Autonomic Reflexes and Homeostasis

3 The Semantic Grid and Autonomic Computing LEARNING OUTCOMES In this chapter, we will study the Semantic Grid and autonomic computing. From this chapter, you will learn: • What the Semantic Grid is about. • The technologies involved in the development of the Semantic Grid. • The state-of-the-art development of the Semantic Grid. • What autonomic computing is about. • Features of autonomic computing. • How to apply autonomic computing techniques to Grid services. CHAPTER OUTLINE 3.1 Introduction 3.2 Metadata and Ontology in the Semantic Web 3.3 Semantic Web Services 3.4 A Layered Structure of the Semantic Grid The Grid: Core Technologies Maozhen Li and Mark Baker © 2005 John Wiley & Sons, Ltd 78 SEMANTIC GRID AND AUTONOMIC COMPUTING 3.5 Semantic Grid Activities 3.6 Autonomic Computing 3.7 Chapter Summary 3.8 Further Reading and Testing 3.1 INTRODUCTION The concept of the Semantic Grid [1] is evolved through the concur- rent development of the Semantic Web and the Grid. The Semantic Web can be defined as “an extension of the current Web in which information is given well-defined meaning, better enabling com- puters and people to work in cooperation” [2]. The aim of the Semantic Web is to augment unstructured Web content so that it may be machine-interpretable information to improve the potential capabilities of Web applications. The aim of the Semantic Grid is to explore the use of Semantic Web technologies to enrich the Grid with semantics. The relationship between the Grid, the Semantic Web and the Semantic Grid is shown in Figure 3.1. The Semantic Grid is layered on top of the Semantic Web and the Grid. It is the application of Semantic Web technologies to the Grid. Meta- data and ontologies play a critical role in the development of the Semantic Web. Metadata can be viewed as data that is used to describe data. Data can be annotated with metadata to specify its origin or its history. In the Semantic Grid, for example, Grid ser- vices can be annotated with metadata associated with an ontology for automatic service discovery. An ontology is a specification of a conceptualization [3]. We will explain metadata and ontology in Section 3.2. Semantic Grid Semantic Web Grid Semantic Web Technology Grid Service Applying Technology Semantic Grid Service Figure 3.1 The Semantic Web, Grid and Semantic Grid 3.2 METADATA AND ONTOLOGY IN THE SEMANTIC WEB 79 The Grid is complex in nature because it tries to couple dis- tributed and heterogeneous resources such as data, computers, operating systems, database systems, applications and special devices, which may run across multiple virtual organizations to provide a uniform platform for technical computing. The com- plexity of managing a large computing system, such as the Grid, has led researchers to consider management techniques that are based on strategies that have evolved in biological systems to deal with complexity, heterogeneity and uncertainty. The approach is referred to autonomic computing [4]. An autonomic computing system is one that has the capabilities of being self-healing, self- configuring, Autonomic Reflexes and Homeostasis Autonomic Reflexes and Homeostasis Bởi: OpenStaxCollege The autonomic nervous system regulates organ systems through circuits that resemble the reflexes described in the somatic nervous system The main difference between the somatic and autonomic systems is in what target tissues are effectors Somatic responses are solely based on skeletal muscle contraction The autonomic system, however, targets cardiac and smooth muscle, as well as glandular tissue Whereas the basic circuit is a reflex arc, there are differences in the structure of those reflexes for the somatic and autonomic systems The Structure of Reflexes One difference between a somatic reflex, such as the withdrawal reflex, and a visceral reflex, which is an autonomic reflex, is in the efferent branch The output of a somatic reflex is the lower motor neuron in the ventral horn of the spinal cord that projects directly to a skeletal muscle to cause its contraction The output of a visceral reflex is a two-step pathway starting with the preganglionic fiber emerging from a lateral horn neuron in the spinal cord, or a cranial nucleus neuron in the brain stem, to a ganglion—followed by the postganglionic fiber projecting to a target effector The other part of a reflex, the afferent branch, is often the same between the two systems Sensory neurons receiving input from the periphery—with cell bodies in the sensory ganglia, either of a cranial nerve or a dorsal root ganglion adjacent to the spinal cord—project into the CNS to initiate the reflex ([link]) The Latin root “effere” means “to carry.” Adding the prefix “ef-” suggests the meaning “to carry away,” whereas adding the prefix “af-” suggests “to carry toward or inward.” 1/14 Autonomic Reflexes and Homeostasis Comparison of Somatic and Visceral Reflexes The afferent inputs to somatic and visceral reflexes are essentially the same, whereas the efferent branches are different Somatic reflexes, for instance, involve a direct connection from the ventral horn of the spinal cord to the skeletal muscle Visceral reflexes involve a projection from the central neuron to a ganglion, followed by a second projection from the ganglion to the target effector Afferent Branch The afferent branch of a reflex arc does differ between somatic and visceral reflexes in some instances Many of the inputs to visceral reflexes are from special or somatic 2/14 Autonomic Reflexes and Homeostasis senses, but particular senses are associated with the viscera that are not part of the conscious perception of the environment through the somatic nervous system For example, there is a specific type of mechanoreceptor, called a baroreceptor, in the walls of the aorta and carotid sinuses that senses the stretch of those organs when blood volume or pressure increases You not have a conscious perception of having high blood pressure, but that is an important afferent branch of the cardiovascular and, particularly, vasomotor reflexes The sensory neuron is essentially the same as any other general sensory neuron The baroreceptor apparatus is part of the ending of a unipolar neuron that has a cell body in a sensory ganglion The baroreceptors from the carotid arteries have axons in the glossopharyngeal nerve, and those from the aorta have axons in the vagus nerve Though visceral senses are not primarily a part of conscious perception, those sensations sometimes make it to conscious awareness If a visceral sense is strong enough, it will be perceived The sensory homunculus—the representation of the body in the primary somatosensory cortex—only has a small region allotted for the perception of internal stimuli If you swallow a large bolus of food, for instance, you will probably feel the lump of that food as it pushes through your esophagus, or even if your stomach is distended after a large meal If you inhale especially cold air, you can feel it as it enters your larynx and trachea These sensations are not the same as feeling high blood pressure or blood sugar levels When particularly strong visceral sensations rise to the level of conscious perception, the sensations are often felt in unexpected places For example, strong visceral sensations of the heart will be felt as pain in the left shoulder and left arm This irregular pattern of projection of conscious perception of visceral sensations is called referred pain Depending on the organ system affected, the referred pain will project to different areas of the body ([link]) The location of referred pain is not random, but a definitive explanation of the mechanism has not been established The most broadly accepted theory for this phenomenon is that the visceral sensory fibers enter into the same level of the spinal cord as the somatosensory fibers of the referred pain location By this explanation, the visceral sensory fibers from the mediastinal region, where the heart is located, would enter the spinal cord at the same level as the spinal nerves from the shoulder ...Modulation of sterol homeostasis by the Cdc42p effectors Cla4p and Ste20p in the yeast Saccharomyces cerevisiae Meng Lin 1, *, Karlheinz Grillitsch 2, *, Gu ¨ nther Daum 2 , Ursula Just 1 and Thomas Ho ¨ fken 1 1 Institute of Biochemistry, Christian Albrecht University, Kiel, Germany 2 Institute of Biochemistry, Graz University of Technology, Austria Keywords cell polarity; p21-activated kinase; sterol; steryl ester; yeast Correspondence T. Ho ¨ fken, Institute of Biochemistry, Christian Albrecht University Kiel, Olshausenstrasse 40, 24098 Kiel, Germany Fax: +49 431 8802609 Tel.: +49 431 8801660 E-mail: thoefken@biochem.uni-kiel.de *These authors contributed equally to this work (Received 2 September 2009, revised 29 September 2009, accepted 12 October 2009) doi:10.1111/j.1742-4658.2009.07433.x The conserved Rho-type GTPase Cdc42p is a key regulator of signal trans- duction and polarity in eukaryotic cells. In the yeast Saccharomyces cerevi- siae, Cdc42p promotes polarized growth through the p21-activated kinases Ste20p and Cla4p. Previously, we demonstrated that Ste20p forms a com- plex with Erg4p, Cbr1p and Ncp1p, which all catalyze important steps in sterol biosynthesis. CLA4 interacts genetically with ERG4 and NCP1. Fur- thermore, Erg4p, Ncp1p and Cbr1p play important roles in cell polariza- tion during vegetative growth, mating and filamentation. As Ste20p and Cla4p are involved in these processes it seems likely that sterol biosynthetic enzymes and p21-activated kinases act in related pathways. Here, we demonstrate that the deletion of either STE20 or CLA4 results in increased levels of sterols. In addition, higher concentrations of steryl esters, the stor- age form of sterols, were observed in cla4D cells. CLA4 expression from a multicopy plasmid reduces enzyme activity of Are2p, the major steryl ester synthase, under aerobic conditions. Altogether, our data suggest that Ste20p and Cla4p may function as negative modulators of sterol biosyn- thesis. Moreover, Cla4p has a negative effect on steryl ester formation. As sterol homeostasis is crucial for cell polarization, Ste20p and Cla4p may regulate cell polarity in part through the modulation of sterol homeostasis. Structured digital abstract l MINT-7291456: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with CBR1 (uniprotkb: P38626)byubiquitin reconstruction (MI:0112) l MINT-7291480: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with BEM1 (uniprotkb: P29366)byubiquitin reconstruction (MI:0112) l MINT-7291468: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with NCP1 (uniprotkb: P16603)byubiquitin reconstruction (MI:0112) l MINT-7291441: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with ERG4 (uniprotkb: P25340)byubiquitin reconstruction (MI:0112) l MINT-7291492: CLA4 (uniprotkb:P48562) physically interacts (MI:0915) with BEM1 (uniprotkb: P29366)byubiquitin reconstruction (MI:0112) l MINT-7291412: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with ARE1 (uniprotkb: P25628)bypull down (MI:0096) l MINT-7291424: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with ARE2 (uniprotkb: P53629)bypull down (MI:0096) Abbreviations GST, glutathione S-transferase; PAK, p21-activated kinase; SC, synthetic complete; SE, steryl esters; YPD, 1% yeast extract, 2% peptone, 2% dextrose. FEBS Journal 276 (2009) 7253–7264 ª 2009 The Authors Journal compilation ª 2009 FEBS 7253 Introduction The Rho-type GTPase Cdc42p plays a crucial role in the establishment and maintenance Humana Press Brain Homeostasis in Health and Disease Edited by Wolfgang Walz The Neuronal Environment The Neuronal Environment Contemporary Neuroscience The Neuronal Environment: Brain Homeostasis in Health and Disease, edited by Wolfgang Walz, 2002 Neurotransmitter Transporters: Structure, Function, and Regulation, 2/e, edited by Maarten E. A. Reith, 2002 Pathogenesis of Neurodegenerative Disorders, edited by Mark P. Mattson, 2001 Stem Cells and CNS Development, edited by Mahendra S. Rao, 2001 Neurobiology of Spinal Cord Injury, edited by Robert G. Kalb and Stephen M. Strittmatter, 2000 Cerebral Signal Transduction: From First to Fourth Messengers, edited by Maarten E. A. Reith, 2000 Central Nervous System Diseases: Innovative Animal Models from Lab to Clinic, edited by Dwaine F. Emerich, Reginald L. Dean, III, and Paul R. Sanberg, 2000 Mitochondrial Inhibitors and Neurodegenerative Disorders, edited by Paul R. Sanberg, Hitoo Nishino, and Cesario V. Borlongan, 2000 Cerebral Ischemia: Molecular and Cellular Pathophysiology, edited by Wolfgang Walz, 1999 Cell Transplantation for Neurological Disorders, edited by Thomas B. Freeman and Håkan Widner,1998 Gene Therapy for Neurological Disorders and Brain Tumors, edited by E. Antonio Chiocca and Xandra O. Breakefield, 1998 Highly Selective Neurotoxins: Basic and Clinical Applications, edited by Richard M. Kostrzewa, 1998 Neuroinflammation: Mechanisms and Management, edited by Paul L. Wood, 1998 Neuroprotective Signal Transduction, edited by Mark P. Mattson, 1998 Clinical Pharmacology of Cerebral Ischemia, edited by Gert J. Ter Horst and Jakob Korf, 1997 Molecular Mechanisms of Dementia, edited by Wilma Wasco and Rudolph E. Tanzi, 1997 Neurotransmitter Transporters: Structure, Function, and Regulation, edited by Maarten E. A. Reith, 1997 Motor Activity and Movement Disorders: Research Issues and Applications, edited by Paul R. Sanberg, Klaus-Peter Ossenkopp, and Martin Kavaliers, 1996 Neurotherapeutics: Emerging Strategies, edited by Linda M. Pullan and Jitendra Patel, 1996 Neuron–Glia Interrelations During Phylogeny: II. Plasticity and Regeneration, edited by Antonia Vernadakis and Betty I. Roots, 1995 Neuron–Glia Interrelations During Phylogeny: I. Phylogeny and Ontogeny of Glial Cells, edited by Antonia Vernadakis and Betty I. Roots, 1995 The Biology of Neuropeptide Y and Related Peptides, edited by William F. Colmers and Claes Wahlestedt, 1993 The Neuronal Environment Brain Homeostasis in Health and Disease Edited by Wolfgang Walz Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchawan, Canada Humana Press Totowa, New Jersey © 2002 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 www.humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permission from the Publisher. The Humana Press Inc. The content and opinions expressed in this book are the sole work of the authors and editors, who have warranted due diligence in the creation and issuance of their work. The publisher, editors, and authors are not responsible for errors or omissions or for any consequences arising from the information or opinions presented in this book and make no warranty, express or implied, with respect to its contents. This publication is printed on acid-free paper. ∞ ANSI Z39.48-1984 (American Standards Institute) Permanence of Paper for Printed Library Materials. Production Editor: Diana Mezzina Cover Illustration: Figure 9 from Chapter 4, “Transmitter-Receptor Mismatches in Central Dopamine, Serotonin, and Neuropeptide Systems,” Quantitative modeling of triacylglycerol homeostasis in yeast – metabolic requirement for lipolysis to promote membrane lipid synthesis and cellular growth Ju ¨ rgen Zanghellini 1, *, Klaus Natter 2, *, Christian Jungreuthmayer 3 , Armin Thalhammer 1 , Christoph F. Kurat 2 , Gabriela Gogg-Fassolter 2 , Sepp D. Kohlwein 2 and Hans-Hennig von Gru ¨ nberg 1 1 Institute of Chemistry, University of Graz, Austria 2 Institute of Molecular Biosciences, University of Graz, Austria 3 Trinity Center of Bioengineering, Trinity College Dublin, Ireland Triacylglycerols (TAG) are important storage com- pounds in pro- and eukaryotes. Not only do these lipids store chemical energy in the form of fatty acids (FA), they also serve to dispose of excess free FA from the cellular milieu, thus precluding FA-induced toxicity [1,2]. Neutral fats, which in yeast consist of TAG and steryl esters (SE), are stockpiled in lipid droplets (LD) during periods of cellular growth [3]. In times of star- vation, esterified FA is then released by lipolysis and recycled into other lipids, or degraded via b-oxidation in order to provide the metabolic energy for cellular maintenance [4]. Recent data have shown that TAG pools in yeast are filled when growth ceases as a result of carbon source (typically glucose) limitation, and cells enter stationary phase [5]. TAG degradation during station- ary phase occurs rather slowly and the specific activi- ties involved have not yet been identified clearly. Surprisingly, on glucose supplementation, quiescent cells rapidly initiate TAG degradation at a high rate when they re-enter the cell cycle [5]. Accordingly, tgl3 tgl4 mutants lacking the ability to hydrolyze TAG show severe growth retardation. These observations indicate that TAG degradation is an important Keywords dynamic flux-balance analysis; lipid metabolism; Saccharomyces cerevisiae; systems biology; triacylglycerol degradation Correspondence J. Zanghellini, Institute of Chemistry, University of Graz, Heinrichstraße 28, A-8010 Graz, Austria Fax: +43 316 380 9850 Tel: +43 316 380 5421 E-mail: juergen.zanghellini@uni-graz.at *These authors contributed equally to this work (Received 11 July 2008, revised 5 September 2008, accepted 9 September 2008) doi:10.1111/j.1742-4658.2008.06681.x Triacylglycerol metabolism in Saccharomyces cerevisiae was analyzed quan- titatively using a systems biological approach. Cellular growth, glucose uptake and ethanol secretion were measured as a function of time and used as input for a dynamic flux-balance model. By combining dynamic mass balances for key metabolites with a detailed steady-state analysis, we trained a model network and simulated the time-dependent degradation of cellular triacylglycerol and its interaction with fatty acid and membrane lipid synthesis. This approach described precisely, both qualitatively and quantitatively, the time evolution of various key metabolites in a consistent and self-contained manner, and the predictions were found to be in excel- lent agreement with experimental data. We showed that, during pre-loga- rithmic growth, lipolysis of triacylglycerol allows for the rapid synthesis of membrane lipids, whereas de novo fatty acid synthesis plays only a minor role during this growth phase. Progress in triacylglycerol hydrolysis directly correlates with an increase in cell size, demonstrating the importance of lipolysis for supporting efficient growth Antioxidant defences and homeostasis of reactive oxygen species in different human mitochondrial DNA-depleted cell lines Lodovica Vergani 1 , Maura Floreani 2 , Aaron Russell 3 , Mara Ceccon 1 , Eleonora Napoli 4 , Anna Cabrelle 5 , Lucia Valente 2 , Federica Bragantini 1 , Bertrand Leger 3 and Federica Dabbeni-Sala 2 1 Dipartimento di Scienze Neurologiche and 2 Dipartimento di Farmacologia e Anestesiologia, Universita ` di Padova, Padova, Italy; 3 Clinique Romande de Re ´ adaptation SUVA Care, Sion, Switzerland; 4 E.Medea Scientific Institute, Conegliano Research Centre, Conegliano, Italy; 5 Dipartimento di Medicina Clinica, Universita ` di Padova, c/o Istituto Veneto di Medicina Molecolare, Padova, Italy Three pairs of parental (q + ) and established mitochondrial DNA depleted (q 0 ) cells, derived from bone, lung and muscle were used to verify the i nfluence of the nuclear background and t he lack of efficient m itocho ndrial r espiratory chain on antioxidant defences and homeostasis of intracellular reactive oxygen s pecies (ROS). Mitochondrial DNA deple- tion significantly lowered glutathion e reductase activity, glutathione ( GSH) content, and consistently altered the GSH 2 : o xidized glutathione ratio i n all of the q 0 cell lines, albeit to differing extents, indicating the most oxidized redox state in bone q 0 cells. Activity, as well as gene expression and protein content, of superoxide dismutase showed a decrease in bone and muscle q 0 cell lines but not in lung q 0 cells. GSH peroxidase activity was four times higher in a ll three q 0 cell lines in comparison to the parental q + , suggesting that this may be a necessary adaptation for survival without a functional respiratory chain. Taken together, these data suggest that the lack of respiratory chain prompts the cells to reduce their need for antioxidant defences in a tissue-specific manner, exposing them t o a major risk of oxidative injury. In fact bone-derived q 0 cells displayed the highest steady-state level of intracellular ROS (measured directly by 2¢,7¢-di- chlorofluorescin, or in directly by aconitase activity) com- paredtoalltheotherq + and q 0 cells, both in the presence or absence of glucose. Analysis of mitochondrial and cytosolic/ iron regulatory protein-1 aconitase indicated that most ROS of bone q 0 cells originate from sources other than mitochondria. Keywords:A549q 0 cells; antioxidant defences; 143 q 0 cells; reactive oxygen species; rhabdomyosarcoma q 0 cells. Cellular reactive oxygen species (ROS), such as superoxide anions (O Æ À 2 ) 1 , and hydrogen peroxide (H 2 O 2 ), have long been held to be harmful by-products of life in an a erobic environment. ROS a re potentially toxic because they are highly reactive and m odify several types of cellular macro- molecules. Lipid, protein and DNA damage can lead to cytotoxicity and mutagenesis [1]. Therefore, cells have evolved elaborate defence systems t o counteract the effects of ROS. These include both nonenzymatic (glutathione, pyridine nucleotides, ascorbate, retinoic acid, thio redoxin and tocopherol) and enzymatic (such as superoxide dis- mutases, catalase, g lutathione peroxidase and p eroxi- redoxin) p athways, w hich limit the rate of oxidation and thereby p rotect cells from oxidative s tress [ 1,2]. N otwith- standing, evidence is emerging that ROS also act as signals or mediators i n many cellular p rocesses, such as c ell pro- liferation, differentiation, a poptosis, a nd senescence [3–5]. The redox environment of a cell may alter the balance between apoptosis .. .Autonomic Reflexes and Homeostasis Comparison of Somatic and Visceral Reflexes The afferent inputs to somatic and visceral reflexes are essentially the same,... does differ between somatic and visceral reflexes in some instances Many of the inputs to visceral reflexes are from special or somatic 2/14 Autonomic Reflexes and Homeostasis senses, but particular... serotonin 13/14 Autonomic Reflexes and Homeostasis B What gland produces a secretion that causes fight-or-flight responses in effectors? adrenal medulla salivatory gland reproductive gland thymus