditions. Systems analysis has suggested that chloroplast PGs function in metabolism of prenyl lipids (e.g., tocopherols, plastoquinone, and phylloquinone); redox and photosynthetic regulation; plastid biogenesis; and senescence, including recycling of phytol, remobilization of thylakoid lipids, and metabolism of jasmonate. These functionalities contribute to chloroplast PGs' role in responses to stresses such as high light and nitrogen starvation. PGs are thus lipid microcompartments with multiple functions integrated into plastid metabolism, developmental transitions, and environmental adaptation. This review provides an in-depth overview of PG experimental observations, summarizes the present understanding of PG features and functions, and provides a conceptual framework for PG research and the realization of opportunities for crop improvement. Expected final online publication date for the Annual Review of Plant Biology Volume 68 is April 29, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  20. Circadian rhythms in myocardial metabolism and contractile function; influence of workload and oleate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple extra-cardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its ...

  1. Hydrodynamics-Based Functional Forms of Activity Metabolism: A Case for the Power-Law Polynomial Function in Animal Swimming Energetics

    PubMed Central

    Papadopoulos, Anthony

    2009-01-01

    The first-degree power-law polynomial function is frequently used to describe activity metabolism for steady swimming animals. This function has been used in hydrodynamics-based metabolic studies to evaluate important parameters of energetic costs, such as the standard metabolic rate and the drag power indices. In theory, however, the power-law polynomial function of any degree greater than one can be used to describe activity metabolism for steady swimming animals. In fact, activity metabolism has been described by the conventional exponential function and the cubic polynomial function, although only the power-law polynomial function models drag power since it conforms to hydrodynamic laws. Consequently, the first-degree power-law polynomial function yields incorrect parameter values of energetic costs if activity metabolism is governed by the power-law polynomial function of any degree greater than one. This issue is important in bioenergetics because correct comparisons of energetic costs among different steady swimming animals cannot be made unless the degree of the power-law polynomial function derives from activity metabolism. In other words, a hydrodynamics-based functional form of activity metabolism is a power-law polynomial function of any degree greater than or equal to one. Therefore, the degree of the power-law polynomial function should be treated as a parameter, not as a constant. This new treatment not only conforms to hydrodynamic laws, but also ensures correct comparisons of energetic costs among different steady swimming animals. Furthermore, the exponential power-law function, which is a new hydrodynamics-based functional form of activity metabolism, is a special case of the power-law polynomial function. Hence, the link between the hydrodynamics of steady swimming and the exponential-based metabolic model is defined. PMID:19333397

  2. Impact of perinatal exposure to acetaminophen on hepatocellular metabolic function in offspring

    PubMed Central

    Wu, Ka; Guo, Chao; Lu, Xiuli; Wu, Xinmou; Pan, Hongmei; Su, Min

    2016-01-01

    Acetaminophen (APAP), an over the counter (OTC) medication, is widely used in antipyretic treatment. Although the risk of dose-dependent cytotoxicity has been known, the potential effect of perinatal exposure to acetaminophen on metabolic function in offspring remains uninvestigated. Therefore, we established a prenatally APAP-exposed pregnancy mouse model to assess the possible adverse effect on liver metabolic function in offspring. Biochemical assays were applied in analysis of basic metabolic parameters in postnatal mice. Further, immunoblotting assay was used to assess the expressions of insulin receptor β (IRβ), insulin receptor substrate 1 (IRS1), phospho-Akt and phospho-GSK-3β proteins in liver cells. In addition, hepatic glucose transporter 2 (GLUT2) immunoactivity was determined by using immunohistochemistry staining. Compared with untreated postnatal mice, APAP-exposed offspring induced impaired glucose metabolism, increased plasma insulin level, and reduced liver glycogen content. In addition, APAP exposure decreased the expressions of IRS1 and phospho-GSK-3β, phospho-AKT proteins and down-regulated the level of glucose-import regulator GLUT2 in the liver. Taken together, our preliminary findings indicate that perinatal APAP exposure-impaired hepatic glucose metabolism in offspring may be associated with disturbance of insulin-dependent AKT signaling in the liver. PMID:28078035

  3. Ongoing resolution of duplicate gene functions shapes the diversification of a metabolic network

    PubMed Central

    Kuang, Meihua Christina; Hutchins, Paul D; Russell, Jason D; Coon, Joshua J; Hittinger, Chris Todd

    2016-01-01

    The evolutionary mechanisms leading to duplicate gene retention are well understood, but the long-term impacts of paralog differentiation on the regulation of metabolism remain underappreciated. Here we experimentally dissect the functions of two pairs of ancient paralogs of the GALactose sugar utilization network in two yeast species. We show that the Saccharomyces uvarum network is more active, even as over-induction is prevented by a second co-repressor that the model yeast Saccharomyces cerevisiae lacks. Surprisingly, removal of this repression system leads to a strong growth arrest, likely due to overly rapid galactose catabolism and metabolic overload. Alternative sugars, such as fructose, circumvent metabolic control systems and exacerbate this phenotype. We further show that S. cerevisiae experiences homologous metabolic constraints that are subtler due to how the paralogs have diversified. These results show how the functional differentiation of paralogs continues to shape regulatory network architectures and metabolic strategies long after initial preservation. DOI: http://dx.doi.org/10.7554/eLife.19027.001 PMID:27690225

  4. Functional coupling as a basic mechanism of feedback regulation of cardiac energy metabolism.

    PubMed

    Saks, V A; Kuznetsov, A V; Vendelin, M; Guerrero, K; Kay, L; Seppet, E K

    2004-01-01

    In this review we analyze the concepts and the experimental data on the mechanisms of the regulation of energy metabolism in muscle cells. Muscular energetics is based on the force-length relationship, which in the whole heart is expressed as a Frank-Starling law, by which the alterations of left ventricle diastolic volume change linearly both the cardiac work and oxygen consumption. The second basic characteristics of the heart is the metabolic stability--almost constant levels of high energy phosphates, ATP and phosphocreatine, which are practically independent of the workload and the rate of oxygen consumption, in contrast to the fast-twitch skeletal muscle with no metabolic stability and rapid fatigue. Analysis of the literature shows that an increase in the rate of oxygen consumption by order of magnitude, due to Frank-Starling law, is observed without any significant changes in the intracellular calcium transients. Therefore, parallel activation of contraction and mitochondrial respiration by calcium ions may play only a minor role in regulation of respiration in the cells. The effective regulation of the respiration under the effect of Frank-Starling law and metabolic stability of the heart are explained by the mechanisms of functional coupling within supramolecular complexes in mitochondria, and at the subcellular level within the intracellular energetic units. Such a complex structural and functional organisation of heart energy metabolism can be described quantitatively by mathematical models.

  5. The effect of natural organic matter polarity and molecular weight on NDMA formation from two antibiotics containing dimethylamine functional groups.

    PubMed

    Leavey-Roback, Shannon L; Krasner, Stuart W; Suffet, Irwin H Mel

    2016-12-01

    N-nitrosodimethylamine (NDMA) is a disinfection byproduct preferentially formed in chloraminated water. NDMA may be formed from certain chemicals containing dimethylamine (DMA) functional groups. This reaction may be slowed by the presence of natural organic matter (NOM). In this study, NOM fractionated by size or polarity was tested for its ability to slow or impede the formation of NDMA from two DMA-containing precursors, the antibiotics tetracycline and spiramycin. The high molecular weight NOM fractions (>10KDa) were shown to be the most effective in reducing the amount of NDMA formed from the precursor chemicals. The filtrate of a C-18 non-polar cartridge was also effective at reducing NDMA formation from tetracycline (spyramycin not tested). Therefore, polar and charged NOM components may be responsible for the reduction in NDMA formation. A possible mechanism for the reduction of NDMA formation from tetracycline is complexation due to the hydrogen bonding of the DMA functional group on tetracycline to polar phenolic functional groups in the NOM.

  6. Proteomic analysis uncovers a metabolic phenotype in C. elegans after nhr-40 reduction of function

    SciTech Connect

    Pohludka, Michal; Simeckova, Katerina; Vohanka, Jaroslav; Yilma, Petr; Novak, Petr; Krause, Michael W.; Kostrouchova, Marta; Kostrouch, Zdenek

    2008-09-12

    Caenorhabditis elegans has an unexpectedly large number (284) of genes encoding nuclear hormone receptors, most of which are nematode-specific and are of unknown function. We have exploited comparative two-dimensional chromatography of synchronized cultures of wild type C. elegans larvae and a mutant in nhr-40 to determine if proteomic approaches will provide additional insight into gene function. Chromatofocusing, followed by reversed-phase chromatography and mass spectrometry, identified altered chromatographic patterns for a set of proteins, many of which function in muscle and metabolism. Prompted by the proteomic analysis, we find that the penetrance of the developmental phenotypes in the mutant is enhanced at low temperatures and by food restriction. The combination of our phenotypic and proteomic analysis strongly suggests that NHR-40 provides a link between metabolism and muscle development. Our results highlight the utility of comparative two-dimensional chromatography to provide a relatively rapid method to gain insight into gene function.

  7. Metabolism-dependent taxis towards (methyl)phenols is coupled through the most abundant of three polar localized Aer-like proteins of Pseudomonas putida.

    PubMed

    Sarand, Inga; Osterberg, Sofia; Holmqvist, Sofie; Holmfeldt, Per; Skärfstad, Eleonore; Parales, Rebecca E; Shingler, Victoria

    2008-05-01

    Comparatively little is known about directed motility of environmental bacteria to common aromatic pollutants. Here, by expressing different parts of a (methyl)phenol-degradative pathway and the use of specific mutants, we show that taxis of Pseudomonas putida towards (methyl)phenols is dictated by its ability to catabolize the aromatic compound. Thus, in contrast to previously described chemoreceptor-mediated chemotaxis mechanisms towards benzoate, naphthalene and toluene, taxis in response to (methyl)phenols is mediated by metabolism-dependent behaviour. Here we show that P. putida differentially expresses three Aer-like receptors that are all polar-localized through interactions with CheA, and that inactivation of the most abundant Aer2 protein significantly decreases taxis towards phenolics. In addition, the participation of a sensory signal transduction protein composed of a PAS, a GGDEF and an EAL domain in motility towards these compounds is demonstrated. The results are discussed in the context of the versatility of metabolism-dependent coupling and the necessity for P. putida to integrate diverse metabolic signals from its native heterogeneous soil and water environments.

  8. Optimizing human hepatocyte models for metabolic phenotype and function: effects of treatment with dimethyl sulfoxide (DMSO).

    PubMed

    Nikolaou, Nikolaos; Green, Charlotte J; Gunn, Pippa J; Hodson, Leanne; Tomlinson, Jeremy W

    2016-11-01

    Primary human hepatocytes are considered to be the "gold standard" cellular model for studying hepatic fatty acid and glucose metabolism; however, they come with limitations. Although the HepG2 cell line retains many of the primary hepatocyte metabolic functions they have a malignant origin and low rates of triglyceride secretion. The aim of this study was to investigate whether dimethyl sulfoxide supplementation in the media of HepG2 cells would enhance metabolic functionality leading to the development of an improved in vitro cell model that closely recapitulates primary human hepatocyte metabolism. HepG2 cells were cultured in media containing 1% dimethyl sulfoxide for 2, 4, 7, 14, and 21 days. Gene expression, protein levels, intracellular triglyceride, and media concentrations of triglyceride, urea, and 3-hydroxybutyrate concentrations were measured. Dimethyl sulfoxide treatment altered the expression of genes involved in lipid (FAS, ACC1, ACC2, DGAT1, DGAT2, SCD) and glucose (PEPCK, G6Pase) metabolism as well as liver functionality (albumin, alpha-1-antitrypsin, AFP). mRNA changes were paralleled by alterations at the protein level. DMSO treatment decreased intracellular triglyceride content and lactate production and increased triglyceride and 3-hydroxybutyrate concentrations in the media in a time-dependent manner. We have demonstrated that the addition of 1% dimethyl sulfoxide to culture media changes the metabolic phenotype of HepG2 cells toward a more primary human hepatocyte phenotype. This will enhance the currently available in vitro model systems for the study of hepatocyte biology related to pathological processes that contribute to disease and their response to specific therapeutic interventions.

  9. Structure and Function of Human Xylulokinase, an Enzyme with Important Roles in Carbohydrate Metabolism*

    PubMed Central

    Bunker, Richard D.; Bulloch, Esther M. M.; Dickson, James M. J.; Loomes, Kerry M.; Baker, Edward N.

    2013-01-01

    d-Xylulokinase (XK; EC 2.7.1.17) catalyzes the ATP-dependent phosphorylation of d-xylulose (Xu) to produce xylulose 5-phosphate (Xu5P). In mammals, XK is the last enzyme in the glucuronate-xylulose pathway, active in the liver and kidneys, and is linked through its product Xu5P to the pentose-phosphate pathway. XK may play an important role in metabolic disease, given that Xu5P is a key regulator of glucose metabolism and lipogenesis. We have expressed the product of a putative human XK gene and identified it as the authentic human d-xylulokinase (hXK). NMR studies with a variety of sugars showed that hXK acts only on d-xylulose, and a coupled photometric assay established its key kinetic parameters as Km(Xu) = 24 ± 3 μm and kcat = 35 ± 5 s−1. Crystal structures were determined for hXK, on its own and in complexes with Xu, ADP, and a fluorinated inhibitor. These reveal that hXK has a two-domain fold characteristic of the sugar kinase/hsp70/actin superfamily, with glycerol kinase as its closest relative. Xu binds to domain-I and ADP to domain-II, but in this open form of hXK they are 10 Å apart, implying that a large scale conformational change is required for catalysis. Xu binds in its linear keto-form, sandwiched between a Trp side chain and polar side chains that provide exquisite hydrogen bonding recognition. The hXK structure provides a basis for the design of specific inhibitors with which to probe its roles in sugar metabolism and metabolic disease. PMID:23179721

  10. Relationships between years of education and gray matter volume, metabolism and functional connectivity in healthy elders.

    PubMed

    Arenaza-Urquijo, Eider M; Landeau, Brigitte; La Joie, Renaud; Mevel, Katell; Mézenge, Florence; Perrotin, Audrey; Desgranges, Béatrice; Bartrés-Faz, David; Eustache, Francis; Chételat, Gaël

    2013-12-01

    More educated elders are less susceptible to age-related or pathological cognitive changes. We aimed at providing a comprehensive contribution to the neural mechanism underlying this effect thanks to a multimodal approach. Thirty-six healthy elders were selected based on neuropsychological assessments and cerebral amyloid imaging, i.e. as presenting normal cognition and a negative florbetapir-PET scan. All subjects underwent structural MRI, FDG-PET and resting-state functional MRI scans. We assessed the relationships between years of education and i) gray matter volume, ii) gray matter metabolism and iii) functional connectivity in the brain areas showing associations with both volume and metabolism. Higher years of education were related to greater volume in the superior temporal gyrus, insula and anterior cingulate cortex and to greater metabolism in the anterior cingulate cortex. The latter thus showed both volume and metabolism increases with education. Seed connectivity analyses based on this region showed that education was positively related to the functional connectivity between the anterior cingulate cortex and the hippocampus as well as the inferior frontal lobe, posterior cingulate cortex and angular gyrus. Increased connectivity was in turn related with improved cognitive performances. Reinforcement of the connectivity of the anterior cingulate cortex with distant cortical areas of the frontal, temporal and parietal lobes appears as one of the mechanisms underlying education-related reserve in healthy elders.

  11. Fatty aldehyde and fatty alcohol metabolism: review and importance for epidermal structure and function.

    PubMed

    Rizzo, William B

    2014-03-01

    Normal fatty aldehyde and alcohol metabolism is essential for epidermal differentiation and function. Long-chain aldehydes are produced by catabolism of several lipids including fatty alcohols, sphingolipids, ether glycerolipids, isoprenoid alcohols and certain aliphatic lipids that undergo α- or ω-oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as ALDH3A2), which also functions to oxidize fatty alcohols as a component of the fatty alcohol:NAD oxidoreductase (FAO) enzyme complex. Genetic deficiency of FALDH/FAO in patients with Sjögren-Larsson syndrome (SLS) results in accumulation of fatty aldehydes, fatty alcohols and related lipids (ether glycerolipids, wax esters) in cultured keratinocytes. These biochemical changes are associated with abnormalities in formation of lamellar bodies in the stratum granulosum and impaired delivery of their precursor membranes to the stratum corneum (SC). The defective extracellular SC membranes are responsible for a leaky epidermal water barrier and ichthyosis. Although lamellar bodies appear to be the pathogenic target for abnormal fatty aldehyde/alcohol metabolism in SLS, the precise biochemical mechanisms are yet to be elucidated. Nevertheless, studies in SLS highlight the critical importance of FALDH and normal fatty aldehyde/alcohol metabolism for epidermal function. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.

  12. 2009 Plant Lipids: Structure, Metabolism & Function Gordon Research Conference - February 1- 6 ,2009

    SciTech Connect

    Kent D. Chapman

    2009-02-06

    The Gordon Research Conference on 'Plant Lipids: Structure, Metabolism and Function' has been instituted to accelerate research productivity in the field of plant lipids. This conference will facilitate wide dissemination of research breakthroughs, support recruitment of young scientists to the field of plant lipid metabolism and encourage broad participation of the plant lipid community in guiding future directions for research in plant lipids. This conference will build upon the strengths of the successful, previous biannual meetings of the National Plant Lipid Cooperative (www.plantlipids.org) that began in 1993, but will reflect a broader scope of topics to include the biochemistry, cell biology, metabolic regulation, and signaling functions of plant acyl lipids. Most importantly, this conference also will serve as a physical focal point for the interaction of the plant lipid research community. Applications to attend this conference will be open to all researchers interested in plant lipids and will provide a venue for the presentation of the latest research results, networking opportunities for young scientists, and a forum for the development and exchange of useful lipid resources and new ideas. By bringing together senior- and junior-level scientists involved in plant lipid metabolism, a broad range of insights will be shared and the community of plant lipid researchers will function more as a network of vested partners. This is important for the vitality of the research community and for the perceived value that will encourage conference attendance into the future.

  13. Fatty Aldehyde and Fatty Alcohol Metabolism: Review and Importance for Epidermal Structure and Function

    PubMed Central

    Rizzo, William B.

    2014-01-01

    Normal fatty aldehyde and alcohol metabolism is essential for epidermal differentiation and function. Long-chain aldehydes are produced by catabolism of several lipids including fatty alcohols, sphingolipids, ether glycerolipids, isoprenoid alcohols and certain aliphatic lipids that undergo α- or ω-oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as ALDH3A2), which also functions to oxidize fatty alcohols as a component of the fatty alcohol:NAD oxidoreductase (FAO) enzyme complex. Genetic deficiency of FALDH/FAO in patients with Sjögren-Larsson syndrome (SLS) results in accumulation of fatty aldehydes, fatty alcohols and related lipids (ether glycerolipids, wax esters) in cultured keratinocytes. These biochemical changes are associated with abnormalities in formation of lamellar bodies in the stratum granulosum and impaired delivery of their precursor membranes to the stratum corneum (SC). The defective extracellular SC membranes are responsible for a leaky epidermal water barrier and ichthyosis. Although lamellar bodies appear to be the pathogenic target for abnormal fatty aldehyde/alcohol metabolism in SLS, the precise biochemical mechanisms are yet to be elucidated. Nevertheless, studies in SLS highlight the critical importance of FALDH and normal fatty aldehyde/alcohol metabolism for epidermal function. PMID:24036493

  14. Overexpressing Superoxide Dismutase 2 Induces a Supernormal Cardiac Function by Enhancing Redox-dependent Mitochondrial Function and Metabolic Dilation*

    PubMed Central

    Kang, Patrick T.; Chen, Chwen-Lih; Ohanyan, Vahagn; Luther, Daniel J.; Meszaros, J. Gary; Chilian, William M.; Chen, Yeong-Renn

    2015-01-01

    During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate × MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, “spilled” over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function. PMID:26374996

  15. Overexpressing superoxide dismutase 2 induces a supernormal cardiac function by enhancing redox-dependent mitochondrial function and metabolic dilation.

    PubMed

    Kang, Patrick T; Chen, Chwen-Lih; Ohanyan, Vahagn; Luther, Daniel J; Meszaros, J Gary; Chilian, William M; Chen, Yeong-Renn

    2015-11-01

    During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate×MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, "spilled" over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function.

  16. A dynamic method for the investigation of induced state metabolic capacities as a function of temperature

    PubMed Central

    2013-01-01

    Background Science-based recombinant bioprocess designs as well as the design of statistical experimental plans for process optimization (Design of Experiments, DoE) demand information on physiological bioprocess boundaries, such as the onset of acetate production, adaptation times, mixed feed metabolic capabilities or induced state maximum metabolic rates as at the desired cultivation temperature. Dynamic methods provide experimental alternatives to determine this information in a fast and efficient way. Information on maximum metabolic capabilities as a function of temperature is needed in case a reduced cultivation temperature is desirable (e.g. to avoid inclusion body formation) and an appropriate feeding profile is to be designed. Results Here, we present a novel dynamic method for the determination of the specific growth rate as a function of temperature for induced recombinant bacterial bioprocesses. The method is based on the control of the residual substrate concentration at non-limiting conditions with dynamic changes in cultivation temperature. The presented method was automated in respect to information extraction and closed loop control by means of in-line Fourier Transformation Infrared Spectroscopy (FTIR) residual substrate measurements and on-line first principle rate-based soft-sensors. Maximum induced state metabolic capabilities as a function of temperature were successfully extracted for a recombinant E. coli C41 fed-batch bioprocess without the need for sampling in a time frame of 20 hours. Conclusions The presented method was concluded to allow the fast and automated extraction of maximum metabolic capabilities (specific growth rate) as a function of temperature. This complements the dynamic toolset necessary for science-based recombinant bacterial bioprocess design and DoE design. PMID:24127686

  17. Regulatory and Functional Aspects of Indolic Metabolism in Plant Systemic Acquired Resistance.

    PubMed

    Stahl, Elia; Bellwon, Patricia; Huber, Stefan; Schlaeppi, Klaus; Bernsdorff, Friederike; Vallat-Michel, Armelle; Mauch, Felix; Zeier, Jürgen

    2016-05-02

    Tryptophan-derived, indolic metabolites possess diverse functions in Arabidopsis innate immunity to microbial pathogen infection. Here, we investigate the functional role and regulatory characteristics of indolic metabolism in Arabidopsis systemic acquired resistance (SAR) triggered by the bacterial pathogen Pseudomonas syringae. Indolic metabolism is broadly activated in both P. syringae-inoculated and distant, non-inoculated leaves. At inoculation sites, camalexin, indol-3-ylmethylamine (I3A), and indole-3-carboxylic acid (ICA) are the major accumulating compounds. Camalexin accumulation is positively affected by MYB122, and the cytochrome P450 genes CYP81F1 and CYP81F2. Local I3A production, by contrast, occurs via indole glucosinolate breakdown by PEN2- dependent and independent pathways. Moreover, exogenous application of the defense hormone salicylic acid stimulates I3A generation at the expense of its precursor indol-3-ylmethylglucosinolate (I3M), and the SAR regulator pipecolic acid primes plants for enhanced P. syringae-induced activation of distinct branches of indolic metabolism. In uninfected systemic tissue, the metabolic response is more specific and associated with enhanced levels of the indolics I3A, ICA, and indole-3-carbaldehyde (ICC). Systemic indole accumulation fully depends on functional CYP79B2/3, PEN2, and MYB34/51/122, and requires functional SAR signaling. Genetic analyses suggest that systemically elevated indoles are dispensable for SAR and associated systemic increases of salicylic acid. However, soil-grown but not hydroponically -cultivated cyp79b2/3 and pen2 plants, both defective in indolic secondary metabolism, exhibit pre-induced immunity, which abrogates their intrinsic ability to induce SAR.

  18. Structure, function and molecular adaptations of haemoglobins of the polar cartilaginous fish Bathyraja eatonii and Raja hyperborea.

    PubMed

    Verde, Cinzia; De Rosa, M Cristina; Giordano, Daniela; Mosca, Donato; De Pascale, Donatella; Raiola, Luca; Cocca, Ennio; Carratore, Vitale; Giardina, Bruno; Di Prisco, Guido

    2005-07-15

    Cartilaginous fish are very ancient organisms. In the Antarctic sea, the modern chondrichthyan genera are poorly represented, with only three species of sharks and eight species of skates; the paucity of chondrichthyans is probably an ecological consequence of unusual trophic or habitat conditions in the Southern Ocean. In the Arctic, there are 26 species belonging to the class Chondrichthyes. Fish in the two polar regions have been subjected to different regional histories that have influenced the development of diversity: Antarctic marine organisms are highly stenothermal, in response to stable water temperatures, whereas the Arctic communities are exposed to seasonal temperature variations. The structure and function of the oxygen-transport haem protein from the Antarctic skate Bathyraja eatonii and from the Arctic skate Raja hyperborea (both of the subclass Elasmobranchii, order Rajiformes, family Rajidae) is reported in the present paper. These species have a single major haemoglobin (Hb 1; over 80% of the total). The Bohr-proton and the organophosphate-binding sites are absent. Thus the haemoglobins of northern and southern polar skates appear functionally similar, whereas differences were observed with several temperate elasmobranchs. Such evidence suggests that, in temperate and polar habitats, physiological adaptations have evolved along distinct pathways, whereas, in this case, the effect of the differences characterizing the two polar environments is negligible.

  19. Metabolomic strategies for the identification of new enzyme functions and metabolic pathways

    PubMed Central

    Prosser, Gareth A; Larrouy-Maumus, Gerald; de Carvalho, Luiz Pedro S

    2014-01-01

    Recent technological advances in accurate mass spectrometry and data analysis have revolutionized metabolomics experimentation. Activity-based and global metabolomic profiling methods allow simultaneous and rapid screening of hundreds of metabolites from a variety of chemical classes, making them useful tools for the discovery of novel enzymatic activities and metabolic pathways. By using the metabolome of the relevant organism or close species, these methods capitalize on biological relevance, avoiding the assignment of artificial and non-physiological functions. This review discusses state-of-the-art metabolomic approaches and highlights recent examples of their use for enzyme annotation, discovery of new metabolic pathways, and gene assignment of orphan metabolic activities across diverse biological sources. PMID:24829223

  20. Structure to function of an α-glucan metabolic pathway that promotes Listeria monocytogenes pathogenesis.

    PubMed

    Light, Samuel H; Cahoon, Laty A; Halavaty, Andrei S; Freitag, Nancy E; Anderson, Wayne F

    2016-11-07

    Here we employ a 'systems structural biology' approach to functionally characterize an unconventional α-glucan metabolic pathway from the food-borne pathogen Listeria monocytogenes (Lm). Crystal structure determination coupled with basic biochemical and biophysical assays allowed for the identification of anabolic, transport, catabolic and regulatory portions of the cycloalternan pathway. These findings provide numerous insights into cycloalternan pathway function and reveal the mechanism of repressor, open reading frame, kinase (ROK) transcription regulators. Moreover, by developing a structural overview we were able to anticipate the cycloalternan pathway's role in the metabolism of partially hydrolysed starch derivatives and demonstrate its involvement in Lm pathogenesis. These findings suggest that the cycloalternan pathway plays a role in interspecies resource competition-potentially within the host gastrointestinal tract-and establish the methodological framework for characterizing bacterial systems of unknown function.

  1. Bridging Between Proline Structure, Functions, Metabolism, and Involvement in Organism Physiology.

    PubMed

    Saibi, Walid; Feki, Kaouthar; Yacoubi, Ines; Brini, Faiçal

    2015-08-01

    Much is now known about proline multifunctionality and metabolism; some aspects of its biological functions are still unclear. Here, we discuss some cases in the proline, structure, definition, metabolism, compartmentalization, accumulation, plausible functions and also its implication in homeostasis and organism physiology. Indeed, we report the role of proline in cellular homeostasis, including redox balance and energy status and their implication as biocatalyst for aldolase activity. Proline can act as a signaling molecule to modulate mitochondrial functions, influence cell proliferation or cell death, and trigger specific gene expression, which can be essential for plant recovery from stresses. Although, the regulation and the function of proline accumulation, during abiotic stresses, are not yet completely understood. The engineering of proline metabolism could lead to new opportunities to improve plant tolerance against environmental stresses. This atypical amino acid has a potential role in the toxicity during growth of some microorganism, vegetal, and mammalian species. Furthermore, we note that the purpose through the work is to provide a rich, concise, and mostly cohesive source on proline, considered as a platform and an anchor between several disciplines and biological functions.

  2. Effect of Dance Exercise on Cognitive Function in Elderly Patients with Metabolic Syndrome: A Pilot Study

    PubMed Central

    Kim, Se-Hong; Kim, Minjeong; Ahn, Yu-Bae; Lim, Hyun-Kook; Kang, Sung-Goo; Cho, Jung-hyoun; Park, Seo-Jin; Song, Sang-Wook

    2011-01-01

    Metabolic syndrome is associated with an increased risk of cognitive impairment. The purpose of this prospective pilot study was to examine the effects of dance exercise on cognitive function in elderly patients with metabolic syndrome. The participants included 38 elderly metabolic syndrome patients with normal cognitive function (26 exercise group and 12 control group). The exercise group performed dance exercise twice a week for 6 months. Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD-K). Repeated-measures ANCOVA was used to assess the effect of dance exercise on cognitive function and cardiometabolic risk factors. Compared with the control group, the exercise group significantly improved in verbal fluency (p = 0.048), word list delayed recall (p = 0.038), word list recognition (p = 0.007), and total CERAD-K score (p = 0.037). However, no significance difference was found in body mass index, blood pressure, waist circumference, fasting plasma glucose, triglyceride, and HDL cholesterol between groups over the 6-month period. In the present study, six months of dance exercise improved cognitive function in older adults with metabolic syndrome. Thus, dance exercise may reduce the risk for cognitive disorders in elderly people with metabolic syndrome. Key points Metabolic syndrome (MS) is associated with an increased risk of cognitive impairment. Aerobic exercise improves cognitive function in elderly people and contributes to the prevention of degenerative neurological disease and brain damage. Dance sport is a form of aerobic exercise that has the additional benefits of stimulating the emotions, promoting social interaction, and exposing subjects to acoustic stimulation and music. In the present study, dance exercise for a 6-month period improved cognitive function in older adults with MS. In particular, positive effects were observed in verbal fluency, word

  3. Effect of dance exercise on cognitive function in elderly patients with metabolic syndrome: a pilot study.

    PubMed

    Kim, Se-Hong; Kim, Minjeong; Ahn, Yu-Bae; Lim, Hyun-Kook; Kang, Sung-Goo; Cho, Jung-Hyoun; Park, Seo-Jin; Song, Sang-Wook

    2011-01-01

    Metabolic syndrome is associated with an increased risk of cognitive impairment. The purpose of this prospective pilot study was to examine the effects of dance exercise on cognitive function in elderly patients with metabolic syndrome. The participants included 38 elderly metabolic syndrome patients with normal cognitive function (26 exercise group and 12 control group). The exercise group performed dance exercise twice a week for 6 months. Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K). Repeated-measures ANCOVA was used to assess the effect of dance exercise on cognitive function and cardiometabolic risk factors. Compared with the control group, the exercise group significantly improved in verbal fluency (p = 0.048), word list delayed recall (p = 0.038), word list recognition (p = 0.007), and total CERAD-K score (p = 0.037). However, no significance difference was found in body mass index, blood pressure, waist circumference, fasting plasma glucose, triglyceride, and HDL cholesterol between groups over the 6-month period. In the present study, six months of dance exercise improved cognitive function in older adults with metabolic syndrome. Thus, dance exercise may reduce the risk for cognitive disorders in elderly people with metabolic syndrome. Key pointsMetabolic syndrome (MS) is associated with an increased risk of cognitive impairment.Aerobic exercise improves cognitive function in elderly people and contributes to the prevention of degenerative neurological disease and brain damage. Dance sport is a form of aerobic exercise that has the additional benefits of stimulating the emotions, promoting social interaction, and exposing subjects to acoustic stimulation and music.In the present study, dance exercise for a 6-month period improved cognitive function in older adults with MS. In particular, positive effects were observed in verbal fluency, word list

  4. Use of carbosilane dendrimer to switch macrophage polarization for the acquisition of antitumor functions

    NASA Astrophysics Data System (ADS)

    Perisé-Barrios, Ana J.; Gómez, Rafael; Corbí, Angel L.; de La Mata, Javier; Domínguez-Soto, Angeles; Muñoz-Fernandez, María A.

    2015-02-01

    Tumor microenvironment favors the escape from immunosurveillance by promoting immunosuppression and blunting pro-inflammatory responses. Since most tumor-associated macrophages (TAM) exhibit an M2-like tumor cell growth promoting polarization, we have studied the role of 2G-03NN24 carbosilane dendrimer in M2 macrophage polarization to evaluate the potential application of dendrimers in tumor immunotherapy. We found that the 2G-03NN24 dendrimer decreases LPS-induced IL-10 production from in vitro generated monocyte-derived M2 macrophages, and also switches their gene expression profile towards the acquisition of M1 polarization markers (INHBA, SERPINE1, FLT1, EGLN3 and ALDH1A2) and the loss of M2 polarization-associated markers (EMR1, IGF1, FOLR2 and SLC40A1). Furthermore, 2G-03NN24 dendrimer decreases STAT3 activation. Our results indicate that the 2G-03NN24 dendrimer can be a useful tool for antitumor therapy by virtue of its potential ability to limit the M2-like polarization of TAM.Tumor microenvironment favors the escape from immunosurveillance by promoting immunosuppression and blunting pro-inflammatory responses. Since most tumor-associated macrophages (TAM) exhibit an M2-like tumor cell growth promoting polarization, we have studied the role of 2G-03NN24 carbosilane dendrimer in M2 macrophage polarization to evaluate the potential application of dendrimers in tumor immunotherapy. We found that the 2G-03NN24 dendrimer decreases LPS-induced IL-10 production from in vitro generated monocyte-derived M2 macrophages, and also switches their gene expression profile towards the acquisition of M1 polarization markers (INHBA, SERPINE1, FLT1, EGLN3 and ALDH1A2) and the loss of M2 polarization-associated markers (EMR1, IGF1, FOLR2 and SLC40A1). Furthermore, 2G-03NN24 dendrimer decreases STAT3 activation. Our results indicate that the 2G-03NN24 dendrimer can be a useful tool for antitumor therapy by virtue of its potential ability to limit the M2-like polarization of TAM

  5. The function of the aerenchyma in arborescent lycopsids: evidence of an unfamiliar metabolic strategy.

    PubMed

    Green, W A

    2010-08-07

    Most species of the modern family Isoëtaceae (Quillworts) some other modern hydrophytes, use a metabolic pathway for carbon fixation that involves uptake of sedimentary carbon and enrichment of CO(2) in internal gas spaces as a carbon-concentrating mechanism. This metabolism, which is related to 'aquatic CAM', is characterized by morphological, physiological and biochemical adaptations for decreasing photorespirative loss, aerating roots and maintaining high growth rates in anoxic, oligotrophic, stressed environments. Some of the closest relatives of the Isoëtaceae were the 'arborescent lycopsids', which were among the dominant taxa in the coal swamps found in lowland ecosystems during the Carboniferous and Permian periods (approx. 300 Ma). Morphological, ecological and geochemical evidence supports the hypothesis that the arborescent lycopsids had an unusual metabolism similar to that of modern Isoëtaceae and processed a biogeochemically significant proportion of organically fixed carbon over a period of about 100 million years in the late Palaeozoic. The temporal coincidence between the dominance of plants with this metabolism and an anomalous global atmosphere (high O(2); low CO(2)) supports the idea that biosphere feedbacks are important in regulating global climatic homeostasis. The potential influence of this metabolism on the global carbon cycle and its specific adaptive function suggest that it should perhaps be considered a fourth major photosynthetic pathway.

  6. Comparative Functional Genomic Analysis of Two Vibrio Phages Reveals Complex Metabolic Interactions with the Host Cell

    PubMed Central

    Skliros, Dimitrios; Kalatzis, Panos G.; Katharios, Pantelis; Flemetakis, Emmanouil

    2016-01-01

    Sequencing and annotation was performed for two large double stranded DNA bacteriophages, φGrn1 and φSt2 of the Myoviridae family, considered to be of great interest for phage therapy against Vibrios in aquaculture live feeds. In addition, phage–host metabolic interactions and exploitation was studied by transcript profiling of selected viral and host genes. Comparative genomic analysis with other large Vibrio phages was also performed to establish the presence and location of homing endonucleases highlighting distinct features for both phages. Phylogenetic analysis revealed that they belong to the “schizoT4like” clade. Although many reports of newly sequenced viruses have provided a large set of information, basic research related to the shift of the bacterial metabolism during infection remains stagnant. The function of many viral protein products in the process of infection is still unknown. Genome annotation identified the presence of several viral open reading frames (ORFs) participating in metabolism, including a Sir2/cobB (sirtuin) protein and a number of genes involved in auxiliary NAD+ and nucleotide biosynthesis, necessary for phage DNA replication. Key genes were subsequently selected for detail study of their expression levels during infection. This work suggests a complex metabolic interaction and exploitation of the host metabolic pathways and biochemical processes, including a possible post-translational protein modification, by the virus during infection. PMID:27895630

  7. Comparative Functional Genomic Analysis of Two Vibrio Phages Reveals Complex Metabolic Interactions with the Host Cell.

    PubMed

    Skliros, Dimitrios; Kalatzis, Panos G; Katharios, Pantelis; Flemetakis, Emmanouil

    2016-01-01

    Sequencing and annotation was performed for two large double stranded DNA bacteriophages, φGrn1 and φSt2 of the Myoviridae family, considered to be of great interest for phage therapy against Vibrios in aquaculture live feeds. In addition, phage-host metabolic interactions and exploitation was studied by transcript profiling of selected viral and host genes. Comparative genomic analysis with other large Vibrio phages was also performed to establish the presence and location of homing endonucleases highlighting distinct features for both phages. Phylogenetic analysis revealed that they belong to the "schizoT4like" clade. Although many reports of newly sequenced viruses have provided a large set of information, basic research related to the shift of the bacterial metabolism during infection remains stagnant. The function of many viral protein products in the process of infection is still unknown. Genome annotation identified the presence of several viral open reading frames (ORFs) participating in metabolism, including a Sir2/cobB (sirtuin) protein and a number of genes involved in auxiliary NAD(+) and nucleotide biosynthesis, necessary for phage DNA replication. Key genes were subsequently selected for detail study of their expression levels during infection. This work suggests a complex metabolic interaction and exploitation of the host metabolic pathways and biochemical processes, including a possible post-translational protein modification, by the virus during infection.

  8. Metabolic risk factors and long-term graft function after paediatric renal transplantation.

    PubMed

    Tainio, Juuso; Qvist, Erik; Hölttä, Tuula; Pakarinen, Mikko; Jahnukainen, Timo; Jalanko, Hannu

    2014-06-01

    The aim of this study was to evaluate metabolic risk factors and their impact on long-term allograft function in paediatric renal transplant (RTx) patients. We reviewed the medical records of 210 RTx patients who underwent transplantation at a median age of 4.5 years (range 0.7-18.2) and a median follow-up of 7.0 years (range 1.5-18.0). Data on lipid and glucose metabolism, uric acid levels, weight and blood pressure were collected up to 13 years post-RTx, and the findings were correlated with the measured glomerular filtration rate (GFR). Beyond the first year, GFR showed gradual deterioration with a mean decline of 2.4 ml/min/1.73 m(2)/year. Metabolic syndrome, overweight, hypertension and type 2 diabetes were diagnosed in 14-19%, 20-23%, 62-87% and 3-5% of the patients, respectively. These entities showed only mild association with the concomitant or long-term GFR values. Dyslipidaemia was common and hypertriglyceridaemia associated with a lower GFR at 1.5 and 5 years post-RTx (P = 0.008 and P = 0.017, respectively). Similarly, hyperuricaemia was frequent and associated significantly with GFR (P < 0.001). Except for hyperuricaemia and hypertriglyceridaemia, metabolic risk factors beyond the first postoperative year associated modestly with the long-term kidney graft function in paediatric RTx patients.

  9. Microbial structures, functions, and metabolic pathways in wastewater treatment bioreactors revealed using high-throughput sequencing.

    PubMed

    Ye, Lin; Zhang, Tong; Wang, Taitao; Fang, Zhiwei

    2012-12-18

    The objective of this study was to explore microbial community structures, functional profiles, and metabolic pathways in a lab-scale and a full-scale wastewater treatment bioreactors. In order to do this, over 12 gigabases of metagenomic sequence data and 600,000 paired-end sequences of bacterial 16S rRNA gene were generated with the Illumina HiSeq 2000 platform, using DNA extracted from activated sludge in the two bioreactors. Three kinds of sequences (16S rRNA gene amplicons, 16S rRNA gene sequences obtained from metagenomic sequencing, and predicted proteins) were used to conduct taxonomic assignments. Specially, relative abundances of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) were analyzed. Compared with quantitative real-time PCR (qPCR), metagenomic sequencing was demonstrated to be a better approach to quantify AOA and AOB in activated sludge samples. It was found that AOB were more abundant than AOA in both reactors. Furthermore, the analysis of the metabolic profiles indicated that the overall patterns of metabolic pathways in the two reactors were quite similar (73.3% of functions shared). However, for some pathways (such as carbohydrate metabolism and membrane transport), the two reactors differed in the number of pathway-specific genes.

  10. Respiratory, metabolic and cardiac functions are altered by disinhibition of subregions of the medial prefrontal cortex

    PubMed Central

    Hassan, Sarah F; Cornish, Jennifer L; Goodchild, Ann K

    2013-01-01

    The prefrontal cortex (PFC) is referred to as the visceral motor cortex; however, little is known about whether this region influences respiratory or metabolic outflows. The aim of this study was to describe simultaneous changes in respiratory, metabolic and cardiovascular functions evoked by disinhibition of the medial PFC (mPFC) and adjacent lateral septal nucleus (LSN). In urethane-anaesthetized rats, bicuculline methiodide was microinjected (2 mm; GABA-A receptor antagonist) into 90 sites in the mPFC at 0.72–4.00 mm from bregma. Phrenic nerve amplitude and frequency, arterial pressure, heart rate, splanchnic and lumbar sympathetic nerve activities (SNA), expired CO2, and core and brown adipose tissue temperatures were measured. Novel findings included disturbances to respiratory rhythm evoked from all subregions of the mPFC. Injections into the cingulate cortex evoked reductions in central respiratory function exclusively, whereas in ventral sites, particularly the infralimbic region, increases in respiratory drive and frequency, and metabolic and cardiac outflows were evoked. Disinhibition of sites in surrounding regions revealed that the LSN could evoke cardiovascular changes accompanied by distinct oscillations in SNA, as well as increases in respiratory amplitude. We show that activation of neurons within the mPFC and LSN influence respiratory, metabolic and cardiac outflows in a site-dependent manner. This study has implications with respect to the altered PFC neuronal activity seen in stress-related and mental health disorders, and suggests how basic physiological systems may be affected. PMID:24042503

  11. Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs.

    PubMed

    Sun, H; Huang, Y; Yin, C; Guo, J; Zhao, R; Yang, X

    2016-07-01

    Most previous studies on the effects of lipopolysaccharide (LPS) in pigs focused on the body's immune response, and few reports paid attention to body metabolism changes. To better understand the glucose metabolism changes in skeletal muscle following LPS challenge and to clarify the possible mechanism, 12 growing pigs were employed. Animals were treated with either 2 ml of saline or 15 µg/kg BW LPS, and samples were collected 6 h later. The glycolysis status and mitochondrial function in the longissimus dorsi (LD) muscle of pigs were analyzed. The results showed that serum lactate content and NADH content in LD muscle significantly increased compared with the control group. Most glycolysis-related genes expression, as well as hexokinase, pyruvate kinase and lactic dehydrogenase activity, in LD muscle was significantly higher compared with the control group. Mitochondrial complexes I and IV significantly increased, while mitochondrial ATP concentration markedly decreased. Significantly increased calcium content in the mitochondria was observed, and endoplasm reticulum (ER) stress has been demonstrated in the present study. The results showed that LPS treatment markedly changes glucose metabolism and mitochondrial function in the LD muscle of pigs, and increased calcium content induced by ER stress was possibly involved. The results provide new clues for clarifying metabolic diseases in muscle induced by LPS.

  12. Interplay between metabolic identities in the intestinal crypt supports stem cell function.

    PubMed

    Rodríguez-Colman, Maria J; Schewe, Matthias; Meerlo, Maaike; Stigter, Edwin; Gerrits, Johan; Pras-Raves, Mia; Sacchetti, Andrea; Hornsveld, Marten; Oost, Koen C; Snippert, Hugo J; Verhoeven-Duif, Nanda; Fodde, Riccardo; Burgering, Boudewijn M T

    2017-03-16

    The small intestinal epithelium self-renews every four or five days. Intestinal stem cells (Lgr5(+) crypt base columnar cells (CBCs)) sustain this renewal and reside between terminally differentiated Paneth cells at the bottom of the intestinal crypt. Whereas the signalling requirements for maintaining stem cell function and crypt homeostasis have been well studied, little is known about how metabolism contributes to epithelial homeostasis. Here we show that freshly isolated Lgr5(+) CBCs and Paneth cells from the mouse small intestine display different metabolic programs. Compared to Paneth cells, Lgr5(+) CBCs display high mitochondrial activity. Inhibition of mitochondrial activity in Lgr5(+) CBCs or inhibition of glycolysis in Paneth cells strongly affects stem cell function, as indicated by impaired organoid formation. In addition, Paneth cells support stem cell function by providing lactate to sustain the enhanced mitochondrial oxidative phosphorylation in the Lgr5(+) CBCs. Mechanistically, we show that oxidative phosphorylation stimulates p38 MAPK activation by mitochondrial reactive oxygen species signalling, thereby establishing the mature crypt phenotype. Together, our results reveal a critical role for the metabolic identity of Lgr5(+) CBCs and Paneth cells in supporting optimal stem cell function, and we identify mitochondria and reactive oxygen species signalling as a driving force of cellular differentiation.

  13. Tristetraprolin disables prostate cancer maintenance by impairing proliferation and metabolic function

    PubMed Central

    Li, Weimin; Yang, Chunying; Fernandez, Mario R.; Schaub, Franz X.; Cleveland, John L.; Rounbehler, Robert J.

    2016-01-01

    Tristetraprolin (TTP) is an RNA-binding protein that post-transcriptionally suppresses gene expression by delivering mRNA cargo to processing bodies (P-bodies) where the mRNA is degraded. TTP functions as a tumor suppressor in a mouse model of B cell lymphoma, and in some human malignancies low TTP expression correlates with reduced survival. Here we report important prognostic and functional roles for TTP in human prostate cancer. First, gene expression analysis of prostate tumors revealed low TTP expression correlates with patients having high-risk Gleason scores and increased biochemical recurrence. Second, in prostate cancer cells with low levels of endogenous TTP, inducible TTP expression inhibits their growth and proliferation, as well as their clonogenic growth. Third, TTP functions as a tumor suppressor in prostate cancer, as forced TTP expression markedly impairs the tumorigenic potential of prostate cancer cells in a mouse xenograft model. Finally, pathway analysis of gene expression data suggested metabolism is altered by TTP expression in prostate tumor cells, and metabolic analyses revealed that such processes are impaired by TTP, including mitochondrial respiration. Collectively, these findings suggest that TTP is an important prognostic indicator for prostate cancer, and augmenting TTP function would effectively disable the metabolism and proliferation of aggressive prostate tumors. PMID:27825143

  14. The effect of metal oxide nanoparticles on functional bacteria and metabolic profiles in agricultural soil.

    PubMed

    Chai, Hankui; Yao, Jun; Sun, Jingjing; Zhang, Chi; Liu, Wenjuan; Zhu, Mijia; Ceccanti, Brunello

    2015-04-01

    A significant knowledge gap in nanotechnology is the absence of standardized protocols for examining the effect of engineered nanoparticles on soil microorganisms. In this study, agricultural soil was exposed to ZnO, SiO2, TiO2 and CeO2 nanoparticles at 1 mg g(-1). The toxicity effect was evaluated by thermal metabolism, the abundance of functional bacteria and enzymatic activity. ZnO and CeO2 nanoparticles were observed to hinder thermogenic metabolism, reduce numbers of soil Azotobacter, P-solubilizing and K-solubilizing bacteria and inhibit enzymatic activities. TiO2 nanoparticles reduced the abundance of functional bacteria and enzymatic activity. SiO2 nanoparticles slightly boosted the soil microbial activity. Pearson's correlation analysis showed that thermodynamic parameters had a strong correlation with abundance of functional bacteria and enzymatic activity. These findings demonstrated that the combined approach of monitoring thermal metabolism, functional bacteria and enzymatic activity is feasible for testing the ecotoxicity of nanoparticles on agricultural soil.

  15. Strain/strain rate imaging of impaired left atrial function in patients with metabolic syndrome.

    PubMed

    Fang, Ning-Ning; Sui, Dong-Xin; Yu, Jin-Gui; Gong, Hui-Ping; Zhong, Ming; Zhang, Yun; Zhang, Wei

    2015-11-01

    Left ventricular (LV) dysfunction has been demonstrated in patients with metabolic syndrome (MetS). However, alterations in left atrial (LA) function in MetS are unknown. We aimed to use strain/strain rate (SR) imaging to investigate the effect of MetS on LA function. A total of 177 MetS patients and 156 normal subjects underwent echocardiography. Strain and SR tissue Doppler imaging values were used to evaluate LA function. Partial correlation and multiple stepwise regression analyses were used to determine the risk factors for impaired LA function. Compared with the controls, the MetS patients showed significantly lower levels of mean strain, mean peak systolic SR and mean peak early diastolic SR (P<0.001 for all), with no difference in the mean peak late diastolic SR. Central obesity, hypertension, dyslipidemia and LV diastolic abnormality were independent risk factors for impaired LA function. LA function was impaired in patients with MetS as a result of metabolic disturbance and LV diastolic abnormality. SR imaging is reliable in assessing LA function in MetS patients.

  16. Relation Between Obesity, Metabolic Syndrome, Successful Long-Term Weight Reduction, and Right Ventricular Function.

    PubMed

    Zeller, Judith; Strack, Christina; Fenk, Sabine; Mohr, Margareta; Loew, Thomas; Schmitz, Gerd; Maier, Lars; Fischer, Marcus; Baessler, Andrea

    2016-07-27

    This study sought to examine the relationships between right ventricular (RV) function and geometry, morbid obesity with and without the metabolic syndrome, and the effect of long-term weight loss. Obese (n = 153, BMI 41.2 ± 8.7 kg/m(2)) and healthy non-obese control subjects (n = 38, BMI 25.5 ± 3.3 kg/m(2)) of similar age and gender distribution were prospectively studied during the course of a 1-year weight reduction program with echocardiography at baseline and after one year of follow up. Function and geometry of the right heart were evaluated by tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TDI S'), RV myocardial performance index (TEI), RV end-diastolic (RVEDD) and end-systolic diameter (RVESD), area of the right atrium (RAA), and systolic pulmonary artery pressure (PAP). Whereas parameters of systolic and diastolic LV function were significantly worse in the obese subjects than those in the non-obese subjects (EF 66 ± 6 versus 69 ± 6%, P = 0.004; E/E' 7.4 ± 2.5 versus 6.3 ± 2.6, P = 0.010), parameters of RV function (TAPSE 25.6 ± 4.5 versus 25.1 ± 3.5 mm, P = 0.528; TDI S' 13.5 ± 2.9 versus 13.8 ± 2.9 mm/second, P = 0.553; TEI 0.25 ± 0.13 versus 0.28 ± 0.09, P = 0.283) as well as geometry measurements were comparable between the obese and non-obese participants and also in obese subjects with full blown metabolic syndrome. Additionally, successful weight reduction did not alter the RV parameters. Nevertheless, in the few obese subjects with RV dysfunction (n = 7), metabolic syndrome parameters were more pronounced than in obese with normal RV function.Morbid obesity with and without the metabolic syndrome is accompanied by an impaired LV systolic and diastolic function. In contrast, RV function appears to be less affected by obesity independent of the presence of the metabolic syndrome.

  17. Diet and Gut Microbial Function in Metabolic and Cardiovascular Disease Risk

    PubMed Central

    Meyer, Katie A.; Bennett, Brian J.

    2017-01-01

    Over the past decade, the gut microbiome has emerged as a novel and largely untapped source of variability for metabolic and cardiovascular disease risk, including diabetes. Animal and human studies support several possible pathways through which the gut microbiome may impact health, including the production of health-related metabolites from dietary sources. Diet is considered important to shaping the gut microbiota; in addition, gut microbiota influence the metabolism of many dietary components. In the present paper, we address the distinction between compositional and functional analysis of the gut microbiota. We focus on literature that highlights the value of moving beyond surveys of microbial composition to measuring gut microbial functioning to delineate mechanisms related to the interplay between diet and gut microbiota in cardiometabolic health. PMID:27541295

  18. Diet and Gut Microbial Function in Metabolic and Cardiovascular Disease Risk.

    PubMed

    Meyer, Katie A; Bennett, Brian J

    2016-10-01

    Over the past decade, the gut microbiome has emerged as a novel and largely unexplored source of variability for metabolic and cardiovascular disease risk, including diabetes. Animal and human studies support several possible pathways through which the gut microbiome may impact health, including the production of health-related metabolites from dietary sources. Diet is considered important to shaping the gut microbiota; in addition, gut microbiota influence the metabolism of many dietary components. In the present paper, we address the distinction between compositional and functional analysis of the gut microbiota. We focus on literature that highlights the value of moving beyond surveys of microbial composition to measuring gut microbial functioning to delineate mechanisms related to the interplay between diet and gut microbiota in cardiometabolic health.

  19. Metabolism of xenobiotics of human environments.

    PubMed

    Croom, Edward

    2012-01-01

    Xenobiotics have been defined as chemicals to which an organism is exposed that are extrinsic to the normal metabolism of that organism. Without metabolism, many xenobiotics would reach toxic concentrations. Most metabolic activity inside the cell requires energy, cofactors, and enzymes in order to occur. Xenobiotic-metabolizing enzymes can be divided into phase I, phase II, and transporter enzymes. Lipophilic xenobiotics are often first metabolized by phase I enzymes, which function to make xenobiotics more polar and provide sites for conjugation reactions. Phase II enzymes are conjugating enzymes and can directly interact with xenobiotics but more commonly interact with metabolites produced by phase I enzymes. Through both passive and active transport, these more polar metabolites are eliminated. Most xenobiotics are cleared through multiple enzymes and pathways. The relationship between chemical concentrations, enzyme affinity and quantity, and cofactor availability often determine which metabolic reactions dominate in a given individual.

  20. Functional Fixedness and Functional Reduction as Common Sense Reasonings in Chemical Equilibrium and in Geometry and Polarity of Molecules.

    ERIC Educational Resources Information Center

    Furio, C.; Calatayud, M. L.; Barcenas, S. L.; Padilla, O. M.

    2000-01-01

    Focuses on learning difficulties in procedural knowledge, and assesses the procedural difficulties of grade 12 and first- and third-year university students based on common sense reasoning in two areas of chemistry--chemical equilibrium and geometry, and polarity of molecules. (Contains 55 references.) (Author/YDS)

  1. Studies on the metabolism and toxicological detection of the amphetamine-like anorectic fenproporex in human urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay.

    PubMed

    Kraemer, T; Theis, G A; Weber, A A; Maurer, H H

    2000-01-28

    Studies on the metabolism and the toxicological analysis of fenproporex (R,S-3-[(1-phenyl-2-propyl)-amino]-propionitrile, FP) using GC-MS and fluorescence polarization immunoassay are described. The metabolites were identified in urine samples of volunteers by GC-MS after cleavage of conjugates, extraction and acetylation. Besides unchanged FP, fourteen metabolites, including amphetamine, could be identified. Two partially overlapping metabolic pathways could be postulated: ring degradation by one- and two-fold aromatic hydroxylation followed by methylation and side chain degradation by N-dealkylation to amphetamine (AM). A minor pathway leads via beta-hydroxylation of AM to norephedrine. For GC-MS detection, the systematic toxicological analysis procedure including acid hydrolysis, extraction at pH 8-9 and acetylation was suitable (detection limits 50 ng/ml for FP and 100 ng/ml for AM). Excretion studies showed, that only AM but neither FP nor its specific metabolites were detectable 30-60 h after ingestion of 20 mg of FP. Therefore, misinterpretation can occur. The Abbott TDx FPIA amphetamine/methamphetamine II gave positive results up to 58 h. All the positive immunoassay results could be confirmed by the described GC-MS procedure.

  2. Studies on the metabolism and toxicological detection of the amphetamine-like anorectic mefenorex in human urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay.

    PubMed

    Kraemer, T; Vernaleken, I; Maurer, H H

    1997-11-21

    Studies on the metabolism and on the toxicological analysis of mefenorex [R,S-N-(3-chloropropyl)-alpha-methylphenethylamine, MF] using gas chromatography-mass spectrometry (GC-MS) and fluorescence polarization immunoassay (FPIA) are described. The metabolites were identified in urine samples of volunteers by GC-MS. Besides MF, thirteen metabolites including amphetamine (AM) could be identified and three partially overlapping metabolic pathways could be postulated. For GC-MS detection, the systematic toxicological analysis procedure including acid hydrolysis, extraction at pH 8-9 and acetylation was suitable (detection limits 50 ng/ml for MF and 100 ng/ml for AM). Excretion studies showed, that only AM but neither MF nor its specific metabolites were detectable between 32 and 68 h after ingestion of 80 mg of MF. Therefore, misinterpretation can occur. The Abbott TDx FPIA amphetamine/methamphetamine II gave positive results up to 68 h. All the positive immunoassay results could be confirmed by the described GC-MS procedure.

  3. Design of strategies to study the metabolic profile of highly polar compounds in plasma by reversed-phase liquid chromatography-high resolution mass spectrometry.

    PubMed

    Sánchez-López, Elena; Crego, Antonio L; Marina, María Luisa

    2017-03-24

    Amino acids and related compounds are paramount analytes which are involved in numerous metabolic pathways. Most of these compounds are unable to be retained on Liquid Chromatography with Reversed-Phase stationary phases due to their high hydrophilic character. An interesting strategy is to reduce their polarity through their derivatization with a labelling reagent, such as the commercially available 9-fluorenylmethyloxycarbonyl (FMOC) which forms stable complexes with primary and secondary amine moieties rapidly. Although some derivatization reagents have been employed in the study of metabolic profiles, as far as we know, FMOC has never been employed for this purpose. In this work, it is demonstrated that the use of RP-LCMS(TOF) using a C18 column and FMOC as labelling agent enables the determination of a larger number of hydrophilic compounds (proteinogenic amino acids, non-proteinogenic amino acids, and biogenic amines) when compared to the use of a fully-wettable pentafluorophenyl column in fully-aqueous conditions (gradient starting in 0% of organic solvent) and HILIC column, both without using compound derivatization. Different strategies for plasma protein elimination were also carefully evaluated. Results revealed that ultrafiltration (UF) offered a lower variability from sample to sample when compared to the protein precipitation (PP) method (from 2 to 12 times lower variability found in UF). Additionally, UF preserved a larger number of possible compounds when compared to the PP approach: 4631 unique molecular features with UF, 666 unique molecular features with PP.

  4. Metabolic Activity and Functional Diversity Changes in Sediment Prokaryotic Communities Organically Enriched with Mussel Biodeposits

    PubMed Central

    Pollet, Thomas; Cloutier, Olivier; Nozais, Christian; McKindsey, Christopher W.; Archambault, Philippe

    2015-01-01

    This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture. PMID:25923715

  5. Metabolic activity and functional diversity changes in sediment prokaryotic communities organically enriched with mussel biodeposits.

    PubMed

    Pollet, Thomas; Cloutier, Olivier; Nozais, Christian; McKindsey, Christopher W; Archambault, Philippe

    2015-01-01

    This experimental microcosm study reports the influence of organic enrichments by mussel biodeposits on the metabolic activity and functional diversity of benthic prokaryotic communities. The different biodeposit enrichment regimes created, which mimicked the quantity of faeces and pseudo-faeces potentially deposited below mussel farms, show a clear stimulatory effect of this organic enrichment on prokaryotic metabolic activity. This effect was detected once a certain level of biodeposition was attained with a tipping point estimated between 3.25 and 10 g day-1 m-2. Prokaryotic communities recovered their initial metabolic activity by 11 days after the cessation of biodeposit additions. However, their functional diversity remained greater than prior to the disturbance suggesting that mussel biodeposit enrichment may disturb the functioning and perhaps the role of prokaryotic communities in benthic ecosystems. This manipulative approach provided new information on the influence of mussel biodeposition on benthic prokaryotic communities and dose-response relationships and may support the development of carrying capacity models for bivalve culture.

  6. Diurnal Changes in Mitochondrial Function Reveal Daily Optimization of Light and Dark Respiratory Metabolism in Arabidopsis*

    PubMed Central

    Lee, Chun Pong; Eubel, Holger; Millar, A. Harvey

    2010-01-01

    Biomass production by plants is often negatively correlated with respiratory rate, but the value of this rate changes dramatically during diurnal cycles, and hence, biomass is the cumulative result of complex environment-dependent metabolic processes. Mitochondria in photosynthetic plant tissues undertake substantially different metabolic roles during light and dark periods that are dictated by substrate availability and the functional capacity of mitochondria defined by their protein composition. We surveyed the heterogeneity of the mitochondrial proteome and its function during a typical night and day cycle in Arabidopsis shoots. This used a staged, quantitative analysis of the proteome across 10 time points covering 24 h of the life of 3-week-old Arabidopsis shoots grown under 12-h dark and 12-h light conditions. Detailed analysis of enzyme capacities and substrate-dependent respiratory processes of isolated mitochondria were also undertaken during the same time course. Together these data reveal a range of dynamic changes in mitochondrial capacity and uncover day- and night-enhanced protein components. Clear diurnal changes were evident in mitochondrial capacities to drive the TCA cycle and to undertake functions associated with nitrogen and sulfur metabolism, redox poise, and mitochondrial antioxidant defense. These data quantify the nature and nuances of a daily rhythm in Arabidopsis mitochondrial respiratory capacity. PMID:20601493

  7. Large-scale functional analysis of the roles of phosphorylation in yeast metabolic pathways.

    PubMed

    Schulz, Juliane Caroline; Zampieri, Mattia; Wanka, Stefanie; von Mering, Christian; Sauer, Uwe

    2014-11-25

    Protein phosphorylation is a widespread posttranslational modification that regulates almost all cellular functions. To investigate the large number of phosphorylation events with unknown functions, we monitored the concentrations of several hundred intracellular metabolites in Saccharomyces cerevisiae yeast strains with deletions of 118 kinases or phosphatases. Whereas most deletion strains had no detectable difference in growth compared to wild-type yeast, two-thirds of deletion strains had alterations in metabolic profiles. For about half of the kinases and phosphatases encoded by the deleted genes, we inferred specific regulatory roles on the basis of knowledge about the affected metabolic pathways. We demonstrated that the phosphatase Ppq1 was required for metal homeostasis. Combining metabolomic data with published phosphoproteomic data in a stoichiometric model enabled us to predict functions for phosphorylation in the regulation of 47 enzymes. Overall, we provided insights and testable predictions covering greater than twice the number of known phosphorylated enzymes in yeast, suggesting extensive phosphorylation-dependent regulation of yeast metabolism.

  8. Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols

    PubMed Central

    Rossetti, Paola; Buscema, Massimo; Condorelli, Rosita Angela; Gullo, Giuseppe; Triolo, Onofrio

    2016-01-01

    Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients' fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS. PMID:27579037

  9. Functional analysis of free fatty acid receptor GPR120 in human eosinophils: implications in metabolic homeostasis.

    PubMed

    Konno, Yasunori; Ueki, Shigeharu; Takeda, Masahide; Kobayashi, Yoshiki; Tamaki, Mami; Moritoki, Yuki; Oyamada, Hajime; Itoga, Masamichi; Kayaba, Hiroyuki; Omokawa, Ayumi; Hirokawa, Makoto

    2015-01-01

    Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express GPR120 and, if present, whether it possesses a functional capacity on eosinophils. Eosinophils isolated from peripheral venous blood expressed GPR120 at both the mRNA and protein levels. Stimulation with a synthetic GPR120 agonist, GW9508, induced rapid down-regulation of cell surface expression of GPR120, suggesting ligand-dependent receptor internalization. Although GPR120 activation did not induce eosinophil chemotactic response and degranulation, we found that GW9508 inhibited eosinophil spontaneous apoptosis and Fas receptor expression. The anti-apoptotic effect was attenuated by phosphoinositide 3-kinase (PI3K) inhibitors and was associated with inhibition of caspase-3 activity. Eosinophil response investigated using ELISpot assay indicated that stimulation with a GPR120 agonist induced IL-4 secretion. These findings demonstrate the novel functional properties of fatty acid sensor GPR120 on human eosinophils and indicate the previously unrecognized link between nutrient metabolism and the immune system.

  10. Air Pollution Exposure During Pregnancy and Fetal Markers of Metabolic function: The MIREC Study.

    PubMed

    Lavigne, Eric; Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E; Hystad, Perry; Johnson, Markey; Crouse, Dan L; Ettinger, Adrienne S; Shapiro, Gabriel D; Fisher, Mandy; Morisset, Anne-Sophie; Taback, Shayne; Bouchard, Maryse F; Sun, Liu; Monnier, Patricia; Dallaire, Renée; Fraser, William D

    2016-05-01

    Previous evidence suggests that exposure to outdoor air pollution during pregnancy could alter fetal metabolic function, which could increase the risk of obesity in childhood. However, to our knowledge, no epidemiologic study has investigated the association between prenatal exposure to air pollution and indicators of fetal metabolic function. We investigated the association between maternal exposure to nitrogen dioxide and fine particulate matter (aerodynamic diameter ≤2.5 µm) and umbilical cord blood leptin and adiponectin levels with mixed-effects linear regression models among 1,257 mother-infant pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, conducted in Canada (2008-2011). We observed that an interquartile-range increase in average exposure to fine particulate matter (3.2 µg/m(3)) during pregnancy was associated with an 11% (95% confidence interval: 4, 17) increase in adiponectin levels. We also observed 13% (95% confidence interval: 6, 20) higher adiponectin levels per interquartile-range increase in average exposure to nitrogen dioxide (13.6 parts per billion) during pregnancy. Significant associations were seen between air pollution markers and cord blood leptin levels in models that adjusted for birth weight z score but not in models that did not adjust for birth weight z score. The roles of prenatal exposure to air pollution and fetal metabolic function in the potential development of childhood obesity should be further explored.

  11. The functional gene composition and metabolic potential of coral-associated microbial communities

    PubMed Central

    Zhang, Yanying; Ling, Juan; Yang, Qingsong; Wen, Chongqing; Yan, Qingyun; Sun, Hongyan; Van Nostrand, Joy D.; Shi, Zhou; Zhou, Jizhong; Dong, Junde

    2015-01-01

    The phylogenetic diversity of coral-associated microbes has been extensively examined, but some contention remains regarding whether coral-associated microbial communities are species-specific or site-specific. It is suggested that corals may associate with microbes in terms of function, although little is known about the differences in coral-associated microbial functional gene composition and metabolic potential among coral species. Here, 16S rRNA Illumina sequencing and functional gene array (GeoChip 5.0) were used to assess coral-associated microbial communities. Our results indicate that both host species and environmental variables significantly correlate with shifts in the microbial community structure and functional potential. Functional genes related to key biogeochemical cycles including carbon, nitrogen, sulfur and phosphorus cycling, metal homeostasis, organic remediation, antibiotic resistance and secondary metabolism were shown to significantly vary between and among the four study corals (Galaxea astreata, Porites lutea, Porites andrewsi and Pavona decussata). Genes specific for anammox were also detected for the first time in the coral holobiont and positively correlated with ammonium. This study reveals that variability in the functional potential of coral-associated microbial communities is largely driven by changes in environmental factors and further demonstrates the importance of linking environmental parameters with genomic data in complex environmental systems. PMID:26536917

  12. Cerebral energy metabolism and the brain's functional network architecture: an integrative review

    PubMed Central

    Lord, Louis-David; Expert, Paul; Huckins, Jeremy F; Turkheimer, Federico E

    2013-01-01

    Recent functional magnetic resonance imaging (fMRI) studies have emphasized the contributions of synchronized activity in distributed brain networks to cognitive processes in both health and disease. The brain's ‘functional connectivity' is typically estimated from correlations in the activity time series of anatomically remote areas, and postulated to reflect information flow between neuronal populations. Although the topological properties of functional brain networks have been studied extensively, considerably less is known regarding the neurophysiological and biochemical factors underlying the temporal coordination of large neuronal ensembles. In this review, we highlight the critical contributions of high-frequency electrical oscillations in the γ-band (30 to 100 Hz) to the emergence of functional brain networks. After describing the neurobiological substrates of γ-band dynamics, we specifically discuss the elevated energy requirements of high-frequency neural oscillations, which represent a mechanistic link between the functional connectivity of brain regions and their respective metabolic demands. Experimental evidence is presented for the high oxygen and glucose consumption, and strong mitochondrial performance required to support rhythmic cortical activity in the γ-band. Finally, the implications of mitochondrial impairments and deficits in glucose metabolism for cognition and behavior are discussed in the context of neuropsychiatric and neurodegenerative syndromes characterized by large-scale changes in the organization of functional brain networks. PMID:23756687

  13. Functional imaging using the retinal function imager: direct imaging of blood velocity, achieving fluorescein angiography-like images without any contrast agent, qualitative oximetry, and functional metabolic signals.

    PubMed

    Izhaky, David; Nelson, Darin A; Burgansky-Eliash, Zvia; Grinvald, Amiram

    2009-07-01

    The Retinal Function Imager (RFI; Optical Imaging, Rehovot, Israel) is a unique, noninvasive multiparameter functional imaging instrument that directly measures hemodynamic parameters such as retinal blood-flow velocity, oximetric state, and metabolic responses to photic activation. In addition, it allows capillary perfusion mapping without any contrast agent. These parameters of retinal function are degraded by retinal abnormalities. This review delineates the development of these parameters and demonstrates their clinical applicability for noninvasive detection of retinal function in several modalities. The results suggest multiple clinical applications for early diagnosis of retinal diseases and possible critical guidance of their treatment.

  14. Development of an Objective Space Suit Mobility Performance Metric Using Metabolic Cost and Functional Tasks

    NASA Technical Reports Server (NTRS)

    McFarland, Shane M.; Norcross, Jason

    2016-01-01

    Existing methods for evaluating EVA suit performance and mobility have historically concentrated on isolated joint range of motion and torque. However, these techniques do little to evaluate how well a suited crewmember can actually perform during an EVA. An alternative method of characterizing suited mobility through measurement of metabolic cost to the wearer has been evaluated at Johnson Space Center over the past several years. The most recent study involved six test subjects completing multiple trials of various functional tasks in each of three different space suits; the results indicated it was often possible to discern between different suit designs on the basis of metabolic cost alone. However, other variables may have an effect on real-world suited performance; namely, completion time of the task, the gravity field in which the task is completed, etc. While previous results have analyzed completion time, metabolic cost, and metabolic cost normalized to system mass individually, it is desirable to develop a single metric comprising these (and potentially other) performance metrics. This paper outlines the background upon which this single-score metric is determined to be feasible, and initial efforts to develop such a metric. Forward work includes variable coefficient determination and verification of the metric through repeated testing.

  15. Regulation of mitochondrial function by voltage dependent anion channels in ethanol metabolism and the Warburg effect.

    PubMed

    Lemasters, John J; Holmuhamedov, Ekhson L; Czerny, Christoph; Zhong, Zhi; Maldonado, Eduardo N

    2012-06-01

    Voltage dependent anion channels (VDAC) are highly conserved proteins that are responsible for permeability of the mitochondrial outer membrane to hydrophilic metabolites like ATP, ADP and respiratory substrates. Although previously assumed to remain open, VDAC closure is emerging as an important mechanism for regulation of global mitochondrial metabolism in apoptotic cells and also in cells that are not dying. During hepatic ethanol oxidation to acetaldehyde, VDAC closure suppresses exchange of mitochondrial metabolites, resulting in inhibition of ureagenesis. In vivo, VDAC closure after ethanol occurs coordinately with mitochondrial uncoupling. Since acetaldehyde passes through membranes independently of channels and transporters, VDAC closure and uncoupling together foster selective and more rapid oxidative metabolism of toxic acetaldehyde to nontoxic acetate by mitochondrial aldehyde dehydrogenase. In single reconstituted VDAC, tubulin decreases VDAC conductance, and in HepG2 hepatoma cells, free tubulin negatively modulates mitochondrial membrane potential, an effect enhanced by protein kinase A. Tubulin-dependent closure of VDAC in cancer cells contributes to suppression of mitochondrial metabolism and may underlie the Warburg phenomenon of aerobic glycolysis. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.

  16. Metabolic functions of Pseudomonas fluorescens strains from Populus deltoides depend on rhizosphere or endosphere isolation compartment

    PubMed Central

    Timm, Collin M.; Campbell, Alisha G.; Utturkar, Sagar M.; Jun, Se-Ran; Parales, Rebecca E.; Tan, Watumesa A.; Robeson, Michael S.; Lu, Tse-Yuan S.; Jawdy, Sara; Brown, Steven D.; Ussery, David W.; Schadt, Christopher W.; Tuskan, Gerald A.; Doktycz, Mitchel J.; Weston, David J.; Pelletier, Dale A.

    2015-01-01

    The bacterial microbiota of plants is diverse, with 1000s of operational taxonomic units (OTUs) associated with any individual plant. In this work, we used phenotypic analysis, comparative genomics, and metabolic models to investigate the differences between 19 sequenced Pseudomonas fluorescens strains. These isolates represent a single OTU and were collected from the rhizosphere and endosphere of Populus deltoides. While no traits were exclusive to either endosphere or rhizosphere P. fluorescens isolates, multiple pathways relevant for plant-bacterial interactions are enriched in endosphere isolate genomes. Further, growth phenotypes such as phosphate solubilization, protease activity, denitrification and root growth promotion are biased toward endosphere isolates. Endosphere isolates have significantly more metabolic pathways for plant signaling compounds and an increased metabolic range that includes utilization of energy rich nucleotides and sugars, consistent with endosphere colonization. Rhizosphere P. fluorescens have fewer pathways representative of plant-bacterial interactions but show metabolic bias toward chemical substrates often found in root exudates. This work reveals the diverse functions that may contribute to colonization of the endosphere by bacteria and are enriched among closely related isolates. PMID:26528266

  17. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome

    PubMed Central

    Mella, Olav; Bruland, Ove; Risa, Kristin; Dyrstad, Sissel E.; Alme, Kine; Rekeland, Ingrid G.; Sapkota, Dipak; Røsland, Gro V.; Fosså, Alexander; Ktoridou-Valen, Irini; Lunde, Sigrid; Sørland, Kari; Lien, Katarina; Herder, Ingrid; Thürmer, Hanne; Gotaas, Merete E.; Baranowska, Katarzyna A.; Bohnen, Louis M.L.J.; Schäfer, Christoph; McCann, Adrian; Sommerfelt, Kristian; Helgeland, Lars; Ueland, Per M.; Dahl, Olav

    2016-01-01

    Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is a debilitating disease of unknown etiology, with hallmark symptoms including postexertional malaise and poor recovery. Metabolic dysfunction is a plausible contributing factor. We hypothesized that changes in serum amino acids may disclose specific defects in energy metabolism in ME/CFS. Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients. The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion. The amino acid changes could not be explained by symptom severity, disease duration, age, BMI, or physical activity level among patients. These findings are in agreement with the clinical disease presentation of ME/CFS, with inadequate ATP generation by oxidative phosphorylation and excessive lactate generation upon exertion. PMID:28018972

  18. Metabolic functions of Pseudomonas fluorescens strains from Populus deltoides depend on rhizosphere or endosphere isolation compartment

    SciTech Connect

    Timm, Collin M.; Campbell, Alicia G.; Utturkar, Sagar M.; Jun, Se Ran; Parales, Rebecca E.; Tan, Mesa; Robeson, Michael S.; Lu, Tse-Yuan S.; Jawdy, Sara; Schadt, Christopher Warren; Doktycz, Mitchel John; Weston, David; Pelletier, Dale A.

    2015-10-14

    The bacterial microbiota of plants is diverse, with ~1000s of operational taxonomic units (OTUs) associated with any individual plant. In this work we investigate how 19 sequenced Pseudomonas fluorescens strains representing a single OTU isolated from Populus deltoides rhizosphere and endosphere differ using phenotypic analysis, comparative genomics, and metabolic models. While no traits were exclusive to either endosphere or rhizosphere P. fluorescens isolates, multiple pathways relevant for bacterial-plant interactions are enriched in endosphere isolate genomes and growth phenotypes such as phosphate solubilization, protease activity, denitrification and root growth promotion are biased towards endosphere isolates. Endosphere isolates have more metabolic pathways for plant signaling compounds and an increased metabolic range that includes utilization of energy rich nucleotides and sugars, consistent with endosphere colonization. Rhizosphere P. fluorescens have fewer pathways important for bacterial-plant interactions but show metabolic bias towards chemical substrates often found in root exudates. This work reveals the diverse functions that may contribute to colonization of the endosphere by bacteria that are enriched in event he most closely related isolates.

  19. Metabolic functions of Pseudomonas fluorescens strains from Populus deltoides depend on rhizosphere or endosphere isolation compartment

    DOE PAGES

    Timm, Collin M.; Campbell, Alicia G.; Utturkar, Sagar M.; ...

    2015-10-14

    The bacterial microbiota of plants is diverse, with ~1000s of operational taxonomic units (OTUs) associated with any individual plant. In this work we investigate how 19 sequenced Pseudomonas fluorescens strains representing a single OTU isolated from Populus deltoides rhizosphere and endosphere differ using phenotypic analysis, comparative genomics, and metabolic models. While no traits were exclusive to either endosphere or rhizosphere P. fluorescens isolates, multiple pathways relevant for bacterial-plant interactions are enriched in endosphere isolate genomes and growth phenotypes such as phosphate solubilization, protease activity, denitrification and root growth promotion are biased towards endosphere isolates. Endosphere isolates have more metabolic pathwaysmore » for plant signaling compounds and an increased metabolic range that includes utilization of energy rich nucleotides and sugars, consistent with endosphere colonization. Rhizosphere P. fluorescens have fewer pathways important for bacterial-plant interactions but show metabolic bias towards chemical substrates often found in root exudates. This work reveals the diverse functions that may contribute to colonization of the endosphere by bacteria that are enriched in event he most closely related isolates.« less

  20. Beneficial effects of herbs, spices and medicinal plants on the metabolic syndrome, brain and cognitive function.

    PubMed

    Panickar, Kiran S

    2013-03-01

    Herbs and spices have been used since ancient times to not only improve the flavor of edible food but also to prevent and treat chronic health maladies. While the scientific evidence for the use of such common herbs and medicinal plants then had been scarce or lacking, the beneficial effects observed from such use were generally encouraging. It is, therefore, not surprising that the tradition of using such herbs, perhaps even after the advent of modern medicine, has continued. More recently, due to an increased interest in understanding the nutritional effects of herbs/spices more comprehensively, several studies have examined the cellular and molecular modes of action of the active chemical components in herbs and their biological properties. Beneficial actions of herbs/spices include anti-inflammatory, antioxidant, anti-hypertensive, gluco-regulatory, and anti-thrombotic effects. One major component of herbs and spices is the polyphenols. Some of the aforementioned properties are attributed to the polyphenols and they are associated with attenuating the metabolic syndrome. Detrimental changes associated with the metabolic syndrome over time affect brain and cognitive function. Metabolic syndrome and type-2 diabetes are also risk factors for Alzheimer's disease and stroke. In addition, the neuroprotective effects of herbs and spices have been demonstrated and, whether directly or indirectly, such beneficial effects may also contribute to an improvement in cognitive function. This review evaluates the current evidence available for herbs/spices in potentially improving the metabolic syndrome, as well as their neuroprotective effects on the brain, and cognitive function in animal and human studies.

  1. Adiponectin Regulates the Polarization and Function of Microglia via PPAR-γ Signaling Under Amyloid β Toxicity

    PubMed Central

    Song, Juhyun; Choi, Seong-Min; Kim, Byeong C.

    2017-01-01

    Alzheimer’s disease (AD), characterized by the abnormal accumulation of amyloid beta (Aβ), is gradually increasing globally. Given that AD is considered a neuroinflammatory disease, recent studies have focused on the cellular mechanisms in brain inflammatory conditions that underlie AD neuropathology. Microglia are macrophage cells in the central nervous system (CNS) that are activated in response to Aβ condition. The function of microglia contributes to the neuroinflammation in AD brain, suggesting that microglia regulate the production of inflammatory mediators and contribute to the regeneration of damaged tissues. Adiponectin, an adipokine derived from adipose tissue, has been known to regulate inflammation and control macrophages during oxidative stress conditions. In present study, we investigated whether adiponectin influences the polarization and function of microglia under Aβ toxicity by examining alterations of BV2 microglia function and polarization by Acrp30 (a globular form of adiponectin) treatment using reverse transcription PCR, western blotting and immunofluorescence staining. Acrp30 promoted the induction of the M2 phenotype, and regulated the inflammatory responses through peroxisome proliferator-activated receptor (PPAR)-γ signaling under Aβ toxicity. In addition, Acrp30 boosted the capacity of Aβ scavenging in microglia. Taken together, we suggest that adiponectin may control the function of microglia by promoting anti-inflammatory responses through PPAR- γ signaling. Hence, we conclude that adiponectin may act as a critical controller of microglia function in the AD brain. PMID:28326017

  2. Polarizing cues.

    PubMed

    Nicholson, Stephen P

    2012-01-01

    People categorize themselves and others, creating ingroup and outgroup distinctions. In American politics, parties constitute the in- and outgroups, and party leaders hold sway in articulating party positions. A party leader's endorsement of a policy can be persuasive, inducing co-partisans to take the same position. In contrast, a party leader's endorsement may polarize opinion, inducing out-party identifiers to take a contrary position. Using survey experiments from the 2008 presidential election, I examine whether in- and out-party candidate cues—John McCain and Barack Obama—affected partisan opinion. The results indicate that in-party leader cues do not persuade but that out-party leader cues polarize. This finding holds in an experiment featuring President Bush in which his endorsement did not persuade Republicans but it polarized Democrats. Lastly, I compare the effect of party leader cues to party label cues. The results suggest that politicians, not parties, function as polarizing cues.

  3. The interplay between genotype, metabolic state and cofactor treatment governs phenylalanine hydroxylase function and drug response.

    PubMed

    Staudigl, Michael; Gersting, Søren W; Danecka, Marta K; Messing, Dunja D; Woidy, Mathias; Pinkas, Daniel; Kemter, Kristina F; Blau, Nenad; Muntau, Ania C

    2011-07-01

    The discovery of a pharmacological treatment for phenylketonuria (PKU) raised new questions about function and dysfunction of phenylalanine hydroxylase (PAH), the enzyme deficient in this disease. To investigate the interdependence of the genotype, the metabolic state (phenylalanine substrate) and treatment (BH(4) cofactor) in the context of enzyme function in vitro and in vivo, we (i) used a fluorescence-based method for fast enzyme kinetic analyses at an expanded range of phenylalanine and BH(4) concentrations, (ii) depicted PAH function as activity landscapes, (iii) retraced the analyses in eukaryotic cells, and (iv) translated this into the human system by analyzing the outcome of oral BH(4) loading tests. PAH activity landscapes uncovered the optimal working range of recombinant wild-type PAH and provided new insights into PAH kinetics. They demonstrated how mutations might alter enzyme function in the space of varying substrate and cofactor concentrations. Experiments in eukaryotic cells revealed that the availability of the active PAH enzyme depends on the phenylalanine-to-BH(4) ratio. Finally, evaluation of data from BH(4) loading tests indicated that the patient's genotype influences the impact of the metabolic state on drug response. The results allowed for visualization and a better understanding of PAH function in the physiological and pathological state as well as in the therapeutic context of cofactor treatment. Moreover, our data underscore the need for more personalized procedures to safely identify and treat patients with BH(4)-responsive PAH deficiency.

  4. Liver disease alters high-density lipoprotein composition, metabolism and function.

    PubMed

    Trieb, Markus; Horvath, Angela; Birner-Gruenberger, Ruth; Spindelboeck, Walter; Stadlbauer, Vanessa; Taschler, Ulrike; Curcic, Sanja; Stauber, Rudolf E; Holzer, Michael; Pasterk, Lisa; Heinemann, Akos; Marsche, Gunther

    2016-07-01

    High-density lipoproteins (HDL) are important endogenous inhibitors of inflammatory responses. Functional impairment of HDL might contribute to the excess mortality experienced by patients with liver disease, but the effect of cirrhosis on HDL metabolism and function remain elusive. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function using apolipoprotein (apo) B-depleted sera from patients with compensated cirrhosis, patients with acutely decompensated cirrhosis and healthy controls. We observed that sera of cirrhotic patients showed reduced levels of HDL-cholesterol and profoundly suppressed activities of several enzymes involved in HDL maturation and metabolism. Native gel electrophoresis analyses revealed that cirrhotic serum HDL shifts towards the larger HDL2 subclass. Proteomic assessment of isolated HDL identified several proteins, including apoA-I, apoC-III, apoE, paraoxonase 1 and acute phase serum amyloid A to be significantly altered in cirrhotic patients. With regard to function, these alterations in levels, composition and structure of HDL were strongly associated with metrics of function of apoB-depleted sera, including cholesterol efflux capability, paraoxonase activity, the ability to inhibit monocyte production of cytokines and endothelial regenerative activities. Of particular interest, cholesterol efflux capacity appeared to be strongly associated with liver disease mortality. Our findings may be clinically relevant and improve our ability to monitor cirrhotic patients at high risk.

  5. Omega-3 fatty acids and adipose tissue function in obesity and metabolic syndrome.

    PubMed

    Martínez-Fernández, Leyre; Laiglesia, Laura M; Huerta, Ana E; Martínez, J Alfredo; Moreno-Aliaga, María J

    2015-09-01

    The n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) have been reported to improve obesity-associated metabolic disorders including chronic inflammation, insulin resistance and dyslipidaemia. Growing evidence exits about adipose tissue as a target in mediating the beneficial effects of these marine n-3 PUFAs in adverse metabolic syndrome manifestations. Therefore, in this manuscript we focus in reviewing the current knowledge about effects of marine n-3 PUFAs on adipose tissue metabolism and secretory functions. This scope includes n-3 PUFAs actions on adipogenesis, lipogenesis and lipolysis as well as on fatty acid oxidation and mitochondrial biogenesis. The effects of n-3 PUFAs on adipose tissue glucose uptake and insulin signaling are also summarized. Moreover, the roles of peroxisome proliferator-activated receptor γ (PPARγ) and AMPK activation in mediating n-3 PUFAs actions on adipose tissue functions are discussed. Finally, the mechanisms underlying the ability of n-3 PUFAs to prevent and/or ameliorate adipose tissue inflammation are also revised, focusing on the role of n-3 PUFAs-derived specialized proresolving lipid mediators such as resolvins, protectins and maresins.

  6. A Wearable Hip Assist Robot Can Improve Gait Function and Cardiopulmonary Metabolic Efficiency in Elderly Adults.

    PubMed

    Lee, Hwang-Jae; Lee, Suhyun; Chang, Won Hyuk; Seo, Keehong; Shim, Youngbo; Choi, Byung-Ok; Ryu, Gyu-Ha; Kim, Yun-Hee

    2017-02-06

    The aims of this study were to investigate the effectiveness of a newly developed wearable hip assist robot that uses an active assist algorithm to improve gait function, muscle effort, and cardiopulmonary metabolic efficiency in elderly adults. Thirty elderly adults (15 males/15 females) participated in this study. The experimental protocol consisted of overground gait at comfortable speed under three different conditions: free gait without robot assistance, robot-assisted gait with zero torque (RAG-Z), and full robot-assisted gait (RAG). Under all conditions, muscle effort was analyzed using a 12-channel surface electromyography system. Spatio-temporal data were collected at 120 Hz using a 3D motion capture system with six infrared cameras. Metabolic cost parameters were collected as oxygen consumption per unit (ml/min/kg) and aerobic energy expenditure (Kcal/min). In the RAG condition, participants demonstrated improved gait function, decreased muscle effort, and reduced metabolic cost. Although the hip assist robot only provides assistance at the hip joint, our results demonstrated a clear reduction in knee and ankle muscle activity in addition to decreased hip flexor and extensor activity. Our findings suggest that this robot has the potential to improve stabilization of the trunk during walking in elderly adults.

  7. Novel metabolic and physiological functions of branched chain amino acids: a review.

    PubMed

    Zhang, Shihai; Zeng, Xiangfang; Ren, Man; Mao, Xiangbing; Qiao, Shiyan

    2017-01-01

    It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis. (2) BCAA, especially isoleucine, play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters. (3) Supplementation of leucine in the diet enhances meat quality in finishing pigs. (4) BCAA are beneficial for mammary health, milk quality and embryo growth. (5) BCAA enhance intestinal development, intestinal amino acid transportation and mucin production. (6) BCAA participate in up-regulating innate and adaptive immune responses. In addition, abnormally elevated BCAA levels in the blood (decreased BCAA catabolism) are a good biomarker for the early detection of obesity, diabetes and other metabolic diseases. This review will provide some insights into these novel metabolic and physiological functions of BCAA.

  8. Sequence divergence and diversity suggests ongoing functional diversification of vertebrate NAD metabolism.

    PubMed

    Gossmann, Toni I; Ziegler, Mathias

    2014-11-01

    NAD is not only an important cofactor in redox reactions but has also received attention in recent years because of its physiological importance in metabolic regulation, DNA repair and signaling. In contrast to the redox reactions, these regulatory processes involve degradation of NAD and therefore necessitate a constant replenishment of its cellular pool. NAD biosynthetic enzymes are common to almost all species in all clades, but the number of NAD degrading enzymes varies substantially across taxa. In particular, vertebrates, including humans, have a manifold of NAD degrading enzymes which require a high turnover of NAD. As there is currently a lack of a systematic study of how natural selection has shaped enzymes involved in NAD metabolism we conducted a comprehensive evolutionary analysis based on intraspecific variation and interspecific divergence. We compare NAD biosynthetic and degrading enzymes in four eukaryotic model species and subsequently focus on human NAD metabolic enzymes and their orthologs in other vertebrates. We find that the majority of enzymes involved in NAD metabolism are subject to varying levels of purifying selection. While NAD biosynthetic enzymes appear to experience a rather high level of evolutionary constraint, there is evidence for positive selection among enzymes mediating NAD-dependent signaling. This is particularly evident for members of the PARP family, a diverse protein family involved in DNA damage repair and programmed cell death. Based on haplotype information and substitution rate analysis we pinpoint sites that are potential targets of positive selection. We also link our findings to a three dimensional structure, which suggests that positive selection occurs in domains responsible for DNA binding and polymerization rather than the NAD catalytic domain. Taken together, our results indicate that vertebrate NAD metabolism is still undergoing functional diversification.

  9. Glucosinolate metabolism, functionality and breeding for the improvement of Brassicaceae vegetables

    PubMed Central

    Ishida, Masahiko; Hara, Masakazu; Fukino, Nobuko; Kakizaki, Tomohiro; Morimitsu, Yasujiro

    2014-01-01

    Unique secondary metabolites, glucosinolates (S-glucopyranosyl thiohydroximates), are naturally occurring S-linked glucosides found mainly in Brassicaceae plants. They are enzymatically hydrolyzed to produce sulfate ions, D-glucose, and characteristic degradation products such as isothiocyanates. The functions of glucosinolates in the plants remain unclear, but isothiocyanates possessing a pungent or irritating taste and odor might be associated with plant defense from microbes. Isothiocyanates have been studied extensively in experimental in vitro and in vivo carcinogenesis models for their cancer chemopreventive properties. The beneficial isothiocyanates, glucosinolates that are functional for supporting human health, have received attention from many scientists studying plant breeding, plant physiology, plant genetics, and food functionality. This review presents a summary of recent topics related with glucosinolates in the Brassica family, along with a summary of the chemicals, metabolism, and genes of glucosinolates in Brassicaceae. The bioavailabilities of isothiocyanates from certain functional glucosinolates and the importance of breeding will be described with emphasis on glucosinolates. PMID:24987290

  10. Effects of acute and chronic systemic methamphetamine on respiratory, cardiovascular and metabolic function, and cardiorespiratory reflexes

    PubMed Central

    Hassan, Sarah F.; Wearne, Travis A.; Cornish, Jennifer L.

    2016-01-01

    Key points Methamphetamine (METH) abuse is escalating worldwide, with the most common cause of death resulting from cardiovascular failure and hyperthermia; however, the underlying physiological mechanisms are poorly understood.Systemic administration of METH in anaesthetised rats reduced the effectiveness of some protective cardiorespiratory reflexes, increased central respiratory activity independently of metabolic function, and increased heart rate, metabolism and respiration in a pattern indicating that non‐shivering thermogenesis contributes to the well‐described hyperthermia.In animals that showed METH‐induced behavioural sensitisation following chronic METH treatment, no changes were evident in baseline cardiovascular, respiratory and metabolic measures and the METH‐evoked effects in these parameters were similar to those seen in saline‐treated or drug naïve animals.Physiological effects evoked by METH were retained but were neither facilitated nor depressed following chronic treatment with METH.These data highlight and identify potential mechanisms for targeted intervention in patients vulnerable to METH overdose. Abstract Methamphetamine (METH) is known to promote cardiovascular failure or life‐threatening hyperthermia; however, there is still limited understanding of the mechanisms responsible for evoking the physiological changes. In this study, we systematically determined the effects on both autonomic and respiratory outflows, as well as reflex function, following acute and repeated administration of METH, which enhances behavioural responses. Arterial pressure, heart rate, phrenic nerve discharge amplitude and frequency, lumbar and splanchnic sympathetic nerve discharge, interscapular brown adipose tissue and core temperatures, and expired CO2 were measured in urethane‐anaesthetised male Sprague‐Dawley rats. Novel findings include potent increases in central inspiratory drive and frequency that are not dependent on METH

  11. Response functions for dimers and square-symmetric molecules in four-wave-mixing experiments with polarized light.

    PubMed

    Smith, Eric Ryan; Farrow, Darcie A; Jonas, David M

    2005-07-22

    Four-wave-mixing nonlinear-response functions are given for intermolecular and intramolecular vibrations of a perpendicular dimer and intramolecular vibrations of a square-symmetric molecule containing a doubly degenerate state. A two-dimensional particle-in-a-box model is used to approximate the electronic wave functions and obtain harmonic potentials for nuclear motion. Vibronic interactions due to symmetry-lowering distortions along Jahn-Teller active normal modes are discussed. Electronic dephasing due to nuclear motion along both symmetric and asymmetric normal modes is included in these response functions, but population transfer between states is not. As an illustration, these response functions are used to predict the pump-probe polarization anisotropy in the limit of impulsive excitation.

  12. THE IMPACT OF SLEEP DISTURBANCES ON ADIPOCYTE FUNCTION AND LIPID METABOLISM

    PubMed Central

    Broussard, Josiane

    2010-01-01

    Classically, sleep has been considered to serve an essential restorative function for the brain. However, there are an increasing number of studies linking decreased sleep quantity and/or quality in humans to an increased obesity and diabetes risk. Reductions in sleep quantity or quality lead to an increase in hunger and appetite, which chronically could predispose an individual to obesity. Carefully controlled studies have shown that two nights of insufficient sleep is causally linked to a decrease in disposition index, the most commonly used predictor of an individual’s diabetes risk, and impairments in glucose tolerance and insulin sensitivity. Thus, sleep appears to play a critical role in modulating energy metabolism in peripheral tissues. Here we will discuss recent work implicating adipose tissue as a potential direct target of disruption of sleep quality, and explore the potential mechanistic links between sleep, adipose tissue and the global control of energy metabolism in humans. PMID:21112024

  13. Structure-Function of CD36 and Importance of Fatty Acid Signal Transduction in Fat Metabolism

    PubMed Central

    Pepino, Marta Yanina; Kuda, Ondrej; Samovski, Dmitri; Abumrad, Nada A

    2015-01-01

    CD36 is a scavenger receptor that functions in high affinity tissue uptake of long chain fatty acids (FA) and contributes under excessive fat supply to lipid accumulation and metabolic dysfunction. This review describes recent evidence regarding the CD36 FA binding site and a potential mechanism for FA transfer. It also presents the view that CD36 and FA signaling coordinate fat utilization based on newly identified CD36 actions that involve oral fat perception, intestinal fat absorption, secretion of the peptides cholecystokinin and secretin, regulation of hepatic lipoprotein output, activation of beta oxidation by muscle and regulation of the production of the FA derived bioactive eicosanoids. Thus abnormalities of fat metabolism and the associated pathology might involve dysfunction of CD36-mediated signal transduction in addition to the changes of FA uptake. PMID:24850384

  14. Metabolic rate of carrying added mass: a function of walking speed, carried mass and mass location.

    PubMed

    Schertzer, Eliran; Riemer, Raziel

    2014-11-01

    The effort of carrying additional mass at different body locations is important in ergonomics and in designing wearable robotics. We investigate the metabolic rate of carrying a load as a function of its mass, its location on the body and the subject's walking speed. Novel metabolic rate prediction equations for walking while carrying loads at the ankle, knees and back were developed based on experiments where subjects walked on a treadmill at 4, 5 or 6km/h bearing different amounts of added mass (up to 2kg per leg and 22kg for back). Compared to previously reported equations, ours are 7-69% more accurate. Results also show that relative cost for carrying a mass at a distal versus a proximal location changes with speed and mass. Contrary to mass carried on the back, mass attached to the leg cannot be modeled as an increase in body mass.

  15. Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

    PubMed

    Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

    2014-09-01

    It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases.

  16. Polarization functions for the modified m6-31G basis sets for atoms Ga through Kr.

    PubMed

    Mitin, Alexander V

    2013-09-05

    The 2df polarization functions for the modified m6-31G basis sets of the third-row atoms Ga through Kr (Int J Quantum Chem, 2007, 107, 3028; Int J. Quantum Chem, 2009, 109, 1158) are proposed. The performances of the m6-31G, m6-31G(d,p), and m6-31G(2df,p) basis sets were examined in molecular calculations carried out by the density functional theory (DFT) method with B3LYP hybrid functional, Møller-Plesset perturbation theory of the second order (MP2), quadratic configuration interaction method with single and double substitutions and were compared with those for the known 6-31G basis sets as well as with the other similar 641 and 6-311G basis sets with and without polarization functions. Obtained results have shown that the performances of the m6-31G, m6-31G(d,p), and m6-31G(2df,p) basis sets are better in comparison with the performances of the known 6-31G, 6-31G(d,p) and 6-31G(2df,p) basis sets. These improvements are mainly reached due to better approximations of different electrons belonging to the different atomic shells in the modified basis sets. Applicability of the modified basis sets in thermochemical calculations is also discussed.

  17. Systematic analysis of the regulatory functions of microRNAs in chicken hepatic lipid metabolism

    PubMed Central

    Li, Hong; Ma, Zheng; Jia, Lijuan; Li, Yanmin; Xu, Chunlin; Wang, Taian; Han, Ruili; Jiang, Ruirui; Li, Zhuanjian; Sun, Guirong; Kang, Xiangtao; Liu, Xiaojun

    2016-01-01

    Laying performance is an important economic trait in hens, and this physiological process is largely influenced by the liver function. The livers of hens at 20- and 30-week-old stages were investigated using the next generation sequencing to identify the differences of microRNA expression profiles. Compared with the 20-week-old hens, 67 down- and 13 up-regulated microRNAs were verified to be significant differentially expressed (false discovery rate, FDR ≤ 0.05) (SDE) in the 30-week-old. We also identified 13 down- and 6 up-regulated novel differentially expressed (DE) microRNAs. miR-22-3p and miR-146b-5p, which exhibit critical roles in mammalian lipid metabolism, showed the most abundant expression and the highest fold-change, respectively. A total of 648 potential target genes of the SDE microRNAs were identified through an integrated analysis of microRNAs and the DE genes obtained in previous RNA-sequencing, including FADS1, FADS2, ELOVL6 and ACSL5, which are critical lipid metabolism-related regulators. Bioinformatic analyses revealed that target genes were mainly enriched in lipid-related metabolism processes. This work provides the first study of the expression patterns of hepatic microRNAs between 20- and 30-week old hens. The findings may serve as a fundamental resource for understanding the detailed functions of microRNAs in the molecular regulatory systems of lipid metabolism. PMID:27535581

  18. Apolipoprotein E: structure and function in lipid metabolism, neurobiology, and Alzheimer's diseases.

    PubMed

    Huang, Yadong; Mahley, Robert W

    2014-12-01

    Apolipoprotein (apo) E is a multifunctional protein with central roles in lipid metabolism, neurobiology, and neurodegenerative diseases. It has three major isoforms (apoE2, apoE3, and apoE4) with different effects on lipid and neuronal homeostasis. A major function of apoE is to mediate the binding of lipoproteins or lipid complexes in the plasma or interstitial fluids to specific cell-surface receptors. These receptors internalize apoE-containing lipoprotein particles; thus, apoE participates in the distribution/redistribution of lipids among various tissues and cells of the body. In addition, intracellular apoE may modulate various cellular processes physiologically or pathophysiologically, including cytoskeletal assembly and stability, mitochondrial integrity and function, and dendritic morphology and function. Elucidation of the functional domains within this protein and of the three-dimensional structure of the major isoforms of apoE has contributed significantly to our understanding of its physiological and pathophysiological roles at a molecular level. It is likely that apoE, with its multiple cellular origins and multiple structural and biophysical properties, is involved widely in processes of lipid metabolism and neurobiology, possibly encompassing a variety of disorders of neuronal repair, remodeling, and degeneration by interacting with different factors through various pathways.

  19. Functional gains in energy and cell metabolism after TSPO gene insertion.

    PubMed

    Liu, Guo-Jun; Middleton, Ryan J; Kam, Winnie Wai-Ying; Chin, David Y; Hatty, Claire R; Chan, Ronald H Y; Banati, Richard B

    2017-03-04

    Recent loss-of-function studies in tissue-specific as well as global Tspo (Translocator Protein 18 kDa) knockout mice have not confirmed its long assumed indispensability for the translocation of cholesterol across the mitochondrial inter-membrane space, a rate-limiting step in steroid biosynthesis. Instead, recent studies in global Tspo knockout mice indicate that TSPO may play a more fundamental role in cellular bioenergetics, which may include the indirect down-stream regulation of transport or metabolic functions. To examine whether overexpression of the TSPO protein alters the cellular bioenergetic profile, Jurkat cells with low to absent endogenous expression were transfected with a TSPO construct to create a stable cell line with de novo expression of exogenous TSPO protein. Expression of TSPO was confirmed by RT-qPCR, radioligand binding with [3H]PK11195 and immunocytochemistry with a TSPO antibody. We demonstrate that TSPO gene insertion causes increased transcription of genes involved in the mitochondrial electron transport chain. Furthermore, TSPO insertion increased mitochondrial ATP production as well as cell excitability, reflected in a decrease in patch clamp recorded rectified K channel currents. These functional changes were accompanied by an increase in cell proliferation and motility, which were inhibited by PK11195, a selective ligand for TSPO. We suggest that TSPO may serve a range of functions that can be viewed as downstream regulatory effects of its primary, evolutionary conserved role in cell metabolism and energy production.

  20. Functional coupling of simultaneous electrical and metabolic activity in the human brain.

    PubMed

    Oakes, Terrence R; Pizzagalli, Diego A; Hendrick, Andrew M; Horras, Katherine A; Larson, Christine L; Abercrombie, Heather C; Schaefer, Stacey M; Koger, John V; Davidson, Richard J

    2004-04-01

    The relationships between brain electrical and metabolic activity are being uncovered currently in animal models using invasive methods; however, in the human brain this relationship remains not well understood. In particular, the relationship between noninvasive measurements of electrical activity and metabolism remains largely undefined. To understand better these relations, cerebral activity was measured simultaneously with electroencephalography (EEG) and positron emission tomography using [(18)f]-fluoro-2-deoxy-D-glucose (PET-FDG) in 12 normal human subjects during rest. Intracerebral distributions of current density were estimated, yielding tomographic maps for seven standard EEG frequency bands. The PET and EEG data were registered to the same space and voxel dimensions, and correlational maps were created on a voxel-by-voxel basis across all subjects. For each band, significant positive and negative correlations were found that are generally consistent with extant understanding of EEG band power function. With increasing EEG frequency, there was an increase in the number of positively correlated voxels, whereas the lower alpha band (8.5-10.0 Hz) was associated with the highest number of negative correlations. This work presents a method for comparing EEG signals with other more traditionally tomographic functional imaging data on a 3-D basis. This method will be useful in the future when it is applied to functional imaging methods with faster time resolution, such as short half-life PET blood flow tracers and functional magnetic resonance imaging.

  1. Functional gains in energy and cell metabolism after TSPO gene insertion

    PubMed Central

    Chin, David Y.; Hatty, Claire R.; Chan, Ronald H. Y.

    2017-01-01

    ABSTRACT Recent loss-of-function studies in tissue-specific as well as global Tspo (Translocator Protein 18 kDa) knockout mice have not confirmed its long assumed indispensability for the translocation of cholesterol across the mitochondrial inter-membrane space, a rate-limiting step in steroid biosynthesis. Instead, recent studies in global Tspo knockout mice indicate that TSPO may play a more fundamental role in cellular bioenergetics, which may include the indirect down-stream regulation of transport or metabolic functions. To examine whether overexpression of the TSPO protein alters the cellular bioenergetic profile, Jurkat cells with low to absent endogenous expression were transfected with a TSPO construct to create a stable cell line with de novo expression of exogenous TSPO protein. Expression of TSPO was confirmed by RT-qPCR, radioligand binding with [3H]PK11195 and immunocytochemistry with a TSPO antibody. We demonstrate that TSPO gene insertion causes increased transcription of genes involved in the mitochondrial electron transport chain. Furthermore, TSPO insertion increased mitochondrial ATP production as well as cell excitability, reflected in a decrease in patch clamp recorded rectified K channel currents. These functional changes were accompanied by an increase in cell proliferation and motility, which were inhibited by PK11195, a selective ligand for TSPO. We suggest that TSPO may serve a range of functions that can be viewed as downstream regulatory effects of its primary, evolutionary conserved role in cell metabolism and energy production. PMID:28103132

  2. Intraspecific variation in flight metabolic rate in the bumblebee Bombus impatiens: repeatability and functional determinants in workers and drones.

    PubMed

    Darveau, Charles-A; Billardon, Fannie; Bélanger, Kasandra

    2014-02-15

    The evolution of flight energetics requires that phenotypes be variable, repeatable and heritable. We studied intraspecific variation in flight energetics in order to assess the repeatability of flight metabolic rate and wingbeat frequency, as well as the functional basis of phenotypic variation in workers and drones of the bumblebee species Bombus impatiens. We showed that flight metabolic rate and wingbeat frequency were highly repeatable in workers, even when controlling for body mass variation using residual analysis. We did not detect significant repeatability in drones, but a smaller range of variation might have prevented us from finding significant values in our sample. Based on our results and previous findings, we associated the high repeatability of flight phenotypes in workers to the functional links between body mass, thorax mass, wing size, wingbeat frequency and metabolic rate. Moreover, differences between workers and drones were as predicted from these functional associations, where drones had larger wings for their size, lower wingbeat frequency and lower flight metabolic rate. We also investigated thoracic muscle metabolic phenotypes by measuring the activity of carbohydrate metabolism enzymes, and we found positive correlations between mass-independent metabolic rate and the activity of all enzymes measured, but in workers only. When comparing workers and drones that differ in flight metabolic rate, only the activity of the enzymes hexokinase and trehalase showed the predicted differences. Overall, our study indicates that there should be correlated evolution among physiological phenotypes at multiple levels of organization and morphological traits associated with flight.

  3. Sequence- and Structure-Based Functional Annotation and Assessment of Metabolic Transporters in Aspergillus oryzae: A Representative Case Study

    PubMed Central

    Raethong, Nachon; Wong-ekkabut, Jirasak; Laoteng, Kobkul; Vongsangnak, Wanwipa

    2016-01-01

    Aspergillus oryzae is widely used for the industrial production of enzymes. In A. oryzae metabolism, transporters appear to play crucial roles in controlling the flux of molecules for energy generation, nutrients delivery, and waste elimination in the cell. While the A. oryzae genome sequence is available, transporter annotation remains limited and thus the connectivity of metabolic networks is incomplete. In this study, we developed a metabolic annotation strategy to understand the relationship between the sequence, structure, and function for annotation of A. oryzae metabolic transporters. Sequence-based analysis with manual curation showed that 58 genes of 12,096 total genes in the A. oryzae genome encoded metabolic transporters. Under consensus integrative databases, 55 unambiguous metabolic transporter genes were distributed into channels and pores (7 genes), electrochemical potential-driven transporters (33 genes), and primary active transporters (15 genes). To reveal the transporter functional role, a combination of homology modeling and molecular dynamics simulation was implemented to assess the relationship between sequence to structure and structure to function. As in the energy metabolism of A. oryzae, the H+-ATPase encoded by the AO090005000842 gene was selected as a representative case study of multilevel linkage annotation. Our developed strategy can be used for enhancing metabolic network reconstruction. PMID:27274991

  4. Magi Is Associated with the Par Complex and Functions Antagonistically with Bazooka to Regulate the Apical Polarity Complex.

    PubMed

    Padash Barmchi, Mojgan; Samarasekera, Gayathri; Gilbert, Mary; Auld, Vanessa J; Zhang, Bing

    2016-01-01

    The mammalian MAGI proteins play important roles in the maintenance of adherens and tight junctions. The MAGI family of proteins contains modular domains such as WW and PDZ domains necessary for scaffolding of membrane receptors and intracellular signaling components. Loss of MAGI leads to reduced junction stability while overexpression of MAGI can lead to increased adhesion and stabilization of epithelial morphology. However, how Magi regulates junction assembly in epithelia is largely unknown. We investigated the single Drosophila homologue of Magi to study the in vivo role of Magi in epithelial development. Magi is localized at the adherens junction and forms a complex with the polarity proteins, Par3/Bazooka and aPKC. We generated a Magi null mutant and found that Magi null mutants were viable with no detectable morphological defects even though the Magi protein is highly conserved with vertebrate Magi homologues. However, overexpression of Magi resulted in the displacement of Baz/Par3 and aPKC and lead to an increase in the level of PIP3. Interestingly, we found that Magi and Baz functioned in an antagonistic manner to regulate the localization of the apical polarity complex. Maintaining the balance between the level of Magi and Baz is an important determinant of the levels and localization of apical polarity complex.

  5. Conditional knockout of polarity complex (atypical) PKCι reveals an anti-inflammatory function mediated by NF-κB

    PubMed Central

    Forteza, Radia; Figueroa, Yolanda; Mashukova, Anastasia; Dulam, Vipin; Salas, Pedro J.

    2016-01-01

    The conserved proteins of the polarity complex made up of atypical PKC (aPKC, isoforms ι and ζ), Par6, and Par3 determine asymmetry in several cell types, from Caenorhabditis elegans oocytes to vertebrate epithelia and neurons. We previously showed that aPKC is down-regulated in intestinal epithelia under inflammatory stimulation. Further, expression of constitutively active PKCι decreases NF-κB activity in an epithelial cell line, the opposite of the effect reported in other cells. Here we tested the hypothesis that aPKC has a dual function in epithelia, inhibiting the NF-κB pathway in addition to having a role in apicobasal polarity. We achieved full aPKC down-regulation in small intestine villi and colon surface epithelium using a conditional epithelium-specific knockout mouse. The results show that aPKC is dispensable for polarity after cell differentiation, except for known targets, including ROCK and ezrin, claudin-4 expression, and barrier permeability. The aPKC defect resulted in increased NF-κB activity, which could be rescued by IKK and ROCK inhibitors. It also increased expression of proinflammatory cytokines. In contrast, expression of anti-inflammatory IL-10 decreased. We conclude that epithelial aPKC acts upstream of multiple mechanisms that participate in the inflammatory response in the intestine, including, but not restricted to, NF-κB. PMID:27226486

  6. Dual function of Yap in the regulation of lens progenitor cells and cellular polarity.

    PubMed

    Song, Ji Yun; Park, Raehee; Kim, Jin Young; Hughes, Lucinda; Lu, Li; Kim, Seonhee; Johnson, Randy L; Cho, Seo-Hee

    2014-02-15

    Hippo-Yap signaling has been implicated in organ size determination via its regulation of cell proliferation, growth and apoptosis (Pan, 2007). The vertebrate lens comprises only two major cell types, lens progenitors and differentiated fiber cells, thereby providing a relatively simple system for studying size-controlling mechanisms. In order to investigate the role of Hippo-Yap signaling in lens size regulation, we conditionally ablated Yap in the developing mouse lens. Lens progenitor-specific deletion of Yap led to near obliteration of the lens primarily due to hypocellularity in the lens epithelium (LE) and accompanying lens fiber (LF) defects. A significantly reduced LE progenitor pool resulted mainly from failed self-renewal and increased apoptosis. Additionally, Yap-deficient lens progenitor cells precociously exited the cell cycle and expressed the LF marker, β-Crystallin. The mutant progenitor cells also exhibited multiple cellular and subcellular alterations including cell and nuclear shape change, organellar polarity disruption, and disorganized apical polarity complex and junction proteins such as Crumbs, Pals1, Par3 and ZO-1. Yap-deficient LF cells failed to anchor to the overlying LE layer, impairing their normal elongation and packaging. Furthermore, our localization study results suggest that, in the developing LE, Yap participates in the cell context-dependent transition from the proliferative to differentiation-competent state by integrating cell density information. Taken together, our results shed new light on Yap's indispensable and novel organizing role in mammalian organ size control by coordinating multiple events including cell proliferation, differentiation, and polarity.

  7. Interaction between SWP9 and Polar Tube Proteins of the Microsporidian Nosema bombycis and Function of SWP9 as a Scaffolding Protein Contribute to Polar Tube Tethering to the Spore Wall.

    PubMed

    Yang, Donglin; Pan, Lixia; Peng, Pai; Dang, Xiaoqun; Li, Chunfeng; Li, Tian; Long, Mengxian; Chen, Jie; Wu, Yujiao; Du, Huihui; Luo, Bo; Song, Yue; Tian, Rui; Luo, Jie; Zhou, Zeyang; Pan, Guoqing

    2017-03-01

    All microsporidia possess a unique, highly specialized invasion mechanism that involves the polar tube and spore wall. The interaction between spore wall proteins (SWPs) and polar tube proteins (PTPs) in the formation, arrangement, orderly orientation, and function of the polar tube and spore wall remains to be determined. This study was undertaken to examine the protein interactions of Nosema bombycis SWP7 (NbSWP7), NbSWP9, and PTPs. Coimmunoprecipitation, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and yeast two-hybrid data demonstrated that NbSWP9, but not NbSWP7, interacts with NbPTP1 and NbPTP2. Furthermore, immunoelectron microscopy (IEM) showed that NbSWP9 was localized mainly in the developing polar tube of sporoblasts, while NbSWP7 was found randomly in the cytoplasm. However, both NbSWP9 and NbSWP7 were located in the polar tube and spore wall of N. bombycis mature spores. The reason why NbSWP7 was localized to the polar tube may be due to the interaction between NbSWP9 and NbSWP7. Interestingly, the majority of NbSWP9, but not NbSWP7, accumulated in the beginning part of the extruded polar tube and the ruptured spore wall called the anchoring disk (AD) when the mature spores germinated under weak-alkaline environmental stimulation. Additionally, anti-NbSWP9 antibody reduced spore germination in a dose-dependent manner. In conclusion, our study further confirmed that NbSWP9 is a scaffolding protein that not only anchors and holds the polar tube but also tethers the polar tube to the spore wall.

  8. Polarization insensitive all-fiber mode-lockers functioned by carbon nanotubes deposited onto tapered fibers

    NASA Astrophysics Data System (ADS)

    Song, Yong-Won; Morimune, Keiyo; Set, Sze Y.; Yamashita, Shinji

    2007-01-01

    The authors demonstrate a nonblocked all-fiber mode locker operated by the interaction of carbon nanotubes with the evanescent field of propagating light in a tapered fiber. Symmetric cross section of the device with the randomly oriented nanotubes guarantees the polarization insensitive operation of the pulse formation. In order to minimize the scattering, the carbon nanotubes are deposited within a designed area around the tapered waist. The demonstrated passively pulsed laser has the repetition rate of 7.3MHz and the pulse width of 829fs.

  9. NAP1 acts with Clb1 to perform mitotic functions and to suppress polar bud growth in budding yeast

    PubMed Central

    1995-01-01

    NAP1 is a 60-kD protein that interacts specifically with mitotic cyclins in budding yeast and frogs. We have examined the ability of the yeast mitotic cyclin Clb2 to function in cells that lack NAP1. Our results demonstrate that Clb2 is unable to carry out its full range of functions without NAP1, even though Clb2/p34CDC28-associated kinase activity rises to normal levels. In the absence of NAP1, Clb2 is unable to efficiently induce mitotic events, and cells undergo a prolonged delay at the short spindle stage with normal levels of Clb2/p34CDC28 kinase activity. NAP1 is also required for the ability of Clb2 to induce the switch from polar to isotropic bud growth. As a result, polar bud growth continues during mitosis, giving rise to highly elongated cells. Our experiments also suggest that NAP1 is required for the ability of the Clb2/p34CDC28 kinase complex to amplify its own production, and that NAP1 plays a role in regulation of microtubule dynamics during mitosis. Together, these results demonstrate that NAP1 is required for the normal function of the activated Clb2/p34CDC28 kinase complex, and provide a step towards understanding how cyclin- dependent kinase complexes induce specific events during the cell cycle. PMID:7622567

  10. Effects of interaction and polarization on spin-charge separation: A time-dependent spin-density-functional theory study

    NASA Astrophysics Data System (ADS)

    Xianlong, Gao

    2010-03-01

    We calculate the nonequilibrium dynamic evolution of a one-dimensional system of two-component fermionic atoms after a strong local quench by using a time-dependent spin-density-functional theory. The interaction quench is also considered to see its influence on the spin-charge separation. It is shown that the charge velocity is larger than the spin velocity for the system of on-site repulsive interaction (Luttinger liquid), and vise versa for the system of on-site attractive interaction (Luther-Emery liquid). We find that both the interaction quench and polarization suppress the spin-charge separation.

  11. Correlating structure and function of drug-metabolizing enzymes: progress and ongoing challenges.

    PubMed

    Johnson, Eric F; Connick, J Patrick; Reed, James R; Backes, Wayne L; Desai, Manoj C; Xu, Lianhong; Estrada, D Fernando; Laurence, Jennifer S; Scott, Emily E

    2014-01-01

    This report summarizes a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics at Experimental Biology held April 20-24 in Boston, MA. Presentations discussed the status of cytochrome P450 (P450) knowledge, emphasizing advances and challenges in relating structure with function and in applying this information to drug design. First, at least one structure of most major human drug-metabolizing P450 enzymes is known. However, the flexibility of these active sites can limit the predictive value of one structure for other ligands. A second limitation is our coarse-grain understanding of P450 interactions with membranes, other P450 enzymes, NADPH-cytochrome P450 reductase, and cytochrome b5. Recent work has examined differential P450 interactions with reductase in mixed P450 systems and P450:P450 complexes in reconstituted systems and cells, suggesting another level of functional control. In addition, protein nuclear magnetic resonance is a new approach to probe these protein/protein interactions, identifying interacting b5 and P450 surfaces, showing that b5 and reductase binding are mutually exclusive, and demonstrating ligand modulation of CYP17A1/b5 interactions. One desired outcome is the application of such information to control drug metabolism and/or design selective P450 inhibitors. A final presentation highlighted development of a CYP3A4 inhibitor that slows clearance of human immunodeficiency virus drugs otherwise rapidly metabolized by CYP3A4. Although understanding P450 structure/function relationships is an ongoing challenge, translational advances will benefit from continued integration of existing and new biophysical approaches.

  12. Correlating Structure and Function of Drug-Metabolizing Enzymes: Progress and Ongoing Challenges

    PubMed Central

    Johnson, Eric F.; Connick, J. Patrick; Reed, James R.; Backes, Wayne L.; Desai, Manoj C.; Xu, Lianhong; Estrada, D. Fernando; Laurence, Jennifer S.

    2014-01-01

    This report summarizes a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics at Experimental Biology held April 20-24 in Boston, MA. Presentations discussed the status of cytochrome P450 (P450) knowledge, emphasizing advances and challenges in relating structure with function and in applying this information to drug design. First, at least one structure of most major human drug-metabolizing P450 enzymes is known. However, the flexibility of these active sites can limit the predictive value of one structure for other ligands. A second limitation is our coarse-grain understanding of P450 interactions with membranes, other P450 enzymes, NADPH–cytochrome P450 reductase, and cytochrome b5. Recent work has examined differential P450 interactions with reductase in mixed P450 systems and P450:P450 complexes in reconstituted systems and cells, suggesting another level of functional control. In addition, protein nuclear magnetic resonance is a new approach to probe these protein/protein interactions, identifying interacting b5 and P450 surfaces, showing that b5 and reductase binding are mutually exclusive, and demonstrating ligand modulation of CYP17A1/b5 interactions. One desired outcome is the application of such information to control drug metabolism and/or design selective P450 inhibitors. A final presentation highlighted development of a CYP3A4 inhibitor that slows clearance of human immunodeficiency virus drugs otherwise rapidly metabolized by CYP3A4. Although understanding P450 structure/function relationships is an ongoing challenge, translational advances will benefit from continued integration of existing and new biophysical approaches. PMID:24130370

  13. A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity.

    PubMed

    Demenescu, Liliana Ramona; Colic, Lejla; Li, Meng; Safron, Adam; Biswal, B; Metzger, Coraline Danielle; Li, Shijia; Walter, Martin

    2017-03-01

    Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p < 0.05 family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p < 0.05) in MDD patients. We showed that the local AI ratio of glutamatergic-creatine metabolism is an underlying candidate subserving functional network disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength.

  14. The Anti-Oxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota

    PubMed Central

    Cai, Jingwei; Zhang, Limin; Jones, Richard A.; Correll, Jared B.; Hatzakis, Emmanuel; Smith, Philip B.; Gonzalez, Frank J.; Patterson, Andrew D.

    2016-01-01

    Recent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver 1H NMR-based metabolomics identified a dose-dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum 1H NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles were observed in germ-free mice thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function resulting in reduced host energy availability and a significant shift in liver metabolism towards a more catabolic state. PMID:26696396

  15. Antioxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota.

    PubMed

    Cai, Jingwei; Zhang, Limin; Jones, Richard A; Correll, Jared B; Hatzakis, Emmanuel; Smith, Philip B; Gonzalez, Frank J; Patterson, Andrew D

    2016-02-05

    Recent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver (1)H NMR-based metabolomics identified a dose-dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum (1)H NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles was observed in germ-free mice, thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function, resulting in reduced host energy availability and a significant shift in liver metabolism toward a more catabolic state.

  16. The Effect of Marine Derived n-3 Fatty Acids on Adipose Tissue Metabolism and Function

    PubMed Central

    Todorčević, Marijana; Hodson, Leanne

    2015-01-01

    Adipose tissue function is key determinant of metabolic health, with specific nutrients being suggested to play a role in tissue metabolism. One such group of nutrients are the n-3 fatty acids, specifically eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3). Results from studies where human, animal and cellular models have been utilised to investigate the effects of EPA and/or DHA on white adipose tissue/adipocytes suggest anti-obesity and anti-inflammatory effects. We review here evidence for these effects, specifically focusing on studies that provide some insight into metabolic pathways or processes. Of note, limited work has been undertaken investigating the effects of EPA and DHA on white adipose tissue in humans whilst more work has been undertaken using animal and cellular models. Taken together it would appear that EPA and DHA have a positive effect on lowering lipogenesis, increasing lipolysis and decreasing inflammation, all of which would be beneficial for adipose tissue biology. What remains to be elucidated is the duration and dose required to see a favourable effect of EPA and DHA in vivo in humans, across a range of adiposity. PMID:26729182

  17. Mitochondrial function, fatty acid metabolism, and immune system are relevant features of pig adipose tissue development.

    PubMed

    Vincent, Annie; Louveau, Isabelle; Gondret, Florence; Lebret, Bénédicte; Damon, Marie

    2012-11-15

    The molecular mechanisms underlying the genetic control of fat development in humans and livestock species still require characterization. To gain insights on gene expression patterns associated with genetic propensity for adiposity, we compared subcutaneous adipose tissue (SCAT) transcriptomics profiles from two contrasted pig breeds for body fatness. Samples were obtained from Large White (LW; lean phenotype) and Basque pigs (B; low growth and high fat content) at 35 kg (n = 5 per breed) or 145 kg body weight (n = 10 per breed). Using a custom adipose tissue microarray, we found 271 genes to be differentially expressed between the two breeds at both stages, out of which 123 were highly expressed in LW pigs and 148 genes were highly expressed in B pigs. Functional enrichment analysis based on gene ontology (GO) terms highlighted gene groups corresponding to the mitochondrial energy metabolism in LW pigs, whereas immune response was found significantly enriched in B pigs. Genes associated with lipid metabolism, such as ELOVL6, a gene involved in fatty acid elongation, had a lower expression in B compared with LW pigs. Furthermore, despite enlarged adipocyte diameters and higher plasma leptin concentration, B pigs displayed reduced lipogenic enzyme activities compared with LW pigs at 145 kg. Altogether, our results suggest that the development of adiposity was associated with a progressive worsening of the metabolic status, leading to a low-grade inflammatory state, and may thus be of significant interest for both livestock production and human health.

  18. Peroxisomes Are Required for Lipid Metabolism and Muscle Function in Drosophila melanogaster

    PubMed Central

    Faust, Joseph E.; Manisundaram, Arvind; Ivanova, Pavlina T.; Milne, Stephen B.; Summerville, James B.; Brown, H. Alex; Wangler, Michael; Stern, Michael; McNew, James A.

    2014-01-01

    Peroxisomes are ubiquitous organelles that perform lipid and reactive oxygen species metabolism. Defects in peroxisome biogenesis cause peroxisome biogenesis disorders (PBDs). The most severe PBD, Zellweger syndrome, is characterized in part by neuronal dysfunction, craniofacial malformations, and low muscle tone (hypotonia). These devastating diseases lack effective therapies and the development of animal models may reveal new drug targets. We have generated Drosophila mutants with impaired peroxisome biogenesis by disrupting the early peroxin gene pex3, which participates in budding of pre-peroxisomes from the ER and peroxisomal membrane protein localization. pex3 deletion mutants lack detectible peroxisomes and die before or during pupariation. At earlier stages of development, larvae lacking Pex3 display reduced size and impaired lipid metabolism. Selective loss of peroxisomes in muscles impairs muscle function and results in flightless animals. Although, hypotonia in PBD patients is thought to be a secondary effect of neuronal dysfunction, our results suggest that peroxisome loss directly affects muscle physiology, possibly by disrupting energy metabolism. Understanding the role of peroxisomes in Drosophila physiology, specifically in muscle cells may reveal novel aspects of PBD etiology. PMID:24945818

  19. Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function

    SciTech Connect

    Berent, S.; Giordani, B.; Lehtinen, S.; Markel, D.; Penney, J.B.; Buchtel, H.A.; Starosta-Rubinstein, S.; Hichwa, R.; Young, A.B.

    1988-06-01

    Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of /sup 18/F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation.

  20. Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions

    PubMed Central

    Vukovic, Milica; van de Lagemaat, Louie N.; Morgan, Marcos; Gonzalez, Marta Vila; Paris, Jasmin; Gezer, Deniz; Wills, Jimi; Coman, David; So, Chi Wai Eric; O’Carroll, Donal; Vernimmen, Douglas; Rodrigues, Neil P.; Pollard, Patrick J.; Morton, Nicholas M.

    2017-01-01

    Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure. Reexpression of extramitochondrial Fh1 (which normalized fumarate levels but not maximal mitochondrial respiration) rescued these phenotypes, indicating the causal role of cellular fumarate accumulation. However, HSCs lacking mitochondrial Fh1 (which had normal fumarate levels but defective maximal mitochondrial respiration) failed to self-renew and displayed lymphoid differentiation defects. In contrast, leukemia-initiating cells lacking mitochondrial Fh1 efficiently propagated Meis1/Hoxa9-driven leukemia. Thus, we identify novel roles for fumarate metabolism in HSC maintenance and hematopoietic differentiation and reveal a differential requirement for mitochondrial Fh1 in normal hematopoiesis and leukemia propagation. PMID:28202494

  1. Impact of obesity and bariatric surgery on metabolism and coronary circulatory function.

    PubMed

    Valenta, Ines; Dilsizian, Vasken; Quercioli, Alessandra; Jüngling, Freimut D; Ambrosio, Giuseppe; Wahl, Richard; Schindler, Thomas H

    2014-01-01

    Increases in intra-abdominal visceral adipose tissue have been widely appreciated as a risk factor for metabolic disorders such as dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, whereas this is not the case for peripheral or subcutaneous obesity. While the underlying mechanisms that contribute to these differences in adipose tissue activity remain uncertain, increases in visceral fat commonly induce metabolic dysregulation, in part because of increased venous effluent of fatty acids and/or adipokines/cytokines to the liver. Increased body weight, paralleled by an increase in plasma markers of the insulin-resistance syndrome and chronic inflammation, is independently associated with coronary circulatory dysfunction. Recent data suggest that plasma proteins originating from the adipose tissue, such as endocannabinoids (EC), leptin, and adiponectin (termed adipocytes) play a central role in the regulation and control of coronary circulatory function in obesity. Positron emission tomography (PET) in concert with tracer kinetic modeling is a well established technique for quantifying regional myocardial blood flow at rest and in response to various forms of vasomotor stress. Myocardial flow reserve assessed by PET provides a noninvasive surrogate of coronary circulatory function. PET also enables the monitoring and characterization of coronary circulatory function in response to gastric bypass-induced weight loss in initially morbidly obese individuals, to medication and/or behavioral interventions related to weight, diet, and physical activity. Whether the observed improvement in coronary circulatory dysfunction via weight loss may translate to diminution in cardiovascular events awaits clinical confirmation.

  2. Sex influences the effect of a lifelong increase in serotonin transporter function on cerebral metabolism.

    PubMed

    Dawson, Neil; Ferrington, Linda; Olverman, Henry J; Harmar, Anthony J; Kelly, Paul A T

    2009-08-01

    Polymorphic variation in the human serotonin transporter (SERT; 5-HTT) gene resulting in a lifelong increase in SERT expression is associated with reduced anxiety and a reduced risk of affective disorder. Evidence also suggests that sex influences the effect of this polymorphism on affective functioning. Here we use novel transgenic mice overexpressing human SERT (hSERT OVR) to investigate the possible influence of sex on the alterations in SERT protein expression and cerebral function that occur in response to increased SERT gene transcription. SERT binding levels were significantly increased in the brain of hSERT OVR mice in a region-dependent manner. The increased SERT binding in hSERT OVR mice was more pronounced in female than in male mice. Cerebral metabolism, as reflected by a quantitative index of local cerebral glucose utilization (iLCMRglu), was significantly decreased in many brain regions in hSERT OVR female as compared with wild-type female mice, whereas there was no evidence for a significant effect in any region in males. The ability of hSERT overexpression to modify cerebral metabolism was significantly greater in females than in males. This effect was particularly pronounced in the medial striatum, globus pallidus, somatosensory cortex, mamillary body, and ventrolateral thalamus. Overall, these findings demonstrate that the influence of a lifelong increase in SERT gene transcription on cerebral function is greater in females than in males and may relate, in part, to the influence of sex on genetically driven increases in SERT protein expression.

  3. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    SciTech Connect

    Xiong, Weili; Abraham, Paul E.; Li, Zhou; Pan, Chongle; Robert L. Hettich

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs. disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.

  4. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    DOE PAGES

    Xiong, Weili; Abraham, Paul E.; Li, Zhou; ...

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs.more » disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.« less

  5. The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity

    PubMed Central

    Heimbucher, Thomas; Liu, Zheng; Bossard, Carine; McCloskey, Richard; Carrano, Andrea C.; Riedel, Christian G.; Tanasa, Bogdan; Klammt, Christian; Fonslow, Bryan R.; Riera, Celine E.; Lillemeier, Bjorn F.; Kemphues, Kenneth; Yates, John R.; O'Shea, Clodagh; Hunter, Tony; Dillin, Andrew

    2015-01-01

    SUMMARY One of the major determinants of aging in organisms ranging from worms to man are FOXO family transcription factors, which are downstream effectors of Insulin/IGF-1 signaling (IIS). The molecular mechanisms that actively promote DAF16/FOXO stability and function are unknown. Here we identify the deubiquitylating enzyme MATH-33 as an essential DAF-16 regulator in IIS, which stabilizes active DAF-16 protein levels and, as a consequence, influences DAF-16 functions, such as metabolism, stress response and longevity in C. elegans. MATH-33 associates with DAF-16 in cellulo and in vitro. MATH-33 functions as a deubiquitylase by actively removing ubiquitin moieties from DAF-16, thus counteracting the action of the RLE-1 E3-ubiquitin ligase. Our findings support a model in which MATH-33 promotes DAF-16 stability in response to decreased IIS by directly modulating its ubiquitylation state, suggesting that regulated oscillations in the stability of DAF-16 protein play an integral role in controlling processes such as metabolism and longevity. PMID:26154057

  6. Functional and metabolic disorders in celiac disease: new implications for nutritional treatment.

    PubMed

    Farnetti, Sara; Zocco, Maria Assunta; Garcovich, Matteo; Gasbarrini, Antonio; Capristo, Esmeralda

    2014-11-01

    Celiac disease (CD) is a chronic disease causing the inflammation of the proximal small intestine, in genetically predisposed individuals. This is triggered by the consumption of the gluten protein and the side effects of the disease are mitigated by a lifelong gluten-free diet (GFD) treatment. The predominant consequence of CD is malnutrition due to malabsorption (with diarrhea, weight loss, nutritional deficiencies, and altered blood parameters), especially in patients who do not show strict adherence to GFD treatment. Recent evidence shows that, despite a lifelong GFD, some functional disorders persist, such as compromised gallbladder function and motility, exocrine pancreatic insufficiency, increased gut permeability, small-intestinal bowel overgrowth, nonalcoholic fatty liver disease (NAFLD), lactose intolerance, and milk allergy. These abnormalities may predispose to the occurrence of overweight and obesity even in CD patients. This review focuses on the principal functional and metabolic disorders in both treated and untreated CD, ranging from alterations of the gastrointestinal system to impaired glucose and lipid metabolism and insulin secretion with the aim of providing new implications beyond a GFD, for an ad hoc nutrition treatment in these patients.

  7. Astrocyte lipid metabolism is critical for synapse development and function in vivo.

    PubMed

    van Deijk, Anne-Lieke F; Camargo, Nutabi; Timmerman, Jaap; Heistek, Tim; Brouwers, Jos F; Mogavero, Floriana; Mansvelder, Huibert D; Smit, August B; Verheijen, Mark H G

    2017-04-01

    The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte-derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte-derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo. Hippocampal protein expression for the sterol regulatory element-binding protein (SREBP) and its target gene fatty acid synthase (Fasn) was found in astrocytes but not in neurons. Diminishing SREBP activity in astrocytes using mice in which the SREBP cleavage-activating protein (SCAP) was deleted from GFAP-expressing cells resulted in decreased cholesterol and phospholipid secretion by astrocytes. Interestingly, SCAP mutant mice showed more immature synapses, lower presynaptic protein SNAP-25 levels as well as reduced numbers of synaptic vesicles, indicating impaired development of the presynaptic terminal. Accordingly, hippocampal short-term and long-term synaptic plasticity were defective in mutant mice. These findings establish a critical role for astrocyte lipid metabolism in presynaptic terminal development and function in vivo. GLIA 2017;65:670-682.

  8. Revisiting Mitochondrial Function and Metabolism in Pluripotent Stem Cells: Where Do We Stand in Neurological Diseases?

    PubMed

    Lopes, Carla; Rego, A Cristina

    2017-04-01

    Pluripotent stem cells (PSCs) are powerful cellular tools that can generate all the different cell types of the body, and thus overcome the often limited access to human disease tissues; this becomes highly relevant when aiming to investigate cellular (dys)function in diseases affecting the central nervous system. Recent studies have demonstrated that PSC and differentiated cells show altered mitochondrial function and metabolic profiles and production of reactive oxygen species. This raises an emerging paradigm about the role of mitochondria in stem cell biology and urges the need to identify mitochondrial pathways involved in these processes. In this respect, this review focuses on the metabolic profile of PSC and how mitochondrial function can influence the reprogramming and differentiation processes. Indeed, both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) favor the glycolytic pathway as a major source of energy production over oxidative phosphorylation. PSC mitochondria are characterized by a spherical shape, low copy number of mitochondrial DNA, and a hyperpolarized state. Indeed, mitochondria appear to have a crucial role in reprogramming iPSC, in the maintenance of a pluripotent state, and in differentiation. Moreover, an increase in mitochondrial oxidative phosphorylation has to occur for differentiation to succeed. Therefore, in vitro differentiation of neural stem cells (NSCs) into neurons can be compromised if those mechanisms are impaired. Future research should shed light on how mitochondrial impairment occurring in pre differentiation neural stages (e.g., in NSC or premature neurons) may contribute for the etiopathogenesis of neurodevelopmental and neurological disorders.

  9. Energy metabolism drives myeloid-derived suppressor cell differentiation and functions in pathology.

    PubMed

    Sica, Antonio; Strauss, Laura

    2017-02-21

    Over the last decade, a heterogeneous population of immature myeloid cells with major regulatory functions has been described in cancer and other pathologic conditions and ultimately defined as MDSCs. Most of the early work on the origins and functions of MDSCs has been in murine and human tumor bearers in which MDSCs are known to be immunosuppressive and to result in both reduced immune surveillance and antitumor cytotoxicity. More recent studies, however, suggest that expansion of these immature myeloid cells may be linked to most, if not all, chronic and acute inflammatory processes. The universal expansion to inflammatory stimuli of MDSCs suggests that these cells may be more of a normal component of the inflammatory response (emergency myelopoiesis) than simply a pathologic response to a growing tumor. Instead of an adverse immunosuppressive response, expansion of these immature myeloid cell populations may result from a complex balance between increased immune surveillance and dampened adaptive immune responses that are common to many inflammatory responses. Within this scenario, new pathways of metabolic reprogramming are emerging as drivers of MDSC differentiation and functions in cancer and inflammatory disorders, crucially linking metabolic syndrome to inflammatory processes.

  10. Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism

    PubMed Central

    Krueger, Sharon K.; Williams, David E.

    2005-01-01

    Flavin-containing monooxygenase (FMO) oxygenates drugs and xenobiotics containing a “soft-nucleophile”, usually nitrogen or sulfur. FMO, like cytochrome P450 (CYP), is a monooxygenase, utilizing the reducing equivalents of NADPH to reduce 1 atom of molecular oxygen to water, while the other atom is used to oxidize the substrate. FMO and CYP also exhibit similar tissue and cellular location, molecular weight, substrate specificity, and exist as multiple enzymes under developmental control. The human FMO functional gene family is much smaller (5 families each with a single member) than CYP. FMO does not require a reductase to transfer electrons from NADPH and the catalytic cycle of the 2 monooxygenases is strikingly different. Another distinction is the lack of induction of FMOs by xenobiotics. In general, CYP is the major contributor to oxidative xenobiotic metabolism. However, FMO activity may be of significance in a number of cases and should not be overlooked. FMO and CYP have overlapping substrate specificities, but often yield distinct metabolites with potentially significant toxicological/pharmacological consequences. The physiological function(s) of FMO are poorly understood. Three of the 5 expressed human FMO genes, FMO1, FMO2 and FMO3, exhibit genetic polymorphisms. The most studied of these is FMO3 (adult human liver) in which mutant alleles contribute to the disease known as trimethylaminuria. The consequences of these FMO genetic polymorphisms in drug metabolism and human health are areas of research requiring further exploration. PMID:15922018

  11. Enhancing enzyme stability and metabolic functional ability of β-galactosidase through functionalized polymer nanofiber immobilization.

    PubMed

    Misson, Mailin; Jin, Bo; Chen, Binghui; Zhang, Hu

    2015-10-01

    A functionalized polystyrene nanofiber (PSNF) immobilized β-galactosidase assembly (PSNF-Gal) was synthesized as a nanobiocatalyst aiming to enhance the biocatalyst stability and functional ability. The PSNF fabricated by electrospinning was functionalized through a chemical oxidation method for enzyme binding. The bioengineering performance of the enzyme carriers was further evaluated for bioconversion of lactose to galacto-oligosaccharides (GOS). The modified PSNF-Gal demonstrated distinguished performances to preserve the same activity as the free β-galactosidase at the optimum pH of 7.0, and to enhance the enzyme stability of PSNF-Gal in an alkaline condition up to pH 10. The PSNF assembly demonstrated improved thermal stability from 37 to 60 °C. The nanobiocatalyst was able to retain 30 % of its initial activity after ninth operation cycles comparing to four cycles with the unmodified counterpart. In contrast with free β-galactosidase, the modified PSNF-Gal enhanced the GOS yield from 14 to 28 %. These findings show the chemically modified PSNF-based nanobiocatalyst may be pertinent for various enzyme-catalysed bioprocessing applications.

  12. Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer.

    PubMed

    Curry, Joseph M; Tuluc, Madalina; Whitaker-Menezes, Diana; Ames, Julie A; Anantharaman, Archana; Butera, Aileen; Leiby, Benjamin; Cognetti, David M; Sotgia, Federica; Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E

    2013-05-01

    Here, we interrogated head and neck cancer (HNSCC) specimens (n = 12) to examine if different metabolic compartments (oxidative vs. glycolytic) co-exist in human tumors. A large panel of well-established biomarkers was employed to determine the metabolic state of proliferative cancer cells. Interestingly, cell proliferation in cancer cells, as marked by Ki-67 immunostaining, was strictly correlated with oxidative mitochondrial metabolism (OXPHOS) and the uptake of mitochondrial fuels, as detected via MCT1 expression (p < 0.001). More specifically, three metabolic tumor compartments were delineated: (1) proliferative and mitochondrial-rich cancer cells (Ki-67+/TOMM20+/COX+/MCT1+); (2) non-proliferative and mitochondrial-poor cancer cells (Ki-67-/TOMM20-/COX-/MCT1-); and (3) non-proliferative and mitochondrial-poor stromal cells (Ki-67-/TOMM20-/COX-/MCT1-). In addition, high oxidative stress (MCT4+) was very specific for cancer tissues. Thus, we next evaluated the prognostic value of MCT4 in a second independent patient cohort (n = 40). Most importantly, oxidative stress (MCT4+) in non-proliferating epithelial cancer cells predicted poor clinical outcome (tumor recurrence; p < 0.0001; log-rank test), and was functionally associated with FDG-PET avidity (p < 0.04). Similarly, oxidative stress (MCT4+) in tumor stromal cells was specifically associated with higher tumor stage (p < 0.03), and was a highly specific marker for cancer-associated fibroblasts (p < 0.001). We propose that oxidative stress is a key hallmark of tumor tissues that drives high-energy metabolism in adjacent proliferating mitochondrial-rich cancer cells, via the paracrine transfer of mitochondrial fuels (such as L-lactate and ketone bodies). New antioxidants and MCT4 inhibitors should be developed to metabolically target "three-compartment tumor metabolism" in head and neck cancers. It is remarkable that two "non-proliferating" populations of cells (Ki-67-/MCT4+) within the tumor can actually

  13. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults

    PubMed Central

    Cheung, Ivy N.; Zee, Phyllis C.; Shalman, Dov; Malkani, Roneil G.; Kang, Joseph; Reid, Kathryn J.

    2016-01-01

    Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (<20lux). Participants were randomized to 3 hours of blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group) or 10.5 hours after wake (n = 10; evening group). All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA-IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism. PMID:27191727

  14. Morning and Evening Blue-Enriched Light Exposure Alters Metabolic Function in Normal Weight Adults.

    PubMed

    Cheung, Ivy N; Zee, Phyllis C; Shalman, Dov; Malkani, Roneil G; Kang, Joseph; Reid, Kathryn J

    2016-01-01

    Increasing evidence points to associations between light-dark exposure patterns, feeding behavior, and metabolism. This study aimed to determine the acute effects of 3 hours of morning versus evening blue-enriched light exposure compared to dim light on hunger, metabolic function, and physiological arousal. Nineteen healthy adults completed this 4-day inpatient protocol under dim light conditions (<20lux). Participants were randomized to 3 hours of blue-enriched light exposure on Day 3 starting either 0.5 hours after wake (n = 9; morning group) or 10.5 hours after wake (n = 10; evening group). All participants remained in dim light on Day 2 to serve as their baseline. Subjective hunger and sleepiness scales were collected hourly. Blood was sampled at 30-minute intervals for 4 hours in association with the light exposure period for glucose, insulin, cortisol, leptin, and ghrelin. Homeostatic model assessment of insulin resistance (HOMA-IR) and area under the curve (AUC) for insulin, glucose, HOMA-IR and cortisol were calculated. Comparisons relative to baseline were done using t-tests and repeated measures ANOVAs. In both the morning and evening groups, insulin total area, HOMA-IR, and HOMA-IR AUC were increased and subjective sleepiness was reduced with blue-enriched light compared to dim light. The evening group, but not the morning group, had significantly higher glucose peak value during blue-enriched light exposure compared to dim light. There were no other significant differences between the morning or the evening groups in response to blue-enriched light exposure. Blue-enriched light exposure acutely alters glucose metabolism and sleepiness, however the mechanisms behind this relationship and its impacts on hunger and appetite regulation remain unclear. These results provide further support for a role of environmental light exposure in the regulation of metabolism.

  15. Abnormal barrier function in the pathogenesis of ichthyosis: Therapeutic implications for lipid metabolic disorders☆

    PubMed Central

    Elias, Peter M.; Williams, Mary L.; Feingold, Kenneth R.

    2013-01-01

    Ichthyoses, including inherited disorders of lipid metabolism, display a permeability barrier abnormality in which the severity of the clinical phenotype parallels the prominence of the barrier defect. The pathogenesis of the cutaneous phenotype represents the consequences of the mutation for epidermal function, coupled with a “best attempt” by affected epidermis to generate a competent barrier in a terrestrial environment. A compromised barrier in normal epidermis triggers a vigorous set of metabolic responses that rapidly normalizes function, but ichthyotic epidermis, which is inherently compromised, only partially succeeds in this effort. Unraveling mechanisms that account for barrier dysfunction in the ichthyoses has identified multiple, subcellular, and biochemical processes that contribute to the clinical phenotype. Current treatment of the ichthyoses remains largely symptomatic: directed toward reducing scale or corrective gene therapy. Reducing scale is often minimally effective. Gene therapy is impeded by multiple pitfalls, including difficulties in transcutaneous drug delivery, high costs, and discomfort of injections. We have begun to use information about disease pathogenesis to identify novel, pathogenesis-based therapeutic strategies for the ichthyoses. The clinical phenotype often reflects not only a deficiency of pathway end product due to reduced-function mutations in key synthetic enzymes but often also accumulation of proximal, potentially toxic metabolites. As a result, depending upon the identified pathomechanism(s) for each disorder, the accompanying ichthyosis can be treated by topical provision of pathway product (eg, cholesterol), with or without a proximal enzyme inhibitor (eg, simvastatin), to block metabolite production. Among the disorders of distal cholesterol metabolism, the cutaneous phenotype in Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects (CHILD syndrome) and X-linked ichthyosis reflect metabolite

  16. Contractile function and energy metabolism of skeletal muscle in rats with secondary carnitine deficiency.

    PubMed

    Roberts, Paul A; Bouitbir, Jamal; Bonifacio, Annalisa; Singh, François; Kaufmann, Priska; Urwyler, Albert; Krähenbühl, Stephan

    2015-08-01

    The consequences of carnitine depletion upon metabolic and contractile characteristics of skeletal muscle remain largely unexplored. Therefore, we investigated the effect of N-trimethyl-hydrazine-3-propionate (THP) administration, a carnitine analog inhibiting carnitine biosynthesis and renal reabsorption of carnitine, on skeletal muscle function and energy metabolism. Male Sprague-Dawley rats were fed a standard rat chow in the absence (CON; n = 8) or presence of THP (n = 8) for 3 wk. Following treatment, rats were fasted for 24 h prior to excision of their soleus and EDL muscles for biochemical characterization at rest and following 5 min of contraction in vitro. THP treatment reduced the carnitine pool by ∼80% in both soleus and EDL muscles compared with CON. Carnitine depletion was associated with a 30% decrease soleus muscle weight, whereas contractile function (expressed per gram of muscle), free coenzyme A, and water content remained unaltered from CON. Muscle fiber distribution and fiber area remained unaffected, whereas markers of apoptosis were increased in soleus muscle of THP-treated rats. In EDL muscle, carnitine depletion was associated with reduced free coenzyme A availability (-25%, P < 0.05), impaired peak tension development (-44%, P < 0.05), and increased glycogen hydrolysis (52%, P < 0.05) during muscle contraction, whereas PDC activation, muscle weight, and water content remained unaltered from CON. In conclusion, myopathy associated with carnitine deficiency can have different causes. Although muscle atrophy, most likely due to increased apoptosis, is predominant in muscle composed predominantly of type I fibers (soleus), disturbance of energy metabolism appears to be the major cause in muscle composed of type II fibers (EDL).

  17. Copepods in ice-covered seas—Distribution, adaptations to seasonally limited food, metabolism, growth patterns and life cycle strategies in polar seas

    NASA Astrophysics Data System (ADS)

    Conover, R. J.; Huntley, M.

    1991-07-01

    While a seasonal ice cover limits light penetration into both polar seas for up to ten months a year, its presence is not entirely negative. The mixed layer under sea ice will generally be shallower than in open water at the same latitude and season. Ice forms a substrate on which primary production can be concentrated, a condition which contrasts with the generally dilute nutritional conditions which prevail in the remaining ocean. The combination of a shallow, generally stable mixed layer with a close proximity to abundant food make the under-ice zone a suitable nursery for both pelagic and benthic species, an upside-down benthos for opportunistic substrate browsers, and a rich feeding environment for species often considered to be neritic in temperate environments. Where the ice cover is not continuous there may be a retreating ice edge that facilitates the seasonal production of phytoplankton primarily through increased stability from the melt water. Ice edge blooms similarly encourage secondary production by pelagic animals. Pseudocalanus acuspes, which may be the most abundant and productive copepod in north polar latitudes, initiates growth at the start of the "spring bloom" of epontic algae, reaching sexual maturity at breakup or slightly before. In the Southern Hemisphere, the small neritic copepod Paralabidocera antarctica and adult krill have been observed to utilize ice algae. Calanus hyperboreus breeds in the dark season at depth and its buoyant eggs, slowly developing on the ascent, reach the under-ice layer in April as nauplii ready to benefit from the primary production there. On the other hand, C. glacialis may initiate ontogenetic migrations and reproduction in response to increased erosion of ice algae due to solar warming and melting at the ice-water interface. While the same species in a phytoplankton bloom near the ice edge reproduces actively, those under still-consolidated ice nearby can have immature gonads. Diel migration and diel feeding

  18. Water versus acetonitrile coordination to uranyl. Density functional study of cooperative polarization effects in solution.

    PubMed

    Bühl, Michael; Sieffert, Nicolas; Chaumont, Alain; Wipff, Georges

    2011-01-03

    Optimizations at the BLYP and B3LYP levels are reported for mixed uranyl-water/acetonitrile complexes [UO(2)(H(2)O)(5-n)(MeCN)(n)](2+) (n = 0-5), in both the gas phase and a polarizable continuum modeling acetonitrile. Car-Parrinello molecular dynamics (CPMD) simulations have been performed for these complexes in the gas phase, and for selected species (n = 0, 1, 3, 5) in a periodic box of liquid acetonitrile. According to structural and energetic data, uranyl has a higher affinity for acetonitrile than for water in the gas phase, in keeping with the higher dipole moment and polarizability of acetonitrile. In acetonitrile solution, however, water is the better ligand because of specific solvation effects. Analysis of the dipole moment of the coordinated water molecule in [UO(2)(H(2)O)(MeCN)(4)](2+) reveals that the interaction with the second-shell solvent molecules (through fairly strong and persistent O-H···N hydrogen bonds) causes a significant increase of this dipole moment (by more than 1 D). This cooperative polarization of water reinforces the uranyl-water bond as well as the water solvation via strengthened (UO(2))OH(2)···NCMe hydrogen bonds. Such cooperativity is essentially absent in the acetonitrile ligands that make much weaker (UO(2))NCMe···NCMe hydrogen bonds. Beyond the uranyl case, this study points to the importance of cooperative polarization effects to enhance the M(n+) ion affinity for water in condensed phases involving M(n+)-OH(2)···A fragments, where A is a H-bond proton acceptor and M(n+) is a hard cation.

  19. Organochloride pesticides impaired mitochondrial function in hepatocytes and aggravated disorders of fatty acid metabolism

    PubMed Central

    Liu, Qian; Wang, Qihan; Xu, Cheng; Shao, Wentao; Zhang, Chunlan; Liu, Hui; Jiang, Zhaoyan; Gu, Aihua

    2017-01-01

    p,p’-dichlorodiphenyldichloroethylene (p, p’-DDE) and β-hexachlorocyclohexane (β-HCH) were two predominant organochlorine pesticides (OCPs) metabolites in human body associated with disorders of fatty acid metabolism. However, the underlying mechanisms have not been fully clarified. In this study, adult male C57BL/6 mice were exposed to low dose of p, p’-DDE and β-HCH for 8 wk. OCPs accumulation in organs, hepatic fatty acid composition, tricarboxylic acid cycle (TCA) metabolites and other metabolite profiles were analyzed. Expression levels of genes involved in hepatic lipogenesis and β-oxidation were measured. Mitochondrial function was evaluated in HepG2 cells exposed to OCPs. High accumulation of p, p’-DDE and β-HCH was found in liver and damaged mitochondria was observed under electron microscopy. Expression of genes in fatty acid synthesis increased and that in mitochondrial fatty acid β-oxidation decreased in OCPs treatment groups. OCPs changed metabolite profiles in liver tissues, varied hepatic fatty acid compositions and levels of several TCA cycle metabolites. Furthermore, MitoTracker Green fluorescence, ATP levels, mitochondrial membrane potential and OCR decreased in HepG2 cells exposed to OCPs. In conclusion, chronic exposure to OCPs at doses equivalent to internal exposures in humans impaired mitochondrial function, decreased fatty acid β-oxidation and aggravated disorders of fatty acid metabolism.

  20. Microbial metaproteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    PubMed Central

    Xiong, Weili; Abraham, Paul; Li, Zhou; Pan, Chongle; Hettich, Robert L.

    2015-01-01

    The human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome is not merely a collection of opportunistic parasites, but rather provides important functions to the host that are absolutely critical to many aspects of health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial metaproteomics provides the ability to characterize the human gut microbiota functions and metabolic activities at a remarkably deep level, revealing information about microbiome development and stability as well as their interactions with their human host. Generally, microbial and human proteins can be extracted and then measured by high performance mass spectrometry (MS)-based proteomics technology. Here we review the field of human gut microbiome metaproteomics, with a focus on the experimental and informatics considerations involved in characterizing systems ranging from low-complexity model gut microbiota in gnotobiotic mice, to the emerging gut microbiome in the GI tract of newborn human infants, and finally to an established gut microbiota in human adults. PMID:25914197

  1. Interferon Regulatory Factor 4 controls TH1 cell effector function and metabolism

    PubMed Central

    Mahnke, Justus; Schumacher, Valéa; Ahrens, Stefanie; Käding, Nadja; Feldhoff, Lea Marie; Huber, Magdalena; Rupp, Jan; Raczkowski, Friederike; Mittrücker, Hans-Willi

    2016-01-01

    The transcription factor Interferon Regulatory Factor 4 (IRF4) is essential for TH2 and TH17 cell formation and controls peripheral CD8+ T cell differentiation. We used Listeria monocytogenes infection to characterize the function of IRF4 in TH1 responses. IRF4−/− mice generated only marginal numbers of listeria-specific TH1 cells. After transfer into infected mice, IRF4−/− CD4+ T cells failed to differentiate into TH1 cells as indicated by reduced T-bet and IFN-γ expression, and showed limited proliferation. Activated IRF4−/− CD4+ T cells exhibited diminished uptake of the glucose analog 2-NBDG, limited oxidative phosphorylation and strongly reduced aerobic glycolysis. Insufficient metabolic adaptation contributed to the limited proliferation and TH1 differentiation of IRF4−/− CD4+ T cells. Our study identifies IRF4 as central regulator of TH1 responses and cellular metabolism. We propose that this function of IRF4 is fundamental for the initiation and maintenance of all TH cell responses. PMID:27762344

  2. Metabolic and osmoregulatory function at low and high (3800 m) altitude.

    PubMed

    Greene, H M; Cogger, E A; Miltenberger, T L; Koch, A K; Bray, R E; Wickler, S J

    2002-09-01

    Altitude evokes physiological adjustments that include not only respiratory and cardiovascular properties, but also metabolic function, renal and endocrine responses. The purpose of the present study was designed to expand our understanding of the physiological process involved with acclimatisation to high altitude in equids. The study examined temporal effects on metabolic and osmoregulatory function in horses (n = 6) at rest and postexercise at 3800 m. Animals were studied at 225 m (Pb = 743 mmHg) and during a 10 day stay at altitude (Pb = 487 mmHg). Rest samples were taken 90 min postprandial at 0830 h and immediately after the gallop phase of a standard exercise test. Changes in glucose, insulin, cortisol, thyroxine, sodium, potassium, chloride and total protein were assessed at both altitudes. Exercise stimulated increases in cortisol, thyroxine, potassium, and chloride; while the concentrations of glucose, insulin, sodium and total protein (regardless of altitude) decreased. Acute (Day 2) altitude exposure (following transport stress) produced significant increases in glucose, cortisol, thyroxine, chloride and protein at rest and exercise. All variables (except cortisol) appeared to stabilise by Day 4 of altitude exposure. Observations from these data (coupled with haematological and blood gases data) indicate that equids acutely acclimate within 2-3 days to this altitude.

  3. Model-driven discovery of underground metabolic functions in Escherichia coli.

    PubMed

    Guzmán, Gabriela I; Utrilla, José; Nurk, Sergey; Brunk, Elizabeth; Monk, Jonathan M; Ebrahim, Ali; Palsson, Bernhard O; Feist, Adam M

    2015-01-20

    Enzyme promiscuity toward substrates has been discussed in evolutionary terms as providing the flexibility to adapt to novel environments. In the present work, we describe an approach toward exploring such enzyme promiscuity in the space of a metabolic network. This approach leverages genome-scale models, which have been widely used for predicting growth phenotypes in various environments or following a genetic perturbation; however, these predictions occasionally fail. Failed predictions of gene essentiality offer an opportunity for targeting biological discovery, suggesting the presence of unknown underground pathways stemming from enzymatic cross-reactivity. We demonstrate a workflow that couples constraint-based modeling and bioinformatic tools with KO strain analysis and adaptive laboratory evolution for the purpose of predicting promiscuity at the genome scale. Three cases of genes that are incorrectly predicted as essential in Escherichia coli--aspC, argD, and gltA--are examined, and isozyme functions are uncovered for each to a different extent. Seven isozyme functions based on genetic and transcriptional evidence are suggested between the genes aspC and tyrB, argD and astC, gabT and puuE, and gltA and prpC. This study demonstrates how a targeted model-driven approach to discovery can systematically fill knowledge gaps, characterize underground metabolism, and elucidate regulatory mechanisms of adaptation in response to gene KO perturbations.

  4. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications

    PubMed Central

    Richard, Dawn M; Dawes, Michael A; Mathias, Charles W; Acheson, Ashley; Hill-Kapturczak, Nathalie; Dougherty, Donald M

    2009-01-01

    An essential component of the human diet, L-tryptophan is critical in a number of metabolic functions and has been widely used in numerous research and clinical trials. This review provides a brief overview of the role of L-tryptophan in protein synthesis and a number of other metabolic functions. With emphasis on L-tryptophan’s role in synthesis of brain serotonin, details are provided on the research uses of L-tryptophan, particularly L-tryptophan depletion, and on clinical trials that have been conducted using L-tryptophan supplementation. The ability to change the rates of serotonin synthesis in the brain by manipulating concentrations of serum tryptophan is the foundation of much research. As the sole precursor of serotonin, experimental research has shown that L-tryptophan’s role in brain serotonin synthesis is an important factor involved in mood, behavior, and cognition. Furthermore, clinical trials have provided some initial evidence of L-tryptophan’s efficacy for treatment of psychiatric disorders, particularly when used in combination with other therapeutic agents. PMID:20651948

  5. Microbial metaproteomics for characterizing the range of metabolic functions and activities of human gut microbiota.

    PubMed

    Xiong, Weili; Abraham, Paul E; Li, Zhou; Pan, Chongle; Hettich, Robert L

    2015-10-01

    The human gastrointestinal tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome is not merely a collection of opportunistic parasites, but rather provides important functions to the host that are absolutely critical to many aspects of health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial metaproteomics provides the ability to characterize the human gut microbiota functions and metabolic activities at a remarkably deep level, revealing information about microbiome development and stability as well as their interactions with their human host. Generally, microbial and human proteins can be extracted and then measured by high performance MS-based proteomics technology. Here, we review the field of human gut microbiome metaproteomics, with a focus on the experimental and informatics considerations involved in characterizing systems ranging from low-complexity model gut microbiota in gnotobiotic mice, to the emerging gut microbiome in the GI tract of newborn human infants, and finally to an established gut microbiota in human adults.

  6. Two chitin metabolic enzyme genes from Hyriopsis cumingii: cloning, characterization, and potential functions.

    PubMed

    Wang, G-L; Xu, B; Bai, Z-Y; Li, J-L

    2012-12-19

    Chitin, the second most important natural polymer in the world, and its N-deacetylated derivative chitosan are found in a wide variety of organisms. These versatile biopolymers are associated with a broad range of biological functions. This article is the first to report the potential functions of 2 chitin metabolic enzyme genes from Hyriopsis cumingii. A chitinase-3 gene (Chi-3) and a chitin deacetylase gene (Cda) were cloned from H. cumingii and characterized. Semi-quantitative reverse transcription polymerase chain reaction analysis revealed that the Cda gene was expressed in blood, mantle, liver, stomach, kidney, intestine, gill, and foot, whereas Chi-3 was also expressed in those tissues but not in blood. The tissue-specific expression of H. cumingii Chi-3 indicated that other Chi genes may be involved in the H. cumingii immune system. Real-time quantitative polymerase chain reaction analysis showed that the expression of Chi-3 was significantly (P < 0.05) upregulated 12 h after shell damage, suggesting that Chi-3 might hydrolyze superfluous chitin after shell recovery and play a role in shell formation. Conversely, Cda expression did not change significantly (P > 0.05) to maintain a certain degree of acetylation in chitin/chitosan. This study enriches the basic research on chitin metabolic genes and lays foundations for further research of shell regeneration in mussels.

  7. Alteration of Fatty-Acid-Metabolizing Enzymes Affects Mitochondrial Form and Function in Hereditary Spastic Paraplegia

    PubMed Central

    Tesson, Christelle; Nawara, Magdalena; Salih, Mustafa A.M.; Rossignol, Rodrigue; Zaki, Maha S.; Al Balwi, Mohammed; Schule, Rebecca; Mignot, Cyril; Obre, Emilie; Bouhouche, Ahmed; Santorelli, Filippo M.; Durand, Christelle M.; Oteyza, Andrés Caballero; El-Hachimi, Khalid H.; Al Drees, Abdulmajeed; Bouslam, Naima; Lamari, Foudil; Elmalik, Salah A.; Kabiraj, Mohammad M.; Seidahmed, Mohammed Z.; Esteves, Typhaine; Gaussen, Marion; Monin, Marie-Lorraine; Gyapay, Gabor; Lechner, Doris; Gonzalez, Michael; Depienne, Christel; Mochel, Fanny; Lavie, Julie; Schols, Ludger; Lacombe, Didier; Yahyaoui, Mohamed; Al Abdulkareem, Ibrahim; Zuchner, Stephan; Yamashita, Atsushi; Benomar, Ali; Goizet, Cyril; Durr, Alexandra; Gleeson, Joseph G.; Darios, Frederic; Brice, Alexis; Stevanin, Giovanni

    2012-01-01

    Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function. PMID:23176821

  8. The neurological effects of ghrelin in brain diseases: Beyond metabolic functions.

    PubMed

    Jiao, Qian; Du, Xixun; Li, Yong; Gong, Bing; Shi, Limin; Tang, Tingting; Jiang, Hong

    2017-02-01

    Ghrelin, a peptide released by the stomach that plays a major role in regulating energy metabolism, has recently been shown to have effects on neurobiological behaviors. Ghrelin enhances neuronal survival by reducing apoptosis, alleviating inflammation and oxidative stress, and accordingly improving mitochondrial function. Ghrelin also stimulates the proliferation, differentiation and migration of neural stem/progenitor cells (NS/PCs). Additionally, the ghrelin is benefit for the recovery of memory, mood and cognitive dysfunction after stroke or traumatic brain injury. Because of its neuroprotective and neurogenic roles, ghrelin may be used as a therapeutic agent in the brain to combat neurodegenerative disease. In this review, we highlight the pre-clinical evidence and the proposed mechanisms underlying the role of ghrelin in physiological and pathological brain function.

  9. Comparison of 432 Pseudomonas strains through integration of genomic, functional, metabolic and expression data

    PubMed Central

    Koehorst, Jasper J.; van Dam, Jesse C. J.; van Heck, Ruben G. A.; Saccenti, Edoardo; dos Santos, Vitor A. P. Martins; Suarez-Diez, Maria; Schaap, Peter J.

    2016-01-01

    Pseudomonas is a highly versatile genus containing species that can be harmful to humans and plants while others are widely used for bioengineering and bioremediation. We analysed 432 sequenced Pseudomonas strains by integrating results from a large scale functional comparison using protein domains with data from six metabolic models, nearly a thousand transcriptome measurements and four large scale transposon mutagenesis experiments. Through heterogeneous data integration we linked gene essentiality, persistence and expression variability. The pan-genome of Pseudomonas is closed indicating a limited role of horizontal gene transfer in the evolutionary history of this genus. A large fraction of essential genes are highly persistent, still non essential genes represent a considerable fraction of the core-genome. Our results emphasize the power of integrating large scale comparative functional genomics with heterogeneous data for exploring bacterial diversity and versatility. PMID:27922098

  10. Gap-filling analysis of the iJO1366 Escherichia coli metabolic network reconstruction for discovery of metabolic functions

    PubMed Central

    2012-01-01

    Background The iJO1366 reconstruction of the metabolic network of Escherichia coli is one of the most complete and accurate metabolic reconstructions available for any organism. Still, because our knowledge of even well-studied model organisms such as this one is incomplete, this network reconstruction contains gaps and possible errors. There are a total of 208 blocked metabolites in iJO1366, representing gaps in the network. Results A new model improvement workflow was developed to compare model based phenotypic predictions to experimental data to fill gaps and correct errors. A Keio Collection based dataset of E. coli gene essentiality was obtained from literature data and compared to model predictions. The SMILEY algorithm was then used to predict the most likely missing reactions in the reconstructed network, adding reactions from a KEGG based universal set of metabolic reactions. The feasibility of these putative reactions was determined by comparing updated versions of the model to the experimental dataset, and genes were predicted for the most feasible reactions. Conclusions Numerous improvements to the iJO1366 metabolic reconstruction were suggested by these analyses. Experiments were performed to verify several computational predictions, including a new mechanism for growth on myo-inositol. The other predictions made in this study should be experimentally verifiable by similar means. Validating all of the predictions made here represents a substantial but important undertaking. PMID:22548736

  11. A sturgeon-derived bioactive compound beneficially modulates nuclear receptors controlling metabolic functions in patients with metabolic syndrome.

    PubMed

    Marotta, Francesco; Lorenzetti, Aldo; Catanzaro, Roberto; Zerbinati, Nicola; Jain, Shalini; Solimene, Umberto; Yaduvanshi, Santos K; Yadav, Hariom; Sapienza, Chiara; Srivastava, Nalini; Milazzo, Michele; Italia, Angelo

    2013-06-19

    The aim of the present study was to test the possible effects of a novel sturgeon-derived compound  (LD-1227) on inflammatory markers related to metabolic nuclear receptors in patients with metabolic syndrome. The study population consisted of 76 patients with metabolic syndrome and 30 healthy subjects who were maintained to their current treatments and randomly supplemented: A) LD-1227 (n=38) or B) placebo (n=38) as compared to C) healthy controls (n=30). LD-1227 or placebo (water-soluble starch) were given daily at breakfast and dinner for three months. Levels of hs-CRP, IL-6, TNF-α, leptin and adiponectin/ resistin index were assayed at the entry, 1 month and 3 months afterwards. At the end of the study period, as compared to B group, LD-1227-treated patients showed a significant improvement of all parameters tested, irrespective of the presence of diabetes. In particular, levels of adiponectin and adiponectin/ resistin index significantly increased following LD-1227 administration. Although the metabolic syndrome remains a multifaceted condition requiring a complex approach, LD-1227 could be a potential safe therapeutic tool to be integrated into a wider treatment and preventive medicine schedule strategy.

  12. Hepatocyte Polarity

    PubMed Central

    Treyer, Aleksandr; Müsch, Anne

    2013-01-01

    Hepatocytes, like other epithelia, are situated at the interface between the organism’s exterior and the underlying internal milieu and organize the vectorial exchange of macromolecules between these two spaces. To mediate this function, epithelial cells, including hepatocytes, are polarized with distinct luminal domains that are separated by tight junctions from lateral domains engaged in cell-cell adhesion and from basal domains that interact with the underlying extracellular matrix. Despite these universal principles, hepatocytes distinguish themselves from other nonstriated epithelia by their multipolar organization. Each hepatocyte participates in multiple, narrow lumina, the bile canaliculi, and has multiple basal surfaces that face the endothelial lining. Hepatocytes also differ in the mechanism of luminal protein trafficking from other epithelia studied. They lack polarized protein secretion to the luminal domain and target single-spanning and glycosylphosphatidylinositol-anchored bile canalicular membrane proteins via transcytosis from the basolateral domain. We compare this unique hepatic polarity phenotype with that of the more common columnar epithelial organization and review our current knowledge of the signaling mechanisms and the organization of polarized protein trafficking that govern the establishment and maintenance of hepatic polarity. The serine/threonine kinase LKB1, which is activated by the bile acid taurocholate and, in turn, activates adenosine monophosphate kinase-related kinases including AMPK1/2 and Par1 paralogues has emerged as a key determinant of hepatic polarity. We propose that the absence of a hepatocyte basal lamina and differences in cell-cell adhesion signaling that determine the positioning of tight junctions are two crucial determinants for the distinct hepatic and columnar polarity phenotypes. PMID:23720287

  13. Structure-function dissection of the frizzled receptor in Drosophila melanogaster suggests different mechanisms of action in planar polarity and canonical Wnt signaling.

    PubMed

    Strutt, David; Madder, Daisy; Chaudhary, Varun; Artymiuk, Peter J

    2012-12-01

    Members of the Frizzled family of sevenpass transmembrane receptors signal via the canonical Wnt pathway and also via noncanonical pathways of which the best characterized is the planar polarity pathway. Activation of both canonical and planar polarity signaling requires interaction between Frizzled receptors and cytoplasmic proteins of the Dishevelled family; however, there has been some dispute regarding whether the Frizzled-Dishevelled interactions are the same in both cases. Studies looking at mutated forms of Dishevelled suggested that stable recruitment of Dishevelled to membranes by Frizzled was required only for planar polarity activity, implying that qualitatively different Frizzled-Dishevelled interactions underlie canonical signaling. Conversely, studies looking at the sequence requirements of Frizzled receptors in the fruit fly Drosophila melanogaster for canonical and planar polarity signaling have concluded that there is most likely a common mechanism of action. To understand better Frizzled receptor function, we have carried out a large-scale mutagenesis in Drosophila to isolate novel mutations in frizzled that affect planar polarity activity and have identified a group of missense mutations in cytosolic-facing regions of the Frizzled receptor that block Dishevelled recruitment. Interestingly, although some of these affect both planar polarity and canonical activity, as previously reported for similar lesions, we find a subset that affect only planar polarity activity. These results support the view that qualitatively different Frizzled-Dishevelled interactions underlie planar polarity and canonical Wnt signaling.

  14. Association between liver function and metabolic syndrome in Chinese men and women

    PubMed Central

    Wang, Sen; Zhang, Jie; Zhu, Li; Song, Linlin; Meng, Zhaowei; Jia, Qiang; Li, Xue; Liu, Na; Hu, Tianpeng; Zhou, Pingping; Zhang, Qing; Liu, Li; Song, Kun; Jia, Qiyu

    2017-01-01

    Metabolic syndrome (MS) could be associated with liver function. Our study aimed to investigate the association between liver function and MS in a large cohort of Chinese men and women. We enrolled 32,768 ostensibly healthy participants. The associations between liver function and MS of both genders were analyzed separately after dividing total bilirubin (TBIL), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) into quartiles. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher MS prevalence. We used TBIL, GGT and ALT quartiles as categorical variables in binary logistic regression models. Significantly decreased MS risks were demonstrated in TBIL quartiles 2 to 4 for males, and quartiles 3 to 4 for females. As to GGT and ALT, significantly increased MS risks were shown in high quartiles for both genders. Aging also resulted in significantly higher MS risks in both genders except for young females. This study displayed close associations between liver function and MS, which were influenced by gender and age. A high TBIL level had protective effect against MS, while high GGT and ALT levels were risk factors for MS. It is meaningful that liver function is used as clinical risk predictors for MS. PMID:28317840

  15. Association between liver function and metabolic syndrome in Chinese men and women.

    PubMed

    Wang, Sen; Zhang, Jie; Zhu, Li; Song, Linlin; Meng, Zhaowei; Jia, Qiang; Li, Xue; Liu, Na; Hu, Tianpeng; Zhou, Pingping; Zhang, Qing; Liu, Li; Song, Kun; Jia, Qiyu

    2017-03-20

    Metabolic syndrome (MS) could be associated with liver function. Our study aimed to investigate the association between liver function and MS in a large cohort of Chinese men and women. We enrolled 32,768 ostensibly healthy participants. The associations between liver function and MS of both genders were analyzed separately after dividing total bilirubin (TBIL), gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) into quartiles. Young males had significantly higher MS prevalence than females, yet after menopause, females had higher MS prevalence. We used TBIL, GGT and ALT quartiles as categorical variables in binary logistic regression models. Significantly decreased MS risks were demonstrated in TBIL quartiles 2 to 4 for males, and quartiles 3 to 4 for females. As to GGT and ALT, significantly increased MS risks were shown in high quartiles for both genders. Aging also resulted in significantly higher MS risks in both genders except for young females. This study displayed close associations between liver function and MS, which were influenced by gender and age. A high TBIL level had protective effect against MS, while high GGT and ALT levels were risk factors for MS. It is meaningful that liver function is used as clinical risk predictors for MS.

  16. Energy metabolism and thyroid function of mice with deleted wolframin (Wfs1) gene.

    PubMed

    Noormets, K; Kõks, S; Ivask, M; Aunapuu, M; Arend, A; Vasar, E; Tillmann, V

    2014-05-01

    There is no data about the energy metabolism of patients with Wolfram syndrome caused by mutations in the wolframin (Wfs1) gene. The aim of this study was to investigate the role of Wfs1 in energy metabolism and thyroid function in Wfs1 deficient mice (Wfs1KO). 16 male (8 Wfs1KO, 8 wild type (wt)) and 16 female (8 Wfs1KO, 8wt) mice aged 11-13 weeks were studied alone in a specific metabolic cage for 48 h. Body weight, food, water and O2 consumption, motor activity, CO2 and heat production of mice were recorded. At the age of 14-20 weeks, plasma levels of thyroxine (T4), TSH and leptin were measured and histology of thyroid tissues examined. Mean CO2 and heat production was not different between the groups. Mean O2 consumption was higher in the Wfs1KO females compared to the Wfs1KO males (3 410.0±127.0 vs. 2 806.0±82.4 ml/kg/h; p<0.05), but not compared to the wt mice. The mean movement activity was not different between the groups except that the Wfs1KO females reared up more often than the wt females (199.8±63.46 vs. 39.26±24.71 cnts/48 h; p<0.05). Both male and female Wfs1KO mice had significantly lower body mass and food intake than wt mice. Male Wfs1KO mice also lost more weight in metabolic cage than wt males (20.43±0.41 vs. 16.07±0.86%; p<0.05) indicating more pronounced response to isolation. Male Wfs1KO mice had significantly lower levels of plasma leptin than wt male mice (3.37±0.40 vs. 5.82±0.71 ng/ml; p<0.01). Thyroid function measured by serum TSH and T4 levels was not different between Wfs1KO and wt groups, but both Wfs1KO and wt male mice had significantly higher mean T4 levels than female mice. The histology of thyroid tissue of Wfs1KO males showed a trend to a smaller mean number of epithelial cells per follicle than the wt male mice.Although Wfs1KO mice were smaller and lost more weight during the experiment, their energy metabolism was not different from wt mice except that the female Wfs1KO mice consumed more O2. As mice in

  17. Parameters inversing of polarized bidirectional reflectance distribution function model for target rough surface

    NASA Astrophysics Data System (ADS)

    Liu, Qing; Zhan, Yong-hong; Yang, Di; Zeng, Chang-e.

    2014-11-01

    In this paper, we try to find a model that can apply to predict the polarization characteristics of the targets on the ground correctly. In the first place, we give an introduction to several kinds of existing models which are divided into three categories: Empirical models are precise but occupy too much source of computer; Physical-based models can predict the phenomenon of reflection exactly but hardly get the final results; Semi-empirical models have both advantages mentioned above and avoid their disadvantages effectively. Then we make an analysis of the Priest-Germer (PG) pBRDF model, one of semi-empirical models, which is suitable for our study. The methods of parameters inversing and testing are proposed based on this model and the test system from which we can get enough data to verify the accuracy of the model is designed independently. At last, we make a simulation of the whole process of the parameters inversing based on PG pBRDF model. From the analysis of the simulation curves, we briefly know the direction we go in the following work to make an amendment.

  18. Gas chromatographic metabolic profiling: a sensitive tool for functional microbial ecology.

    PubMed

    Coucheney, Elsa; Daniell, Tim J; Chenu, Claire; Nunan, Naoise

    2008-12-01

    Microbial metabolomics, which consists of a non-targeted analysis of the metabolites released from ('exometabolome') or existing in ('endometabolome') a cell has mostly been used to study the metabolism of particular microbes. Metabolomes also represent a picture of microbial activity and we suggest that the exometabolome may also contain pertinent information for studying microbial interaction networks. Gas chromatography coupled to mass spectrometry is the most commonly used technique in metabolomics studies. It allows a wide range of metabolites to be detected but requires the derivatisation of compounds prior to detection. This type of non-targeted analysis can introduce biases to the detection and quantification of the different metabolites, particularly at the extraction and derivatisation steps. The aims of this study, therefore, were to quantify the sources of variability and to test the sensitivity of the GC metabolic profiling approach to small environmental changes such as shifts in temperature. The temperature sensitivity of metabolic profiles was compared with that of catabolic profiles obtained using Biolog microplates. Analytical variability was compared with biological variability by incubating bacterial strains isolated from soil with fructose at 20 degrees C and by replicating each step of the protocol (incubation, extraction and derivatisation). For both the endo- and the exometabolome, more than 70% of the total variability was of biological origin and principal components analysis clearly separated the strains along the first ordination axis. The endometabolome distinguished bacterial strains at the species level only, whereas separation was evident at the species and group level with the exometabolome. Temperature had a significant but differential effect on the metabolite production of the bacterial strains whilst their catabolic profiles remained relatively unaffected. The exometabolome was more sensitive to temperature shifts than the

  19. Apolipoprotein E metabolism and functions in brain and its role in Alzheimer's disease

    PubMed Central

    Liao, Fan; Yoon, Hyejin; Kim, Jungsu

    2017-01-01

    Purpose of review APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheimer's disease. Recent findings ApoE isoforms have differential effects on amyloid β metabolism. Recent studies demonstrated that ApoE-interacting proteins, such as ATP-binding cassette A1 (ABCA1) and LDL receptor, may be promising therapeutic targets for Alzheimer's disease treatment. Activation of liver X receptor and retinoid X receptor pathway induces ABCA1 and other genes, leading to amyloid β clearance. Inhibition of the negative regulators of ABCA1, such as microRNA-33, also induces ABCA1 and decreases the levels of ApoE and amyloid β. In addition, genetic inactivation of an E3 ubiquitin ligase, myosin regulatory light chain interacting protein, increases LDL receptor levels and inhibits amyloid accumulation. Although amyloid β-dependent pathways have been extensively investigated, there have been several recent studies linking ApoE with vascular function, neuroinflammation, metabolism, synaptic plasticity, and transcriptional regulation. For example, ApoE was identified as a ligand for a microglial receptor, TREM2, and studies suggested that ApoE may affect the TREM2-mediated microglial phagocytosis. Summary Emerging data suggest that ApoE affects several amyloid β-independent pathways. These underexplored pathways may provide new insights into Alzheimer's disease pathogenesis. However, it will be important to determine to what extent each mechanism contributes to the pathogenesis of Alzheimer's disease. PMID:27922847

  20. Gene therapy to improve high-density lipoprotein metabolism and function.

    PubMed

    Van Craeyveld, Eline; Gordts, Stephanie; Jacobs, Frank; De Geest, Bart

    2010-05-01

    Plasma levels of high-density lipoprotein (HDL) cholesterol and its major apolipoprotein (apo), apo A-I, are inversely correlated with the incidence of ischemic cardiovascular diseases. Till now, evaluation of the hypothesis that elevation of HDL cholesterol reduces atherosclerotic burden and/or decreases ischemic cardiovascular events in humans has been hampered by the lack of drugs that selectively increase HDL cholesterol. In contrast to the lack of clinical data, evidence for a direct causal role of HDL in modulating atherogenesis in experimental models has been provided by investigations in human apo A-I transgenic mice and rabbits. The development of gene transfer technologies with a sufficiently high therapeutic index may pave the road for a selective and effective HDL raising therapeutic intervention. The goal of a therapeutic strategy that modulates HDL metabolism is not an increase of HDL cholesterol as such, but an enhancement of HDL function. The value of HDL cholesterol as a surrogate end-point to predict reduced atherosclerosis or a decrease in clinical events may be highly dependent on the mechanism leading to an increased level of HDL cholesterol. In the case of gene transfer, this implies that beneficial effects of increasing HDL cholesterol will be dependent on the transgene that is expressed. Here, we critically review HDL metabolism and HDL function in relation to the development of HDL raising gene transfer, advances and drawbacks of different gene transfer technologies, and experimental gene transfer studies evaluating the effect of raised HDL on histological and functional outcomes in animal models.

  1. Time Rate of Blood Pressure Variation Is Associated With Endothelial Function in Patients With Metabolic Syndrome.

    PubMed

    Ruan, Yanping; Wei, Wanlin; Yan, Jianhua; Sun, Lixian; Lian, Hui; Zhao, Xiaoyi; Liang, Ruijuan; Xiaole, Liu; Fan, Zhongjie

    2016-01-01

    The time rate of blood pressure (BP) variation indicates the speed of BP fluctuations. Previous studies have demonstrated that the time rate of BP variation was associated with target organ damage. However, the association between time rate of BP variation and endothelial function has not been evaluated.24-hour ambulatory blood pressure monitoring (ABPM) was performed in 61 patients with metabolic syndrome. Time rate of BP variation was calculated from BP recordings of ABPM. Endothelial function was assessed using reactive hyperemia-peripheral arterial tonometry index (RHI) by EndoPat2000. Multiple linear regression models were used to detect the association between time rate of BP variation and RHI.Among all the subjects (n = 61), the multiple linear regression models revealed that the daytime rate of systolic blood pressure (SBP) variation was independently associated with RHI (β = -0.334, P = 0.008). A 0.1 mmHg/minute increase in the daytime rate of SBP variation correlated with a decline of 0.20 in RHI. The same effect was also found in the subjects with eGFR ≥ 60 mL/ (minute*1.73 m(2)). A greater association was found in those who were not taking a statin, β-blocker, ACEI/ARB, or diuretic and those without diabetes compared with those with any antihypertensive medication or with diabetes. Other ambulatory blood pressure parameters and central hemodynamics were not found to be associated with RHI.Our findings have shown that the daytime rate of SBP variation was associated with endothelial function in patients with metabolic syndrome, independent of other BP parameters and central hemodynamics.

  2. Comparing Two Intestinal Porcine Epithelial Cell Lines (IPECs): Morphological Differentiation, Function and Metabolism

    PubMed Central

    Nossol, Constanze; Barta-Böszörményi, Anicò; Kahlert, Stefan; Zuschratter, Werner; Faber-Zuschratter, Heidi; Reinhardt, Nicole; Ponsuksili, Siriluk; Wimmers, Klaus; Diesing, Anne-Kathrin; Rothkötter, Hermann-Josef

    2015-01-01

    The pig shows genetical and physiological resemblance to human, which predestines it as an experimental animal model especially for mucosal physiology. Therefore, the intestinal epithelial cell lines 1 and J2 (IPEC-1, IPEC-J2) - spontaneously immortalised cell lines from the porcine intestine - are important tools for studying intestinal function. A microarray (GeneChip Porcine Genome Array) was performed to compare the genome wide gene expression of IPECs. Different significantly up-regulated pathways were identified, like “lysosome”, “pathways in cancer”, “regulation of actin cytoskeleton” and “oxidative phosphorylation” in IPEC-J2 in comparison to IPEC-1. On the other hand, “spliceosome”, “ribosome”, “RNA-degradation” and “tight junction” are significantly down-regulated pathways in IPEC-J2 in comparison to IPEC-1. Examined pathways were followed up by functional analyses. ATP-, oxygen, glucose and lactate-measurement provide evidence for up-regulation of oxidative phosphorylation in IPEC-J2. These cells seem to be more active in their metabolism than IPEC-1 cells due to a significant higher ATP-content as well as a higher O2- and glucose-consumption. The down-regulated pathway “ribosome” was followed up by measurement of RNA- and protein content. In summary, IPEC-J2 is a morphologically and functionally more differentiated cell line in comparison to IPEC-1. In addition, IPEC-J2 cells are a preferential tool for in vitro studies with the focus on metabolism. PMID:26147118

  3. Novel Functions of Ect2 in Polar Lamellipodia Formation and Polarity Maintenance during “Contractile Ring-Independent” Cytokinesis in Adherent Cells

    PubMed Central

    Kanada, Masamitsu; Nagasaki, Akira

    2008-01-01

    Some mammalian cells are able to divide via both the classic contractile ring-dependent method (cytokinesis A) and a contractile ring-independent, adhesion-dependent method (cytokinesis B). Cytokinesis A is triggered by RhoA, which, in HeLa cells, is activated by the guanine nucleotide-exchange factor Ect2 localized at the central spindle and equatorial cortex. Here, we show that in HT1080 cells undergoing cytokinesis A, Ect2 does not localize in the equatorial cortex, though RhoA accumulates there. Moreover, Ect2 depletion resulted in only modest multinucleation of HT1080 cells, enabling us to establish cell lines in which Ect2 was constitutively depleted. Thus, RhoA is activated via an Ect2-independent pathway during cytokinesis A in HT1080 cells. During cytokinesis B, Ect2-depleted cells showed narrower accumulation of RhoA at the equatorial cortex, accompanied by compromised pole-to-equator polarity, formation of ectopic lamellipodia in regions where RhoA normally would be distributed, and delayed formation of polar lamellipodia. Furthermore, C3 exoenzyme inhibited equatorial RhoA activation and polar lamellipodia formation. Conversely, expression of dominant active Ect2 in interphase HT1080 cells enhanced RhoA activity and suppressed lamellipodia formation. These results suggest that equatorial Ect2 locally suppresses lamellipodia formation via RhoA activation, which indirectly contributes to restricting lamellipodia formation to polar regions during cytokinesis B. PMID:17942602

  4. Metasurface polarization splitter.

    PubMed

    Slovick, Brian A; Zhou, You; Yu, Zhi Gang; Kravchenko, Ivan I; Briggs, Dayrl P; Moitra, Parikshit; Krishnamurthy, Srini; Valentine, Jason

    2017-03-28

    Polarization beam splitters, devices that separate the two orthogonal polarizations of light into different propagation directions, are among the most ubiquitous optical elements. However, traditionally polarization splitters rely on bulky optical materials, while emerging optoelectronic and photonic circuits require compact, chip-scale polarization splitters. Here, we show that a rectangular lattice of cylindrical silicon Mie resonators functions as a polarization splitter, efficiently reflecting one polarization while transmitting the other. We show that the polarization splitting arises from the anisotropic permittivity and permeability of the metasurface due to the twofold rotational symmetry of the rectangular unit cell. The high polarization efficiency, low loss and low profile make these metasurface polarization splitters ideally suited for monolithic integration with optoelectronic and photonic circuits.This article is part of the themed issue 'New horizons for nanophotonics'.

  5. The interaction of human natural killer cells with either unpolarized or polarized macrophages results in different functional outcomes.

    PubMed

    Bellora, Francesca; Castriconi, Roberta; Dondero, Alessandra; Reggiardo, Giorgio; Moretta, Lorenzo; Mantovani, Alberto; Moretta, Alessandro; Bottino, Cristina

    2010-12-14

    The cross-talk among cells of the innate immunity can greatly affect both innate and adaptive responses. Here we analyzed the molecular interactions between human natural killer (NK) cells and autologous macrophages. Activated NK cells killed M0 and M2, whereas M1 macrophages were more resistant to lysis because of their higher expression of HLA class I molecules. Following exposure to LPS or bacillus Calmette-Guérin, M0 and M2, but not polarized (endotoxin tolerant) M1 macrophages, induced strong activation of resting NK cells. The expression of CD69 and CD25 activation markers and the acquisition of cytotoxicity against tumor cells and immature dendritic cells required soluble factors being mostly contact independent. On the contrary, IFN-γ production was contact dependent and required the interaction of DNAM-1 and 2B4 (on NK) with their ligands on macrophages as well as IL-18. IL-18 was involved also in the acquisition of CCR7 by NK cells. Interestingly, M0 and M2 cells expressed a membrane-bound form of IL-18, which was released in small amounts after LPS treatment. Our data indicate that, upon interaction with M0 macrophages exposed to microbial products, NK cells may amplify classical type 1 immune responses. In addition, M1-polarizing stimuli can rescue M2 macrophages from their immunomodulatory state and shape their functional behavior toward NK stimulatory capability.

  6. In vivo effects of environmental concentrations of produced water on the reproductive function of polar cod (Boreogadus saida).

    PubMed

    Geraudie, P; Nahrgang, J; Forget-Leray, J; Minier, C; Camus, L

    2014-01-01

    Offshore oil and gas drilling processes generate operational discharges such as produced water (PW), a complex mixture of seawater with polycyclic aromatic hydrocarbons (PAH) and alkylphenols (AP). Some of these compounds may interact with the endocrine system of marine organisms and alter reproductive functions. In this study, polar cod were exposed for up to 28 d to a mixture of PAH, alkylated PAH, and AP simulating the composition of North Sea PW, at low and high concentrations (1:2000 and 1:1000 dilution of the original concentrate, respectively). Potential adverse effects of PW on polar cod physiology were investigated through biomarkers of biotransformation (hepatic ethoxyresorufin O-deethylase [EROD] activity and bile PAH metabolites), endocrine disruption (plasma vitellogenin [VTG] levels and sex steroid concentrations), and gonad histology. Plasma sexual steroid levels in fish were not markedly affected by PW exposure, while higher plasma VTG concentrations were measured in females exposed to the high PW treatment for 7 and 28 d. In males exposed to the higher PW concentration, inhibition of spermatogenesis was observed after 28 d in addition to increase of melano-macrophage occurrence in testis. Females exposed to the high PW treatment for 21 d showed a significant increase of atresia incidence. Finally, a significant decrease in oocyte number was observed in high PW exposed female ovaries after 28 d of exposure.

  7. Graphing Polar Curves

    ERIC Educational Resources Information Center

    Lawes, Jonathan F.

    2013-01-01

    Graphing polar curves typically involves a combination of three traditional techniques, all of which can be time-consuming and tedious. However, an alternative method--graphing the polar function on a rectangular plane--simplifies graphing, increases student understanding of the polar coordinate system, and reinforces graphing techniques learned…

  8. Energy metabolism of rabbit retina as related to function: high cost of Na+ transport.

    PubMed

    Ames, A; Li, Y Y; Heher, E C; Kimble, C R

    1992-03-01

    Experiments designed to examine the energy requirements of neurophysiological function were performed on isolated rabbit retina. Function was altered by photic stimulation or by function-specific drugs, and the response of energy metabolism was assessed by simultaneous measurements of O2 consumption and lactate production. In other experiments, the supply of O2 or glucose was reduced and the effect on energy metabolism and electrophysiological function was observed. Energy requirements under control conditions in darkness were high, with O2 consumption (per gm dry wt) at 11.3 mumol min-1, with lactate production at 14.8 mumol min-1, and with the derived value for glucose consumption at 9.3 mumol min-1 and for high-energy phosphate (approximately P) generation at 82.6 mumol min-1. Energy reserves were small. Removing glucose abolished the b-wave of the electroretinogram (ERG) with a t1/2 of 1 min, but did not immediately affect O2 consumption or the PIII of the ERG. Removing O2 caused increases of up to 2.7-fold in glycolysis (Pasteur effect) and caused both PIII and b-wave to fail, with a t1/2 of about 5 min. Neurotransmission through the inner retina was supported almost entirely by glycolysis, as evidenced by large increases in lactate production in response to flashing light and decreases in response to transmitter blockers (2.3-fold overall change), with no change in O2 consumption. Phototransduction, on the other hand, was normally supported by oxidative metabolism. The dark current accounted for 41% of the retina's O2 consumption. With O2 reduced, the dark current was partially supported by glycolysis, which accounts (at least in part) for the large Pasteur effect. Na+ transport by NaK ATPase accounted for about half of all energy used, as evidenced by the response to strophanthidin, that is, for 49% of the oxidative energy and 58% of the glycolytic energy. The t1/2 for the turnover of intracellular Na+ was calculated from these data to be less than 1 min

  9. Understanding the structure-function relationship between FGF19 and its mitogenic and metabolic activities.

    PubMed

    Wu, Xinle; Li, Yang

    2012-01-01

    FGF19 differs from the classical FGFs in that it has a much-reduced heparan sulfate proteoglycan binding affinity that allows it to act as endocrine hormone. Although FGF19 regulates several different metabolic activities, it still activates downstream signaling pathways through FGF receptors, in a similar manner to that seen in classical FGFs. Aberrant FGF signaling has been implicated in tumor development, and mouse models have confirmed that FGF19 has the potential to induce hepatocellular carcinoma. Treatment with anti-FGF19 antibody suppressed tumor progression in both FGF19 transgenic mice and colon cancer cell xenograft models. FGFR4, the predominant FGF receptor expressed in the liver, may play an important role in FGF19-mediated tumorigenesis. This review reports the current advances in understanding the structure-function relationship between FGF19 and its interactions with FGFRs, its physiological activities, and its differences from FGF21. The review also discusses strategies to separate the mitogenic and metabolic activities for the development of potential therapeutic molecules based on FGF19.

  10. Damaging effects of hyperglycemia on cardiovascular function: spotlight on glucose metabolic pathways.

    PubMed

    Mapanga, Rudo F; Essop, M Faadiel

    2016-01-15

    The incidence of cardiovascular complications associated with hyperglycemia is a growing global health problem. This review discusses the link between hyperglycemia and cardiovascular diseases onset, focusing on the role of recently emerging downstream mediators, namely, oxidative stress and glucose metabolic pathway perturbations. The role of hyperglycemia-mediated activation of nonoxidative glucose pathways (NOGPs) [i.e., the polyol pathway, hexosamine biosynthetic pathway, advanced glycation end products (AGEs), and protein kinase C] in this process is extensively reviewed. The proposal is made that there is a unique interplay between NOGPs and a downstream convergence of detrimental effects that especially affect cardiac endothelial cells, thereby contributing to contractile dysfunction. In this process the AGE pathway emerges as a crucial mediator of hyperglycemia-mediated detrimental effects. In addition, a vicious metabolic cycle is established whereby hyperglycemia-induced NOGPs further fuel their own activation by generating even more oxidative stress, thereby exacerbating damaging effects on cardiac function. Thus NOGP inhibition, and particularly that of the AGE pathway, emerges as a novel therapeutic intervention for the treatment of cardiovascular complications such as acute myocardial infarction in the presence hyperglycemia.

  11. Influence of tacrolimus metabolism rate on renal function after solid organ transplantation

    PubMed Central

    Thölking, Gerold; Gerth, Hans Ulrich; Schuette-Nuetgen, Katharina; Reuter, Stefan

    2017-01-01

    The calcineurin inhibitor (CNI) tacrolimus (TAC) is an integral part of the immunosuppressive regimen after solid organ transplantation. Although TAC is very effective in prevention of acute rejection episodes, its highly variable pharmacokinetic and narrow therapeutic window require frequent monitoring of drug levels and dose adjustments. TAC can cause CNI nephrotoxicity even at low blood trough levels (4-6 ng/mL). Thus, other factors besides the TAC trough level might contribute to CNI-related kidney injury. Unfortunately, TAC pharmacokinetic is determined by a whole bunch of parameters. However, for daily clinical routine a simple application strategy is needed. To address this problem, we and others have evaluated a simple calculation method in which the TAC blood trough concentration (C) is divided by the daily dose (D). Fast TAC metabolism (C/D ratio < 1.05) was identified as a potential risk factor for an inferior kidney function after transplantation. In this regard, we recently showed a strong association between fast TAC metabolism and CNI nephrotoxicity as well as BKV infection. Therefore, the TAC C/D ratio may assist transplant clinicians in a simple way to individualize the immunosuppressive regimen. PMID:28280692

  12. SVD identifies transcript length distribution functions from DNA microarray data and reveals evolutionary forces globally affecting GBM metabolism.

    PubMed

    Bertagnolli, Nicolas M; Drake, Justin A; Tennessen, Jason M; Alter, Orly

    2013-01-01

    To search for evolutionary forces that might act upon transcript length, we use the singular value decomposition (SVD) to identify the length distribution functions of sets and subsets of human and yeast transcripts from profiles of mRNA abundance levels across gel electrophoresis migration distances that were previously measured by DNA microarrays. We show that the SVD identifies the transcript length distribution functions as "asymmetric generalized coherent states" from the DNA microarray data and with no a-priori assumptions. Comparing subsets of human and yeast transcripts of the same gene ontology annotations, we find that in both disparate eukaryotes, transcripts involved in protein synthesis or mitochondrial metabolism are significantly shorter than typical, and in particular, significantly shorter than those involved in glucose metabolism. Comparing the subsets of human transcripts that are overexpressed in glioblastoma multiforme (GBM) or normal brain tissue samples from The Cancer Genome Atlas, we find that GBM maintains normal brain overexpression of significantly short transcripts, enriched in transcripts that are involved in protein synthesis or mitochondrial metabolism, but suppresses normal overexpression of significantly longer transcripts, enriched in transcripts that are involved in glucose metabolism and brain activity. These global relations among transcript length, cellular metabolism and tumor development suggest a previously unrecognized physical mode for tumor and normal cells to differentially regulate metabolism in a transcript length-dependent manner. The identified distribution functions support a previous hypothesis from mathematical modeling of evolutionary forces that act upon transcript length in the manner of the restoring force of the harmonic oscillator.

  13. Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites.

    PubMed

    Blevins-Primeau, Andrea S; Sun, Dongxiao; Chen, Gang; Sharma, Arun K; Gallagher, Carla J; Amin, Shantu; Lazarus, Philip

    2009-03-01

    Tamoxifen (TAM) is a selective estrogen receptor modulator widely used in the prevention and treatment of breast cancer. A major mode of metabolism of the major active metabolites of TAM, 4-OH-TAM and endoxifen, is by glucuronidation via the UDP-glucuronosyltransferase (UGT) family of enzymes. To examine whether polymorphisms in the UGT enzymes responsible for the glucuronidation of active TAM metabolites play an important role in interindividual differences in TAM metabolism, cell lines overexpressing wild-type or variant UGTs were examined for their activities against TAM metabolites in vitro. For variants of active extrahepatic UGTs, the UGT1A8(173Ala/277Tyr) variant exhibited no detectable glucuronidation activity against the trans isomers of either 4-OH-TAM or endoxifen. Little or no difference in TAM glucuronidating activity was observed for the UGT1A8(173Gly/277Cys) or UGT1A10(139Lys) variants compared with their wild-type counterparts. For active hepatic UGTs, the UGT2B7(268Tyr) variant exhibited significant (P < 0.01) 2- and 5-fold decreases in activity against the trans isomers of 4-OH-TAM and endoxifen, respectively, compared with wild-type UGT2B7(268His). In studies of 111 human liver microsomal specimens, the rate of O-glucuronidation against trans-4-OH-TAM and trans-endoxifen was 28% (P < 0.001) and 27% (P = 0.002) lower, respectively, in individuals homozygous for the UGT2B7 Tyr(268)Tyr genotype compared with subjects with the UGT2B7 His(268)His genotype, with a significant (P < 0.01) trend of decreasing activity against both substrates with increasing numbers of the UGT2B7(268His) allele. These results suggest that functional polymorphisms in TAM-metabolizing UGTs, including UGT2B7 and potentially UGT1A8, may be important in interindividual variability in TAM metabolism and response to TAM therapy.

  14. Structure functions in the polarized Drell-Yan processes with spin-1/2 and spin-1 hadrons. II. Parton model

    NASA Astrophysics Data System (ADS)

    Hino, S.; Kumano, S.

    1999-09-01

    We analyze the polarized Drell-Yan processes with spin-1/2 and spin-1 hadrons in a parton model. Quark and antiquark correlation functions are expressed in terms of possible combinations of Lorentz vectors and pseudovectors with the constrains of Hermiticity, parity conservation, and time-reversal invariance. Then, we find tensor-polarized distributions for a spin-1 hadron. The naive parton model predicts that there exist 19 structure functions. However, there are only four or five nonvanishing structure functions, depending on whether the cross section is integrated over the virtual-photon transverse momentum Q-->T or the limit QT-->0 is taken. One of the finite structure functions is related to the tensor-polarized distribution b1, and it does not exist in the proton-proton reactions. The vanishing structure functions should be associated with higher-twist physics. The tensor distributions can be measured by the quadrupole polarization measurements. The Drell-Yan process has an advantage over the lepton reaction in the sense that the antiquark tensor polarization could be extracted rather easily.

  15. Lung function and heart disease in American Indian adults with high frequency of metabolic abnormalities (from the Strong Heart Study).

    PubMed

    Yeh, Fawn; Dixon, Anne E; Best, Lyle G; Marion, Susan M; Lee, Elisa T; Ali, Tauqeer; Yeh, Jeunliang; Rhoades, Everett R; Howard, Barbara V; Devereux, Richard B

    2014-07-15

    The associations of pulmonary function with cardiovascular disease (CVD) independent of diabetes mellitus (DM) and metabolic syndrome have not been examined in a population-based setting. We examined prevalence and incidence CVD in relation to lower pulmonary function in the Strong Heart Study second examination (1993 to 1995) in 352 CVD and 2,873 non-CVD adults free of overt lung disease (mean age 60 years). Lung function was assessed by standard spirometry. Participants with metabolic syndrome or DM with or without CVD had lower pulmonary function than participants without these conditions after adjustment for hypertension, age, gender, abdominal obesity, smoking, physical activity index, and study field center. CVD participants with DM had significantly lower forced vital capacity than participants with CVD alone. Significant associations were observed between reduced pulmonary function, preclinical CVD, and prevalent CVD after adjustment for multiple CVD risk factors. During follow-up (median 13.3 years), pulmonary function did not predict CVD incidence, it predicted CVD mortality. Among 3,225 participants, 412 (298 without baseline CVD) died from CVD by the end of 2008. In models adjusted for multiple CVD risk factors, DM, metabolic syndrome, and baseline CVD, compared with highest quartile of lung function, lower lung function predicted CVD mortality (relative risk up to 1.5, 95% confidence interval 1.1 to 2.0, p<0.05). In conclusion, a population with a high prevalence of DM and metabolic syndrome and lower lung function was independently associated with prevalent clinical and preclinical CVD, and its impairment predicted CVD mortality. Additional research is needed to identify mechanisms linking metabolic abnormalities, low lung function, and CVD.

  16. Linkage of organic anion transporter-1 to metabolic pathways through integrated "omics"-driven network and functional analysis.

    PubMed

    Ahn, Sun-Young; Jamshidi, Neema; Mo, Monica L; Wu, Wei; Eraly, Satish A; Dnyanmote, Ankur; Bush, Kevin T; Gallegos, Tom F; Sweet, Douglas H; Palsson, Bernhard Ø; Nigam, Sanjay K

    2011-09-09

    The main kidney transporter of many commonly prescribed drugs (e.g. penicillins, diuretics, antivirals, methotrexate, and non-steroidal anti-inflammatory drugs) is organic anion transporter-1 (OAT1), originally identified as NKT (Lopez-Nieto, C. E., You, G., Bush, K. T., Barros, E. J., Beier, D. R., and Nigam, S. K. (1997) J. Biol. Chem. 272, 6471-6478). Targeted metabolomics in knockouts have shown that OAT1 mediates the secretion or reabsorption of many important metabolites, including intermediates in carbohydrate, fatty acid, and amino acid metabolism. This observation raises the possibility that OAT1 helps regulate broader metabolic activities. We therefore examined the potential roles of OAT1 in metabolic pathways using Recon 1, a functionally tested genome-scale reconstruction of human metabolism. A computational approach was used to analyze in vivo metabolomic as well as transcriptomic data from wild-type and OAT1 knock-out animals, resulting in the implication of several metabolic pathways, including the citric acid cycle, polyamine, and fatty acid metabolism. Validation by in vitro and ex vivo analysis using Xenopus oocyte, cell culture, and kidney tissue assays demonstrated interactions between OAT1 and key intermediates in these metabolic pathways, including previously unknown substrates, such as polyamines (e.g. spermine and spermidine). A genome-scale metabolic network reconstruction generated some experimentally supported predictions for metabolic pathways linked to OAT1-related transport. The data support the possibility that the SLC22 and other families of transporters, known to be expressed in many tissues and primarily known for drug and toxin clearance, are integral to a number of endogenous pathways and may be involved in a larger remote sensing and signaling system (Ahn, S. Y., and Nigam, S. K. (2009) Mol. Pharmacol. 76, 481-490, and Wu, W., Dnyanmote, A. V., and Nigam, S. K. (2011) Mol. Pharmacol. 79, 795-805). Drugs may alter metabolism by

  17. Nutritional control of immunity: Balancing the metabolic requirements with an appropriate immune function.

    PubMed

    De Rosa, Veronica; Galgani, Mario; Santopaolo, Marianna; Colamatteo, Alessandra; Laccetti, Roberta; Matarese, Giuseppe

    2015-09-01

    The immune system is a highly integrated network of cells sensitive to a number of environmental factors. Interestingly, recent years have seen a dramatic increase in our understanding of how diet makes a crucial contribution to human health, affecting the immune system, secretion of adipocytokines and metabolic pathways. Recent experimental evidence indicates that diet and its components are able to profoundly influence immune responses, thus affecting the development of inflammatory and autoimmune diseases. This review aims to discuss some of the main topics concerning the impact of nutrients and their relative composition on immune cell development and function that may be particularly important for regulating the balance between inflammatory and tolerogenic processes. We also highlight the effects of diet on commensal bacteria and how changes in the composition of the microbiota alter intestinal and systemic immune homeostasis. Finally, we summarize the effects of dietary compounds on epigenetic mechanisms involved in the regulation of several immune related genes.

  18. Functional characterization of an invertase inhibitor gene involved in sucrose metabolism in tomato fruit.

    PubMed

    Zhang, Ning; Jiang, Jing; Yang, Yan-li; Wang, Zhi-he

    2015-10-01

    In this study, we produced tomato plants overexpressing an invertase inhibitor gene (Sly-INH) from tomato, using a simple and efficient transient transformation system. Compared with control plants, the expression of Sly-INH was highly upregulated in Sly-INH overexpressing plants, as indicated by real-time polymerase chain reaction (PCR). Physiological analysis revealed that Sly-INH inhibited the activity of cell wall invertase (CWIN), which increased sugar accumulation in tomato fruit. Furthermore, Sly-INH mediated sucrose metabolism by regulating CWIN activity. Our results suggest that invertase activity is potentially regulated by the Sly-INH inhibitor at the post-translational level, and they demonstrate that the transient transformation system is an effective method for determining the functions of genes in tomato.

  19. Emerging model systems for functional genomics analysis of Crassulacean acid metabolism.

    PubMed

    Hartwell, James; Dever, Louisa V; Boxall, Susanna F

    2016-06-01

    Crassulacean acid metabolism (CAM) is one of three main pathways of photosynthetic carbon dioxide fixation found in higher plants. It stands out for its ability to underpin dramatic improvements in plant water use efficiency, which in turn has led to a recent renaissance in CAM research. The current ease with which candidate CAM-associated genes and proteins can be identified through high-throughput sequencing has opened up a new horizon for the development of diverse model CAM species that are amenable to genetic manipulations. The adoption of these model CAM species is underpinning rapid advances in our understanding of the complete gene set for CAM. We highlight recent breakthroughs in the functional characterisation of CAM genes that have been achieved through transgenic approaches.

  20. Fatty acid metabolism and the basis of brown adipose tissue function

    PubMed Central

    Calderon-Dominguez, María; Mir, Joan F.; Fucho, Raquel; Weber, Minéia; Serra, Dolors; Herrero, Laura

    2016-01-01

    ABSTRACT Obesity has reached epidemic proportions, leading to severe associated pathologies such as insulin resistance, cardiovascular disease, cancer and type 2 diabetes. Adipose tissue has become crucial due to its involvement in the pathogenesis of obesity-induced insulin resistance, and traditionally white adipose tissue has captured the most attention. However in the last decade the presence and activity of heat-generating brown adipose tissue (BAT) in adult humans has been rediscovered. BAT decreases with age and in obese and diabetic patients. It has thus attracted strong scientific interest, and any strategy to increase its mass or activity might lead to new therapeutic approaches to obesity and associated metabolic diseases. In this review we highlight the mechanisms of fatty acid uptake, trafficking and oxidation in brown fat thermogenesis. We focus on BAT's morphological and functional characteristics and fatty acid synthesis, storage, oxidation and use as a source of energy. PMID:27386151

  1. Jatropha curcas, a biofuel crop: functional genomics for understanding metabolic pathways and genetic improvement.

    PubMed

    Maghuly, Fatemeh; Laimer, Margit

    2013-10-01

    Jatropha curcas is currently attracting much attention as an oilseed crop for biofuel, as Jatropha can grow under climate and soil conditions that are unsuitable for food production. However, little is known about Jatropha, and there are a number of challenges to be overcome. In fact, Jatropha has not really been domesticated; most of the Jatropha accessions are toxic, which renders the seedcake unsuitable for use as animal feed. The seeds of Jatropha contain high levels of polyunsaturated fatty acids, which negatively impact the biofuel quality. Fruiting of Jatropha is fairly continuous, thus increasing costs of harvesting. Therefore, before starting any improvement program using conventional or molecular breeding techniques, understanding gene function and the genome scale of Jatropha are prerequisites. This review presents currently available and relevant information on the latest technologies (genomics, transcriptomics, proteomics and metabolomics) to decipher important metabolic pathways within Jatropha, such as oil and toxin synthesis. Further, it discusses future directions for biotechnological approaches in Jatropha breeding and improvement.

  2. Systems analysis of plant functional, transcriptional, physical interaction, and metabolic networks.

    PubMed

    Bassel, George W; Gaudinier, Allison; Brady, Siobhan M; Hennig, Lars; Rhee, Seung Y; De Smet, Ive

    2012-10-01

    Physiological responses, developmental programs, and cellular functions rely on complex networks of interactions at different levels and scales. Systems biology brings together high-throughput biochemical, genetic, and molecular approaches to generate omics data that can be analyzed and used in mathematical and computational models toward uncovering these networks on a global scale. Various approaches, including transcriptomics, proteomics, interactomics, and metabolomics, have been employed to obtain these data on the cellular, tissue, organ, and whole-plant level. We summarize progress on gene regulatory, cofunction, protein interaction, and metabolic networks. We also illustrate the main approaches that have been used to obtain these networks, with specific examples from Arabidopsis thaliana, and describe the pros and cons of each approach.

  3. Metabolic Profiling of Right Ventricular-Pulmonary Vascular Function Reveals Circulating Biomarkers of Pulmonary Hypertension

    PubMed Central

    Lewis, Gregory D.; Ngo, Debby; Hemnes, Anna R.; Farrell, Laurie; Domos, Carly; Pappagianopoulos, Paul P.; Dhakal, Bishnu P.; Souza, Amanda; Shi, Xu; Pugh, Meredith E.; Beloiartsev, Arkadi; Sinha, Sumita; Clish, Clary B.; Gerszten, Robert E.

    2016-01-01

    BACKGROUND Pulmonary hypertension and associated right ventricular (RV) dysfunction are important determinants of morbidity and mortality, which are optimally characterized by invasive hemodynamic measurements. OBJECTIVES This study sought to determine whether metabolite profiling could identify plasma signatures of right ventricular-pulmonary vascular (RV-PV) dysfunction. METHODS We measured plasma concentrations of 105 metabolites using targeted mass spectrometry in 71 individuals (discovery cohort) who underwent comprehensive physiological assessment with right-sided heart catheterization and radionuclide ventriculography at rest and during exercise. Our findings were validated in a second cohort undergoing invasive hemodynamic evaluations (n = 71), as well as in an independent cohort with or without known pulmonary arterial (PA) hypertension (n = 30). RESULTS In the discovery cohort, 21 metabolites were associated with 2 or more hemodynamic indicators of RV-PV function (i.e., resting right atrial pressure, mean PA pressure, pulmonary vascular resistance [PVR], and PVR and PA pressure-flow response [ΔPQ] during exercise). We identified novel associations of RV-PV dysfunction with circulating indoleamine 2,3-dioxygenase (IDO)–dependent tryptophan metabolites (TMs), tricarboxylic acid intermediates, and purine metabolites and confirmed previously described associations with arginine–nitric oxide metabolic pathway constituents. IDO-TM levels were inversely related to RV ejection fraction and were particularly well correlated with exercise PVR and ΔPQ. Multisite sampling demonstrated transpulmonary release of IDO-TMs. IDO-TMs also identified RV-PV dysfunction in a validation cohort with known risk factors for pulmonary hypertension and in patients with established PA hypertension. CONCLUSIONS Metabolic profiling identified reproducible signatures of RV-PV dysfunction, highlighting both new biomarkers and pathways for further functional characterization. PMID

  4. Scopolamine impairs behavioural function and arginine metabolism in the rat dentate gyrus.

    PubMed

    Knox, Logan T; Jing, Yu; Fleete, Michael S; Collie, Nicola D; Zhang, Hu; Liu, Ping

    2011-12-01

    Alzheimer's disease (AD) is a neurodegenerative disorder with progressive memory loss. It has been shown that the cholinergic neurotransmission deficit is one of the neurochemical characteristics of AD, and that L-arginine and its metabolites also play a prominent role in AD pathogenesis. Scopolamine, a non-selective muscarinic receptor antagonist, blocks cholinergic neurotransmission and impairs behavioural function, including learning and memory. This study investigated the effects of scopolamine on animals' behavioural performance and L-arginine metabolism in the hippocampus and prefrontal cortex. Rats were given intraperitoneal injections of scopolamine (0.8 mg/kg) or saline (1 ml/kg) and tested in the Y-maze, open field, water maze and elevated plus maze 30 min post-treatment. After completion of the behavioural testing, the CA1, CA2/3 and dentate gyrus (DG) sub-regions of the hippocampus and the prefrontal cortex were harvested to measure the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of L-arginine, L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, glutamate and GABA. Scopolamine treated rats displayed reduced alternation and exploratory behaviour, increased swimming speed and impaired spatial learning and memory. There were significantly decreased NOS activity, increased arginase activity, and increased L-ornithine and putrescine levels in the DG, but not other regions examined, in the scopolamine treated rats as compared to the controls. These findings suggest that scopolamine impairs behavioural function and alters L-arginine metabolism in the DG sub-region of the hippocampus specifically. The underlying mechanisms of it remain to be explored further.

  5. Abnormalities of mitochondrial functioning can partly explain the metabolic disorders encountered in sarcopenic gastrocnemius.

    PubMed

    Martin, Caroline; Dubouchaud, Hervé; Mosoni, Laurent; Chardigny, Jean-Michel; Oudot, Alexandra; Fontaine, Eric; Vergely, Catherine; Keriel, Christiane; Rochette, Luc; Leverve, Xavier; Demaison, Luc

    2007-04-01

    Aging triggers several abnormalities in muscle glycolytic fibers including increased proteolysis, reactive oxygen species (ROS) production and apoptosis. Since the mitochondria are the main site of substrate oxidation, ROS production and programmed cell death, we tried to know whether the cellular disorders encountered in sarcopenia are due to abnormal mitochondrial functioning. Gastrocnemius mitochondria were extracted from adult (6 months) and aged (21 months) male Wistar rats. Respiration parameters, opening of the permeability transition pore and ROS production, with either glutamate (amino acid metabolism) or pyruvate (glucose metabolism) as a respiration substrate, were evaluated at different matrix calcium concentrations. Pyruvate dehydrogenase and respiratory complex activities as well as their contents measured by Western blotting analysis were determined. Furthermore, the fatty acid profile of mitochondrial phospholipids was also measured. At physiological calcium concentration, state III respiration rate was lowered by aging in pyruvate conditions (-22%), but not with glutamate. The reduction of pyruvate oxidation resulted from a calcium-dependent inactivation of the pyruvate dehydrogenase system and could provide for the well-known proteolysis encountered during sarcopenia. Matrix calcium loading and aging increased ROS production. They also reduced the oxidative phosphorylation. This was associated with lower calcium retention capacities, suggesting that sarcopenic fibers are more prone to programmed cell death. Aging was also associated with a reduced mitochondrial superoxide dismutase activity, which does not intervene in toxic ROS overproduction but could explain the lower calcium retention capacities. Despite a lower content, cytochrome c oxidase displayed an increased activity associated with an increased n-6/n-3 polyunsaturated fatty acid ratio of mitochondrial phospholipids. In conclusion, we propose that mitochondria obtained from aged muscle

  6. The quality of metabolic pathway resources depends on initial enzymatic function assignments: a case for maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As metabolic pathway resources become more commonly available, researchers have unprecedented access to information about their organism of interest. Despite efforts to ensure consistency between various resources, information content and quality can vary widely. Two maize metabolic pathway resource...

  7. The aPKC/Par3/Par6 Polarity Complex and Membrane Order Are Functionally Interdependent in Epithelia During Vertebrate Organogenesis.

    PubMed

    Abu-Siniyeh, Ahmed; Owen, Dylan M; Benzing, Carola; Rinkwitz, Silke; Becker, Thomas S; Majumdar, Arindam; Gaus, Katharina

    2016-01-01

    The differential distribution of lipids between apical and basolateral membranes is necessary for many epithelial cell functions, but how this characteristic membrane organization is integrated within the polarity network during ductal organ development is poorly understood. Here we quantified membrane order in the gut, kidney and liver ductal epithelia in zebrafish larvae at 3-11 days post fertilization (dpf) with Laurdan 2-photon microscopy. We then applied a combination of Laurdan imaging, antisense knock-down and analysis of polarity markers to understand the relationship between membrane order and apical-basal polarity. We found a reciprocal relationship between membrane order and the cell polarity network. Reducing membrane condensation by exogenously added oxysterol or depletion of cholesterol reduced apical targeting of the polarity protein, aPKC. Conversely, using morpholino knock down in zebrafish, we found that membrane order was dependent upon the Crb3 and Par3 polarity protein expression in ductal epithelia. Hence our data suggest that the biophysical property of membrane lipid packing is a regulatory element in apical basal polarity.

  8. Plastoquinone and Ubiquinone in Plants: Biosynthesis, Physiological Function and Metabolic Engineering

    PubMed Central

    Liu, Miaomiao; Lu, Shanfa

    2016-01-01

    Plastoquinone (PQ) and ubiquinone (UQ) are two important prenylquinones, functioning as electron transporters in the electron transport chain of oxygenic photosynthesis and the aerobic respiratory chain, respectively, and play indispensable roles in plant growth and development through participating in the biosynthesis and metabolism of important chemical compounds, acting as antioxidants, being involved in plant response to stress, and regulating gene expression and cell signal transduction. UQ, particularly UQ10, has also been widely used in people’s life. It is effective in treating cardiovascular diseases, chronic gingivitis and periodontitis, and shows favorable impact on cancer treatment and human reproductive health. PQ and UQ are made up of an active benzoquinone ring attached to a polyisoprenoid side chain. Biosynthesis of PQ and UQ is very complicated with more than thirty five enzymes involved. Their synthetic pathways can be generally divided into two stages. The first stage leads to the biosynthesis of precursors of benzene quinone ring and prenyl side chain. The benzene quinone ring for UQ is synthesized from tyrosine or phenylalanine, whereas the ring for PQ is derived from tyrosine. The prenyl side chains of PQ and UQ are derived from glyceraldehyde 3-phosphate and pyruvate through the 2-C-methyl-D-erythritol 4-phosphate pathway and/or acetyl-CoA and acetoacetyl-CoA through the mevalonate pathway. The second stage includes the condensation of ring and side chain and subsequent modification. Homogentisate solanesyltransferase, 4-hydroxybenzoate polyprenyl diphosphate transferase and a series of benzene quinone ring modification enzymes are involved in this stage. PQ exists in plants, while UQ widely presents in plants, animals and microbes. Many enzymes and their encoding genes involved in PQ and UQ biosynthesis have been intensively studied recently. Metabolic engineering of UQ10 in plants, such as rice and tobacco, has also been tested. In this

  9. Effects of black raspberry on lipid profiles and vascular endothelial function in patients with metabolic syndrome.

    PubMed

    Jeong, Han Saem; Hong, Soon Jun; Lee, Tae-Bum; Kwon, Ji-Wung; Jeong, Jong Tae; Joo, Hyung Joon; Park, Jae Hyoung; Ahn, Chul-Min; Yu, Cheol Woong; Lim, Do-Sun

    2014-10-01

    Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p < 0.05, respectively) and total cholesterol/HDL ratio (-0.31 ± 0.64 vs. 0.07 ± 0.58, p < 0.05, respectively) were significantly greater in the group with black raspberry than in the placebo group. Increases in baFMD at the 12-week follow-up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p < 0.05, respectively). Decreases from the baseline in IL-6 (-0.4 ± 1.5 pg/mL vs. -0.1 ± 1.0 pg/mL, p < 0.05, respectively) and TNF-α (-2.9 ± 4.7 pg/mL vs. 0.1 ± 3.6 pg/mL, p < 0.05, respectively) were significantly greater in the group with black raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12-week follow-up.

  10. Why iron? A spin-polarized conceptual density functional theory study on metal-binding specificity of porphyrin.

    PubMed

    Feng, Xin-Tian; Yu, Jian-Guo; Liu, Ruo-Zhuang; Lei, Ming; Fang, Wei-Hai; De Proft, Frank; Liu, Shubin

    2010-06-03

    Heme is a key cofactor of hemoproteins in which porphyrin is often found to be preferentially metalated by the iron cation. In our previous work [Feng, X. T.; Yu, J. G.; Lei, M.; Fang, W. H.; Liu, S. B. J. Phys. Chem. B 2009, 113, 13381], conceptual density functional theory (CDFT) descriptors have been applied to understand the metal-binding specificity of porphyrin. We found that the iron-porphyrin complex significantly differs in many aspects from porphyrin complexes with other metal cations except Ru, for which similar behaviors for the reactivity descriptors were discovered. In this study, we employ the spin-polarized version of CDFT to investigate the reactivity for a series of (pyridine)(n)-M(ll)-porphyrin complexes-where M = Mg, Ca, Cr, Mn, Co, Ni, Cu, Zn, Ru, and Cd, and n = 0, 1, and 2-to further appreciate the metal-binding specificity of porphyrin. Both global and local descriptors were examined within this framework. We found that, within the spin resolution, not only chemical reactivity descriptors from CDFT of the iron complex are markedly different from that of other metal complexes, but we also discovered substantial differences in reactivity descriptors between Fe and Ru complexes. These results confirm that spin properties play a highly important role in physiological functions of hemoproteins. Quantitative reactivity relationships have been revealed between global and local spin-polarized reactivity descriptors. These results contribute to our better understanding of the metal binding specificity and reactivity for heme-containing enzymes and other metalloproteins alike.

  11. Estradiol selectively regulates innate immune function by polarized human uterine epithelial cells in culture

    PubMed Central

    Fahey, JV; Wright, JA; Shen, L; Smith, JM; Ghosh, M; Rossoll, RM; Wira, CR

    2016-01-01

    The goal of this study was to examine the role of E2 in regulating innate immune protection by human uterine epithelial cells (UECs). Recognizing that UECs produce cytokines and chemokines to recruit and activate immune cells as well as viral and bacterial antimicrobials, we sought to examine the effect of E2 on constitutive and Toll-like receptor (TLR) agonist (lipopolysaccharide (LPS) and poly (I:C))-induced immune responses. The secretion by polarized UECs in culture of interleukin (IL)-6, macrophage inhibitory factor (MIF), and secretory leukocyte protease inhibitor (SLPI) was examined as well as the mRNA expression of human β-defensin-2 (HBD2), tumor necrosis factor (TNF)-α, IL-8, and nuclear factor (NF)-kB. When incubated with E2 for 24–48 h, we found that E2 stimulated UEC secretion of SLPI (fourfold) and mRNA expression of HBD2 (fivefold). Moreover, when antibacterial activity in UEC secretions was measured using Staphylococcus aureus, E2 increased the secretion of soluble factor(s) with antibacterial activity. In contrast, E2 had no effect on constitutive secretion of proinflammatory cytokines and chemokines by UECs but completely inhibited LPS- and poly (I:C)-induced secretion of MIF, IL-6, and IL-8. Estradiol also reversed the stimulatory effects of IL-1β on mRNA expression of TNF-α, IL-8, and NF-kB by 85, 95, and 70%, respectively. As SLPI is known to inhibit NF-kB expression, these findings suggest that E2 inhibition of proinflammatory cytokines may be mediated through SLPI regulation of NF-kB. Overall, these findings indicate that the production of cytokines, chemokines, and antimicrobials by UECs are differentially regulated by E2. Further, it suggests that with E2 regulation, epithelial cells that line the uterine cavity have evolved immunologically to be sensitive to viral and bacterial infections as well as the constraints of procreation. PMID:19079193

  12. Loss of GSNOR1 function leads to compromised auxin signaling and polar auxin transport

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nitric oxide (NO) and auxin phytohormone cross talk has been implicated in plant development and growth. Addition and removal of NO to cysteine residues of proteins, is termed S-nitrosylation and de-nitrosylation, respectively and functions as an on/off switch of protein activity. This dynamic proce...

  13. High Performance 3D PET Reconstruction Using Spherical Basis Functions on a Polar Grid

    PubMed Central

    Cabello, J.; Gillam, J. E.; Rafecas, M.

    2012-01-01

    Statistical iterative methods are a widely used method of image reconstruction in emission tomography. Traditionally, the image space is modelled as a combination of cubic voxels as a matter of simplicity. After reconstruction, images are routinely filtered to reduce statistical noise at the cost of spatial resolution degradation. An alternative to produce lower noise during reconstruction is to model the image space with spherical basis functions. These basis functions overlap in space producing a significantly large number of non-zero elements in the system response matrix (SRM) to store, which additionally leads to long reconstruction times. These two problems are partly overcome by exploiting spherical symmetries, although computation time is still slower compared to non-overlapping basis functions. In this work, we have implemented the reconstruction algorithm using Graphical Processing Unit (GPU) technology for speed and a precomputed Monte-Carlo-calculated SRM for accuracy. The reconstruction time achieved using spherical basis functions on a GPU was 4.3 times faster than the Central Processing Unit (CPU) and 2.5 times faster than a CPU-multi-core parallel implementation using eight cores. Overwriting hazards are minimized by combining a random line of response ordering and constrained atomic writing. Small differences in image quality were observed between implementations. PMID:22548047

  14. Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review

    PubMed Central

    Kagota, Satomi; Maruyama, Kana; McGuire, John J.

    2016-01-01

    Proteinase-activated receptor 2 (PAR2) is a cell surface receptor activated by serine proteinases or specific synthetic compounds. Interest in PAR2 as a pharmaceutical target for various diseases is increasing. Here we asked two questions relevant to endothelial dysfunction and diabetes: How is PAR2 function affected in blood vessels? What role does PAR2 have in promoting obesity, diabetes, and/or metabolic syndrome, specifically via the endothelium and adipose tissues? We conducted a systematic review of the published literature in PubMed and Scopus (July 2015; search terms: par2, par-2, f2lr1, adipose, obesity, diabetes, and metabolic syndrome). Seven studies focused on PAR2 and vascular function. The obesity, diabetes, or metabolic syndrome animal models differed amongst studies, but each reported that PAR2-mediated vasodilator actions were preserved in the face of endothelial dysfunction. The remaining studies focused on nonvascular functions and provided evidence supporting the concept that PAR2 activation promoted obesity. Key studies showed that PAR2 activation regulated cellular metabolism, and PAR2 antagonists inhibited adipose gain and metabolic dysfunction in rats. We conclude that PAR2 antagonists for treatment of obesity indeed show early promise as a therapeutic strategy; however, endothelial-specific PAR2 functions, which may offset mechanisms that produce vascular dysfunction in diabetes, warrant additional study. PMID:27006943

  15. PTENα, a PTEN isoform translated through alternative initiation, regulates mitochondrial function and energy metabolism.

    PubMed

    Liang, Hui; He, Shiming; Yang, Jingyi; Jia, Xinying; Wang, Pan; Chen, Xi; Zhang, Zhong; Zou, Xiajuan; McNutt, Michael A; Shen, Wen Hong; Yin, Yuxin

    2014-05-06

    PTEN is one of the most frequently mutated genes in human cancer. It is known that PTEN has a wide range of biological functions beyond tumor suppression. Here, we report that PTENα, an N-terminally extended form of PTEN, functions in mitochondrial metabolism. Translation of PTENα is initiated from a CUG codon upstream of and in-frame with the coding region of canonical PTEN. Eukaryotic translation initiation factor 2A (eIF2A) controls PTENα translation, which requires a CUG-centered palindromic motif. We show that PTENα induces cytochrome c oxidase activity and ATP production in mitochondria. TALEN-mediated somatic deletion of PTENα impairs mitochondrial respiratory chain function. PTENα interacts with canonical PTEN to increase PINK1 protein levels and promote energy production. Our studies demonstrate the importance of eIF2A-mediated alternative translation for generation of protein diversity in eukaryotic systems and provide insights into the mechanism by which the PTEN family is involved in multiple cellular processes.

  16. Ovarian Function in Samoan Women Shows Stronger Association with Signals of Energy Metabolism than Fat Reserves

    PubMed Central

    McGarvey, Stephen T.; Sesepasara, Margaret L.; Ellison, Peter T.

    2015-01-01

    Objectives The relative influence of prominent energetic hormones such as insulin and leptin on ovarian steroid production has yet to be determined and demonstrated consistently in vivo. This study reports preliminary findings on the relationship between insulin, leptin, and estradiol, a major ovarian steroid, in a sample of Samoan women. Methods Participants were 34 regularly cycling, premenopausal women in the follicular phase of their menstrual cycle with indicators of normal glucose tolerance. Fasting serum samples provided one-time, cross-sectional measures of glucose, insulin, leptin, and estradiol. Main statistical analyses consisted of Student's t-tests, used to determine significant differences in mean estradiol level between contrasting groups of insulin and leptin. Results Relatively high insulin levels within the normal range of variation showed a positive association with estradiol levels whereas relatively high leptin levels did not. The relationship between insulin and estradiol appeared to conform to a step-like categorical function -- with the highest insulin levels exerting the greatest positive effect -- rather than a dose-response linear function. Conslusions The current study adds to the growing evidence that peripheral regulation of ovarian function likely involves permissive signals that emphasize a state of energy surplus, related primarily to energy metabolism rather than energy reserves, and warrant more extensive study. PMID:24375833

  17. Dietary Exercise as a Novel Strategy for the Prevention and Treatment of Metabolic Syndrome: Effects on Skeletal Muscle Function

    PubMed Central

    Aoi, Wataru; Naito, Yuji; Yoshikawa, Toshikazu

    2011-01-01

    A sedentary lifestyle can cause metabolic syndrome to develop. Metabolic syndrome is associated with metabolic function in the skeletal muscle, a major consumer of nutrients. Dietary exercise, along with an adequate diet, is reported to be one of the major preventive therapies for metabolic syndrome; exercise improves the metabolic capacity of muscles and prevents the loss of muscle mass. Epidemiological studies have shown that physical activity reduces the risk of various common diseases such as cardiovascular disease, diabetes, and cancer; it also helps in reducing visceral adipose tissue. In addition, laboratory studies have demonstrated the mechanisms underlying the benefits of single-bout and regular exercise. Exercise regulates the expression/activity of proteins associated with metabolic and anabolic signaling in muscle, leading to a change in phenotype. The extent of these changes depends on the intensity, the duration, and the frequency of the exercise. The effect of exercise is also partly due to a decrease in inflammation, which has been shown to be closely related to the development of various diseases. Furthermore, it has been suggested that several phytochemicals contained in natural foods can improve nutrient metabolism and prevent protein degradation in the muscle. PMID:21773023

  18. Structure functions in the polarized Drell-Yan processes with spin-1/2 and spin-1 hadrons. I. General formalism

    NASA Astrophysics Data System (ADS)

    Hino, S.; Kumano, S.

    1999-05-01

    We discuss a general formalism for the structure functions which can be investigated in the polarized Drell-Yan processes with spin-1/2 and spin-1 hadrons. To be specific, the formalism can be applied to the proton-deuteron Drell-Yan processes. Because of the spin-1 nature, there are new structure functions which cannot be studied in the proton-proton reactions. Imposing Hermiticity, parity conservation, and time-reversal invariance, we find that 108 structure functions exist in the Drell-Yan processes. However, the number reduces to 22 after integrating the cross section over the virtual-photon transverse momentum Q-->T or after taking the limit QT-->0. There are 11 new structure functions in addition to the 11 in the Drell-Yan processes of spin-1/2 hadrons. The additional structure functions are associated with the tensor structure of the spin-1 hadron, and they could be measured by quadrupole spin asymmetries. For example, the structure functions exist for ``intermediate'' polarization although their contributions vanish in the longitudinal and transverse polarization reactions. We show a number of spin asymmetries for extracting the polarized structure functions. The proton-deuteron reaction may be realized in the RHIC-SPIN project and other future ones, and it could be a new direction of next generation high-energy spin physics.

  19. Glycemia and cognitive function in metabolic syndrome and coronary heart disease

    PubMed Central

    Avadhani, Radhika; Fowler, Kristen; Barbato, Corinne; Thomas, Sherine; Wong, Winnie; Paul, Camille; Aksakal, Mehmet; Hauser, Thomas H.; Weinger, Katie; Goldfine, Allison B.

    2014-01-01

    Objective Higher hemoglobin A1c (HbA1c) is associated with lower cognitive function in type 2 diabetes. To determine if associations persist at lower levels of dysglycemia in patients who have established cardiovascular disease, cognitive performance was assessed in the Targeting Inflammation Using Salsalate in Cardiovascular Disease (TINSAL-CVD) trial. Research Design and Methods The age-adjusted relationships between HbA1c and cognitive performance measured by the Mini-mental State Examination (MMSE), Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT), and Categorical Verbal Fluency (CVF) were assessed in 226 men with metabolic syndrome and established stable coronary artery disease. Results 61.5% of participants had normoglycemia, 20.8% impaired fasting glucose, and 17.7% type 2 diabetes. HbA1c was associated with cognitive function tests of DSST, RAVLT, TMT and CVF (all P<0.02), but not MMSE. In an age-adjusted model, a 1% (11 mmol/mol) higher HbA1c value was associated with a 5.9 lower DSST score (95%CI: −9.58 to −2.21; P<0.0001); a 2.44 lower RAVLT score (95%CI: −4.00 to −0.87; P<0.0001); a 15.6 higher TMT score (95%CI: 5.73 to 25.6; P<0.0001); and a 3.71 lower CVF score (95%CI: −6.41 to −1.01; P<0.02). In multivariate model adjusting for age, education and cardiovascular covariates, HbA1c remains associated with cognitive function tests of RAVLT (R2=0.27, P<0.0001), TMT (R2=0.18, P<0.0001), and CVF (R2=0.20, P<0.0001) although association with DSST was reduced. Conclusion Higher HbA1c is associated with lower cognitive function performance scores across multiple domain tests in men with metabolic syndrome and coronary artery disease. Future studies may demonstrate whether glucose lowering within the normative range improves cognitive health. PMID:25220612

  20. A novel terahertz device with multi-function of polarization and switch based on phase transition of VO2

    NASA Astrophysics Data System (ADS)

    Gu, Wen-hao; Chang, Sheng-jiang; Fan, Fei

    2016-11-01

    A terahertz (THz) polarizer and switch structure is proposed based on the phase transition of vanadium dioxide (VO2). When VO2 is in the insulation phase, the resonance frequencies of the proposed structure are 1.49 THz and 1.22 THz for the x- and y-polarization, respectively. It can perform as a THz polarizer with extinction ratios of 52.5 dB and 17 dB for the y- and x-polarization, respectively; When VO2 transforms into metallic phase, the resonance frequency for x-polarization wave shifts from 1.49 THz to 1.22 THz, while that remains still for the y-polarization component. It means that the structure can work as a polarization-dependent THz switch with a high extinction ratio of 32 dB.

  1. Photoluminescence changes of III-Nitride lateral polarity structures after chemical functionalization

    NASA Astrophysics Data System (ADS)

    Berg, Nora G.; Franke, Alexander; Kirste, Ronny; Collazo, Ramon; Ivanisevic, Albena

    2016-12-01

    The photoluminescence changes of a III-Nitride semiconductor with various surface topographies were studied after chemical functionalization. Al x Ga1-x N with a composition of 70% aluminum was used and the surfaces were functionalized with a fluorophore dye-terminated peptide using a linker molecule. The stability of the wafers in water was studied using inductively coupled plasma mass spectrometry prior to modifying the material. The leaching data demonstrated that the AlGaN material in highly stable in biological conditions over 7 d. The attachment of the dye to the wafer was investigated using x-ray photoelectron spectroscopy and photoluminescence spectroscopy (PL). The PL spectrum showed a clear signature of the dye with a pronounced emission peak at approximately 260 nm, indicating a successful attachment to the surface.

  2. Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function

    PubMed Central

    Fleisch, Abby F.; Rifas-Shiman, Sheryl L.; Mora, Ana M.; Calafat, Antonia M.; Ye, Xiaoyun; Luttmann-Gibson, Heike; Gillman, Matthew W.; Oken, Emily; Sagiv, Sharon K.

    2016-01-01

    .3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: –15.6% (95% CI: –25.4, –4.6) vs. –6.1% (95% CI: –16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring.Results: Children with higher PFAS concentrations had lower HOMA-IR [e.g., –10.1% (95% CI: –17.3, –2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: –15.6% (95% CI: –25.4, –4.6) vs. –6.1% (95% CI: –16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. Conclusions: We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance.Conclusions: We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481–487; http://dx.doi.org/10.1289/EHP303Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481–487; http://dx.doi.org/10.1289/EHP303 PMID:27586368

  3. The proportion of genes in a functional category is linked to mass-specific metabolic rate and lifespan.

    PubMed

    Takemoto, Kazuhiro; Kawakami, Yuko

    2015-05-06

    Metabolic rate and lifespan are important biological parameters that are studied in a wide range of research fields. They are known to correlate with body mass, but their association with gene (protein) functions is poorly understood. In this study, we collected data on the metabolic rate and lifespan of various organisms and investigated the relationship of these parameters with their genomes. We showed that the proportion of genes in a functional category, but not genome size, was correlated with mass-specific metabolic rate and maximal lifespan. In particular, the proportion of genes in oxic reactions (which occur in the presence of oxygen) was significantly associated with these two biological parameters. Additionally, we found that temperature, taxonomy, and mode-of-life traits had little effect on the observed associations. Our findings emphasize the importance of considering the biological functions of genes when investigating the relationships between genome, metabolic rate, and lifespan. Moreover, this provides further insights into these relationships, and may be useful for estimating metabolic rate and lifespan in individuals and the ecosystem using a combination of body mass measurements and genomic data.

  4. Endocrine and metabolic function in male Carioca High-conditioned Freezing rats.

    PubMed

    Mousovich-Neto, F; Lourenço, A L; Landeira-Fernandez, J; Corrêa da Costa, V M

    2015-04-01

    The aim of this study was to characterize Carioca High-conditioned Freezing rats (CHF) regarding their endocrine and metabolic backgrounds. We found an increase in serum corticosterone (CTRL: 96.7 ± 21.65 vs CHF: 292.0 ± 4 0.71 ng/ml) and leptin (CTRL: 9.5 ± 1.51 vs CHF: 19.2 ± 4.32 ng/ml). Serum testosterone (CTRL: 3.3 ± 0.29 vs CHF: 2.0 ± 0.28 ng/ml) and T3 (CTRL: 52.4 ± 2.74 vs CHF: 42.7 ± 2.94 ng/dl) were decreased in the CHF group, but serum TSH and T4 were unaffected. Body weight and food intake were unchanged, nevertheless retroperitoneal fat (CTRL: 2.2 ± 0.24 vs CHF: 4.8 ± 0.64 g) and epididymal fat (CTRL: 2.6 ± 0.20 vs CHF: 4.8 ± 0.37 g) depot weights were around 2-fold higher in CHF animals. BAT weight was similar in both groups. Serum triglycerides (CTRL: 41.4 ± 6.03 vs CHF: 83.2 ± 17.09 mg/dl) and total cholesterol (CTRL: 181.6 ± 5.61 vs CHF: 226.4 ± 13.04 mg/dl) were higher in the CHF group. Fasting glycemia (CTRL: 68.7 ± 3.04 vs CHF: 82.3 ± 2.99 mg/dl) was also higher in the CHF group, however glucose tolerance test response and serum insulin levels were similar between the groups. Oxygen consumption (CTRL: 10.5 ± 0.40 vs CHF: 7.9 ± 0.58 VO2ml/min/kg(0.75)) and BAT D2 activity (CTRL: 0.7 ± 0.17 vs CHF: 0.3 ± 0.04 fmolT4/min/mg ptn) were lower in the CHF group. Our data show that anxiety could impair endocrine and metabolic functions and may contribute to the development of metabolic diseases.

  5. Psychological and metabolic improvement after an outpatient teaching program for functional intensified insulin therapy (FIT).

    PubMed

    Langewitz, W; Wössmer, B; Iseli, J; Berger, W

    1997-09-01

    To be the master of their disease and not its slave is the ultimate goal of many patients with diabetes. Intensified functional insulin therapy (FIT) helps to establish this goal by an intensive patient education: each patient learns in five small-group sessions how s/he reacts to standardized challenges of glucose homeostasis (e.g. 24 h fasting; physical exercise; various carbohydrate loads). We investigated in 43 patients with long-standing diabetes type 1 (mean age: 33 +/- 10 years; mean duration of diabetes: 15 +/- 10 years) whether FIT improves quality of life, influences metabolic control and doctor-patient relationship. The following instruments were used: diabetes specific quality of life questionnaire (DQOL), hierarchical distance and cohesion between doctor and patient (FAST), anxiety and depression (HAD). Pre and post intervention values were compared with paired t-tests. HbA1c and number of hypoglycaemic episodes were also assessed 1 year after FIT and 1 year prior to FIT. Metabolic control was improved: HbA1c in the year before FIT: 6.72 +/- 1.35; 4 months before FIT: 6.61 +/- 1.46; 4 months after FIT: 6.29 +/- 1.09 (P < 0.05 compared to 4 months before FIT); 1 year after FIT: 6.46 +/- 1.12 (n.s. compared to 1 year before FIT). Dissatisfaction with life decreases from 33.3 +/- 8.0 to 28.5 +/- 7.7 (P < 0.001). Moments free of disease-specific strain increase from 74.3 +/- 13.9 to 78.1 +/- 16.1 (P = 0.07). Hierarchical distance between doctor and patient decreases from 1.1 +/- to 0.6 +/- 0.8 (P < 0.001), cohesion increases from 9.3 +/- 1.5 to 9.9 +/- 1.1 (P < 0.001). Anxiety and depression both decreases significantly: anxiety, 6.5 +/- 3.3-->4.6 +/- 3.2 (P < 0.001); depression, 2.7 +/- 2.5-->1.5 +/- 1.6 (P < 0.001). The number of patients with severe hypoglycaemic episodes (level 4) decreases from five (11.6%) to one (2.3%) after intervention (P < 0.05). In conclusion, FIT enhances quality of life in diabetic individuals. It helps to establish a less

  6. Effects of Acute Exposure to Moderate Altitude on Vascular Function, Metabolism and Systemic Inflammation

    PubMed Central

    Stöwhas, Anne-Christin; Latshang, Tsogyal D.; Lo Cascio, Christian M.; Lautwein, Sina; Stadelmann, Katrin; Tesler, Noemi; Ayers, Lisa; Berneis, Kaspar; Gerber, Philipp A.; Huber, Reto; Achermann, Peter; Bloch, Konrad E.; Kohler, Malcolm

    2013-01-01

    Background Travel to mountain areas is popular. However, the effects of acute exposure to moderate altitude on the cardiovascular system and metabolism are largely unknown. Objectives To investigate the effects of acute exposure to moderate altitude on vascular function, metabolism and systemic inflammation. Methods In 51 healthy male subjects with a mean (SD) age of 26.9 (9.3) years, oxygen saturation, blood pressure, heart rate, arterial stiffness, lipid profiles, low density lipoprotein (LDL) particle size, insulin resistance (HOMA-index), highly-sensitive C-reactive protein and pro-inflammatory cytokines were measured at 490 m (Zurich) and during two days at 2590 m, (Davos Jakobshorn, Switzerland) in randomized order. The largest differences in outcomes between the two altitudes are reported. Results Mean (SD) oxygen saturation was significantly lower at 2590 m, 91.0 (2.0)%, compared to 490 m, 96.0 (1.0)%, p<0.001. Mean blood pressure (mean difference +4.8 mmHg, p<0.001) and heart rate (mean difference +3.3 bpm, p<0.001) were significantly higher at 2590 m, compared to 490 m, but this was not associated with increased arterial stiffness. At 2590 m, lipid profiles improved (median difference triglycerides −0.14 mmol/l, p = 0.012, HDL +0.08 mmol/l, p<0.001, total cholesterol/HDL-ratio −0.25, p = 0.001), LDL particle size increased (median difference +0.45 nm, p = 0.048) and hsCRP decreased (median difference −0.18 mg/l, p = 0.024) compared to 490 m. No significant change in pro-inflammatory cytokines or insulin resistance was observed upon ascent to 2590 m. Conclusions Short-term stay at moderate altitude is associated with increased blood pressure and heart rate likely due to augmented sympathetic activity. Exposure to moderate altitude improves the lipid profile and systemic inflammation, but seems to have no significant effect on glucose metabolism. Trial Registration ClinicalTrials.gov NCT01130948 PMID:23936377

  7. Spin-dependent structure functions in nuclear matter and the polarized EMC effect

    SciTech Connect

    I.C. Cloet; W. Bentz; A.W. Thomas

    2005-04-01

    An excellent description of both spin-independent and spin-dependent quark distributions and structure functions has been obtained with a modified Nambu-Jona-Lasinio model, which is free of unphysical thresholds for nucleon decay into quarks--hence incorporating an important aspect of confinement. We utilize this model to investigate nuclear medium modifications to structure functions, and find that we are readily able to reproduce both nuclear matter saturation and the experimental F{sub 2N}{sup A}/F{sub 2N} ratio, that is, the EMC effect. Applying this framework to determine g{sub 1p}{sup A}, we find that the ratio g{sub 1p}{sup A}/g{sub 1p} differs significantly from 1, with the quenching caused by the nuclear medium being about twice that of the spin-independent case. This represents an exciting result, which if confirmed experimentally, will reveal much about the quark structure of nuclear matter.

  8. Simultaneous PET-MRI reveals brain function in activated and resting state on metabolic, hemodynamic and multiple temporal scales.

    PubMed

    Wehrl, Hans F; Hossain, Mosaddek; Lankes, Konrad; Liu, Chih-Chieh; Bezrukov, Ilja; Martirosian, Petros; Schick, Fritz; Reischl, Gerald; Pichler, Bernd J

    2013-09-01

    Combined positron emission tomography (PET) and magnetic resonance imaging (MRI) is a new tool to study functional processes in the brain. Here we study brain function in response to a barrel-field stimulus simultaneously using PET, which traces changes in glucose metabolism on a slow time scale, and functional MRI (fMRI), which assesses fast vascular and oxygenation changes during activation. We found spatial and quantitative discrepancies between the PET and the fMRI activation data. The functional connectivity of the rat brain was assessed by both modalities: the fMRI approach determined a total of nine known neural networks, whereas the PET method identified seven glucose metabolism-related networks. These results demonstrate the feasibility of combined PET-MRI for the simultaneous study of the brain at activation and rest, revealing comprehensive and complementary information to further decode brain function and brain networks.

  9. Functional genomics tools applied to plant metabolism: a survey on plant respiration, its connections and the annotation of complex gene functions

    PubMed Central

    Araújo, Wagner L.; Nunes-Nesi, Adriano; Williams, Thomas C. R.

    2012-01-01

    The application of post-genomic techniques in plant respiration studies has greatly improved our ability to assign functions to gene products. In addition it has also revealed previously unappreciated interactions between distal elements of metabolism. Such results have reinforced the need to consider plant respiratory metabolism as part of a complex network and making sense of such interactions will ultimately require the construction of predictive and mechanistic models. Transcriptomics, proteomics, metabolomics, and the quantification of metabolic flux will be of great value in creating such models both by facilitating the annotation of complex gene function, determining their structure and by furnishing the quantitative data required to test them. In this review, we highlight how these experimental approaches have contributed to our current understanding of plant respiratory metabolism and its interplay with associated process (e.g., photosynthesis, photorespiration, and nitrogen metabolism). We also discuss how data from these techniques may be integrated, with the ultimate aim of identifying mechanisms that control and regulate plant respiration and discovering novel gene functions with potential biotechnological implications. PMID:22973288

  10. Transcription of genes coding for metabolic key functions in Nitrosomonas europaea during aerobic and anaerobic growth.

    PubMed

    Beyer, Sonja; Gilch, Stefan; Meyer, Ortwin; Schmidt, Ingo

    2009-01-01

    Nitrosomonas europaea can grow under conditions of chemolithoautotrophic aerobic (oxygen as oxidant) as well as anaerobic [nitrogen dioxide (NO(2)) as oxidant] nitrification or chemoorganotrophic anaerobic pyruvate-dependent denitrification. In this study, the adaptation of the transcription (mRNA synthesis/concentration) of N. europaea to aerobic and anaerobic growth conditions was evaluated and the transcription of genes coding for metabolic key functions was analyzed: nitrogen and energy metabolism (amoA, hao, rh1, nirK, norB, nsc, aceE, ldhA, ppc, gltA, odhA, coxA), carbon dioxide fixation (cbbL), gluconeogenesis (ppsA), cell growth (ftsZ), and oxidative stress (sodB). During aerobic ammonia oxidation the specific activities of ammonia oxidation, nitrite reduction, and the growth rates correlated with the transcription level of the corresponding genes amoA/hao, nirK/norB/nsc, and cbbL/ftsZ. In anaerobically ammonia-oxidizing cells of N. europaea, the cellular mRNA concentrations of amoA, hao, rh1,coxA, cbbL, ftsZ, and sodB were reduced compared with aerobically nitrifying cells, but the mRNA levels of nirK, norB, and nsc were significantly increased. During anaerobic pyruvate-dependent denitrification, the mRNA abundance of nirK, norB, nsc, aceE, gltA, and odhA was increased, while the concentrations of amoA,hao, rh1, coxAcbbL, ftsZ, and sodB were significantly reduced. Temperature, pH value, and NH(4)(+), O(2), NO, and NO(2) concentrations had comparatively small effects on the transcription of the studied genes.

  11. Effects of nutritional restriction on metabolic, endocrine, and ovarian function in llamas (Lama glama).

    PubMed

    Norambuena, M C; Silva, M; Urra, F; Ulloa-Leal, C; Fernández, A; Adams, G P; Huanca, W; Ratto, M H

    2013-05-01

    The objectives of the study were to determine the effects of nutritional restriction on ovarian function in llamas. Mature female llamas were assigned randomly to a Control group, fed 100% of maintenance energy requirements (MER) (n=8), or a Restricted group (n=8) fed from 70% to 40% of MER until a body condition score of 2.5 was attained. Blood samples were taken every-other-day to determine plasma concentrations of LH, estradiol, leptin and metabolic markers, and follicular dynamics were monitored daily by ultrasonography for 30 days (Experiment 1). Llamas were then treated with GnRH to compare the ovulatory response and corpus luteus (CL) development between groups (Experiment 2). Blood samples were taken to measure LH, leptin, progesterone and metabolic markers and ovarian structures were assessed as in Experiment 1. Llamas in the Restricted group had lower body mass and body condition scores than those in the Control group (P<0.001). Plasma concentrations of cholesterol, non-esterified fatty acids, triglycerides, and urea were higher in the Restricted group (P<0.05) than in the Control group. The day-to-day diameter profiles of the dominant follicles were smaller (P<0.05) in the Restricted group than in the Control group but plasma estradiol concentration did not differ. The ovulation rate and LH secretion in response to GnRH did not differ. Day-to-day profiles of CL diameter, plasma progesterone and leptin concentrations were smaller (P<0.01) in the Restricted group. In conclusion, nutritional restriction in llamas was associated with suppressed follicle and CL development, and lower plasma concentrations of progesterone and leptin.

  12. Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health

    PubMed Central

    Ha, Connie WY; Lam, Yan Y; Holmes, Andrew J

    2014-01-01

    Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging. PMID:25469018

  13. MicroRNA 211 Functions as a Metabolic Switch in Human Melanoma Cells

    PubMed Central

    Mazar, Joseph; Qi, Feng; Lee, Bongyong; Marchica, John; Govindarajan, Subramaniam; Shelley, John; Li, Jian-Liang; Ray, Animesh

    2016-01-01

    MicroRNA 211 (miR-211) negatively regulates genes that drive invasion of metastatic melanoma. Compared to normal human melanocytes, miR-211 expression is significantly reduced or absent in nonpigmented melanoma cells and lost during human melanoma progression. To investigate the molecular mechanism of its tumor suppressor function, miR-211 was ectopically expressed in nonpigmented melanoma cells. Ectopic expression of miR-211 reduced hypoxia-inducible factor 1α (HIF-1α) protein levels and decreased cell growth during hypoxia. HIF-1α protein loss was correlated with the downregulation of a miR-211 target gene, pyruvate dehydrogenase kinase 4 (PDK4). We present evidence that resumption of miR-211-mediated downregulation of PDK4 in melanoma cells causes inhibition of invasion by nonpigmented melanomas via HIF-1α protein destabilization. Thus, the tumor suppressor miR-211 acts as a metabolic switch, and its loss is expected to promote cancer hallmarks in human melanomas. Melanoma, one of the deadliest forms of skin cancer, kills nearly 10,000 people in the United States per year. We had previously shown that a small noncoding RNA, termed miR-211, suppresses invasion and the growth of aggressive melanoma cells. The results presented here support the hypothesis that miR-211 loss in melanoma cells causes abnormal regulation of energy metabolism, which in turn allows cancer cells to survive under low oxygen concentrations—a condition that generally kills normal cells. These findings highlight a novel mechanism of melanoma formation: miR-211 is a molecular switch that is turned off in melanoma cells, raising the hope that in the future we might be able to turn the switch back on, thus providing a better treatment option for melanoma. PMID:26787841

  14. The effect of dehydroepiandrosterone (DHEA) on renal function and metabolism in diabetic rats.

    PubMed

    Jahn, Matheus Parmegiani; Gomes, Luana Ferreira; Jacob, Maria Helena Vianna Metello; da Rocha Janner, Daiane; Araújo, Alex Sander da Rosa; Belló-Klein, Adriane; Ribeiro, Maria Flávia Marques; Kucharski, Luiz Carlos

    2011-05-01

    Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions in humans and rodents, but its effects on renal tissue have not yet been fully understood. The aim of this study is to assess the effect of DHEA treatment on diabetic rats, mainly in relation to renal function and metabolism. Diabetic rats were treated with subcutaneous injections of a 10mg/kg dose of DHEA diluted in oil. Plasma glucose and creatinine, in addition to urine creatinine, were quantified espectophotometrically. Glucose uptake and oxidation were quantified using radioactive glucose, the urinary Transforming Growth Factor β(1) (TGF-β(1)) was assessed by enzyme immunoassay, and the total glutathione in the renal tissue was also measured. The diabetic rats displayed higher levels of glycemia, and DHEA treatment reduced hyperglycemia. Plasmatic creatinine levels were higher in the diabetic rats treated with DHEA, while creatinine clearance was lower. Glucose uptake and oxidation were lower in the renal medulla of the diabetic rats treated with DHEA, and urinary TGF-β(1), as well as total gluthatione levels, were higher in the diabetic rats treated with DHEA. DHEA treatment was not beneficial to renal tissue, since it reduced the glomerular filtration rate and renal medulla metabolism, while increasing the urinary excretion of TGF-β(1) and the compensatory response by the glutathione system, probably due to a mechanism involving a pro-oxidant action or a pro-fibrotic effect of this androgen or its derivatives. In conclusion, this study reports that DHEA treatment may be harmful to renal tissue, but the mechanisms of this action have not yet been fully understood.

  15. Plasminogen activator inhibitor-1 is elevated in patients with COPD independent of metabolic and cardiovascular function

    PubMed Central

    Waschki, Benjamin; Watz, Henrik; Holz, Olaf; Magnussen, Helgo; Olejnicka, Beata; Welte, Tobias; Rabe, Klaus F; Janciauskiene, Sabina

    2017-01-01

    Introduction Plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of fibrinolysis, is associated with thrombosis, obesity, insulin resistance, dyslipidemia, and premature aging, which all are coexisting conditions of chronic obstructive pulmonary disease (COPD). The role of PAI-1 in COPD with respect to metabolic and cardiovascular functions is unclear. Methods In this study, which was nested within a prospective cohort study, the serum levels of PAI-1 were cross-sectionally measured in 74 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages I–IV) and 18 controls without lung disease. In addition, triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, waist circumference, blood pressure, smoking status, high-sensitive C-reactive protein (hs-CRP), adiponectin, ankle–brachial index, N-terminal pro-B-type natriuretic peptide, and history of comorbidities were also determined. Results The serum levels of PAI-1 were significantly higher in COPD patients than in controls, independent of a broad spectrum of possible confounders including metabolic and cardiovascular dysfunction. A multivariate regression analysis revealed triglyceride and hs-CRP levels to be the best predictors of PAI-1 within COPD. GOLD Stages II and III remained independently associated with higher PAI-1 levels in a final regression analysis. Conclusion The data from the present study showed that the serum levels of PAI-1 are higher in patients with COPD and that moderate-to-severe airflow limitation, hypertriglyceridemia, and systemic inflammation are independent predictors of an elevated PAI-1 level. PAI-1 may be a potential biomarker candidate for COPD-specific and extra-pulmonary manifestations. PMID:28356730

  16. Decreased in vitro mitochondrial function is associated with enhanced brain metabolism, blood flow, and memory in Surf1-deficient mice.

    PubMed

    Lin, Ai-Ling; Pulliam, Daniel A; Deepa, Sathyaseelan S; Halloran, Jonathan J; Hussong, Stacy A; Burbank, Raquel R; Bresnen, Andrew; Liu, Yuhong; Podlutskaya, Natalia; Soundararajan, Anuradha; Muir, Eric; Duong, Timothy Q; Bokov, Alex F; Viscomi, Carlo; Zeviani, Massimo; Richardson, Arlan G; Van Remmen, Holly; Fox, Peter T; Galvan, Veronica

    2013-10-01

    Recent studies have challenged the prevailing view that reduced mitochondrial function and increased oxidative stress are correlated with reduced longevity. Mice carrying a homozygous knockout (KO) of the Surf1 gene showed a significant decrease in mitochondrial electron transport chain Complex IV activity, yet displayed increased lifespan and reduced brain damage after excitotoxic insults. In the present study, we examined brain metabolism, brain hemodynamics, and memory of Surf1 KO mice using in vitro measures of mitochondrial function, in vivo neuroimaging, and behavioral testing. We show that decreased respiration and increased generation of hydrogen peroxide in isolated Surf1 KO brain mitochondria are associated with increased brain glucose metabolism, cerebral blood flow, and lactate levels, and with enhanced memory in Surf1 KO mice. These metabolic and functional changes in Surf1 KO brains were accompanied by higher levels of hypoxia-inducible factor 1 alpha, and by increases in the activated form of cyclic AMP response element-binding factor, which is integral to memory formation. These findings suggest that Surf1 deficiency-induced metabolic alterations may have positive effects on brain function. Exploring the relationship between mitochondrial activity, oxidative stress, and brain function will enhance our understanding of cognitive aging and of age-related neurologic disorders.

  17. Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress

    PubMed Central

    Picard, Martin; McManus, Meagan J.; Gray, Jason D.; Nasca, Carla; Moffat, Cynthia; Kopinski, Piotr K.; Seifert, Erin L.; McEwen, Bruce S.; Wallace, Douglas C.

    2015-01-01

    The experience of psychological stress triggers neuroendocrine, inflammatory, metabolic, and transcriptional perturbations that ultimately predispose to disease. However, the subcellular determinants of this integrated, multisystemic stress response have not been defined. Central to stress adaptation is cellular energetics, involving mitochondrial energy production and oxidative stress. We therefore hypothesized that abnormal mitochondrial functions would differentially modulate the organism’s multisystemic response to psychological stress. By mutating or deleting mitochondrial genes encoded in the mtDNA [NADH dehydrogenase 6 (ND6) and cytochrome c oxidase subunit I (COI)] or nuclear DNA [adenine nucleotide translocator 1 (ANT1) and nicotinamide nucleotide transhydrogenase (NNT)], we selectively impaired mitochondrial respiratory chain function, energy exchange, and mitochondrial redox balance in mice. The resulting impact on physiological reactivity and recovery from restraint stress were then characterized. We show that mitochondrial dysfunctions altered the hypothalamic–pituitary–adrenal axis, sympathetic adrenal–medullary activation and catecholamine levels, the inflammatory cytokine IL-6, circulating metabolites, and hippocampal gene expression responses to stress. Each mitochondrial defect generated a distinct whole-body stress-response signature. These results demonstrate the role of mitochondrial energetics and redox balance as modulators of key pathophysiological perturbations previously linked to disease. This work establishes mitochondria as stress-response modulators, with implications for understanding the mechanisms of stress pathophysiology and mitochondrial diseases. PMID:26627253

  18. Improvement of mitochondrial function and dynamics by the metabolic enhancer piracetam.

    PubMed

    Stockburger, Carola; Kurz, Christopher; Koch, Konrad A; Eckert, Schamim H; Leuner, Kristina; Müller, Walter E

    2013-10-01

    The metabolic enhancer piracetam is used in many countries to treat cognitive impairment in aging, brain injuries, as well as dementia such as AD (Alzheimer's disease). As a specific feature of piracetam, beneficial effects are usually associated with mitochondrial dysfunction. In previous studies we were able to show that piracetam enhanced ATP production, mitochondrial membrane potential as well as neurite outgrowth in cell and animal models for aging and AD. To investigate further the effects of piracetam on mitochondrial function, especially mitochondrial fission and fusion events, we decided to assess mitochondrial morphology. Human neuroblastoma cells were treated with the drug under normal conditions and under conditions imitating aging and the occurrence of ROS (reactive oxygen species) as well as in stably transfected cells with the human wild-type APP (amyloid precursor protein) gene. This AD model is characterized by expressing only 2-fold more human Aβ (amyloid β-peptide) compared with control cells and therefore representing very early stages of AD when Aβ levels gradually increase over decades. Interestingly, these cells exhibit an impaired mitochondrial function and morphology under baseline conditions. Piracetam is able to restore this impairment and shifts mitochondrial morphology back to elongated forms, whereas there is no effect in control cells. After addition of a complex I inhibitor, mitochondrial morphology is distinctly shifted to punctate forms in both cell lines. Under these conditions piracetam is able to ameliorate morphology in cells suffering from the mild Aβ load, as well as mitochondrial dynamics in control cells.

  19. Aldehyde Dehydrogenases in Arabidopsis thaliana: Biochemical Requirements, Metabolic Pathways, and Functional Analysis.

    PubMed

    Stiti, Naim; Missihoun, Tagnon D; Kotchoni, Simeon O; Kirch, Hans-Hubert; Bartels, Dorothea

    2011-01-01

    Aldehyde dehydrogenases (ALDHs) are a family of enzymes which catalyze the oxidation of reactive aldehydes to their corresponding carboxylic acids. Here we summarize molecular genetic and biochemical analyses of selected ArabidopsisALDH genes. Aldehyde molecules are very reactive and are involved in many metabolic processes but when they accumulate in excess they become toxic. Thus activity of aldehyde dehydrogenases is important in regulating the homeostasis of aldehydes. Overexpression of some ALDH genes demonstrated an improved abiotic stress tolerance. Despite the fact that several reports are available describing a role for specific ALDHs, their precise physiological roles are often still unclear. Therefore a number of genetic and biochemical tools have been generated to address the function with an emphasis on stress-related ALDHs. ALDHs exert their functions in different cellular compartments and often in a developmental and tissue specific manner. To investigate substrate specificity, catalytic efficiencies have been determined using a range of substrates varying in carbon chain length and degree of carbon oxidation. Mutational approaches identified amino acid residues critical for coenzyme usage and enzyme activities.

  20. Further Work on the Shaping of Cortical Development and Function by Synchrony and Metabolic Competition

    PubMed Central

    Wright, James J.; Bourke, Paul D.

    2016-01-01

    This paper furthers our attempts to resolve two major controversies—whether gamma synchrony plays a role in cognition, and whether cortical columns are functionally important. We have previously argued that the configuration of cortical cells that emerges in development is that which maximizes the magnitude of synchronous oscillation and minimizes metabolic cost. Here we analyze the separate effects in development of minimization of axonal lengths, and of early Hebbian learning and selective distribution of resources to growing synapses, by showing in simulations that these effects are partially antagonistic, but their interaction during development produces accurate anatomical and functional properties for both columnar and non-columnar cortex. The resulting embryonic anatomical order can provide a cortex-wide scaffold for postnatal learning that is dimensionally consistent with the representation of moving sensory objects, and, as learning progressively overwrites the embryonic order, further associations also occur in a dimensionally consistent framework. The role ascribed to cortical synchrony does not demand specific frequency, amplitude or phase variation of pulses to mediate “feature linking.” Instead, the concerted interactions of pulse synchrony with short-term synaptic dynamics, and synaptic resource competition can further explain cortical information processing in analogy to Hopfield networks and quantum computation. PMID:28018202

  1. Hypothalamic tanycytes—masters and servants of metabolic, neuroendocrine, and neurogenic functions

    PubMed Central

    Goodman, Timothy; Hajihosseini, Mohammad K.

    2015-01-01

    There is a resurgent interest in tanycytes, a radial glial-like cell population occupying the floor and ventro-lateral walls of the third ventricle (3V). Tanycytes reside in close proximity to hypothalamic neuronal nuclei that regulate appetite and energy expenditure, with a subset sending projections into these nuclei. Moreover, tanycytes are exposed to 3V cerebrospinal fluid and have privileged access to plasma metabolites and hormones, through fenestrated capillaries. Indeed, some tanycytes act as conduits for trafficking of these molecules into the brain parenchyma. Tanycytes can also act as neural stem/progenitor cells, supplying the postnatal and adult hypothalamus with new neurons. Collectively, these findings suggest that tanycytes regulate and integrate important trophic and metabolic processes and possibly endow functional malleability to neuronal circuits of the hypothalamus. Hence, manipulation of tanycyte biology could provide a valuable tool for modulating hypothalamic functions such as energy uptake and expenditure in order to tackle prevalent eating disorders such as obesity and anorexia. PMID:26578855

  2. Oestrogen synthesis, oestrogen metabolism and functional oestrogen receptors in bovine aortic endothelial cells.

    PubMed

    Bayard, F; Clamens, S; Delsol, G; Blaes, N; Maret, A; Faye, J C

    1995-01-01

    In order to investigate the mechanisms by which oestrogenic hormones influence the vascular system, we have studied their metabolism and the functioning of oestrogen receptors in bovine aortic endothelial cells from primo-secondary cultures, a widely studied model of vascular pathophysiology. We have demonstrated the enzymic activity of oestradiol-17 beta-hydroxysteroid dehydrogenase, 17-ketoreductase and aromatase in these cells. Immunocytochemical analyses, using two different monoclonal antibodies that recognize epitopes in the A/B domain of the oestrogen receptor, showed that this molecule has a predominantly cytoplasmic localization even after the addition of oestrogen to the culture medium. We showed that the hormone-receptor complexes were functional by demonstrating their transactivating ability in transfection experiments using the luciferase gene reporter and an oestrogen-responsive element transcriptional enhancer, although the amplitude of the response was in the range of only 140-150%: this was not a consequence of the presence of a specific limiting factor, but instead might be related to the peculiar subcellular localization of the oestrogen receptor.

  3. Functional Operons in Secondary Metabolic Gene Clusters in Glarea lozoyensis (Fungi, Ascomycota, Leotiomycetes)

    PubMed Central

    Yue, Qun; Chen, Li; Li, Yan; Bills, Gerald F.; Zhang, Xinyu; Xiang, Meichun; Li, Shaojie; Che, Yongsheng; Niu, Xuemei

    2015-01-01

    ABSTRACT Operons are multigene transcriptional units which occur mostly in prokaryotes but rarely in eukaryotes. Protein-coding operons have not been reported in the Fungi even though they represent a very diverse kingdom of organisms. Here, we report a functional operon involved in the secondary metabolism of the fungus Glarea lozoyensis belonging to Leotiomycetes (Ascomycota). Two contiguous genes, glpks3 and glnrps7, encoding polyketide synthase and nonribosomal peptide synthetase, respectively, are cotranscribed into one dicistronic mRNA under the control of the same promoter, and the mRNA is then translated into two individual proteins, GLPKS3 and GLNRPS7. Heterologous expression in Aspergillus nidulans shows that the GLPKS3-GLNRPS7 enzyme complex catalyzes the biosynthesis of a novel pyrrolidinedione-containing compound, xenolozoyenone (compound 1), which indicates the operon is functional. Although it is structurally similar to prokaryotic operons, the glpks3-glnrps7 operon locus has a monophylogenic origin from fungi rather than having been horizontally transferred from prokaryotes. Moreover, two additional operons, glpks28-glnrps8 and glpks29-glnrps9, were verified at the transcriptional level in the same fungus. This is the first report of protein-coding operons in a member of the Fungi. PMID:26081635

  4. Oestradiol metabolism and androgen receptor genotypes are associated with right ventricular function

    PubMed Central

    Ventetuolo, Corey E.; Mitra, Nandita; Wan, Fei; Manichaikul, Ani; Barr, R. Graham; Johnson, Craig; Bluemke, David A.; Lima, Joao A.C.; Tandri, Hari; Ouyang, Pamela; Kawut, Steven M.

    2016-01-01

    Sex hormones are linked to right ventricular (RV) function, but the relationship between genetic variation in these pathways and RV function is unknown. We performed a cross-sectional study of 2761 genotyped adults without cardiovascular disease. The relationships between RV measures and single nucleotide polymorphisms (SNPs) in 10 candidate genes were assessed. Urinary oestradiol (E2) metabolites produced by cytochrome P4501B1 (CYP1B1) and serum testosterone were measured in women and men respectively. In African-American (AA) women, the CYP1B1 SNP rs162561 was associated with RV ejection fraction (RVEF), such that each copy of the A allele was associated with a 2.0% increase in RVEF. Haplotype analysis revealed associations with RVEF in AA (global p<7.2×10−6) and white (global p=0.05) women. In white subjects, higher E2 metabolite levels were associated with significantly higher RVEF. In men, androgen receptors SNPs (rs1337080; rs5918764) were significantly associated with all RV measures and modified the relationship between testosterone and RVEF. Genetic variation in E2 metabolism and androgen signalling was associated with RV morphology in a sex-specific manner. The CYP1B1 SNP identified is in tight linkage disequilibrium with SNPs associated with pulmonary hypertension and oncogenesis, suggesting these pathways may underpin sexual dimorphism in RV failure. PMID:26647441

  5. Functional polarity of dendrites and axons of primate A1 amacrine cells

    PubMed Central

    Davenport, Christopher M.; Detwiler, Peter B.; Dacey, Dennis M.

    2011-01-01

    The A1 cell is an axon-bearing amacrine cell of the primate retina with a diffusely stratified, moderately branched dendritic tree (~400 µm diameter). Axons arise from proximal dendrites forming a second concentric, larger arborization (>4 mm diameter) of thin processes with bouton-like swellings along their length. A1 cells are ON-OFF transient cells that fire a brief high frequency burst of action potentials in response to light (Stafford & Dacey, 1997). It has been hypothesized that A1 cells receive local input to their dendrites, with action potentials propagating output via the axons across the retina, serving a global inhibitory function. To explore this hypothesis we recorded intracellularly from A1 cells in an in vitro macaque monkey retina preparation. A1 cells have an antagonistic center-surround receptive field structure for the ON and OFF components of the light response. Blocking the ON pathway with L-AP4 eliminated ON center responses but not OFF center responses or ON or OFF surround responses. Blocking GABAergic inhibition with picrotoxin increased response amplitudes without affecting receptive field structure. TTX abolished action potentials, with little effect on the sub-threshold light response or basic receptive field structure. We also used multi-photon laser scanning microscopy to record light-induced calcium transients in morphologically identified dendrites and axons of A1 cells. TTX completely abolished such calcium transients in the axons but not in the dendrites. Together these results support the current model of A1 function, whereby the dendritic tree receives synaptic input that determines the center-surround receptive field; and action potentials arise in the axons, which propagate away from the dendritic field across the retina. PMID:17550636

  6. Distinct Domains of Yeast Cortical Tag Proteins Bud8p and Bud9p Confer Polar Localization and Functionality

    PubMed Central

    Krappmann, Anne-Brit; Taheri, Naimeh; Heinrich, Melanie

    2007-01-01

    In Saccharomyces cerevisiae, diploid yeast cells follow a bipolar budding program, which depends on the two transmembrane glycoproteins Bud8p and Bud9p that potentially act as cortical tags to mark the cell poles. Here, we have performed systematic structure-function analyses of Bud8p and Bud9p to identify functional domains. We find that polar transport of Bud8p and Bud9p does not depend on N-terminal sequences but instead on sequences in the median part of the proteins and on the C-terminal parts that contain the transmembrane domains. We show that the guanosine diphosphate (GDP)/guanosine triphosphate (GTP) exchange factor Bud5p, which is essential for bud site selection and physically interacts with Bud8p, also interacts with Bud9p. Regions of Bud8p and Bud9p predicted to reside in the extracellular space are likely to confer interaction with the N-terminal region of Bud5p, implicating indirect interactions between the cortical tags and the GDP/GTP exchange factor. Finally, we have identified regions of Bud8p and Bud9p that are required for interaction with the cortical tag protein Rax1p. In summary, our study suggests that Bud8p and Bud9p carry distinct domains for delivery of the proteins to the cell poles, for interaction with the general budding machinery and for association with other cortical tag proteins. PMID:17581861

  7. Electrophoresis of polar fluorescent tracers through the nerve sheath labels neuronal populations for anatomical and functional imaging

    PubMed Central

    Isaacson, Matthew D.; Hedwig, Berthold

    2017-01-01

    The delivery of tracers into populations of neurons is essential to visualize their anatomy and analyze their function. In some model systems genetically-targeted expression of fluorescent proteins is the method of choice; however, these genetic tools are not available for most organisms and alternative labeling methods are very limited. Here we describe a new method for neuronal labelling by electrophoretic dye delivery from a suction electrode directly through the neuronal sheath of nerves and ganglia in insects. Polar tracer molecules were delivered into the locust auditory nerve without destroying its function, simultaneously staining peripheral sensory structures and central axonal projections. Local neuron populations could be labelled directly through the surface of the brain, and in-vivo optical imaging of sound-evoked activity was achieved through the electrophoretic delivery of calcium indicators. The method provides a new tool for studying how stimuli are processed in peripheral and central sensory pathways and is a significant advance for the study of nervous systems in non-model organisms. PMID:28084413

  8. Synthesis of end-functionalized polyacetylenes that contain polar groups by employing well-defined palladium catalysts.

    PubMed

    Rodriguez Castanon, Jesus; Kuwata, Keiko; Shiotsuki, Masashi; Sanda, Fumio

    2012-10-29

    A series of [(dppf)PdBr(R)]-type complexes (dppf=1,1'-bis(diphenylphosphino)ferrocene; R=p-cyanophenyl (1 a), o-hydroxymethylphenyl (1 b), and triphenylvinyl (1 c)), in combination with silver trifluoromethanesulfonate (AgOTf), were demonstrated to be active for the polymerization of monosubstituted polar acetylene monomers HC≡CCONHC(4)H(9) (2), HC≡CCO(2)C(8)H(17) (3), HC≡CCH(2)OCONHC(6)H(13) (4), HC≡CCH(2)OCO(2)C(6)H(13) (5), and HC≡CCH(CH(3))OH (6). The yields and molecular weights of the polymers depended on the combination of the Pd catalyst and monomer that was employed. Matrix-assisted laser-desorption/ionization-time of flight (MALDI-TOF) mass spectrometric analysis indicated the formation of polymers that contained the "R" and "H" groups at the chain ends. IR spectroscopic analysis supported the R-end-functionalization of the polymers. NMR spectroscopy and MS identified the presence of species that were formed by single, double, and triple insertion of the monomers into the Pd-C(6)H(4)-p-CN bond, thereby giving solid evidence for an insertion mechanism for the present system. Density functional theory (DFT) calculations suggested the preference for 1,2-insertion of the monomer compared to 2,1-insertion.

  9. Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions

    PubMed Central

    Cavalcanti-Galdino, M.K.; da Silva, J.A.; Mendes, L.C.; dos Santos, N.A.; Simas, M.L.B.

    2014-01-01

    The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions. PMID:24676473

  10. Acute effect of alcohol intake on sine-wave Cartesian and polar contrast sensitivity functions.

    PubMed

    Cavalcanti-Galdino, M K; Silva, J A da; Mendes, L C; Santos, N A da; Simas, M L B

    2014-04-01

    The aim of this study was to assess contrast sensitivity for angular frequency stimuli as well as for sine-wave gratings in adults under the effect of acute ingestion of alcohol. We measured the contrast sensitivity function (CSF) for gratings of 0.25, 1.25, 2.5, 4, 10, and 20 cycles per degree of visual angle (cpd) as well as for angular frequency stimuli of 1, 2, 4, 24, 48, and 96 cycles/360°. Twenty adults free of ocular diseases, with normal or corrected-to-normal visual acuity, and no history of alcoholism were enrolled in two experimental groups: 1) no alcohol intake (control group) and 2) alcohol ingestion (experimental group). The average concentration of alcohol in the experimental group was set to about 0.08%. We used a paradigm involving a forced-choice method. Maximum sensitivity to contrast for sine-wave gratings in the two groups occurred at 4 cpd sine-wave gratings and at 24 and 48 cycles/360° for angular frequency stimuli. Significant changes in contrast sensitivity were observed after alcohol intake compared with the control condition at spatial frequency of 4 cpd and 1, 24, and 48 cycles/360° for angular frequency stimuli. Alcohol intake seems to affect the processing of sine-wave gratings at maximum sensitivity and at the low and high frequency ends for angular frequency stimuli, both under photopic luminance conditions.

  11. A single transcription factor regulates evolutionarily diverse but functionally linked metabolic pathways in response to nutrient availability.

    PubMed

    Schmid, Amy K; Reiss, David J; Pan, Min; Koide, Tie; Baliga, Nitin S

    2009-01-01

    During evolution, enzyme-coding genes are acquired and/or replaced through lateral gene transfer and compiled into metabolic pathways. Gene regulatory networks evolve to fine tune biochemical fluxes through such metabolic pathways, enabling organisms to acclimate to nutrient fluctuations in a competitive environment. Here, we demonstrate that a single TrmB family transcription factor in Halobacterium salinarum NRC-1 globally coordinates functionally linked enzymes of diverse phylogeny in response to changes in carbon source availability. Specifically, during nutritional limitation, TrmB binds a cis-regulatory element to activate or repress 113 promoters of genes encoding enzymes in diverse metabolic pathways. By this mechanism, TrmB coordinates the expression of glycolysis, TCA cycle, and amino-acid biosynthesis pathways with the biosynthesis of their cognate cofactors (e.g. purine and thiamine). Notably, the TrmB-regulated metabolic network includes enzyme-coding genes that are uniquely archaeal as well as those that are conserved across all three domains of life. Simultaneous analysis of metabolic and gene regulatory network architectures suggests an ongoing process of co-evolution in which TrmB integrates the expression of metabolic enzyme-coding genes of diverse origins.

  12. The micro-architecture of the cerebral cortex: Functional neuroimaging models and metabolism

    PubMed Central

    Riera, Jorge J.; Schousboe, Arne; Waagepetersen, Helle S.; Howarth, Clare; Hyder, Fahmeed

    2014-01-01

    In order to interpret/integrate data obtained with different functional neuroimaging modalities (e.g. fMRI, EEG/MEG, PET/SPECT, fNIRS), forward-generative models of a diversity of brain mechanisms at the mesoscopic level are considered necessary. For the cerebral cortex, the brain structure with possibly the most relevance for functional neuroimaging, a variety of such biophysical models has been proposed over the last decade. The development of technological tools to investigate in vitro the physiological, anatomical and biochemical principles at the microscopic scale in comparative studies formed the basis for such theoretical progresses. However, with the most recent introduction of systems to record electrical (e.g. miniaturized probes chronically/acutely implantable in the brain), optical (e.g. two-photon laser scanning microscopy) and atomic nuclear spectral (e.g. nuclear magnetic resonance spectroscopy) signals using living laboratory animals, the field is receiving even greater attention. Major advances have been achieved by combining such sophisticated recording systems with new experimental strategies (e.g. transgenic/knock-out animals, high resolution stereotaxic manipulation systems for probe-guidance and cellular-scale chemical-delivery). Theoreticians may now be encouraged to re-consider previously formulated mesoscopic level models in order to incorporate important findings recently made at the microscopic scale. In this series of reviews, we summarize the background at the microscopic scale, which we suggest will constitute the foundations for upcoming representations at the mesoscopic level. In this first part, we focus our attention on the nerve ending particles in order to summarize basic principles and mechanisms underlying cellular metabolism in the cerebral cortex. It will be followed by two parts highlighting major features in its organization/working-principles to regulate both cerebral blood circulation and neuronal activity, respectively

  13. Functional impairment of skeletal muscle oxidative metabolism during knee extension exercise after bed rest

    PubMed Central

    Salvadego, Desy; Lazzer, Stefano; Marzorati, Mauro; Porcelli, Simone; Rejc, Enrico; Šimunič, Bostjan; Pišot, Rado; di Prampero, Pietro Enrico

    2011-01-01

    A functional evaluation of skeletal muscle oxidative metabolism during dynamic knee extension (KE) incremental exercises was carried out following a 35-day bed rest (BR) (Valdoltra 2008 BR campaign). Nine young male volunteers (age: 23.5 ± 2.2 yr; mean ± SD) were evaluated. Pulmonary gas exchange, heart rate and cardiac output (by impedance cardiography), skeletal muscle (vastus lateralis) fractional O2 extraction, and brain (frontal cortex) oxygenation (by near-infrared spectroscopy) were determined during incremental KE. Values at exhaustion were considered “peak”. Peak heart rate (147 ± 18 beats/min before vs. 146 ± 17 beats/min after BR) and peak cardiac output (17.8 ± 3.3 l/min before vs. 16.1 ± 1.8 l/min after BR) were unaffected by BR. As expected, brain oxygenation did not decrease during KE. Peak O2 uptake was lower after vs. before BR, both when expressed as liters per minute (0.99 ± 0.17 vs. 1.26 ± 0.27) and when normalized per unit of quadriceps muscle mass (46.5 ± 6.4 vs. 56.9 ± 11.0 ml·min−1·100 g−1). Skeletal muscle peak fractional O2 extraction, expressed as a percentage of the maximal values obtained during a transient limb ischemia, was lower after (46.3 ± 12.1%) vs. before BR (66.5 ± 11.2%). After elimination, by the adopted exercise protocol, of constraints related to cardiovascular O2 delivery, a decrease in peak O2 uptake and muscle peak capacity of fractional O2 extraction was found after 35 days of BR. These findings suggest a substantial impairment of oxidative function at the muscle level, “downstream” with respect to bulk blood flow to the exercising muscles, that is possibly at the level of blood flow distribution/O2 utilization inside the muscle, peripheral O2 diffusion, and intracellular oxidative metabolism. PMID:21921243

  14. Structure and chemical reactivity of the polar three-fold surfaces of GaPd: A density-functional study

    NASA Astrophysics Data System (ADS)

    Krajčí, M.; Hafner, J.

    2013-03-01

    The polar threefold surfaces of the GaPd compound crystallizing in the B20 (FeSi-type) structure (space group P213) have been investigated using density-functional methods. Because of the lack of inversion symmetry the B20 structure exists in two enantiomorphic forms denoted as A and B. The threefold {111} surfaces have polar character. In both nonequivalent (111) and (bar{1}bar{1}bar{1}) directions several surface terminations differing in structure and chemical composition are possible. The formation of the threefold surfaces has been studied by simulated cleavage experiments and by calculations of the surface energies. Because of the polar character of the threefold surfaces calculations for stoichiometric slabs permit only the determination of the average energy of the surfaces exposed on both sides of the slab. Calculations for nonstoichiometric slabs performed in the grand canonical ensemble yield differences of the surface energies for the possible terminations as a function of the chemical potential in the reactive atmosphere above the surface and predict a transition between Ga- and Pd-terminated surfaces as a function of the chemical potential. The {100} surfaces are stoichiometric and uniquely defined. The calculated surface energies are identical to the average energies of the {100} surfaces of the pure metals. The {210} surfaces are also stoichiometric, with an energy very close to that of the {100} surfaces. Assuming that for the {111} surfaces the energies of different possible terminations are in a proportion equal to that of the concentration-weighted energies of the {111} surfaces of the pure metals, surface energies for all possible {111} terminations may be calculated. The preferable termination perpendicular to the A⟨111⟩ direction consists of a bilayer with three Ga atoms in the upper and three Pd atoms in the lower part. The surface energy of this termination further decreases if the Pd triplet is covered by additional Ga atom

  15. PROTEIN METABOLISM IN REGENERATING WOUND TISSUE: FUNCTION OF THE SULFUR AMINO ACIDS.

    DTIC Science & Technology