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Sample records for physiological role structure

  1. DGK-θ: Structure, Enzymology, and Physiological Roles

    PubMed Central

    Tu-Sekine, Becky; Goldschmidt, Hana L.; Raben, Daniel M.

    2016-01-01

    Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PtdOH). The recognition of the importance of these enzymes has been increasing ever since it was determined that they played a role in the phosphatidylinositol (PtdIns) cycle and a number of excellent reviews have already been written [(see van Blitterswijk and Houssa, 2000; Kanoh et al., 2002; Mérida et al., 2008; Tu-Sekine and Raben, 2009, 2011; Shulga et al., 2011; Tu-Sekine et al., 2013) among others]. We now know there are ten mammalian DGKs that are organized into five classes. DGK-θ is the lone member of the Type V class of DGKs and remains as one of the least studied. This review focuses on our current understanding of the structure, enzymology, regulation, and physiological roles of this DGK and suggests some future areas of research to understand this DGK isoform.

  2. DGK-θ: Structure, Enzymology, and Physiological Roles.

    PubMed

    Tu-Sekine, Becky; Goldschmidt, Hana L; Raben, Daniel M

    2016-01-01

    Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PtdOH). The recognition of the importance of these enzymes has been increasing ever since it was determined that they played a role in the phosphatidylinositol (PtdIns) cycle and a number of excellent reviews have already been written [(see van Blitterswijk and Houssa, 2000; Kanoh et al., 2002; Mérida et al., 2008; Tu-Sekine and Raben, 2009, 2011; Shulga et al., 2011; Tu-Sekine et al., 2013) among others]. We now know there are ten mammalian DGKs that are organized into five classes. DGK-θ is the lone member of the Type V class of DGKs and remains as one of the least studied. This review focuses on our current understanding of the structure, enzymology, regulation, and physiological roles of this DGK and suggests some future areas of research to understand this DGK isoform. PMID:27683659

  3. DGK-θ: Structure, Enzymology, and Physiological Roles

    PubMed Central

    Tu-Sekine, Becky; Goldschmidt, Hana L.; Raben, Daniel M.

    2016-01-01

    Diacylglycerol kinases (DGKs) are a family of enzymes that catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to phosphatidic acid (PtdOH). The recognition of the importance of these enzymes has been increasing ever since it was determined that they played a role in the phosphatidylinositol (PtdIns) cycle and a number of excellent reviews have already been written [(see van Blitterswijk and Houssa, 2000; Kanoh et al., 2002; Mérida et al., 2008; Tu-Sekine and Raben, 2009, 2011; Shulga et al., 2011; Tu-Sekine et al., 2013) among others]. We now know there are ten mammalian DGKs that are organized into five classes. DGK-θ is the lone member of the Type V class of DGKs and remains as one of the least studied. This review focuses on our current understanding of the structure, enzymology, regulation, and physiological roles of this DGK and suggests some future areas of research to understand this DGK isoform. PMID:27683659

  4. HUMAN PARAOXONASE-1 (PON1): GENE STRUCTURE AND EXPRESSION, PROMISCUOUS ACTIVITIES AND MULTIPLE PHYSIOLOGICAL ROLES

    PubMed Central

    Mackness, Mike; Mackness, Bharti

    2015-01-01

    Human PON1 is a HDL-associated lipolactonase capable of preventing LDL and cell membrane oxidation and is therefore considered to be atheroprotective. PON1 contributes to the antioxidative function of HDL and reductions in HDL-PON1 activity, prevalent in a wide variety of diseases with an inflammatory component, is believed to lead to dysfunctional HDL which can promote inflammation and atherosclerosis. However, PON1 is multifunctional and may contribute to other HDL functions such as in innate immunity, preventing infection by quorum sensing gram negative bacteria by destroying acyl lactone mediators of quorum sensing, and putative new roles in cancer development and the promotion of healthy ageing. In this review we explore the physiological roles of PON1 in disease development, as well as PON1 gene and protein structure, promiscuous activities and the roles of SNPs and ethnicity in determining PON1 activity. PMID:25965560

  5. Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): present and future.

    PubMed

    Pérez-Pérez, María-Jesús; Priego, Eva-María; Hernández, Ana-Isabel; Familiar, Olga; Camarasa, María-José; Negri, Ana; Gago, Federico; Balzarini, Jan

    2008-09-01

    Human mitochondrial thymidine kinase (TK2) is a pyrimidine deoxynucleoside kinase (dNK) that catalyzes the phosphorylation of pyrimidine deoxynucleosides to their corresponding deoxynucleoside 5'-monophosphates by gamma-phosphoryl transfer from ATP. In resting cells, TK2 is suggested to play a key role in the mitochondrial salvage pathway to provide pyrimidine nucleotides for mitochondrial DNA (mtDNA) synthesis and maintenance. However, recently the physiological role of TK2turned out to have direct clinical relevance as well. Point mutations in the gene encoding TK2 have been correlated to mtDNA disorders in a heterogeneous group of patients suffering from the so-called mtDNA depletion syndrome (MDS). TK2 activity could also be involved in mitochondrial toxicity associated to prolonged treatment with antiviral nucleoside analogues like AZT and FIAU. Therefore, TK2 inhibitors can be considered as valuable tools to unravel the role of TK2 in the maintenance and homeostasis of mitochondrial nucleotide pools and mtDNA, and to clarify the contribution of TK2 activity to mitochondrial toxicity of certain antivirals. Highly selective TK-2 inhibitors having an acyclic nucleoside structure and efficiently discriminating between TK-2 and the closely related TK-1 have already been reported. It is actually unclear whether these agents efficiently reach the inner mitochondrial compartment. In the present review article,structural features of TK2, MDS-related mutations observed in TK2 and their role in MDS will be discussed. Also, an update on novel and selective TK2 inhibitors will be provided.

  6. The Growing Outer Epidermal Wall: Design and Physiological Role of a Composite Structure

    PubMed Central

    Kutschera, U.

    2008-01-01

    Background The cells of growing plant organs secrete an extracellular fibrous composite (the primary wall) that allows the turgid protoplasts to expand irreversibly via wall-yielding events, which are regulated by processes within the cytoplasm. The role of the epidermis in the control of stem elongation is described with special reference to the outer epidermal wall (OEW), which forms a ‘tensile skin’. Novel Facts The OEW is much thicker and less extensible than the walls of the inner tissues. Moreover, in the OEW the amount of cellulose per unit wall mass is considerably greater than in the inner tissues. Ultrastructural studies have shown that the expanding OEW is composed of a highly ordered internal and a diffuse outer half, with helicoidally organized cellulose microfibrils in the inner (load-bearing) region of this tension-stressed organ wall. The structural and mechanical backbone of the wall consists of helicoids, i.e. layers of parallel, inextensible cellulose microfibrils. These ‘plywood laminates’ contain crystalline ‘cables’ orientated in all directions with respect to the axis of elongation (isotropic material). Cessation of cell elongation is accompanied by a loss of order, i.e. the OEW is a dynamic structure. Helicoidally arranged extracellular polymers have also been found in certain bacteria, algae, fungi and animals. In the insect cuticle crystalline cutin nanofibrils form characteristic ‘OEW-like’ herringbone patterns. Conclusions Theoretical considerations, in vitro studies and computer simulations suggest that extracellular biological helicoids form by directed self-assembly of the crystalline biopolymers. This spontaneous generation of complex design ‘without an intelligent designer’ evolved independently in the protective ‘skin’ of plants, animals and many other organisms. PMID:18258808

  7. Crystal structure and potential physiological role of zebra fish thioesterase superfamily member 2 (fTHEM2)

    SciTech Connect

    Yu, Shanshan; Li, Han; Gao, Feng; Zhou, Ying

    2015-08-07

    Thioesterase superfamily member 2 (THEM2) is an essential protein for mammalian cell proliferation. It belongs to the hotdog-fold thioesterase superfamily and catalyzes hydrolysis of thioester bonds of acyl-CoA in vitro, while its in vivo function remains unrevealed. In this study, Zebra fish was selected as a model organism to facilitate the investigations on THEM2. First, we solved the crystal structure of recombinant fTHEM2 at the resolution of 1.80 Å, which displayed a similar scaffolding as hTHEM2. Second, functional studies demonstrated that fTHEM2 is capable of hydrolyzing palmitoyl-CoA in vitro. In addition, injection of morpholino against fTHEM2 at one-cell stage resulted in distorted early embryo development, including delayed cell division, retarded development and increased death rate. The above findings validated our hypothesis that fTHEM2 could serve as an ideal surrogate for studying the physiological functions of THEM2. - Highlights: • The crystal structure of recombinant fTHEM2 is presented. • fTHEM2 is capable of hydrolyzing palmitoyl-CoA. • The influence of fTHEM2 on early embryo development is demonstrated.

  8. Physiological Roles of Pneumococcal Peptidases

    PubMed Central

    Johnson, Mary K.

    1974-01-01

    A methionyl-specific dipeptidase from Streptococcus pneumoniae has been described. This enzyme and the pneumococcal tripeptidase have been shown to be intracellular, soluble, and constitutive. In addition to their function in cleavage of peptide nutrients, these peptidases may play a role in protein synthesis and turnover. PMID:4212242

  9. Advanced physiological roles of guanidinoacetic acid.

    PubMed

    Ostojic, Sergej M

    2015-12-01

    Dietary guanidinoacetic acid (GAA) seems to improve cellular bioenergetics by stimulating creatine biosynthesis. However, GAA could have other biological functions that might affect its possible use as a food ingredient in human nutrition. In this paper, we identified several alternative physiological roles of supplemental GAA, including the stimulation of hormonal release and neuromodulation, an alteration of metabolic utilization of arginine, and an adjustment of oxidant-antioxidant status. A better knowledge of how GAA affects human physiology may facilitate its use as an experimental nutritional intervention for novel purposes and conditions. PMID:26411433

  10. [The role of physiology in modern surgery].

    PubMed

    2006-04-01

    Through the analysis of recent achievements in the field of surgery we have demonstrated convincingly that physiological studies in both humans and animal models are the keystone of modern surgery. Physiological studies of blood circulation, respiration, digestion and other functions have laid the foundations for major fields of surgery. Their role is the most evident in the development of cardiac surgery. Notably, one of the outstanding breakthroughs in the medical science of the 20th century--the extracorporeal blood circulation--was made by the Russian physiologist S. S. Bryukhovenko. We have shown that noninvasive diagnostic procedures such as echocardiography are of outmost significance on all stages of the surgical treatment (pre- and intraoperational diagnostics and medical rehabilitation). The great impact of physiology on the development of surgery has also led to the progress of related fields of medicine--anesthesiology, intensive care, functional diagnostics, transplantation, rehabilitation, and many others.

  11. Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role in Mycobacterium tuberculosis physiology and host-pathogen interaction.

    PubMed

    Mishra, Arun K; Driessen, Nicole N; Appelmelk, Ben J; Besra, Gurdyal S

    2011-11-01

    Approximately one third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. This bacterium has an unusual lipid-rich cell wall containing a vast repertoire of antigens, providing a hydrophobic impermeable barrier against chemical drugs, thus representing an attractive target for vaccine and drug development. Apart from the mycolyl-arabinogalactan-peptidoglycan complex, mycobacteria possess several immunomodulatory constituents, notably lipomannan and lipoarabinomannan. The availability of whole-genome sequences of M. tuberculosis and related bacilli over the past decade has led to the identification and functional characterization of various enzymes and the potential drug targets involved in the biosynthesis of these glycoconjugates. Both lipomannan and lipoarabinomannan possess highly variable chemical structures, which interact with different receptors of the immune system during host-pathogen interactions, such as Toll-like receptors-2 and C-type lectins. Recently, the availability of mutants defective in the synthesis of these glycoconjugates in mycobacteria and the closely related bacterium, Corynebacterium glutamicum, has paved the way for host-pathogen interaction studies, as well as, providing attenuated strains of mycobacteria for the development of new vaccine candidates. This review provides a comprehensive account of the structure, biosynthesis and immunomodulatory properties of these important glycoconjugates.

  12. Physiological Roles of Aquaporin-4 in Brain

    PubMed Central

    Nagelhus, Erlend A.

    2013-01-01

    Aquaporin-4 (AQP4) is one of the most abundant molecules in the brain and is particularly prevalent in astrocytic membranes at the blood-brain and brain-liquor interfaces. While AQP4 has been implicated in a number of pathophysiological processes, its role in brain physiology has remained elusive. Only recently has evidence accumulated to suggest that AQP4 is involved in such diverse functions as regulation of extracellular space volume, potassium buffering, cerebrospinal fluid circulation, interstitial fluid resorption, waste clearance, neuroinflammation, osmosensation, cell migration, and Ca2+ signaling. AQP4 is also required for normal function of the retina, inner ear, and olfactory system. A review will be provided of the physiological roles of AQP4 in brain and of the growing list of data that emphasize the polarized nature of astrocytes. PMID:24137016

  13. Edaphic, structural and physiological contrasts across Amazon Basin forest-savanna ecotones suggest a role for potassium as a key modulator of tropical woody vegetation structure and function

    NASA Astrophysics Data System (ADS)

    Lloyd, J.; Domingues, T. F.; Schrodt, F.; Ishida, F. Y.; Feldpausch, T. R.; Saiz, G.; Quesada, C. A.; Schwarz, M.; Torello-Raventos, M.; Gilpin, M.; Marimon, B. S.; Marimon-Junior, B. H.; Ratter, J. A.; Grace, J.; Nardoto, G. B.; Veenendaal, E.; Arroyo, L.; Villarroel, D.; Killeen, T. J.; Steininger, M.; Phillips, O. L.

    2015-11-01

    Sampling along a precipitation gradient in tropical South America extending from ca. 0.8 to 2.0 m a-1, savanna soils had consistently lower exchangeable cation concentrations and higher C / N ratios than nearby forest plots. These soil differences were also reflected in canopy averaged leaf traits with savanna trees typically having higher leaf mass per unit area but lower mass-based nitrogen (Nm) and potassium (Km). Both Nm and Km also increased with declining mean annual precipitation (PA), but most area-based leaf traits such as leaf photosynthetic capacity showed no systematic variation with PA or vegetation type. Despite this invariance, when taken in conjunction with other measures such as mean canopy height, area-based soil exchangeable potassium content, [K]sa , proved to be an excellent predictor of several photosynthetic properties (including 13C isotope discrimination). Moreover, when considered in a multivariate context with PA and soil plant available water storage capacity (θP) as covariates, [K]sa also proved to be an excellent predictor of stand-level canopy area, providing drastically improved fits as compared to models considering just PA and/or θP. Neither calcium, nor magnesium, nor soil pH could substitute for potassium when tested as alternative model predictors (ΔAIC > 10). Nor for any model could simple soil texture metrics such as sand or clay content substitute for either [K]sa or θP. Taken in conjunction with recent work in Africa and the forests of the Amazon Basin, this suggests - in combination with some newly conceptualised interacting effects of PA and θP also presented here - a critical role for potassium as a modulator of tropical vegetation structure and function.

  14. Metabolic methanol: molecular pathways and physiological roles.

    PubMed

    Dorokhov, Yuri L; Shindyapina, Anastasia V; Sheshukova, Ekaterina V; Komarova, Tatiana V

    2015-04-01

    Methanol has been historically considered an exogenous product that leads only to pathological changes in the human body when consumed. However, in normal, healthy individuals, methanol and its short-lived oxidized product, formaldehyde, are naturally occurring compounds whose functions and origins have received limited attention. There are several sources of human physiological methanol. Fruits, vegetables, and alcoholic beverages are likely the main sources of exogenous methanol in the healthy human body. Metabolic methanol may occur as a result of fermentation by gut bacteria and metabolic processes involving S-adenosyl methionine. Regardless of its source, low levels of methanol in the body are maintained by physiological and metabolic clearance mechanisms. Although human blood contains small amounts of methanol and formaldehyde, the content of these molecules increases sharply after receiving even methanol-free ethanol, indicating an endogenous source of the metabolic methanol present at low levels in the blood regulated by a cluster of genes. Recent studies of the pathogenesis of neurological disorders indicate metabolic formaldehyde as a putative causative agent. The detection of increased formaldehyde content in the blood of both neurological patients and the elderly indicates the important role of genetic and biochemical mechanisms of maintaining low levels of methanol and formaldehyde.

  15. Selenoproteins: Molecular Pathways and Physiological Roles

    PubMed Central

    Labunskyy, Vyacheslav M.; Hatfield, Dolph L.; Gladyshev, Vadim N.

    2014-01-01

    Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by selenium-containing proteins (selenoproteins) that are present in all three domains of life. Although selenoproteins represent diverse molecular pathways and biological functions, all these proteins contain at least one selenocysteine (Sec), a selenium-containing amino acid, and most serve oxidoreductase functions. Sec is cotranslationally inserted into nascent polypeptide chains in response to the UGA codon, whose normal function is to terminate translation. To decode UGA as Sec, organisms evolved the Sec insertion machinery that allows incorporation of this amino acid at specific UGA codons in a process requiring a cis-acting Sec insertion sequence (SECIS) element. Although the basic mechanisms of Sec synthesis and insertion into proteins in both prokaryotes and eukaryotes have been studied in great detail, the identity and functions of many selenoproteins remain largely unknown. In the last decade, there has been significant progress in characterizing selenoproteins and selenoproteomes and understanding their physiological functions. We discuss current knowledge about how these unique proteins perform their functions at the molecular level and highlight new insights into the roles that selenoproteins play in human health. PMID:24987004

  16. Selenoproteins: molecular pathways and physiological roles.

    PubMed

    Labunskyy, Vyacheslav M; Hatfield, Dolph L; Gladyshev, Vadim N

    2014-07-01

    Selenium is an essential micronutrient with important functions in human health and relevance to several pathophysiological conditions. The biological effects of selenium are largely mediated by selenium-containing proteins (selenoproteins) that are present in all three domains of life. Although selenoproteins represent diverse molecular pathways and biological functions, all these proteins contain at least one selenocysteine (Sec), a selenium-containing amino acid, and most serve oxidoreductase functions. Sec is cotranslationally inserted into nascent polypeptide chains in response to the UGA codon, whose normal function is to terminate translation. To decode UGA as Sec, organisms evolved the Sec insertion machinery that allows incorporation of this amino acid at specific UGA codons in a process requiring a cis-acting Sec insertion sequence (SECIS) element. Although the basic mechanisms of Sec synthesis and insertion into proteins in both prokaryotes and eukaryotes have been studied in great detail, the identity and functions of many selenoproteins remain largely unknown. In the last decade, there has been significant progress in characterizing selenoproteins and selenoproteomes and understanding their physiological functions. We discuss current knowledge about how these unique proteins perform their functions at the molecular level and highlight new insights into the roles that selenoproteins play in human health. PMID:24987004

  17. Development of the field of structural physiology.

    PubMed

    Fujiyoshi, Yoshinori

    2015-01-01

    Electron crystallography is especially useful for studying the structure and function of membrane proteins - key molecules with important functions in neural and other cells. Electron crystallography is now an established technique for analyzing the structures of membrane proteins in lipid bilayers that closely simulate their natural biological environment. Utilizing cryo-electron microscopes with helium-cooled specimen stages that were developed through a personal motivation to understand the functions of neural systems from a structural point of view, the structures of membrane proteins can be analyzed at a higher than 3 Å resolution. This review covers four objectives. First, I introduce the new research field of structural physiology. Second, I recount some of the struggles involved in developing cryo-electron microscopes. Third, I review the structural and functional analyses of membrane proteins mainly by electron crystallography using cryo-electron microscopes. Finally, I discuss multifunctional channels named "adhennels" based on structures analyzed using electron and X-ray crystallography.

  18. Physiological roles of connexins and pannexins in reproductive organs.

    PubMed

    Kibschull, Mark; Gellhaus, Alexandra; Carette, Diane; Segretain, Dominique; Pointis, Georges; Gilleron, Jerome

    2015-08-01

    Reproductive organs are complex and well-structured tissues essential to perpetuate the species. In mammals, the male and female reproductive organs vary on their organization, morphology and function. Connectivity between cells in such tissues plays pivotal roles in organogenesis and tissue functions through the regulation of cellular proliferation, migration, differentiation and apoptosis. Connexins and pannexins can be seen as major regulators of these physiological processes. In the present review, we assembled several lines of evidence demonstrating that these two families of proteins are essential for male and female reproduction.

  19. Structural physiology based on electron crystallography

    PubMed Central

    Fujiyoshi, Yoshinori

    2011-01-01

    There are many questions in brain science, which are extremely interesting but very difficult to answer. For example, how do education and other experiences during human development influence the ability and personality of the adult? The molecular mechanisms underlying such phenomena are still totally unclear. However, technological and instrumental advancements of electron microscopy have facilitated comprehension of the structures of biological components, cells, and organelles. Electron crystallography is especially good for studying the structure and function of membrane proteins, which are key molecules of signal transduction in neural and other cells. Electron crystallography is now an established technique to analyze the structures of membrane proteins in lipid bilayers, which are close to their natural biological environment. By utilizing cryo-electron microscopes with helium cooled specimen stages, which were developed through a personal motivation to understand functions of neural systems from a structural point of view, structures of membrane proteins were analyzed at a resolution higher than 3 Å. This review has four objectives. First, it is intended to introduce the new research field of structural physiology. Second, it introduces some of the personal struggles, which were involved in developing the cryo-electron microscope. Third, it discusses some of the technology for the structural analysis of membrane proteins based on cryo-electron microscopy. Finally, it reviews structural and functional analyses of membrane proteins. PMID:21416541

  20. Structural and Functional Studies of γ-Carboxyglutamic Acid Domains of Factor VIIa and Activated Protein C: Role of Magnesium at Physiological Calcium

    PubMed Central

    Vadivel, Kanagasabai; Agah, Sayeh; Messer, Amanda S.; Cascio, Duilio; Bajaj, Madhu S.; Krishnaswamy, Sriram; Esmon, Charles T; Padmanabhan, Kaillathe; Bajaj, S. Paul

    2014-01-01

    Crystal structures of factor (F) VIIa/soluble (s) tissue factor (TF), obtained under high Mg2+ (50 mM Mg2+/5 mM Ca2+), have three of seven Ca2+-sites in the γ-Carboxyglutamic Acid (Gla) domain replaced by Mg2+ at positions 1, 4 and 7. We now report structures under low Mg2+ (2.5 mM Mg2+/5 mM Ca2+) as well as under high Ca2+ (5 mM Mg2+/45 mM Ca2+). Under low Mg2+, four Ca2+ and three Mg2+ occupy the same positions as in high Mg2+ structures. Conversely, under low Mg2+, reexamination of the structure of Gla domain of activated Protein C (APC) complexed with sEPCR has position 4 occupied by Ca2+ and positions 1 and 7 by Mg2+. Nonetheless, in direct binding experiments, Mg2+ replaced three Ca2+-sites in the unliganded Protein C or APC. Further, the high Ca2+-condition was necessary to replace Mg4 in the FVIIa/sTF structure. In biological studies, Mg2+ enhanced phospholipid binding to FVIIa and APC at physiological Ca2+. Additionally, Mg2+ potentiated phospholipid-dependent activations of FIX and FX by FVIIa/TF, and inactivation of FVa by APC. Since APC and FVIIa bind to sEPCR involving similar interactions, we conclude that under the low Mg2+-condition, sEPCR binding to APC-Gla (or FVIIa-Gla) replaces Mg4 by Ca4 with an attendant conformational change in the Gla domain ω-loop. Moreover, since phospholipid and sEPCR bind to FVIIa or APC via the ω-loop, we predict that phospholipid-binding also induces the functional Ca4 conformation in this loop. Cumulatively, the data illustrate that Mg2+ and Ca2+ act in concert to promote coagulation and anticoagulation. PMID:23454357

  1. Development of the field of structural physiology

    PubMed Central

    FUJIYOSHI, Yoshinori

    2015-01-01

    Electron crystallography is especially useful for studying the structure and function of membrane proteins — key molecules with important functions in neural and other cells. Electron crystallography is now an established technique for analyzing the structures of membrane proteins in lipid bilayers that closely simulate their natural biological environment. Utilizing cryo-electron microscopes with helium-cooled specimen stages that were developed through a personal motivation to understand the functions of neural systems from a structural point of view, the structures of membrane proteins can be analyzed at a higher than 3 Å resolution. This review covers four objectives. First, I introduce the new research field of structural physiology. Second, I recount some of the struggles involved in developing cryo-electron microscopes. Third, I review the structural and functional analyses of membrane proteins mainly by electron crystallography using cryo-electron microscopes. Finally, I discuss multifunctional channels named “adhennels” based on structures analyzed using electron and X-ray crystallography. PMID:26560835

  2. Role of quercetin in vascular physiology.

    PubMed

    Chirumbolo, Salvatore

    2012-12-01

    A recent paper in the Canadian Journal of Physiology and Pharmacology has shown that quercetin has a vascular protective effect associated with eNOS up-regulation, blood GSH redox ratio, and reduction of oxidative stress. Recent reports have recommended the consumption of quercetin, as it may contribute to a reduction in the risk of cardiovascular disease. However, the mechanisms by which quercetin exerts its action have not been fully elucidated. The majority of these mechanisms have been identified with models using animals treated with quercetin, and relatively few have been corroborated in human studies, which indicates the need for further investigation.

  3. Physiological and pathological roles of the mitochondrial permeability transition pore in the heart

    PubMed Central

    Kwong, Jennifer Q; Molkentin, Jeffery D

    2015-01-01

    Summary Prolonged mitochondrial permeability transition pore (MPTP) opening results in mitochondrial energetic dysfunction, organelle swelling, rupture and typically a type of necrotic cell death. However, acute opening of the MPTP has a critical physiologic role in regulating mitochondrial Ca2+ handling and metabolism. Despite the physiological and pathological roles that the MPTP orchestrates, the proteins that comprise the pore itself remain an area of ongoing investigation. Here, we will discuss the molecular composition of the MPTP and its role in regulating cardiac physiology and disease. A better understanding of MPTP structure and function will likely suggest novel cardioprotective therapeutic approaches. PMID:25651175

  4. Role of connexins and pannexins in cardiovascular physiology.

    PubMed

    Meens, Merlijn J; Kwak, Brenda R; Duffy, Heather S

    2015-08-01

    Connexins and pannexins form connexons, pannexons and membrane channels, which are critically involved in many aspects of cardiovascular physiology. For that reason, a vast number of studies have addressed the role of connexins and pannexins in the arterial and venous systems as well as in the heart. Moreover, a role for connexins in lymphatics has recently also been suggested. This review provides an overview of the current knowledge regarding the involvement of connexins and pannexins in cardiovascular physiology.

  5. Bioactive Pigments from Marine Bacteria: Applications and Physiological Roles

    PubMed Central

    Soliev, Azamjon B.; Hosokawa, Kakushi; Enomoto, Keiichi

    2011-01-01

    Research into natural products from the marine environment, including microorganisms, has rapidly increased over the past two decades. Despite the enormous difficulty in isolating and harvesting marine bacteria, microbial metabolites are increasingly attractive to science because of their broad-ranging pharmacological activities, especially those with unique color pigments. This current review paper gives an overview of the pigmented natural compounds isolated from bacteria of marine origin, based on accumulated data in the literature. We review the biological activities of marine compounds, including recent advances in the study of pharmacological effects and other commercial applications, in addition to the biosynthesis and physiological roles of associated pigments. Chemical structures of the bioactive compounds discussed are also presented. PMID:21961023

  6. Insights into the physiological role of CNS regeneration inhibitors

    PubMed Central

    Baldwin, Katherine T.; Giger, Roman J.

    2015-01-01

    The growth inhibitory nature of injured adult mammalian central nervous system (CNS) tissue constitutes a major barrier to robust axonal outgrowth and functional recovery following trauma or disease. Prototypic CNS regeneration inhibitors are broadly expressed in the healthy and injured brain and spinal cord and include myelin-associated glycoprotein (MAG), the reticulon family member NogoA, oligodendrocyte myelin glycoprotein (OMgp), and chondroitin sulfate proteoglycans (CSPGs). These structurally diverse molecules strongly inhibit neurite outgrowth in vitro, and have been most extensively studied in the context of nervous system injury in vivo. The physiological role of CNS regeneration inhibitors in the naïve, or uninjured, CNS remains less well understood, but has received growing attention in recent years and is the focus of this review. CNS regeneration inhibitors regulate myelin development and axon stability, consolidate neuronal structure shaped by experience, and limit activity-dependent modification of synaptic strength. Altered function of CNS regeneration inhibitors is associated with neuropsychiatric disorders, suggesting crucial roles in brain development and health. PMID:26113809

  7. Structural investigation into physiological DNA phosphorothioate modification

    PubMed Central

    Lan, Wenxian; Hu, Zhongpei; Shen, Jie; Wang, Chunxi; Jiang, Feng; Liu, Huili; Long, Dewu; Liu, Maili; Cao, Chunyang

    2016-01-01

    DNA phosphorothioate (PT) modification, with sulfur replacing a nonbridging phosphate oxygen in a sequence and stereo specific manner, is a novel physiological variation in bacteria. But what effects on DNA properties PT modification has is still unclear. To address this, we prepared three double-stranded (ds) DNA decamers, d(CGPXGCCGCCGA) with its complementary strand d(TCGGCGPXGCCG) (where X = O or S, i.e., PT-free dsDNA, [Sp, Sp]-PT dsDNA or [Rp, Rp]-PT dsDNA) located in gene of Streptomyces lividans. Their melting temperature (Tm) measurement indicates that [Rp, Rp]-PT dsDNA is most unstable. Their electron transfer potential detection presents an order of anti-oxidation properties: Sp-PT DNA > Rp-PT DNA > PT-free DNA. Their NMR structures demonstrate that PT modification doesn’t change their B-form conformation. The sulfur in [Rp, Rp]-PT dsDNA locates in the major groove, with steric effects on protons in the sugar close to modification sites, resulting in its unstability, and facilitating its selectively interactions with ScoMcrA. We thought that PT modification was dialectical to the bacteria. It protects the hosting bacteria by working as antioxidant against H2O2, and acts as a marker, directing restriction enzyme observed in other hosts, like ScoMcrA, to correctly cleave the PT modified DNA, so that bacteria cannot spread and survive. PMID:27169778

  8. Separating foliar physiology from morphology reveals the relative roles of vertically structured transpiration factors within red maple crowns and limitations of larger scale models.

    PubMed

    Bauerle, William L; Bowden, Joseph D

    2011-08-01

    A spatially explicit mechanistic model, MAESTRA, was used to separate key parameters affecting transpiration to provide insights into the most influential parameters for accurate predictions of within-crown and within-canopy transpiration. Once validated among Acer rubrum L. genotypes, model responses to different parameterization scenarios were scaled up to stand transpiration (expressed per unit leaf area) to assess how transpiration might be affected by the spatial distribution of foliage properties. For example, when physiological differences were accounted for, differences in leaf width among A. rubrum L. genotypes resulted in a 25% difference in transpiration. An in silico within-canopy sensitivity analysis was conducted over the range of genotype parameter variation observed and under different climate forcing conditions. The analysis revealed that seven of 16 leaf traits had a ≥5% impact on transpiration predictions. Under sparse foliage conditions, comparisons of the present findings with previous studies were in agreement that parameters such as the maximum Rubisco-limited rate of photosynthesis can explain ∼20% of the variability in predicted transpiration. However, the spatial analysis shows how such parameters can decrease or change in importance below the uppermost canopy layer. Alternatively, model sensitivity to leaf width and minimum stomatal conductance was continuous along a vertical canopy depth profile. Foremost, transpiration sensitivity to an observed range of morphological and physiological parameters is examined and the spatial sensitivity of transpiration model predictions to vertical variations in microclimate and foliage density is identified to reduce the uncertainty of current transpiration predictions.

  9. The role of cystatins in tick physiology and blood feeding

    PubMed Central

    Schwarz, Alexandra; Valdés, James J.; Kotsyfakis, Michalis

    2012-01-01

    Summary Ticks, as obligate hematophagous ectoparasites, impact greatly on animal and human health because they transmit various pathogens worldwide. Over the last decade, several cystatins from different hard and soft ticks were identified and biochemically analyzed for their role in the physiology and blood feeding lifestyle of ticks. All these cystatins are potent inhibitors of papain-like cysteine proteases, but not of legumain. Tick cystatins were either detected in the salivary glands and/or the midgut, key tick organs responsible for blood digestion and the expression of pharmacologically potent salivary proteins for blood feeding. For example, the transcription of two cystatins named HlSC-1 and Sialostatin L2 was highly upregulated in these tick tissues during feeding. Vaccinating hosts against Sialostatin L2 and Om-cystatin 2 as well as silencing of a cystatin gene from Amblyomma americanum significantly inhibited the feeding ability of ticks. Additionally, Om-cystatin 2 and Sialostatin L possessed strong host immunosuppressive properties by inhibiting dendritic cell maturation due to their interaction with cathepsin S. These two cystatins, together with Sialostatin L2 are the first tick cystatins with resolved three-dimensional structure. Sialostatin L, furthermore, showed preventive properties against autoimmune diseases. In the case of the cystatin Hlcyst-2, experimental evidence showed its role in tick innate immunity, since increased Hlcyst-2 transcript levels were detected in Babesia gibsoni-infected larval ticks and the protein inhibited Babesia growth. Other cystatins, such as Hlcyst-1 or Om-cystatin 2 are assumed to be involved in regulating blood digestion. Only for Bmcystatin was a role in tick embryogenesis suggested. Finally, all the biochemically analyzed tick cystatins are powerful protease inhibitors, and some may be novel antigens for developing anti-tick vaccines and drugs of medical importance due to their stringent target specificity

  10. The role of cystatins in tick physiology and blood feeding.

    PubMed

    Schwarz, Alexandra; Valdés, James J; Kotsyfakis, Michalis

    2012-06-01

    Ticks, as obligate hematophagous ectoparasites, impact greatly on animal and human health because they transmit various pathogens worldwide. Over the last decade, several cystatins from different hard and soft ticks were identified and biochemically analyzed for their role in the physiology and blood feeding lifestyle of ticks. All these cystatins are potent inhibitors of papain-like cysteine proteases, but not of legumain. Tick cystatins were either detected in the salivary glands and/or the midgut, key tick organs responsible for blood digestion and the expression of pharmacologically potent salivary proteins for blood feeding. For example, the transcription of two cystatins named HlSC-1 and Sialostatin L2 was highly upregulated in these tick tissues during feeding. Vaccinating hosts against Sialostatin L2 and Om-cystatin 2 as well as silencing of a cystatin gene from Amblyomma americanum significantly inhibited the feeding ability of ticks. Additionally, Om-cystatin 2 and Sialostatin L possessed strong host immunosuppressive properties by inhibiting dendritic cell maturation due to their interaction with cathepsin S. These two cystatins, together with Sialostatin L2 are the first tick cystatins with resolved three-dimensional structure. Sialostatin L, furthermore, showed preventive properties against autoimmune diseases. In the case of the cystatin Hlcyst-2, experimental evidence showed its role in tick innate immunity, since increased Hlcyst-2 transcript levels were detected in Babesia gibsoni-infected larval ticks and the protein inhibited Babesia growth. Other cystatins, such as Hlcyst-1 or Om-cystatin 2 are assumed to be involved in regulating blood digestion. Only for Bmcystatin was a role in tick embryogenesis suggested. Finally, all the biochemically analyzed tick cystatins are powerful protease inhibitors, and some may be novel antigens for developing anti-tick vaccines and drugs of medical importance due to their stringent target specificity.

  11. Fluid-Structure Interaction in Internal Physiological Flows

    NASA Astrophysics Data System (ADS)

    Heil, Matthias; Hazel, Andrew L.

    2011-01-01

    We provide a selective review of recent progress in the analysis of several physiological and physiologically inspired fluid-structure interaction problems, our aim being to explain the underlying physical mechanisms that cause the observed behaviors. Specifically, we discuss recent studies of self-excited oscillations in collapsible tubes, focusing primarily on studies of an idealized model system, the Starling resistor -- a device used in most laboratory experiments. We next review studies of a particular physiological, flow-induced oscillation: vocal-fold oscillations during phonation. Finally, we discuss the closure and reopening of pulmonary airways, physiological fluid-structure interaction problems that also involve the airways' liquid lining.

  12. Role of hydrogen sulfide in the physiology of penile erection.

    PubMed

    Qiu, Xuefeng; Villalta, Jackie; Lin, Guiting; Lue, Tom F

    2012-01-01

    Hydrogen sulfide (H(2)S), which is a well-known toxic gas, has recently been recognized as a biological messenger that plays an important role in physiological and pathophysiological conditions. Relatively high levels of H(2)S have been discovered in mammalian tissues. It is mainly synthesized by 2 enzymes, including cystathionine β-synthase and cystathionine γ-lysase, which utilize L-cysteine as substrate to produce H(2)S. H(2)S has been demonstrated to exhibit potent vasodilator activity both in vitro and in vivo by relaxing vascular smooth muscle. Recently, H(2)S has been discovered in penile tissue with smooth muscle relaxant effects. Furthermore, other effects of H(2)S could play a role in the physiology of erection. Understanding H(2)S in the physiology of erection might provide alternative erectile dysfunction strategies for those patients with poor or no response to type 5 phosphodiesterase inhibitors. This review intends to present the H(2)S pathway in penile tissue and the potential role of H(2)S in the physiology of erections.

  13. Structure and physiological function of calpains.

    PubMed Central

    Sorimachi, H; Ishiura, S; Suzuki, K

    1997-01-01

    For a long time now, two ubiquitously expressed mammalian calpain isoenzymes have been used to explore the structure and function of calpain. Although these two calpains, mu- and m-calpains, still attract intensive interest because of their unique characteristics, various distinct homologues to the protease domain of mu- and m-calpains have been identified in a variety of organisms. Some of these 'novel' calpain homologues are involved in important biological functions. For example, p94 (also called calpain 3), a mammalian calpain homologue predominantly expressed in skeletal muscle, is genetically proved to be responsible for limb-girdle muscular dystrophy type 2A. Tra-3, a calpain homologue in nematodes, is involved in the sex determination cascade during early development. PalB, a key gene product involved in the alkaline adaptation of Aspergillus nidulans, is the first example of a calpain homologue present in fungi. These findings indicate various important functional roles for intracellular proteases belonging to the calpain superfamily. PMID:9396712

  14. ClC-5: Physiological role and biophysical mechanisms.

    PubMed

    Pusch, Michael; Zifarelli, Giovanni

    2015-07-01

    Cl(-) transport in animal cells has fundamental physiological roles and it is mediated by a variety of protein families, one of them being the CLC family of ion channels and transporters. Besides their physiological relevance, CLC proteins show peculiar biophysical properties. This review will focus on a member of the CLC protein family, the endosomal Cl(-)/H(+) antiporter ClC-5. ClC-5 mutations cause Dent's disease, a renal syndrome due to defective protein reabsorption in the proximal tubule. This established the critical function of ClC-5 for endocytosis. However, our understanding of ClC-5's molecular role in endosomes and of its biophysical properties has proved elusive in spite of important progress achieved in the last two decades. Early models in which ClC-5 would provide a shunt conductance to enable efficient endosomal acidification conflicted with the antiport activity of ClC-5 that has more recently emerged. Currently, the physiological role of ClC-5 is hotly debated and its biophysical properties are still not fully understood.

  15. Dietary boron: progress in establishing essential roles in human physiology.

    PubMed

    Hunt, Curtiss D

    2012-06-01

    This review summarizes the progress made in establishing essential roles for boron in human physiology and assesses that progress in view of criteria for essentiality of elements. The evidence to date suggests that humans and at least some higher animals may use boron to support normal biological functions. These include roles in calcium metabolism, bone growth and maintenance, insulin metabolism, and completion of the life cycle. The biochemical mechanisms responsible for these effects are poorly understood but the nature of boron biochemistry suggests further characterization of the cell signaling molecules capable of complexing with boron. Such characterization may provide insights into the biochemical function(s) of boron in humans.

  16. The role thermal physiology plays in species invasion

    PubMed Central

    Kelley, Amanda L.

    2014-01-01

    The characterization of physiological phenotypes that may play a part in the establishment of non-native species can broaden our understanding about the ecology of species invasion. Here, an assessment was carried out by comparing the responses of invasive and native species to thermal stress. The goal was to identify physiological patterns that facilitate invasion success and to investigate whether these traits are widespread among invasive ectotherms. Four hypotheses were generated and tested using a review of the literature to determine whether they could be supported across taxonomically diverse invasive organisms. The four hypotheses are as follows: (i) broad geographical temperature tolerances (thermal width) confer a higher upper thermal tolerance threshold for invasive rather than native species; (ii) the upper thermal extreme experienced in nature is more highly correlated with upper thermal tolerance threshold for invasive vs. native animals; (iii) protein chaperone expression—a cellular mechanism that underlies an organism's thermal tolerance threshold—is greater in invasive organisms than in native ones; and (iv) acclimation to higher temperatures can promote a greater range of thermal tolerance for invasive compared with native species. Each hypothesis was supported by a meta-analysis of the invasive/thermal physiology literature, providing further evidence that physiology plays a substantial role in the establishment of invasive ectotherms. PMID:27293666

  17. Clarifying the Roles of Homeostasis and Allostasis in Physiological Regulation

    PubMed Central

    Ramsay, Douglas S.; Woods, Stephen C.

    2014-01-01

    Homeostasis, the dominant explanatory framework for physiological regulation, has undergone significant revision in recent years, with contemporary models differing significantly from the original formulation. Allostasis, an alternative view of physiological regulation, goes beyond its homeostatic roots, offering novel insights relevant to our understanding and treatment of several chronic health conditions. Despite growing enthusiasm for allostasis, the concept remains diffuse, due in part to ambiguity as to how the term is understood and used, impeding meaningful translational and clinical research on allostasis. Here we provide a more focused understanding of homeostasis and allostasis by explaining how both play a role in physiological regulation, and a critical analysis of regulation suggests how homeostasis and allostasis can be distinguished. Rather than focusing on changes in the value of a regulated variable (e.g., body temperature, body adiposity, or reward), research investigating the activity and relationship among the multiple regulatory loops that influence the value of these regulated variables may be the key to distinguishing homeostasis and allostasis. The mechanisms underlying physiological regulation and dysregulation are likely to have important implications for health and disease. PMID:24730599

  18. The role of antimicrobial peptides in cardiovascular physiology and disease.

    PubMed

    Li, Yifeng

    2009-12-18

    Antimicrobial peptides are natural peptide antibiotics, existing ubiquitously in both plant and animal kingdoms. They exhibit broad-spectrum antimicrobial activity and play an important role in host defense against invading microbes. Recently, these peptides have been shown to possess activities unrelated to direct microbial killing and be involved in the complex network of immune responses and inflammation. Thus, their role has now broadened beyond that of endogenous antibiotics. Because of their wide involvement in inflammatory response and the emerging role of inflammation in atherosclerosis, antimicrobial peptides have been proposed to represent an important link between inflammation and the pathogenesis of atherosclerotic cardiovascular diseases. This review highlights recent findings that support a role of these peptides in cardiovascular physiology and disease.

  19. Physiological Roles of Adipokines, Hepatokines, and Myokines in Ruminants.

    PubMed

    Roh, Sang-Gun; Suzuki, Yutaka; Gotoh, Takafumi; Tatsumi, Ryuichi; Katoh, Kazuo

    2016-01-01

    Since the discovery of leptin secreted from adipocytes, specialized tissues and cells have been found that secrete the several peptides (or cytokines) that are characterized to negatively and positively regulate the metabolic process. Different types of adipokines, hepatokines, and myokines, which act as cytokines, are secreted from adipose, liver, and muscle tissue, respectively, and have been identified and examined for their physiological roles in humans and disease in animal models. Recently, various studies of these cytokines have been conducted in ruminants, including dairy cattle, beef cattle, sheep, and goat. Interestingly, a few cytokines from these tissues in ruminants play an important role in the post-parturition, lactation, and fattening (marbling) periods. Thus, understanding these hormones is important for improving nutritional management in dairy cows and beef cattle. However, to our knowledge, there have been no reviews of the characteristics of these cytokines in beef and dairy products in ruminants. In particular, lipid and glucose metabolism in adipose tissue, liver tissue, and muscle tissue are very important for energy storage, production, and synthesis, which are regulated by these cytokines in ruminant production. In this review, we summarize the physiological roles of adipokines, hepatokines, and myokines in ruminants. This discussion provides a foundation for understanding the role of cytokines in animal production of ruminants. PMID:26732322

  20. Physiological Roles of Adipokines, Hepatokines, and Myokines in Ruminants

    PubMed Central

    Roh, Sang-Gun; Suzuki, Yutaka; Gotoh, Takafumi; Tatsumi, Ryuichi; Katoh, Kazuo

    2016-01-01

    Since the discovery of leptin secreted from adipocytes, specialized tissues and cells have been found that secrete the several peptides (or cytokines) that are characterized to negatively and positively regulate the metabolic process. Different types of adipokines, hepatokines, and myokines, which act as cytokines, are secreted from adipose, liver, and muscle tissue, respectively, and have been identified and examined for their physiological roles in humans and disease in animal models. Recently, various studies of these cytokines have been conducted in ruminants, including dairy cattle, beef cattle, sheep, and goat. Interestingly, a few cytokines from these tissues in ruminants play an important role in the post-parturition, lactation, and fattening (marbling) periods. Thus, understanding these hormones is important for improving nutritional management in dairy cows and beef cattle. However, to our knowledge, there have been no reviews of the characteristics of these cytokines in beef and dairy products in ruminants. In particular, lipid and glucose metabolism in adipose tissue, liver tissue, and muscle tissue are very important for energy storage, production, and synthesis, which are regulated by these cytokines in ruminant production. In this review, we summarize the physiological roles of adipokines, hepatokines, and myokines in ruminants. This discussion provides a foundation for understanding the role of cytokines in animal production of ruminants. PMID:26732322

  1. RANKL/OPG; Critical role in bone physiology.

    PubMed

    Martin, T John; Sims, Natalie A

    2015-06-01

    After it was proposed that the osteoblast lineage controlled the formation of osteoclasts, cell culture methods were developed that established this to be the case. Evidence was obtained that cytokines and hormones that promote osteoclast formation act first on osteoblast lineage cells to promote the production of a membrane-bound regulator of osteoclastogenesis. This proved to be receptor activator of NF-kB ligand (RANKL) a member of the tumor necrosis factor ligand family that acts upon its receptor RANK in the hematopoietic lineage, with interaction restricted by a decoy soluble receptor osteoprotegerin (OPG), also a product of the osteoblast lineage. The physiological roles of these factors were established through genetic and pharmacological studies, have led to a new physiology of bone, with complete revision of older ideas over the last 15 years, ultimately leading to the development of new pharmaceutical agents for bone disease.

  2. Physiological Implications of Myocardial Scar Structure.

    PubMed

    Richardson, William J; Clarke, Samantha A; Quinn, T Alexander; Holmes, Jeffrey W

    2015-10-01

    Once myocardium dies during a heart attack, it is replaced by scar tissue over the course of several weeks. The size, location, composition, structure, and mechanical properties of the healing scar are all critical determinants of the fate of patients who survive the initial infarction. While the central importance of scar structure in determining pump function and remodeling has long been recognized, it has proven remarkably difficult to design therapies that improve heart function or limit remodeling by modifying scar structure. Many exciting new therapies are under development, but predicting their long-term effects requires a detailed understanding of how infarct scar forms, how its properties impact left ventricular function and remodeling, and how changes in scar structure and properties feed back to affect not only heart mechanics but also electrical conduction, reflex hemodynamic compensations, and the ongoing process of scar formation itself. In this article, we outline the scar formation process following a myocardial infarction, discuss interpretation of standard measures of heart function in the setting of a healing infarct, then present implications of infarct scar geometry and structure for both mechanical and electrical function of the heart and summarize experiences to date with therapeutic interventions that aim to modify scar geometry and structure. One important conclusion that emerges from the studies reviewed here is that computational modeling is an essential tool for integrating the wealth of information required to understand this complex system and predict the impact of novel therapies on scar healing, heart function, and remodeling following myocardial infarction. PMID:26426470

  3. Physiological Implications of Myocardial Scar Structure

    PubMed Central

    Richardson, WJ; Clarke, SA; Quinn, TA; Holmes, JW

    2016-01-01

    Once myocardium dies during a heart attack, it is replaced by scar tissue over the course of several weeks. The size, location, composition, structure and mechanical properties of the healing scar are all critical determinants of the fate of patients who survive the initial infarction. While the central importance of scar structure in determining pump function and remodeling has long been recognized, it has proven remarkably difficult to design therapies that improve heart function or limit remodeling by modifying scar structure. Many exciting new therapies are under development, but predicting their long-term effects requires a detailed understanding of how infarct scar forms, how its properties impact left ventricular function and remodeling, and how changes in scar structure and properties feed back to affect not only heart mechanics but also electrical conduction, reflex hemodynamic compensations, and the ongoing process of scar formation itself. In this article, we outline the scar formation process following an MI, discuss interpretation of standard measures of heart function in the setting of a healing infarct, then present implications of infarct scar geometry and structure for both mechanical and electrical function of the heart and summarize experiences to date with therapeutic interventions that aim to modify scar geometry and structure. One important conclusion that emerges from the studies reviewed here is that computational modeling is an essential tool for integrating the wealth of information required to understand this complex system and predict the impact of novel therapies on scar healing, heart function, and remodeling following myocardial infarction. PMID:26426470

  4. Luteinizing hormone and human chorionic gonadotropin: distinguishing unique physiologic roles.

    PubMed

    Choi, Janet; Smitz, Johan

    2014-03-01

    Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are integral components of the hypothalamic-pituitary-gonadal axis, which controls sexual maturation and functionality. In the absence of signaling through their shared receptor, fetal sexual differentiation and post-natal development cannot proceed normally. Although they share a high degree of homology, the physiologic roles of these hormones are unique, governed by differences in expression pattern, biopotency and regulation. Whereas LH is a key regulator of gonadal steroidogenesis and ovulation, hCG is predominantly active in pregnancy and fetal development. Emerging evidence has revealed endogenous functions not previously ascribed to hCG, including participation in ovulation and fertilization, implantation, placentation and other activities in support of successful pregnancy. Spontaneous and induced mutations in LH, hCG and their mutual receptor have contributed substantially to our understanding of reproductive development and function. The lack of naturally occurring, functionally significant mutations in the β-subunit of hCG reinforce its putative role in establishment of pregnancy. Rescue of reproductive abnormalities resulting from aberrant gonadotropin signaling is possible in certain clinical contexts, depending on the nature of the underlying defect. By understanding the physiologic roles of LH and hCG in normal and pathologic states, we may better harness their diagnostic, prognostic and therapeutic potential.

  5. The physiologic role of alternative oxidase in Ustilago maydis.

    PubMed

    Juárez, Oscar; Guerra, Guadalupe; Velázquez, Isabel; Flores-Herrera, Oscar; Rivera-Pérez, R E; Pardo, Juan P

    2006-10-01

    Alternative oxidase (AOX) is a ubiquitous respiratory enzyme found in plants, fungi, protists and some bacterial species. One of the major questions about this enzyme is related to its metabolic role(s) in cellular physiology, due to its capacity to bypass the proton-pumping cytochrome pathway, and as a consequence it has great energy-wasting potential. In this study, the physiological role and regulatory mechanisms of AOX in the fungal phytopathogen Ustilago maydis were studied. We found evidence for at least two metabolic functions for AOX in this organism, as a major part of the oxidative stress-handling machinery, a well-described issue, and as part of the mechanisms that increase the metabolic plasticity of the cell, a role that might be valuable for organisms exposed to variations in temperature, nutrient source and availability, and biotic or abiotic factors that limit the activity of the cytochrome pathway. Experiments under different culture conditions of ecological significance for this organism revealed that AOX activity is modified by the growth stage of the culture, amino acid availability and growth temperature. In addition, nucleotide content, stimulation of AOX by AMP and respiratory rates obtained after inhibition of the cytochrome pathway showed that fungal/protist AOX is activated under low-energy conditions, in contrast to plant AOX, which is activated under high-energy conditions. An estimation of the contribution of AOX to cell respiration was performed by comparing the steady-state concentration of adenine nucleotides, the mitochondrial membrane potential, and the respiratory rate.

  6. Roles of lysophosphatidic acid in cardiovascular physiology and disease.

    PubMed

    Smyth, Susan S; Cheng, Hsin-Yuan; Miriyala, Sumitra; Panchatcharam, Manikandan; Morris, Andrew J

    2008-09-01

    The bioactive lipid mediator lysophosphatidic acid (LPA) exerts a range of effects on the cardiovasculature that suggest a role in a variety of critical cardiovascular functions and clinically important cardiovascular diseases. LPA is an activator of platelets from a majority of human donors identifying a possible role as a regulator of acute thrombosis and platelet function in atherogenesis and vascular injury responses. Of particular interest in this context, LPA is an effective phenotypic modulator of vascular smooth muscle cells promoting the de-differentiation, proliferation and migration of these cells that are required for the development of intimal hyperplasia. Exogenous administration of LPA results in acute and systemic changes in blood pressure in different animal species, suggesting a role for LPA in both normal blood pressure regulation and hypertension. Advances in our understanding of the molecular machinery responsible for the synthesis, actions and inactivation of LPA now promise to provide the tools required to define the role of LPA in cardiovascular physiology and disease. In this review we discuss aspects of LPA signaling in the cardiovasculature focusing on recent advances and attempting to highlight presently unresolved issues and promising avenues for further investigation.

  7. Roles of Lysophosphatidic Acid in Cardiovascular Physiology and Disease

    PubMed Central

    Smyth, Susan S.; Cheng, Hsin-Yuan; Miriyala, Sumitra; Panchatcharam, Manikandan; Morris, Andrew J.

    2008-01-01

    The bioactive lipid mediator lysophosphatidic acid (LPA) exerts a range of effects on the cardiovasculature that suggest a role in a variety of critical cardiovascular functions and clinically important cardiovascular diseases. LPA is an activator of platelets from a majority of human donors identifying a possible role as a regulator of acute thrombosis and platelet function in atherogenesis and vascular injury responses. Of particular interest in this context, LPA is an effective phenotypic modulator of vascular smooth muscle cells promoting the de-differentiation, proliferation and migration of these cells that is required for the development of intimal hyperplasia. Exogenous administration of LPA results in acute and systemic changes in blood pressure in different animal species, suggesting a role for LPA in both normal blood pressure regulation and hypertension. Advances in our understanding of the molecular machinery responsible for the synthesis, actions and inactivation of LPA now promises to provide the tools required to define the role of LPA in cardiovascular physiology and disease. In this review we discuss aspects of LPA signaling in the cardiovasculature focusing on recent advances and attempting to highlight presently unresolved issues and promising avenues for further investigation. PMID:18586114

  8. Microbial 2-Cys Peroxiredoxins: Insights into Their Complex Physiological Roles

    PubMed Central

    Toledano, Michel B.; Huang, Bo

    2016-01-01

    The peroxiredoxins (Prxs) constitute a very large and highly conserved family of thiol-based peroxidases that has been discovered only very recently. We consider here these enzymes through the angle of their discovery, and of some features of their molecular and physiological functions, focusing on complex phenotypes of the gene mutations of the 2-Cys Prxs subtype in yeast. As scavengers of the low levels of H2O2 and as H2O2 receptors and transducers, 2-Cys Prxs have been highly instrumental to understand the biological impact of H2O2, and in particular its signaling function. 2-Cys Prxs can also become potent chaperone holdases, and unveiling the in vivo relevance of this function, which is still not established, should further increase our knowledge of the biological impact and toxicity of H2O2. The diverse molecular functions of 2-Cys Prx explain the often-hard task of relating them to peroxiredoxin genes phenotypes, which underscores the pleiotropic physiological role of these enzymes and complex biologic impact of H2O2. PMID:26813659

  9. Membrane localization diversity of TPK channels and their physiological role

    PubMed Central

    Isayenkov, Stanislav; Isner, Jean-Charles

    2011-01-01

    Potassium (K) is one of the major nutrients that is essential for plant growth and development. The majority of cellular K+ resides in the vacuole and tonoplast K+ channels of the TPK (Two Pore K) family are main players in cellular K+ homeostasis. All TPK channels were previously reported to be expressed in the tonoplast of the large central lytic vacuole (LV) except for one isoform in Arabidopsis that resides in the plasma membrane. However, plant cells often contain more than one type of vacuole that coexist in the same cell. We recently showed that two TPK isoforms (OsTPKa and OsTPKb) from Oryza sativa localize to different vacuoles with OsTPKa predominantly found in the LV tonoplast and OsTPKb primarily in smaller compartments that resemble small vacuoles (SVs). Our study further revealed that it is the C-terminal domain that determines differential targeting of OsTPKa and OsTPKb. Three C-terminal amino acids were particularly relevant for targeting TPKs to their respective endomembranes. In this addendum we further evaluate how the different localization of TPKa and TPKb impact on their physiological role and how TPKs provide a potential tool to study the physiology of different types of vacuole. PMID:21757998

  10. The role of physiological studies and apnoea monitoring in infants.

    PubMed

    Horne, Rosemary S C; Nixon, Gillian M

    2014-12-01

    There is evidence that failure of cardio-respiratory control mechanisms plays a role in the final event of the Sudden Infant Death Syndrome (SIDS). Physiological studies during sleep in both healthy term born infants and those at increased risk for SIDS have been widely used to investigate how the major risk and protective factors for SIDS identified from epidemiological studies might alter infant physiology. Clinical polysomnography (PSG) in infants who eventually succumbed to SIDS however demonstrated abnormalities that were neither sufficiently distinctive nor predictive to support routine use of PSG for infants at risk for SIDS. PSG findings have also been shown to be not predictive of recurrence of Apparent Life Threatening Events (ALTE) and thus international guidelines state that PSG is not indicated for routine evaluation in infants with an uncomplicated ALTE, although PSG may be indicated when there is clinical evidence of a sleep related breathing disorder. A decision to undertake home apnoea monitoring should consider the potential advantages and disadvantages of monitoring for that individual, in the knowledge that there is no evidence of the efficacy of such devices in preventing SIDS. PMID:25304428

  11. Role of bone morphogenetic proteins in adrenal physiology and disease.

    PubMed

    Johnsen, Inga K; Beuschlein, Felix

    2010-04-01

    Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily of ligands that impact on a multitude of biological processes including cell type specification, differentiation and organogenesis. Furthermore, a large body of evidence points towards important BMP-dependent mechanisms in tumorigenesis. In accordance with their diverse actions, BMPs have been demonstrated to serve as auto-, para- and endocrine modulators also in a number of hormonal systems. In this review, we highlight novel aspects of BMP-dependent regulatory networks that pertain to adrenal physiology and disease, which have been uncovered during recent years. These aspects include the role of BMP-dependent mechanism during adrenal development, modulating effects on catecholamine synthesis and steroidogenesis and dysregulation of BMP signalling in adrenal tumorigenesis. Furthermore, we summarize potential therapeutic approaches that are based on reconstitution of BMP signalling in adrenocortical tumour cells. PMID:20133384

  12. [Steroid hormones: their physiological role and diagnostic value during pregnancy].

    PubMed

    Shmagel', K V; Chereshnev, V A

    2004-01-01

    Steroid hormones play a key role in the beginning, development and termination of gestation. This reveiw is devoted for physiological effects of estrogens, progesterone, cortisole, ACTH, CRH in various pregnancy events: implantation, fetus development, maternal adaptation and birth initiation. Priority is fixed for estrogens--steroids that vastly increase maternal circulating blood value, induce progesterone action on uterus, regulate fetal "hypothalamic-pituitary-adrenocortical" axis, control free cortisole level in feminine blood. Diagnostic criterions of steroid hormone determination durijng pregnancy are presented. To day unconjugated estriol is the only steroid hormone that implicated in total pregnancy screening programs. Its concentration reduction has been noted in pregnancies with Dawn syndrome, some child enzyme defetcs, intrauterine growth retardation and fetal death incidents.

  13. Porifera Lectins: Diversity, Physiological Roles and Biotechnological Potential.

    PubMed

    Gardères, Johan; Bourguet-Kondracki, Marie-Lise; Hamer, Bojan; Batel, Renato; Schröder, Heinz C; Müller, Werner E G

    2015-08-07

    An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using affinity chromatography and gel filtration techniques. Other protocols were also developed in order to collect and study sponge lectins, including screening of sponge genomes and expression in heterologous bacterial systems. The characterization of the lectins was performed by Edman degradation or mass spectrometry. Regarding their physiological roles, sponge lectins showed to be involved in morphogenesis and cell interaction, biomineralization and spiculogenesis, as well as host defense mechanisms and potentially in the association between the sponge and its microorganisms. In addition, these lectins exhibited a broad range of bioactivities, including modulation of inflammatory response, antimicrobial and cytotoxic activities, as well as anticancer and neuromodulatory activity. In view of their potential pharmacological applications, sponge lectins constitute promising molecules of biotechnological interest.

  14. The molecular mechanism and physiological role of cytoplasmic streaming.

    PubMed

    Tominaga, Motoki; Ito, Kohji

    2015-10-01

    Cytoplasmic streaming occurs widely in plants ranging from algae to angiosperms. However, the molecular mechanism and physiological role of cytoplasmic streaming have long remained unelucidated. Recent molecular genetic approaches have identified specific myosin members (XI-2 and XI-K as major and XI-1, XI-B, and XI-I as minor motive forces) for the generation of cytoplasmic streaming among 13 myosin XIs in Arabidopsis thaliana. Simultaneous knockout of these myosin XI members led to a reduced velocity of cytoplasmic streaming and marked defects of plant development. Furthermore, the artificial modifications of myosin XI-2 velocity changed plant and cell sizes along with the velocity of cytoplasmic streaming. Therefore, we assume that cytoplasmic streaming is one of the key regulators in determining plant size.

  15. Biology 23. Unit One -- The Cell: Structure and Physiology.

    ERIC Educational Resources Information Center

    Nederland Independent School District, TX.

    GRADES OR AGES: Not given. SUBJECT MATTER: Biology, the structure and physiology of the cell. ORGANIZATION AND PHYSICAL APPEARANCE: There are four sections: a) objectives for the unit, b) bibliography, c) activities, and d) evaluation. The guide is directed to the student rather than the teacher. The guide is mimeographed and stapled, with no…

  16. Physiology

    ERIC Educational Resources Information Center

    Kay, Ian

    2008-01-01

    Underlying recent developments in health care and new treatments for disease are advances in basic medical sciences. This edition of "Webwatch" focuses on sites dealing with basic medical sciences, with particular attention given to physiology. There is a vast amount of information on the web related to physiology. The sites that are included here…

  17. Physiologic evidence for the interpersonal role of laughter during psychotherapy.

    PubMed

    Marci, Carl D; Moran, Erin K; Orr, Scott P

    2004-10-01

    The role of laughter during psychotherapy is poorly understood. This study examined 10 unique sessions of psychodynamic psychotherapy with digital videotape and simultaneous measures of skin conductivity (SC) from patients and therapists. Independent observers coded laugh episodes using published criteria. Observers identified 167 laugh responses. Of the 119 patient laughs, 91 (76.5%) were patient as speaker, compared with 28 (23.4%) as nonspeaker audience. In contrast, of the 48 therapist laughs, only five (10.4%) were therapist as speaker, whereas 43 (90.3%) were as nonspeaker audience. The difference was highly significant (p < .001). Physiologic data showed that mean SC level increased regardless of role as patient, therapist, speaker, or audience (p < .001). Two-factor analysis of variance indicated that SC change scores were significantly larger when patients and therapists laughed together compared with laughing alone (p < .05). The results support an empirically based approach to the study of laughter and the use of psychophysiology as a measure of process during psychotherapy.

  18. The role of heart rate variability in sports physiology

    PubMed Central

    DONG, JIN-GUO

    2016-01-01

    Heart rate variability (HRV) is a relevant marker reflecting cardiac modulation by sympathetic and vagal components of the autonomic nervous system (ANS). Although the clinical application of HRV is mainly associated with the prediction of sudden cardiac death and assessing cardiovascular and metabolic illness progression, recent observations have suggested its applicability to physical exercise training. HRV is becoming one of the most useful tools for tracking the time course of training adaptation/maladaptation of athletes and in setting the optimal training loads leading to improved performances. However, little is known regarding the role of HRV and the internal effects of physical exercise on an athlete, which may be useful in designing fitness programs ensuring sufficient training load that may correspond with the specific ability of the athlete. In this review, we offer a comprehensive assessment of investigations concerning the interrelation between HRV and ANS, and examine how the application of HRV to physical exercise may play a role in sports physiology. PMID:27168768

  19. The role of endogenous H2S in cardiovascular physiology.

    PubMed

    Skovgaard, Nini; Gouliaev, Anja; Aalling, Mathilde; Simonsen, Ulf

    2011-09-01

    Recent research has shown that the endogenous gas hydrogen sulphide (H2S) is a signalling molecule of considerable biological potential and has been suggested to be involved in a vast number of physiological processes. In the vascular system, H2S is synthesized from cysteine by cystathionine-γ-lyase (CSE) in smooth muscle cells (SMC) and 3- mercaptopyruvate sulfuresterase (3MST) and CSE in the endothelial cells. In pulmonary and systemic arteries, H2S induces relaxation and/or contraction dependent on the concentration of H2S, type of vessel and species. H2S relaxes SMC through a direct effect on KATP-channels or Kv-channels causing hyperpolarization and closure of voltage-dependent Ca2+-channels followed by a reduction in intracellular calcium. H2S also relaxes SMC through the release of endothelium- derived hyperpolarizing factor (EDHF) and nitric oxide (NO) from the endothelium. H2S contracts SMC through a reduction in nitric oxide (NO) availability by reacting with NO forming a nitrosothiol compound and through an inhibitory effect on endothelial nitric oxide synthase (eNOS) as well as a reduction in SMC cyclic AMP concentration. Evidence supports a role for H2S in oxygen sensing. Furthermore, reduced endogenous H2S production may also play a role in ischemic heart diseases and hypertension, and treatment with H2S donors and cysteine analogues may be beneficial in treatment of cardiovascular disease.

  20. The role of endogenous aryl hydrocarbon receptor signaling in cardiovascular physiology

    PubMed Central

    Zhang, Nan

    2011-01-01

    The aryl hydrocarbon receptor (AHR) is an orphan nuclear receptor with a primary function of mediating xenobiotic metabolism through transcriptional activation of Phase I and Phase II drug-metabolizing enzymes. Although no high-affinity physiological activators of AHR have been discovered, the endogenous signaling of the AHR pathway is believed to play an important role in the development and function of the cardiovascular system, based on the observations on ahr gene-deficient mice. The AHR knockout mice develop cardiac hypertrophy, abnormal vascular structure in multiple organs and altered blood pressure depending on their host environment. In this review, the endogenous role of AHR in cardiovascular physiology, including heart function, vascular development and blood pressure regulation has been summarized and discussed. PMID:21814412

  1. The role of endogenous aryl hydrocarbon receptor signaling in cardiovascular physiology.

    PubMed

    Zhang, Nan

    2011-04-01

    The aryl hydrocarbon receptor (AHR) is an orphan nuclear receptor with a primary function of mediating xenobiotic metabolism through transcriptional activation of Phase I and Phase II drug-metabolizing enzymes. Although no high-affinity physiological activators of AHR have been discovered, the endogenous signaling of the AHR pathway is believed to play an important role in the development and function of the cardiovascular system, based on the observations on ahr gene-deficient mice. The AHR knockout mice develop cardiac hypertrophy, abnormal vascular structure in multiple organs and altered blood pressure depending on their host environment. In this review, the endogenous role of AHR in cardiovascular physiology, including heart function, vascular development and blood pressure regulation has been summarized and discussed.

  2. Porifera Lectins: Diversity, Physiological Roles and Biotechnological Potential

    PubMed Central

    Gardères, Johan; Bourguet-Kondracki, Marie-Lise; Hamer, Bojan; Batel, Renato; Schröder, Heinz C.; Müller, Werner E. G.

    2015-01-01

    An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using affinity chromatography and gel filtration techniques. Other protocols were also developed in order to collect and study sponge lectins, including screening of sponge genomes and expression in heterologous bacterial systems. The characterization of the lectins was performed by Edman degradation or mass spectrometry. Regarding their physiological roles, sponge lectins showed to be involved in morphogenesis and cell interaction, biomineralization and spiculogenesis, as well as host defense mechanisms and potentially in the association between the sponge and its microorganisms. In addition, these lectins exhibited a broad range of bioactivities, including modulation of inflammatory response, antimicrobial and cytotoxic activities, as well as anticancer and neuromodulatory activity. In view of their potential pharmacological applications, sponge lectins constitute promising molecules of biotechnological interest. PMID:26262628

  3. [Protein carbonylation and its role in physiological processes in plants].

    PubMed

    Debska, Karolina; Bogatek, Renata; Gniazdowska, Agnieszka

    2012-01-01

    Plant cells produce reactive oxygen species (ROS) continuously as a byproducts of oxygen metabolism and reaction to various environmental stresses. ROS are considered as chemicals inducing damage of cellular components (DNA, lipids and proteins), but also might act as signaling agents. Protein oxidation is one of covalent modification of protein induced by ROS or other products of oxidative stress. Carbonylation of particular amino acid residues (arginine, lysine, treonine or proline) is one of the most commonly occurring oxidative modification of proteins. This modification might lead to alteration in protein activity, its proteolytic breakdown or, in the opposite, aggregate formation. Carbonylated proteins have been identified in many plant species at different stage of growth and development. The analysis of subcellular localization of carbonylated proteins arised the hypothesis on their signaling function. We summarize the current knowledge on the detection of carbonylation protein in plants taking to the account the conditions which may influence their production or removal. We present also their putative role in plant physiology and discuss interaction between ROS and RNS in regulation of protein carbonylation. PMID:23214127

  4. Porifera Lectins: Diversity, Physiological Roles and Biotechnological Potential.

    PubMed

    Gardères, Johan; Bourguet-Kondracki, Marie-Lise; Hamer, Bojan; Batel, Renato; Schröder, Heinz C; Müller, Werner E G

    2015-08-01

    An overview on the diversity of 39 lectins from the phylum Porifera is presented, including 38 lectins, which were identified from the class of demosponges, and one lectin from the class of hexactinellida. Their purification from crude extracts was mainly performed by using affinity chromatography and gel filtration techniques. Other protocols were also developed in order to collect and study sponge lectins, including screening of sponge genomes and expression in heterologous bacterial systems. The characterization of the lectins was performed by Edman degradation or mass spectrometry. Regarding their physiological roles, sponge lectins showed to be involved in morphogenesis and cell interaction, biomineralization and spiculogenesis, as well as host defense mechanisms and potentially in the association between the sponge and its microorganisms. In addition, these lectins exhibited a broad range of bioactivities, including modulation of inflammatory response, antimicrobial and cytotoxic activities, as well as anticancer and neuromodulatory activity. In view of their potential pharmacological applications, sponge lectins constitute promising molecules of biotechnological interest. PMID:26262628

  5. Role of adult hippocampal neurogenesis in cognition in physiology and disease: pharmacological targets and biomarkers.

    PubMed

    Costa, Veronica; Lugert, Sebastian; Jagasia, Ravi

    2015-01-01

    Adult hippocampal neurogenesis is a remarkable form of brain structural plasticity by which new functional neurons are generated from adult neural stem cells/precursors. Although the precise role of this process remains elusive, adult hippocampal neurogenesis is important for learning and memory and it is affected in disease conditions associated with cognitive impairment, depression, and anxiety. Immature neurons in the adult brain exhibit an enhanced structural and synaptic plasticity during their maturation representing a unique population of neurons to mediate specific hippocampal function. Compelling preclinical evidence suggests that hippocampal neurogenesis is modulated by a broad range of physiological stimuli which are relevant in cognitive and emotional states. Moreover, multiple pharmacological interventions targeting cognition modulate adult hippocampal neurogenesis. In addition, recent genetic approaches have shown that promoting neurogenesis can positively modulate cognition associated with both physiology and disease. Thus the discovery of signaling pathways that enhance adult neurogenesis may lead to therapeutic strategies for improving memory loss due to aging or disease. This chapter endeavors to review the literature in the field, with particular focus on (1) the role of hippocampal neurogenesis in cognition in physiology and disease; (2) extrinsic and intrinsic signals that modulate hippocampal neurogenesis with a focus on pharmacological targets; and (3) efforts toward novel strategies pharmacologically targeting neurogenesis and identification of biomarkers of human neurogenesis.

  6. Role of adult hippocampal neurogenesis in cognition in physiology and disease: pharmacological targets and biomarkers.

    PubMed

    Costa, Veronica; Lugert, Sebastian; Jagasia, Ravi

    2015-01-01

    Adult hippocampal neurogenesis is a remarkable form of brain structural plasticity by which new functional neurons are generated from adult neural stem cells/precursors. Although the precise role of this process remains elusive, adult hippocampal neurogenesis is important for learning and memory and it is affected in disease conditions associated with cognitive impairment, depression, and anxiety. Immature neurons in the adult brain exhibit an enhanced structural and synaptic plasticity during their maturation representing a unique population of neurons to mediate specific hippocampal function. Compelling preclinical evidence suggests that hippocampal neurogenesis is modulated by a broad range of physiological stimuli which are relevant in cognitive and emotional states. Moreover, multiple pharmacological interventions targeting cognition modulate adult hippocampal neurogenesis. In addition, recent genetic approaches have shown that promoting neurogenesis can positively modulate cognition associated with both physiology and disease. Thus the discovery of signaling pathways that enhance adult neurogenesis may lead to therapeutic strategies for improving memory loss due to aging or disease. This chapter endeavors to review the literature in the field, with particular focus on (1) the role of hippocampal neurogenesis in cognition in physiology and disease; (2) extrinsic and intrinsic signals that modulate hippocampal neurogenesis with a focus on pharmacological targets; and (3) efforts toward novel strategies pharmacologically targeting neurogenesis and identification of biomarkers of human neurogenesis. PMID:25977081

  7. Role of Computer Graphics in Simulations for Teaching Physiology.

    ERIC Educational Resources Information Center

    Modell, H. I.; And Others

    1983-01-01

    Discusses a revision of existing respiratory physiology simulations to promote active learning experiences for individual students. Computer graphics were added to aid student's conceptualization of the physiological system. Specific examples are provided, including those dealing with alveolar gas equations and effects of anatomic shunt flow on…

  8. Discovery of cytoglobin and its roles in physiology and pathology of hepatic stellate cells

    PubMed Central

    YOSHIZATO, Katsutoshi; THUY, Le Thi Thanh; SHIOTA, Goshi; KAWADA, Norifumi

    2016-01-01

    Cytoglobin (CYGB), a new member of the globin family, was discovered in 2001 as a protein associated with stellate cell activation (stellate cell activation-associated protein [STAP]). Knowledge of CYGB, including its crystal, gene, and protein structures as well as its physiological and pathological importance, has increased progressively. We investigated the roles of oxygen (O2)-binding CYGB as STAP in hepatic stellate cells (HSCs) to understand the part played by this protein in their pathophysiological activities. Studies involving CYGB-gene-deleted mice have led us to suppose that CYGB functions as a regulator of O2 homeostasis; when O2 homeostasis is disrupted, HSCs are activated and play a key role(s) in hepatic fibrogenesis. In this review, we discuss the rationale for this hypothesis. PMID:26972599

  9. The Evolving Role of Animal Laboratories in Physiology Instruction

    ERIC Educational Resources Information Center

    Ra'anan, Alice W.

    2005-01-01

    Laboratory exercises are intended to illustrate concepts and add an active learning component to courses. Since the 1980s, there has been a decline in animal laboratories offered in conjunction with medical physiology courses. The most important single reason for this is cost, but other contributing factors include the development of computer…

  10. [Epicardial adipose tissue and its role in cardiac physiology and disease].

    PubMed

    Toczyłowski, Kacper; Gruca, Michał; Baranowski, Marcin

    2013-06-20

    Adipose tissue secretes a number of cytokines, referred to as adipokines. Intensive studies conducted over the last two decades showed that adipokines exert broad effects on cardiac metabolism and function. In addition, the available data strongly suggests that these cytokines play an important role in development of cardiovascular diseases. Epicardial adipose tissue (EAT) has special properties that distinguish it from other deposits of visceral fat. Overall, there appears to be a close functional and anatomic relationship between the EAT and the cardiac muscle. They share the same coronary blood supply, and there is no structure separating the adipose tissue from the myocardium or coronary arteries. The role of EAT in osierdziocardiac physiology remains unclear. Its putative functions include buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, regulating fatty acid homeostasis in the coronary microcirculation, thermogenesis, and neuroprotection of the cardiac autonomic ganglia and nerves. Obesity (particularly the abdominal phenotype) leads to elevated EAT content, and the available data suggests that high amount of this fat depot is associated with increased risk of ischemic heart disease, cardiac hypertrophy and diastolic dysfunction. The mass of EAT is small compared to other fat deposits in the body. Nevertheless, its close anatomic relationship to the heart suggests that this organ is highly exposed to EAT-derived adipokines which makes this tissue a very promising area of research. In this paper we review the current knowledge on the role of EAT in cardiac physiology and development of heart disease.

  11. The role of physiologically based pharmacokinetic modeling in regulatory review.

    PubMed

    Huang, S-M; Rowland, M

    2012-03-01

    During regulatory review of clinical pharmacology data in new drug applications and biologics license applications, questions are routinely asked about how intrinsic factors (e.g., organ dysfunction, age, and genetics) and extrinsic factors (e.g., drug-drug interactions) might influence dose-response and exposure-response and about the impact of these individual factors on the efficacy and safety of the candidate compound. Physiologically based pharmacokinetic (PBPK) modeling and simulation is one of the tools that can be used to address these critical questions. PMID:22318616

  12. Exosomes: Fundamental Biology and Roles in Cardiovascular Physiology.

    PubMed

    Ibrahim, Ahmed; Marbán, Eduardo

    2016-01-01

    Exosomes are nanosized membrane particles that are secreted by cells that transmit information from cell to cell. The information within exosomes prominently includes their protein and RNA payloads. Exosomal microRNAs in particular can potently and fundamentally alter the transcriptome of recipient cells. Here we summarize what is known about exosome biogenesis, content, and transmission, with a focus on cardiovascular physiology and pathophysiology. We also highlight some of the questions currently under active investigation regarding these extracellular membrane vesicles and their potential in diagnostic and therapeutic applications.

  13. [The physiological determinants of the parallelism (unity) of histological structures].

    PubMed

    Natochin, Iu V

    1986-03-01

    The theory of structural parallelism put forward by A. A. Zavarzin (Senior) has been supported by the analysis of cytological specificity of effector organs involved in water-salt homeostasis, and of the excretory system of vertebrates and invertebrates. The similarity in morphofunctional organization of different excretory organs (i.e. the presence of ultrafiltration apparatus and cells which make it possible to absorb all vitally important substances) is likely to result from the fact that the excretory organ should excrete not only the final products of metabolism, but also any exogenic substances in addition to those which although important, are excessive for the organism. The brush border of asymmetrical epithelial cells of excretory organs is presumably a morphological expression of the structure which accounts for the inward transport of all physiologically important substances. Specificity of the membrane mechanism of water and sodium transport accounts for the identical principles in the structure of cells and areas of cell contacts of epithelia in different organs involved in the formation of hypotonic (saliva glands, renal tubules) or hypertonic fluids (salt glands, marine teleost gills). PMID:3715974

  14. The Cajal school and the physiological role of astrocytes: a way of thinking

    PubMed Central

    Navarrete, Marta; Araque, Alfonso

    2014-01-01

    Cajal is widely recognized by the scientific community for his important contributions to our knowledge of the neuronal organization of the nervous system. His studies on neuroglial cells are less recognized, yet they are no less relevant to our current understanding of the cellular bases of brain structure. Two pioneering studies published a century ago –“Something about the physiological significance of neuroglia” (Ramón y Cajal, 1897) and “A contribution to the understanding of neuroglia in the human brain” (Ramón y Cajal, 1913)—focused on glial cells and their role in brain physiology. Novel findings obtained using state-of-the-art and sophisticated technologies largely confirm many of the groundbreaking hypotheses proposed by Cajal related to the structural-functional properties of neuroglia. Here we propose to the reader a journey guided by the ideas of Cajal through the recent findings on the functional significance of astrocytes, the most abundant neuroglial cell type in the nervous system. Astrocyte–neuron interaction, which represents an emerging field in current neuroscience with important implications for our understanding of the cellular processes underlying brain function, has its roots in many of the original concepts proposed by Cajal. PMID:24904302

  15. [Arterial baroreflex--physiological role and assessment of functioning].

    PubMed

    Tkaczyszyn, Michał; Rydlewska, Agnieszka; Ponikowska, Beata; Borodulin-Nadzieja, Ludmiła; Banasiak, Waldemar; Ponikowski, Piotr; Jankowska, Ewa A

    2013-08-01

    Arterial baroreflex is one of the key mechanisms responsible for the homeostasis maintenance within the cardiovascular system. Through the modulation of sympathetic and parasympathetic drive within the autonomic nervous system, baroreflex enables to stabilize arterial blood pressure and maintain perfusion within critical organs (e.g. brain, heart). This review provides the physiological background of the baroreflex functioning and describes the methodology for assessing the arterial baroreflex sensitivity (BRS). Decreased BRS reflects autonomic imbalance and predicts unfavorable outcome in cardiovascular diseases accompanied by the autonomic dysfunction, such as arterial hypertension and heart failure. BRS assessment methods can be divided into those that are performed in resting conditions (the measurements of spontaneous BRS, e.g. the sequence or spectral analysis method) and methods with the application of the external stimuli, which may be either non-invasive (e.g. the controlled breathing method) or invasive (e.g. the phenylephrine method). PMID:24052991

  16. Role of renal sensory nerves in physiological and pathophysiological conditions

    PubMed Central

    2014-01-01

    Whether activation of afferent renal nerves contributes to the regulation of arterial pressure and sodium balance has been long overlooked. In normotensive rats, activating renal mechanosensory nerves decrease efferent renal sympathetic nerve activity (ERSNA) and increase urinary sodium excretion, an inhibitory renorenal reflex. There is an interaction between efferent and afferent renal nerves, whereby increases in ERSNA increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by activation of the renorenal reflexes to maintain low ERSNA to minimize sodium retention. High-sodium diet enhances the responsiveness of the renal sensory nerves, while low dietary sodium reduces the responsiveness of the renal sensory nerves, thus producing physiologically appropriate responses to maintain sodium balance. Increased renal ANG II reduces the responsiveness of the renal sensory nerves in physiological and pathophysiological conditions, including hypertension, congestive heart failure, and ischemia-induced acute renal failure. Impairment of inhibitory renorenal reflexes in these pathological states would contribute to the hypertension and sodium retention. When the inhibitory renorenal reflexes are suppressed, excitatory reflexes may prevail. Renal denervation reduces arterial pressure in experimental hypertension and in treatment-resistant hypertensive patients. The fall in arterial pressure is associated with a fall in muscle sympathetic nerve activity, suggesting that increased ARNA contributes to increased arterial pressure in these patients. Although removal of both renal sympathetic and afferent renal sensory nerves most likely contributes to the arterial pressure reduction initially, additional mechanisms may be involved in long-term arterial pressure reduction since sympathetic and sensory nerves reinnervate renal tissue in a similar time-dependent fashion following renal denervation. PMID:25411364

  17. Physiological Roles of Class I HDAC Complex and Histone Demethylase

    PubMed Central

    Hayakawa, Tomohiro; Nakayama, Jun-ichi

    2011-01-01

    Epigenetic gene silencing is one of the fundamental mechanisms for ensuring proper gene expression patterns during cellular differentiation and development. Histone deacetylases (HDACs) are evolutionally conserved enzymes that remove acetyl modifications from histones and play a central role in epigenetic gene silencing. In cells, HDAC forms a multiprotein complex (HDAC complex) in which the associated proteins are believed to help HDAC carry out its cellular functions. Though each HDAC complex contains distinct components, the presence of isoforms for some of the components expands the variety of complexes and the diversity of their cellular roles. Recent studies have also revealed a functional link between HDAC complexes and specific histone demethylases. In this paper, we summarize the distinct and cooperative roles of four class I HDAC complexes, Sin3, NuRD, CoREST, and NCoR/SMRT, with respect to their component diversity and their relationship with specific histone demethylases. PMID:21049000

  18. The emerging roles of inositol pyrophosphates in eukaryotic cell physiology.

    PubMed

    Thota, Swarna Gowri; Bhandari, Rashna

    2015-09-01

    Inositol pyrophosphates are water soluble derivatives of inositol that contain pyrophosphate or diphosphate moieties in addition to monophosphates. The best characterised inositol pyrophosphates, are IP7 (diphosphoinositol pentakisphosphate or PP-IP5), and IP8 (bisdiphosphoinositol tetrakisphosphate or (PP)2-IP4). These energy-rich small molecules are present in all eukaryotic cells, from yeast to mammals, and are involved in a wide range of cellular functions including apoptosis, vesicle trafficking, DNA repair, osmoregulation, phosphate homeostasis, insulin sensitivity, immune signalling, cell cycle regulation, and ribosome synthesis. Identified more than 20 years ago, there is still only a rudimentary understanding of the mechanisms by which inositol pyrophosphates participate in these myriad pathways governing cell physiology and homeostasis. The unique stereochemical and bioenergetic properties these molecules possess as a consequence of the presence of one or two pyrophosphate moieties in the vicinity of densely packed monophosphates are likely to form the molecular basis for their participation in multiple signalling and metabolic pathways. The aim of this review is to provide first time researchers in this area with an introduction to inositol pyrophosphates and a comprehensive overview on their cellular functions.

  19. A physiological role for HgII during phototrophic growth

    NASA Astrophysics Data System (ADS)

    Grégoire, D. S.; Poulain, A. J.

    2016-02-01

    The bioaccumulation of toxic monomethylmercury is influenced by the redox reactions that determine the amount of mercury (Hg) substrate--HgII or Hg0 (refs ,)--that is available for methylation. Phototrophic microorganisms can reduce HgII to Hg0 (ref. ). This reduction has been linked to a mixotrophic lifestyle, in which microbes gain energy photosynthetically but acquire diverse carbon compounds for biosynthesis from the environment. Photomixotrophs must maintain redox homeostasis to disperse excess reducing power due to the accumulation of reduced enzyme cofactors. Here we report laboratory experiments in which we exposed purple bacteria growing in a bioreactor to HgII and monitored Hg0 concentrations. We show that phototrophs use HgII as an electron sink to maintain redox homeostasis. Hg0 concentrations increased only when bacteria grew phototrophically, and when bacterial enzyme cofactor ratios indicated the presence of an intracellular redox imbalance. Under such conditions, bacterial growth rates increased with increasing HgII concentrations; when alternative electron sinks were added, Hg0 production decreased. We conclude that Hg can fulfil a physiological function in bacteria, and that photomixotrophs can modify the availability of Hg to methylation sites.

  20. Thyroid circadian timing: roles in physiology and thyroid malignancies.

    PubMed

    Philippe, Jacques; Dibner, Charna

    2015-04-01

    The circadian clock represents an anticipatory mechanism, well preserved in evolution. It has a critical impact on most aspects of the physiology of light-sensitive organisms. These rhythmic processes are governed by environmental cues (fluctuations in light intensity and temperature), an internal circadian timing system, and interactions between this timekeeping system and environmental signals. Endocrine body rhythms, including hypothalamic-pituitary-thyroid (HPT) axis rhythms, are tightly regulated by the circadian system. Although the circadian profiles of thyroid-releasing hormone (TRH), thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) in blood have been well described, relatively few studies have analyzed molecular mechanisms governing the circadian regulation of HPT axis function. In this review, we will discuss the latest findings in the area of complex regulation of thyroid gland function by the circadian oscillator. We will also highlight the molecular makeup of the human thyroid oscillator as well as the potential link between thyroid malignant transformation and alterations in the clockwork. PMID:25411240

  1. Cytosolic phospholipase A2: physiological function and role in disease

    PubMed Central

    Leslie, Christina C.

    2015-01-01

    The group IV phospholipase A2 (PLA2) family is comprised of six intracellular enzymes (GIVA, -B, -C, -D, -E, and -F) commonly referred to as cytosolic PLA2 (cPLA2)α, -β, -γ, -δ, -ε, and -ζ. They contain a Ser-Asp catalytic dyad and all except cPLA2γ have a C2 domain, but differences in their catalytic activities and subcellular localization suggest unique regulation and function. With the exception of cPLA2α, the focus of this review, little is known about the in vivo function of group IV enzymes. cPLA2α catalyzes the hydrolysis of phospholipids to arachidonic acid and lysophospholipids that are precursors of numerous bioactive lipids. The regulation of cPLA2α is complex, involving transcriptional and posttranslational processes, particularly increases in calcium and phosphorylation. cPLA2α is a highly conserved widely expressed enzyme that promotes lipid mediator production in human and rodent cells from a variety of tissues. The diverse bioactive lipids produced as a result of cPLA2α activation regulate normal physiological processes and disease pathogenesis in many organ systems, as shown using cPLA2α KO mice. However, humans recently identified with cPLA2α deficiency exhibit more pronounced effects on health than observed in mice lacking cPLA2α, indicating that much remains to be learned about this interesting enzyme. PMID:25838312

  2. Physiological roles revealed by ghrelin and ghrelin receptor deficient mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ghrelin is a hormone made in the stomach and known primarily for its growth hormone releasing and orexigenic properties. Nevertheless, ghrelin through its receptor, the GHS-R1a, has been shown to exert many roles including regulation of glucose homeostasis, memory & learning, food addiction and neur...

  3. Physiological roles of bacillithiol in intracellular metal processing.

    PubMed

    Rosario-Cruz, Zuelay; Boyd, Jeffrey M

    2016-02-01

    Glutathione (GSH) is an abundantly produced low-molecular-weight (LMW) thiol in many organisms. However, a number of Gram-positive bacteria do not produce GSH, but instead produce bacillithiol (BSH) as one of the major LMW thiols. Similar to GSH, studies have found that BSH has various roles in the cell, including protection against hydrogen peroxide, hypochlorite and disulfide stress. BSH also participates in the detoxification of thiol-reactive antibiotics and the electrophilic metabolite methylglyoxal. Recently, a number of studies have highlighted additional roles for BSH in the processing of intracellular metals. Herein, we examine the potential functions of BSH in the biogenesis of Fe-S clusters, cytosolic metal buffering and the prevention of metal intoxication. PMID:26259870

  4. Physiological roles and transport mechanisms of boron: perspectives from plants.

    PubMed

    Tanaka, Mayuki; Fujiwara, Toru

    2008-07-01

    Boron, an orphan of the periodic table of the elements, is unique not only in its chemical properties but also in its roles in biology. Its requirement in plants was described more than 80 years ago. Understandings of the molecular basis of the requirement and transport have been advanced greatly in the last decade. This article reviews recent findings of boron function and transport in plants and discusses possible implication to other organisms including humans. PMID:17965876

  5. Physiology, structure, and regulation of the cloned organic anion transporters

    PubMed Central

    SRIMAROENG, C.; PERRY, J. L.; PRITCHARD, J. B.

    2009-01-01

    1. The transport of negatively charged drugs, xenobiotics, and metabolites by epithelial tissues, particularly the kidney, plays critical roles in controlling their distribution, concentration, and retention in the body. Thus, organic anion transporters (OATs) impact both their therapeutic efficacy and potential toxicity. 2. This review summarizes current knowledge of the properties and functional roles of the cloned OATs, the relationships between transporter structure and function, and those factors that determine the efficacy of transport. Such factors include plasma protein binding of substrates, genetic polymorphisms among the transporters, and regulation of transporter expression. 3. Clearly, much progress has been made in the decade since the first OAT was cloned. However, unresolved questions remain. Several of these issues — drug–drug interactions, functional characterization of newly cloned OATs, tissue differences in expression and function, and details of the nature and consequences of transporter regulation at genomic and intracellular sites — are discussed in the concluding Perspectives section. PMID:18668434

  6. Understanding Protein Synthesis: A Role-Play Approach in Large Undergraduate Human Anatomy and Physiology Classes

    ERIC Educational Resources Information Center

    Sturges, Diana; Maurer, Trent W.; Cole, Oladipo

    2009-01-01

    This study investigated the effectiveness of role play in a large undergraduate science class. The targeted population consisted of 298 students enrolled in 2 sections of an undergraduate Human Anatomy and Physiology course taught by the same instructor. The section engaged in the role-play activity served as the study group, whereas the section…

  7. Crystal Structure of Human Senescence Marker Protein 30: Insights Linking Structural, Enzymatic, and Physiological Functions

    SciTech Connect

    Chakraborti, Subhendu; Bahnson, Brian J.

    2010-05-25

    Human senescence marker protein 30 (SMP30), which functions enzymatically as a lactonase, hydrolyzes various carbohydrate lactones. The penultimate step in vitamin-C biosynthesis is catalyzed by this enzyme in nonprimate mammals. It has also been implicated as an organophosphate hydrolase, with the ability to hydrolyze diisopropyl phosphofluoridate and other nerve agents. SMP30 was originally identified as an aging marker protein, whose expression decreased androgen independently in aging cells. SMP30 is also referred to as regucalcin and has been suggested to have functions in calcium homeostasis. The crystal structure of the human enzyme has been solved from X-ray diffraction data collected to a resolution of 1.4 {angstrom}. The protein has a 6-bladed {beta}-propeller fold, and it contains a single metal ion. Crystal structures have been solved with the metal site bound with either a Ca{sup 2+} or a Zn{sup 2+} atom. The catalytic role of the metal ion has been confirmed by mutagenesis of the metal coordinating residues. Kinetic studies using the substrate gluconolactone showed a k{sub cat} preference of divalent cations in the order Zn{sup 2+} > Mn{sup 2+} > Ca{sup 2+} > Mg{sup 2+}. Notably, the Ca{sup 2+} had a significantly higher value of K{sub d} compared to those of the other metal ions tested (566, 82, 7, and 0.6 {micro}m for Ca{sup 2+}, Mg{sup 2+}, Zn{sup 2+}, and Mn{sup 2+}, respectively), suggesting that the Ca{sup 2+}-bound form may be physiologically relevant for stressed cells with an elevated free calcium level.

  8. Physiological and Pharmacological Roles of FGF21 in Cardiovascular Diseases.

    PubMed

    Cheng, Peng; Zhang, Fangfang; Yu, Lechu; Lin, Xiufei; He, Luqing; Li, Xiaokun; Lu, Xuemian; Yan, Xiaoqing; Tan, Yi; Zhang, Chi

    2016-01-01

    Cardiovascular disease (CVD) is one of the most severe diseases in clinics. Fibroblast growth factor 21 (FGF21) is regarded as an important metabolic regulator playing a therapeutic role in diabetes and its complications. The heart is a key target as well as a source of FGF21 which is involved in heart development and also induces beneficial effects in CVDs. Our review is to clarify the roles of FGF21 in CVDs. Strong evidence showed that the development of CVDs including atherosclerosis, coronary heart disease, myocardial ischemia, cardiac hypertrophy, and diabetic cardiomyopathy is associated with serum FGF21 levels increase which was regarded as a compensatory response to induced cardiac protection. Furthermore, administration of FGF21 suppressed the above CVDs. Mechanistic studies revealed that FGF21 induced cardiac protection likely by preventing cardiac lipotoxicity and the associated oxidative stress, inflammation, and apoptosis. Normally, FGF21 induced therapeutic effects against CVDs via activation of the above kinases-mediated pathways by directly binding to the FGF receptors of the heart in the presence of β-klotho. However, recently, growing evidence showed that FGF21 induced beneficial effects on peripheral organs through an indirect way mediated by adiponectin. Therefore whether adiponectin is also involved in FGF21-induced cardiac protection still needs further investigation. PMID:27247947

  9. Physiological and Pharmacological Roles of FGF21 in Cardiovascular Diseases

    PubMed Central

    Cheng, Peng; Zhang, Fangfang; Yu, Lechu; Lin, Xiufei; He, Luqing; Li, Xiaokun; Lu, Xuemian; Yan, Xiaoqing; Tan, Yi; Zhang, Chi

    2016-01-01

    Cardiovascular disease (CVD) is one of the most severe diseases in clinics. Fibroblast growth factor 21 (FGF21) is regarded as an important metabolic regulator playing a therapeutic role in diabetes and its complications. The heart is a key target as well as a source of FGF21 which is involved in heart development and also induces beneficial effects in CVDs. Our review is to clarify the roles of FGF21 in CVDs. Strong evidence showed that the development of CVDs including atherosclerosis, coronary heart disease, myocardial ischemia, cardiac hypertrophy, and diabetic cardiomyopathy is associated with serum FGF21 levels increase which was regarded as a compensatory response to induced cardiac protection. Furthermore, administration of FGF21 suppressed the above CVDs. Mechanistic studies revealed that FGF21 induced cardiac protection likely by preventing cardiac lipotoxicity and the associated oxidative stress, inflammation, and apoptosis. Normally, FGF21 induced therapeutic effects against CVDs via activation of the above kinases-mediated pathways by directly binding to the FGF receptors of the heart in the presence of β-klotho. However, recently, growing evidence showed that FGF21 induced beneficial effects on peripheral organs through an indirect way mediated by adiponectin. Therefore whether adiponectin is also involved in FGF21-induced cardiac protection still needs further investigation. PMID:27247947

  10. The role of ACE2 in cardiovascular physiology.

    PubMed

    Oudit, Gavin Y; Crackower, Michael A; Backx, Peter H; Penninger, Josef M

    2003-04-01

    The renin-angiotensin system (RAS) is critically involved in cardiovascular and renal function and in disease conditions, and has been shown to be a far more complex system than initially thought. A recently discovered homologue of angiotensin-converting enzyme (ACE)--ACE2--appears to negatively regulate the RAS. ACE2 cleaves Ang I and Ang II into the inactive Ang 1-9 and Ang 1-7, respectively. ACE2 is highly expressed in kidney and heart and is especially confined to the endothelium. With quantitative trait locus (QTL) mapping, ACE2 was defined as a QTL on the X chromosome in rat models of hypertension. In these animal models, kidney ACE2 messenger RNA and protein expression were markedly reduced, making ACE2 a candidate gene for this QTL. Targeted disruption of ACE2 in mice failed to elicit hypertension, but resulted in severe impairment in myocardial contractility with increased angiotensin II levels. Genetic ablation of ACE in the ACE2 null mice rescued the cardiac phenotype. These genetic data show that ACE2 is an essential regulator of heart function in vivo. Basal renal morphology and function were not altered by the inactivation of ACE2. The novel role of ACE2 in hydrolyzing several other peptides-such as the apelin peptides, opioids, and kinin metabolites-raises the possibility that peptide systems other than angiotensin and its derivatives also may have an important role in regulating cardiovascular and renal function.

  11. [Biological role of heterogeneous glycoprotein structures].

    PubMed

    Jakab, Lajos

    2016-07-01

    Carbohydrate molecules connected mostly with covalent junctions to protein chains are called glycoproteins. These carbohydrate molecules are attached to the protein core in different qualities and order. When the protein core is connected with acidic components such as uronic acid or SO4 radicals, they are called proteoglycans. The currently used name "glycosaminoglycan" in this case is not entirely correct. In the living world polymannane structures occur, too. Glycoproteins do not only exceptionally hold acidic groups but they have neuraminic acid derivatives. Tissue, cellular and matrix structures, and mostly all serum "proteins" are mainly glycoproteins. In the everyday clinical practice glycoproteins are mentioned as proteins. Nevertheless, the inadequate use of the concept may cause errors in the attitudes, too. This paper aims to correct this notion, because the term of "glycobiology" has already been expanded to be an independent scientific field. The practical clinical consequences of recent knowledge in this field are also summarized including novel findings on glycoprotein structures and functions. The importance of the quantity of carbohydrates, and their structural arrangements are also presented. In short, significance of glycoprotein-carbohydrate structures, as well as their physiological and pathological roles are reviewed in order to introduce the field of "glycobiology". Orosomucoid and immunoglobulins are discussed separately. Orv. Hetil., 2016, 157(30), 1185-1192.

  12. A Role for Antibiotics in Mineral Dissolution and Biofilm Physiology

    NASA Astrophysics Data System (ADS)

    Newman, D. K.

    2002-12-01

    Respiration by bacteria is remarkable due to their ability to use a variety of compounds, including insoluble minerals, as terminal electron acceptors. How bacteria solve the problem of breathing something that is solid is poorly understood, but recent evidence points to the role of redox active natural products in shuttling electrons between microbes and minerals. Given the ubiquity of these substances in natural waters and soils, we must now revisit previous conclusions about whether direct contact between microbes and minerals is necessary to promote reductive mineral dissolution. To explore the degree to which extracellular electron transfer catalyzes important biogeochemical processes, we are studying the types of molecules that function as electron shuttles, including redox active antibiotics. I will discuss my laboratory's current understanding of how interspecies exchange of these molecules promotes mineral dissolution, as well as our emerging hypotheses regarding their function in biofilms.

  13. Physiological role of alternative oxidase (from yeasts to plants).

    PubMed

    Rogov, A G; Zvyagilskaya, R A

    2015-04-01

    Mitochondria of all so far studied organisms, with the exception of Archaea, mammals, some yeasts, and protists, contain, along with the classical phosphorylating cytochrome pathway, a so-called cyanide-insensitive alternative oxidase (AOX) localized on the matrix side of the mitochondrial inner membrane, and electron transport through which is not coupled with ATP synthesis and energy accumulation. Mechanisms underlying plentiful functions of AOX in organisms at various levels of organization ranging from yeasts to plants are considered. First and foremost, AOX provides a chance of cell survival after inhibiting the terminal components of the main respiratory chain or losing the ability to synthesize these components. The vitally important role of AOX is obvious in thermogenesis of thermogenic plant organs where it becomes the only terminal oxidase with a very high activity, and the energy of substrate oxidation by this respiratory pathway is converted into heat, thus promoting evaporation of volatile substances attracting pollinating insects. AOX plays a fundamentally significant role in alleviating or preventing oxidative stress, thus ensuring the defense against a wide range of stresses and adverse environmental conditions, such as changes in temperature and light intensities, osmotic stress, drought, and attack by incompatible strains of bacterial pathogens, phytopathogens, or their elicitors. Participation of AOX in pathogen survival during its existence inside the host, in antivirus defense, as well as in metabolic rearrangements in plants during embryogenesis and cell differentiation is described. Examples are given to demonstrate that AOX might be an important tool to overcome the adverse aftereffects of restricted activity of the main respiratory chain in cells and whole animals.

  14. Physiological role of alternative oxidase (from yeasts to plants).

    PubMed

    Rogov, A G; Zvyagilskaya, R A

    2015-04-01

    Mitochondria of all so far studied organisms, with the exception of Archaea, mammals, some yeasts, and protists, contain, along with the classical phosphorylating cytochrome pathway, a so-called cyanide-insensitive alternative oxidase (AOX) localized on the matrix side of the mitochondrial inner membrane, and electron transport through which is not coupled with ATP synthesis and energy accumulation. Mechanisms underlying plentiful functions of AOX in organisms at various levels of organization ranging from yeasts to plants are considered. First and foremost, AOX provides a chance of cell survival after inhibiting the terminal components of the main respiratory chain or losing the ability to synthesize these components. The vitally important role of AOX is obvious in thermogenesis of thermogenic plant organs where it becomes the only terminal oxidase with a very high activity, and the energy of substrate oxidation by this respiratory pathway is converted into heat, thus promoting evaporation of volatile substances attracting pollinating insects. AOX plays a fundamentally significant role in alleviating or preventing oxidative stress, thus ensuring the defense against a wide range of stresses and adverse environmental conditions, such as changes in temperature and light intensities, osmotic stress, drought, and attack by incompatible strains of bacterial pathogens, phytopathogens, or their elicitors. Participation of AOX in pathogen survival during its existence inside the host, in antivirus defense, as well as in metabolic rearrangements in plants during embryogenesis and cell differentiation is described. Examples are given to demonstrate that AOX might be an important tool to overcome the adverse aftereffects of restricted activity of the main respiratory chain in cells and whole animals. PMID:25869356

  15. TRPV4 channels: physiological and pathological role in cardiovascular system.

    PubMed

    Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

    2015-11-01

    TRPV4 channels are non-selective cation channels permeable to Ca(2+), Na(+), and Mg(2+) ions. Recently, TRPV4 channels have received considerable attention as these channels are widely expressed in the cardiovascular system including endothelial cells, cardiac fibroblasts, vascular smooth muscles, and peri-vascular nerves. Therefore, these channels possibly play a pivotal role in the maintenance of cardiovascular homeostasis. TRPV4 channels critically regulate flow-induced arteriogenesis, TGF-β1-induced differentiation of cardiac fibroblasts into myofibroblasts, and heart failure-induced pulmonary edema. These channels also mediate hypoxia-induced increase in proliferation and migration of pulmonary artery smooth muscle cells and progression of pulmonary hypertension. These channels also maintain flow-induced vasodilation and preserve vascular function by directly activating Ca(2+)-dependent KCa channels. Furthermore, these may also induce vasodilation and maintain blood pressure indirectly by evoking the release of NO, CGRP, and substance P. The present review discusses the evidences and the potential mechanisms implicated in diverse responses including arteriogenesis, cardiac remodeling, congestive heart failure-induced pulmonary edema, pulmonary hypertension, flow-induced dilation, regulation of blood pressure, and hypoxic preconditioning.

  16. Linking vegetation structure, function and physiology through spectroscopic remote sensing

    NASA Astrophysics Data System (ADS)

    Serbin, S.; Singh, A.; Couture, J. J.; Shiklomanov, A. N.; Rogers, A.; Desai, A. R.; Kruger, E. L.; Townsend, P. A.

    2015-12-01

    Terrestrial ecosystem process models require detailed information on ecosystem states and canopy properties to properly simulate the fluxes of carbon (C), water and energy from the land to the atmosphere and assess the vulnerability of ecosystems to perturbations. Current models fail to adequately capture the magnitude, spatial variation, and seasonality of terrestrial C uptake and storage, leading to significant uncertainties in the size and fate of the terrestrial C sink. By and large, these parameter and process uncertainties arise from inadequate spatial and temporal representation of plant traits, vegetation structure, and functioning. With increases in computational power and changes to model architecture and approaches, it is now possible for models to leverage detailed, data rich and spatially explicit descriptions of ecosystems to inform parameter distributions and trait tradeoffs. In this regard, spectroscopy and imaging spectroscopy data have been shown to be invaluable observational datasets to capture broad-scale spatial and, eventually, temporal dynamics in important vegetation properties. We illustrate the linkage of plant traits and spectral observations to supply key data constraints for model parameterization. These constraints can come either in the form of the raw spectroscopic data (reflectance, absorbtance) or physiological traits derived from spectroscopy. In this presentation we highlight our ongoing work to build ecological scaling relationships between critical vegetation characteristics and optical properties across diverse and complex canopies, including temperate broadleaf and conifer forests, Mediterranean vegetation, Arctic systems, and agriculture. We focus on work at the leaf, stand, and landscape scales, illustrating the importance of capturing the underlying variability in a range of parameters (including vertical variation within canopies) to enable more efficient scaling of traits related to functional diversity of ecosystems.

  17. The role of silicon in physiology of the medicinal plant (Lonicera japonica L.) under salt stress

    NASA Astrophysics Data System (ADS)

    Gengmao, Zhao; Shihui, Li; Xing, Sun; Yizhou, Wang; Zipan, Chang

    2015-08-01

    Silicon(Si) is the only element which can enhance the resistance to multiple stresses. However, the role of silicon in medicinal plants under salt stress is not yet understood. This experiment was conducted to study the effects of silicon addition on the growth, osmotic adjustments, photosynthetic characteristics, chloroplast ultrastructure and Chlorogenic acid (CGA) production of Honeysuckle plant (Lonicera japonica L.) under salt-stressed conditions. Salinity exerted an adverse effect on the plant fresh weight and dry weight, whilst 0.5 g L-1 K2SiO3·nH2O addition obviously improved the plant growth. Although Na+ concentration in plant organs was drastically increased with increasing salinity, higher levels of K+/Na+ ratio was obtained after K2SiO3·nH2O addition. Salinity stress induced the destruction of the chloroplast envelope; however, K2SiO3·nH2O addition counteracted the adverse effect by salinity on the structure of the photosynthetic apparatus. K2SiO3·nH2O addition also enhanced the activities of superoxide dismutase and catalase. To sum up, exogenous Si plays a key role in enhancing its resistance to salt stresses in physiological base, thereby improving the growth and CGA production of Honeysuckle plant.

  18. The role of silicon in physiology of the medicinal plant (Lonicera japonica L.) under salt stress.

    PubMed

    Gengmao, Zhao; Shihui, Li; Xing, Sun; Yizhou, Wang; Zipan, Chang

    2015-08-03

    Silicon(Si) is the only element which can enhance the resistance to multiple stresses. However, the role of silicon in medicinal plants under salt stress is not yet understood. This experiment was conducted to study the effects of silicon addition on the growth, osmotic adjustments, photosynthetic characteristics, chloroplast ultrastructure and Chlorogenic acid (CGA) production of Honeysuckle plant (Lonicera japonica L.) under salt-stressed conditions. Salinity exerted an adverse effect on the plant fresh weight and dry weight, whilst 0.5 g L(-1) K2SiO3 · nH2O addition obviously improved the plant growth. Although Na(+) concentration in plant organs was drastically increased with increasing salinity, higher levels of K(+)/Na(+) ratio was obtained after K2SiO3 · nH2O addition. Salinity stress induced the destruction of the chloroplast envelope; however, K2SiO3 · nH2O addition counteracted the adverse effect by salinity on the structure of the photosynthetic apparatus. K2SiO3 · nH2O addition also enhanced the activities of superoxide dismutase and catalase. To sum up, exogenous Si plays a key role in enhancing its resistance to salt stresses in physiological base, thereby improving the growth and CGA production of Honeysuckle plant.

  19. The role of silicon in physiology of the medicinal plant (Lonicera japonica L.) under salt stress.

    PubMed

    Gengmao, Zhao; Shihui, Li; Xing, Sun; Yizhou, Wang; Zipan, Chang

    2015-01-01

    Silicon(Si) is the only element which can enhance the resistance to multiple stresses. However, the role of silicon in medicinal plants under salt stress is not yet understood. This experiment was conducted to study the effects of silicon addition on the growth, osmotic adjustments, photosynthetic characteristics, chloroplast ultrastructure and Chlorogenic acid (CGA) production of Honeysuckle plant (Lonicera japonica L.) under salt-stressed conditions. Salinity exerted an adverse effect on the plant fresh weight and dry weight, whilst 0.5 g L(-1) K2SiO3 · nH2O addition obviously improved the plant growth. Although Na(+) concentration in plant organs was drastically increased with increasing salinity, higher levels of K(+)/Na(+) ratio was obtained after K2SiO3 · nH2O addition. Salinity stress induced the destruction of the chloroplast envelope; however, K2SiO3 · nH2O addition counteracted the adverse effect by salinity on the structure of the photosynthetic apparatus. K2SiO3 · nH2O addition also enhanced the activities of superoxide dismutase and catalase. To sum up, exogenous Si plays a key role in enhancing its resistance to salt stresses in physiological base, thereby improving the growth and CGA production of Honeysuckle plant. PMID:26235534

  20. Novel and potential physiological roles of vacuolar-type H+-ATPase in marine organisms.

    PubMed

    Tresguerres, Martin

    2016-07-15

    The vacuolar-type H(+)-ATPase (VHA) is a multi-subunit enzyme that uses the energy from ATP hydrolysis to transport H(+) across biological membranes. VHA plays a universal role in essential cellular functions, such as the acidification of lysosomes and endosomes. In addition, the VHA-generated H(+)-motive force can drive the transport of diverse molecules across cell membranes and epithelia for specialized physiological functions. Here, I discuss diverse physiological functions of VHA in marine animals, focusing on recent discoveries about base secretion in shark gills, potential bone dissolution by Osedax bone-eating worms and its participation in a carbon-concentrating mechanism that promotes coral photosynthesis. Because VHA is evolutionarily conserved among eukaryotes, it is likely to play many other essential physiological roles in diverse marine organisms. Elucidating and characterizing basic VHA-dependent mechanisms could help to determine species responses to environmental stress, including (but not limited to) that resulting from climate change. PMID:27445397

  1. Physiological roles of mycothiol in detoxification and tolerance to multiple poisonous chemicals in Corynebacterium glutamicum.

    PubMed

    Liu, Ying-Bao; Long, Ming-Xiu; Yin, Ya-Jie; Si, Mei-Ru; Zhang, Lei; Lu, Zhi-Qiang; Wang, Yao; Shen, Xi-Hui

    2013-06-01

    Mycothiol (MSH) plays important roles in maintaining cytosolic redox homeostasis and in adapting to reactive oxygen species in the high-(G + C)-content Gram-positive Actinobacteria. However, its physiological roles are ill defined compared to glutathione, the functional analog of MSH in Gram-negative bacteria and most eukaryotes. In this research, we explored the impact of intracellular MSH on cellular physiology by using MSH-deficient mutants in the model organism Corynebacterium glutamicum. We found that intracellular MSH contributes significantly to resistance to alkylating agents, glyphosate, ethanol, antibiotics, heavy metals and aromatic compounds. In addition, intracellular MSH is beneficial for withstanding oxidative stress induced by various oxidants in C. glutamicum. This study greatly expanded our current knowledge on the physiological functions of mycothiol in C. glutamicum and could be applied to improve the robustness of this scientifically and commercially important species in the future. PMID:23615850

  2. Physiological Regulation of Stress in Referred Adolescents: The Role of the Parent-Adolescent Relationship

    ERIC Educational Resources Information Center

    Willemen, Agnes M.; Schuengel, Carlo; Koot, Hans M.

    2009-01-01

    Background: Psychopathology in youth appears to be linked to deficits in regulating affective responses to stressful situations. In children, high-quality parental support facilitates affect regulation. However, in adolescence, the role of parent-child interaction in the regulation of affect is unclear. This study examined physiological reactivity…

  3. Early Childcare, Executive Functioning, and the Moderating Role of Early Stress Physiology

    ERIC Educational Resources Information Center

    Berry, Daniel; Willoughby, Michael T.; Blair, Clancy; Ursache, Alexandra; Granger, Douglas A.

    2014-01-01

    Intervention studies indicate that children's childcare experiences can be leveraged to support the development of executive functioning (EF). The role of more normative childcare experiences is less clear. Increasingly, theory and empirical work suggest that individual differences in children's physiological stress systems may be…

  4. From Tusko to Titin: the role for comparative physiology in an era of molecular discovery.

    PubMed

    Lindstedt, S L; Nishikawa, K C

    2015-06-15

    As we approach the centenary of the term "comparative physiology," we reexamine its role in modern biology. Finding inspiration in Krogh's classic 1929 paper, we first look back to some timeless contributions to the field. The obvious and fascinating variation among animals is much more evident than is their shared physiological unity, which transcends both body size and specific adaptations. The "unity in diversity" reveals general patterns and principles of physiology that are invisible when examining only one species. Next, we examine selected contemporary contributions to comparative physiology, which provides the context in which reductionist experiments are best interpreted. We discuss the sometimes surprising insights provided by two comparative "athletes" (pronghorn and rattlesnakes), which demonstrate 1) animals are not isolated molecular mechanisms but highly integrated physiological machines, a single "rate-limiting" step may be exceptional; and 2) extremes in nature are rarely the result of novel mechanisms, but rather employ existing solutions in novel ways. Furthermore, rattlesnake tailshaker muscle effectively abolished the conventional view of incompatibility of simultaneous sustained anaerobic glycolysis and oxidative ATP production. We end this review by looking forward, much as Krogh did, to suggest that a comparative approach may best lend insights in unraveling how skeletal muscle stores and recovers mechanical energy when operating cyclically. We discuss and speculate on the role of the largest known protein, titin (the third muscle filament), as a dynamic spring capable of storing and recovering elastic recoil potential energy in skeletal muscle. PMID:25855309

  5. From Tusko to Titin: the role for comparative physiology in an era of molecular discovery.

    PubMed

    Lindstedt, S L; Nishikawa, K C

    2015-06-15

    As we approach the centenary of the term "comparative physiology," we reexamine its role in modern biology. Finding inspiration in Krogh's classic 1929 paper, we first look back to some timeless contributions to the field. The obvious and fascinating variation among animals is much more evident than is their shared physiological unity, which transcends both body size and specific adaptations. The "unity in diversity" reveals general patterns and principles of physiology that are invisible when examining only one species. Next, we examine selected contemporary contributions to comparative physiology, which provides the context in which reductionist experiments are best interpreted. We discuss the sometimes surprising insights provided by two comparative "athletes" (pronghorn and rattlesnakes), which demonstrate 1) animals are not isolated molecular mechanisms but highly integrated physiological machines, a single "rate-limiting" step may be exceptional; and 2) extremes in nature are rarely the result of novel mechanisms, but rather employ existing solutions in novel ways. Furthermore, rattlesnake tailshaker muscle effectively abolished the conventional view of incompatibility of simultaneous sustained anaerobic glycolysis and oxidative ATP production. We end this review by looking forward, much as Krogh did, to suggest that a comparative approach may best lend insights in unraveling how skeletal muscle stores and recovers mechanical energy when operating cyclically. We discuss and speculate on the role of the largest known protein, titin (the third muscle filament), as a dynamic spring capable of storing and recovering elastic recoil potential energy in skeletal muscle.

  6. Probing Temporal Structures in the Nonstationarity of Physiological Signals

    NASA Astrophysics Data System (ADS)

    Ivanov, Plamen Ch.; Bernaola-Galvan, Pedro; Amaral, Luis A. N.; Goldberger, Ary L.; Stanley, H. Eugene

    2000-03-01

    We ask if there is an element of complexity to the nonstationarity in physiological signals. We hypothesise that appearence of segments with different mean values in the signal is related to different physiologic responses to external stimuli. We focus on the statistical properties and temporal organization of segments in the signal with well defined mean, significantly different from the mean of the adjacent segments. For that we subdivide heartbeat time series in such a way as to maximize the difference in the mean values between adjacent segments. To identify different segments we develop a new technique based on the Student's statistics. We observe that the distribution of the lenghts of segments follows a power law for the data during wake activity from both healthy subjects and patients with congestive heart failure. Data from both groups during sleep showes a breakdown in this power-law behavior with a crossover at lenght at ≈ 300 beats.

  7. The physiologic and therapeutic role of heparin in implantation and placentation.

    PubMed

    Quaranta, Michela; Erez, Offer; Mastrolia, Salvatore Andrea; Koifman, Arie; Leron, Elad; Eshkoli, Tamar; Mazor, Moshe; Holcberg, Gershon

    2015-01-01

    Implantation, trophoblast development and placentation are crucial processes in the establishment and development of normal pregnancy. Abnormalities of these processes can lead to pregnancy complications known as the great obstetrical syndromes: preeclampsia, intrauterine growth restriction, fetal demise, premature prelabor rupture of membranes, preterm labor, and recurrent pregnancy loss. There is mounting evidence regarding the physiological and therapeutic role of heparins in the establishment of normal gestation and as a modality for treatment and prevention of pregnancy complications. In this review, we will summarize the properties and the physiological contributions of heparins to the success of implantation, placentation and normal pregnancy.

  8. The physiologic and therapeutic role of heparin in implantation and placentation

    PubMed Central

    Quaranta, Michela; Mastrolia, Salvatore Andrea; Koifman, Arie; Leron, Elad; Eshkoli, Tamar; Mazor, Moshe; Holcberg, Gershon

    2015-01-01

    Implantation, trophoblast development and placentation are crucial processes in the establishment and development of normal pregnancy. Abnormalities of these processes can lead to pregnancy complications known as the great obstetrical syndromes: preeclampsia, intrauterine growth restriction, fetal demise, premature prelabor rupture of membranes, preterm labor, and recurrent pregnancy loss. There is mounting evidence regarding the physiological and therapeutic role of heparins in the establishment of normal gestation and as a modality for treatment and prevention of pregnancy complications. In this review, we will summarize the properties and the physiological contributions of heparins to the success of implantation, placentation and normal pregnancy. PMID:25653897

  9. Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems - role in ageing and disease

    PubMed Central

    Thornalley, Paul J.

    2009-01-01

    Glycation of proteins, nucleotides and basic phospholipids by glyoxal and methylglyoxal – physiological substrates of glyoxalase 1 - is potentially damaging to the proteome, genome and lipidome. Glyoxalase 1 suppresses glycation by these α-oxoaldehyde metabolites and thereby represents part of the enzymatic defence against glycation. Albert Szent-Gyorgyi pioneered and struggled to understand the physiological function of methylglyoxal and the glyoxalase system. We now appreciate glyoxalase 1 protects against dicarbonyl modifications of the proteome, genome and lipome. Latest research suggests there are functional modifications of this process – implying a role in cell signalling, ageing and disease. PMID:18533367

  10. The physiologic role of erythrocytes in oxygen delivery and implications for blood storage.

    PubMed

    Benedik, Penelope S; Hamlin, Shannan K

    2014-09-01

    Erythrocytes are not just oxygen delivery devices but play an active metabolic role in modulating microvascular blood flow. Hemoglobin and red blood cell morphology change as local oxygen levels fall, eliciting the release of adenosine triphosphate and nitric oxide to initiate local vasodilation. Aged erythrocytes undergo physical and functional changes such that some of the red cell's most physiologically helpful attributes are diminished. This article reviews the functional anatomy and applied physiology of the erythrocyte and the microcirculation with an emphasis on how erythrocytes modulate microvascular function. The effects of cell storage on the metabolic functions of the erythrocyte are also briefly discussed.

  11. Physiological and pathological roles of tissue plasminogen activator and its inhibitor neuroserpin in the nervous system

    PubMed Central

    Lee, Tet Woo; Tsang, Vicky W. K.; Birch, Nigel P.

    2015-01-01

    Although its roles in the vascular space are most well-known, tissue plasminogen activator (tPA) is widely expressed in the developing and adult nervous system, where its activity is believed to be regulated by neuroserpin, a predominantly brain-specific member of the serpin family of protease inhibitors. In the normal physiological state, tPA has been shown to play roles in the development and plasticity of the nervous system. Ischemic damage, however, may lead to excess tPA activity in the brain and this is believed to contribute to neurodegeneration. In this article, we briefly review the physiological and pathological roles of tPA in the nervous system, which includes neuronal migration, axonal growth, synaptic plasticity, neuroprotection and neurodegeneration, as well as a contribution to neurological disease. We summarize tPA's multiple mechanisms of action and also highlight the contributions of the inhibitor neuroserpin to these processes. PMID:26528129

  12. NADPH–Cytochrome P450 Oxidoreductase: Roles in Physiology, Pharmacology, and Toxicology

    PubMed Central

    Ding, Xinxin; Wolf, C. Roland; Porter, Todd D.; Pandey, Amit V.; Zhang, Qing-Yu; Gu, Jun; Finn, Robert D.; Ronseaux, Sebastien; McLaughlin, Lesley A.; Henderson, Colin J.; Zou, Ling; Flück, Christa E.

    2013-01-01

    This is a report on a symposium sponsored by the American Society for Pharmacology and Experimental Therapeutics and held at the Experimental Biology 2012 meeting in San Diego, California, on April 25, 2012. The symposium speakers summarized and critically evaluated our current understanding of the physiologic, pharmacological, and toxicological roles of NADPH–cytochrome P450 oxidoreductase (POR), a flavoprotein involved in electron transfer to microsomal cytochromes P450 (P450), cytochrome b5, squalene mono-oxygenase, and heme oxygenase. Considerable insight has been derived from the development and characterization of mouse models with conditional Por deletion in particular tissues or partial suppression of POR expression in all tissues. Additional mouse models with global or conditional hepatic deletion of cytochrome b5 are helping to clarify the P450 isoform- and substrate-specific influences of cytochrome b5 on P450 electron transfer and catalytic function. This symposium also considered studies using siRNA to suppress POR expression in a hepatoma cell–culture model to explore the basis of the hepatic lipidosis phenotype observed in mice with conditional deletion of Por in liver. The symposium concluded with a strong translational perspective, relating the basic science of human POR structure and function to the impacts of POR genetic variation on human drug and steroid metabolism. PMID:23086197

  13. A dual physiological character for sexual function: the role of serotonergic receptors.

    PubMed

    Motofei, Ion G

    2008-03-01

    Anatomically, sexual reflexes are mixed (somatic-autonomic) circuits, represented by emission (sympathetic centre and somatic afferents), expulsion (parasympathetic centre and somatic efferents) and erection (parasympathetic centre and somatic afferents). Physiologically, ejaculation has a dual autonomic mediation, consisting of two distinct and opposite autonomic centres (emission and expulsion), both with a positive contribution to the respective function. Experimentally, serotonin (5HT) has two distinct, opposite and positive effects on sexual function, with 5HT-(1A) agonists decreasing intravaginal ejaculatory latency and erection, and 5HT-(2C) agonists increasing both erection and ejaculatory latency. In this review I assume that 5HT modulates sexual reflexes, establishing a functional connection between the involved somatic and autonomic structures. The 5HT-(1A) receptors are assumed to make the connection between somatic pathways and sympathetic centres while the 5HT-(2C) receptors could establish the connection between somatic pathways and parasympathetic centres. Further studies will develop the cerebral sexual duality, explaining the implication of psychological factors in sexual function and the role of sexuality in psychosocial behaviour. PMID:17922864

  14. The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society.

    PubMed

    Vlachopoulos, Charalambos; Xaplanteris, Panagiotis; Aboyans, Victor; Brodmann, Marianne; Cífková, Renata; Cosentino, Francesco; De Carlo, Marco; Gallino, Augusto; Landmesser, Ulf; Laurent, Stéphane; Lekakis, John; Mikhailidis, Dimitri P; Naka, Katerina K; Protogerou, Athanasios D; Rizzoni, Damiano; Schmidt-Trucksäss, Arno; Van Bortel, Luc; Weber, Thomas; Yamashina, Akira; Zimlichman, Reuven; Boutouyrie, Pierre; Cockcroft, John; O'Rourke, Michael; Park, Jeong Bae; Schillaci, Giuseppe; Sillesen, Henrik; Townsend, Raymond R

    2015-08-01

    While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.

  15. Effect of noisy stimulation on neurobiological sensitization systems and its role for normal and pathological physiology

    NASA Astrophysics Data System (ADS)

    Huber, Martin; Braun, Hans; Krieg, J.\\:Urgen-Christian

    2004-03-01

    Sensitization is discussed as an important phenomenon playing a role in normal physiology but also with respect to the initiation and progression of a variety of neuropsychiatric disorders such as epilepsia, substance-related disorders or recurrent affective disorders. The relevance to understand the dynamics of sensitization phenomena is emphasized by recent findings that even single stimulations can induce longlasting changes in biological systems. To address specific questions associated with the sensitization dynamics, we use a computational approach and develop simple but physiologically-plausible models. In the present study we examine the effect of noisy stimulation on sensitization development in the model. We consider sub- and suprathresold stimulations with varying noise intensities and determine as response measures the (i) absolute number of stimulus-induced sensitzations and (ii) the temporal relsation of stimulus-sensitization coupling. The findings indicate that stochastic effects including stochastic resonance might well contribute to the physiology of sensitization mechanisms under both nomal and pathological conditions.

  16. Rapid Sensitization of Physiological, Neuronal, and Locomotor Effects of Nicotine: Critical Role of Peripheral Drug Actions

    PubMed Central

    Lenoir, Magalie; Tang, Jeremy S.; Woods, Amina S.

    2013-01-01

    Repeated exposure to nicotine and other psychostimulant drugs produces persistent increases in their psychomotor and physiological effects (sensitization), a phenomenon related to the drugs' reinforcing properties and abuse potential. Here we examined the role of peripheral actions of nicotine in nicotine-induced sensitization of centrally mediated physiological parameters (brain, muscle, and skin temperatures), cortical and VTA EEG, neck EMG activity, and locomotion in freely moving rats. Repeated injections of intravenous nicotine (30 μg/kg) induced sensitization of the drug's effects on all these measures. In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrrolidine methiodide (nicotinePM, 30 μg/kg, i.v.) resulted in habituation (tolerance) of the same physiological, neuronal, and behavioral measures. However, after repeated nicotine exposure, acute nicotinePM injections induced nicotine-like physiological responses: powerful cortical and VTA EEG desynchronization, EMG activation, a large brain temperature increase, but weaker hyperlocomotion. Additionally, both the acute locomotor response to nicotine and nicotine-induced locomotor sensitization were attenuated by blockade of peripheral nicotinic receptors by hexamethonium (3 mg/kg, i.v.). These data suggest that the peripheral actions of nicotine, which precede its direct central actions, serve as a conditioned interoceptive cue capable of eliciting nicotine-like physiological and neural responses after repeated nicotine exposure. Thus, by providing a neural signal to the CNS that is repeatedly paired with the direct central effects of nicotine, the drug's peripheral actions play a critical role in the development of nicotine-induced physiological, neural, and behavioral sensitization. PMID:23761889

  17. Physiological roles of peroxido-vanadium complexes: Leitmotif as their signal transduction pathway.

    PubMed

    Matsugo, Seiichi; Kanamori, Kan; Sugiyama, Hironori; Misu, Hirofumi; Takamura, Toshinari

    2015-06-01

    Evidence exists that supports the various physiological roles of vanadium compounds, although the amount of vanadium in our body is limited. This limited concentration in our body does not attract much attention of the biological chemists, although the fact is present; even in the 19th century, vanadium derivatives were used for the therapeutic reagents. In the middle of the 20th century, the main focus of vanadium chemistry is mainly on the chemical and material fields. After the first discovery of vanadium compounds expressing ATPase activity, oxidovanadium(IV) sulfate was reported to have insulin mimic activity. Additionally, because some vanadium compounds possess cellular toxicity, trials were also carried out to examine the possible use of vanadium compounds as cancer therapeutics. The application of vanadium complexes was extended in recent years especially in the 21st century. In this review, we briefly explain the historical background of vanadium chemistry and also summarize the physiological role of vanadium complexes mainly focusing on the synthesis and physiological role of peroxidovanadium compounds and their interactions with insulin signal transduction pathways.

  18. A role for maternal physiological state in preserving auditory cortical plasticity for salient infant calls

    PubMed Central

    Lin, Frank G.; Galindo-Leon, Edgar E.; Ivanova, Tamara N.; Mappus, Rudolph C.; Liu, Robert C.

    2013-01-01

    A growing interest in sensory system plasticity in the natural context of motherhood has created the need to investigate how intrinsic physiological state (e.g., hormonal, motivational, etc.) interacts with sensory experience to drive adaptive cortical plasticity for behaviorally relevant stimuli. Using a maternal mouse model of auditory cortical inhibitory plasticity for ultrasonic pup calls, we examined the role of pup care versus maternal physiological state in the long-term retention of this plasticity. Very recent experience caring for pups by Early Cocarers, which are virgins, produced stronger call-evoked lateral-band inhibition in auditory cortex. However, this plasticity was absent when measured post-weaning in Cocarers, even though it was present at the same time point in Mothers, whose pup experience occurred under a maternal physiological state. A two-alternative choice phonotaxis task revealed that the same animal groups (Early Cocarers and Mothers) demonstrating stronger lateral-band inhibition also preferred pup calls over a neutral sound, a correlation consistent with the hypothesis that this inhibitory mechanism may play a mnemonic role and is engaged to process sounds that are particularly salient. Our electrophysiological data hints at a possible mechanism through which the maternal physiological state may act to preserve the cortical plasticity: selectively suppressing detrimental spontaneous activity in neurons that are responsive to calls, an effect observed only in Mothers. Taken together, the maternal physiological state during the care of pups may help maintain the memory trace of behaviorally salient infant cues within core auditory cortex, potentially ensuring a more rapid induction of future maternal behavior. PMID:23707982

  19. Causal Structure of Brain Physiology after Brain Injury from Subarachnoid Hemorrhage

    PubMed Central

    Claassen, Jan; Rahman, Shah Atiqur; Huang, Yuxiao; Frey, Hans-Peter; Schmidt, J. Michael; Albers, David; Falo, Cristina Maria; Park, Soojin; Agarwal, Sachin; Connolly, E. Sander; Kleinberg, Samantha

    2016-01-01

    High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology. PMID:27123582

  20. Causal Structure of Brain Physiology after Brain Injury from Subarachnoid Hemorrhage.

    PubMed

    Claassen, Jan; Rahman, Shah Atiqur; Huang, Yuxiao; Frey, Hans-Peter; Schmidt, J Michael; Albers, David; Falo, Cristina Maria; Park, Soojin; Agarwal, Sachin; Connolly, E Sander; Kleinberg, Samantha

    2016-01-01

    High frequency physiologic data are routinely generated for intensive care patients. While massive amounts of data make it difficult for clinicians to extract meaningful signals, these data could provide insight into the state of critically ill patients and guide interventions. We develop uniquely customized computational methods to uncover the causal structure within systemic and brain physiologic measures recorded in a neurological intensive care unit after subarachnoid hemorrhage. While the data have many missing values, poor signal-to-noise ratio, and are composed from a heterogeneous patient population, our advanced imputation and causal inference techniques enable physiologic models to be learned for individuals. Our analyses confirm that complex physiologic relationships including demand and supply of oxygen underlie brain oxygen measurements and that mechanisms for brain swelling early after injury may differ from those that develop in a delayed fashion. These inference methods will enable wider use of ICU data to understand patient physiology. PMID:27123582

  1. The 2-Hydroxycarboxylate Transporter Family: Physiology, Structure, and Mechanism

    PubMed Central

    Sobczak, Iwona; Lolkema, Juke S.

    2005-01-01

    The 2-hydroxycarboxylate transporter family is a family of secondary transporters found exclusively in the bacterial kingdom. They function in the metabolism of the di- and tricarboxylates malate and citrate, mostly in fermentative pathways involving decarboxylation of malate or oxaloacetate. These pathways are found in the class Bacillales of the low-CG gram-positive bacteria and in the gamma subdivision of the Proteobacteria. The pathways have evolved into a remarkable diversity in terms of the combinations of enzymes and transporters that built the pathways and of energy conservation mechanisms. The transporter family includes H+ and Na+ symporters and precursor/product exchangers. The proteins consist of a bundle of 11 transmembrane helices formed from two homologous domains containing five transmembrane segments each, plus one additional segment at the N terminus. The two domains have opposite orientations in the membrane and contain a pore-loop or reentrant loop structure between the fourth and fifth transmembrane segments. The two pore-loops enter the membrane from opposite sides and are believed to be part of the translocation site. The binding site is located asymmetrically in the membrane, close to the interface of membrane and cytoplasm. The binding site in the translocation pore is believed to be alternatively exposed to the internal and external media. The proposed structure of the 2HCT transporters is different from any known structure of a membrane protein and represents a new structural class of secondary transporters. PMID:16339740

  2. The Integrative Role of the Sigh in Psychology, Physiology, Pathology, and Neurobiology

    PubMed Central

    Ramirez, Jan-Marino

    2015-01-01

    “Sighs, tears, grief, distress” expresses Johann Sebastian Bach in a musical example for the relationship between sighs and deep emotions. This review explores the neurobiological basis of the sigh and its relationship with psychology, physiology, and pathology. Sighs monitor changes in brain states, induce arousal, and reset breathing variability. These behavioral roles homeostatically regulate breathing stability under physiological and pathological conditions. Sighs evoked in hypoxia evoke arousal and thereby become critical for survival. Hypoarousal and failure to sigh have been associated with sudden infant death syndrome. Increased breathing irregularity may provoke excessive sighing and hyperarousal, a behavioral sequence that may play a role in panic disorders. Essential for generating sighs and breathing is the pre-Bötzinger complex. Modulatory and synaptic interactions within this local network and between networks located in the brainstem, cerebellum, cortex, hypothalamus, amygdala, and the periaqueductal gray may govern the relationships between physiology, psychology, and pathology. Unraveling these circuits will lead to a better understanding of how we balance emotions and how emotions become pathological. PMID:24746045

  3. The integrative role of the sigh in psychology, physiology, pathology, and neurobiology.

    PubMed

    Ramirez, Jan-Marino

    2014-01-01

    "Sighs, tears, grief, distress" expresses Johann Sebastian Bach in a musical example for the relationship between sighs and deep emotions. This review explores the neurobiological basis of the sigh and its relationship with psychology, physiology, and pathology. Sighs monitor changes in brain states, induce arousal, and reset breathing variability. These behavioral roles homeostatically regulate breathing stability under physiological and pathological conditions. Sighs evoked in hypoxia evoke arousal and thereby become critical for survival. Hypoarousal and failure to sigh have been associated with sudden infant death syndrome. Increased breathing irregularity may provoke excessive sighing and hyperarousal, a behavioral sequence that may play a role in panic disorders. Essential for generating sighs and breathing is the pre-Bötzinger complex. Modulatory and synaptic interactions within this local network and between networks located in the brainstem, cerebellum, cortex, hypothalamus, amygdala, and the periaqueductal gray may govern the relationships between physiology, psychology, and pathology. Unraveling these circuits will lead to a better understanding of how we balance emotions and how emotions become pathological.

  4. The Physiological Role of Arcuate Kisspeptin Neurons in the Control of Reproductive Function in Female Rats

    PubMed Central

    Beale, K.E.; Kinsey-Jones, J.S.; Gardiner, J.V.; Harrison, E.K.; Thompson, E.L.; Hu, M.H.; Sleeth, M.L.; Sam, A.H.; Greenwood, H.C.; McGavigan, A.K.; Dhillo, W.S.; Mora, J.M.; Li, X.F.; Franks, S.; Bloom, S.R.; O'Byrne, K.T.

    2014-01-01

    Kisspeptin plays a pivotal role in pubertal onset and reproductive function. In rodents, kisspeptin perikarya are located in 2 major populations: the anteroventral periventricular nucleus and the hypothalamic arcuate nucleus (ARC). These nuclei are believed to play functionally distinct roles in the control of reproduction. The anteroventral periventricular nucleus population is thought to be critical in the generation of the LH surge. However, the physiological role played by the ARC kisspeptin neurons remains to be fully elucidated. We used bilateral stereotactic injection of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC of adult female rats to investigate the physiological role of kisspeptin neurons in this nucleus. Female rats with kisspeptin knockdown in the ARC displayed a significantly reduced number of both regular and complete oestrous cycles and significantly longer cycles over the 100-day period of the study. Further, kisspeptin knockdown in the ARC resulted in a decrease in LH pulse frequency. These data suggest that maintenance of ARC-kisspeptin levels is essential for normal pulsatile LH release and oestrous cyclicity. PMID:24424033

  5. Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology

    PubMed Central

    Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

    2016-01-01

    Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins’ regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. PMID:26123302

  6. The role of plant physiology in hydrology: looking backwards and forwards

    NASA Astrophysics Data System (ADS)

    Roberts, J.

    2007-01-01

    conservative? An important contribution both to the similar and low transpiration is the likely reduction of stomatal conductance of the foliage associated with increasing air humidity deficit. A greater response is usually found when initial conductances are highest. Also contributing to similarities in transpiration from forest stands would be a compensatory role of understories and that deficits in soil moisture may not come into play until severe soil water deficits occur. Physiological studies have been conducted in many locations overseas. The modest transpiration of tropical rainforest is intriguing - Why is tropical rainforest transpiration so low? In common with temperate trees the reduction of stomatal conductance of tropical trees in association with increasing air humidity deficit will limit transpiration. In addition the high leaf area index of tropical rainforest creates conditions in the lower canopy layers that mean transpiration from those layers is much reduced from what might be possible. As well as being used to quantify and understand transpiration, physiological techniques might be used to assess when plants require water. What is the first signal that plants need water? Studies on sugar cane in Mauritius indicated that leaf growth was the most sensitive measure. A look forward to the future suggests that there will be a continued need for physiological measurements particularly where other techniques more suited to extensive vegetation are not appropriate. There are many unresolved issues about water use from fragmented, heterogeneous vegetation and physiological approaches are best suited to these. The measurement of sap flow in individual stems will be an important methodology in the future but there are still methodological issues to resolve.

  7. 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.

  8. Monomeric Alpha-Synuclein Exerts a Physiological Role on Brain ATP Synthase

    PubMed Central

    Ludtmann, Marthe H.R.; Angelova, Plamena R.; Ninkina, Natalia N.; Gandhi, Sonia

    2016-01-01

    Misfolded α-synuclein is a key factor in the pathogenesis of Parkinson's disease (PD). However, knowledge about a physiological role for the native, unfolded α-synuclein is limited. Using brains of mice lacking α-, β-, and γ-synuclein, we report that extracellular monomeric α-synuclein enters neurons and localizes to mitochondria, interacts with ATP synthase subunit α, and modulates ATP synthase function. Using a combination of biochemical, live-cell imaging and mitochondrial respiration analysis, we found that brain mitochondria of α-, β-, and γ-synuclein knock-out mice are uncoupled, as characterized by increased mitochondrial respiration and reduced mitochondrial membrane potential. Furthermore, synuclein deficiency results in reduced ATP synthase efficiency and lower ATP levels. Exogenous application of low unfolded α-synuclein concentrations is able to increase the ATP synthase activity that rescues the mitochondrial phenotypes observed in synuclein deficiency. Overall, the data suggest that α-synuclein is a previously unrecognized physiological regulator of mitochondrial bioenergetics through its ability to interact with ATP synthase and increase its efficiency. This may be of particular importance in times of stress or PD mutations leading to energy depletion and neuronal cell toxicity. SIGNIFICANCE STATEMENT Misfolded α-synuclein aggregations in the form of Lewy bodies have been shown to be a pathological hallmark in histological staining of Parkinson's disease (PD) patient brains. It is known that misfolded α-synuclein is a key driver in PD pathogenesis, but the physiological role of unfolded monomeric α-synuclein remains unclear. Using neuronal cocultures and isolated brain mitochondria of α-, β-, and γ-synuclein knock-out mice and monomeric α-synuclein, this current study shows that α-synuclein in its unfolded monomeric form improves ATP synthase efficiency and mitochondrial function. The ability of monomeric α-synuclein to enhance

  9. Estradiol protective role in atherogenesis through LDL structure modification

    NASA Astrophysics Data System (ADS)

    Papi, Massimiliano; Brunelli, Roberto; Ciasca, Gabriele; Maiorana, Alessandro; Maulucci, Giuseppe; Palmieri, Valentina; Parasassi, Tiziana; De Spirito, Marco

    2016-07-01

    Relevant physiological functions are exerted by circulating low density lipoprotein (LDL) as well as eventual pathological processes triggering atherogenesis. Modulation of these functions can well be founded on modifications of LDL structure. Given its large dimension, multicomponent organization and strong interactions between the protein apoB-100 and lipids, determining LDL 3D structure remains a challenge. We propose a novel quantitative physical approach to this complex biological problem. We introduce a three-component model, fitted to small angle x-ray scattering data on LDL maintained in physiological conditions, able to achieve a consistent 3D structure. Unexpected features include three distinct protein domains protruding out of a sphere, quite rough in its surface, where several core lipid areas are exposed. All LDL components are affected by 17-β-estradiol (E2) binding to apoB-100. Mostly one of the three protruding protein domains, dramatically reducing its presence on the surface and with a consequent increase of core lipids’ exposure. This result suggests a structural basis for some E2 protecting roles and LDL physiological modifications.

  10. A differential role for nitric oxide in two forms of physiological angiogenesis in mouse

    PubMed Central

    Williams, James L; Cartland, David; Hussain, Arif; Egginton, Stuart

    2006-01-01

    NO plays a role in a variety of in vitro models of angiogenesis, although confounding effects of NO on non-endothelial tissues make its role during in vivo angiogenesis unclear. We therefore examined the effects of NO on two physiological models of angiogenesis in mouse skeletal muscle: (1) administration of prazosin (50 mg l−1) thereby increasing blood flow; and (2) muscle overload from surgical ablation of a functional synergist. These models induce angiogenesis via longitudinal splitting and capillary sprouting, respectively. Administration of NG-nitro-l-arginine (l-NNA) abolished the increase in capillary to fibre ratio (C:F) in response to prazosin administration, along with the increases in luminal filopodia and large endothelial vacuoles. l-NNA prevented luminal filopodia and vacuolisation in response to extirpation, but had no effect on abluminal sprouting, and little effect on C:F. Comparison of mice lacking endothelial (eNOS−/−) and neuronal NO synthase (nNOS−/−) showed that longitudinal splitting is eNOS-dependent, and Western blotting demonstrated an increase in eNOS but not inducible NOS (iNOS) expression. These data show that there are two pathways of physiological angiogenesis in skeletal muscle characterised by longitudinal splitting and capillary sprouting, respectively. NO generated by eNOS plays an essential role in splitting but not in sprouting angiogenesis, which has important implications for angiogenic therapies that target NO. PMID:16293647

  11. Central role of soluble adenylyl cyclase and cAMP in sperm physiology

    PubMed Central

    Buffone, Mariano G.; Wertheimer, Eva V.; Visconti, Pablo E.; Krapf, Dario

    2014-01-01

    Cyclic adenosine 3′,5′-monophosphate (cAMP), the first second messenger to be described, plays a central role in cell signaling in a wide variety of cell types. Over the last decades, a wide body of literature addressed the different roles of cAMP in cell physiology, mainly in response to neurotransmitters and hormones. cAMP is synthesized by a wide variety of adenylyl cylases that can generally be grouped in two types: transmembrane adenylyl cyclase and soluble adenylyl cyclases. In particular, several aspects of sperm physiology are regulated by cAMP produced by a single atypical adenylyl cyclase (Adcy10, aka sAC, SACY). The signature that identifies sAC among other ACs, is their direct stimulation by bicarbonate. The essential nature of cAMP in sperm function has been demonstrated using gain of function as well as loss of function approaches. This review unifies state of the art knowledge of the role of cAMP and those enzymes involved in cAMP signaling pathways required for the acquisition of fertilizing capacity of mammalian sperm. PMID:25066614

  12. Heterogeneity in vascular smooth muscle cell embryonic origin in relation to adult structure, physiology, and disease

    PubMed Central

    Pfaltzgraff, Elise R.; Bader, David M.

    2015-01-01

    Regional differences in vascular physiology and disease response exist throughout the vascular tree. While these differences in physiology and disease correspond to regional vascular environmental conditions, there is also compelling evidence that the embryonic origins of the smooth muscle inherent to the vessels may play a role. Here we review what is known regarding the role of embryonic origin of vascular smooth muscle cells during vascular development. The focus of this review is to highlight the heterogeneity in the origins of vascular smooth muscle cells and the resulting regional physiologies of the vessels. Our goal is to stimulate future investigation into this area and provide a better understanding of vascular organogenesis and disease. PMID:25546231

  13. The kinin-kallikrein system: physiological roles, pathophysiology and its relationship to cancer biomarkers.

    PubMed

    Kashuba, Elena; Bailey, James; Allsup, David; Cawkwell, Lynn

    2013-06-01

    The kinin-kallikrein system (KKS) is an endogenous multiprotein cascade, the activation of which leads to triggering of the intrinsic coagulation pathway and enzymatic hydrolysis of kininogens with the consequent release of bradykinin-related peptides. This system plays a crucial role in inflammation, vasodilation, smooth muscle contraction, cardioprotection, vascular permeability, blood pressure control, coagulation and pain. In this review, we will outline the physiology and pathophysiology of the KKS and also highlight the association of this system with carcinogenesis and cancer progression. PMID:23672534

  14. Senescence Marker Protein 30: Functional and Structural Insights to its Unknown Physiological Function

    PubMed Central

    Scott, Stephanie H.; Bahnson, Brian J.

    2011-01-01

    Senescence marker protein 30 (SMP30) is a multifunctional protein involved in cellular Ca2+ homeostasis and the biosynthesis of ascorbate in non-primate mammals. The primary structure of the protein is highly conserved among vertebrates, suggesting the existence of a significant physiological function common to all mammals, including primates. Enzymatic activities of SMP30 include aldonolactone and organophosphate hydrolysis. Protective effects against apoptosis and oxidative stress have been reported. X-ray crystallography revealed that SMP30 is a six-bladed β-propeller with structural similarity to paraoxonase 1, another protein with lactonase and organophosphate hydrolase activities. SMP30 has recently been tied to several physiological conditions including osteoporosis, liver fibrosis, diabetes, and cancer. This review aims to describe the recent advances made toward understanding the connection between molecular structure, enzymatic activity and physiological function of this highly conserved, multifaceted protein. PMID:22844387

  15. From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology.

    PubMed

    Ligresti, Alessia; De Petrocellis, Luciano; Di Marzo, Vincenzo

    2016-10-01

    Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one Δ(9)-tetrahydrocannabinol, and 2) the adaptive pro-homeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field. PMID:27630175

  16. The Role of Nature in Coping with Psycho-Physiological Stress: A Literature Review on Restorativeness

    PubMed Central

    Berto, Rita

    2014-01-01

    Physical settings can play a role in coping with stress; in particular experimental research has found strong evidence between exposure to natural environments and recovery from physiological stress and mental fatigue, giving support to both Stress Recovery Theory and Attention Restoration Theory. In fact, exposure to natural environments protects people against the impact of environmental stressors and offer physiological, emotional and attention restoration more so than urban environments. Natural places that allow the renewal of personal adaptive resources to meet the demands of everyday life are called restorative environments. Natural environments elicit greater calming responses than urban environments, and in relation to their vision there is a general reduction of physiological symptoms of stress. Exposure to natural scenes mediates the negative effects of stress reducing the negative mood state and above all enhancing positive emotions. Moreover, one can recover the decrease of cognitive performance associated with stress, especially reflected in attention tasks, through the salutary effect of viewing nature. Giving the many benefits of contact with nature, plans for urban environments should attend to restorativeness. PMID:25431444

  17. The role of nature in coping with psycho-physiological stress: a literature review on restorativeness.

    PubMed

    Berto, Rita

    2014-01-01

    Physical settings can play a role in coping with stress; in particular experimental research has found strong evidence between exposure to natural environments and recovery from physiological stress and mental fatigue, giving support to both Stress Recovery Theory and Attention Restoration Theory. In fact, exposure to natural environments protects people against the impact of environmental stressors and offer physiological, emotional and attention restoration more so than urban environments. Natural places that allow the renewal of personal adaptive resources to meet the demands of everyday life are called restorative environments. Natural environments elicit greater calming responses than urban environments, and in relation to their vision there is a general reduction of physiological symptoms of stress. Exposure to natural scenes mediates the negative effects of stress reducing the negative mood state and above all enhancing positive emotions. Moreover, one can recover the decrease of cognitive performance associated with stress, especially reflected in attention tasks, through the salutary effect of viewing nature. Giving the many benefits of contact with nature, plans for urban environments should attend to restorativeness. PMID:25431444

  18. The Role of Psychological and Physiological Factors in Decision Making under Risk and in a Dilemma

    PubMed Central

    Fooken, Jonas; Schaffner, Markus

    2016-01-01

    Different methods to elicit risk attitudes of individuals often provide differing results despite a common theory. Reasons for such inconsistencies may be the different influence of underlying factors in risk-taking decisions. In order to evaluate this conjecture, a better understanding of underlying factors across methods and decision contexts is desirable. In this paper we study the difference in result of two different risk elicitation methods by linking estimates of risk attitudes to gender, age, and personality traits, which have been shown to be related. We also investigate the role of these factors during decision-making in a dilemma situation. For these two decision contexts we also investigate the decision-maker's physiological state during the decision, measured by heart rate variability (HRV), which we use as an indicator of emotional involvement. We found that the two elicitation methods provide different individual risk attitude measures which is partly reflected in a different gender effect between the methods. Personality traits explain only relatively little in terms of driving risk attitudes and the difference between methods. We also found that risk taking and the physiological state are related for one of the methods, suggesting that more emotionally involved individuals are more risk averse in the experiment. Finally, we found evidence that personality traits are connected to whether individuals made a decision in the dilemma situation, but risk attitudes and the physiological state were not indicative for the ability to decide in this decision context. PMID:26834591

  19. From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology.

    PubMed

    Ligresti, Alessia; De Petrocellis, Luciano; Di Marzo, Vincenzo

    2016-10-01

    Apart from having been used and misused for at least four millennia for, among others, recreational and medicinal purposes, the cannabis plant and its most peculiar chemical components, the plant cannabinoids (phytocannabinoids), have the merit to have led humanity to discover one of the most intriguing and pleiotropic endogenous signaling systems, the endocannabinoid system (ECS). This review article aims to describe and critically discuss, in the most comprehensive possible manner, the multifaceted aspects of 1) the pharmacology and potential impact on mammalian physiology of all major phytocannabinoids, and not only of the most famous one Δ(9)-tetrahydrocannabinol, and 2) the adaptive pro-homeostatic physiological, or maladaptive pathological, roles of the ECS in mammalian cells, tissues, and organs. In doing so, we have respected the chronological order of the milestones of the millennial route from medicinal/recreational cannabis to the ECS and beyond, as it is now clear that some of the early steps in this long path, which were originally neglected, are becoming important again. The emerging picture is rather complex, but still supports the belief that more important discoveries on human physiology, and new therapies, might come in the future from new knowledge in this field.

  20. Influence of phosphorus availability on the community structure and physiology of cultured biofilms.

    PubMed

    Li, Shuangshuang; Wang, Chun; Qin, Hongjie; Li, Yinxia; Zheng, Jiaoli; Peng, Chengrong; Li, Dunhai

    2016-04-01

    Biofilms have important effects on nutrient cycling in aquatic ecosystems. However, publications about the community structure and functions under laboratory conditions are rare. This study focused on the developmental and physiological properties of cultured biofilms under various phosphorus concentrations performed in a closely controlled continuous flow incubator. The results showed that the biomass (Chl a) and photosynthesis of algae were inhibited under P-limitation conditions, while the phosphatase activity and P assimilation rate were promoted. The algal community structure of biofilms was more likely related to the colonization stage than with the phosphorus availability. Cyanobacteria were more competitive than other algae in biofilms, particularly when cultured under low P levels. A dominance shift occurred from non-filamentous algae in the early stage to filamentous algae in the mid and late stages under P concentrations of 0.01, 0.1 and 0.6 mg/L. However, the total N content, dry weight biomass and bacterial community structure of biofilms were unaffected by phosphorus availability. This may be attributed to the low respiration rate, high accumulation of extracellular polymeric substances and high alkaline phosphatase activity in biofilms when phosphorus availability was low. The bacterial community structure differed over time, while there was little difference between the four treatments, which indicated that it was mainly affected by the colonization stage of the biofilms rather than the phosphorus availability. Altogether, these results suggested that the development of biofilms was influenced by the phosphorus availability and/or the colonization stage and hence determined the role that biofilms play in the overlying water. PMID:27090691

  1. Interpreting the possible ecological role(s) of cyanotoxins: compounds for competitive advantage and/or physiological aide?

    PubMed

    Holland, Aleicia; Kinnear, Susan

    2013-06-27

    To date, most research on freshwater cyanotoxin(s) has focused on understanding the dynamics of toxin production and decomposition, as well as evaluating the environmental conditions that trigger toxin production, all with the objective of informing management strategies and options for risk reduction. Comparatively few research studies have considered how this information can be used to understand the broader ecological role of cyanotoxin(s), and the possible applications of this knowledge to the management of toxic blooms. This paper explores the ecological, toxicological, and genetic evidence for cyanotoxin production in natural environments. The possible evolutionary advantages of toxin production are grouped into two main themes: That of "competitive advantage" or "physiological aide". The first grouping illustrates how compounds produced by cyanobacteria may have originated from the need for a cellular defence mechanism, in response to grazing pressure and/or resource competition. The second grouping considers the contribution that secondary metabolites make to improved cellular physiology, through benefits to homeostasis, photosynthetic efficiencies, and accelerated growth rates. The discussion also includes other factors in the debate about possible evolutionary roles for toxins, such as different modes of exposures and effects on non-target (i.e., non-competitive) species. The paper demonstrates that complex and multiple factors are at play in driving evolutionary processes in aquatic environments. This information may provide a fresh perspective on managing toxic blooms, including the need to use a "systems approach" to understand how physico-chemical conditions, as well biological stressors, interact to trigger toxin production.

  2. Physiological roles for the subfornical organ: a dynamic transcriptome shaped by autonomic state.

    PubMed

    Hindmarch, Charles Colin Thomas; Ferguson, Alastair V

    2016-03-15

    The subfornical organ (SFO) is a circumventricular organ recognized for its ability to sense and integrate hydromineral and hormonal circulating fluid balance signals, information which is transmitted to central autonomic nuclei to which SFO neurons project. While the role of SFO was once synonymous with physiological responses to osmotic, volumetric and cardiovascular challenge, recent data suggest that SFO neurons also sense and integrate information from circulating signals of metabolic status. Using microarrays, we have confirmed the expression of receptors already described in the SFO, and identified many novel transcripts expressed in this circumventricular organ including receptors for many of the critical circulating energy balance signals such as adiponectin, apelin, endocannabinoids, leptin, insulin and peptide YY. This transcriptome analysis also identified SFO transcripts, the expressions of which are significantly changed by either 72 h dehydration, or 48 h starvation, compared to fed and euhydrated controls. Expression and potential roles for many of these targets are yet to be confirmed and elucidated. Subsequent validation of data for adiponectin and leptin receptors confirmed that receptors for both are expressed in the SFO, that discrete populations of neurons in this tissue are functionally responsive to these adipokines, and that such responsiveness is regulated by physiological state. Thus, transcriptomic analysis offers great promise for understanding the integrative complexity of these physiological systems, especially with development of technologies allowing description of the entire transcriptome of single, carefully phenotyped, SFO neurons. These data will ultimately elucidate mechanisms through which these uniquely positioned neurons respond to and integrate complex circulating signals.

  3. Mechanisms and Physiological Roles of the CBL-CIPK Networking System in Arabidopsis thaliana

    PubMed Central

    Mao, Jingjing; Manik, S. M. Nuruzzaman; Shi, Sujuan; Chao, Jiangtao; Jin, Yirong; Wang, Qian; Liu, Haobao

    2016-01-01

    Calcineurin B-like protein (CBL)-CBL-interacting protein kinase (CIPK) network is one of the vital regulatory mechanisms which decode calcium signals triggered by environmental stresses. Although the complicated regulation mechanisms and some novel functions of CBL-CIPK signaling network in plants need to be further elucidated, numerous advances have been made in its roles involved in the abiotic stresses. This review chiefly introduces the progresses about protein interaction, classification and expression pattern of different CBLs and CIPKs in Arabidopsis thaliana, summarizes the physiological roles of CBL-CIPK pathway while pointing out some new research ideas in the future, and finally presents some unique perspectives for the further study. The review might provide new insights into the functional characterization of CBL-CIPK pathway in Arabidopsis, and contribute to a deeper understanding of CBL-CIPK network in other plants or stresses. PMID:27618104

  4. Insights into the physiological role of WT1 from studies of genetically modified mice.

    PubMed

    Discenza, Maria Teresa; Pelletier, Jerry

    2004-02-13

    The identification of WT1 gene mutations in children with WAGR and Denys-Drash syndromes pointed toward a role for WT1 in genitourinary system development. Biochemical analysis of the different WT1 protein isoforms showed that WT1 is a transcription factor and also has the ability to bind RNA. Analysis of WT1 complexes identified several target genes and protein partners capable of interacting with WT1. Some of these studies placed WT1, its downstream targets, and protein partners in a transcriptional regulatory network that controls urogenital system development. We review herein studies on WT1 knockout and transgenic models that have been instrumental in defining a physiological role for WT1 in normal and abnormal urogenital development.

  5. Mechanisms and Physiological Roles of the CBL-CIPK Networking System in Arabidopsis thaliana.

    PubMed

    Mao, Jingjing; Manik, S M Nuruzzaman; Shi, Sujuan; Chao, Jiangtao; Jin, Yirong; Wang, Qian; Liu, Haobao

    2016-01-01

    Calcineurin B-like protein (CBL)-CBL-interacting protein kinase (CIPK) network is one of the vital regulatory mechanisms which decode calcium signals triggered by environmental stresses. Although the complicated regulation mechanisms and some novel functions of CBL-CIPK signaling network in plants need to be further elucidated, numerous advances have been made in its roles involved in the abiotic stresses. This review chiefly introduces the progresses about protein interaction, classification and expression pattern of different CBLs and CIPKs in Arabidopsis thaliana, summarizes the physiological roles of CBL-CIPK pathway while pointing out some new research ideas in the future, and finally presents some unique perspectives for the further study. The review might provide new insights into the functional characterization of CBL-CIPK pathway in Arabidopsis, and contribute to a deeper understanding of CBL-CIPK network in other plants or stresses. PMID:27618104

  6. Glucose transporters in the uterus: an analysis of tissue distribution and proposed physiological roles

    PubMed Central

    Frolova, Antonina I; Moley, Kelle H

    2016-01-01

    Facilitative glucose transport molecules (glucose transporters, GLUTs) are responsible for glucose transport across cellular membranes. Of the 14 family members, expression of nine has been reported in the murine uterus and seven in the human uterus. Some studies reveal that adequate glucose uptake and metabolism are essential for the proper differentiation of the uterine endometrium toward a receptive state capable of supporting embryo implantation. However, the mechanistic role of GLUTs in endometrial function remains poorly understood. This review aims to present the current knowledge about GLUT expression in the uterus and distribution among the different cell types within the endometrium. In addition, it analyzes the available data in the context of roles GLUTs may play in normal uterine physiology as well as the pathological conditions of infertility, endometrial cancer, and polycystic ovarian syndrome. PMID:21642384

  7. The different role of sex hormones on female cardiovascular physiology and function: not only oestrogens.

    PubMed

    Salerni, Sara; Di Francescomarino, Samanta; Cadeddu, Christian; Acquistapace, Flavio; Maffei, Silvia; Gallina, Sabina

    2015-06-01

    Human response to different physiologic stimuli and cardiovascular (CV) adaptation to various pathologies seem to be gender specific. Sex-steroid hormones have been postulated as the major contributors towards these sex-related differences. This review will discuss current evidence on gender differences in CV function and remodelling, and will present the different role of the principal sex-steroid hormones on female heart. Starting from a review of sex hormones synthesis, receptors and CV signalling, we will summarize the current knowledge concerning the role of sex hormones on the regulation of our daily activities throughout the life, via the modulation of autonomic nervous system, excitation-contraction coupling pathway and ion channels activity. Many unresolved questions remain even if oestrogen effects on myocardial remodelling and function have been extensively studied. So this work will focus attention also on the controversial and complex relationship existing between androgens, progesterone and female heart.

  8. A Trial of the Objective Structured Practical Examination in Physiology at Melaka Manipal Medical College, India

    ERIC Educational Resources Information Center

    Abraham, Reem Rachel; Raghavendra, Rao; Surekha, Kamath; Asha, Kamath

    2009-01-01

    A single examination does not fulfill all the functions of assessment. The present study was undertaken to determine the reliability and student satisfaction regarding the objective structured practical examination (OSPE) as a method of assessment of laboratory exercises in physiology before implementing it in the forthcoming university…

  9. Fabrication of Dendrimer-Based Polyion Complex Submicrometer-Scaled Structures with Enhanced Stability under Physiological Conditions.

    PubMed

    Naoyama, Kenshiro; Mori, Takeshi; Katayama, Yoshiki; Kishimura, Akihiro

    2016-07-01

    Submicrometer-scaled (subμ-) self-assembled materials have been developed based on polyion complex (PIC) formation, in particular for biomedical-applications. However, sufficient stability under physiological conditions is required for their practical use. In this study, PIC formation behavior is examined using a block aniomer, poly(ethylene glycol)-b-poly(aspartic acid), and homocatiomers, poly(l-lysine) (LPK) and dendritic poly(l-lysine) (DPK) with different generations, to elucidate the contribution of the dendritic architecture to stability enhancement. LPK-based PIC shows a subμ-vesicular structure only at 25 °C in the absence of NaCl; in contrast, DPK-based PIC forms a subμ-structure under physiological salt concentration and temperature conditions, even when the number of charges of a single molecule is much smaller than that of LPK. Moreover, the formation of subμ-vesicular and -spherical micellar structures is dependent on DPK generation. Thus, the molecular backbone architecture of the PIC component plays an important role not only in expanding the preparation conditions and enhancing stability, but also in controlling the self-assembled structures, mainly due to the spatially restricted structures of dendrimers. PMID:27191793

  10. The role of anger in the consciousness development of peace activists: where physiology and history intersect.

    PubMed

    Adams, D

    1986-07-01

    The focus of this paper concerns the role of anger in the development of consciousness in peace activists. By looking at this from 3 perspectives we can see an intersection of physiology and history. Looked at most closely, anger is a physiological event that recurs in the life of an individual. From a broader perspective, anger plays a critical role and a particular step in the development of consciousness. And from the broadest perspective, we may see how individual peace activists play a role in history by helping to resolve those contradictions (such as the present one between war and peace) by which history jerks its way forward. To put the proposition most carefully, it will be argued that anger is the personal fuel in the social motor that resolves the institutional contradictions that arise in the course of history. The materials on which this paper is based come from two sources. First is the study I have conducted in recent years on the development of consciousness in peace activists. Wishing to contribute my scientific skills to the peace movement, I have analyzed autobiographies of famous peace activists and oral histories of contemporary activists in Connecticut where I live. Since results from both the autobiographies and the oral histories are similar for present purposes, I will not make any distinction between them. The second source of material is the work that I and other researchers have conducted for many years on the brain mechanisms, behavioral complexities and evolutionary trends of aggressive behavior in rats, cats and monkeys. This material has been extensively published and is referred to in the bibliography (Adams, 1979, 1980).

  11. Physiological roles of glucocorticoids during early embryonic development of the zebrafish (Danio rerio)

    PubMed Central

    Wilson, K S; Matrone, G; Livingstone, D E W; Al-Dujaili, E A S; Mullins, J J; Tucker, C S; Hadoke, P W F; Kenyon, C J; Denvir, M A

    2013-01-01

    While glucocorticoids (GCs) are known to be present in the zebrafish embryo, little is known about their physiological roles at this stage. We hypothesised that GCs play key roles in stress response, hatching and swim activity during early development. To test this, whole embryo cortisol (WEC) and corticosteroid-related genes were measured in embryos from 6 to 120 h post fertilisation (hpf) by enzyme linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Stress response was assessed by change in WEC following stirring, hypoxia or brief electrical impulses applied to the bathing water. The impact of pharmacological and molecular GC manipulation on the stress response, spontaneous hatching and swim activity at different stages of development was also assessed. WEC levels demonstrated a biphasic pattern during development with a decrease from 0 to 36 hpf followed by a progressive increase towards 120 hpf. This was accompanied by a significant and sustained increase in the expression of genes encoding cyp11b1 (GC biosynthesis), hsd11b2 (GC metabolism) and gr (GC receptor) from 48 to 120 hpf. Metyrapone (Met), an inhibitor of 11β-hydroxylase (encoded by cyp11b1), and cyp11b1 morpholino (Mo) knockdown significantly reduced basal and stress-induced WEC levels at 72 and 120 hpf but not at 24 hpf. Spontaneous hatching and swim activity were significantly affected by manipulation of GC action from approximately 48 hpf onwards. We have identified a number of key roles of GCs in zebrafish embryos contributing to adaptive physiological responses under adverse conditions. The ability to alter GC action in the zebrafish embryo also highlights its potential value for GC research. PMID:24167225

  12. Role of light wavelengths in synchronization of circadian physiology in songbirds.

    PubMed

    Yadav, G; Malik, S; Rani, S; Kumar, V

    2015-03-01

    This study investigated whether at identical duration and equal energy level birds presented with short (450nm; blue, B) and long (640nm; red, R) light wavelengths would differentially interpret them and exhibit wavelength-dependent circadian behavioral and physiological responses, despite the difference in their breeding latitudes. Temperate migratory blackheaded buntings (Emberiza melanocephala) and subtropical non-migratory Indian weaverbirds (Ploceus philippinus) initially entrained to 12h light:12h darkness (12L:12D; L=0.33μM/m(2)/s, D=0μM/m(2)/s) in two groups of each, groups 1 and 2, were subjected to constant light (LL, 0.33μM/m(2)/s), which rendered them arrhythmic in the activity behavior. They were then exposed for about two weeks each to 12B:12R and 12R:12B (group 1) or 12R:12B and 12B:12R (group 2) at 0.33μM/m(2)/s light energy level. Blue and red light periods were interpreted as the day and night, respectively, with activity and no-activity in non-migratory weaverbirds or activity and intense activity (Zugunruhe, migratory night restlessness) in the migratory buntings. Consistent with this, plasma melatonin levels under B:R, not R:B, light cycle were low and high in blue and red light periods, respectively. A similar diurnal pattern was absent in the cortisol levels, however. These results show an important role of light wavelengths in synchronization of the circadian clock governed behavior and physiology to the photoperiodic environment, and suggest that photoperiodic timing might be a conserved physiological adaptation in many more birds, regardless of the difference in breeding latitudes, than has been generally envisaged.

  13. Interpreting the Possible Ecological Role(s) of Cyanotoxins: Compounds for Competitive Advantage and/or Physiological Aide?

    PubMed Central

    Holland, Aleicia; Kinnear, Susan

    2013-01-01

    To date, most research on freshwater cyanotoxin(s) has focused on understanding the dynamics of toxin production and decomposition, as well as evaluating the environmental conditions that trigger toxin production, all with the objective of informing management strategies and options for risk reduction. Comparatively few research studies have considered how this information can be used to understand the broader ecological role of cyanotoxin(s), and the possible applications of this knowledge to the management of toxic blooms. This paper explores the ecological, toxicological, and genetic evidence for cyanotoxin production in natural environments. The possible evolutionary advantages of toxin production are grouped into two main themes: That of “competitive advantage” or “physiological aide”. The first grouping illustrates how compounds produced by cyanobacteria may have originated from the need for a cellular defence mechanism, in response to grazing pressure and/or resource competition. The second grouping considers the contribution that secondary metabolites make to improved cellular physiology, through benefits to homeostasis, photosynthetic efficiencies, and accelerated growth rates. The discussion also includes other factors in the debate about possible evolutionary roles for toxins, such as different modes of exposures and effects on non-target (i.e., non-competitive) species. The paper demonstrates that complex and multiple factors are at play in driving evolutionary processes in aquatic environments. This information may provide a fresh perspective on managing toxic blooms, including the need to use a “systems approach” to understand how physico-chemical conditions, as well biological stressors, interact to trigger toxin production. PMID:23807545

  14. Focus on Extracellular Vesicles: Physiological Role and Signalling Properties of Extracellular Membrane Vesicles

    PubMed Central

    Iraci, Nunzio; Leonardi, Tommaso; Gessler, Florian; Vega, Beatriz; Pluchino, Stefano

    2016-01-01

    Extracellular vesicles (EVs) are a heterogeneous population of secreted membrane vesicles, with distinct biogenesis routes, biophysical properties and different functions both in physiological conditions and in disease. The release of EVs is a widespread biological process, which is conserved across species. In recent years, numerous studies have demonstrated that several bioactive molecules are trafficked with(in) EVs, such as microRNAs, mRNAs, proteins and lipids. The understanding of their final impact on the biology of specific target cells remains matter of intense debate in the field. Also, EVs have attracted great interest as potential novel cell-free therapeutics. Here we describe the proposed physiological and pathological functions of EVs, with a particular focus on their molecular content. Also, we discuss the advances in the knowledge of the mechanisms regulating the secretion of EV-associated molecules and the specific pathways activated upon interaction with the target cell, highlighting the role of EVs in the context of the immune system and as mediators of the intercellular signalling in the brain. PMID:26861302

  15. The role of IL-6 in the physiologic versus hypertensive blood pressure actions of angiotensin II

    PubMed Central

    Manhiani, M Marlina; Seth, Dale M; Banes-Berceli, Amy K L; Satou, Ryosuke; Navar, L Gabriel; Brands, Michael W

    2015-01-01

    Angiotensin II (AngII) is a critical physiologic regulator of volume homeostasis and mean arterial pressure (MAP), yet it also is known to induce immune mechanisms that contribute to hypertension. This study determined the role of interleukin-6 (IL-6) in the physiologic effect of AngII to maintain normal MAP during low-salt (LS) intake, and whether hypertension induced by plasma AngII concentrations measured during LS diet required IL-6. IL-6 knockout (KO) and wild-type (WT) mice were placed on LS diet for 7 days, and MAP was measured 19 h/day with telemetry. MAP was not affected by LS in either group, averaging 101 ± 4 and 100 ± 4 mmHg in WT and KO mice, respectively, over the last 3 days. Seven days of ACEI decreased MAP ∼25 mmHg in both groups. In other KO and WT mice, AngII was infused at 200 ng/kg per minute to approximate plasma AngII levels during LS. Surgical reduction of kidney mass and high-salt diet were used to amplify the blood pressure effect. The increase in MAP after 7 days was not different, averaging 20 ± 5 and 22 ± 6 mmHg in WT and KO mice, respectively. Janus Kinase 2 (JAK2)/signal transducer of activated transcription (STAT3) phosphorylation were not affected by LS, but were increased by AngII infusion at 200 and 800 ng/kg per minute. These data suggest that physiologic levels of AngII do not activate or require IL-6 to affect blood pressure significantly, whether AngII is maintaining blood pressure on LS diet or causing blood pressure to increase. JAK2/STAT3 activation, however, is tightly associated with AngII hypertension, even when caused by physiologic levels of AngII. PMID:26486161

  16. Prokaryotic toxin-antitoxin systems--the role in bacterial physiology and application in molecular biology.

    PubMed

    Bukowski, Michal; Rojowska, Anna; Wladyka, Benedykt

    2011-01-01

    Bacteria have developed multiple complex mechanisms ensuring an adequate response to environmental changes. In this context, bacterial cell division and growth are subject to strict control to ensure metabolic balance and cell survival. A plethora of studies cast light on toxin-antitoxin (TA) systems as metabolism regulators acting in response to environmental stress conditions. Many of those studies suggest direct relations between the TA systems and the pathogenic potential or antibiotic resistance of relevant bacteria. Other studies point out that TA systems play a significant role in ensuring stability of mobile genetic material. The evolutionary origin and relations between various TA systems are still a subject of a debate. The impact of toxin-antitoxin systems on bacteria physiology prompted their application in molecular biology as tools allowing cloning of some hard-to-maintain genes, plasmid maintenance and production of recombinant proteins.

  17. The role of methane in mammalian physiology-is it a gasotransmitter?

    PubMed

    Boros, Mihály; Tuboly, Eszter; Mészáros, András; Amann, Anton

    2015-01-27

    Mammalian methanogenesis is widely considered to be an exclusive sign of anaerobic microbial activity in the gastrointestinal tract. This commonly held view was challenged, however, when in vitro and in vivo investigations demonstrated the possibility of nonmicrobial methane formation in aerobic organisms, in plants and animals. The aim of this review is to discuss the available literature data on the biological role of methane. When we evaluate the significance of methane generation in the mammalian physiology, the question may be examined: is it a gas mediator? Overall the data do not fully support the gasotransmitter concept, but they do support the notion that methane liberation may be linked to redox regulation and may be connected with hypoxic events leading to, or associated with a mitochondrial dysfunction. In this respect, the available information suggests that hypoxia-induced methane generation may be a necessary phenomenon of aerobic life, and perhaps a surviving evolutionary trait in the eukaryote cell.

  18. Physiological roles for two periplasmic nitrate reductases in Rhodobacter sphaeroides 2.4.3 (ATCC 17025).

    PubMed

    Hartsock, Angela; Shapleigh, James P

    2011-12-01

    The metabolically versatile purple bacterium Rhodobacter sphaeroides 2.4.3 is a denitrifier whose genome contains two periplasmic nitrate reductase-encoding gene clusters. This work demonstrates nonredundant physiological roles for these two enzymes. One cluster is expressed aerobically and repressed under low oxygen while the second is maximally expressed under low oxygen. Insertional inactivation of the aerobically expressed nitrate reductase eliminated aerobic nitrate reduction, but cells of this strain could still respire nitrate anaerobically. In contrast, when the anaerobic nitrate reductase was absent, aerobic nitrate reduction was detectable, but anaerobic nitrate reduction was impaired. The aerobic nitrate reductase was expressed but not utilized in liquid culture but was utilized during growth on solid medium. Growth on a variety of carbon sources, with the exception of malate, the most oxidized substrate used, resulted in nitrite production on solid medium. This is consistent with a role for the aerobic nitrate reductase in redox homeostasis. These results show that one of the nitrate reductases is specific for respiration and denitrification while the other likely plays a role in redox homeostasis during aerobic growth. PMID:21949073

  19. The mechanistic basis of Myxococcus xanthus rippling behavior and its physiological role during predation.

    PubMed

    Zhang, Haiyang; Vaksman, Zalman; Litwin, Douglas B; Shi, Peng; Kaplan, Heidi B; Igoshin, Oleg A

    2012-01-01

    Myxococcus xanthus cells self-organize into periodic bands of traveling waves, termed ripples, during multicellular fruiting body development and predation on other bacteria. To investigate the mechanistic basis of rippling behavior and its physiological role during predation by this Gram-negative soil bacterium, we have used an approach that combines mathematical modeling with experimental observations. Specifically, we developed an agent-based model (ABM) to simulate rippling behavior that employs a new signaling mechanism to trigger cellular reversals. The ABM has demonstrated that three ingredients are sufficient to generate rippling behavior: (i) side-to-side signaling between two cells that causes one of the cells to reverse, (ii) a minimal refractory time period after each reversal during which cells cannot reverse again, and (iii) physical interactions that cause the cells to locally align. To explain why rippling behavior appears as a consequence of the presence of prey, we postulate that prey-associated macromolecules indirectly induce ripples by stimulating side-to-side contact-mediated signaling. In parallel to the simulations, M. xanthus predatory rippling behavior was experimentally observed and analyzed using time-lapse microscopy. A formalized relationship between the wavelength, reversal time, and cell velocity has been predicted by the simulations and confirmed by the experimental data. Furthermore, the results suggest that the physiological role of rippling behavior during M. xanthus predation is to increase the rate of spreading over prey cells due to increased side-to-side contact-mediated signaling and to allow predatory cells to remain on the prey longer as a result of more periodic cell motility.

  20. Phospholipases of Mineralization Competent Cells and Matrix Vesicles: Roles in Physiological and Pathological Mineralizations

    PubMed Central

    Mebarek, Saida; Abousalham, Abdelkarim; Magne, David; Do, Le Duy; Bandorowicz-Pikula, Joanna; Pikula, Slawomir; Buchet, René

    2013-01-01

    The present review aims to systematically and critically analyze the current knowledge on phospholipases and their role in physiological and pathological mineralization undertaken by mineralization competent cells. Cellular lipid metabolism plays an important role in biological mineralization. The physiological mechanisms of mineralization are likely to take place in tissues other than in bones and teeth under specific pathological conditions. For instance, vascular calcification in arteries of patients with renal failure, diabetes mellitus or atherosclerosis recapitulates the mechanisms of bone formation. Osteoporosis—a bone resorbing disease—and rheumatoid arthritis originating from the inflammation in the synovium are also affected by cellular lipid metabolism. The focus is on the lipid metabolism due to the effects of dietary lipids on bone health. These and other phenomena indicate that phospholipases may participate in bone remodelling as evidenced by their expression in smooth muscle cells, in bone forming osteoblasts, chondrocytes and in bone resorbing osteoclasts. Among various enzymes involved, phospholipases A1 or A2, phospholipase C, phospholipase D, autotaxin and sphingomyelinase are engaged in membrane lipid remodelling during early stages of mineralization and cell maturation in mineralization-competent cells. Numerous experimental evidences suggested that phospholipases exert their action at various stages of mineralization by affecting intracellular signaling and cell differentiation. The lipid metabolites—such as arachidonic acid, lysophospholipids, and sphingosine-1-phosphate are involved in cell signaling and inflammation reactions. Phospholipases are also important members of the cellular machinery engaged in matrix vesicle (MV) biogenesis and exocytosis. They may favour mineral formation inside MVs, may catalyse MV membrane breakdown necessary for the release of mineral deposits into extracellular matrix (ECM), or participate in

  1. The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and disease.

    PubMed

    Oudit, Gavin Y; Sun, Hui; Kerfant, Benoit-Gilles; Crackower, Michael A; Penninger, Josef M; Backx, Peter H

    2004-08-01

    Phosphoinositide-3 kinases (PI3Ks) are a family of evolutionary conserved lipid kinases that mediate many cellular responses in both physiologic and pathophysiologic states. Class I PI3K can be activated by either receptor tyrosine kinase (RTK)/cytokine receptor activation (class I(A)) or G-protein-coupled receptors (GPCR) (class I(B)). Once activated PI3Ks generate phosphatidylinositols (PtdIns) (3,4,5)P(3) leading to the recruitment and activation of Akt/protein kinase B (PKB), PDK1 and monomeric G-proteins (e.g. Rac-GTPases), which then activate a range of downstream targets including glycogen synthase kinase-3beta (GSK-3beta), mammalian target of rapamycin (mTOR), p70S6 kinase, endothelial nitric oxide synthase (eNOS) and several anti-apoptotic effectors. Class I(A) (PI3Kalpha, beta and delta) and class I(B) (PI3Kgamma) PI3Ks mediate distinct phenotypes in the heart and under negative control by the 3'-lipid phosphatase, phosphatase and tensin homolog on chromosome ten (PTEN) which dephosphorylate PtdIns(3,4,5)P(3) into PtdIns(4,5)P(2). PI3Kalpha, gamma and PTEN are expressed in cardiomyocytes, fibroblasts, endothelial cells and vascular smooth muscle cells where they modulate cell survival/apoptosis, hypertrophy, contractility, metabolism and mechanotransduction. Several transgenic and knockout models support a fundamental role of PI3K/PTEN signaling in the regulation of myocardial contractility and hypertrophy. Consequently the PI3K/PTEN signaling pathways are involved in a wide variety of diseases including cardiac hypertrophy, heart failure, preconditioning and hypertension. In this review, we discuss the biochemistry and molecular biology of PI3K (class I isoforms) and PTEN and their critical role in cardiovascular physiology and diseases.

  2. [The role of endocannabinoid system in physiological and pathological processes in the eye].

    PubMed

    Nadolska, Krystyna; Goś, Roman

    2008-01-01

    Plant of Cannabis sativa/ marihuana except for its psychotropic effects possesses a range of pharmacological properties, that has been utilized for medical purposes over a period of millenia. Investigations concerning biochemical mechanism of action of the main and most active pharmacological compound of Cannabis sativa, cannabinoid 9-THC, contributed to the discovery of cannabinoid receptors both in the central nervous system (CNS) and peripheral tissues, that mediated actions of this substance. The discovery made possible identification of a new, endogenous signaling system reffered to as the endocannabinoid system. Besides cannabinoid receptors CB1 and CB2, the system includes it's endogenic ligands (endocannabinoids) and compounds that participate in their biosynthesis and inactivation. Structure and functioning of the endocannabinoid system is conservative in all vertebrates. It's activation with plant, synthetic and endogenous cannabinoids has an influence on multiple physiological and pathological processes within the eye.

  3. The Role of Exercise in Cardiac Aging: From Physiology to Molecular Mechanisms.

    PubMed

    Roh, Jason; Rhee, James; Chaudhari, Vinita; Rosenzweig, Anthony

    2016-01-22

    Aging induces structural and functional changes in the heart that are associated with increased risk of cardiovascular disease and impaired functional capacity in the elderly. Exercise is a diagnostic and therapeutic tool, with the potential to provide insights into clinical diagnosis and prognosis, as well as the molecular mechanisms by which aging influences cardiac physiology and function. In this review, we first provide an overview of how aging impacts the cardiac response to exercise, and the implications this has for functional capacity in older adults. We then review the underlying molecular mechanisms by which cardiac aging contributes to exercise intolerance, and conversely how exercise training can potentially modulate aging phenotypes in the heart. Finally, we highlight the potential use of these exercise models to complement models of disease in efforts to uncover new therapeutic targets to prevent or treat heart disease in the aging population.

  4. Analysis of Structural and Physiological Profiles To Assess the Effects of Cu on Biofilm Microbial Communities

    PubMed Central

    Massieux, B.; Boivin, M. E. Y.; van den Ende, F. P.; Langenskiöld, J.; Marvan, P.; Barranguet, C.; Admiraal, W.; Laanbroek, H. J.; Zwart, G.

    2004-01-01

    We investigated the effects of copper on the structure and physiology of freshwater biofilm microbial communities. For this purpose, biofilms that were grown during 4 weeks in a shallow, slightly polluted ditch were exposed, in aquaria in our laboratory, to a range of copper concentrations (0, 1, 3, and 10 μM). Denaturing gradient gel electrophoresis (DGGE) revealed changes in the bacterial community in all aquaria. The extent of change was related to the concentration of copper applied, indicating that copper directly or indirectly caused the effects. Concomitantly with these changes in structure, changes in the metabolic potential of the heterotrophic bacterial community were apparent from changes in substrate use profiles as assessed on Biolog plates. The structure of the phototrophic community also changed during the experiment, as observed by microscopic analysis in combination with DGGE analysis of eukaryotic microorganisms and cyanobacteria. However, the extent of community change, as observed by DGGE, was not significantly greater in the copper treatments than in the control. Yet microscopic analysis showed a development toward a greater proportion of cyanobacteria in the treatments with the highest copper concentrations. Furthermore, copper did affect the physiology of the phototrophic community, as evidenced by the fact that a decrease in photosynthetic capacity was detected in the treatment with the highest copper concentration. Therefore, we conclude that copper affected the physiology of the biofilm and had an effect on the structure of the communities composing this biofilm. PMID:15294780

  5. Transient Receptor Potential Channels in Microglia: Roles in Physiology and Disease.

    PubMed

    Echeverry, Santiago; Rodriguez, María Juliana; Torres, Yolima P

    2016-10-01

    Microglia modulate the nervous system cellular environment and induce neuroprotective and neurotoxic effects. Various molecules are involved in these processes, including families of ion channels expressed in microglial cells, such as transient receptor potential (TRP) channels. TRP channels comprise a family of non-selective cation channels that can be activated by mechanical, thermal, and chemical stimuli, and which contribute to the regulation of intracellular calcium concentrations. TRP channels have been shown to be involved in cellular processes such as osmotic regulation, cytokine production, proliferation, activation, cell death, and oxidative stress responses. Given the significance of these processes in microglial activity, studies of TRP channels in microglia have focused on determining their roles in both neuroprotective and neurotoxic processes. TRP channel activity has been proposed to play an important function in neurodegenerative diseases, ischemia, inflammatory responses, and neuropathic pain. Modulation of TRP channel activity may thus be considered as a potential therapeutic strategy for the treatment of various diseases associated with alterations of the central nervous system (CNS). In this review, we describe the expression of different subfamilies of TRP channels in microglia, focusing on their physiological and pathophysiological roles, and consider their potential use as therapeutic targets in CNS diseases. PMID:27260222

  6. Transient Receptor Potential Channels in Microglia: Roles in Physiology and Disease.

    PubMed

    Echeverry, Santiago; Rodriguez, María Juliana; Torres, Yolima P

    2016-10-01

    Microglia modulate the nervous system cellular environment and induce neuroprotective and neurotoxic effects. Various molecules are involved in these processes, including families of ion channels expressed in microglial cells, such as transient receptor potential (TRP) channels. TRP channels comprise a family of non-selective cation channels that can be activated by mechanical, thermal, and chemical stimuli, and which contribute to the regulation of intracellular calcium concentrations. TRP channels have been shown to be involved in cellular processes such as osmotic regulation, cytokine production, proliferation, activation, cell death, and oxidative stress responses. Given the significance of these processes in microglial activity, studies of TRP channels in microglia have focused on determining their roles in both neuroprotective and neurotoxic processes. TRP channel activity has been proposed to play an important function in neurodegenerative diseases, ischemia, inflammatory responses, and neuropathic pain. Modulation of TRP channel activity may thus be considered as a potential therapeutic strategy for the treatment of various diseases associated with alterations of the central nervous system (CNS). In this review, we describe the expression of different subfamilies of TRP channels in microglia, focusing on their physiological and pathophysiological roles, and consider their potential use as therapeutic targets in CNS diseases.

  7. Tomato Plant Proteins Actively Responding to Fungal Applications and Their Role in Cell Physiology

    PubMed Central

    Bashir, Zoobia; Shafique, Sobiya; Ahmad, Aqeel; Shafique, Shazia; Yasin, Nasim A.; Ashraf, Yaseen; Ibrahim, Asma; Akram, Waheed; Noreen, Sibgha

    2016-01-01

    The pattern of protein induction in tomato plants has been investigated after the applications of pathogenic and non-pathogenic fungal species. Moreover, particular roles of the most active protein against biological applications were also determined using chromatographic techniques. Alternaria alternata and Penicillium oxalicum were applied as a pathogenic and non-pathogenic fungal species, respectively. Protein profile analysis revealed that a five protein species (i.e., protein 1, 6, 10, 12, and 13) possessed completely coupled interaction with non-pathogenic inducer application (P. oxalicum). However, three protein species (i.e., 10, 12, and 14) recorded a strong positive interaction with both fungal species. Protein 14 exhibited the maximum interaction with fungal applications, and its role in plant metabolism was studied after its identification as protein Q9M1W6. It was determined that protein Q1M1W6 was involved in guaiacyl lignin biosynthesis, and its inhibition increased the coumarin contents in tomato plants. Moreover, it was also observed that the protein Q9M1W6 takes significant part in the biosynthesis of jasmonic acid and Indole acetic acid contents, which are defense and growth factors of tomato plants. The study will help investigators to design fundamental rules of plant proteins affecting cell physiology under the influence of external fungal applications. PMID:27445848

  8. Emerging roles of aquaporins in relation to the physiology of blood-feeding arthropods.

    PubMed

    Benoit, Joshua B; Hansen, Immo A; Szuter, Elise M; Drake, Lisa L; Burnett, Denielle L; Attardo, Geoffrey M

    2014-10-01

    Aquaporins (AQPs) are proteins that span plasma membranes allowing the movement of water and small solutes into or out of cells. The type, expression levels and activity of AQPs play a major role in the relative permeability of each cell to water or other solutes. Research on arthropod AQPs has expanded in the last 10 years due to the completion of several arthropod genome projects and the increased availability of genetic information accessible through other resources such as de novo transcriptome assemblies. In particular, there has been significant advancement in elucidating the roles that AQPs serve in relation to the physiology of blood-feeding arthropods of medical importance. The focus of this review is upon the significance of AQPs in relation to hematophagy in arthropods. This will be accomplished via a narrative describing AQP functions during the life history of hematophagic arthropods that includes the following critical phases: (1) Saliva production necessary to blood feeding, (2) Intake and excretion of water during blood digestion, (3) Reproduction and egg development and (4) Off-host environmental stress tolerance. The concentration on these phases will highlight known vulnerabilities in the biology of hematophagic arthropods that could be used to develop novel control strategies as well as research topics that have yet to be examined.

  9. Tomato Plant Proteins Actively Responding to Fungal Applications and Their Role in Cell Physiology.

    PubMed

    Bashir, Zoobia; Shafique, Sobiya; Ahmad, Aqeel; Shafique, Shazia; Yasin, Nasim A; Ashraf, Yaseen; Ibrahim, Asma; Akram, Waheed; Noreen, Sibgha

    2016-01-01

    The pattern of protein induction in tomato plants has been investigated after the applications of pathogenic and non-pathogenic fungal species. Moreover, particular roles of the most active protein against biological applications were also determined using chromatographic techniques. Alternaria alternata and Penicillium oxalicum were applied as a pathogenic and non-pathogenic fungal species, respectively. Protein profile analysis revealed that a five protein species (i.e., protein 1, 6, 10, 12, and 13) possessed completely coupled interaction with non-pathogenic inducer application (P. oxalicum). However, three protein species (i.e., 10, 12, and 14) recorded a strong positive interaction with both fungal species. Protein 14 exhibited the maximum interaction with fungal applications, and its role in plant metabolism was studied after its identification as protein Q9M1W6. It was determined that protein Q1M1W6 was involved in guaiacyl lignin biosynthesis, and its inhibition increased the coumarin contents in tomato plants. Moreover, it was also observed that the protein Q9M1W6 takes significant part in the biosynthesis of jasmonic acid and Indole acetic acid contents, which are defense and growth factors of tomato plants. The study will help investigators to design fundamental rules of plant proteins affecting cell physiology under the influence of external fungal applications. PMID:27445848

  10. Role of the cAMP-binding protein Epac in cardiovascular physiology and pathophysiology.

    PubMed

    Métrich, Mélanie; Berthouze, Magali; Morel, Eric; Crozatier, Bertrand; Gomez, Ana Maria; Lezoualc'h, Frank

    2010-03-01

    Exchange proteins directly activated by cyclic AMP (Epac) were discovered 10 years ago as new sensors for the second messenger cyclic AMP (cAMP). Epac family, including Epac1 and Epac2, are guanine nucleotide exchange factors for the Ras-like small GTPases Rap1 and Rap2 and function independently of protein kinase A. Given the importance of cAMP in the cardiovascular system, numerous molecular and cellular studies using specific Epac agonists have analyzed the role and the regulation of Epac proteins in cardiovascular physiology and pathophysiology. The specific functions of Epac proteins may depend upon their microcellular environments as well as their expression and localization. This review discusses recent data showing the involvement of Epac in vascular cell migration, endothelial permeability, and inflammation through specific signaling pathways. In addition, we present evidence that Epac regulates the activity of various cellular compartments of the cardiac myocyte and influences calcium handling and excitation-contraction coupling. The potential role of Epac in cardiovascular disorders such as cardiac hypertrophy and remodeling is also discussed.

  11. Role of coronary physiology in the contemporary management of coronary artery disease

    PubMed Central

    Ruparelia, Neil; Kharbanda, Rajesh K

    2015-01-01

    Coronary artery disease (CAD) remains the leading cause of death worldwide with approximately 1 in 30 patients with stable CAD experiencing death or acute myocardial infarction each year. The presence and extent of resultant myocardial ischaemia has been shown to confer an increased risk of adverse outcomes. Whilst, optimal medical therapy (OMT) forms the cornerstone of the management of patients with stable CAD, a significant number of patients present with ischaemia refractory to OMT. Historically coronary angiography alone has been used to determine coronary lesion severity in both stable and acute settings. It is increasingly clear that this approach fails to accurately identify the haemodynamic significance of lesions; especially those that are visually “intermediate” in severity. Revascularisation based upon angiographic appearances alone may not reduce coronary events above OMT. Technological advances have enabled the measurement of physiological indices including the fractional flow reserve, the index of microcirculatory resistance and the coronary flow reserve. The integration of these parameters into the routine management of patients presenting to the cardiac catheterization laboratory with CAD represents a critical adjunctive tool in the optimal management of these patients by identifying patients that would most benefit from revascularisation and importantly also highlighting patients that would not gain benefit and therefore reducing the likelihood of adverse outcomes associated with coronary revascularisation. Furthermore, these techniques are applicable to a broad range of patients including those with left main stem disease, proximal coronary disease, diabetes mellitus, previous percutaneous coronary intervention and with previous coronary artery bypass grafting. This review will discuss current concepts relevant to coronary physiology assessment, its role in the management of both stable and acute patients and future applications. PMID

  12. Questions and controversies in innate immune research: what is the physiological role of NLRP3?

    PubMed

    Coll, R C; O'Neill, Laj; Schroder, K

    2016-01-01

    The NLRP3 inflammasome is a key component of the innate immune system that induces pro-inflammatory cytokine production and cell death. Although NLRP3 is activated by many pathogens, it only appears to be critical for host defense for a limited number of specific infections. NLRP3 is however strongly associated with the initiation and pathology of many inflammatory diseases. If NLRP3 function is largely redundant for host defense, but drives a number of inflammatory diseases, this raises the important question of why evolution has elected to maintain NLRP3 function. We propose that the primary physiological functions of NLRP3 in health are to engage pathways to clear noxious substances (e.g. protein aggregates and crystals), and to regulate metabolism. We discuss the newly identified functions for NLRP3 in metabolic homeostasis, and how NLRP3 beneficial functions in homeostasis may become detrimental during the onset of inflammatory and metabolic diseases. A common feature of most NLRP3-driven diseases is that they are associated with ageing or metabolic excess, and indeed, Nlrp3 deficiency promotes 'healthspan' in ageing mice. This suggests that beneficial functions of NLRP3 in youth may become increasingly countered by NLRP3-dependent pathology as an individual ages, and we propose a general model by which ageing or nutrient excess may provide a tipping point to switch NLRP3 function from beneficial to pathological. The physiological role of NLRP3 in healthy individuals remains incompletely understood and future research will need to address this if NLRP3 is to become a successful therapeutic target for the clinical management of inflammatory diseases. PMID:27551512

  13. Questions and controversies in innate immune research: what is the physiological role of NLRP3?

    PubMed Central

    Coll, RC; O’Neill, LAJ; Schroder, K

    2016-01-01

    The NLRP3 inflammasome is a key component of the innate immune system that induces pro-inflammatory cytokine production and cell death. Although NLRP3 is activated by many pathogens, it only appears to be critical for host defense for a limited number of specific infections. NLRP3 is however strongly associated with the initiation and pathology of many inflammatory diseases. If NLRP3 function is largely redundant for host defense, but drives a number of inflammatory diseases, this raises the important question of why evolution has elected to maintain NLRP3 function. We propose that the primary physiological functions of NLRP3 in health are to engage pathways to clear noxious substances (e.g. protein aggregates and crystals), and to regulate metabolism. We discuss the newly identified functions for NLRP3 in metabolic homeostasis, and how NLRP3 beneficial functions in homeostasis may become detrimental during the onset of inflammatory and metabolic diseases. A common feature of most NLRP3-driven diseases is that they are associated with ageing or metabolic excess, and indeed, Nlrp3 deficiency promotes ‘healthspan’ in ageing mice. This suggests that beneficial functions of NLRP3 in youth may become increasingly countered by NLRP3-dependent pathology as an individual ages, and we propose a general model by which ageing or nutrient excess may provide a tipping point to switch NLRP3 function from beneficial to pathological. The physiological role of NLRP3 in healthy individuals remains incompletely understood and future research will need to address this if NLRP3 is to become a successful therapeutic target for the clinical management of inflammatory diseases. PMID:27551512

  14. Central role of the BK channel in urinary bladder smooth muscle physiology and pathophysiology

    PubMed Central

    2014-01-01

    The physiological functions of the urinary bladder are to store and periodically expel urine. These tasks are facilitated by the contraction and relaxation of the urinary bladder smooth muscle (UBSM), also known as detrusor smooth muscle, which comprises the bladder wall. The large-conductance voltage- and Ca2+-activated K+ (BK, BKCa, MaxiK, Slo1, or KCa1.1) channel is highly expressed in UBSM and is arguably the most important physiologically relevant K+ channel that regulates UBSM function. Its significance arises from the fact that the BK channel is the only K+ channel that is activated by increases in both voltage and intracellular Ca2+. The BK channels control UBSM excitability and contractility by maintaining the resting membrane potential and shaping the repolarization phase of the spontaneous action potentials that determine UBSM spontaneous rhythmic contractility. In UBSM, these channels have complex regulatory mechanisms involving integrated intracellular Ca2+ signals, protein kinases, phosphodiesterases, and close functional interactions with muscarinic and β-adrenergic receptors. BK channel dysfunction is implicated in some forms of bladder pathologies, such as detrusor overactivity, and related overactive bladder. This review article summarizes the current state of knowledge of the functional role of UBSM BK channels under normal and pathophysiological conditions and provides new insight toward the BK channels as targets for pharmacological or genetic control of UBSM function. Modulation of UBSM BK channels can occur by directly or indirectly targeting their regulatory mechanisms, which has the potential to provide novel therapeutic approaches for bladder dysfunction, such as overactive bladder and detrusor underactivity. PMID:24990859

  15. Role of coronary physiology in the contemporary management of coronary artery disease.

    PubMed

    Ruparelia, Neil; Kharbanda, Rajesh K

    2015-02-16

    Coronary artery disease (CAD) remains the leading cause of death worldwide with approximately 1 in 30 patients with stable CAD experiencing death or acute myocardial infarction each year. The presence and extent of resultant myocardial ischaemia has been shown to confer an increased risk of adverse outcomes. Whilst, optimal medical therapy (OMT) forms the cornerstone of the management of patients with stable CAD, a significant number of patients present with ischaemia refractory to OMT. Historically coronary angiography alone has been used to determine coronary lesion severity in both stable and acute settings. It is increasingly clear that this approach fails to accurately identify the haemodynamic significance of lesions; especially those that are visually "intermediate" in severity. Revascularisation based upon angiographic appearances alone may not reduce coronary events above OMT. Technological advances have enabled the measurement of physiological indices including the fractional flow reserve, the index of microcirculatory resistance and the coronary flow reserve. The integration of these parameters into the routine management of patients presenting to the cardiac catheterization laboratory with CAD represents a critical adjunctive tool in the optimal management of these patients by identifying patients that would most benefit from revascularisation and importantly also highlighting patients that would not gain benefit and therefore reducing the likelihood of adverse outcomes associated with coronary revascularisation. Furthermore, these techniques are applicable to a broad range of patients including those with left main stem disease, proximal coronary disease, diabetes mellitus, previous percutaneous coronary intervention and with previous coronary artery bypass grafting. This review will discuss current concepts relevant to coronary physiology assessment, its role in the management of both stable and acute patients and future applications.

  16. A physiological role for cyanate-induced carbonic anhydrase in Escherichia coli.

    PubMed Central

    Guilloton, M B; Lamblin, A F; Kozliak, E I; Gerami-Nejad, M; Tu, C; Silverman, D; Anderson, P M; Fuchs, J A

    1993-01-01

    Cyanate induces expression of the cyn operon in Escherichia coli. The cyn operon includes the gene cynS, encoding cyanase, which catalyzes the reaction of cyanate with bicarbonate to give ammonia and carbon dioxide. A carbonic anhydrase activity was recently found to be encoded by the cynT gene, the first gene of the cyn operon; it was proposed that carbonic anhydrase prevents depletion of bicarbonate during cyanate decomposition due to loss of CO2 by diffusion out of the cell (M. B. Guilloton, J. J. Korte, A. F. Lamblin, J. A. Fuchs, and P. M. Anderson, J. Biol. Chem. 267:3731-3734, 1992). The function of the product of the third gene of this operon, cynX, is unknown. In the study reported here, the physiological roles of cynT and cynX were investigated by construction of chromosomal mutants in which each of the three genes was rendered inactive. The delta cynT chromosomal mutant expressed an active cyanase but no active carbonic anhydrase. In contrast to the wild-type strain, the growth of the delta cynT strain was inhibited by cyanate, and the mutant strain was unable to degrade cyanate and therefore could not use cyanate as the sole nitrogen source when grown at a partial CO2 pressures (pCO2) of 0.03% (air). At a high pCO2 (3%), however, the delta cynT strain behaved like the wild-type strain; it was significantly less sensitive to the toxic effects of cyanate and could degrade cyanate and use cyanate as the sole nitrogen source for growth. These results are consistent with the proposed function for carbonic anhydrase. The chromosomal mutant carrying cynS::kan expressed induced carbonic anhydrase activity but no active cyanase. The cynS::kan mutant was found to be much less sensitive to cyanate than the delta cynT mutant at a low pCO2, indicating that bicarbonate depletion due to the reaction of bicarbonate with cyanate catalyzed by cyanase is more deleterious to growth than direct inhibition by cyanate. Mutants carrying a nonfunctional cynX gene (cynX::kan and

  17. A physiological role for cyanate-induced carbonic anhydrase in Escherichia coli.

    PubMed

    Guilloton, M B; Lamblin, A F; Kozliak, E I; Gerami-Nejad, M; Tu, C; Silverman, D; Anderson, P M; Fuchs, J A

    1993-03-01

    Cyanate induces expression of the cyn operon in Escherichia coli. The cyn operon includes the gene cynS, encoding cyanase, which catalyzes the reaction of cyanate with bicarbonate to give ammonia and carbon dioxide. A carbonic anhydrase activity was recently found to be encoded by the cynT gene, the first gene of the cyn operon; it was proposed that carbonic anhydrase prevents depletion of bicarbonate during cyanate decomposition due to loss of CO2 by diffusion out of the cell (M. B. Guilloton, J. J. Korte, A. F. Lamblin, J. A. Fuchs, and P. M. Anderson, J. Biol. Chem. 267:3731-3734, 1992). The function of the product of the third gene of this operon, cynX, is unknown. In the study reported here, the physiological roles of cynT and cynX were investigated by construction of chromosomal mutants in which each of the three genes was rendered inactive. The delta cynT chromosomal mutant expressed an active cyanase but no active carbonic anhydrase. In contrast to the wild-type strain, the growth of the delta cynT strain was inhibited by cyanate, and the mutant strain was unable to degrade cyanate and therefore could not use cyanate as the sole nitrogen source when grown at a partial CO2 pressures (pCO2) of 0.03% (air). At a high pCO2 (3%), however, the delta cynT strain behaved like the wild-type strain; it was significantly less sensitive to the toxic effects of cyanate and could degrade cyanate and use cyanate as the sole nitrogen source for growth. These results are consistent with the proposed function for carbonic anhydrase. The chromosomal mutant carrying cynS::kan expressed induced carbonic anhydrase activity but no active cyanase. The cynS::kan mutant was found to be much less sensitive to cyanate than the delta cynT mutant at a low pCO2, indicating that bicarbonate depletion due to the reaction of bicarbonate with cyanate catalyzed by cyanase is more deleterious to growth than direct inhibition by cyanate. Mutants carrying a nonfunctional cynX gene (cynX::kan and

  18. The Physiology of Fear: Reconceptualizing the Role of the Central Amygdala in Fear Learning.

    PubMed

    Keifer, Orion P; Hurt, Robert C; Ressler, Kerry J; Marvar, Paul J

    2015-09-01

    The historically understood role of the central amygdala (CeA) in fear learning is to serve as a passive output station for processing and plasticity that occurs elsewhere in the brain. However, recent research has suggested that the CeA may play a more dynamic role in fear learning. In particular, there is growing evidence that the CeA is a site of plasticity and memory formation, and that its activity is subject to tight regulation. The following review examines the evidence for these three main roles of the CeA as they relate to fear learning. The classical role of the CeA as a routing station to fear effector brain structures like the periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the hypothalamus will be briefly reviewed, but specific emphasis is placed on recent literature suggesting that the CeA 1) has an important role in the plasticity underlying fear learning, 2) is involved in regulation of other amygdala subnuclei, and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss the parallels of human and mouse CeA involvement in fear disorders and fear conditioning, respectively.

  19. The Physiology of Fear: Reconceptualizing the Role of the Central Amygdala in Fear Learning

    PubMed Central

    Keifer, Orion P.; Hurt, Robert C.; Ressler, Kerry J.

    2015-01-01

    The historically understood role of the central amygdala (CeA) in fear learning is to serve as a passive output station for processing and plasticity that occurs elsewhere in the brain. However, recent research has suggested that the CeA may play a more dynamic role in fear learning. In particular, there is growing evidence that the CeA is a site of plasticity and memory formation, and that its activity is subject to tight regulation. The following review examines the evidence for these three main roles of the CeA as they relate to fear learning. The classical role of the CeA as a routing station to fear effector brain structures like the periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the hypothalamus will be briefly reviewed, but specific emphasis is placed on recent literature suggesting that the CeA 1) has an important role in the plasticity underlying fear learning, 2) is involved in regulation of other amygdala subnuclei, and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss the parallels of human and mouse CeA involvement in fear disorders and fear conditioning, respectively. PMID:26328883

  20. Does cadmium play a physiological role in the hyperaccumulator Thlaspi caerulescens?

    PubMed

    Liu, Mei-Qing; Yanai, Junta; Jiang, Rong-Feng; Zhang, Fusuo; McGrath, Steve P; Zhao, Fang-Jie

    2008-04-01

    The southern French (Ganges) ecotype of Thlaspi caerulescens J & C Presl is able to hyperaccumulate several thousand mg Cd kg(-1) shoot dry weight without suffering from phytotoxicity. We investigated the effect of Cd on growth and the activity of carbonic anhydrase (CA), a typical Zn-requiring enzyme, of T. caerulescens in soil and hydroponic experiments. In one of the hydroponic experiments, T. caerulescens was compared to the non-accumulator Thlaspi ferganense N. Busch. In the soil experiment, additions of Cd at 5-500 mg kg(-1) soil increased the growth of T. caerulescens significantly. In the hydroponic experiments, exposure to Cd at 1-50 microM for three weeks had no significant effect on the growth of T. caerulescens, but decreased the growth of T. ferganense markedly even at the lowest concentration of Cd (1muM). Cadmium exposure significantly increased the CA activity in T. caerulescens, but decreased it in T. ferganense. The CA activity in T. caerulescens correlated positively with the Cd concentration in the shoots up to 6000 mg kg(-1), even though shoot Zn concentration was decreased by the Cd treatments. For comparison, Cd treatments had no consistent effect on the activity of superoxide dismutase in T. caerulescens. The results suggest that Cd may play a physiological role in the Cd-hyperaccumulating ecotype of T. caerulescens by enhancing the activities of some enzymes such as CA. Further research is needed to establish whether a Cd-requiring CA exists in T. caerulescens. PMID:18262587

  1. Dominance of Saccharomyces cerevisiae in alcoholic fermentation processes: role of physiological fitness and microbial interactions.

    PubMed

    Albergaria, Helena; Arneborg, Nils

    2016-03-01

    Winemaking, brewing and baking are some of the oldest biotechnological processes. In all of them, alcoholic fermentation is the main biotransformation and Saccharomyces cerevisiae the primary microorganism. Although a wide variety of microbial species may participate in alcoholic fermentation and contribute to the sensory properties of end-products, the yeast S. cerevisiae invariably dominates the final stages of fermentation. The ability of S. cerevisiae to outcompete other microbial species during alcoholic fermentation processes, such as winemaking, has traditionally been ascribed to its high fermentative power and capacity to withstand the harsh environmental conditions, i.e. high levels of ethanol and organic acids, low pH values, scarce oxygen availability and depletion of certain nutrients. However, in recent years, several studies have raised evidence that S. cerevisiae, beyond its remarkable fitness for alcoholic fermentation, also uses defensive strategies mediated by different mechanisms, such as cell-to-cell contact and secretion of antimicrobial peptides, to combat other microorganisms. In this paper, we review the main physiological features underlying the special aptitude of S. cerevisiae for alcoholic fermentation and discuss the role of microbial interactions in its dominance during alcoholic fermentation, as well as its relevance for winemaking.

  2. Acylcarnitines--old actors auditioning for new roles in metabolic physiology.

    PubMed

    McCoin, Colin S; Knotts, Trina A; Adams, Sean H

    2015-10-01

    Perturbations in metabolic pathways can cause substantial increases in plasma and tissue concentrations of long-chain acylcarnitines (LCACs). For example, the levels of LCACs and other acylcarnitines rise in the blood and muscle during exercise, as changes in tissue pools of acyl-coenzyme A reflect accelerated fuel flux that is incompletely coupled to mitochondrial energy demand and capacity of the tricarboxylic acid cycle. This natural ebb and flow of acylcarnitine generation and accumulation contrasts with that of inherited fatty acid oxidation disorders (FAODs), cardiac ischaemia or type 2 diabetes mellitus. These conditions are characterized by very high (FAODs, ischaemia) or modestly increased (type 2 diabetes mellitus) tissue and blood levels of LCACs. Although specific plasma concentrations of LCACs and chain-lengths are widely used as diagnostic markers of FAODs, research into the potential effects of excessive LCAC accumulation or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. Nevertheless, a growing body of evidence has highlighted possible effects of LCACs on disparate aspects of pathophysiology, such as cardiac ischaemia outcomes, insulin sensitivity and inflammation. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among individuals with metabolic disorders. PMID:26303601

  3. Left Atrial Appendage: Physiology, Pathology, and Role as a Therapeutic Target.

    PubMed

    Regazzoli, Damiano; Ancona, Francesco; Trevisi, Nicola; Guarracini, Fabrizio; Radinovic, Andrea; Oppizzi, Michele; Agricola, Eustachio; Marzi, Alessandra; Sora, Nicoleta Carmen; Della Bella, Paolo; Mazzone, Patrizio

    2015-01-01

    Atrial fibrillation (AF) is the most common clinically relevant cardiac arrhythmia. AF poses patients at increased risk of thromboembolism, in particular ischemic stroke. The CHADS2 and CHA2DS2-VASc scores are useful in the assessment of thromboembolic risk in nonvalvular AF and are utilized in decision-making about treatment with oral anticoagulation (OAC). However, OAC is underutilized due to poor patient compliance and contraindications, especially major bleedings. The Virchow triad synthesizes the pathogenesis of thrombogenesis in AF: endocardial dysfunction, abnormal blood stasis, and altered hemostasis. This is especially prominent in the left atrial appendage (LAA), where the low flow reaches its minimum. The LAA is the remnant of the embryonic left atrium, with a complex and variable morphology predisposing to stasis, especially during AF. In patients with nonvalvular AF, 90% of thrombi are located in the LAA. So, left atrial appendage occlusion could be an interesting and effective procedure in thromboembolism prevention in AF. After exclusion of LAA as an embolic source, the remaining risk of thromboembolism does not longer justify the use of oral anticoagulants. Various surgical and catheter-based methods have been developed to exclude the LAA. This paper reviews the physiological and pathophysiological role of the LAA and catheter-based methods of LAA exclusion.

  4. Essential Role of microRNA in Skin Physiology and Disease.

    PubMed

    Glavač, Damjan; Ravnik-Glavač, Metka

    2015-01-01

    The identification and characterization of microRNAs (miRNAs) is a rapidly growing area of research also in dermatology. Skin represents the largest organ in the human body, and its morphogenesis has been shown to require a highly coordinated and undisrupted miRNA profile. High expression of several miRNAs in the epidermis and hair follicles is necessary for normal skin development. Profiling studies have identified numerous differentially regulated miRNAs associated with either normal physiological status of the skin or some pathological processes or both. This chapter covers current knowledge of the important roles of miRNAs in the pathogenesis of some skin diseases including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), psoriasis (PS), and skin cancer, especially malignant melanoma (MM). In addition, the diagnostic and therapeutic relevance of miRNAs that are involved in pathological processes of the skin are elucidated providing further information for some possible clinical implications especially for their use as therapeutic targets or disease biomarkers. PMID:26663190

  5. Beyond cellular detoxification: a plethora of physiological roles for MDR transporter homologs in plants

    PubMed Central

    Remy, Estelle; Duque, Paula

    2014-01-01

    Higher plants possess a multitude of Multiple Drug Resistance (MDR) transporter homologs that group into three distinct and ubiquitous families—the ATP-Binding Cassette (ABC) superfamily, the Major Facilitator Superfamily (MFS), and the Multidrug And Toxic compound Extrusion (MATE) family. As in other organisms, such as fungi, mammals, and bacteria, MDR transporters make a primary contribution to cellular detoxification processes in plants, mainly through the extrusion of toxic compounds from the cell or their sequestration in the central vacuole. This review aims at summarizing the currently available information on the in vivo roles of MDR transporters in plant systems. Taken together, these data clearly indicate that the biological functions of ABC, MFS, and MATE carriers are not restricted to xenobiotic and metal detoxification. Importantly, the activity of plant MDR transporters also mediates biotic stress resistance and is instrumental in numerous physiological processes essential for optimal plant growth and development, including the regulation of ion homeostasis and polar transport of the phytohormone auxin. PMID:24910617

  6. Physiological and therapeutical roles of ginger and turmeric on endocrine functions.

    PubMed

    Al-Suhaimi, Ebtesam A; Al-Riziza, Noorah A; Al-Essa, Reham A

    2011-01-01

    The natural product ginger (Zingiber officinale) has active constituents gingerol, Shogaol and Zerumbone, while turmeric (Curcuma longa) contains three active major curcuminoids, namely, curcumin, demethoxycurcumin, and bisdemethoxycurcumin. They have the same scientific classification and are reported to have anti-inflammatory and many therapeutic effects. This article reviews the physiological and therapeutic effects of ginger and turmeric on some endocrine gland functions, and signal pathways involved to mediate their actions. With some systems and adipose tissue, ginger and turmeric exert their actions through some/all of the following signals or molecular mechanisms: (1) through reduction of high levels of some hormones (as: T4, leptin) or interaction with hormone receptors; (2) by inhibition of cytokines/adipokine expression; (3) acting as a potent inhibitor of reactive oxygen species (ROS)-generating enzymes, which play an essential role between inflammation and progression of diseases; (4) mediation of their effects through the inhibition of signaling transcription factors; and/or (5) decrease the proliferative potent by down-regulation of antiapoptotic genes, which may suppress tumor promotion by blocking signal transduction pathways in the target cells. These multiple mechanisms of protection against inflammation and oxidative damage make ginger and curcumin particularly promising natural agents in fighting the ravages of aging and degenerative diseases, and need to be paid more attention by studies.

  7. Data supporting the role of enzymes and polysaccharides during cassava postharvest physiological deterioration.

    PubMed

    Uarrota, Virgílio Gavicho; Moresco, Rodolfo; Schmidt, Eder Carlos; Bouzon, Zenilda Laurita; da Costa Nunes, Eduardo; de Oliveira Neubert, Enilto; Peruch, Luiz Augusto Martins; Rocha, Miguel; Maraschin, Marcelo

    2016-03-01

    This data article is referred to the research article entitled The role of ascorbate peroxidase, guaiacol peroxidase, and polysaccharides in cassava (Manihot esculenta Crantz) roots under postharvest physiological deterioration by Uarrota et al. (2015). Food Chemistry 197, Part A, 737-746. The stress duo to PPD of cassava roots leads to the formation of ROS which are extremely harmful and accelerates cassava spoiling. To prevent or alleviate injuries from ROS, plants have evolved antioxidant systems that include non-enzymatic and enzymatic defence systems such as ascorbate peroxidase, guaiacol peroxidase and polysaccharides. In this data article can be found a dataset called "newdata", in RData format, with 60 observations and 06 variables. The first 02 variables (Samples and Cultivars) and the last 04, spectrophotometric data of ascorbate peroxidase, guaiacol peroxidase, tocopherol, total proteins and arcsined data of cassava PPD scoring. For further interpretation and analysis in R software, a report is also provided. Means of all variables and standard deviations are also provided in the Supplementary tables ("data.long3.RData, data.long4.RData and meansEnzymes.RData"), raw data of PPD scoring without transformation (PPDmeans.RData) and days of storage (days.RData) are also provided for data analysis reproducibility in R software.

  8. Biological underpinnings of breastfeeding challenges: the role of genetics, diet, and environment on lactation physiology.

    PubMed

    Lee, Sooyeon; Kelleher, Shannon L

    2016-08-01

    Lactation is a dynamic process that has evolved to produce a complex biological fluid that provides nutritive and nonnutritive factors to the nursing offspring. It has long been assumed that once lactation is successfully initiated, the primary factor regulating milk production is infant demand. Thus, most interventions have focused on improving breastfeeding education and early lactation support. However, in addition to infant demand, increasing evidence from studies conducted in experimental animal models, production animals, and breastfeeding women suggests that a diverse array of maternal factors may also affect milk production and composition. In this review, we provide an overview of our current understanding of the role of maternal genetics and modifiable factors, such as diet and environmental exposures, on reproductive endocrinology, lactation physiology, and the ability to successfully produce milk. To identify factors that may affect lactation in women, we highlight some information gleaned from studies in experimental animal models and production animals. Finally, we highlight the gaps in current knowledge and provide commentary on future research opportunities aimed at improving lactation outcomes in breastfeeding women to improve the health of mothers and their infants. PMID:27354238

  9. Data supporting the role of enzymes and polysaccharides during cassava postharvest physiological deterioration

    PubMed Central

    Uarrota, Virgílio Gavicho; Moresco, Rodolfo; Schmidt, Eder Carlos; Bouzon, Zenilda Laurita; da Costa Nunes, Eduardo; de Oliveira Neubert, Enilto; Peruch, Luiz Augusto Martins; Rocha, Miguel; Maraschin, Marcelo

    2016-01-01

    This data article is referred to the research article entitled The role of ascorbate peroxidase, guaiacol peroxidase, and polysaccharides in cassava (Manihot esculenta Crantz) roots under postharvest physiological deterioration by Uarrota et al. (2015). Food Chemistry 197, Part A, 737–746. The stress duo to PPD of cassava roots leads to the formation of ROS which are extremely harmful and accelerates cassava spoiling. To prevent or alleviate injuries from ROS, plants have evolved antioxidant systems that include non-enzymatic and enzymatic defence systems such as ascorbate peroxidase, guaiacol peroxidase and polysaccharides. In this data article can be found a dataset called “newdata”, in RData format, with 60 observations and 06 variables. The first 02 variables (Samples and Cultivars) and the last 04, spectrophotometric data of ascorbate peroxidase, guaiacol peroxidase, tocopherol, total proteins and arcsined data of cassava PPD scoring. For further interpretation and analysis in R software, a report is also provided. Means of all variables and standard deviations are also provided in the Supplementary tables (“data.long3.RData, data.long4.RData and meansEnzymes.RData”), raw data of PPD scoring without transformation (PPDmeans.RData) and days of storage (days.RData) are also provided for data analysis reproducibility in R software. PMID:26900596

  10. Acylcarnitines--old actors auditioning for new roles in metabolic physiology.

    PubMed

    McCoin, Colin S; Knotts, Trina A; Adams, Sean H

    2015-10-01

    Perturbations in metabolic pathways can cause substantial increases in plasma and tissue concentrations of long-chain acylcarnitines (LCACs). For example, the levels of LCACs and other acylcarnitines rise in the blood and muscle during exercise, as changes in tissue pools of acyl-coenzyme A reflect accelerated fuel flux that is incompletely coupled to mitochondrial energy demand and capacity of the tricarboxylic acid cycle. This natural ebb and flow of acylcarnitine generation and accumulation contrasts with that of inherited fatty acid oxidation disorders (FAODs), cardiac ischaemia or type 2 diabetes mellitus. These conditions are characterized by very high (FAODs, ischaemia) or modestly increased (type 2 diabetes mellitus) tissue and blood levels of LCACs. Although specific plasma concentrations of LCACs and chain-lengths are widely used as diagnostic markers of FAODs, research into the potential effects of excessive LCAC accumulation or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. Nevertheless, a growing body of evidence has highlighted possible effects of LCACs on disparate aspects of pathophysiology, such as cardiac ischaemia outcomes, insulin sensitivity and inflammation. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among individuals with metabolic disorders.

  11. Genetic and pharmacological analysis identifies a physiological role for the AHR in epidermal differentiation

    PubMed Central

    van den Bogaard, Ellen; Podolsky, Michael; Smits, Jos; Cui, Xiao; John, Christian; Gowda, Krishne; Desai, Dhimant; Amin, Shantu; Schalkwijk, Joost; Perdew, Gary H.

    2015-01-01

    Stimulation of the aryl hydrocarbon receptor (AHR) by xenobiotics is known to affect epidermal differentiation and skin barrier formation. The physiological role of endogenous AHR signaling in keratinocyte differentiation is not known. We used murine and human skin models to address the hypothesis that AHR activation is required for normal keratinocyte differentiation. Using transcriptome analysis of Ahr-/- and Ahr+/+ murine keratinocytes, we found significant enrichment of differentially expressed genes linked to epidermal differentiation. Primary Ahr-/- keratinocytes showed a significant reduction in terminal differentiation gene and protein expression, similar to Ahr+/+ keratinocytes treated with AHR antagonists GNF351 and CH223191, or the selective AHR modulator (SAhRM), SGA360. In vitro keratinocyte differentiation led to increased AHR levels and subsequent nuclear translocation, followed by induced CYP1A1 gene expression. Monolayer cultured primary human keratinocytes treated with AHR antagonists also showed an impaired terminal differentiation program. Inactivation of AHR activity during human skin equivalent development severely impaired epidermal stratification, terminal differentiation protein expression and stratum corneum formation. As disturbed epidermal differentiation is a main feature of many skin diseases, pharmacological agents targeting AHR signaling or future identification of endogenous keratinocyte-derived AHR ligands should be considered as potential new drugs in dermatology. PMID:25602157

  12. Cytochrome c maturation and the physiological role of c-type cytochromes in Vibrio cholerae.

    PubMed

    Braun, Martin; Thöny-Meyer, Linda

    2005-09-01

    Vibrio cholerae lives in different habitats, varying from aquatic ecosystems to the human intestinal tract. The organism has acquired a set of electron transport pathways for aerobic and anaerobic respiration that enable adaptation to the various environmental conditions. We have inactivated the V. cholerae ccmE gene, which is required for cytochrome c biogenesis. The resulting strain is deficient of all c-type cytochromes and allows us to characterize the physiological role of these proteins. Under aerobic conditions in rich medium, V. cholerae produces at least six c-type cytochromes, none of which is required for growth. Wild-type V. cholerae produces active fumarate reductase, trimethylamine N-oxide reductase, cbb3 oxidase, and nitrate reductase, of which only the fumarate reductase does not require maturation of c-type cytochromes. The reduction of nitrate in the medium resulted in the accumulation of nitrite, which is toxic for the cells. This suggests that V. cholerae is able to scavenge nitrate from the environment only in the presence of other nitrite-reducing organisms. The phenotypes of cytochrome c-deficient V. cholerae were used in a transposon mutagenesis screening to search for additional genes required for cytochrome c maturation. Over 55,000 mutants were analyzed for nitrate reductase and cbb3 oxidase activity. No transposon insertions other than those within the ccm genes for cytochrome c maturation and the dsbD gene, which encodes a disulphide bond reductase, were found. In addition, the role of a novel CcdA-like protein in cbb3 oxidase assembly is discussed.

  13. Thiamine triphosphate: a ubiquitous molecule in search of a physiological role.

    PubMed

    Bettendorff, Lucien; Lakaye, Bernard; Kohn, Gregory; Wins, Pierre

    2014-12-01

    Thiamine triphosphate (ThTP) was discovered over 60 years ago and it was long thought to be a specifically neuroactive compound. Its presence in most cell types, from bacteria to mammals, would suggest a more general role but this remains undefined. In contrast to thiamine diphosphate (ThDP), ThTP is not a coenzyme. In E. coli cells, ThTP is transiently produced in response to amino acid starvation, while in mammalian cells, it is constitutively produced at a low rate. Though it was long thought that ThTP was synthesized by a ThDP:ATP phosphotransferase, more recent studies indicate that it can be synthesized by two different enzymes: (1) adenylate kinase 1 in the cytosol and (2) FoF1-ATP synthase in brain mitochondria. Both mechanisms are conserved from bacteria to mammals. Thus ThTP synthesis does not seem to require a specific enzyme. In contrast, its hydrolysis is catalyzed, at least in mammalian tissues, by a very specific cytosolic thiamine triphosphatase (ThTPase), controlling the steady-state cellular concentration of ThTP. In some tissues where adenylate kinase activity is high and ThTPase is absent, ThTP accumulates, reaching ≥ 70% of total thiamine, with no obvious physiological consequences. In some animal tissues, ThTP was able to phosphorylate proteins, and activate a high-conductance anion channel in vitro. These observations raise the possibility that ThTP is part of a still uncharacterized cellular signaling pathway. On the other hand, its synthesis by a chemiosmotic mechanism in mitochondria and respiring bacteria might suggest a role in cellular energetics.

  14. ROLE OF ANTHROPOGENIC AND ENVIRONMENTAL VARIABLE ON THE PHYSIOLOGICAL AND ECOLOGICAL RESPONSES OF OYSTERS IN SOUTHWEST FLORIDA ESTUARIES

    EPA Science Inventory

    The role of freshwater alterations and seasonal changes on the ecological and physiological responses of oysters were investigated in the Caloosahatchee River, Estero Bay and Faka-Union estuaries in SW Florida. Condition index, oyster density, and disease incidence of Perkinsus m...

  15. Use of Wikiversity and Role Play to Increase Student Engagement during Student-Led Physiology Seminars

    ERIC Educational Resources Information Center

    Singh, Satendra

    2013-01-01

    The Undergraduate Medical Program (Bachelor of Medicine and Bachelor of Surgery) at University College of Medical Sciences (Delhi, India) is a 4.5-yr, intense academic program where physiology is taught in the first year. To make the learning experience enriching, the Department of Physiology organizes four student seminars (two seminars/semester)…

  16. Drug Sensitivity in Older Adults: The Role of Physiologic and Pharmacokinetic Factors.

    ERIC Educational Resources Information Center

    Cherry, Katie E.; Morton, Mark R.

    1989-01-01

    Notes that age-related changes in physiology and pharmacokinetics (how drugs are used in the body) lead to increased drug sensitivity and potentially harmful drug effects. Addresses heightened sensitivity to drug effects seen in older adults. Presents three examples of physiologic decline and discusses some broad considerations for geriatric…

  17. Arterial calcification and bone physiology: role of the bone-vascular axis

    PubMed Central

    Thompson, Bithika; Towler, Dwight A.

    2012-01-01

    Bone never forms without vascular interactions. This simple statement of fact does not adequately reflect the physiological and pharmacological implications of the relationship. The vasculature is the conduit for nutrient exchange between bone and the rest of the body. The vasculature provides the sustentacular niche for development of osteoblast progenitors, and is the conduit for egress of bone marrow cell products arising, in turn, from the osteoblast-dependent hematopoietic niche. Importantly, the second most calcified structure in humans after the skeleton is the vasculature. Once considered a passive process of dead and dying cells, vascular calcification has emerged as an actively regulated form of tissue biomineralization. Skeletal morphogens and osteochondrogenic transcription factors are elaborated by cells within the vessel wall, regulating the deposition of vascular calcium. Osteotropic hormones including parathyroid hormone regulate both vascular and skeletal mineralization. Cellular, endocrine, and metabolic signals flow bidirectionally between the vasculature and bone that are necessary for both bone health and vascular health. Dysmetabolic states including diabetes, uremia, and hyperlipidemia perturb the bone-vascular axis, giving rise to devastating vascular and skeletal disease. A detailed understanding of bone-vascular interactions is needed to address the unmet clinical needs of our increasingly aged and dysmetabolic population. PMID:22473330

  18. A role for water in cell structure.

    PubMed Central

    Watterson, J G

    1987-01-01

    The question of a role for water in biochemical and cellular events is ignored by most workers (apart from its obvious role in hydrolysis reactions, which is not under discussion here). But much recent research has pointed to the importance of physical, as well as biochemical, processes of the cell, which focus attention on such straightforward elementary questions as position and relationship in space of cell components. In this communication these questions are examined in terms of a new model of water structure. A radically new feature of this model is that water clusters have long-term rather than flickering existence and are as large as the macromolecular components of the cell. These properties allow the clusters and other components to pack together spatially so giving rise to integrated, large-scale, subcellular structures. PMID:3435470

  19. Experimental evidence for the physiological role of bacterial luciferase in the protection of cells against oxidative stress.

    PubMed

    Szpilewska, Hanna; Czyz, Agata; Wegrzyn, Grzegorz

    2003-11-01

    The origin and function of bioluminescence was considered a problematic question of the Charles Darwin theory. Early evolution of bacterial luminescence and its current physiological importance seem to be especially mysterious. Recently, it was proposed that stimulation of DNA repair may be a physiological role for production of light by bacterial cells. On the other hand, it was also proposed that primary role of luminescent systems could be detoxification of the deleterious oxygen derivatives. Although some previous results might suggest that this hypothesis can be correct, until now experimental evidence for such a mechanism operating in bacterial cells and having physiological importance was generally lacking. Here we demonstrate that in the presence of various oxidants (hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide, and ferrous ions) at certain concentrations in the culture medium, growth of Vibrio harveyi mutants luxA and luxB, but not of the mutant luxD, is severely impaired relative to wild-type bacteria. This deleterious effect of oxidants on the mutants luxA and luxB could be significantly reduced by addition of the antioxidants A-TEMPO or 40H-TEMPO. We conclude that bacterial luciferase may indeed play a physiological role in the protection of cells against oxidative stress.

  20. Physiological enzymology: The next frontier in understanding protein structure and function at the cellular level.

    PubMed

    Lee, Irene; Berdis, Anthony J

    2016-01-01

    Historically, the study of proteins has relied heavily on characterizing the activity of a single purified protein isolated from other cellular components. This classic approach allowed scientists to unambiguously define the intrinsic kinetic and chemical properties of that protein. The ultimate hope was to extrapolate this information toward understanding how the enzyme or receptor behaves within its native cellular context. These types of detailed in vitro analyses were necessary to reduce the innate complexities of measuring the singular activity and biochemical properties of a specific enzyme without interference from other enzymes and potential competing substrates. However, recent developments in fields encompassing cell biology, molecular imaging, and chemical biology now provide the unique chemical tools and instrumentation to study protein structure, function, and regulation in their native cellular environment. These advancements provide the foundation for a new field, coined physiological enzymology, which quantifies the function and regulation of enzymes and proteins at the cellular level. In this Special Edition, we explore the area of Physiological Enzymology and Protein Function through a series of review articles that focus on the tools and techniques used to measure the cellular activity of proteins inside living cells. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions.

  1. Physiology complements population structure of two endemic log-dwelling beetles.

    PubMed

    Schmuki, Christina; Woodman, James D; Sunnucks, Paul

    2007-06-01

    Given rapid, global land modification and the likelihood of major global climate changes, it is becoming increasingly important to understand the physiological limits and capabilities of species to allow more accurate prediction of species' distributions under different scenarios of climate and landscape management. We studied whether the different habitat requirements of two species of tenebrionid beetles in temperate eucalypt forest could explain their patterns of dispersal and gene flow by applying flow-through respirometry to analysis of their physiological responses to different, ecologically relevant temperatures. Both Adelium calosomoides and Apasis puncticeps showed sensitivity to increasing temperatures (in terms of water loss), but Ap. puncticeps lost more water per unit of CO2 produced than did Ad. calosomoides. Recovery time from chill coma was also significantly longer for Ap. puncticeps than Ad. calosomoides. This supported prior qualitative assessment that Ap. puncticeps is more of a habitat specialist than Ad. calosomoides, at least concerning the critical factor of moisture requirements, and is consistent with stronger population genetic patterning and inferred low mobility of Ap. puncticeps. Despite its relatively lower mobility as deduced from population genetic structure, Ap. puncticeps walked four times faster than Ad. calosomoides in a laboratory assay, indicating that, for these species, mobility and gene flow are influenced more by physiological limitations than by speed.

  2. Hydrogen sulphide and the kidney: important roles in renal physiology and pathogenesis and treatment of kidney injury and disease.

    PubMed

    Lobb, I; Sonke, E; Aboalsamh, G; Sener, A

    2015-04-30

    The kidney is an essential mammalian organ that serves to filter toxins and metabolic by-products out of the blood, which are then excreted through urine. Hydrogen sulphide (H2S) is a recently characterized, endogenous gaseous molecule with important physiological roles. Many interesting roles continue to be identified for H2S related specifically to the kidney. The current review discusses how production and action of H2S influences normal physiology of the kidney. We investigate as well the many roles H2S plays in the pathogenesis and treatment of kidney injury and disease, such as chronic kidney disease (CKD), ureteral obstruction (UO), hyperhomocysteinaemia (HHcy), drug-induced nephrotoxicity (DIN) and renal ischaemia reperfusion injury (IRI). We suggest that H2S plays a complex and essential role in the normal function of the kidney and dysregulation of H2S production can directly or indirectly contribute to the pathogenesis of renal disease and injury. Also, H2S could be a promising potential therapeutic treatment to decrease the severity of several renal diseases. Further research will identify increasingly important and complex roles for H2S in renal physiology and how H2S can be effectively utilized to improve clinical outcomes of renal disease.

  3. The Role of CO2 Physiological Forcing in Driving Future Precipitation Variability and Precipitation Extremes

    NASA Astrophysics Data System (ADS)

    Skinner, C. B.; Poulsen, C. J.

    2015-12-01

    Transpired water contributes roughly 25% to total precipitation over the Earth's land surface. In addition to transpiration's impact on climatological mean precipitation, recent work suggests that transpiration reduces daily and intraseasonal precipitation variability in tropical forest regions. Projected increases in the concentration of CO2 are expected to reduce transpiration through changes in plant physiology (termed the CO2 physiological effect). Here, we use an ensemble of climate model experiments to assess the potential contribution of the CO2 physiological effect to future changes in precipitation variability and extreme precipitation events. Within our model simulations, precipitation responses to the physiological effects of increased CO2 concentrations are greatest throughout the tropics. In most tropical forest regions CO2 physiological forcing increases the annual number of dry (less than 0.1 mm/day) and extremely wet (rainfall exceeds 95th percentile) days. Changes in precipitation are primarily driven by an increase in surface temperature and subsequent changes in atmospheric stability and moisture convergence over vegetated tropical land regions. Our results suggest that the plant physiological response to CO2 forcing may serve as an important contributor to future precipitation variability in the tropics, and that future work should aim to reduce uncertainty in the response of plant physiology to changes in climate.

  4. A Physiologically Based, Multi-Scale Model of Skeletal Muscle Structure and Function

    PubMed Central

    Röhrle, O.; Davidson, J. B.; Pullan, A. J.

    2012-01-01

    Models of skeletal muscle can be classified as phenomenological or biophysical. Phenomenological models predict the muscle’s response to a specified input based on experimental measurements. Prominent phenomenological models are the Hill-type muscle models, which have been incorporated into rigid-body modeling frameworks, and three-dimensional continuum-mechanical models. Biophysically based models attempt to predict the muscle’s response as emerging from the underlying physiology of the system. In this contribution, the conventional biophysically based modeling methodology is extended to include several structural and functional characteristics of skeletal muscle. The result is a physiologically based, multi-scale skeletal muscle finite element model that is capable of representing detailed, geometrical descriptions of skeletal muscle fibers and their grouping. Together with a well-established model of motor-unit recruitment, the electro-physiological behavior of single muscle fibers within motor units is computed and linked to a continuum-mechanical constitutive law. The bridging between the cellular level and the organ level has been achieved via a multi-scale constitutive law and homogenization. The effect of homogenization has been investigated by varying the number of embedded skeletal muscle fibers and/or motor units and computing the resulting exerted muscle forces while applying the same excitatory input. All simulations were conducted using an anatomically realistic finite element model of the tibialis anterior muscle. Given the fact that the underlying electro-physiological cellular muscle model is capable of modeling metabolic fatigue effects such as potassium accumulation in the T-tubular space and inorganic phosphate build-up, the proposed framework provides a novel simulation-based way to investigate muscle behavior ranging from motor-unit recruitment to force generation and fatigue. PMID:22993509

  5. Biochemical properties and physiological roles of NADP-dependent malic enzyme in Escherichia coli.

    PubMed

    Wang, Baojuan; Wang, Peng; Zheng, Enxia; Chen, Xiangxian; Zhao, Hanjun; Song, Ping; Su, Ruirui; Li, Xiaoning; Zhu, Guoping

    2011-10-01

    Malic enzymes catalyze the reversible oxidative decarboxylation of L-malate using NAD(P)(+) as a cofactor. NADP-dependent malic enzyme (MaeB) from Escherichia coli MG1655 was expressed and purified as a fusion protein. The molecular weight of MaeB was about 83 kDa, as determined by SDS-PAGE. The recombinant MaeB showed a maximum activity at pH 7.8 and 46°C. MaeB activity was dependent on the presence of Mn(2+) but was strongly inhibited by Zn(2+). In order to understand the physiological roles, recombinant E. coli strains (icd (NADP)/ΔmaeB and icd (NAD)/ΔmaeB) containing NADP-dependent isocitrate dehydrogenase (IDH), or engineered NAD-dependent IDH with the deletion of the maeB gene, were constructed using homologous recombination. During growth on acetate, icd (NAD)/ΔmaeB grew poorly, having a growth rate only 60% that of the wild-type strain (icd (NADP)). Furthermore, icd (NADP)/ΔmaeB exhibited a 2-fold greater adaptability to acetate than icd (NAD)/ΔmaeB, which may be explained by more NADPH production for biosynthesis in icd (NADP)/ΔmaeB due to its NADP-dependent IDH. These results indicated that MaeB was important for NADPH production for bacterial growth on acetate. We also observed that MaeB activity was significantly enhanced (7.83-fold) in icd (NAD), which was about 3-fold higher than that in icd (NADP), when switching from glucose to acetate. The marked increase of MaeB activity was probably induced by the shortage of NADPH in icd (NAD). Evidently, MaeB contributed to the NADPH generation needed for bacterial growth on two carbon compounds.

  6. Gene Expression and Physiological Role of Pseudomonas aeruginosa Methionine Sulfoxide Reductases during Oxidative Stress

    PubMed Central

    Romsang, Adisak; Atichartpongkul, Sopapan; Trinachartvanit, Wachareeporn; Vattanaviboon, Paiboon

    2013-01-01

    Pseudomonas aeruginosa PAO1 has two differentially expressed methionine sulfoxide reductase genes: msrA (PA5018) and msrB (PA2827). The msrA gene is expressed constitutively at a high level throughout all growth phases, whereas msrB expression is highly induced by oxidative stress, such as sodium hypochlorite (NaOCl) treatment. Inactivation of either msrA or msrB or both genes (msrA msrB mutant) rendered the mutants less resistant than the parental PAO1 strain to oxidants such as NaOCl and H2O2. Unexpectedly, msr mutants have disparate resistance patterns when exposed to paraquat, a superoxide generator. The msrA mutant had a higher paraquat resistance level than the msrB mutant, which had a lower paraquat resistance level than the PAO1 strain. The expression levels of msrA showed an inverse correlation with the paraquat resistance level, and this atypical paraquat resistance pattern was not observed with msrB. Virulence testing using a Drosophila melanogaster model revealed that the msrA, msrB, and, to a greater extent, msrA msrB double mutants had an attenuated virulence phenotype. The data indicate that msrA and msrB are essential genes for oxidative stress protection and bacterial virulence. The pattern of expression and mutant phenotypes of P. aeruginosa msrA and msrB differ from previously characterized msr genes from other bacteria. Thus, as highly conserved genes, the msrA and msrB have diverse expression patterns and physiological roles that depend on the environmental niche where the bacteria thrive. PMID:23687271

  7. Differential role of Hedgehog signaling in human pancreatic (patho-) physiology: An up to date review.

    PubMed

    Klieser, Eckhard; Swierczynski, Stefan; Mayr, Christian; Jäger, Tarkan; Schmidt, Johanna; Neureiter, Daniel; Kiesslich, Tobias; Illig, Romana

    2016-05-15

    Since the discovery of the Hedgehog (Hh) pathway in drosophila melanogaster, our knowledge of the role of Hh in embryonic development, inflammation, and cancerogenesis in humans has dramatically increased over the last decades. This is the case especially concerning the pancreas, however, real therapeutic breakthroughs are missing until now. In general, Hh signaling is essential for pancreatic organogenesis, development, and tissue maturation. In the case of acute pancreatitis, Hh has a protective role, whereas in chronic pancreatitis, Hh interacts with pancreatic stellate cells, leading to destructive parenchym fibrosis and atrophy, as well as to irregular tissue remodeling with potency of initiating cancerogenesis. In vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor microenvironment. The application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials (phases 1 and 2). Furthermore, a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic approach. In this review, we give a structured survey of the role of the Hh pathway in pancreatic development, pancreatitis, pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer.

  8. Differential role of Hedgehog signaling in human pancreatic (patho-) physiology: An up to date review

    PubMed Central

    Klieser, Eckhard; Swierczynski, Stefan; Mayr, Christian; Jäger, Tarkan; Schmidt, Johanna; Neureiter, Daniel; Kiesslich, Tobias; Illig, Romana

    2016-01-01

    Since the discovery of the Hedgehog (Hh) pathway in drosophila melanogaster, our knowledge of the role of Hh in embryonic development, inflammation, and cancerogenesis in humans has dramatically increased over the last decades. This is the case especially concerning the pancreas, however, real therapeutic breakthroughs are missing until now. In general, Hh signaling is essential for pancreatic organogenesis, development, and tissue maturation. In the case of acute pancreatitis, Hh has a protective role, whereas in chronic pancreatitis, Hh interacts with pancreatic stellate cells, leading to destructive parenchym fibrosis and atrophy, as well as to irregular tissue remodeling with potency of initiating cancerogenesis. In vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor microenvironment. The application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials (phases 1 and 2). Furthermore, a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic approach. In this review, we give a structured survey of the role of the Hh pathway in pancreatic development, pancreatitis, pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer. PMID:27190692

  9. Molecular Analysis of Atypical Family 18 Chitinase from Fujian Oyster Crassostrea angulata and Its Physiological Role in the Digestive System.

    PubMed

    Yang, Bingye; Zhang, Mingming; Li, Lingling; Pu, Fei; You, Weiwei; Ke, Caihuan

    2015-01-01

    Chitinolytic enzymes have an important physiological significance in immune and digestive systems in plants and animals, but chitinase has not been identified as having a role in the digestive system in molluscan. In our study, a novel chitinase homologue, named Ca-Chit, has been cloned and characterized as the oyster Crassostrea angulate. The 3998bp full-length cDNA of Ca-Chit consisted of 23bp 5-UTR, 3288 ORF and 688bp 3-UTR. The deduced amino acids sequence shares homologue with the chitinase of family 18. The molecular weight of the protein was predicted to be 119.389 kDa, with a pI of 6.74. The Ca-Chit protein was a modular enzyme composed of a glycosyl hydrolase family 18 domain, threonine-rich region profile and a putative membrane anchor domain. Gene expression profiles monitored by quantitative RT-PCR in different adult tissues showed that the mRNA of Ca-Chit expressed markedly higher visceral mass than any other tissues. The results of the whole mount in-situ hybridization displayed that Ca-Chit starts to express the visceral mass of D-veliger larvae and then the digestive gland forms a crystalline structure during larval development. Furthermore, the adult oysters challenged by starvation indicated that the Ca-Chit expression would be regulated by feed. All the observations made suggest that Ca-Chit plays an important role in the digestive system of the oyster, Crassostrea angulate. PMID:26046992

  10. Impact of physiology, structure and BRDF in hyperspectral time series of a Citrus orchard

    NASA Astrophysics Data System (ADS)

    Stuckens, J.; Dzikiti, S.; Verstraeten, W. W.; Verreynne, J. S.; Swinnen, R.; Coppin, P.

    2010-05-01

    Monitoring of plant production systems using remote sensing requires an understanding of the mechanisms in which physiological and structural changes as well as the quality and direction of incident light alter the measured canopy reflectance. Due to the evergreen nature of Citrus, the benefits of year-round monitoring of spectral changes are counterweighted by more subtle changes and seasonal trends than in other perennials. This study presents the results of a 14 months field measurement campaign in a commercial Citrus sinensis ‘Midknight Valencia' orchard in Wellington, Western Cape Province, South-Africa. Hyperspectral data were collected of canopy and leaf reflectance (350 - 2500 nm) of 16 representative trees at monthly intervals and supplemented with local climatology, orchard management records, sap stream, water potential and leaf and soil nutrient analysis. The aim of this research is to translate spectral changes and trends at the leaf and at canopy levels into physiological processes such as plant nutrient and carbohydrate balances and stress responses. Specific research questions include the spectral detection of flowering (date of anthesis, flowering intensity), fruit drop, fruit number and coloration, vegetative flushes, leaf senescence and drop and pruning. Attention is paid to the detection and the impact of sunburn (photo-damage). In order to separate physiological and structural changes from changes caused by seasonal changes in solar elevation during measurement time (bidirectional reflectance) a normalization function is constructed using simulated and measured data. Additional research is done to up-scale measurements from tree level to orchard level, which includes the tree variability, the influence of soil and weeds and different amounts of shading.

  11. Physiological time structure of the tibialis anterior motor activity during sleep in mice, rats and humans.

    PubMed

    Silvani, Alessandro; Lo Martire, Viviana; Salvadè, Agnese; Bastianini, Stefano; Ferri, Raffaele; Berteotti, Chiara; Baracchi, Francesca; Pace, Marta; Bassetti, Claudio L; Zoccoli, Giovanna; Manconi, Mauro

    2015-12-01

    The validation of rodent models for restless legs syndrome (Willis-Ekbom disease) and periodic limb movements during sleep requires knowledge of physiological limb motor activity during sleep in rodents. This study aimed to determine the physiological time structure of tibialis anterior activity during sleep in mice and rats, and compare it with that of healthy humans. Wild-type mice (n = 9) and rats (n = 8) were instrumented with electrodes for recording the electroencephalogram and electromyogram of neck muscles and both tibialis anterior muscles. Healthy human subjects (31 ± 1 years, n = 21) underwent overnight polysomnography. An algorithm for automatic scoring of tibialis anterior electromyogram events of mice and rats during non-rapid eye movement sleep was developed and validated. Visual scoring assisted by this algorithm had inter-rater sensitivity of 92-95% and false-positive rates of 13-19% in mice and rats. The distribution of the time intervals between consecutive tibialis anterior electromyogram events during non-rapid eye movement sleep had a single peak extending up to 10 s in mice, rats and human subjects. The tibialis anterior electromyogram events separated by intervals <10 s mainly occurred in series of two-three events, their occurrence rate in humans being lower than in mice and similar to that in rats. In conclusion, this study proposes reliable rules for scoring tibialis anterior electromyogram events during non-rapid eye movement sleep in mice and rats, demonstrating that their physiological time structure is similar to that of healthy young human subjects. These results strengthen the basis for translational rodent models of periodic limb movements during sleep and restless legs syndrome/Willis-Ekbom disease.

  12. [The formative role of the laboratory in teaching the science of physiology].

    PubMed

    Guevara-Guzmán, Rosalinda; Urrutia Aguilar, María Esther

    2014-12-01

    Physiology teaching began with Claudius Galenus (c. 126-199 AD), known as Galen, who is considered the initiator of experimental physiology. This discipline was consolidated in the XIX century with the discoveries of Claude Bernard, which influenced the way of teaching this discipline in universities, independently from Anatomy. In Mexico, physiology teaching started in 1580. It was at the beginning of the XIX century when Valentín Gómez Farías created the professorship in Medical Sciences and Daniel Vergara Lope carried out its consolidation when he implemented a lab course. Doctor José Joaquín Izquierdo established that this subject ought to be taught by teachers with experience in research. Undoubtedly, formative physiology teaching carried out in labs must strengthen the application of method and scientific methodology in students. In this symposium, we put forward that the change in physiology teaching must promote multidisciplinary research in students, who will formulate a research question and develop an experimental model that will let them integrate their basic knowledge of physiology, pharmacology, biochemistry, and functional anatomy under the supervision of a research teacher.

  13. Physiological vagility: correlations with dispersal and population genetic structure of amphibians.

    PubMed

    Hillman, Stanley S; Drewes, Robert C; Hedrick, Michael S; Hancock, Thomas V

    2014-01-01

    Physiological vagility represents the capacity to move sustainably and is central to fully explaining the processes involved in creating fine-scale genetic structure of amphibian populations, because movement (vagility) and the duration of movement determine the dispersal distance individuals can move to interbreed. The tendency for amphibians to maintain genetic differentiation over relatively short distances (isolation by distance) has been attributed to their limited dispersal capacity (low vagility) compared with other vertebrates. Earlier studies analyzing genetic isolation and population differentiation with distance treat all amphibians as equally vagile and attempt to explain genetic differentiation only in terms of physical environmental characteristics. We introduce a new quantitative metric for vagility that incorporates aerobic capacity, body size, body temperature, and the cost of transport and is independent of the physical characteristics of the environment. We test our metric for vagility with data for dispersal distance and body mass in amphibians and correlate vagility with data for genetic differentiation (F'(ST)). Both dispersal distance and vagility increase with body size. Differentiation (F'(ST)) of neutral microsatellite markers with distance was inversely and significantly (R2=0.61) related to ln vagility. Genetic differentiation with distance was not significantly related to body mass alone. Generalized observations are validated with several specific amphibian studies. These results suggest that interspecific differences in physiological capacity for movement (vagility) can contribute to genetic differentiation and metapopulation structure in amphibians.

  14. Physiological roles of axonal ankyrins in survival of premyelinated axons and localization of voltage-gated sodium channels.

    PubMed

    Bennett, V; Lambert, S

    1999-01-01

    440 kD ankyrin-B and 480/270 kD ankyrin-G are membrane skeletal proteins with closely related biochemical properties yet distinctive physiological roles in axons. These proteins associate with spectrin-actin networks and also bind to integral membrane proteins including the L1 CAM family of cell adhesion molecules and voltage-gated sodium channels. 440 kD ankyrin-B is expressed with L1 in premyelinated axon tracts, and is essential for survival of these axons, at least in the case of the optic nerve. 440 ankyrin-B may collaborate with L1 in transcellular structures that mediate axon fasciculation and mechanically stabilize axon bundles, although these proteins may also be involved in axon pathfinding. Ankyrin-B (-/-) mice exhibit loss of L1 from premyelinated axon tracts and a similar, although much more severe, phenotype to L1 (-/-) mice and humans with L1 mutations. Ankyrin-B and L1 thus are candidates to collaborate in the same structural pathway and defects in this pathway can lead to nervous system malformations and mental retardation. 480/270 kD ankyrin-G are highly concentrated along with the L1CAM family members neurofascin and NrCAM at nodes of Ranvier and axon initial segments. Voltage-gated sodium channels bind directly to ankyrins, and are likely to associate in a ternary complex containing neurofascin/NrCAM, and ankyrin-G. Mice with ankyrin-G expression abolished in the cerebellum exhibit loss of ability of Purkinje neurons to fire action potentials, as well as loss of restriction of neurofascin/NrCAM to axon initial segments. Ankyrin-G thus is a key component in assembly of functional components of the axon initial segment and possibly the node of Ranvier.

  15. Mitotic Checkpoint Kinase Mps1 Has a Role in Normal Physiology which Impacts Clinical Utility.

    PubMed

    Martinez, Ricardo; Blasina, Alessandra; Hallin, Jill F; Hu, Wenyue; Rymer, Isha; Fan, Jeffery; Hoffman, Robert L; Murphy, Sean; Marx, Matthew; Yanochko, Gina; Trajkovic, Dusko; Dinh, Dac; Timofeevski, Sergei; Zhu, Zhou; Sun, Peiquing; Lappin, Patrick B; Murray, Brion W

    2015-01-01

    Cell cycle checkpoint intervention is an effective therapeutic strategy for cancer when applied to patients predisposed to respond and the treatment is well-tolerated. A critical cell cycle process that could be targeted is the mitotic checkpoint (spindle assembly checkpoint) which governs the metaphase-to-anaphase transition and insures proper chromosomal segregation. The mitotic checkpoint kinase Mps1 was selected to explore whether enhancement in genomic instability is a viable therapeutic strategy. The basal-a subset of triple-negative breast cancer was chosen as a model system because it has a higher incidence of chromosomal instability and Mps1 expression is up-regulated. Depletion of Mps1 reduces tumor cell viability relative to normal cells. Highly selective, extremely potent Mps1 kinase inhibitors were created to investigate the roles of Mps1 catalytic activity in tumor cells and normal physiology (PF-7006, PF-3837; Ki<0.5 nM; cellular IC50 2-6 nM). Treatment of tumor cells in vitro with PF-7006 modulates expected Mps1-dependent biology as demonstrated by molecular and phenotypic measures (reduced pHH3-Ser10 levels, shorter duration of mitosis, micro-nucleation, and apoptosis). Tumor-bearing mice treated with PF-7006 exhibit tumor growth inhibition concomitant with pharmacodynamic modulation of a downstream biomarker (pHH3-Ser10). Unfortunately, efficacy only occurs at drug exposures that cause dose-limiting body weight loss, gastrointestinal toxicities, and neutropenia. Mps1 inhibitor toxicities may be mitigated by inducing G1 cell cycle arrest in Rb1-competent cells with the cyclin-dependent kinase-4/6 inhibitor palbociclib. Using an isogenic cellular model system, PF-7006 is shown to be selectively cytotoxic to Rb1-deficient cells relative to Rb1-competent cells (also a measure of kinase selectivity). Human bone marrow cells pretreated with palbociclib have decreased PF-7006-dependent apoptosis relative to cells without palbociclib pretreatment

  16. Mitotic Checkpoint Kinase Mps1 Has a Role in Normal Physiology which Impacts Clinical Utility

    PubMed Central

    Martinez, Ricardo; Blasina, Alessandra; Hallin, Jill F.; Hu, Wenyue; Rymer, Isha; Fan, Jeffery; Hoffman, Robert L.; Murphy, Sean; Marx, Matthew; Yanochko, Gina; Trajkovic, Dusko; Dinh, Dac; Timofeevski, Sergei; Zhu, Zhou; Sun, Peiquing; Lappin, Patrick B.; Murray, Brion W.

    2015-01-01

    Cell cycle checkpoint intervention is an effective therapeutic strategy for cancer when applied to patients predisposed to respond and the treatment is well-tolerated. A critical cell cycle process that could be targeted is the mitotic checkpoint (spindle assembly checkpoint) which governs the metaphase-to-anaphase transition and insures proper chromosomal segregation. The mitotic checkpoint kinase Mps1 was selected to explore whether enhancement in genomic instability is a viable therapeutic strategy. The basal-a subset of triple-negative breast cancer was chosen as a model system because it has a higher incidence of chromosomal instability and Mps1 expression is up-regulated. Depletion of Mps1 reduces tumor cell viability relative to normal cells. Highly selective, extremely potent Mps1 kinase inhibitors were created to investigate the roles of Mps1 catalytic activity in tumor cells and normal physiology (PF-7006, PF-3837; Ki<0.5 nM; cellular IC50 2–6 nM). Treatment of tumor cells in vitro with PF-7006 modulates expected Mps1-dependent biology as demonstrated by molecular and phenotypic measures (reduced pHH3-Ser10 levels, shorter duration of mitosis, micro-nucleation, and apoptosis). Tumor-bearing mice treated with PF-7006 exhibit tumor growth inhibition concomitant with pharmacodynamic modulation of a downstream biomarker (pHH3-Ser10). Unfortunately, efficacy only occurs at drug exposures that cause dose-limiting body weight loss, gastrointestinal toxicities, and neutropenia. Mps1 inhibitor toxicities may be mitigated by inducing G1 cell cycle arrest in Rb1-competent cells with the cyclin-dependent kinase-4/6 inhibitor palbociclib. Using an isogenic cellular model system, PF-7006 is shown to be selectively cytotoxic to Rb1-deficient cells relative to Rb1-competent cells (also a measure of kinase selectivity). Human bone marrow cells pretreated with palbociclib have decreased PF-7006-dependent apoptosis relative to cells without palbociclib pretreatment

  17. Recent functional insights into the role of (p)ppGpp in bacterial physiology.

    PubMed

    Hauryliuk, Vasili; Atkinson, Gemma C; Murakami, Katsuhiko S; Tenson, Tanel; Gerdes, Kenn

    2015-05-01

    The alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively referred to as (p)ppGpp) are involved in regulating growth and several different stress responses in bacteria. In recent years, substantial progress has been made in our understanding of the molecular mechanisms of (p)ppGpp metabolism and (p)ppGpp-mediated regulation. In this Review, we summarize these recent insights, with a focus on the molecular mechanisms governing the activity of the RelA/SpoT homologue (RSH) proteins, which are key players that regulate the cellular levels of (p)ppGpp. We also discuss the structural basis of transcriptional regulation by (p)ppGpp and the role of (p)ppGpp in GTP metabolism and in the emergence of bacterial persisters.

  18. Recent functional insights into the role of (p)ppGpp in bacterial physiology

    PubMed Central

    Hauryliuk, Vasili; Atkinson, Gemma C.; Murakami, Katsuhiko S.; Tenson, Tanel; Gerdes, Kenn

    2015-01-01

    The alarmone (p)ppGpp is involved in regulating growth and several different stress responses in bacteria. In recent years, substantial progress has been made in our understanding of the molecular mechanisms of (p)ppGpp metabolism and (p)ppGpp-mediated regulation. In this Review, we summarize these recent insights, with a focus on the molecular mechanisms governing the activity of the RelA/SpoT Homologue (RSH) proteins, which are key players that regulate the cellular leves of (p)ppGpp, the structural basis of transcriptional regulation by (p)ppGpp and the role of (p)ppGpp in GTP metabolism and in the emergence of bacterial persisters. PMID:25853779

  19. The UV-B photoreceptor UVR8: from structure to physiology.

    PubMed

    Jenkins, Gareth I

    2014-01-01

    Low doses of UV-B light (280 to 315 nm) elicit photomorphogenic responses in plants that modify biochemical composition, photosynthetic competence, morphogenesis, and defense. UV RESISTANCE LOCUS8 (UVR8) mediates photomorphogenic responses to UV-B by regulating transcription of a set of target genes. UVR8 differs from other known photoreceptors in that it uses specific Trp amino acids instead of a prosthetic chromophore for light absorption during UV-B photoreception. Absorption of UV-B dissociates the UVR8 dimer into monomers, initiating signal transduction through interaction with CONSTITUTIVELY PHOTOMORPHOGENIC1. However, much remains to be learned about the physiological role of UVR8 and its interaction with other signaling pathways, the molecular mechanism of UVR8 photoreception, how the UVR8 protein initiates signaling, how it is regulated, and how UVR8 regulates transcription of its target genes.

  20. The UV-B Photoreceptor UVR8: From Structure to Physiology

    PubMed Central

    Jenkins, Gareth I.

    2014-01-01

    Low doses of UV-B light (280 to 315 nm) elicit photomorphogenic responses in plants that modify biochemical composition, photosynthetic competence, morphogenesis, and defense. UV RESISTANCE LOCUS8 (UVR8) mediates photomorphogenic responses to UV-B by regulating transcription of a set of target genes. UVR8 differs from other known photoreceptors in that it uses specific Trp amino acids instead of a prosthetic chromophore for light absorption during UV-B photoreception. Absorption of UV-B dissociates the UVR8 dimer into monomers, initiating signal transduction through interaction with CONSTITUTIVELY PHOTOMORPHOGENIC1. However, much remains to be learned about the physiological role of UVR8 and its interaction with other signaling pathways, the molecular mechanism of UVR8 photoreception, how the UVR8 protein initiates signaling, how it is regulated, and how UVR8 regulates transcription of its target genes. PMID:24481075

  1. Anatomy & Physiology

    MedlinePlus

    ... Central Nervous System Peripheral Nervous System Review Quiz Endocrine System Characteristics of Hormones Endocrine Glands & Their Hormones Pituitary & ... Thyroid & Parathyroid Glands Adrenal Gland Pancreas Gonads Other Endocrine Glands ... Cardiovascular System Heart Structure of the Heart Physiology of the ...

  2. The Role of Odor-Evoked Memory in Psychological and Physiological Health

    PubMed Central

    Herz, Rachel S.

    2016-01-01

    This article discusses the special features of odor-evoked memory and the current state-of-the-art in odor-evoked memory research to show how these unique experiences may be able to influence and benefit psychological and physiological health. A review of the literature leads to the conclusion that odors that evoke positive autobiographical memories have the potential to increase positive emotions, decrease negative mood states, disrupt cravings, and reduce physiological indices of stress, including systemic markers of inflammation. Olfactory perception factors and individual difference characteristics that would need to be considered in therapeutic applications of odor-evoked-memory are also discussed. This article illustrates how through the experimentally validated mechanisms of odor-associative learning and the privileged neuroanatomical relationship that exists between olfaction and the neural substrates of emotion, odors can be harnessed to induce emotional and physiological responses that can improve human health and wellbeing. PMID:27447673

  3. The Role of Odor-Evoked Memory in Psychological and Physiological Health.

    PubMed

    Herz, Rachel S

    2016-01-01

    This article discusses the special features of odor-evoked memory and the current state-of-the-art in odor-evoked memory research to show how these unique experiences may be able to influence and benefit psychological and physiological health. A review of the literature leads to the conclusion that odors that evoke positive autobiographical memories have the potential to increase positive emotions, decrease negative mood states, disrupt cravings, and reduce physiological indices of stress, including systemic markers of inflammation. Olfactory perception factors and individual difference characteristics that would need to be considered in therapeutic applications of odor-evoked-memory are also discussed. This article illustrates how through the experimentally validated mechanisms of odor-associative learning and the privileged neuroanatomical relationship that exists between olfaction and the neural substrates of emotion, odors can be harnessed to induce emotional and physiological responses that can improve human health and wellbeing. PMID:27447673

  4. Invariance in current dipole moment density across brain structures and species: Physiological constraint for neuroimaging

    PubMed Central

    Murakami, Shingo; Okada, Yoshio

    2015-01-01

    Although anatomical constraints have been shown to be effective for MEG and EEG inverse solutions, there are still no effective physiological constraints. Strength of the current generator is normally described by the moment of an equivalent current dipole Q. This value is quite variable since it depends on size of active tissue. In contrast, the current dipole moment density q, defined as Q per surface area of active cortex, is independent of size of active tissue. Here we studied whether the value of q has a maximum in physiological conditions across brain structures and species. We determined the value due to the primary neuronal current (qprimary) alone, correcting for distortions due to measurement conditions and secondary current sources at boundaries separating regions of differing electrical conductivity. The values were in the same range for turtle cerebellum (0.56–1.48 nAm/mm2), guinea pig hippocampus (0.30–1.34 nAm/mm2), and swine neocortex (0.18–1.63 nAm/mm2), rat neocortex (~2.2 nAm/mm2), monkey neocortex (~0.40 nAm/mm2) and human neocortex (0.16–0.77 nAm/mm2). Thus, there appears to be a maximum value across the brain structures and species (1–2 nAm/mm2). The empirical values closely matched the theoretical values obtained with our independently validated neural network model (1.6–2.8 nAm/mm2 for initial spike and 0.7–3.1 nAm/mm2 for burst), indicating that the apparent invariance is not coincidental. Our model study shows that a single maximum value may exist across a wide range of brain structures and species, varying in neuron density, due to fundamental electrical properties of neurons. The maximum value of qprimary may serve as an effective physiological constraint for MEG/EEG inverse solutions. PMID:25680520

  5. Climate, physiological tolerance and sex-biased dispersal shape genetic structure of Neotropical orchid bees.

    PubMed

    López-Uribe, Margarita M; Zamudio, Kelly R; Cardoso, Carolina F; Danforth, Bryan N

    2014-04-01

    Understanding the impact of past climatic events on the demographic history of extant species is critical for predicting species' responses to future climate change. Palaeoclimatic instability is a major mechanism of lineage diversification in taxa with low dispersal and small geographical ranges in tropical ecosystems. However, the impact of these climatic events remains questionable for the diversification of species with high levels of gene flow and large geographical distributions. In this study, we investigate the impact of Pleistocene climate change on three Neotropical orchid bee species (Eulaema bombiformis, E. meriana and E. cingulata) with transcontinental distributions and different physiological tolerances. We first generated ecological niche models to identify species-specific climatically stable areas during Pleistocene climatic oscillations. Using a combination of mitochondrial and nuclear markers, we inferred calibrated phylogenies and estimated historical demographic parameters to reconstruct the phylogeographical history of each species. Our results indicate species with narrower physiological tolerance experienced less suitable habitat during glaciations and currently exhibit strong population structure in the mitochondrial genome. However, nuclear markers with low and high mutation rates show lack of association with geography. These results combined with lower migration rate estimates from the mitochondrial than the nuclear genome suggest male-biased dispersal. We conclude that despite large effective population sizes and capacity for long-distance dispersal, climatic instability is an important mechanism of maternal lineage diversification in orchid bees. Thus, these Neotropical pollinators are susceptible to disruption of genetic connectivity in the event of large-scale climatic changes.

  6. The role of reduced oxygen in the developmental physiology of growth and metamorphosis initiation in Drosophila

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rearing oxygen level is known to affect final body size in a variety of insects, but the physiological mechanisms by which oxygen affects size are incompletely understood. In Manduca and Drosophila, the larval size at which metamorphosis is initiated largely determines adult size, and metamorphosis ...

  7. The Role of Physiological Arousal in Time Perception: Psychophysiological Evidence from an Emotion Regulation Paradigm

    ERIC Educational Resources Information Center

    Mella, N.; Conty, L.; Pouthas, V.

    2011-01-01

    Time perception, crucial for adaptive behavior, has been shown to be altered by emotion. An arousal-dependent mechanism is proposed to account for such an effect. Yet, physiological measure of arousal related with emotional timing is still lacking. We addressed this question using skin conductance response (SCR) in an emotion regulation paradigm.…

  8. Dissociating Motivational From Physiological Withdrawal in Alcohol Dependence: Role of Central Amygdala κ-Opioid Receptors.

    PubMed

    Kissler, Jessica L; Walker, Brendan M

    2016-01-01

    Chronic intermittent alcohol vapor exposure leads to increased dynorphin (DYN) A-like peptide expression and heightened kappa-opioid receptor (KOR) signaling in the central nucleus of the amygdala (CeA) and these neuroadaptive responses differentiate alcohol-dependent from non-dependent phenotypes. Important for therapeutic development efforts is understanding the nature of the stimulus that drives dependence-like phenotypes such as escalated alcohol self-administration. Accordingly, the present study examined the impact of intra-CeA KOR antagonism on escalated operant alcohol self-administration and physiological withdrawal symptoms during acute withdrawal and protracted abstinence in rats previously exposed to chronic intermittent alcohol vapor. Following operant training, rats were implanted with intra-CeA guide cannula and exposed to long-term intermittent alcohol vapor exposure that resulted in escalated alcohol self-administration and elevated physiological withdrawal signs during acute withdrawal. Animals received intra-CeA infusions of the KOR antagonist nor-binaltorphimine (nor-BNI; 0, 2, 4, or 6 μg) prior to operant alcohol self-administration sessions and physiological withdrawal assessment during acute withdrawal and protracted abstinence. The results indicated that site-specific KOR antagonism in the CeA ameliorated escalated alcohol self-administration during both acute withdrawal and protracted abstinence test sessions, whereas KOR antagonism had no effect on physiological withdrawal scores at either time point. These results dissociate escalated alcohol self-administration from physiological withdrawal symptoms in relation to KOR signaling in the CeA and help clarify the nature of the stimulus that drives escalated alcohol self-administration during acute withdrawal and protracted abstinence.

  9. The role of relaxin in mare reproductive physiology: A comparative review with other species.

    PubMed

    Klein, Claudia

    2016-07-01

    Relaxin is a peptide hormone best known for its action during the latter half of pregnancy, in particular for its softening effect on pelvic ligaments that aids in preparation of the birth canal for the impending delivery of the fetus. The source of relaxin during early pregnancy varies across species, with the CL being the main source in a number of species. The main source of relaxin during late equine pregnancy is the placenta. In mares with impaired placental function, circulating relaxin levels decline before abortion. During early pregnancy, relaxin promotes endometrial angiogenesis through upregulating endometrial expression of vascular endothelial growth factor. The horse is unique in that the equine conceptus expresses relaxin messenger RNA as early as 8 days after ovulation, with levels increasing as conceptus development proceeds. Although secretion of functional relaxin has not been verified, it is likely, given that the embryo also expresses transcripts coding for enzymes processing the prohormone to yield the mature hormone. Furin, an enzyme which belongs to the subtilisin-like proprotein convertase family known to process preprorelaxin, appears to be the foremost convertase expressed by equine conceptuses. Conceptus-derived relaxin could drive endometrial angiogenesis and also act in an autocrine fashion to promote the embryo's own development. Relaxin is also expressed by ovarian structures during the nonpregnant estrous cycle. In the mare, follicular expression of relaxin is comparable among follicles of varying size and has been localized to granulosa and theca cells. In women and pigs, relaxin appears to promote follicular development. In the rat, multiple lines of evidence indicate that relaxin is involved in the ovulatory process. In the mare, relaxin might play a similar role in the ovulatory process, as in equine ovarian stromal cells relaxin promotes the secretion of gelatinases and tissue inhibitors of metalloproteinases; local proteolysis

  10. [Effect of mechanical grinding of Sphagnum on the structure and physiological state of bacterial communities].

    PubMed

    Dobrovol'skaya, T G; Golovchenko, A V; Yakushev, A V; Manucharova, N A; Yurchenko, E N

    2014-01-01

    The microcosm method was used to demonstrate an increase in bacterial numbers and drastic changes in the taxonomic structure of saprotrophic bacteria as a result of mechanical grinding of Sphagnum moss. Ekkrisotrophic agrobacteria predominant in untreated moss were replaced by hydrolytic bacteria. Molecular biological approaches revealed such specific hydrolytic bacteria as Janthinobacterium agaricum and Streptomyces purpurascens among the dominant taxa. The application of kinetic technique for determination of the physiological state of bacteria in situ revealed higher functional diversity of hydrolytic bacteria in ground moss than in untreated samples. A considerable decrease of the C/N ratio in ground samples of living Sphagnum incubated using the microcosm technique indicated decomposition of this substrate. PMID:25941721

  11. Mapping physiological G protein-coupled receptor signaling pathways reveals a role for receptor phosphorylation in airway contraction

    PubMed Central

    Bradley, Sophie J.; Iglesias, Max Maza; Kong, Kok Choi; Butcher, Adrian J.; Plouffe, Bianca; Goupil, Eugénie; Bourgognon, Julie-Myrtille; Macedo-Hatch, Timothy; LeGouill, Christian; Russell, Kirsty; Laporte, Stéphane A.; König, Gabriele M.; Kostenis, Evi; Bouvier, Michel; Chung, Kian Fan; Amrani, Yassine; Tobin, Andrew B.

    2016-01-01

    G protein-coupled receptors (GPCRs) are known to initiate a plethora of signaling pathways in vitro. However, it is unclear which of these pathways are engaged to mediate physiological responses. Here, we examine the distinct roles of Gq/11-dependent signaling and receptor phosphorylation-dependent signaling in bronchial airway contraction and lung function regulated through the M3-muscarinic acetylcholine receptor (M3-mAChR). By using a genetically engineered mouse expressing a G protein-biased M3-mAChR mutant, we reveal the first evidence, to our knowledge, of a role for M3-mAChR phosphorylation in bronchial smooth muscle contraction in health and in a disease state with relevance to human asthma. Furthermore, this mouse model can be used to distinguish the physiological responses that are regulated by M3-mAChR phosphorylation (which include control of lung function) from those responses that are downstream of G protein signaling. In this way, we present an approach by which to predict the physiological/therapeutic outcome of M3-mAChR–biased ligands with important implications for drug discovery. PMID:27071102

  12. "Transcription physiology" of pigment formation in melanocytes: central role of MITF.

    PubMed

    Vachtenheim, Jiri; Borovanský, Jan

    2010-07-01

    Melanin production is the primary mechanism protecting human skin against the UV light-induced damage. The polymeric compound melanin is synthesized within melanocytes in the specialized subcellular organelles, termed melanosomes, which are then transferred to surrounding keratinocytes. The genes for melanin synthesis and deposition are coordinately expressed in melanocytes. The transcription factor MITF, which has been reported to activate more than 25 genes in pigment cells, has emerged as an essential regulator not only for melanocyte development, proliferation and survival, but also for the expression of enzymes and structural proteins ensuring the production of melanin. MITF is a transcriptional activator of several genes which encode melanosome-localized proteins involved both in melanin synthesis and in melanosome biogenesis and transport, including genes whose mutations are associated with human oculocutaneous and ocular forms of albinism. Here, we outline the mechanisms of transcriptional regulation of genes associated with the biosynthesis of melanin in melanocytes and melanoma cells. MITF is crucial in this process, while several other factors seem to have only an auxiliary role to play under specific circumstances. PMID:20201954

  13. The effect of physiological conditions on the surface structure of proteins: Setting the scene for human digestion of emulsions

    NASA Astrophysics Data System (ADS)

    Maldonado-Valderrama, J.; Gunning, A. P.; Ridout, M. J.; Wilde, P. J.; Morris, V. J.

    2009-10-01

    Understanding and manipulating the interfacial mechanisms that control human digestion of food emulsions is a crucial step towards improved control of dietary intake. This article reports initial studies on the effects of the physiological conditions within the stomach on the properties of the film formed by the milk protein ( β -lactoglobulin) at the air-water interface. Atomic force microscopy (AFM), surface tension and surface rheology techniques were used to visualize and examine the effect of gastric conditions on the network structure. The effects of changes in temperature, pH and ionic strength on a pre-formed interfacial structure were characterized in order to simulate the actual digestion process. Changes in ionic strength had little effect on the surface properties. In isolation, acidification reduced both the dilatational and the surface shear modulus, mainly due to strong repulsive electrostatic interactions within the surface layer and raising the temperature to body temperature accelerated the rearrangements within the surface layer, resulting in a decrease of the dilatational response and an increase of surface pressure. Together pH and temperature display an unexpected synergism, independent of the ionic strength. Thus, exposure of a pre-formed interfacial β -lactoglobulin film to simulated gastric conditions reduced the surface dilatational modulus and surface shear moduli. This is attributed to a weakening of the surface network in which the surface rearrangements of the protein prior to exposure to gastric conditions might play a crucial role.

  14. A worldwide analysis of within-canopy variations in leaf structural, chemical and physiological traits across plant functional types.

    PubMed

    Niinemets, Ülo; Keenan, Trevor F; Hallik, Lea

    2015-02-01

    Extensive within-canopy light gradients importantly affect the photosynthetic productivity of leaves in different canopy positions and lead to light-dependent increases in foliage photosynthetic capacity per area (AA). However, the controls on AA variations by changes in underlying traits are poorly known. We constructed an unprecedented worldwide database including 831 within-canopy gradients with standardized light estimates for 304 species belonging to major vascular plant functional types, and analyzed within-canopy variations in 12 key foliage structural, chemical and physiological traits by quantitative separation of the contributions of different traits to photosynthetic acclimation. Although the light-dependent increase in AA is surprisingly similar in different plant functional types, they differ fundamentally in the share of the controls on AA by constituent traits. Species with high rates of canopy development and leaf turnover, exhibiting highly dynamic light environments, actively change AA by nitrogen reallocation among and partitioning within leaves. By contrast, species with slow leaf turnover exhibit a passive AA acclimation response, primarily determined by the acclimation of leaf structure to growth light. This review emphasizes that different combinations of traits are responsible for within-canopy photosynthetic acclimation in different plant functional types, and solves an old enigma of the role of mass- vs area-based traits in vegetation acclimation. PMID:25318596

  15. A worldwide analysis of within-canopy variations in leaf structural, chemical and physiological traits across plant functional types.

    PubMed

    Niinemets, Ülo; Keenan, Trevor F; Hallik, Lea

    2015-02-01

    Extensive within-canopy light gradients importantly affect the photosynthetic productivity of leaves in different canopy positions and lead to light-dependent increases in foliage photosynthetic capacity per area (AA). However, the controls on AA variations by changes in underlying traits are poorly known. We constructed an unprecedented worldwide database including 831 within-canopy gradients with standardized light estimates for 304 species belonging to major vascular plant functional types, and analyzed within-canopy variations in 12 key foliage structural, chemical and physiological traits by quantitative separation of the contributions of different traits to photosynthetic acclimation. Although the light-dependent increase in AA is surprisingly similar in different plant functional types, they differ fundamentally in the share of the controls on AA by constituent traits. Species with high rates of canopy development and leaf turnover, exhibiting highly dynamic light environments, actively change AA by nitrogen reallocation among and partitioning within leaves. By contrast, species with slow leaf turnover exhibit a passive AA acclimation response, primarily determined by the acclimation of leaf structure to growth light. This review emphasizes that different combinations of traits are responsible for within-canopy photosynthetic acclimation in different plant functional types, and solves an old enigma of the role of mass- vs area-based traits in vegetation acclimation.

  16. PEDF and its roles in physiological and pathological conditions: implication in diabetic and hypoxia-induced angiogenic diseases

    PubMed Central

    He, Xuemin; Cheng, Rui; Benyajati, Siribhinya

    2015-01-01

    Pigment epithelium-derived factor (PEDF) is a broadly expressed multifunctional member of the serine proteinase inhibitor (serpin) family. This widely studied protein plays critical roles in many physiological and pathophysiological processes, including neuroprotection, angiogenesis, fibrogenesis and inflammation. The present review summarizes the temporal and spatial distribution patterns of PEDF in a variety of developing and adult organs, and discusses its functions in maintaining physiological homoeostasis. The major focus of the present review is to discuss the implication of PEDF in diabetic and hypoxia-induced angiogenesis, and the pathways mediating PEDF's effects under these conditions. Furthermore, the regulatory mechanisms of PEDF expression, function and degradation are also reviewed. Finally, the therapeutic potential of PEDF as an anti-angiogenic drug is briefly summarized. PMID:25881671

  17. The role of thermal physiology in recent declines of birds in a biodiversity hotspot

    PubMed Central

    Milne, Robyn; Cunningham, Susan J.; Lee, Alan T. K.; Smit, Ben

    2015-01-01

    We investigated whether observed avian range contractions and population declines in the Fynbos biome of South Africa were mechanistically linked to recent climate warming. We aimed to determine whether there were correlations between preferred temperature envelope, or changes in temperature within species' ranges, and recent changes in range and population size, for 12 Fynbos-resident bird species, including six that are endemic to the biome. We then measured the physiological responses of each species at air temperatures ranging from 24 to 42°C to determine whether physiological thermal thresholds could provide a mechanistic explanation for observed population trends. Our data show that Fynbos-endemic species occupying the coolest regions experienced the greatest recent reductions in range and population size (>30% range reduction between 1991 and the present). In addition, species experiencing the largest increases in air temperature within their ranges showed the greatest declines. However, evidence for a physiological mechanistic link between warming and population declines was equivocal, with only the larger species showing low thermal thresholds for their body mass, compared with other birds globally. In addition, some species appear more vulnerable than others to air temperatures in their ranges above physiological thermal thresholds. Of these, the high-altitude specialist Cape rockjumper (Chaetops frenatus) seems most at risk from climate warming. This species showed: (i) the lowest threshold for increasing evaporative water loss at high temperatures; and (ii) population declines specifically in those regions of its range recording significant warming trends. Our findings suggest that caution must be taken when attributing causality explicitly to thermal stress, even when population trends are clearly correlated with rates of warming. Studies explicitly investigating the mechanisms underlying such correlations will be key to appropriate conservation

  18. Role of hydroxyurea during structured treatment interruptions.

    PubMed

    Foli, A; Seminari, E; Ravot, E; Lisziewicz, J; Lori, F

    2002-01-01

    Highly active antiretroviral therapies (HAART) represent a major advance in the treatment of HIV infection. Although with HAART a substantial suppression of viral replication can be obtained, eradication of the virus from the body cannot be achieved. Therefore, HIV-infected subjects have to be treated for the rest of their lives. Long term treatment will increase the frequency of: i) drug-related side effects; ii) onset of drug-resistant viral strains; iii) non-adherence of the patients to the treatment. Structured treatment interruptions (STI)-HAART might represent a feasible alternative and preliminary studies have shown that STI-HAART might induce immune control in patients treated in the early stage of infection. This regimen does not produce similar effects in patients treated during the chronic phase of the infection. However, there are some clinical data suggesting a possible role of hydroxyurea (HU) in inducing control of HIV replication in patients with established infection. In this manuscript in vitro and in vivo data indicating that HU might play a major role in the setting of STI-HAART will be presented.

  19. The Role of Physiological Markers of Health in the Association between Demographic Factors and Periodontal Disease

    PubMed Central

    Levine, ME; Kim, JK; Crimmins, EM

    2012-01-01

    Objectives This study examines whether the association between periodontal disease and demographic factors is mediated by physiological measures of health. Background Age is highly related to oral health status. The higher prevalence of oral disease within sub-groups of the population may reflect a tendency towards “early aging” and dysregulation of multiple physiological systems. Methods Logistic regression was used to examine whether biomarkers and demographic factors, such as SES and race/ethnicity, were associated with periodontal disease, and then whether the strength of these relationships could be attributed to associations between demographic variables and physiological measures of systemic health. Results Periodontal disease was associated with measures of SES and race/ethnicity. Furthermore, one unit increases in CMV optical density, CRP, and HbA1c were associated with a 25% (OR=1.25; 95% CI: 1.14–1.36), 13% (OR: 1.13; 95% CI: 1.03–1.24), and 19% (OR: 1.19; 95% CI: 1.12–1.27) increased likelihood of periodontal disease, respectively. However, when biomarkers and sociodemographic variables were both included in the model, their associations with periodontal disease were significantly reduced or eliminated. Conclusions The risk of periodontal disease is higher among blacks and/or low income individuals; however, these associations appear to be partly due to the greater probability of elevated levels of CRP, CMV, or HbA1c among these groups. PMID:23231345

  20. Predicting organismal vulnerability to climate warming: roles of behaviour, physiology and adaptation.

    PubMed

    Huey, Raymond B; Kearney, Michael R; Krockenberger, Andrew; Holtum, Joseph A M; Jess, Mellissa; Williams, Stephen E

    2012-06-19

    A recently developed integrative framework proposes that the vulnerability of a species to environmental change depends on the species' exposure and sensitivity to environmental change, its resilience to perturbations and its potential to adapt to change. These vulnerability criteria require behavioural, physiological and genetic data. With this information in hand, biologists can predict organisms most at risk from environmental change. Biologists and managers can then target organisms and habitats most at risk. Unfortunately, the required data (e.g. optimal physiological temperatures) are rarely available. Here, we evaluate the reliability of potential proxies (e.g. critical temperatures) that are often available for some groups. Several proxies for ectotherms are promising, but analogous ones for endotherms are lacking. We also develop a simple graphical model of how behavioural thermoregulation, acclimation and adaptation may interact to influence vulnerability over time. After considering this model together with the proxies available for physiological sensitivity to climate change, we conclude that ectotherms sharing vulnerability traits seem concentrated in lowland tropical forests. Their vulnerability may be exacerbated by negative biotic interactions. Whether tropical forest (or other) species can adapt to warming environments is unclear, as genetic and selective data are scant. Nevertheless, the prospects for tropical forest ectotherms appear grim.

  1. Predicting organismal vulnerability to climate warming: roles of behaviour, physiology and adaptation

    PubMed Central

    Huey, Raymond B.; Kearney, Michael R.; Krockenberger, Andrew; Holtum, Joseph A. M.; Jess, Mellissa; Williams, Stephen E.

    2012-01-01

    A recently developed integrative framework proposes that the vulnerability of a species to environmental change depends on the species' exposure and sensitivity to environmental change, its resilience to perturbations and its potential to adapt to change. These vulnerability criteria require behavioural, physiological and genetic data. With this information in hand, biologists can predict organisms most at risk from environmental change. Biologists and managers can then target organisms and habitats most at risk. Unfortunately, the required data (e.g. optimal physiological temperatures) are rarely available. Here, we evaluate the reliability of potential proxies (e.g. critical temperatures) that are often available for some groups. Several proxies for ectotherms are promising, but analogous ones for endotherms are lacking. We also develop a simple graphical model of how behavioural thermoregulation, acclimation and adaptation may interact to influence vulnerability over time. After considering this model together with the proxies available for physiological sensitivity to climate change, we conclude that ectotherms sharing vulnerability traits seem concentrated in lowland tropical forests. Their vulnerability may be exacerbated by negative biotic interactions. Whether tropical forest (or other) species can adapt to warming environments is unclear, as genetic and selective data are scant. Nevertheless, the prospects for tropical forest ectotherms appear grim. PMID:22566674

  2. The causes of physiological suppression among female meerkats: a role for subordinate restraint due to the threat of infanticide?

    PubMed

    Young, Andrew J; Monfort, Steven L; Clutton-Brock, Tim H

    2008-01-01

    In many animal societies, subordinates exhibit down-regulated reproductive endocrine axes relative to those of dominants, but whether this 'physiological suppression' arises from active interference by dominants or subordinate self-restraint is a matter of debate. Here we investigate the roles that these processes play in precipitating physiological suppression among subordinate female meerkats, Suricata suricatta. We show that, while subordinate females are known to suffer stress-related physiological suppression during periodic temporary evictions by the dominant female, their low estrogen levels while within their groups cannot be readily attributed to chronic stress, as their fecal glucocorticoid metabolite levels during this time are comparable to those of dominants. The low estrogen levels of subordinate females also cannot be explained simply by self-restraint due to factors that could reduce their payoff from maintaining their fertility regardless of the presence of the dominant female (young age, a lack of unrelated mates, poor body condition and limited breeding experience), as substantial rank-related differences in fecal total-estrogen metabolite levels remain when such factors are controlled. We suggest that this residual difference in estrogen levels may reflect a degree of subordinate restraint due in part to the dominant female's ability to kill their young. Accordingly, subordinate female estrogen levels vary in association with temporal variation in the likelihood of infanticide by the dominant. Attempts to identify the causes of physiological suppression should be cautious if rejecting any role for dominant interference in favor of subordinate restraint, as the dominant's capacity to interfere may often be the reason why subordinates exercise restraint.

  3. The causes of physiological suppression among female meerkats: a role for subordinate restraint due to the threat of infanticide?

    PubMed

    Young, Andrew J; Monfort, Steven L; Clutton-Brock, Tim H

    2008-01-01

    In many animal societies, subordinates exhibit down-regulated reproductive endocrine axes relative to those of dominants, but whether this 'physiological suppression' arises from active interference by dominants or subordinate self-restraint is a matter of debate. Here we investigate the roles that these processes play in precipitating physiological suppression among subordinate female meerkats, Suricata suricatta. We show that, while subordinate females are known to suffer stress-related physiological suppression during periodic temporary evictions by the dominant female, their low estrogen levels while within their groups cannot be readily attributed to chronic stress, as their fecal glucocorticoid metabolite levels during this time are comparable to those of dominants. The low estrogen levels of subordinate females also cannot be explained simply by self-restraint due to factors that could reduce their payoff from maintaining their fertility regardless of the presence of the dominant female (young age, a lack of unrelated mates, poor body condition and limited breeding experience), as substantial rank-related differences in fecal total-estrogen metabolite levels remain when such factors are controlled. We suggest that this residual difference in estrogen levels may reflect a degree of subordinate restraint due in part to the dominant female's ability to kill their young. Accordingly, subordinate female estrogen levels vary in association with temporal variation in the likelihood of infanticide by the dominant. Attempts to identify the causes of physiological suppression should be cautious if rejecting any role for dominant interference in favor of subordinate restraint, as the dominant's capacity to interfere may often be the reason why subordinates exercise restraint. PMID:17976602

  4. Physiological, pharmacological and toxicological considerations of drug-induced structural cardiac injury

    PubMed Central

    Cross, M J; Berridge, B R; Clements, P J M; Cove-Smith, L; Force, T L; Hoffmann, P; Holbrook, M; Lyon, A R; Mellor, H R; Norris, A A; Pirmohamed, M; Tugwood, J D; Sidaway, J E; Park, B K

    2015-01-01

    The incidence of drug-induced structural cardiotoxicity, which may lead to heart failure, has been recognized in association with the use of anthracycline anti-cancer drugs for many years, but has also been shown to occur following treatment with the new generation of targeted anti-cancer agents that inhibit one or more receptor or non-receptor tyrosine kinases, serine/threonine kinases as well as several classes of non-oncology agents. A workshop organized by the Medical Research Council Centre for Drug Safety Science (University of Liverpool) on 5 September 2013 and attended by industry, academia and regulatory representatives, was designed to gain a better understanding of the gaps in the field of structural cardiotoxicity that can be addressed through collaborative efforts. Specific recommendations from the workshop for future collaborative activities included: greater efforts to identify predictive (i) preclinical; and (ii) clinical biomarkers of early cardiovascular injury; (iii) improved understanding of comparative physiology/pathophysiology and the clinical predictivity of current preclinical in vivo models; (iv) the identification and use of a set of cardiotoxic reference compounds for comparative profiling in improved animal and human cellular models; (v) more sharing of data (through publication/consortia arrangements) on target-related toxicities; (vi) strategies to develop cardio-protective agents; and (vii) closer interactions between preclinical scientists and clinicians to help ensure best translational efforts. PMID:25302413

  5. Molecular Aspects of Structure, Gating, and Physiology of pH-Sensitive Background K2P and Kir K+-Transport Channels

    PubMed Central

    Sepúlveda, Francisco V.; Pablo Cid, L.; Teulon, Jacques; Niemeyer, María Isabel

    2015-01-01

    K+ channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K+ channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K+ homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K+-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge. PMID:25540142

  6. Molecular aspects of structure, gating, and physiology of pH-sensitive background K2P and Kir K+-transport channels.

    PubMed

    Sepúlveda, Francisco V; Pablo Cid, L; Teulon, Jacques; Niemeyer, María Isabel

    2015-01-01

    K(+) channels fulfill roles spanning from the control of excitability to the regulation of transepithelial transport. Here we review two groups of K(+) channels, pH-regulated K2P channels and the transport group of Kir channels. After considering advances in the molecular aspects of their gating based on structural and functional studies, we examine their participation in certain chosen physiological and pathophysiological scenarios. Crystal structures of K2P and Kir channels reveal rather unique features with important consequences for the gating mechanisms. Important tasks of these channels are discussed in kidney physiology and disease, K(+) homeostasis in the brain by Kir channel-equipped glia, and central functions in the hearing mechanism in the inner ear and in acid secretion by parietal cells in the stomach. K2P channels fulfill a crucial part in central chemoreception probably by virtue of their pH sensitivity and are central to adrenal secretion of aldosterone. Finally, some unorthodox behaviors of the selectivity filters of K2P channels might explain their normal and pathological functions. Although a great deal has been learned about structure, molecular details of gating, and physiological functions of K2P and Kir K(+)-transport channels, this has been only scratching at the surface. More molecular and animal studies are clearly needed to deepen our knowledge.

  7. Physiological roles of pyruvate ferredoxin oxidoreductase and pyruvate formate-lyase in Thermoanaerobacterium saccharolyticum JW/SL-YS485

    SciTech Connect

    Zhou, Jilai; Olson, Daniel G.; Lanahan, Anthony A.; Tian, Liang; Murphy, Sean Jean-Loup; Lo, Jonathan; Lynd, Lee R.

    2015-09-15

    We report that Thermoanaerobacter saccharolyticum is a thermophilic microorganism that has been engineered to produce ethanol at high titer (30–70 g/L) and greater than 90 % theoretical yield. However, few genes involved in pyruvate to ethanol production pathway have been unambiguously identified. In T. saccharolyticum, the products of six putative pfor gene clusters and one pfl gene may be responsible for the conversion of pyruvate to acetyl-CoA. To gain insights into the physiological roles of PFOR and PFL, we studied the effect of deletions of several genes thought to encode these activities. We found that that pyruvate ferredoxin oxidoreductase enzyme (PFOR) is encoded by the pforA gene and plays a key role in pyruvate dissimilation. We further demonstrated that pyruvate formate-lyase activity (PFL) is encoded by the pfl gene. Although the pfl gene is normally expressed at low levels, it is crucial for biosynthesis in T. saccharolyticum. In pforA deletion strains, pfl expression increased and was able to partially compensate for the loss of PFOR activity. Deletion of both pforA and pfl resulted in a strain that required acetate and formate for growth and produced lactate as the primary fermentation product, achieving 88 % theoretical lactate yield. PFOR encoded by Tsac_0046 and PFL encoded by Tsac_0628 are only two routes for converting pyruvate to acetyl-CoA in T. saccharolyticum. The physiological role of PFOR is pyruvate dissimilation, whereas that of PFL is supplying C1 units for biosynthesis.

  8. Role of mTOR1 and mTOR2 complexes in MEG-01 cell physiology.

    PubMed

    López, Esther; Berna-Erro, Alejandro; López, Javier J; Granados, María P; Bermejo, Nuria; Brull, Jose M; Salido, Ginés M; Rosado, Juan A; Redondo, Pedro C

    2015-11-01

    The function of the mammalian target of rapamycin (mTOR) is upregulated in response to cell stimulation with growing and differentiating factors. Active mTOR controls cell proliferation, differentiation and death. Since mTOR associates with different proteins to form two functional macromolecular complexes, we aimed to investigate the role of the mTOR1 and mTOR2 complexes in MEG-01 cell physiology in response to thrombopoietin (TPO). By using mTOR antagonists and overexpressing FKBP38, we have explored the role of both mTOR complexes in proliferation, apoptosis, maturation-like mechanisms, endoplasmic reticulum-stress and the intracellular location of both active mTOR complexes during MEG-01 cell stimulation with TPO. The results demonstrate that mTOR1 and mTOR2 complexes play different roles in the physiology of MEG-01 cells and in the maturation-like mechanisms; hence, these findings might help to understand the mechanism underlying generation of platelets.

  9. Use of antiserum to neurotensin reveals a physiological role for the peptide in rat prolactin release.

    PubMed Central

    Vijayan, E; Carraway, R; Leeman, S E; McCann, S M

    1988-01-01

    Previous studies have indicated that the brain peptide neurotensin can stimulate prolactin release by direct action on the pituitary gland, whereas its action within the hypothalamus is inhibitory. The inhibitory action is mediated by the release of dopamine into the hypophyseal portal veins, which deliver the neurotransmitter to the anterior pituitary gland to inhibit prolactin release. Our experiments were done to evaluate the physiologic significance of these neurotensin actions by injecting the globulin fraction of highly specific neurotensin antiserum either intravenously or intraventricularly. Injection into the third ventricle of either 1 or 3 microliter of neurotensin antiserum significantly increased plasma prolactin concentrations in (i) ovariectomized and (ii) ovariectomized estrogen- and progesterone-primed rats within 1 hr of injection. The response was more pronounced in the ovariectomized than in the ovariectomized estrogen- and progesterone-treated animals and was dose related. Intraventricular injection of these doses of neurotensin antiserum also evoked elevations in plasma prolactin in intact males, which were significant but smaller in magnitude than those seen in female rats. To evaluate the effect of the antiserum on the pituitary directly, the antiserum was injected intravenously at a dose of 40 microliter, which was sufficient to block the blood pressure-lowering effect of neurotensin. After the intravenous injection of antiserum, a highly significant suppression of plasma prolactin occurred, detectable when first measured at 1 hr after injection in both ovariectomized and ovariectomized estrogen- and progesterone-treated animals; however, the intravenous injection of antiserum had no significant effect on the prolactin release in males. These data indicate the physiological significance of the hypothalamic inhibitory actions of neurotensin on prolactin release, which are probably mediated by its stimulation of dopamine release that in turn

  10. Studying Multisensory Processing and Its Role in the Representation of Space through Pathological and Physiological Crossmodal Extinction

    PubMed Central

    Jacobs, Stéphane; Brozzoli, Claudio; Hadj-Bouziane, Fadila; Meunier, Martine; Farnè, Alessandro

    2011-01-01

    The study of crossmodal extinction has brought a considerable contribution to our understanding of how the integration of stimuli perceived in multiple sensory modalities is used by the nervous system to build coherent representations of the space that directly surrounds us. Indeed, by revealing interferences between stimuli in a disturbed system, extinction provides an invaluable opportunity to investigate the interactions that normally exist between those stimuli in an intact system. Here, we first review studies on pathological crossmodal extinction, from the original demonstration of its existence, to its role in the exploration of the multisensory neural representation of space and the current theoretical accounts proposed to explain the mechanisms involved in extinction and multisensory competition. Then, in the second part of this paper, we report recent findings showing that physiological multisensory competition phenomena resembling clinical crossmodal extinction exist in the healthy brain. We propose that the development of a physiological model of sensory competition is fundamental to deepen our understanding of the cerebral mechanisms of multisensory perception and integration. In addition, a similar approach to develop a model of physiological sensory competition in non-human primates should allow combining functional neuroimaging with more invasive techniques, such as transient focal lesions, in order to bridge the gap between works done in the two species and at different levels of analysis. PMID:21687458

  11. The myths and physiology surrounding intrapartum decelerations: the critical role of the peripheral chemoreflex.

    PubMed

    Lear, Christopher A; Galinsky, Robert; Wassink, Guido; Yamaguchi, Kyohei; Davidson, Joanne O; Westgate, Jenny A; Bennet, Laura; Gunn, Alistair J

    2016-09-01

    A distinctive pattern of recurrent rapid falls in fetal heart rate, called decelerations, are commonly associated with uterine contractions during labour. These brief decelerations are mediated by vagal activation. The reflex triggering this vagal response has been variably attributed to a mechanoreceptor response to fetal head compression, to baroreflex activation following increased blood pressure during umbilical cord compression, and/or a Bezold-Jarisch reflex response to reduced venous return from the placenta. Although these complex explanations are still widespread today, there is no consistent evidence that they are common during labour. Instead, the only mechanism that has been systematically investigated, proven to be reliably active during labour and, crucially, capable of producing rapid decelerations is the peripheral chemoreflex. The peripheral chemoreflex is triggered by transient periods of asphyxia that are a normal phenomenon associated with all uterine contractions. This should not cause concern as the healthy fetus has a remarkable ability to adapt to these repeated but short periods of asphyxia. This means that the healthy fetus is typically not at risk of hypotension and injury during uncomplicated labour even during repeated brief decelerations. The physiologically incorrect theories surrounding decelerations that ignore the natural occurrence of repeated asphyxia probably gained widespread support to help explain why many babies are born healthy despite repeated decelerations during labour. We propose that a unified and physiological understanding of intrapartum decelerations that accepts the true nature of labour is critical to improve interpretation of intrapartum fetal heart rate patterns. PMID:27328617

  12. Affective and physiological responses to racism: the roles of afrocentrism and mode of presentation.

    PubMed

    Jones, D R; Harrell, J P; Morris-Prather, C E; Thomas, J; Omowale, N

    1996-01-01

    Recent experiments have examined the subjective and physiological responses of African Americans to racism using video-taped vignettes or emotional imagery. These studies reported changes in mood and increases in cardiovascular (CV) and electromyographic (EMG) activity when analogs of the stressful situations were encountered. In addition, individual differences in responses were found to be related to various personality measures. The present study examined the mood, CV and EMG responses of 60 African-American women as they encountered social situations that included blatant and more subtle forms of racism. Half of the sample viewed both vignettes while the remainder imagined them. The relationship between responses and Afrocentrism, a measure related to black identity, was examined. Significant changes in heart rate, digital blood flow and facial muscle activity in the corrugator regions resulted. The most pronounced changes occurred when blatantly racist material was encountered. Mood changes tended to be stronger when material was imagined versus viewed. In general, Afrocentricity was not related to physiological responses to the scripts, though mood responses and Afrocentricity were related in several instances. The findings indicate that CV, as well as EMG and mood responses, are sensitive to various forms of racism presented in imagery and video modes.

  13. A physiological role for androgen actions in the absence of androgen receptor DNA binding activity.

    PubMed

    Pang, Tammy P S; Clarke, Michele V; Ghasem-Zadeh, Ali; Lee, Nicole K L; Davey, Rachel A; MacLean, Helen E

    2012-01-01

    We tested the hypothesis that androgens have physiological actions via non-DNA binding-dependent androgen receptor (AR) signaling pathways in males, using our genetically modified mice that express a mutant AR with deletion of the 2nd zinc finger of the DNA binding domain (AR(ΔZF2)) that cannot bind DNA. In cultured genital skin fibroblasts, the mutant AR(ΔZF2) has normal ligand binding ability, phosphorylates ERK-1/2 in response to 1 min DHT treatment (blocked by the AR antagonist bicalutamide), but has reduced androgen-dependent nuclear localization compared to wildtype (WT). AR(ΔZF2) males have normal baseline ERK-1/2 phosphorylation, with a 1.5-fold increase in Akt phosphorylation in AR(ΔZF2) muscle vs WT. To identify physiological actions of non-DNA binding-dependent AR signaling, AR(ΔZF2) males were treated for 6 weeks with dihydrotestosterone (DHT). Cortical bone growth was suppressed by DHT in AR(ΔZF2) mice (6% decrease in periosteal and 7% decrease in medullary circumference vs untreated AR(ΔZF2) males). In conclusion, these data suggest that non-DNA binding dependent AR actions suppress cortical bone growth, which may provide a mechanism to fine-tune the response to androgens in bone.

  14. [Structural and physiological diversity among cystlike resting cells of bacteria of the genus Pseudomonas].

    PubMed

    Muliukin, A L; Suzina, N E; Duda, V I; El'-Registan, G I

    2008-01-01

    Cystlike resting cells (CRC) of non-spore-forming gram-negative bacteria of the genus Pseudomonas, P. aurantiaca and P. fluorescens, were obtained and characterized for the first time; their physiological and morphological diversity was demonstrated. The following properties were common for all the revealed types of CRC as dormant forms: (1) long-term (up to 6 months or longer) maintenance of viability in the absence of culture growth and cell respiration; (2) absence of an experimentally detectable level of metabolism; (3) higher resistance to damage and autolysis under the action of provoking factors than in metabolically active vegetative cells; and (4) specific features of ultrastructural organization absent in vegetative cells: thickened and lamellar envelopes, clumpy structure of the cytoplasm, and condensed DNA in nucleoid. The differences in various types of CRC concern the thickness and lamellar structure of cell envelopes, as well as the presence and thickness of the capsular layer. In particular, forms ultrastructurally similar to typical bacterial cysts were revealed in pseudomonad populations growing on soil agar. Physiological diversity was revealed in different levels of viability preservation and thermal resistance in various types of CRC and depended on the conditions of their formation. The optimal conditions and procedures for obtaining P. aurantiaca and P. fluorescens CRC that retain the ability to form colonies on standard nutrient media are as follows: (1) a twofold decrease of nitrogen content in the growth medium; (2) an increased level of anabiosis autoinducer (C12-AHB, 10(-4) M) in stationary cultures; (3) transfer of the cells from stationary cultures to a starvation medium with silica; (4) cultivation in soil extract; and (5) development of cultures on soil agar. The CRC from the cultures grown in soil extract or starvation medium with silica proved to be resistant to heat treatment (60 degrees C, 5 min). In the CRC formed in nitrogen

  15. Phylogenomic Analysis and Predicted Physiological Role of the Proton-Translocating NADH:Quinone Oxidoreductase (Complex I) Across Bacteria

    PubMed Central

    Spero, Melanie A.; Aylward, Frank O.; Currie, Cameron R.

    2015-01-01

    ABSTRACT The proton-translocating NADH:quinone oxidoreductase (complex I) is a multisubunit integral membrane enzyme found in the respiratory chains of both bacteria and eukaryotic organelles. Although much research has focused on the enzyme’s central role in the mitochondrial respiratory chain, comparatively little is known about its role in the diverse energetic lifestyles of different bacteria. Here, we used a phylogenomic approach to better understand the distribution of complex I across bacteria, the evolution of this enzyme, and its potential roles in shaping the physiology of different bacterial groups. By surveying 970 representative bacterial genomes, we predict complex I to be present in ~50% of bacteria. While this includes bacteria with a wide range of energetic schemes, the presence of complex I is associated with specific lifestyles, including aerobic respiration and specific types of phototrophy (bacteria with only a type II reaction center). A phylogeny of bacterial complex I revealed five main clades of enzymes whose evolution is largely congruent with the evolution of the bacterial groups that encode complex I. A notable exception includes the gammaproteobacteria, whose members encode one of two distantly related complex I enzymes predicted to participate in different types of respiratory chains (aerobic versus anaerobic). Comparative genomic analyses suggest a broad role for complex I in reoxidizing NADH produced from various catabolic reactions, including the tricarboxylic acid (TCA) cycle and fatty acid beta-oxidation. Together, these findings suggest diverse roles for complex I across bacteria and highlight the importance of this enzyme in shaping diverse physiologies across the bacterial domain. PMID:25873378

  16. The Physiology and Biochemistry of Receptors.

    ERIC Educational Resources Information Center

    Spitzer, Judy A., Ed.

    1983-01-01

    The syllabus for a refresher course on the physiology and biochemistry of receptors (presented at the 1983 American Physiological Society meeting) is provided. Topics considered include receptor regulation, structural/functional aspects of receptors for insulin and insulin-like growth factors, calcium channel inhibitors, and role of lipoprotein…

  17. Role of motor unit structure in defining function

    NASA Technical Reports Server (NTRS)

    Monti, R. J.; Roy, R. R.; Edgerton, V. R.

    2001-01-01

    Motor units, defined as a motoneuron and all of its associated muscle fibers, are the basic functional units of skeletal muscle. Their activity represents the final output of the central nervous system, and their role in motor control has been widely studied. However, there has been relatively little work focused on the mechanical significance of recruiting variable numbers of motor units during different motor tasks. This review focuses on factors ranging from molecular to macroanatomical components that influence the mechanical output of a motor unit in the context of the whole muscle. These factors range from the mechanical properties of different muscle fiber types to the unique morphology of the muscle fibers constituting a motor unit of a given type and to the arrangement of those motor unit fibers in three dimensions within the muscle. We suggest that as a result of the integration of multiple levels of structural and physiological levels of organization, unique mechanical properties of motor units are likely to emerge. Copyright 2001 John Wiley & Sons, Inc.

  18. The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter.

    PubMed

    Pan, Xin; Liu, Jie; Nguyen, Tiffany; Liu, Chengyu; Sun, Junhui; Teng, Yanjie; Fergusson, Maria M; Rovira, Ilsa I; Allen, Michele; Springer, Danielle A; Aponte, Angel M; Gucek, Marjan; Balaban, Robert S; Murphy, Elizabeth; Finkel, Toren

    2013-12-01

    Mitochondrial calcium has been postulated to regulate a wide range of processes from bioenergetics to cell death. Here, we characterize a mouse model that lacks expression of the recently discovered mitochondrial calcium uniporter (MCU). Mitochondria derived from MCU(-/-) mice have no apparent capacity to rapidly uptake calcium. Whereas basal metabolism seems unaffected, the skeletal muscle of MCU(-/-) mice exhibited alterations in the phosphorylation and activity of pyruvate dehydrogenase. In addition, MCU(-/-) mice exhibited marked impairment in their ability to perform strenuous work. We further show that mitochondria from MCU(-/-) mice lacked evidence for calcium-induced permeability transition pore (PTP) opening. The lack of PTP opening does not seem to protect MCU(-/-) cells and tissues from cell death, although MCU(-/-) hearts fail to respond to the PTP inhibitor cyclosporin A. Taken together, these results clarify how acute alterations in mitochondrial matrix calcium can regulate mammalian physiology.

  19. Phagoptosis - Cell Death By Phagocytosis - Plays Central Roles in Physiology, Host Defense and Pathology.

    PubMed

    Brown, G C; Vilalta, A; Fricker, M

    2015-01-01

    Cell death by phagocytosis - termed 'phagoptosis' for short - is a form of cell death caused by the cell being phagocytosed i.e. recognised, engulfed and digested by another cell. Phagocytes eat cells that: i) expose 'eat-me' signals, ii) lose 'don't-eat-me' signals, and/or iii) bind opsonins. Live cells may express such signals as a result of cell stress, damage, activation or senescence, which can result in phagoptosis. Phagoptosis may be the most abundant form of cell death physiologically as it mediates erythrocyte turnover. It also regulates: reproduction by phagocytosis of sperm, development by removal stem cells and excess cells, and immunity by removal of activated neutrophils and T cells. Phagoptosis mediates the recognition of non-self and host defence against pathogens and cancer cells. However, in inflammatory conditions, excessive phagoptosis may kill our cells, leading to conditions such as hemophagy and neuronal loss.

  20. Diverse functional roles of monosaccharide transporters and their homologs in vascular plants: a physiological perspective.

    PubMed

    Slewinski, Thomas L

    2011-07-01

    Vascular plants contain two gene families that encode monosaccharide transporter proteins. The classical monosaccharide transporter(-like) gene superfamily is large and functionally diverse, while the recently identified SWEET transporter family is smaller and, thus far, only found to transport glucose. These transporters play essential roles at many levels, ranging from organelles to the whole plant. Many family members are essential for cellular homeostasis and reproductive success. Although most transporters do not directly participate in long-distance transport, their indirect roles greatly impact carbon allocation and transport flux to the heterotrophic tissues of the plant. Functional characterization of some members from both gene families has revealed their diverse roles in carbohydrate partitioning, phloem function, resource allocation, plant defense, and sugar signaling. This review highlights the broad impacts and implications of monosaccharide transport by describing some of the functional roles of the monosaccharide transporter(-like) superfamily and the SWEET transporter family.

  1. Establishment of procedures for studying mPR-interacting agents and physiological roles of mPR.

    PubMed

    Tokumoto, Toshinobu; Hossain, Md Babul; Wang, Jun

    2016-07-01

    More than 10years have passed since the discovery of membrane progestin receptors (mPRs). Although the identification of mPR genes in various organisms and mPR expression patterns have been described since then, the precise physiological roles of mPRs are still unclear, except their function as a receptor for maturation-inducing steroid in fish. The wide distribution of mPRs suggests variable actions for progestins through mPRs in the tissues. Information about the physiological roles of mPRs, such as roles in the progression of breast cancer and T-cell proliferation, has gradually accumulated recently. These results suggest that mPRs are possible targets for new pharmaceuticals. We established a cell line that was transformed with cDNAs for mPRα and a recombinant luciferase gene named GloSensor. The cells can be used for monitoring the effects of ligands on mPRα based on intracellular cyclic adenosine monophosphate (cAMP) levels. Studies using these cell lines indicated that the cAMP concentration is decreased by ligands for mPRα. The results provide support for previous results suggesting that mPRα is coupled to inhibitory G protein (Gi). We also established screening methods that make it possible to screen ligands for mPR. Recently, we succeeded in expressing and purifying recombinant mPR protein in the yeast Pichia pastoris. Relatively large amounts of mPR protein with hormonal binding activity can be purified by our method. The recombinant protein will be applicable to establishing a molecular probe to detect mPR-interacting agents. To obtain decisive evidence for the roles of mPRs, we are establishing strains of medaka fish that are deficient in mPRs. In medaka, four subtypes of mPR genes (α, β, γ, and α2) have been identified. By reverse genetic screening, we have selected three to four strains in which a point mutation has been induced in the coding sequence of the mPR subtypes. However, homozygous mutants of each mPR gene showed no phenotype. The

  2. Identification and Characterization of the Corazonin Receptor and Possible Physiological Roles of the Corazonin-Signaling Pathway in Rhodnius prolixus.

    PubMed

    Hamoudi, Zina; Lange, Angela B; Orchard, Ian

    2016-01-01

    Neuropeptides control many physiological and endocrinological processes in animals, acting as neuroactive chemicals within the central and peripheral nervous systems. Corazonin (CRZ) is one such neuropeptide that has a variety of physiological roles associated with control of heartbeat, ecdysis behavior initiation, and cuticle coloration. These physiological effects are mediated by the CRZ receptor (CRZR). In order to understand the role of the CRZ-signaling pathway in Rhodnius prolixus, the cDNA sequence encoding the Rhopr-CRZR was isolated and cloned revealing two splice variants (Rhopr-CRZR-α and β). Sequence analysis revealed characteristics of rhodopsin-like GPCRs. Rhopr-CRZR-α and β were dose-dependently activated by Rhopr-CRZ with EC50 values of 2.7 and 1 nM, respectively, when tested in a functional receptor assay using CHOKI-aeq cells. Neither receptors were activated by the evolutionarily-related peptides, Rhopr-AKH, or Rhopr-ACP. For 5th instars, qPCR revealed expression of Rhopr-CRZR transcript in the CNS, the dorsal vessel, abdominal dorsal epidermis, and prothoracic glands with associated fat body. Interestingly, transcript expression was also found in the female and male reproductive tissues. Rhopr-CRZR transcript was reduced after injection of dsCRZR into adult R. prolixus. In these insects, the basal heartbeat rate was reduced in vivo, and the increase in heartbeat frequency normally produced by CRZ on dorsal vessel in vitro was much reduced. No effect of dsCRZR injection was seen on ecdysis or coloration of the cuticle. PMID:27536213

  3. Identification and Characterization of the Corazonin Receptor and Possible Physiological Roles of the Corazonin-Signaling Pathway in Rhodnius prolixus

    PubMed Central

    Hamoudi, Zina; Lange, Angela B.; Orchard, Ian

    2016-01-01

    Neuropeptides control many physiological and endocrinological processes in animals, acting as neuroactive chemicals within the central and peripheral nervous systems. Corazonin (CRZ) is one such neuropeptide that has a variety of physiological roles associated with control of heartbeat, ecdysis behavior initiation, and cuticle coloration. These physiological effects are mediated by the CRZ receptor (CRZR). In order to understand the role of the CRZ-signaling pathway in Rhodnius prolixus, the cDNA sequence encoding the Rhopr-CRZR was isolated and cloned revealing two splice variants (Rhopr-CRZR-α and β). Sequence analysis revealed characteristics of rhodopsin-like GPCRs. Rhopr-CRZR-α and β were dose-dependently activated by Rhopr-CRZ with EC50 values of 2.7 and 1 nM, respectively, when tested in a functional receptor assay using CHOKI-aeq cells. Neither receptors were activated by the evolutionarily-related peptides, Rhopr-AKH, or Rhopr-ACP. For 5th instars, qPCR revealed expression of Rhopr-CRZR transcript in the CNS, the dorsal vessel, abdominal dorsal epidermis, and prothoracic glands with associated fat body. Interestingly, transcript expression was also found in the female and male reproductive tissues. Rhopr-CRZR transcript was reduced after injection of dsCRZR into adult R. prolixus. In these insects, the basal heartbeat rate was reduced in vivo, and the increase in heartbeat frequency normally produced by CRZ on dorsal vessel in vitro was much reduced. No effect of dsCRZR injection was seen on ecdysis or coloration of the cuticle. PMID:27536213

  4. Role of central vagal 5-HT3 receptors in gastrointestinal physiology and pathophysiology

    PubMed Central

    Browning, Kirsteen N.

    2015-01-01

    Vagal neurocircuits are vitally important in the co-ordination and modulation of GI reflexes and homeostatic functions. 5-hydroxytryptamine (5-HT; serotonin) is critically important in the regulation of several of these autonomic gastrointestinal (GI) functions including motility, secretion and visceral sensitivity. While several 5-HT receptors are involved in these physiological responses, the ligand-gated 5-HT3 receptor appears intimately involved in gut-brain signaling, particularly via the afferent (sensory) vagus nerve. 5-HT is released from enterochromaffin cells in response to mechanical or chemical stimulation of the GI tract which leads to activation of 5-HT3 receptors on the terminals of vagal afferents. 5-HT3 receptors are also present on the soma of vagal afferent neurons, including GI vagal afferent neurons, where they can be activated by circulating 5-HT. The central terminals of vagal afferents also exhibit 5-HT3 receptors that function to increase glutamatergic synaptic transmission to second order neurons of the nucleus tractus solitarius within the brainstem. While activation of central brainstem 5-HT3 receptors modulates visceral functions, it is still unclear whether central vagal neurons, i.e., nucleus of the tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMV) neurons themselves also display functional 5-HT3 receptors. Thus, activation of 5-HT3 receptors may modulate the excitability and activity of gastrointestinal vagal afferents at multiple sites and may be involved in several physiological and pathophysiological conditions, including distention- and chemical-evoked vagal reflexes, nausea, and vomiting, as well as visceral hypersensitivity. PMID:26578870

  5. The role of ascorbate peroxidase, guaiacol peroxidase, and polysaccharides in cassava (Manihot esculenta Crantz) roots under postharvest physiological deterioration.

    PubMed

    Uarrota, Virgílio Gavicho; Moresco, Rodolfo; Schmidt, Eder Carlos; Bouzon, Zenilda Laurita; Nunes, Eduardo da Costa; Neubert, Enilto de Oliveira; Peruch, Luiz Augusto Martins; Rocha, Miguel; Maraschin, Marcelo

    2016-04-15

    This study aimed to investigate the role of ascorbate peroxidase (APX), guaiacol peroxidase (GPX), polysaccharides, and protein contents associated with the early events of postharvest physiological deterioration (PPD) in cassava roots. Increases in APX and GPX activity, as well as total protein contents occurred from 3 to 5 days of storage and were correlated with the delay of PPD. Cassava samples stained with Periodic Acid-Schiff (PAS) highlighted the presence of starch and cellulose. Degradation of starch granules during PPD was also detected. Slight metachromatic reaction with toluidine blue is indicative of increasing of acidic polysaccharides and may play an important role in PPD delay. Principal component analysis (PCA) classified samples according to their levels of enzymatic activity based on the decision tree model which showed GPX and total protein amounts to be correlated with PPD. The Oriental (ORI) cultivar was more susceptible to PPD.

  6. Effects of simulated microgravity on Streptococcus mutans physiology and biofilm structure.

    PubMed

    Cheng, Xingqun; Xu, Xin; Chen, Jing; Zhou, Xuedong; Cheng, Lei; Li, Mingyun; Li, Jiyao; Wang, Renke; Jia, Wenxiang; Li, Yu-Qing

    2014-10-01

    Long-term spaceflights will eventually become an inevitable occurrence. Previous studies have indicated that oral infectious diseases, including dental caries, were more prevalent in astronauts due to the effect of microgravity. However, the impact of the space environment, especially the microgravity environment, on the virulence factors of Streptococcus mutans, a major caries-associated bacterium, is yet to be explored. In the present study, we investigated the impact of simulated microgravity on the physiology and biofilm structure of S. mutans. We also explored the dual-species interaction between S. mutans and Streptococcus sanguinis under a simulated microgravity condition. Results indicated that the simulated microgravity condition can enhance the acid tolerance ability, modify the biofilm architecture and extracellular polysaccharide distribution of S. mutans, and increase the proportion of S. mutans within a dual-species biofilm, probably through the regulation of various gene expressions. We hypothesize that the enhanced competitiveness of S. mutans under simulated microgravity may cause a multispecies micro-ecological imbalance, which would result in the initiation of dental caries. Our current findings are consistent with previous studies, which revealed a higher astronaut-associated incidence of caries. Further research is required to explore the detailed mechanisms. PMID:25109245

  7. Cardiac structure and function in humans: a new cardiovascular physiology laboratory

    PubMed Central

    Song, Su; Burleson, Paul D.; Passo, Stanley; Messina, Edward J.; Levine, Norman; Thompson, Carl I.; Belloni, Francis L.; Recchia, Fabio A.; Ojaimi, Caroline; Kaley, Gabor

    2009-01-01

    As the traditional cardiovascular control laboratory has disappeared from the first-year medical school curriculum, we have recognized the need to develop another “hands-on” experience as a vehicle for wide-ranging discussions of cardiovascular control mechanisms. Using an echocardiograph, an automatic blood pressure cuff, and a reclining bicycle, we developed protocols to illustrate the changes in cardiac and vascular function that occur with changes in posture, venous return, and graded exercise. We use medical student volunteers and a professional echocardiographer to generate and acquire data, respectively. In small-group sessions, we developed an interactive approach to discuss the data and to make a large number of calculations from a limited number of measurements. The sequence of cardiac events and cardiac structure in vivo were illustrated with the volunteers lying down, standing, and then with their legs raised passively above the heart to increase venous return. Volunteers were then asked to peddle the bicycle to achieve steady-state heart rates of 110 and 150 beats/min. Data were collected in all these states, and calculations were performed and used as the basis of a small-group discussion to illustrate physiological principles. Information related to a surprisingly large number of cardiovascular control mechanisms was derived, and its relevance to cardiovascular dysfunction was explored. This communication describes our experience in developing a new cardiovascular control laboratory to reinforce didactic material presented in lectures and small-group sessions. PMID:19745049

  8. Cardiac structure and function in humans: a new cardiovascular physiology laboratory.

    PubMed

    Song, Su; Burleson, Paul D; Passo, Stanley; Messina, Edward J; Levine, Norman; Thompson, Carl I; Belloni, Francis L; Recchia, Fabio A; Ojaimi, Caroline; Kaley, Gabor; Hintze, Thomas H

    2009-09-01

    As the traditional cardiovascular control laboratory has disappeared from the first-year medical school curriculum, we have recognized the need to develop another "hands-on" experience as a vehicle for wide-ranging discussions of cardiovascular control mechanisms. Using an echocardiograph, an automatic blood pressure cuff, and a reclining bicycle, we developed protocols to illustrate the changes in cardiac and vascular function that occur with changes in posture, venous return, and graded exercise. We use medical student volunteers and a professional echocardiographer to generate and acquire data, respectively. In small-group sessions, we developed an interactive approach to discuss the data and to make a large number of calculations from a limited number of measurements. The sequence of cardiac events and cardiac structure in vivo were illustrated with the volunteers lying down, standing, and then with their legs raised passively above the heart to increase venous return. Volunteers were then asked to peddle the bicycle to achieve steady-state heart rates of 110 and 150 beats/min. Data were collected in all these states, and calculations were performed and used as the basis of a small-group discussion to illustrate physiological principles. Information related to a surprisingly large number of cardiovascular control mechanisms was derived, and its relevance to cardiovascular dysfunction was explored. This communication describes our experience in developing a new cardiovascular control laboratory to reinforce didactic material presented in lectures and small-group sessions.

  9. Numerical Bifurcation Analysis of Physiologically Structured Populations: Consumer-Resource, Cannibalistic and Trophic Models.

    PubMed

    Sánchez Sanz, Julia; Getto, Philipp

    2016-07-01

    With the aim of applying numerical methods, we develop a formalism for physiologically structured population models in a new generality that includes consumer-resource, cannibalism and trophic models. The dynamics at the population level are formulated as a system of Volterra functional equations coupled to ODE. For this general class, we develop numerical methods to continue equilibria with respect to a parameter, detect transcritical and saddle-node bifurcations and compute curves in parameter planes along which these bifurcations occur. The methods combine curve continuation, ODE solvers and test functions. Finally, we apply the methods to the above models using existing data for Daphnia magna consuming Algae and for Perca fluviatilis feeding on Daphnia magna. In particular, we validate the methods by deriving expressions for equilibria and bifurcations with respect to which we compute errors, and by comparing the obtained curves with curves that were computed earlier with other methods. We also present new curves to show how the methods can easily be applied to derive new biological insight. Schemes of algorithms are included. PMID:27484496

  10. Effects of simulated microgravity on Streptococcus mutans physiology and biofilm structure.

    PubMed

    Cheng, Xingqun; Xu, Xin; Chen, Jing; Zhou, Xuedong; Cheng, Lei; Li, Mingyun; Li, Jiyao; Wang, Renke; Jia, Wenxiang; Li, Yu-Qing

    2014-10-01

    Long-term spaceflights will eventually become an inevitable occurrence. Previous studies have indicated that oral infectious diseases, including dental caries, were more prevalent in astronauts due to the effect of microgravity. However, the impact of the space environment, especially the microgravity environment, on the virulence factors of Streptococcus mutans, a major caries-associated bacterium, is yet to be explored. In the present study, we investigated the impact of simulated microgravity on the physiology and biofilm structure of S. mutans. We also explored the dual-species interaction between S. mutans and Streptococcus sanguinis under a simulated microgravity condition. Results indicated that the simulated microgravity condition can enhance the acid tolerance ability, modify the biofilm architecture and extracellular polysaccharide distribution of S. mutans, and increase the proportion of S. mutans within a dual-species biofilm, probably through the regulation of various gene expressions. We hypothesize that the enhanced competitiveness of S. mutans under simulated microgravity may cause a multispecies micro-ecological imbalance, which would result in the initiation of dental caries. Our current findings are consistent with previous studies, which revealed a higher astronaut-associated incidence of caries. Further research is required to explore the detailed mechanisms.

  11. The Role of Gap Junction Channels During Physiologic and Pathologic Conditions of the Human Central Nervous System

    PubMed Central

    Basilio, Daniel; Sáez, Juan C.; Orellana, Juan A.; Raine, Cedric S.; Bukauskas, Feliksas; Bennett, Michael V. L.; Berman, Joan W.

    2013-01-01

    Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP3, and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system. PMID:22438035

  12. Investigations of Protein Structure and Function Using the Scientific Literature: An Assignment for an Undergraduate Cell Physiology Course

    ERIC Educational Resources Information Center

    Mulnix, Amy B.

    2003-01-01

    Undergraduate biology curricula are being modified to model and teach the activities of scientists better. The assignment described here, one that investigates protein structure and function, was designed for use in a sophomore-level cell physiology course at Earlham College. Students work in small groups to read and present in poster format on…

  13. Structural and Physiological Analyses of the Alkanesulphonate-Binding Protein (SsuA) of the Citrus Pathogen Xanthomonas citri

    PubMed Central

    Tófoli de Araújo, Fabiano; Bolanos-Garcia, Victor M.; Pereira, Cristiane T.; Sanches, Mario; Oshiro, Elisa E.; Ferreira, Rita C. C.; Chigardze, Dimitri Y.; Barbosa, João Alexandre Gonçalves; de Souza Ferreira, Luís Carlos; Benedetti, Celso E.; Blundell, Tom L.; Balan, Andrea

    2013-01-01

    Background The uptake of sulphur-containing compounds plays a pivotal role in the physiology of bacteria that live in aerobic soils where organosulfur compounds such as sulphonates and sulphate esters represent more than 95% of the available sulphur. Until now, no information has been available on the uptake of sulphonates by bacterial plant pathogens, particularly those of the Xanthomonas genus, which encompasses several pathogenic species. In the present study, we characterised the alkanesulphonate uptake system (Ssu) of Xanthomonas axonopodis pv. citri 306 strain (X. citri), the etiological agent of citrus canker. Methodology/Principal Findings A single operon-like gene cluster (ssuEDACB) that encodes both the sulphur uptake system and enzymes involved in desulphurisation was detected in the genomes of X. citri and of the closely related species. We characterised X. citri SsuA protein, a periplasmic alkanesulphonate-binding protein that, together with SsuC and SsuB, defines the alkanesulphonate uptake system. The crystal structure of SsuA bound to MOPS, MES and HEPES, which is herein described for the first time, provides evidence for the importance of a conserved dipole in sulphate group coordination, identifies specific amino acids interacting with the sulphate group and shows the presence of a rather large binding pocket that explains the rather wide range of molecules recognised by the protein. Isolation of an isogenic ssuA-knockout derivative of the X. citri 306 strain showed that disruption of alkanesulphonate uptake affects both xanthan gum production and generation of canker lesions in sweet orange leaves. Conclusions/Significance The present study unravels unique structural and functional features of the X. citri SsuA protein and provides the first experimental evidence that an ABC uptake system affects the virulence of this phytopathogen. PMID:24282519

  14. Gender Differences in Subjective and Physiological Responses to Caffeine and the Role of Steroid Hormones

    PubMed Central

    Ziegler, Amanda M.

    2011-01-01

    Background We have shown previously that male and female adolescents differ in their responses to caffeine, but to date, the mechanisms underlying these gender differences are unknown. Objective The purpose of this study was to test the hypothesis that differences in circulating steroid hormones mediate gender differences in response to caffeine. Methods Subjective and physiological responses to caffeine were tested in adolescents using a double-blind, placebo controlled, crossover design. Participants were tested every 2 weeks for 8 weeks and received placebo and caffeine (2 mg/kg) twice each. Females were tested with placebo and caffeine in each phase of their menstrual cycle. Salivary concentrations of testosterone, estradiol, and progesterone were also measured. Results Males showed greater positive subjective effects than females. In females, higher levels of estradiol were associated with little or no subjective responses to caffeine, but lower levels of estradiol were associated with negative subjective responses to caffeine relative to placebo. There were gender differences in cardiovascular responses to caffeine, with males showing greater decreases in heart rate after caffeine administration than females, but females showing greater increases in diastolic blood pressure than males after caffeine administration. These gender differences may be related to steroid hormone concentrations. Blood pressure responses to caffeine were lower in males when estradiol was high, but higher in females when estradiol was high. Conclusions When taken together, these findings suggest that males and females differ in their responses to caffeine and that these differences may be mediated by changes in circulating steroid hormones. PMID:24761262

  15. GI stem cells – new insights into roles in physiology and pathophysiology

    PubMed Central

    von Furstenberg, Richard J.

    2016-01-01

    Abstract This overview gives a brief historical summary of key discoveries regarding stem cells of the small intestine. The current concept is that there are two pools of intestinal stem cells (ISCs): an actively cycling pool that is marked by Lgr5, is relatively homogeneous and is responsible for daily turnover of the epithelium; and a slowly cycling or quiescent pool that functions as reserve ISCs. The latter pool appears to be quite heterogeneous and may include partially differentiated epithelial lineages that can reacquire stem cell characteristics following injury to the intestine. Markers and methods of isolation for active and quiescent ISC populations are described as well as the numerous important advances that have been made in approaches to the in vitro culture of ISCs and crypts. Factors regulating ISC biology are briefly summarized and both known and unknown aspects of the ISC niche are discussed. Although most of our current knowledge regarding ISC physiology and pathophysiology has come from studies with mice, recent work with human tissue highlights the potential translational applications arising from this field of research. Many of these topics are further elaborated in the following articles. PMID:27107928

  16. Deciphering physiological role of the mechanosensitive TRPV4 channel in the distal nephron

    PubMed Central

    Mamenko, M.; Zaika, O.; Boukelmoune, N.; O'Neil, R. G.

    2014-01-01

    Long-standing experimental evidence suggests that epithelial cells in the renal tubule are able to sense osmotic and pressure gradients caused by alterations in ultrafiltrate flow by elevating intracellular Ca2+ concentration. These responses are viewed as critical regulators of a variety of processes ranging from transport of water and solutes to cellular growth and differentiation. A loss in the ability to sense mechanical stimuli has been implicated in numerous pathologies associated with systemic imbalance of electrolytes and to the development of polycystic kidney disease. The molecular mechanisms conferring mechanosensitive properties to epithelial tubular cells involve activation of transient receptor potential (TRP) channels, such as TRPV4, allowing direct Ca2+ influx to increase intracellular Ca2+ concentration. In this review, we critically analyze the current evidence about signaling determinants of TRPV4 activation by luminal flow in the distal nephron and discuss how dysfunction of this mechanism contributes to the progression of polycystic kidney disease. We also review the physiological relevance of TRPV4-based mechanosensitivity in controlling flow-dependent K+ secretion in the distal renal tubule. PMID:25503733

  17. Role of physiological mechanisms and EPSPS gene expression in glyphosate resistance in wild soybeans (Glycine soja).

    PubMed

    Gao, Yue; Tao, Bo; Qiu, Lijuan; Jin, Longguo; Wu, Jing

    2014-02-01

    The physiological mechanisms underlying glyphosate resistance in wild soybean germplasm and relevant EPSPS gene expression were evaluated. These germplasms were selected by gradually increasing glyphosate selection pressure started from 2010. As indicated by a whole-plant dose response bioassay, ZYD-254 plants were resistant to glyphosate at concentrations of 1230gaeha(-1), but the susceptible plants (ZYD-16) were unable to survive in the presence of 300gaeha(-1) glyphosate. The ED50 values of resistant germplasm were approximately 8.8 times of the susceptible germplasm. Chlorophyll content was significantly decreased in ZYD-16 plants in comparison with ZYD-254 plants. ZYD-16 plants accumulated 10.1 times more shikimate in leaves at 5days after glyphosate treatment at 1230gaeha(-1) than ZYD-254 did. GST activity differed between ZYD-254 and ZYD-16 in three tissues. It was highest in leaves. There were no significant differences in EPSPS1 or EPSPS3 expression between two germplasms before exposure to glyphosate treatment. After glyphosate treatment, there was a 2- to 4-fold increase in EPSPS1 mRNA levels in ZYD-254, but there was no change in EPSPS3 mRNA levels in ZYD-254 or ZYD-16.

  18. The Application of Physiologically Based Pharmacokinetic Modeling to Predict the Role of Drug Transporters: Scientific and Regulatory Perspectives.

    PubMed

    Pan, Yuzhuo; Hsu, Vicky; Grimstein, Manuela; Zhang, Lei; Arya, Vikram; Sinha, Vikram; Grillo, Joseph A; Zhao, Ping

    2016-07-01

    Transporters play an important role in drug absorption, disposition, and drug action. The evaluation of drug transporters requires a comprehensive understanding of transporter biology and pharmacology. Physiologically based pharmacokinetic (PBPK) models may offer an integrative platform to quantitatively evaluate the role of drug transporters and its interplay with other drug disposition processes such as passive drug diffusion and elimination by metabolizing enzymes. To date, PBPK modeling and simulations integrating drug transporters lag behind that for drug-metabolizing enzymes. In addition, predictive performance of PBPK has not been well established for predicting the role of drug transporters in the pharmacokinetics of a drug. To enhance overall predictive performance of transporter-based PBPK models, it is necessary to have a detailed understanding of transporter biology for proper representation in the models and to have a quantitative understanding of the contribution of transporters in the absorption and metabolism of a drug. This article summarizes PBPK-based submissions evaluating the role of drug transporters to the Office of Clinical Pharmacology of the US Food and Drug Administration. PMID:27385170

  19. Physiological Roles of the β-Substituted Alanine Synthase Gene Family in Arabidopsis1[W][OA

    PubMed Central

    Watanabe, Mutsumi; Kusano, Miyako; Oikawa, Akira; Fukushima, Atsushi; Noji, Masaaki; Saito, Kazuki

    2008-01-01

    The β-substituted alanine (Ala) synthase (Bsas) family in the large superfamily of pyridoxal 5′-phosphate-dependent enzymes comprises cysteine (Cys) synthase (CSase) [O-acetyl-serine (thiol) lyase] and β-cyano-Ala synthase (CASase) in plants. Nine genomic sequences encode putative Bsas proteins in Arabidopsis thaliana. The physiological roles of these Bsas isoforms in vivo were investigated by the characterization of T-DNA insertion mutants. Analyses of gene expression, activities of CSase and CASase, and levels of Cys and glutathione in the bsas mutants indicated that cytosolic Bsas1;1, plastidic Bsas2;1, and mitochondrial Bsas2;2 play major roles in Cys biosynthesis. Cytosolic Bsas1;1 has the most dominant contribution both in leaf and root, and mitochondrial Bsas2;2 plays a significant role in root. Mitochondrial Bsas3;1 is a genuine CASase. Nontargeted metabolome analyses of knockout mutants were carried out by a combination of gas chromatography time-of-flight mass spectrometry and capillary electrophoresis time-of-flight mass spectrometry. The level of γ-glutamyl-β-cyano-Ala decreased in the mutant bsas3;1, indicating the crucial role of Bsas3;1 in β-cyano-Ala metabolism in vivo. PMID:18024555

  20. Physiological roles of pyruvate ferredoxin oxidoreductase and pyruvate formate-lyase in Thermoanaerobacterium saccharolyticum JW/SL-YS485

    DOE PAGESBeta

    Zhou, Jilai; Olson, Daniel G.; Lanahan, Anthony A.; Tian, Liang; Murphy, Sean Jean-Loup; Lo, Jonathan; Lynd, Lee R.

    2015-09-15

    We report that Thermoanaerobacter saccharolyticum is a thermophilic microorganism that has been engineered to produce ethanol at high titer (30–70 g/L) and greater than 90 % theoretical yield. However, few genes involved in pyruvate to ethanol production pathway have been unambiguously identified. In T. saccharolyticum, the products of six putative pfor gene clusters and one pfl gene may be responsible for the conversion of pyruvate to acetyl-CoA. To gain insights into the physiological roles of PFOR and PFL, we studied the effect of deletions of several genes thought to encode these activities. We found that that pyruvate ferredoxin oxidoreductase enzymemore » (PFOR) is encoded by the pforA gene and plays a key role in pyruvate dissimilation. We further demonstrated that pyruvate formate-lyase activity (PFL) is encoded by the pfl gene. Although the pfl gene is normally expressed at low levels, it is crucial for biosynthesis in T. saccharolyticum. In pforA deletion strains, pfl expression increased and was able to partially compensate for the loss of PFOR activity. Deletion of both pforA and pfl resulted in a strain that required acetate and formate for growth and produced lactate as the primary fermentation product, achieving 88 % theoretical lactate yield. PFOR encoded by Tsac_0046 and PFL encoded by Tsac_0628 are only two routes for converting pyruvate to acetyl-CoA in T. saccharolyticum. The physiological role of PFOR is pyruvate dissimilation, whereas that of PFL is supplying C1 units for biosynthesis.« less

  1. The critical role of GRP78 in physiologic and pathologic stress

    PubMed Central

    Pfaffenbach, Kyle T.; Lee, Amy S.

    2010-01-01

    GRP78 is a major endoplasmic reticulum chaperone as well as a master regulator of the unfolded protein response. In addition to playing an essential role in early embryonic development, recent studies have emerged specifically implicating GRP78 and chaperone integrity in the aging process and age-related diseases. Another exciting discovery is the regulation of GRP78 by insulin/IGF-1 signaling pathways impacting cell proliferation and survival. Mouse models of cancer, in combination with cell culture studies, validate the critical role of GRP78 in tumorigenesis and tumor angiogenesis. Further, these studies demonstrate the ability of GRP78 to suppress oncogenic PI3K/AKT signaling. The discovery of cell surface GRP78, in cancer cells and cells undergoing ER stress, presents a novel therapeutic strategy. PMID:20970977

  2. The physiology of opiate hedonic effects and the role of opioids in motivated behavior.

    PubMed

    Carr, K D

    1984-01-01

    The topics discussed in this article are the neural mechanisms of opiate hedonic effects and the role of endogenous opioids in regulating motivational-affective responses of the organism. First, research on the mechanisms of opiate hedonic effects is briefly reviewed; evidence is discussed which suggests the existence of separate neural substrates for the mediation of opiate analgesia, amelioration of aversive emotion, and reward. In the remainder of the article, recent work of our laboratory is summarized which concerns the role of endogenous opioids in regulating feeding and reward elicited by electrical stimulation in the lateral hypothalamus; evidence is presented which indicates that opioid activity associated with the state of food motivation potentiates reward processes. In addition, evidence is discussed which suggests that this opioid activity may concurrently diminish the organism's emotional responsiveness to competing aversive stimuli. The relevance of this area of research to human opiate abuse is discussed. PMID:6388274

  3. Photosystem I cyclic electron flow via chloroplast NADH dehydrogenase-like complex performs a physiological role for photosynthesis at low light.

    PubMed

    Yamori, Wataru; Shikanai, Toshiharu; Makino, Amane

    2015-09-11

    Cyclic electron transport around photosystem I (PS I) was discovered more than a half-century ago and two pathways have been identified in angiosperms. Although substantial progress has been made in understanding the structure of the chloroplast NADH dehydrogenase-like (NDH) complex, which mediates one route of the cyclic electron transport pathways, its physiological function is not well understood. Most studies focused on the role of the NDH-dependent PS I cyclic electron transport in alleviation of oxidative damage in strong light. In contrast, here it is shown that impairment of NDH-dependent cyclic electron flow in rice specifically causes a reduction in the electron transport rate through PS I (ETR I) at low light intensity with a concomitant reduction in CO2 assimilation rate, plant biomass and importantly, grain production. There was no effect on PS II function at low or high light intensity. We propose a significant physiological function for the chloroplast NDH at low light intensities commonly experienced during the reproductive and ripening stages of rice cultivation that have adverse effects crop yield.

  4. Managing Brain Extracellular K+ during Neuronal Activity: The Physiological Role of the Na+/K+-ATPase Subunit Isoforms

    PubMed Central

    Larsen, Brian Roland; Stoica, Anca; MacAulay, Nanna

    2016-01-01

    During neuronal activity in the brain, extracellular K+ rises and is subsequently removed to prevent a widespread depolarization. One of the key players in regulating extracellular K+ is the Na+/K+-ATPase, although the relative involvement and physiological impact of the different subunit isoform compositions of the Na+/K+-ATPase remain unresolved. The various cell types in the brain serve a certain temporal contribution in the face of network activity; astrocytes respond directly to the immediate release of K+ from neurons, whereas the neurons themselves become the primary K+ absorbers as activity ends. The kinetic characteristics of the catalytic α subunit isoforms of the Na+/K+-ATPase are, partly, determined by the accessory β subunit with which they combine. The isoform combinations expressed by astrocytes and neurons, respectively, appear to be in line with the kinetic characteristics required to fulfill their distinct physiological roles in clearance of K+ from the extracellular space in the face of neuronal activity. Understanding the nature, impact and effects of the various Na+/K+-ATPase isoform combinations in K+ management in the central nervous system might reveal insights into pathological conditions such as epilepsy, migraine, and spreading depolarization following cerebral ischemia. In addition, particular neurological diseases occur as a result of mutations in the α2- (familial hemiplegic migraine type 2) and α3 isoforms (rapid-onset dystonia parkinsonism/alternating hemiplegia of childhood). This review addresses aspects of the Na+/K+-ATPase in the regulation of extracellular K+ in the central nervous system as well as the related pathophysiology. Understanding the physiological setting in non-pathological tissue would provide a better understanding of the pathological events occurring during disease. PMID:27148079

  5. The acute physiological and mood effects of tea and coffee: the role of caffeine level.

    PubMed

    Quinlan, P T; Lane, J; Moore, K L; Aspen, J; Rycroft, J A; O'Brien, D C

    2000-05-01

    The objective of this study was to determine the effect of caffeine level in tea and coffee on acute physiological responses and mood. Randomised full crossover design in subjects after overnight caffeine abstention was studied. In study 1 (n = 17) the caffeine level was manipulated naturalistically by preparing tea and coffee at different strengths (1 or 2 cups equivalent). Caffeine levels were 37.5 and 75 mg in tea, 75 and 150 mg in coffee, with water and no-drink controls. In study 2 (n = 15) caffeine level alone was manipulated (water, decaffeinated tea, plus 0, 25, 50, 100, and 200 mg caffeine). Beverage volume and temperature (55 degrees C) were constant. SBP, DBP, heart rate, skin temperature, skin conductance, and mood were monitored over each 3-h study session. In study 1, tea and coffee produced mild autonomic stimulation and an elevation in mood. There were no effects of tea vs. coffee or caffeine dose, despite a fourfold variation in the latter. Increasing beverage strength was associated with greater increases in DBP and energetic arousal. In study 2, caffeinated beverages increased SBP, DBP, and skin conductance and lowered heart rate and skin temperature compared to water. Significant dose-response relationships to caffeine were seen only for SBP, heart rate, and skin temperature. There were significant effects of caffeine on energetic arousal but no consistent dose-response effects. Caffeinated beverages acutely stimulate the autonomic nervous system and increase alertness. Although caffeine can exert dose-dependent effects on a number of acute autonomic responses, caffeine level is not an important factor. Factors besides caffeine may contribute to these acute effects.

  6. The acute physiological and mood effects of tea and coffee: the role of caffeine level.

    PubMed

    Quinlan, P T; Lane, J; Moore, K L; Aspen, J; Rycroft, J A; O'Brien, D C

    2000-05-01

    The objective of this study was to determine the effect of caffeine level in tea and coffee on acute physiological responses and mood. Randomised full crossover design in subjects after overnight caffeine abstention was studied. In study 1 (n = 17) the caffeine level was manipulated naturalistically by preparing tea and coffee at different strengths (1 or 2 cups equivalent). Caffeine levels were 37.5 and 75 mg in tea, 75 and 150 mg in coffee, with water and no-drink controls. In study 2 (n = 15) caffeine level alone was manipulated (water, decaffeinated tea, plus 0, 25, 50, 100, and 200 mg caffeine). Beverage volume and temperature (55 degrees C) were constant. SBP, DBP, heart rate, skin temperature, skin conductance, and mood were monitored over each 3-h study session. In study 1, tea and coffee produced mild autonomic stimulation and an elevation in mood. There were no effects of tea vs. coffee or caffeine dose, despite a fourfold variation in the latter. Increasing beverage strength was associated with greater increases in DBP and energetic arousal. In study 2, caffeinated beverages increased SBP, DBP, and skin conductance and lowered heart rate and skin temperature compared to water. Significant dose-response relationships to caffeine were seen only for SBP, heart rate, and skin temperature. There were significant effects of caffeine on energetic arousal but no consistent dose-response effects. Caffeinated beverages acutely stimulate the autonomic nervous system and increase alertness. Although caffeine can exert dose-dependent effects on a number of acute autonomic responses, caffeine level is not an important factor. Factors besides caffeine may contribute to these acute effects. PMID:10837840

  7. The NR4A subgroup: immediate early response genes with pleiotropic physiological roles

    PubMed Central

    Maxwell, Megan A.; Muscat, George E.O.

    2006-01-01

    The nuclear hormone receptor (NR) superfamily includes the orphan NR4A subgroup, comprised of Nur77 (NR4A1), Nurr1 (NR4A2) and NOR-1 (NR4A3). These NRs are classified as early response genes, are induced by a diverse range of signals, including fatty acids, stress, growth factors, cytokines, peptide hormones, phorbol esters, neurotransmitters, and physical stimuli (for example magnetic fields, shear stress). The ability to sense and rapidly respond to changes in the cellular environment thus appears to be a hallmark of this subfamily. The members of the NR4A subgroup are well conserved in the DNA binding domain (~91-95%) and the C-terminal ligand-binding domain (~60%), but are divergent in the N-terminal AB region. These receptors bind as monomers, homodimers and heterodimers with RXRs (to mediate retinoid signaling) to different permutations of the canonical NR binding motif. The NR4A subgroup activates gene expression in a constitutive ligand-independent manner. NR4A-mediated trans-activation (LBD) involves unusually active N-terminal AF-1 domains that mediate coactivator recruitment. Moreover, the NR4A receptors encode atypical LBDs and AF-2 domains. For example, the LBDs contain no cavity due to bulky hydrophobic residue side chains, and lack the classical coactivator-binding cleft constituted by helices 3, 4 and 12. However, a hydrophobic patch exists between helices 11 and 12, that encodes a novel cofactor interface that modulates transcriptional activity. In line with the pleiotropic physiological stimuli that induce the NR4A subgroup, these orphan NRs have been implicated in cell cycle regulation (and apoptosis), neurological disease, steroidogenesis, inflammation, carcinogenesis and atherogenesis. PMID:16604165

  8. Role of soluble guanylate cyclase in the molecular mechanism underlying the physiological effects of nitric oxide.

    PubMed

    Severina, I S

    1998-07-01

    In this review the molecular mechanisms underlying the antihypertensive and antiaggregatory actions of nitric oxide (NO) are discussed. It has been shown that these effects are directly connected with the activation of soluble guanylate cyclase and the accumulation of cyclic 3;,5;-guanosine monophosphate (cGMP). The mechanism of guanylate cyclase activation by NO is analyzed, especially the role and biological significance of the nitrosyl--heme complex formed as a result of interaction of guanylate cyclase heme with NO and the role of sulfhydryl groups of the enzyme in this process. Using new approaches for studying the antihypertensive and antiaggregatory actions of nitric oxide in combination with the newly obtained data on the regulatory role of guanylate cyclase in the platelet aggregation process, the most important results were obtained regarding the molecular bases providing for a directed search for and creation of new effective antihypertensive and antiaggregatory preparations. In studying the molecular mechanism for directed activation of soluble guanylate cyclase by new NO donors, a series of hitherto unknown enzyme activators generating NO and involved in the regulation of hemostasis and vascular tone were revealed. PMID:9721331

  9. Role of ROS and RNS Sources in Physiological and Pathological Conditions

    PubMed Central

    Victor, Victor Manuel

    2016-01-01

    There is significant evidence that, in living systems, free radicals and other reactive oxygen and nitrogen species play a double role, because they can cause oxidative damage and tissue dysfunction and serve as molecular signals activating stress responses that are beneficial to the organism. Mitochondria have been thought to both play a major role in tissue oxidative damage and dysfunction and provide protection against excessive tissue dysfunction through several mechanisms, including stimulation of opening of permeability transition pores. Until recently, the functional significance of ROS sources different from mitochondria has received lesser attention. However, the most recent data, besides confirming the mitochondrial role in tissue oxidative stress and protection, show interplay between mitochondria and other ROS cellular sources, so that activation of one can lead to activation of other sources. Thus, it is currently accepted that in various conditions all cellular sources of ROS provide significant contribution to processes that oxidatively damage tissues and assure their survival, through mechanisms such as autophagy and apoptosis. PMID:27478531

  10. Distinct physiological roles for the two L-asparaginase isozymes of Escherichia coli

    SciTech Connect

    Srikhanta, Yogitha N.; Atack, John M.; Beacham, Ifor R.; Jennings, Michael P.

    2013-07-05

    Highlights: •Escherichia coli contains two L-asparaginase isozymes with distinct localization, kinetics and regulation. •Mutant strains were used to examine the roles of these enzymes in L-asparagine utilization. •We report that L-asparaginase II permits growth on asparagine and glycerol under anaerobic conditions. •We propose that this enzyme is the first step in a co-regulated pathway leading to fumarate. •The pathway is regulated by anaerobiosis and cAMP and provides a terminal elector acceptor. -- Abstract: Escherichia coli expresses two L-asparaginase (EC 3.5.1.1) isozymes: L-asparaginse I, which is a low affinity, cytoplasmic enzyme that is expressed constitutively, and L-asparaginase II, a high affinity periplasmic enzyme that is under complex co-transcriptional regulation by both Fnr and Crp. The distinct localisation and regulation of these enzymes suggest different roles. To define these roles, a set of isogenic mutants was constructed that lacked either or both enzymes. Evidence is provided that L-asparaginase II, in contrast to L-asparaginase I, can be used in the provision of an anaerobic electron acceptor when using a non-fermentable carbon source in the presence of excess nitrogen.

  11. The application of mass and energy conservation laws in physiologically structured population models of heterotrophic organisms

    PubMed

    Kooijman; Kooi; Hallam

    1999-04-01

    Rules for energy uptake, and subsequent utilization, form the basis of population dynamics and, therefore, explain the dynamics of the ecosystem structure in terms of changes in standing crops and size distributions of individuals. Mass fluxes are concomitant with energy flows and delineate functional aspects of ecosystems by defining the roles of individuals and populations. The assumption of homeostasis of body components, and an assumption about the general structure of energy budgets, imply that mass fluxes can be written as weighted sums of three organizing energy fluxes with the weight coefficients determined by the conservation law of mass. These energy fluxes are assimilation, maintenance and growth, and provide a theoretical underpinning of the widely applied empirical method of indirect calorimetry, which relates dissipating heat linearly to three mass fluxes: carbon dioxide production, oxygen consumption and N-waste production. A generic approach to the stoichiometry of population energetics from the perspective of the individual organism is proposed and illustrated for heterotrophic organisms. This approach indicates that mass transformations can be identified by accounting for maintenance requirements and overhead costs for the various metabolic processes at the population level. The theoretical background for coupling the dynamics of the structure of communities to nutrient cycles, including the water balance, as well as explicit expressions for the dissipating heat at the population level are obtained based on the conservation law of energy. Specifications of the general theory employ the Dynamic Energy Budget model for individuals. Copyright 1999 Academic Press.

  12. Physiological Role of Kv1.3 Channel in T Lymphocyte Cell Investigated Quantitatively by Kinetic Modeling

    PubMed Central

    Feng, Jing; Wang, Wei; Wu, Yingliang; Ding, Jiuping

    2014-01-01

    Kv1.3 channel is a delayed rectifier channel abundant in human T lymphocytes. Chronic inflammatory and autoimmune disorders lead to the over-expression of Kv1.3 in T cells. To quantitatively study the regulatory mechanism and physiological function of Kv1.3 in T cells, it is necessary to have a precise kinetic model of Kv1.3. In this study, we firstly established a kinetic model capable to precisely replicate all the kinetic features for Kv1.3 channels, and then constructed a T-cell model composed of ion channels including Ca2+-release activated calcium (CRAC) channel, intermediate K+ (IK) channel, TASK channel and Kv1.3 channel for quantitatively simulating the changes in membrane potentials and local Ca2+ signaling messengers during activation of T cells. Based on the experimental data from current-clamp recordings, we successfully demonstrated that Kv1.3 dominated the membrane potential of T cells to manipulate the Ca2+ influx via CRAC channel. Our results revealed that the deficient expression of Kv1.3 channel would cause the less Ca2+ signal, leading to the less efficiency in secretion. This was the first successful attempt to simulate membrane potential in non-excitable cells, which laid a solid basis for quantitatively studying the regulatory mechanism and physiological role of channels in non-excitable cells. PMID:24594979

  13. Physiological roles of group X-secreted phospholipase A2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function.

    PubMed

    Sato, Hiroyasu; Isogai, Yuki; Masuda, Seiko; Taketomi, Yoshitaka; Miki, Yoshimi; Kamei, Daisuke; Hara, Shuntaro; Kobayashi, Tetsuyuki; Ishikawa, Yukio; Ishii, Toshiharu; Ikeda, Kazutaka; Taguchi, Ryo; Ishimoto, Yoshikazu; Suzuki, Noriko; Yokota, Yasunori; Hanasaki, Kohji; Suzuki-Yamamoto, Toshiko; Yamamoto, Kei; Murakami, Makoto

    2011-04-01

    Although the secreted phospholipase A(2) (sPLA(2)) family has been generally thought to participate in pathologic events such as inflammation and atherosclerosis, relatively high and constitutive expression of group X sPLA(2) (sPLA(2)-X) in restricted sites such as reproductive organs, the gastrointestinal tract, and peripheral neurons raises a question as to the roles played by this enzyme in the physiology of reproduction, digestion, and the nervous system. Herein we used mice with gene disruption or transgenic overexpression of sPLA(2)-X to clarify the homeostatic functions of this enzyme at these locations. Our results suggest that sPLA(2)-X regulates 1) the fertility of spermatozoa, not oocytes, beyond the step of flagellar motility, 2) gastrointestinal phospholipid digestion, perturbation of which is eventually linked to delayed onset of a lean phenotype with reduced adiposity, decreased plasma leptin, and improved muscle insulin tolerance, and 3) neuritogenesis of dorsal root ganglia and the duration of peripheral pain nociception. Thus, besides its inflammatory action proposed previously, sPLA(2)-X participates in physiologic processes including male fertility, gastrointestinal phospholipid digestion linked to adiposity, and neuronal outgrowth and sensing.

  14. Calcium signaling in plant endosymbiotic organelles: mechanism and role in physiology.

    PubMed

    Nomura, Hironari; Shiina, Takashi

    2014-07-01

    Recent studies have demonstrated that chloroplasts and mitochondria evoke specific Ca(2+) signals in response to biotic and abiotic stresses in a stress-dependent manner. The identification of Ca(2+) transporters and Ca(2+) signaling molecules in chloroplasts and mitochondria implies that they play roles in controlling not only intra-organellar functions, but also extra-organellar processes such as plant immunity and stress responses. It appears that organellar Ca(2+) signaling might be more important to plant cell functions than previously thought. This review briefly summarizes what is known about the molecular basis of Ca(2+) signaling in plant mitochondria and chloroplasts.

  15. 20 years of leptin: Role of leptin in cardiomyocyte physiology and physiopathology.

    PubMed

    Feijóo-Bandín, S; Portolés, M; Roselló-Lletí, E; Rivera, M; González-Juanatey, J R; Lago, F

    2015-11-01

    Since the discovery of leptin in 1994 by Zhang et al., there have been a number of reports showing its implication in the development of a wide range of cardiovascular diseases. However, there exists some controversy about how leptin can induce or preserve cardiovascular function, as different authors have found contradictory results about leptin beneficial or detrimental effects in leptin deficient/resistant murine models and in wild type tissue and cardiomyocytes. Here, we will focus on the main discoveries about the leptin functions at cardiac level within the last two decades, focusing on its role in cardiac metabolism, remodeling and contractile function.

  16. Family Role Structure and Food-Related Roles in Mexican-American Families.

    ERIC Educational Resources Information Center

    Yetley, Elizabeth A.; And Others

    1981-01-01

    The cultural, behavioral, and sociopsychological dimensions of role structures were examined in this study of food-related roles of Mexican-American families (N=141 females interviewed) living in South Texas border communities. (DS)

  17. [The physiology of glucagon-like peptide-1 and its role in the pathophysiology of type 2 diabetes mellitus].

    PubMed

    Escalada, Francisco Javier

    2014-09-01

    The hormone glucagon-like peptide-1 (GLP-1) is synthesized and secreted by L cells in the small intestine in response to food ingestion. After reaching the general circulation it has a half-life of 2-3 minutes due to degradation by the enzyme dipeptidyl peptidase-4. Its physiological role is directed to control plasma glucose concentration, though GLP-1 also plays other different metabolic functions following nutrient absorption. Biological activities of GLP-1 include stimulation of insulin biosynthesis and glucose-dependent insulin secretion by pancreatic beta cell, inhibition of glucagon secretion, delay of gastric emptying and inhibition of food intake. GLP-1 is able to reduce plasma glucose levels in patients with type 2 diabetes and also can restore beta cell sensitivity to exogenous secretagogues, suggesting that the increasing GLP-1 concentration may be an useful therapeutic strategy for the treatment of patients with type 2 diabetes.

  18. [The physiology of glucagon-like peptide-1 and its role in the pathophysiology of type 2 diabetes mellitus].

    PubMed

    Escalada, Francisco Javier

    2014-01-01

    The hormone glucagon-like peptide-1 (GLP-1) is synthesized and secreted by L cells in the small intestine in response to food ingestion. After reaching the general circulation it has a half-life of 2-3 minutes due to degradation by the enzyme dipeptidyl peptidase-4. Its physiological role is directed to control plasma glucose concentration, though GLP-1 also plays other different metabolic functions following nutrient absorption. Biological activities of GLP-1 include stimulation of insulin biosynthesis and glucose-dependent insulin secretion by pancreatic beta cell, inhibition of glucagon secretion, delay of gastric emptying and inhibition of food intake. GLP-1 is able to reduce plasma glucose levels in patients with type 2 diabetes and also can restore beta cell sensitivity to exogenous secretagogues, suggesting that the increasing GLP-1 concentration may be an useful therapeutic strategy for the treatment of patients with type 2 diabetes.

  19. [The physiology of glucagon-like peptide-1 and its role in the pathophysiology of type 2 diabetes mellitus].

    PubMed

    Escalada, Francisco Javier

    2014-01-01

    The hormone glucagon-like peptide-1 (GLP-1) is synthesized and secreted by L cells in the small intestine in response to food ingestion. After reaching the general circulation it has a half-life of 2-3 minutes due to degradation by the enzyme dipeptidyl peptidase-4. Its physiological role is directed to control plasma glucose concentration, though GLP-1 also plays other different metabolic functions following nutrient absorption. Biological activities of GLP-1 include stimulation of insulin biosynthesis and glucose-dependent insulin secretion by pancreatic beta cell, inhibition of glucagon secretion, delay of gastric emptying and inhibition of food intake. GLP-1 is able to reduce plasma glucose levels in patients with type 2 diabetes and also can restore beta cell sensitivity to exogenous secretagogues, suggesting that the increasing GLP-1 concentration may be an useful therapeutic strategy for the treatment of patients with type 2 diabetes. PMID:25326836

  20. [The physiology of glucagon-like peptide-1 and its role in the pathophysiology of type 2 diabetes mellitus].

    PubMed

    Escalada, Francisco Javier

    2014-09-01

    The hormone glucagon-like peptide-1 (GLP-1) is synthesized and secreted by L cells in the small intestine in response to food ingestion. After reaching the general circulation it has a half-life of 2-3 minutes due to degradation by the enzyme dipeptidyl peptidase-4. Its physiological role is directed to control plasma glucose concentration, though GLP-1 also plays other different metabolic functions following nutrient absorption. Biological activities of GLP-1 include stimulation of insulin biosynthesis and glucose-dependent insulin secretion by pancreatic beta cell, inhibition of glucagon secretion, delay of gastric emptying and inhibition of food intake. GLP-1 is able to reduce plasma glucose levels in patients with type 2 diabetes and also can restore beta cell sensitivity to exogenous secretagogues, suggesting that the increasing GLP-1 concentration may be an useful therapeutic strategy for the treatment of patients with type 2 diabetes. PMID:25437458

  1. Structural-functional characterization and physiological significance of ferredoxin-NADP reductase from Xanthomonas axonopodis pv. citri.

    PubMed

    Tondo, María Laura; Musumeci, Matías A; Delprato, María Laura; Ceccarelli, Eduardo A; Orellano, Elena G

    2011-01-01

    Xanthomonas axonopodis pv. citri is a phytopathogen bacterium that causes severe citrus canker disease. Similar to other phytopathogens, after infection by this bacterium, plants trigger a defense mechanism that produces reactive oxygen species. Ferredoxin-NADP(+) reductases (FNRs) are redox flavoenzymes that participate in several metabolic functions, including the response to reactive oxygen species. Xanthomonas axonopodis pv. citri has a gene (fpr) that encodes for a FNR (Xac-FNR) that belongs to the subclass I bacterial FNRs. The aim of this work was to search for the physiological role of this enzyme and to characterize its structural and functional properties. The functionality of Xac-FNR was tested by cross-complementation of a FNR knockout Escherichia coli strain, which exhibit high susceptibility to agents that produce an abnormal accumulation of (•)O(2)(-). Xac-FNR was able to substitute for the FNR in E. coli in its antioxidant role. The expression of fpr in X. axonopodis pv. citri was assessed using semiquantitative RT-PCR and Western blot analysis. A 2.2-fold induction was observed in the presence of the superoxide-generating agents methyl viologen and 2,3-dimethoxy-1,4-naphthoquinone. Structural and functional studies showed that Xac-FNR displayed different functional features from other subclass I bacterial FNRs. Our analyses suggest that these differences may be due to the unusual carboxy-terminal region. We propose a further classification of subclass I bacterial FNRs, which is useful to determine the nature of their ferredoxin redox partners. Using sequence analysis, we identified a ferredoxin (XAC1762) as a potential substrate of Xac-FNR. The purified ferredoxin protein displayed the typical broad UV-visible spectrum of [4Fe-4S] clusters and was able to function as substrate of Xac-FNR in the cytochrome c reductase activity. Our results suggest that Xac-FNR is involved in the oxidative stress response of Xanthomonas axonopodis pv. citri and

  2. The physiological role of the brain GLP-1 system in stress

    PubMed Central

    Holt, Marie K.; Trapp, Stefan

    2016-01-01

    Abstract Glucagon-like peptide-1 (GLP-1) within the brain is a potent regulator of food intake and most studies have investigated the anorexic effects of central GLP-1. A range of brain regions have now been found to be involved in GLP-1 mediated anorexia, including some which are not traditionally associated with appetite regulation. However, a change in food intake can be indicative of not only reduced energy demand, but also changes in the organism’s motivation to eat following stressful stimuli. In fact, acute stress is well-known to reduce food intake. Recently, more research has focused on the role of GLP-1 in stress and the central GLP-1 system has been found to be activated in response to stressful stimuli. The source of GLP-1 within the brain, the preproglucagon (PPG) neurons, are ideally situated in the brainstem to receive and relay signals of stress and our recent data on the projection pattern of the PPG neurons to the spinal cord suggest a potential strong link with the sympathetic nervous system. We review here the role of central GLP-1 in the regulation of stress responses and discuss the potential involvement of the endogenous source of GLP-1 within the brain, the PPG neurons. PMID:27722184

  3. Physiological roles of preproghrelin-derived peptides in GH secretion and feeding.

    PubMed

    Zizzari, Philippe; Hassouna, Rim; Grouselle, Dominique; Epelbaum, Jacques; Tolle, Virginie

    2011-11-01

    Among the factors playing a crucial role in the regulation of energy metabolism, gastro-intestinal peptides are essential signals to maintain energy homeostasis as they relay to the central nervous system the informations about the nutritional status of the body. Among these factors, preproghrelin is a unique prohormone as it encodes ghrelin, a powerful GH secretagogue and the only orexigenic signal from the gastrointestinal tract and obestatin, a proposed functional ghrelin antagonist. These preproghrelin-derived peptides may contribute to balance energy intake, metabolism and body composition by regulating the activity of the GH/IGF-1 axis and appetite. Whereas the contribution of ghrelin has been well characterized, the role of the more recently identified obestatin, in this regulatory process is still controversial. In this chapter, we describe the contribution of these different preproghrelin-derived peptides and their receptors in the regulation of GH secretion and feeding. Data obtained from pharmacological approaches, mutant models and evaluation of the hormones in animal and human models are discussed.

  4. Physiological Roles for Two Periplasmic Nitrate Reductases in Rhodobacter sphaeroides 2.4.3 (ATCC 17025)▿

    PubMed Central

    Hartsock, Angela; Shapleigh, James P.

    2011-01-01

    The metabolically versatile purple bacterium Rhodobacter sphaeroides 2.4.3 is a denitrifier whose genome contains two periplasmic nitrate reductase-encoding gene clusters. This work demonstrates nonredundant physiological roles for these two enzymes. One cluster is expressed aerobically and repressed under low oxygen while the second is maximally expressed under low oxygen. Insertional inactivation of the aerobically expressed nitrate reductase eliminated aerobic nitrate reduction, but cells of this strain could still respire nitrate anaerobically. In contrast, when the anaerobic nitrate reductase was absent, aerobic nitrate reduction was detectable, but anaerobic nitrate reduction was impaired. The aerobic nitrate reductase was expressed but not utilized in liquid culture but was utilized during growth on solid medium. Growth on a variety of carbon sources, with the exception of malate, the most oxidized substrate used, resulted in nitrite production on solid medium. This is consistent with a role for the aerobic nitrate reductase in redox homeostasis. These results show that one of the nitrate reductases is specific for respiration and denitrification while the other likely plays a role in redox homeostasis during aerobic growth. PMID:21949073

  5. Surface Glycans of Candida albicans and Other Pathogenic Fungi: Physiological Roles, Clinical Uses, and Experimental Challenges

    PubMed Central

    Masuoka, James

    2004-01-01

    Although fungi have always been with us as commensals and pathogens, fungal infections have been increasing in frequency over the past few decades. There is a growing body of literature describing the involvement of carbohydrate groups in various aspects of fungal disease. Carbohydrates comprising the cell wall or capsule, or as a component of glycoproteins, are the fungal cell surface entities most likely to be exposed to the surrounding environment. Thus, the fungus-host interaction is likely to involve carbohydrates before DNA, RNA, or even protein. The interaction between fungal and host cells is also complex, and early studies using whole cells or crude cell fractions often produced seemingly conflicting results. What was needed, and what has been developing, is the ability to identify specific glycan structures and determine how they interact with immune system components. Carbohydrate analysis is complicated by the complexity of glycan structures and by the challenges of separating and detecting carbohydrates experimentally. Advances in carbohydrate chemistry have enabled us to move from the foundation of composition analysis to more rapid characterization of specific structures. This, in turn, will lead to a greater understanding of how fungi coexist with their hosts as commensals or exist in conflict as pathogens. PMID:15084502

  6. Insight into a Physiological Role for the EC Night-Time Repressor in the Arabidopsis Circadian Clock.

    PubMed

    Mizuno, Takeshi; Kitayama, Miki; Takayama, Chieko; Yamashino, Takafumi

    2015-09-01

    Life cycle adaptation to seasonal variation in photoperiod and temperature is a major determinant of ecological success of widespread domestication of Arabidopsis thaliana. The circadian clock plays a role in the underlying mechanism for adaptation. Nevertheless, the mechanism by which the circadian clock tracks seasonal changes in photoperiod and temperature is a longstanding subject of research in the field. We previously showed that a set of the target genes (i.e. GI, LNK1. PRR9 and PRR7) of the Evening Complex (EC) consisting of LUX-ELF3-ELF4 is synergistically induced in response to both warm-night and night-light signals. Here, we further show that the responses occur within a wide range of growth-compatible temperatures (16-28°C) in response to a small change in temperature (Δ4°C). A dim light pulse (<1 µmol m(-2) s(-1)) causes the enhanced effect on the transcription of EC targets. The night-light pulse antagonizes against a positive effect of the cool-night signal on the EC activity. The mechanism of double-checking external temperature and light signals through the EC nighttime repressor might enable plants to ignore (or tolerate) daily fluctuation of ambient temperature within a short time interval in their natural habitats. Taken together, the EC night-time repressor might play a physiological role in tracking seasonal variation in photoperiod and temperature by conservatively double-checking both the light and temperature conditions. Another EC target output gene PIF4 regulating plant morphologies is also regulated by both the temperature and light stimuli during the night. Hence, the EC night-time repressor is also implicated in a physiological output of the PIF4-mediated regulation of morphologies in response to seasonal variation in photoperiod and ambient temperature.

  7. Electron nanodiffraction and high-resolution electron microscopy studies of the structure and composition of physiological and pathological ferritin.

    PubMed

    Quintana, C; Cowley, J M; Marhic, C

    2004-08-01

    Structures of core nanocrystals of physiological (horse spleen, human liver, and brain) and pathological human brain of patients with progressive supranuclear palsy (PSP) and Alzheimer's disease (AD) ferritin molecules were determined using electron nanodiffraction and high-resolution transmission electron microscopy. The poly-phasic structure of the ferritin cores is confirmed. There are significant differences in the mineral composition between the physiological and pathological ferritins. The physiological ferritin cores mainly consist of single nanocrystals containing hexagonal ferrihydrite (Fh) and hematite (Hm) and some cubic magnetite/maghemite phase. In the pathological cores, Fh is present but only as a minor phase and Hm is absent. The major phases are a face-centered-cubic (fcc) structure with a = 0.43 nm and a high degree of disorder, related to wustite, and a cubic magnetite-like structure. These two cubic phases are also present in human aged normal brain. Evidence for the presence of hemosiderin together with ferritin in the pathological brains is deduced from the similarities of the diffraction patterns with those from patients with primary hemochromatosis, and differences in the shapes and protein composition of the protein shell. These findings suggest a disfunction of the ferritin associated with PSP and AD, associated with an increase in the concentration of brain ferrous toxic iron.

  8. Heuristic Presentations: The Role of Structuring.

    ERIC Educational Resources Information Center

    Leron, Uri

    1985-01-01

    Discusses insufficiency of the linear method and some informal practices (or heuristics) used by expositors in trying to alleviate it. Uses the Cantor-Bernstein theorem to illustrate the linear proof, structuring, and the structure proof. Argues that the informal practices considered be consistently applied to the presentation of pivots and…

  9. [Role of endocannabinoid 2-arachidonoylglycerol in the physiology and pathophysiology of the cardiovascular system].

    PubMed

    Karabowicz, Piotr; Grzęda, Emilia; Baranowska-Kuczko, Marta; Malinowska, Barbara

    2014-06-12

    Cannabinoids, the active ingredients of Cannabis sativa var. indica, have been used by humans as recreational and therapeutic agents for thousands of years. This group of substances also includes synthetic ligands and, synthesized in the body of humans and animals, endocannabinoids. The best known compound classified as an endogenous cannabinoid is anandamide. However, recent studies show that another compound of this group, 2-arachidonoylglycerol (2-AG), also performs many important functions in the organism. 2-Arachidonoylglycerol plays an important role in the regulation of the circulatory system via direct and/or indirect, through their metabolites, effects on blood vessels and/or heart. Accumulating evidence reveals that 2-AG is involved in the pathogenesis of various shocks and atherosclerosis. Thus, it may be a novel attractive therapeutic target. However, because of rapid metabolism and opposite effects dependent on the experimental model, the function of 2-AG still remains to be established.

  10. [Role of endocannabinoid 2-arachidonoylglycerol in the physiology and pathophysiology of the cardiovascular system].

    PubMed

    Karabowicz, Piotr; Grzęda, Emilia; Baranowska-Kuczko, Marta; Malinowska, Barbara

    2014-01-01

    Cannabinoids, the active ingredients of Cannabis sativa var. indica, have been used by humans as recreational and therapeutic agents for thousands of years. This group of substances also includes synthetic ligands and, synthesized in the body of humans and animals, endocannabinoids. The best known compound classified as an endogenous cannabinoid is anandamide. However, recent studies show that another compound of this group, 2-arachidonoylglycerol (2-AG), also performs many important functions in the organism. 2-Arachidonoylglycerol plays an important role in the regulation of the circulatory system via direct and/or indirect, through their metabolites, effects on blood vessels and/or heart. Accumulating evidence reveals that 2-AG is involved in the pathogenesis of various shocks and atherosclerosis. Thus, it may be a novel attractive therapeutic target. However, because of rapid metabolism and opposite effects dependent on the experimental model, the function of 2-AG still remains to be established. PMID:24934539

  11. The biological role of a-ketoglutaric acid in physiological processes and its therapeutic potential.

    PubMed

    Grzesiak, Paulina; Słupecka-Ziemilska, Monika; Woliński, Jarosław

    2016-01-01

    In this article we present the results of recent studies on the mechanism of action and biological role of α-ketoglutaric acid (AKG) in animals including developmental period of life. AKG is an intermediate in the Krebs cycle, which generates energy for life processes. Administration of AKG has been shown to be beneficial for proper development and function of the skeletal system during growth of young organisms, as well as in adulthood. In the form of a dietary supplement it also contributes to inhibition of osteoporosis in women. Moreover, it promotes the growth of muscle mass and accelerates wound healing. AKG has a significant impact on the morphology of the gastrointestinal tract in healthy animals and animals with damaged gastrointestinal tract mucosa. It is also a promising substance for the treatment of patients with short bowel syndrome, as it stimulates beneficial changes in intestinal morphology. Recent research has also revealed that AKG has neuroprotective effects. PMID:27416627

  12. Structure–Function Relations, Physiological Roles, and Evolution of Mammalian ER-Resident Selenoproteins

    PubMed Central

    Shchedrina, Valentina A.; Zhang, Yan; Labunskyy, Vyacheslav M.; Hatfield, Dolph L.

    2010-01-01

    Abstract Selenium is an essential trace element in mammals. The major biological form of this micronutrient is the amino acid selenocysteine, which is present in the active sites of selenoenzymes. Seven of 25 mammalian selenoproteins have been identified as residents of the endoplasmic reticulum, including the 15-kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins K, M, N, S, and T. Most of these proteins are poorly characterized. However, recent studies implicate some of them in quality control of protein folding in the ER, retrotranslocation of misfolded proteins from the ER to the cytosol, metabolism of the thyroid hormone, and regulation of calcium homeostasis. In addition, some of these proteins are involved in regulation of glucose metabolism and inflammation. This review discusses evolution and structure–function relations of the ER-resident selenoproteins and summarizes recent findings on these proteins, which reveal the emerging important role of selenium and selenoproteins in ER function. Antioxid. Redox Signal. 12, 839–849. PMID:19747065

  13. Emerging evidence on the role of the Hippo/YAP pathway in liver physiology and cancer.

    PubMed

    Yimlamai, Dean; Fowl, Brendan H; Camargo, Fernando D

    2015-12-01

    The Hippo pathway and its regulatory target, YAP, has recently emerged as an important biochemical signaling pathway that tightly governs epithelial tissue growth. Initially defined in Drosophilia, this pathway has shown remarkable conservation in vertebrate systems with many components of the Hippo/YAP pathway showing biochemical and functional conservation. The liver is particularly sensitive to changes in Hippo/YAP signaling with rapid increases in liver size becoming manifest on the order of days to weeks after perturbation. The first identified direct targets of Hippo/YAP signaling were pro-proliferative and anti-apoptotic gene programs, but recent work has now implicated this pathway in cell fate choice, stem cell maintenance/renewal, epithelial to mesenchymal transition, and oncogenesis. The mechanisms by which Hippo/YAP signaling is changed endogenously are beginning to come to light as well as how this pathway interacts with other signaling pathways, and important details for designing new therapeutic interventions. This review focuses on the known roles for Hippo/YAP signaling in the liver and promising avenues for future study.

  14. Physiological roles of the kisspeptin/GPR54 system in the neuroendocrine control of reproduction.

    PubMed

    Pineda, Rafael; Aguilar, Enrique; Pinilla, Leonor; Tena-Sempere, Manuel

    2010-01-01

    Reproductive maturation and function are maintained by a complex neurohormonal network that integrates at the so-called hypothalamic-pituitary-gonadal (HPG) axis. This system is hierarchically controlled by the decapeptide, GnRH, which in turn is under the dynamic regulation of multiple stimulatory and inhibitory pathways, including peripheral signals (prominently, sex steroids) and different central modulators. Among the latter, considerable interest has been raised recently by the identification of the major roles and mechanisms of action of kisspeptins, a family of neuropeptides encoded by the Kiss1 gene, which acting via the G protein-coupled receptor, GPR54, have been shown to play essential functions as potent activators and major gatekeepers of the HPG axis. Indeed, kisspeptin neurons, whose mere existence and neuroendocrine dimension had escaped from general attention up to five years ago, have been now universally recognized as key players in the control of critical aspects of reproductive development and function, from sexual differentiation to regulation of GnRH/gonadotropin secretion and the metabolic gating of fertility. In this chapter, we will provide a concise summary of the state of the art in this rapidly evolving area of neuroendocrinology, with special emphasis on recent developments and contentious issues that are likely to attract considerable attention in the coming years.

  15. Understanding the physiological roles of polyhydroxybutyrate (PHB) in Rhodospirillum rubrum S1 under aerobic chemoheterotrophic conditions.

    PubMed

    Narancic, Tanja; Scollica, Elisa; Kenny, Shane T; Gibbons, Helena; Carr, Eibhlin; Brennan, Lorraine; Cagney, Gerard; Wynne, Kieran; Murphy, Cormac; Raberg, Matthias; Heinrich, Daniel; Steinbüchel, Alexander; O'Connor, Kevin E

    2016-10-01

    Polyhydroxybutyrate (PHB) is an important biopolymer accumulated by bacteria and associated with cell survival and stress response. Here, we make two surprising findings in the PHB-accumulating species Rhodospirillum rubrum S1. We first show that the presence of PHB promotes the increased assimilation of acetate preferentially into biomass rather than PHB. When R. rubrum is supplied with (13)C-acetate as a PHB precursor, 83.5 % of the carbon in PHB comes from acetate. However, only 15 % of the acetate ends up in PHB with the remainder assimilated as bacterial biomass. The PHB-negative mutant of R. rubrum assimilates 2-fold less acetate into biomass compared to the wild-type strain. Acetate assimilation proceeds via the ethylmalonyl-CoA pathway with (R)-3-hydroxybutyrate as a common intermediate with the PHB pathway. Secondly, we show that R. rubrum cells accumulating PHB have reduced ribulose 1,5-bisphosphate carboxylase (RuBisCO) activity. RuBisCO activity reduces 5-fold over a 36-h period after the onset of PHB. In contrast, a PHB-negative mutant maintains the same level of RuBisCO activity over the growth period. Since RuBisCO controls the redox potential in R. rubrum, PHB likely replaces RuBisCO in this role. R. rubrum is the first bacterium found to express RuBisCO under aerobic chemoheterotrophic conditions. PMID:27480532

  16. Expression of peach sucrose transporters in heterologous systems points out their different physiological role.

    PubMed

    Zanon, Laura; Falchi, Rachele; Hackel, Aleksandra; Kühn, Christina; Vizzotto, Giannina

    2015-09-01

    Sucrose is the major phloem-translocated component in a number of economically important plant species. The comprehension of the mechanisms involved in sucrose transport in peach fruit appears particularly relevant, since the accumulation of this sugar, during ripening, is crucial for the growth and quality of the fruit. Here, we report the functional characterisation and subcellular localisation of three sucrose transporters (PpSUT1, PpSUT2, PpSUT4) in peach, and we formulate novel hypotheses about their role in accumulation of sugar. We provide evidence, about the capability of both PpSUT1 and PpSUT4, expressed in mutant yeast strains to transport sucrose. The functionality of PpSUT1 at the plasma membrane, and of PpSUT4 at the tonoplast, has been demonstrated. On the other hand, the functionality of PpSUT2 was not confirmed: this protein is unable to complement two sucrose uptake-deficient mutant yeast strains. Our results corroborate the hypotheses that PpSUT1 partakes in phloem loading in leaves, and PpSUT4 sustains cell metabolism by regulating sucrose efflux from the vacuole.

  17. Looking for the physiological role of anthocyanins in the leaves of Coffea arabica.

    PubMed

    Domingues Júnior, Adilson Pereira; Shimizu, Milton Massao; Moura, Jullyana Cristina Magalhães Silva; Catharino, Rodrigo Ramos; Ramos, Rômulo Augusto; Ribeiro, Rafael Vasconcelos; Mazzafera, Paulo

    2012-01-01

    The aim of this study was to determine which anthocyanins are related to the purple coloration of young leaves in Coffea arabica var. Purpurascens and assess their impact on photosynthesis as compared to C. arabica var. Catuaí, with green leaves. Two delphinidin glicosides were identified and histological cross-sections showed they were located throughout the adaxial epidermis in young leaves, disappearing as the leaves mature. Regardless the irradiance level, the photosynthetic performance of Purpurascens leaves did not differ from that observed in leaves of the Catuaí variety, providing no evidence that anthocyanins improve photosynthetic performance in coffee plants. To analyze the photoprotective action of anthocyanins, we evaluated the isomerization process for chlorogenic acids (CGAs) in coffee leaves exposed to UV-B radiation. No differences were observed in the total concentration of phenolic compounds in either variety before or after the UV treatment; however, we observed less degradation of CGA isomers in the Purpurascens leaves and a relative increase of cis-5-caffeoylquinic acid, a positional isomer of one of the most abundant form of CQA in coffee leaves, trans-5-caffeoylquinic acid, suggesting a possible protective role for anthocyanins in this purple coffee variety. PMID:22372995

  18. The roles of O-linked β-N-acetylglucosamine in cardiovascular physiology and disease

    PubMed Central

    2012-01-01

    More than 1,000 proteins of the nucleus, cytoplasm, and mitochondria are dynamically modified by O-linked β-N-acetylglucosamine (O-GlcNAc), an essential post-translational modification of metazoans. O-GlcNAc, which modifies Ser/Thr residues, is thought to regulate protein function in a manner analogous to protein phosphorylation and, on a subset of proteins, appears to have a reciprocal relationship with phosphorylation. Like phosphorylation, O-GlcNAc levels change dynamically in response to numerous signals including hyperglycemia and cellular injury. Recent data suggests that O-GlcNAc appears to be a key regulator of the cellular stress response, the augmentation of which is protective in models of acute vascular injury, trauma hemorrhage, and ischemia-reperfusion injury. In contrast to these studies, O-GlcNAc has also been implicated in the development of hypertension and type II diabetes, leading to vascular and cardiac dysfunction. Here we summarize the current understanding of the roles of O-GlcNAc in the heart and vasculature. PMID:22287582

  19. The roles of O-linked β-N-acetylglucosamine in cardiovascular physiology and disease.

    PubMed

    Zachara, Natasha E

    2012-05-15

    More than 1,000 proteins of the nucleus, cytoplasm, and mitochondria are dynamically modified by O-linked β-N-acetylglucosamine (O-GlcNAc), an essential post-translational modification of metazoans. O-GlcNAc, which modifies Ser/Thr residues, is thought to regulate protein function in a manner analogous to protein phosphorylation and, on a subset of proteins, appears to have a reciprocal relationship with phosphorylation. Like phosphorylation, O-GlcNAc levels change dynamically in response to numerous signals including hyperglycemia and cellular injury. Recent data suggests that O-GlcNAc appears to be a key regulator of the cellular stress response, the augmentation of which is protective in models of acute vascular injury, trauma hemorrhage, and ischemia-reperfusion injury. In contrast to these studies, O-GlcNAc has also been implicated in the development of hypertension and type II diabetes, leading to vascular and cardiac dysfunction. Here we summarize the current understanding of the roles of O-GlcNAc in the heart and vasculature.

  20. Looking for the physiological role of anthocyanins in the leaves of Coffea arabica.

    PubMed

    Domingues Júnior, Adilson Pereira; Shimizu, Milton Massao; Moura, Jullyana Cristina Magalhães Silva; Catharino, Rodrigo Ramos; Ramos, Rômulo Augusto; Ribeiro, Rafael Vasconcelos; Mazzafera, Paulo

    2012-01-01

    The aim of this study was to determine which anthocyanins are related to the purple coloration of young leaves in Coffea arabica var. Purpurascens and assess their impact on photosynthesis as compared to C. arabica var. Catuaí, with green leaves. Two delphinidin glicosides were identified and histological cross-sections showed they were located throughout the adaxial epidermis in young leaves, disappearing as the leaves mature. Regardless the irradiance level, the photosynthetic performance of Purpurascens leaves did not differ from that observed in leaves of the Catuaí variety, providing no evidence that anthocyanins improve photosynthetic performance in coffee plants. To analyze the photoprotective action of anthocyanins, we evaluated the isomerization process for chlorogenic acids (CGAs) in coffee leaves exposed to UV-B radiation. No differences were observed in the total concentration of phenolic compounds in either variety before or after the UV treatment; however, we observed less degradation of CGA isomers in the Purpurascens leaves and a relative increase of cis-5-caffeoylquinic acid, a positional isomer of one of the most abundant form of CQA in coffee leaves, trans-5-caffeoylquinic acid, suggesting a possible protective role for anthocyanins in this purple coffee variety.

  1. The role of fetuin-A in physiological and pathological mineralization.

    PubMed

    Brylka, Laura; Jahnen-Dechent, Willi

    2013-10-01

    Mineralization in higher vertebrates is restricted to bones and teeth. Pathological calcification is mostly known in vasculature but can basically affect all soft tissues. Simply put, tissue mineralization occurs through the interplay of three key determinants: extracellular matrix suitable for mineralization, extracellular levels of inorganic phosphate and calcium, and the levels of mineralization inhibitors that may be expressed systemically or locally. In this article we describe the role of a prototypic systemic inhibitor protein of mineralization, the hepatic plasma protein α2-Heremans-Schmid glycoprotein/fetuin-A. Fetuin-A mediates the formation of stable colloidal mineral-protein complexes called calciprotein particles (CPPs). Thus, fetuin-A is important in the stabilization and clearance of amorphous mineral precursor phases. Efficient clearance of CPPs and, thus, of excess mineral from circulation prevents local buildup of mineral and calcification of soft tissue. Besides calcium phosphate binding, fetuin-A also acts as a carrier for lipids, which may influence calcification, inflammation, and apoptosis. Fetuin-A-deficient (Ahsg(-/-)) mice show impaired growth of their long bones and premature growth plate closure. We posit that the absence of fetuin-A in the growth plate causes simultaneous lack of calcification inhibition and excess lipid hormone signaling, leading to premature growth plate mineralization and shortened long bones. This suggests that fetuin-A regulates endochondral ossification through mineralization inhibition and lipid (hormone) binding.

  2. Expression of peach sucrose transporters in heterologous systems points out their different physiological role.

    PubMed

    Zanon, Laura; Falchi, Rachele; Hackel, Aleksandra; Kühn, Christina; Vizzotto, Giannina

    2015-09-01

    Sucrose is the major phloem-translocated component in a number of economically important plant species. The comprehension of the mechanisms involved in sucrose transport in peach fruit appears particularly relevant, since the accumulation of this sugar, during ripening, is crucial for the growth and quality of the fruit. Here, we report the functional characterisation and subcellular localisation of three sucrose transporters (PpSUT1, PpSUT2, PpSUT4) in peach, and we formulate novel hypotheses about their role in accumulation of sugar. We provide evidence, about the capability of both PpSUT1 and PpSUT4, expressed in mutant yeast strains to transport sucrose. The functionality of PpSUT1 at the plasma membrane, and of PpSUT4 at the tonoplast, has been demonstrated. On the other hand, the functionality of PpSUT2 was not confirmed: this protein is unable to complement two sucrose uptake-deficient mutant yeast strains. Our results corroborate the hypotheses that PpSUT1 partakes in phloem loading in leaves, and PpSUT4 sustains cell metabolism by regulating sucrose efflux from the vacuole. PMID:26259193

  3. RPGR: Its role in photoreceptor physiology, human disease, and future therapies

    PubMed Central

    Megaw, Roly D.; Soares, Dinesh C.; Wright, Alan F.

    2015-01-01

    Mammalian photoreceptors contain specialised connecting cilia that connect the inner (IS) to the outer segments (OS). Dysfunction of the connecting cilia due to mutations in ciliary proteins are a common cause of the inherited retinal dystrophy retinitis pigmentosa (RP). Mutations affecting the Retinitis Pigmentosa GTPase Regulator (RPGR) protein is one such cause, affecting 10–20% of all people with RP and the majority of those with X-linked RP. RPGR is located in photoreceptor connecting cilia. It interacts with a wide variety of ciliary proteins, but its exact function is unknown. Recently, there have been important advances both in our understanding of RPGR function and towards the development of a therapy. This review summarises the existing literature on human RPGR function and dysfunction, and suggests that RPGR plays a role in the function of the ciliary gate, which controls access of both membrane and soluble proteins to the photoreceptor outer segment. We discuss key models used to investigate and treat RPGR disease and suggest that gene augmentation therapy offers a realistic therapeutic approach, although important questions still remain to be answered, while cell replacement therapy based on retinal progenitor cells represents a more distant prospect. PMID:26093275

  4. [Physiological changes in the morphology of the main structural enamel unit - hydroxyapatite crystal - during its life span (in vitro study)].

    PubMed

    Shumilovich, B R; Sadovsky, V V; Sushchenko, A V; Kharitonov, Yu M

    2015-01-01

    The in vitro study by means of complex laboratory techniques including X-ray faze analysis, infrared spectroscopy, scanning electron and atomic force microscopy defined age-related physiological mineralization process as a shift of the structural enamel unit - nanocrystalline hydroxyapatite crystals - TO microcrystal phase. Relevant anatomical sites with age-dependent enamel optical characteristics corresponding to certain ratio of hydroxyapatite phases and the compliance of their color characteristics to composites enamel layers were revealed.

  5. Post-feeding physiology in Rhodnius prolixus: the possible role of FGLamide-related allatostatins.

    PubMed

    Zandawala, Meet; Orchard, Ian

    2013-12-01

    Allatostatins (ASTs) are neuropeptides that were first identified as inhibitors of juvenile hormone biosynthesis by the corpora allata of some insect species. The FGLamide-related ASTs (FGLa/ASTs) belong to one of three families of insect ASTs. Previously, we showed that Rhodnius prolixus FGLa/ASTs (Rhopr-FGLa/ASTs) are present throughout the R. prolixus central nervous system and are associated with 5 dorsal unpaired median (DUM) neurons in the mesothoracic ganglionic mass. A similar set of neurons contain serotonin which is a diuretic hormone in R. prolixus. Rhopr-FGLa/ASTs inhibit both spontaneous contractions of the anterior midgut and leucokinin-1-induced hindgut contractions. Since these tissues are involved with post-feeding diuresis, these data suggest a possible role for FGLa/ASTs in events associated with feeding, and a possible interaction with serotonin. To investigate this possibility, we have examined the DUM neurons in more detail with regard to their peptide content, examined the potential release of Rhopr-FGLa/ASTs into the haemolymph following feeding, and further investigated the effects of Rhopr-FGLa/ASTs on feeding-related tissues. There are 10 DUM neurons in the abdominal neuromeres, 5 of which express serotonin-like immunoreactivity and the other 5 express FGLa/AST-like immunoreactivity. FGLa/AST-like immunoreactivity is reduced in the 5 DUM neuron cell bodies and their neurohaemal sites on abdominal nerves at 3-5 h post feeding. Rhopr-FGLa/ASTs do not inhibit serotonin-stimulated anterior midgut absorption or Malpighian tubule secretion but do inhibit hindgut contractions induced by an endogenous kinin, suggesting that they may only indirectly affect post-feeding diuresis in R. prolixus. PMID:24161751

  6. Physiological responses of erythrocytes of goats to transportation and the mondulatory role of ascorbic acid.

    PubMed

    Minka, Ndazo Salka; Ayo, Joseph Olusegun

    2010-07-01

    Experiments were performed with the aim of investigating the effect of road transportation for 12 hr on erythrocytes of goats during the hot-dry season and the modulatory role of ascorbic acid. Forty 2.5-3-year-old Red Sokoto goats weighing 23-25 kg and belonging to both sexes served as the subjects of the study. Twenty of the goats served as the experimental group and were administered ascorbic acid (AA) per os at a dosage rate of 100 mg/kg body weight; the other 20 served as controls and were given 10 ml each of sterile water. Forty minutes after the administration and loading, the goats were transported for 12 hr. EDTA blood samples collected before loading, after loading, immediately after transportation and subsequently on the 3rd and 7th days of post-transportation were used to determine the red blood cell (RBC) count, packed cell volume (PCV), hemoglobin (Hb), erythrocyte osmotic fragility (EOF), hematimetric (intrinsic) indices and hemoglobin index levels. The obtained results showed that handling, loading and transportation of the control goats induced significant (P<0.05) increases in RBC, Hb, EOF and hypochromic erythrocytes and a decrease (P<0.05) in the volume and average Hb content in RBCs. AA administration ameliorated all these changes. The present results suggest that road transportation for 12 hr during the hot-dry season could induce serious stress, resulting in hemolysis of erythrocytes, which was ameliorated by AA administration. In addition, the results demonstrated that EOF could be used as a diagnostic tool in road transportation stress.

  7. STRUCTURED LEARNING AND TRAINING ENVIRONMENTS--A PREPARATION LABORATORY FOR ADVANCED MAMMALIAN PHYSIOLOGY.

    ERIC Educational Resources Information Center

    FIEL, NICHOLAS J.; JOHNSTON, RAYMOND F.

    A PREPARATION LABORATORY WAS DESIGNED TO FAMILIARIZE STUDENTS IN ADVANCED MAMMALIAN PHYSIOLOGY WITH LABORATORY SKILLS AND TECHNIQUES AND THUS SHORTEN THE TIME THEY SPEND IN SETTING UP ACTUAL EXPERIMENTS. THE LABORATORY LASTS 30 MINUTES, IS FLEXIBLE AND SIMPLE OF OPERATION, AND DOES NOT REQUIRE A PROFESSOR'S PRESENCE. THE BASIC TRAINING UNIT IS THE…

  8. Developing an Objective Structured Clinical Examination to Assess Work-Integrated Learning in Exercise Physiology

    ERIC Educational Resources Information Center

    Naumann, Fiona; Moore, Keri; Mildon, Sally; Jones, Philip

    2014-01-01

    This paper aims to develop a valid method to assess the key competencies of the exercise physiology profession acquired through work-integrated learning (WIL). In order to develop a competency-based assessment, the key professional tasks needed to be identified and the test designed so students' competency in different tasks and settings could be…

  9. A role for membrane shape and information processing in cardiac physiology.

    PubMed

    Knöll, Ralph

    2015-01-01

    While the heart is a dynamic organ and one of its major functions is to provide the organism with sufficient blood supply, the regulatory feedback systems, which allow adaptation to hemodynamic changes, remain not well understood. Our current description of mechanosensation focuses on stretch-sensitive ion channels, cytoskeletal components, structures such as the sarcomeric Z-disc, costameres, caveolae, or the concept of tensegrity, but these models appear incomplete as the remarkable plasticity of the myocardium in response to biomechanical stress and heart rate variations remains unexplained. Signaling activity at membranes depends on their geometric parameters such as surface area and curvature, which links shape to information processing. In the heart, continuous cycles of contraction and relaxation reshape membrane morphology and hence affect cardio-mechanic signaling. This article provides a brief review on current models of mechanosensation and focuses on how signaling, cardiac myocyte dynamics, and membrane shape interact and potentially give rise to a self-organized system that uses shape to sense the extra- and intracellular environment. This novel concept may help to explain how changes in frequency, and thus membrane shape, affect cardiac plasticity. One of the conclusions is that hypertrophy and associated fibrosis, which have been considered as necessary to cope with increased wall stress, can also be seen as part of complex feedback systems which use local membrane inhomogeneity in different cardiac cell types to influence whole organphysiology and which are predicted to fine-tune and thus regulate membrane-mediated signaling. PMID:25129123

  10. Characterization of ML-IAP protein stability and physiological role in vivo.

    PubMed

    Varfolomeev, Eugene; Moradi, Elham; Dynek, Jasmin N; Zha, Jiping; Fedorova, Anna V; Deshayes, Kurt; Fairbrother, Wayne J; Newton, Kim; Le Couter, Jennifer; Vucic, Domagoj

    2012-11-01

    ML-IAP [melanoma IAP (inhibitor of apoptosis)] is an anti-apoptotic protein that is expressed highly in melanomas where it contributes to resistance to apoptotic stimuli. The anti-apoptotic activity and elevated expression of IAP family proteins in many human cancers makes IAP proteins attractive targets for inhibition by cancer therapeutics. Small-molecule IAP antagonists that bind with high affinities to select BIR (baculovirus IAP repeat) domains have been shown to stimulate auto-ubiquitination and rapid proteasomal degradation of c-IAP1 (cellular IAP1) and c-IAP2 (cellular IAP2). In the present paper, we report ML-IAP proteasomal degradation in response to bivalent, but not monovalent, IAP antagonists. This degradation required ML-IAP ubiquitin ligase activity and was independent of c-IAP1 or c-IAP2. Although ML-IAP is best characterized in melanoma cells, we show that ML-IAP expression in normal mammalian tissues is restricted largely to the eye, being most abundant in ciliary body epithelium and retinal pigment epithelium. Surprisingly, given this pattern of expression, gene-targeted mice lacking ML-IAP exhibited normal intraocular pressure as well as normal retinal structure and function. The results of the present study indicate that ML-IAP is dispensable for both normal mouse development and ocular homoeostasis.

  11. p21Cip1 plays a critical role in the physiological adaptation to fasting through activation of PPARα

    PubMed Central

    Lopez-Guadamillas, Elena; Fernandez-Marcos, Pablo J.; Pantoja, Cristina; Muñoz-Martin, Maribel; Martínez, Dolores; Gómez-López, Gonzalo; Campos-Olivas, Ramón; Valverde, Angela M.; Serrano, Manuel

    2016-01-01

    Fasting is a physiological stress that elicits well-known metabolic adaptations, however, little is known about the role of stress-responsive tumor suppressors in fasting. Here, we have examined the expression of several tumor suppressors upon fasting in mice. Interestingly, p21 mRNA is uniquely induced in all the tissues tested, particularly in liver and muscle (>10 fold), and this upregulation is independent of p53. Remarkably, in contrast to wild-type mice, p21-null mice become severely morbid after prolonged fasting. The defective adaptation to fasting of p21-null mice is associated to elevated energy expenditure, accelerated depletion of fat stores, and premature activation of protein catabolism in the muscle. Analysis of the liver transcriptome and cell-based assays revealed that the absence of p21 partially impairs the transcriptional program of PPARα, a key regulator of fasting metabolism. Finally, treatment of p21-null mice with a PPARα agonist substantially protects them from their accelerated loss of fat upon fasting. We conclude that p21 plays a relevant role in fasting adaptation through the positive regulation of PPARα. PMID:27721423

  12. A physiological role of cyclic electron transport around photosystem I in sustaining photosynthesis under fluctuating light in rice

    PubMed Central

    Yamori, Wataru; Makino, Amane; Shikanai, Toshiharu

    2016-01-01

    Plants experience a highly variable light environment over the course of the day. To reveal the molecular mechanisms of their photosynthetic response to fluctuating light, we examined the role of two cyclic electron flows around photosystem I (CEF-PSI)—one depending on PROTON GRADIENT REGULATION 5 (PGR5) and one on NADH dehydrogenase-like complex (NDH)—in photosynthetic regulation under fluctuating light in rice (Oryza sativa L.). The impairment of PGR5-dependent CEF-PSI suppressed the photosynthetic response immediately after sudden irradiation, whereas the impairment of NDH-dependent CEF-PSI did not. However, the impairment of either PGR5-dependent or NDH-dependent CEF-PSl reduced the photosynthetic rate under fluctuating light, leading to photoinhibition at PSI and consequently a reduction in plant biomass. The results highlight that (1) PGR5-dependent CEF-PSI is a key regulator of rapid photosynthetic responses to high light intensity under fluctuating light conditions after constant high light; and (2) both PGR5-dependent and NDH-dependent CEF-PSI have physiological roles in sustaining photosynthesis and plant growth in rice under repeated light fluctuations. The highly responsive regulatory system managed by CEF-PSI appears able to optimize photosynthesis and plant growth under naturally fluctuating light conditions. PMID:26832990

  13. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations

    PubMed Central

    Nakatsu, Yusuke; Matsunaga, Yasuka; Yamamotoya, Takeshi; Ueda, Koji; Inoue, Yuki; Mori, Keiichi; Sakoda, Hideyuki; Fujishiro, Midori; Ono, Hiraku; Kushiyama, Akifumi; Asano, Tomoichiro

    2016-01-01

    Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14). Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer’s disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions. PMID:27618008

  14. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations.

    PubMed

    Nakatsu, Yusuke; Matsunaga, Yasuka; Yamamotoya, Takeshi; Ueda, Koji; Inoue, Yuki; Mori, Keiichi; Sakoda, Hideyuki; Fujishiro, Midori; Ono, Hiraku; Kushiyama, Akifumi; Asano, Tomoichiro

    2016-09-07

    Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14). Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer's disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.

  15. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations.

    PubMed

    Nakatsu, Yusuke; Matsunaga, Yasuka; Yamamotoya, Takeshi; Ueda, Koji; Inoue, Yuki; Mori, Keiichi; Sakoda, Hideyuki; Fujishiro, Midori; Ono, Hiraku; Kushiyama, Akifumi; Asano, Tomoichiro

    2016-01-01

    Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14). Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer's disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions. PMID:27618008

  16. Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology.

    PubMed

    Griendling, K K; Sorescu, D; Lassègue, B; Ushio-Fukai, M

    2000-10-01

    Emerging evidence indicates that reactive oxygen species, especially superoxide and hydrogen peroxide, are important signaling molecules in cardiovascular cells. Their production is regulated by hormone-sensitive enzymes such as the vascular NAD(P)H oxidases, and their metabolism is coordinated by antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Both of these reactive oxygen species serve as second messengers to activate multiple intracellular proteins and enzymes, including the epidermal growth factor receptor, c-Src, p38 mitogen-activated protein kinase, Ras, and Akt/protein kinase B. Activation of these signaling cascades and redox-sensitive transcription factors leads to induction of many genes with important functional roles in the physiology and pathophysiology of vascular cells. Thus, reactive oxygen species participate in vascular smooth muscle cell growth and migration; modulation of endothelial function, including endothelium-dependent relaxation and expression of a proinflammatory phenotype; and modification of the extracellular matrix. All of these events play important roles in vascular diseases such as hypertension and atherosclerosis, suggesting that the sources of reactive oxygen species and the signaling pathways that they modify may represent important therapeutic targets.

  17. Preparation of Single-cohort Colonies and Hormone Treatment of Worker Honeybees to Analyze Physiology Associated with Role and/or Endocrine System.

    PubMed

    Ueno, Takayuki; Kawasaki, Kiyoshi; Kubo, Takeo

    2016-01-01

    Honeybee workers are engaged in various tasks related to maintaining colony activity. The tasks of the workers change according to their age (age-related division of labor). Young workers are engaged in nursing the brood (nurse bees), while older workers are engaged in foraging for nectar and pollen (foragers). The physiology of the workers changes in association with this role shift. For example, the main function of the hypopharyngeal glands (HPGs) changes from the secretion of major royal jelly proteins (MRJPs) to the secretion of carbohydrate-metabolizing enzymes. Because worker tasks change as the workers age in typical colonies, it is difficult to discriminate the physiological changes that occur with aging from those that occur with the role shift. To study the physiological changes in worker tissues, including the HPGs, in association with the role shift, it would be useful to manipulate the honeybee colony population by preparing single-cohort colonies in which workers of almost the same age perform different tasks. Here we describe a detailed protocol for preparing single-cohort colonies for this analysis. Six to eight days after single-cohort colony preparation, precocious foragers that perform foraging tasks earlier than usual appear in the colony. Representative results indicated role-associated changes in HPG gene expression, suggesting role-associated HPG function. In addition to manipulating the colony population, analysis of the endocrine system is important for investigating role-associated physiology. Here, we also describe a detailed protocol for treating workers with 20-hydroxyecdysone (20E), an active form of ecdysone, and methoprene, a juvenile hormone analogue. The survival rate of treated bees was sufficient to examine gene expression in the HPGs. Gene expression changes were observed in response to 20E- and/or methoprene-treatment, suggesting that hormone treatments induce physiological changes of the HPGs. The protocol for hormone

  18. Preparation of Single-cohort Colonies and Hormone Treatment of Worker Honeybees to Analyze Physiology Associated with Role and/or Endocrine System.

    PubMed

    Ueno, Takayuki; Kawasaki, Kiyoshi; Kubo, Takeo

    2016-09-06

    Honeybee workers are engaged in various tasks related to maintaining colony activity. The tasks of the workers change according to their age (age-related division of labor). Young workers are engaged in nursing the brood (nurse bees), while older workers are engaged in foraging for nectar and pollen (foragers). The physiology of the workers changes in association with this role shift. For example, the main function of the hypopharyngeal glands (HPGs) changes from the secretion of major royal jelly proteins (MRJPs) to the secretion of carbohydrate-metabolizing enzymes. Because worker tasks change as the workers age in typical colonies, it is difficult to discriminate the physiological changes that occur with aging from those that occur with the role shift. To study the physiological changes in worker tissues, including the HPGs, in association with the role shift, it would be useful to manipulate the honeybee colony population by preparing single-cohort colonies in which workers of almost the same age perform different tasks. Here we describe a detailed protocol for preparing single-cohort colonies for this analysis. Six to eight days after single-cohort colony preparation, precocious foragers that perform foraging tasks earlier than usual appear in the colony. Representative results indicated role-associated changes in HPG gene expression, suggesting role-associated HPG function. In addition to manipulating the colony population, analysis of the endocrine system is important for investigating role-associated physiology. Here, we also describe a detailed protocol for treating workers with 20-hydroxyecdysone (20E), an active form of ecdysone, and methoprene, a juvenile hormone analogue. The survival rate of treated bees was sufficient to examine gene expression in the HPGs. Gene expression changes were observed in response to 20E- and/or methoprene-treatment, suggesting that hormone treatments induce physiological changes of the HPGs. The protocol for hormone

  19. Gastrin-releasing peptide signaling plays a limited and subtle role in amygdala physiology and aversive memory.

    PubMed

    Chaperon, Frederique; Fendt, Markus; Kelly, Peter H; Lingenhoehl, Kurt; Mosbacher, Johannes; Olpe, Hans-Rudolf; Schmid, Peter; Sturchler, Christine; McAllister, Kevin H; van der Putten, P Herman; Gee, Christine E

    2012-01-01

    Links between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and persistent fear after single-trial associative learning. Here, we confirmed these initial findings and examined whether they extrapolate to more aspects of amygdala physiology and to other forms of aversive associative learning. GRP application in brain slices from wildtype but not GRPR KO mice increased spontaneous inhibitory activity in LA pyramidal neurons. In amygdala slices from GRPR KO mice, GRP did not increase inhibitory activity. In comparison to wildtype, short- but not long-term plasticity was increased in the cortico-lateral amygdala (LA) pathway of GRPR KO amygdala slices, whereas no changes were detected in the thalamo-LA pathway. In addition, GRPR KO mice showed enhanced fear evoked by single-trial conditioning and reduced spontaneous firing of neurons in the central nucleus of the amygdala (CeA). Altogether, these results are consistent with a potentially important modulatory role of GRP/GRPR signaling in the amygdala. However, administration of GRP or the GRPR antagonist (D-Phe(6), Leu-NHEt(13), des-Met(14))-Bombesin (6-14) did not affect amygdala LTP in brain slices, nor did they affect the expression of conditioned fear following intra-amygdala administration. GRPR KO mice also failed to show differences in fear expression and extinction after multiple-trial fear conditioning, and there were no differences in conditioned taste aversion or gustatory neophobia. Collectively, our data indicate that GRP/GRPR signaling modulates amygdala physiology in a paradigm-specific fashion that likely is insufficient to generate therapeutic effects across amygdala-dependent disorders.

  20. A novel role of h2-calponin in regulating whole blood thrombosis and platelet adhesion during physiologic flow.

    PubMed

    Hines, Patrick C; Gao, Xiufeng; White, Jennell C; D'Agostino, Ashley; Jin, Jian-Ping

    2014-12-01

    Calponin is an actin filament-associated protein reported in platelets, although the specific isoform expressed and functional role were not identified. The h2-calponin isoform is expressed in myeloid-derived peripheral blood monocytes, where it regulates adhesion. Our objective was to characterize the presence and function of the h2 isoform of calponin in platelets. H2-calponin was detected in human and mouse platelets via Western blotting. Immunofluorescent staining demonstrated h2-calponin and actin colocalized in both human and wild-type mouse platelets at rest and following collagen activation. The kinetics of platelet adhesion and whole blood thrombosis during physiologic flow was evaluated in a microfluidic flow-based thrombosis assay. The time to initiation of rapid platelet/thrombus accumulation (lag time) was significantly longer in h2-calponin knockout versus wild-type mouse blood (130.02 ± 3.74 sec and 72.95 ± 16.23 sec, respectively, P < 0.05). There was no significant difference in the rate of platelet/thrombus accumulation during the rapid phase or the maximum platelet/thrombus accumulation. H2-calponin knockout mice also had prolonged bleeding time and blood loss. H2-calponin in platelets facilitates early interactions between platelets and collagen during physiologic flow, but does not significantly affect the rate or magnitude of platelet/thrombus accumulation. H2-calponin knockout mice take 2.3 times longer to achieve hemostasis compared to wild-type controls in a tail bleeding model. The ability to delay platelet accumulation without inhibiting downstream thrombotic potential would be of significant therapeutic value, thus h2-calponin may be a novel target for therapeutic platelet inhibition. PMID:25472609

  1. Gastrin-Releasing Peptide Signaling Plays a Limited and Subtle Role in Amygdala Physiology and Aversive Memory

    PubMed Central

    Chaperon, Frederique; Fendt, Markus; Kelly, Peter H.; Lingenhoehl, Kurt; Mosbacher, Johannes; Olpe, Hans-Rudolf; Schmid, Peter; Sturchler, Christine; McAllister, Kevin H.; van der Putten, P. Herman; Gee, Christine E.

    2012-01-01

    Links between synaptic plasticity in the lateral amygdala (LA) and Pavlovian fear learning are well established. Neuropeptides including gastrin-releasing peptide (GRP) can modulate LA function. GRP increases inhibition in the LA and mice lacking the GRP receptor (GRPR KO) show more pronounced and persistent fear after single-trial associative learning. Here, we confirmed these initial findings and examined whether they extrapolate to more aspects of amygdala physiology and to other forms of aversive associative learning. GRP application in brain slices from wildtype but not GRPR KO mice increased spontaneous inhibitory activity in LA pyramidal neurons. In amygdala slices from GRPR KO mice, GRP did not increase inhibitory activity. In comparison to wildtype, short- but not long-term plasticity was increased in the cortico-lateral amygdala (LA) pathway of GRPR KO amygdala slices, whereas no changes were detected in the thalamo-LA pathway. In addition, GRPR KO mice showed enhanced fear evoked by single-trial conditioning and reduced spontaneous firing of neurons in the central nucleus of the amygdala (CeA). Altogether, these results are consistent with a potentially important modulatory role of GRP/GRPR signaling in the amygdala. However, administration of GRP or the GRPR antagonist (D-Phe6, Leu-NHEt13, des-Met14)-Bombesin (6–14) did not affect amygdala LTP in brain slices, nor did they affect the expression of conditioned fear following intra-amygdala administration. GRPR KO mice also failed to show differences in fear expression and extinction after multiple-trial fear conditioning, and there were no differences in conditioned taste aversion or gustatory neophobia. Collectively, our data indicate that GRP/GRPR signaling modulates amygdala physiology in a paradigm-specific fashion that likely is insufficient to generate therapeutic effects across amygdala-dependent disorders. PMID:22509372

  2. A novel role of h2‐calponin in regulating whole blood thrombosis and platelet adhesion during physiologic flow

    PubMed Central

    Hines, Patrick C.; Gao, Xiufeng; White, Jennell C.; D'Agostino, Ashley; Jin, Jian‐Ping

    2014-01-01

    Abstract Calponin is an actin filament‐associated protein reported in platelets, although the specific isoform expressed and functional role were not identified. The h2‐calponin isoform is expressed in myeloid‐derived peripheral blood monocytes, where it regulates adhesion. Our objective was to characterize the presence and function of the h2 isoform of calponin in platelets. H2‐calponin was detected in human and mouse platelets via Western blotting. Immunofluorescent staining demonstrated h2‐calponin and actin colocalized in both human and wild‐type mouse platelets at rest and following collagen activation. The kinetics of platelet adhesion and whole blood thrombosis during physiologic flow was evaluated in a microfluidic flow‐based thrombosis assay. The time to initiation of rapid platelet/thrombus accumulation (lag time) was significantly longer in h2‐calponin knockout versus wild‐type mouse blood (130.02 ± 3.74 sec and 72.95 ± 16.23 sec, respectively, P < 0.05). There was no significant difference in the rate of platelet/thrombus accumulation during the rapid phase or the maximum platelet/thrombus accumulation. H2‐calponin knockout mice also had prolonged bleeding time and blood loss. H2‐calponin in platelets facilitates early interactions between platelets and collagen during physiologic flow, but does not significantly affect the rate or magnitude of platelet/thrombus accumulation. H2‐calponin knockout mice take 2.3 times longer to achieve hemostasis compared to wild‐type controls in a tail bleeding model. The ability to delay platelet accumulation without inhibiting downstream thrombotic potential would be of significant therapeutic value, thus h2‐calponin may be a novel target for therapeutic platelet inhibition. PMID:25472609

  3. Microtubule-associated protein 1B (MAP1B)-deficient neurons show structural presynaptic deficiencies in vitro and altered presynaptic physiology.

    PubMed

    Bodaleo, Felipe J; Montenegro-Venegas, Carolina; Henríquez, Daniel R; Court, Felipe A; Gonzalez-Billault, Christian

    2016-01-01

    Microtubule-associated protein 1B (MAP1B) is expressed predominantly during the early stages of development of the nervous system, where it regulates processes such as axonal guidance and elongation. Nevertheless, MAP1B expression in the brain persists in adult stages, where it participates in the regulation of the structure and physiology of dendritic spines in glutamatergic synapses. Moreover, MAP1B expression is also found in presynaptic synaptosomal preparations. In this work, we describe a presynaptic phenotype in mature neurons derived from MAP1B knockout (MAP1B KO) mice. Mature neurons express MAP1B, and its deficiency does not alter the expression levels of a subgroup of other synaptic proteins. MAP1B KO neurons display a decrease in the density of presynaptic and postsynaptic terminals, which involves a reduction in the density of synaptic contacts, and an increased proportion of orphan presynaptic terminals. Accordingly, MAP1B KO neurons present altered synaptic vesicle fusion events, as shown by FM4-64 release assay, and a decrease in the density of both synaptic vesicles and dense core vesicles at presynaptic terminals. Finally, an increased proportion of excitatory immature symmetrical synaptic contacts in MAP1B KO neurons was detected. Altogether these results suggest a novel role for MAP1B in presynaptic structure and physiology regulation in vitro. PMID:27425640

  4. Microtubule-associated protein 1B (MAP1B)-deficient neurons show structural presynaptic deficiencies in vitro and altered presynaptic physiology

    PubMed Central

    Bodaleo, Felipe J.; Montenegro-Venegas, Carolina; Henríquez, Daniel R.; Court, Felipe A.; Gonzalez-Billault, Christian

    2016-01-01

    Microtubule-associated protein 1B (MAP1B) is expressed predominantly during the early stages of development of the nervous system, where it regulates processes such as axonal guidance and elongation. Nevertheless, MAP1B expression in the brain persists in adult stages, where it participates in the regulation of the structure and physiology of dendritic spines in glutamatergic synapses. Moreover, MAP1B expression is also found in presynaptic synaptosomal preparations. In this work, we describe a presynaptic phenotype in mature neurons derived from MAP1B knockout (MAP1B KO) mice. Mature neurons express MAP1B, and its deficiency does not alter the expression levels of a subgroup of other synaptic proteins. MAP1B KO neurons display a decrease in the density of presynaptic and postsynaptic terminals, which involves a reduction in the density of synaptic contacts, and an increased proportion of orphan presynaptic terminals. Accordingly, MAP1B KO neurons present altered synaptic vesicle fusion events, as shown by FM4-64 release assay, and a decrease in the density of both synaptic vesicles and dense core vesicles at presynaptic terminals. Finally, an increased proportion of excitatory immature symmetrical synaptic contacts in MAP1B KO neurons was detected. Altogether these results suggest a novel role for MAP1B in presynaptic structure and physiology regulation in vitro. PMID:27425640

  5. Physiological Heterogeneity: Fractals Link Determinism and Randomness in Structures and Functions

    PubMed Central

    Bassingthwaighte, James B.

    2010-01-01

    Spatial variation in concentrations or flows within an organ and temporal variation in reaction rates or flows appear to broaden as one refines the scale of observation. How can we characterize heterogeneity independently of scale? Fractals come to our rescue! A system is fractal if its features adhere to the same rules through a succession of different scales. Fractals efficiently describe many types of observations, geometric and kinetic, and help to integrate physiological knowledge. PMID:20871797

  6. Conservation physiology for applied management of marine fish: an overview with perspectives on the role and value of telemetry

    PubMed Central

    Metcalfe, J. D.; Le Quesne, W. J. F.; Cheung, W. W. L.; Righton, D. A.

    2012-01-01

    Physiological studies focus on the responses of cells, tissues and individuals to stressors, usually in laboratory situations. Conservation and management, on the other hand, focus on populations. The field of conservation physiology addresses the question of how abiotic drivers of physiological responses at the level of the individual alter requirements for successful conservation and management of populations. To achieve this, impacts of physiological effects at the individual level need to be scaled to impacts on population dynamics, which requires consideration of ecology. Successfully realizing the potential of conservation physiology requires interdisciplinary studies incorporating physiology and ecology, and requires that a constructive dialogue develops between these traditionally disparate fields. To encourage this dialogue, we consider the increasingly explicit incorporation of physiology into ecological models applied to marine fish conservation and management. Conservation physiology is further challenged as the physiology of an individual revealed under laboratory conditions is unlikely to reflect realized responses to the complex variable stressors to which it is exposed in the wild. Telemetry technology offers the capability to record an animal's behaviour while simultaneously recording environmental variables to which it is exposed. We consider how the emerging insights from telemetry can strengthen the incorporation of physiology into ecology. PMID:22566680

  7. Within-catchment variation in regulation of water use by eucalypts, and the roles of stomatal anatomy and physiology

    NASA Astrophysics Data System (ADS)

    Gharun, Mana; Turnbull, Tarryn; Adams, Mark

    2014-05-01

    Understanding how environmental cues impact water use of forested catchments is crucial for accurate calculation of water balance and effective catchment management in terrestrial ecosystems. We characterised structural and physiological properties of leaves and canopies of Eucalyptus delegatensis, E. pauciflora and E. radiata, the most common species in high-country catchments in temperate Australia. These properties were related to whole-tree water transport to assess differences in water use strategies among the three species. Stomatal conductance, instantaneous transpiration efficiency, stomatal occlusion (through cuticular ledges) and leaf area index differed significantly among species. Whole-tree water use of all species was strongly coupled to changes in vapour pressure deficit (VPD) and photosynthetically active radiation (Q), yet stomatal closure reduced water transport at VPD > 1 kPa in all species, even when soil water was not limiting. The observed differences in leaf traits and related water use strategies reflect species-specific adaptations to dominant environmental conditions within the landscape matrix of catchments. The generalist E. radiata seems to follow an opportunistic, while the two more spatially restricted species have adopted a pessimistic water use strategy. Catchment-scale models of carbon and water fluxes will need to reflect such variation in structure and function, if they are to fully capture species effects on water balance and yield.

  8. The alignment of technology and structure through roles and networks.

    PubMed

    Barley, S R

    1990-03-01

    This paper outlines a role-based approach for conceptualizing and investigating the contention in some previous research that technologies change organizational and occupational structures by transforming patterns of action and interaction. Building on Nadel's theory of social structure, the paper argues that the microsocial dynamics occasioned by new technologies reverberate up levels of analysis in an orderly manner. Specifically, a technology's material attributes are said to have an immediate impact on the nonrelational elements of one or more work roles. These changes, in turn, influence the role's relational elements, which eventually affect the structure of an organization's social networks. Consequently, roles and social networks are held to mediate a technology's structural effects. The theory is illustrated by ethnographic and sociometric data drawn from a comparative field study of the use of traditional and computerized imaging devices in two radiology departments. PMID:10106582

  9. Aegerolysins: Structure, function, and putative biological role

    PubMed Central

    Berne, Sabina; Lah, Ljerka; Sepčić, Kristina

    2009-01-01

    Aegerolysins, discovered in fungi, bacteria and plants, are highly similar proteins with interesting biological properties. Certain aegerolysins possess antitumoral, antiproliferative, and antibacterial activities. Further possible medicinal applications include their use in the prevention of atherosclerosis, or as vaccines. Additional biotechnological value of fungal aegerolysins lies in their involvement in development, which could improve cultivation of commercially important edible mushrooms. Besides, new insights on microheterogeneity of raft-like membrane domains could be gained by using aegerolysins as specific markers in cell and molecular biology. Although the exact function of aegerolysins in their producing organisms remains to be explained, they are biochemically well characterized all-β structured proteins sharing the following common features: low isoelectric points, similar molecular weights (15–17 kDa), and stability in a wide pH range. PMID:19309687

  10. Physiological and structural analysis of light-harvesting mutants of Rhodobacter sphaeroides.

    PubMed

    Kiley, P J; Varga, A; Kaplan, S

    1988-03-01

    Two mutants of Rhodobacter sphaeroides defective in formation of light-harvesting spectral complexes were examined in detail. Mutant RS103 lacked the B875 spectral complex despite the fact that substantial levels of the B875-alpha polypeptide (and presumably the beta polypeptide) were present. The B800-850 spectral complex was derepressed in RS103, even at high light intensities, and the growth rate was near normal at high light intensity but decreased relative to the wild type as the light intensity used for growth decreased. Mutant RS104 lacked colored carotenoids and the B800-850 spectral complex, as well as the cognate apoproteins. This strain grew normally at high light intensity and, as with RS103, the growth rate decreased as the light intensity used for growth decreased. At very low light intensities, however, RS104 would grow, whereas RS103 would not. Structural analysis of these mutants as well as others revealed that the morphology of the intracytoplasmic membrane invaginations is associated with the presence or absence of the B800-850 complex as well as of carotenoids. A low-molecular-weight intracytoplasmic membrane polypeptide, which may play a role in B800-850 complex formation, is described, as is a 62,000-dalton polypeptide whose abundance is directly related to light intensity as well as the absence of either of the light-harvesting spectral complexes. These data, obtained from studies of mutant strains and the wild type, are discussed in light of photosynthetic membrane formation and the abundance of spectral complexes per unit area of membrane. Finally, a method for the bulk preparation of the B875 complex from wild-type strain 2.4.1 is reported.

  11. Role Identification and Game Structure: Effects on Political Attitudes.

    ERIC Educational Resources Information Center

    Livingston, Samuel A.; Kidder, Steven J.

    The research study measures changes in political attitudes of high school students after playing the game "Democracy." The primary purpose of the experiment was to determine if role identification and game structure are primarily responsible for the effects of the game upon the player's attitudes. The player takes the role of a congressman who…

  12. Critical role of hypoxia and A2A adenosine receptors in liver tissue-protecting physiological anti-inflammatory pathway.

    PubMed

    Choukèr, Alexander; Thiel, Manfred; Lukashev, Dmitriy; Ward, Jerrold M; Kaufmann, Ines; Apasov, Sergey; Sitkovsky, Michail V; Ohta, Akio

    2008-01-01

    Whole body exposure of wild type control littermates and A2A adenosine receptor (A2AR) gene deleted mice to low oxygen containing inspired gas mixture allowed the investigation of the mechanism that controls inflammatory liver damage and protects the liver using a mouse model of T cell-mediated viral and autoimmune hepatitis. We tested the hypothesis that the inflammatory tissue damage-associated hypoxia and extracellular adenosine --> A2AR signaling plays an important role in the physiological anti-inflammatory mechanism that limits liver damage during fulminant hepatitis. After induction of T cell-mediated hepatitis, mice were kept in modular chambers either under normoxic (21% oxygen) or hypoxic (10% oxygen) conditions for 8 h. It was shown that the whole body exposure to hypoxic atmosphere caused tissue hypoxia in healthy animals as evidenced by a decrease in the arterial blood oxygen tension and increase of the plasma adenosine concentration (P < 0.05). This "hypoxic" treatment resulted in significantly reduced hepatocellular damage and attenuated levels of serum cytokines in mice with acute liver inflammation. The anti-inflammatory effects of hypoxia were not observed in the absence of A2AR in studies of A2AR gene-deficient mice or when A2AR have been pharmacologically antagonized with synthetic antagonist. The presented data demonstrate that total body hypoxia-triggered pathway provides protection in acute hepatitis and that hypoxia (upstream) and A2AR (downstream) function in the same immunosuppressive and liver tissue-protecting pathway.

  13. Role of heat shock protein Hsp25 in the response of the orofacial nuclei motor system to physiological stress

    NASA Technical Reports Server (NTRS)

    Murashov, A. K.; Talebian, S.; Wolgemuth, D. J.

    1998-01-01

    Although expression of the small heat shock protein family member Hsp25 has been previously observed in the central nervous system (CNS), both constitutively and upon induction, its function in the CNS remains far from clear. In the present study we have characterized the spatial pattern of expression of Hsp25 in the normal adult mouse brain as well as the changes in expression patterns induced by subjecting mice to experimental hyperthermia or hypoxia. Immunohistochemical analysis revealed a surprisingly restricted pattern of constitutive expression of Hsp25 in the brain, limited to the facial, trigeminal, ambiguus, hypoglossal and vagal motor nuclei of the brainstem. After hyperthermia or hypoxia treatment, significant increases in the levels of Hsp25 were observed in these same areas and also in fibers of the facial and trigeminal nerve tracts. Immunoblot analysis of protein lysates from brainstem also showed the same pattern of induction of Hsp25. Surprisingly, no other area in the brain showed expression of Hsp25, in either control or stressed animals. The highly restricted expression of Hsp25 implies that this protein may have a specific physiological role in the orofacial motor nuclei, which govern precise coordination between muscles of mastication and the pharynx, larynx, and face. Its rapid induction after stress further suggests that Hsp25 may serve as a specific molecular chaperone in the lower cholinergic motor neurons and along their fibers under conditions of stress or injury. Copyright 1998 Elsevier Science B.V.

  14. From Discovery to Function: The Expanding Roles of Long NonCoding RNAs in Physiology and Disease

    PubMed Central

    Sun, Miao

    2015-01-01

    Long noncoding RNAs (lncRNAs) are a relatively poorly understood class of RNAs with little or no coding capacity transcribed from a set of incompletely annotated genes. They have received considerable attention in the past few years and are emerging as potentially important players in biological regulation. Here we discuss the evolving understanding of this new class of molecular regulators that has emerged from ongoing research, which continues to expand our databases of annotated lncRNAs and provide new insights into their physical properties, molecular mechanisms of action, and biological functions. We outline the current strategies and approaches that have been employed to identify and characterize lncRNAs, which have been instrumental in revealing their multifaceted roles ranging from cis- to trans-regulation of gene expression and from epigenetic modulation in the nucleus to posttranscriptional control in the cytoplasm. In addition, we highlight the molecular and biological functions of some of the best characterized lncRNAs in physiology and disease, especially those relevant to endocrinology, reproduction, metabolism, immunology, neurobiology, muscle biology, and cancer. Finally, we discuss the tremendous diagnostic and therapeutic potential of lncRNAs in cancer and other diseases. PMID:25426780

  15. The barley anion channel, HvALMT1, has multiple roles in guard cell physiology and grain metabolism.

    PubMed

    Xu, Muyun; Gruber, Benjamin D; Delhaize, Emmanuel; White, Rosemary G; James, Richard A; You, Jiangfeng; Yang, Zhenming; Ryan, Peter R

    2015-01-01

    The barley (Hordeum vulgare) gene HvALMT1 encodes an anion channel in guard cells and in certain root tissues indicating that it may perform multiple roles. The protein localizes to the plasma membrane and facilitates malate efflux from cells when constitutively expressed in barley plants and Xenopus oocytes. This study investigated the function of HvALMT1 further by identifying its tissue-specific expression and by generating and characterizing RNAi lines with reduced HvALMT1 expression. We show that transgenic plants with 18-30% of wild-type HvALMT1 expression had impaired guard cell function. They maintained higher stomatal conductance in low light intensity and lost water more rapidly from excised leaves than the null segregant control plants. Tissue-specific expression of HvALMT1 was investigated in developing grain and during germination using transgenic barley lines expressing the green fluorescent protein (GFP) with the HvALMT1 promoter. We found that HvALMT1 is expressed in the nucellar projection, the aleurone layer and the scutellum of developing barley grain. Malate release measured from isolated aleurone layers prepared from imbibed grain was significantly lower in the RNAi barley plants compared with control plants. These data provide molecular and physiological evidence that HvALMT1 functions in guard cells, in grain development and during germination. We propose that HvALMT1 releases malate and perhaps other anions from guard cells to promote stomatal closure. The likely roles of HvALMT1 during seed development and grain germination are also discussed.

  16. Role of neuregulin-1/ErbB signaling in cardiovascular physiology and disease: implications for therapy of heart failure.

    PubMed

    Lemmens, Katrien; Doggen, Kris; De Keulenaer, Gilles W

    2007-08-21

    Since the discovery that neuregulin-1 (NRG-1)/ErbB signaling is indispensable in cardiac development, evidence has shown that this system also plays a crucial role in the adult heart. In patients, an inhibitory ErbB2 antibody, trastuzumab, used in the treatment of mammary carcinomas, increases the risk for the development of cardiotoxic cardiomyopathy. Postnatal disruption of NRG-1/ErbB signaling by gene targeting in mice leads to dilated cardiomyopathy. Initially, the search for the mechanisms behind these observations focused mainly on the effects of NRG-1 on cardiomyocyte growth and survival and revealed that NRG-1 has Akt-dependent antiapoptotic effects in cultured cardiomyocytes. In vivo studies, however, did not uniformly reinforce a role for apoptosis in the development of cardiomyopathy induced by impaired NRG-1/ErbB signaling. More recent studies have revealed that NRG-1 is involved in the regulation of cardiac sympathovagal balances by counterbalancing adrenergic stimulation of the adult myocardium and through an obligatory interaction with the muscarinic cholinergic system. NRG-1 is synthesized and released by the endocardial and cardiac microvascular endothelium, dynamically controlled by neurohormonal and biomechanical stimuli. The physiology of the cardiac NRG-1/ErbB system has implications for the treatment of both cancer and heart failure. Clinical studies in breast cancer with novel ErbB inhibitors are currently underway. Novel oncological indications for ErbB inhibition are emerging; cardiovascular side effects need to be carefully monitored. On the other hand, pharmacological activation of ErbB signaling is likely an unrecognized and beneficial effect of currently used drugs in heart failure and a promising therapeutic approach to prevent or reverse myocardial dysfunction.

  17. Observed and simulated effect of plant physiology and structure on land surface energy fluxes and soil conditions

    NASA Astrophysics Data System (ADS)

    Lu, Yen-Sen; Rihani, Jehan; Langensiepen, Matthias; Simmer, Clemens

    2016-04-01

    The parameterization of stomatal conductance and leaf area index (LAI) in land surface models largely influence simulated terrestrial system states. While stomatal conductance mainly controls transpiration, latent heat flux, and root-water-uptake, LAI impacts additionally the radiative energy exchange. Thus both affect canopy evaporation and transpiration and land surface energy and water fluxes as a whole. Common parameterizations of stomatal conductance follow either semi-mechanistic forms based on photosynthesis (Ball-Berry Type (BB)) or forms which consider environmental factors such as impact of light, temperature, humidity and soil moisture (Jarvis-Stewart Type (JS)). Both approaches differ also in the interpretation of humidity effects and light-use efficiency. While soil moisture plays an important role for root-water-uptake there is no clear conclusion yet about how soil moisture interacts with stomata activity. Values for LAI can be obtained from field measurements, satellite estimates or modelling and are used as an essential model input. While field measurements are very time consuming and only represent single points, satellite estimates may have biases caused by variable albedo and sensor limitations. Representing LAI within land surface models requires complex schemes in order to represent all processes contributing to plant growth. We use the Terrestrial System Modelling Platform (TerrSysMP) over the Rur watershed in Germany for studying the influence of plant physiology and structure on the state of the terrestrial system. The Transregional Collaborative Research Center 32 (TR32) extensively monitors this catchment for almost a decade. The land surface (CLM3.5) and the subsurface (ParFlow) modules of TerrSysMP are conditioned based on satellite-retrieved land cover and the soil map from FAO and forced with a high-resolution reanalysis by DWD. For studying the effect of plant physiology, the Ball-Berry-Leuning, and Jarvis-Stewart stomatal

  18. Desiccation Tolerance in the Moss Polytrichum formosum: Physiological and Fine-structural Changes during Desiccation and Recovery

    PubMed Central

    Proctor, Michael C. F.; Ligrone, Roberto; Duckett, Jeffrey G.

    2007-01-01

    Background and Aims This study explores basic physiological features and time relations of recovery of photosynthetic activity and CO2 uptake following rehydration of a desiccation-tolerant moss in relation to the full temporal sequence of cytological changes associated with recovery to the normal hydrated state. It seeks reconciliation of the apparently conflicting published physiological and cytological evidence on recovery from desiccation in bryophytes. Methods Observations were made of water-stress responses and recovery using infrared gas analysis and modulated chlorophyll fluorescence, and of structural and ultrastructural changes by light and transmission electron microscopy. Key Results Net CO2 uptake fell to zero at approx. 40 % RWC, paralleling the fluorescence parameter ΦPSII at 200 µmol m–2 s–1 PPFD. On re-wetting the moss after 9–18 d desiccation, the initially negative net CO2 uptake became positive 10–30 min after re-wetting, restoring a net carbon balance after approx. 0·3–1 h. The parameter Fv/Fm reached approx. 80 % of its pre-desiccation value within approx. 10 min of re-wetting. In the presence of the protein-synthesis inhibitors chloramphenicol and cycloheximide, recovery of Fv/Fm (and CO2 exchange) proceeded normally in the dark, but declined rapidly in the light. Though initial recovery was rapid, both net CO2 uptake and Fv/Fm required approx. 24 h to recover completely to pre-desiccation values. The fixation protocols produced neither swelling of tissues nor plasmolysis. Thylakoids, grana and mitochondrial cristae remained intact throughout the drying–re-wetting cycle, but there were striking changes in the form of the organelles, especially the chloroplasts, which had prominent lobes and lamellar extensions in the normally hydrated state, but rounded off when desiccated, returning slowly to their normal state within approx. 24 h of re-wetting. Sub-cellular events during desiccation and re-wetting were generally

  19. Spatial Distribution, Structure, Biomass, and Physiology of Microbial Assemblages across the Southern Ocean Frontal Zones during the Late Austral Winter

    PubMed Central

    Hanson, Roger B.; Lowery, H. Kenneth

    1985-01-01

    We examined the spatial distributions of picoplankton, nanoplankton, and microplankton biomass and physiological state relative to the hydrography of the Southern Ocean along 90° W longitude and across the Drake Passage in the late austral winter. The eastern South Pacific Ocean showed some large-scale biogeographical differences and size class variability. Microbial ATP biomass was greatest in euphotic surface waters. The horizontal distributions of microbial biomass and physiological state (adenylate energy charge ratio) coincided with internal currents (fronts) of the Antarctic Circumpolar Current. In the Drake Passage, the biological scales in the euphotic and aphotic zones were complex, and ATP, total adenylate, and adenylate energy charge ratio isopleths were compressed due to the extension of the sea ice from Antarctica and constriction of the Circumpolar Current through the narrow passage. The physiological state of microbial assemblages and biomass were much higher in the Drake Passage than in the eastern South Pacific Ocean. The temperature of Antarctic waters, not dissolved organic carbon, was the major variable controlling picoplankton growth. Estimates of picoplankton production based on ATP increments with time suggest that production under reduced predation pressure was 1 to 10 μg of carbon per liter per day. Our results demonstrate the influence of large-scale hydrographic processes on the distribution and structure of microplankton, nanoplankton, and picoplankton across the Southern Ocean. PMID:16346777

  20. Spatial Distribution, Structure, Biomass, and Physiology of Microbial Assemblages across the Southern Ocean Frontal Zones during the Late Austral Winter.

    PubMed

    Hanson, R B; Lowery, H K

    1985-05-01

    We examined the spatial distributions of picoplankton, nanoplankton, and microplankton biomass and physiological state relative to the hydrography of the Southern Ocean along 90 degrees W longitude and across the Drake Passage in the late austral winter. The eastern South Pacific Ocean showed some large-scale biogeographical differences and size class variability. Microbial ATP biomass was greatest in euphotic surface waters. The horizontal distributions of microbial biomass and physiological state (adenylate energy charge ratio) coincided with internal currents (fronts) of the Antarctic Circumpolar Current. In the Drake Passage, the biological scales in the euphotic and aphotic zones were complex, and ATP, total adenylate, and adenylate energy charge ratio isopleths were compressed due to the extension of the sea ice from Antarctica and constriction of the Circumpolar Current through the narrow passage. The physiological state of microbial assemblages and biomass were much higher in the Drake Passage than in the eastern South Pacific Ocean. The temperature of Antarctic waters, not dissolved organic carbon, was the major variable controlling picoplankton growth. Estimates of picoplankton production based on ATP increments with time suggest that production under reduced predation pressure was 1 to 10 mug of carbon per liter per day. Our results demonstrate the influence of large-scale hydrographic processes on the distribution and structure of microplankton, nanoplankton, and picoplankton across the Southern Ocean.

  1. The Role of Aerobic and Anaerobic Training Programs on CD(34+) Stem Cells and Chosen Physiological Variables.

    PubMed

    Shalaby, Mohammed Nader; Saad, Mohammed; Akar, Samy; Reda, Mubarak Abdelreda Ali; Shalgham, Ahmed

    2012-12-01

    Exercise is one of the most powerful non-pharmacological strategies, which can affect nearly all cells and organs in the body. Changes in the behavior of adult stem cells have been shown to occur in response to exercise. Exercise may act on regenerative potential of tissues by altering the ability to generate new stem cells and differentiated cells that are able to carry out tissue specific functions. The purpose of this study was to reveal the role of aerobic and anaerobic training programs on CD34+ Stem Cells and chosen physiological variables. Twenty healthy male athletes aged 18-24 years were recruited for this study. Healthy low active males and BMI matched participants (n=10) aged 20-22 years were recruited as controls. Aerobic and anaerobic training programs for 12 weeks were conducted. VO2max pulse observation was carried out using the Astrand Rhyming protocol. RBCs, WBCs, HB and hematocrit were estimated using a coulter counter, lactate by the Accusport apparatus, CD34+ stem cells by flow cytometry. VO2max was increased significantly in case of the aerobic training program compared to anaerobic one (62±2.2 ml/kg/min vs. 54±2.1 ml/kg/min). Haemotological values increased significantly in the anaerobic program when compared to the aerobic one, RBCs (5.3±0.3 and 4.9±0.2 mln/ul), WBCs (6.6±0.5 and 6.1±0.4 thous/ul), HB (15.4±0.4 and 14.2±0.5 g/de), Hematocrit (4.6±1.2 and 4.4±1.1 %), CD34+ stem cells count increased significantly in case of the anaerobic program compared to the aerobic (251.6±21.64 and 130±14.61) and sedentary one (172±24.10). These findings suggest that anaerobic training programs provoke better adaptation to exercise and stem cell counts may differ between trained and sedentary subjects. Circulating immature cells are likely to be involved in angiogenesis and repair process, both mechanisms being associated with strenuous exercise. Knowledge of the physiological effects of training on stem cells might be of potential clinical

  2. The Role of Aerobic and Anaerobic Training Programs on CD34+ Stem Cells and Chosen Physiological Variables

    PubMed Central

    Shalaby, Mohammed Nader; Saad, Mohammed; Akar, Samy; Reda, Mubarak Abdelreda Ali; Shalgham, Ahmed

    2012-01-01

    Exercise is one of the most powerful non-pharmacological strategies, which can affect nearly all cells and organs in the body. Changes in the behavior of adult stem cells have been shown to occur in response to exercise. Exercise may act on regenerative potential of tissues by altering the ability to generate new stem cells and differentiated cells that are able to carry out tissue specific functions. The purpose of this study was to reveal the role of aerobic and anaerobic training programs on CD34+ Stem Cells and chosen physiological variables. Twenty healthy male athletes aged 18–24 years were recruited for this study. Healthy low active males and BMI matched participants (n=10) aged 20–22 years were recruited as controls. Aerobic and anaerobic training programs for 12 weeks were conducted. VO2max pulse observation was carried out using the Astrand Rhyming protocol. RBCs, WBCs, HB and hematocrit were estimated using a coulter counter, lactate by the Accusport apparatus, CD34+ stem cells by flow cytometry. VO2max was increased significantly in case of the aerobic training program compared to anaerobic one (62±2.2 ml/kg/min vs. 54±2.1 ml/kg/min). Haemotological values increased significantly in the anaerobic program when compared to the aerobic one, RBCs (5.3±0.3 and 4.9±0.2 mln/ul), WBCs (6.6±0.5 and 6.1±0.4 thous/ul), HB (15.4±0.4 and 14.2±0.5 g/de), Hematocrit (4.6±1.2 and 4.4±1.1 %), CD34+ stem cells count increased significantly in case of the anaerobic program compared to the aerobic (251.6±21.64 and 130±14.61) and sedentary one (172±24.10). These findings suggest that anaerobic training programs provoke better adaptation to exercise and stem cell counts may differ between trained and sedentary subjects. Circulating immature cells are likely to be involved in angiogenesis and repair process, both mechanisms being associated with strenuous exercise. Knowledge of the physiological effects of training on stem cells might be of potential

  3. Hyper-temporal LiDAR for tracking fine-scale changes in vegetation structure, phenology, and physiology

    NASA Astrophysics Data System (ADS)

    Magney, T. S.; Vierling, L. A.; Eitel, J.; Greaves, H.

    2015-12-01

    Vegetation three-dimensional (3-D) structure is inherently dynamic - plants alter both the allocation of resources within the canopy and branch/shoot morphology at short time-steps to acclimate to local environmental conditions and maximize photosynthetic potential. However, 3-D structure is often ignored in ecological studies because it is difficult to characterize using traditional field methods. Terrestrial laser scanning (TLS) is a rapidly maturing technique to complement and enhance traditional field methods for quantifying 3-D geometric properties of ecosystems. Two major limitations of TLS include the low temporal resolution that often exists between each data acquisition, and the relatively high cost of such systems (entry level systems cost >$40,000 USD) that puts this method out of reach for many potential users. Consequently, TLS is currently limited as a mainstream method for capturing 3-D geometric ecosystem dynamics. Over the last several years, we have been developing a field-ready autonomously operating terrestrial laser scanner (ATLS) capable of monitoring fine-scale changes in vegetation structure on a daily time-step. We will present an overview of recent findings using the ATLS to track changes in vegetation structure in low-stature ecosystems - from cropping system dynamics to Arctic tundra phenology. Further, we will discuss the potential for laser intensity return information from both an ATLS and TLS to track changes in plant phenology and physiology (Chlorophyll content, photoprotective mechanisms, moisture) that occur simultaneously - or prior to - changes in vegetation structure. Our results suggest that fine-scale mapping of plant structure, phenology, and physiology using information from TLS and ATLS could provide new insights into vegetation dynamics in space and time.

  4. Biostabilization of cohesive sediments: revisiting the role of abiotic conditions, physiology and diversity of microbes, polymeric secretion, and biofilm architecture.

    PubMed

    Gerbersdorf, S U; Wieprecht, S

    2015-01-01

    In aquatic habitats, micro-organisms successfully adhere to and mediate particles, thus changing the erosive response of fine sediments to hydrodynamic forcing by secreting glue-like extracellular polymeric substances (EPS). Because sediment dynamics is vital for many ecological and economic aspects of watersheds and coastal regions, biostabilization of cohesive sediments is one of the important ecosystem services provided by biofilms. Although the research on biostabilization has gained momentum over the last 20 years, we still have limited insights principally due to the complex nature of this topic, the varying spatial, temporal, and community scales examined, oversimplified ecohydraulic experiments with little natural relevance, and the often partial views of the disciplines involved. This review highlights the current state of our knowledge on biostabilization and identifies important areas for future research on: (A) the influence of abiotic conditions on initial colonization and subsequent biofilm growth, focusing on hydrodynamics, substratum, salinity, nutrition, and light climate; (B) the response of microbes in terms of physiological activity and species diversity to environmental settings as well as biotic conditions such as competition and grazing; and (C) the effects of the former on the EPS matrix, its main constituents, their composition, functional groups/substitutes, and structures/linkages. The review focuses specifically on how the numerous mutual feedback mechanisms between abiotic and biotic conditions influence microbial stabilization capacity, and thus cohesive sediment dynamics.

  5. Physiological and Pathological Aging Affects Chromatin Dynamics, Structure and Function at the Nuclear Edge

    PubMed Central

    Robin, Jérôme D.; Magdinier, Frédérique

    2016-01-01

    Lamins are intermediate filaments that form a complex meshwork at the inner nuclear membrane. Mammalian cells express two types of Lamins, Lamins A/C and Lamins B, encoded by three different genes, LMNA, LMNB1, and LMNB2. Mutations in the LMNA gene are associated with a group of phenotypically diverse diseases referred to as laminopathies. Lamins interact with a large number of binding partners including proteins of the nuclear envelope but also chromatin-associated factors. Lamins not only constitute a scaffold for nuclear shape, rigidity and resistance to stress but also contribute to the organization of chromatin and chromosomal domains. We will discuss here the impact of A-type Lamins loss on alterations of chromatin organization and formation of chromatin domains and how disorganization of the lamina contributes to the patho-physiology of premature aging syndromes.

  6. Physiological and Pathological Aging Affects Chromatin Dynamics, Structure and Function at the Nuclear Edge.

    PubMed

    Robin, Jérôme D; Magdinier, Frédérique

    2016-01-01

    Lamins are intermediate filaments that form a complex meshwork at the inner nuclear membrane. Mammalian cells express two types of Lamins, Lamins A/C and Lamins B, encoded by three different genes, LMNA, LMNB1, and LMNB2. Mutations in the LMNA gene are associated with a group of phenotypically diverse diseases referred to as laminopathies. Lamins interact with a large number of binding partners including proteins of the nuclear envelope but also chromatin-associated factors. Lamins not only constitute a scaffold for nuclear shape, rigidity and resistance to stress but also contribute to the organization of chromatin and chromosomal domains. We will discuss here the impact of A-type Lamins loss on alterations of chromatin organization and formation of chromatin domains and how disorganization of the lamina contributes to the patho-physiology of premature aging syndromes. PMID:27602048

  7. Physiological and Pathological Aging Affects Chromatin Dynamics, Structure and Function at the Nuclear Edge

    PubMed Central

    Robin, Jérôme D.; Magdinier, Frédérique

    2016-01-01

    Lamins are intermediate filaments that form a complex meshwork at the inner nuclear membrane. Mammalian cells express two types of Lamins, Lamins A/C and Lamins B, encoded by three different genes, LMNA, LMNB1, and LMNB2. Mutations in the LMNA gene are associated with a group of phenotypically diverse diseases referred to as laminopathies. Lamins interact with a large number of binding partners including proteins of the nuclear envelope but also chromatin-associated factors. Lamins not only constitute a scaffold for nuclear shape, rigidity and resistance to stress but also contribute to the organization of chromatin and chromosomal domains. We will discuss here the impact of A-type Lamins loss on alterations of chromatin organization and formation of chromatin domains and how disorganization of the lamina contributes to the patho-physiology of premature aging syndromes. PMID:27602048

  8. The regulatory role of the tetrapeptide AcSDKP in skin and hair physiology and the prevention of ageing effects in these tissues--a potential cosmetic role.

    PubMed

    Hajem, N; Chapelle, A; Bignon, J; Pinault, A; Liu, J-M; Salah-Mohellibi, N; Lati, E; Wdzieczak-Bakala, J

    2013-06-01

    The naturally occurring tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) recognized as a potent angiogenic factor was shown recently to contribute to the repair of cutaneous injuries. In the current article, we report the ability of AcSDKP to exert a beneficial effect on normal healthy skin and scalp and to compensate for the ageing process. In vitro AcSDKP at 10⁻¹¹-10⁻⁷ M significantly stimulates the growth of human keratinocytes, fibroblasts and follicle dermal papilla cells. Moreover, it enhances the growth of human epidermal keratinocyte progenitor and stem cells as shown in a clonogenic survival assay. Topical treatment of ex vivo cultured skin explants with 10⁻⁵ M AcSDKP increases the thickness of the epidermis and upregulates the synthesis of keratins 14 and 19, fibronectin, collagen III and IV as well as the glycoaminoglycans (GAGs). In the ex vivo-cultured hair follicles, AcSDKP promotes hair shaft elongation and induces morphological and molecular modifications matching the criteria of hair growth. Furthermore, AcSDKP at 10⁻¹¹-10⁻⁷ M was shown to improve epidermal barrier, stimulating expression of three protein components of tight junctions (claudin-1, occludin, ZO-1) playing an important role in connecting neighbouring cells. This tetrapeptide exercises also activation of SIRT1 implicated in the control of cell longevity. Indeed, a two-fold increase in the synthesis of SIRT1 by cultured keratinocytes was observed in the presence of 10⁻¹¹-10⁻⁷ M AcSDKP. In conclusion, these findings provide convincing evidence of the regulatory role of AcSDKP in skin and hair physiology and suggest a cosmetic use of this natural tetrapeptide to prevent skin ageing and hair loss and to promote the cutaneous regeneration and hair growth.

  9. The regulatory role of the tetrapeptide AcSDKP in skin and hair physiology and the prevention of ageing effects in these tissues--a potential cosmetic role.

    PubMed

    Hajem, N; Chapelle, A; Bignon, J; Pinault, A; Liu, J-M; Salah-Mohellibi, N; Lati, E; Wdzieczak-Bakala, J

    2013-06-01

    The naturally occurring tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) recognized as a potent angiogenic factor was shown recently to contribute to the repair of cutaneous injuries. In the current article, we report the ability of AcSDKP to exert a beneficial effect on normal healthy skin and scalp and to compensate for the ageing process. In vitro AcSDKP at 10⁻¹¹-10⁻⁷ M significantly stimulates the growth of human keratinocytes, fibroblasts and follicle dermal papilla cells. Moreover, it enhances the growth of human epidermal keratinocyte progenitor and stem cells as shown in a clonogenic survival assay. Topical treatment of ex vivo cultured skin explants with 10⁻⁵ M AcSDKP increases the thickness of the epidermis and upregulates the synthesis of keratins 14 and 19, fibronectin, collagen III and IV as well as the glycoaminoglycans (GAGs). In the ex vivo-cultured hair follicles, AcSDKP promotes hair shaft elongation and induces morphological and molecular modifications matching the criteria of hair growth. Furthermore, AcSDKP at 10⁻¹¹-10⁻⁷ M was shown to improve epidermal barrier, stimulating expression of three protein components of tight junctions (claudin-1, occludin, ZO-1) playing an important role in connecting neighbouring cells. This tetrapeptide exercises also activation of SIRT1 implicated in the control of cell longevity. Indeed, a two-fold increase in the synthesis of SIRT1 by cultured keratinocytes was observed in the presence of 10⁻¹¹-10⁻⁷ M AcSDKP. In conclusion, these findings provide convincing evidence of the regulatory role of AcSDKP in skin and hair physiology and suggest a cosmetic use of this natural tetrapeptide to prevent skin ageing and hair loss and to promote the cutaneous regeneration and hair growth. PMID:23488645

  10. Structural characteristics of thermosensitive chitosan glutamate hydrogels in variety of physiological environments

    NASA Astrophysics Data System (ADS)

    Modrzejewska, Z.; Nawrotek, K.; Maniukiewicz, W.; Douglas, T.

    2014-09-01

    In this paper the properties of thermosensitive chitosan hydrogels prepared with the use of chitosan glutamate and β-glycerophosphate are presented. The study is focused on the determination of changes in the hydrogel structure in different environments: during conditioning in water and buffer at pH 7 and pH 2 respectively. The structure of gels was observed under the Scanning Electron Microscopy (SEM) and was investigated by infrared (IR) spectroscopy. The crystallinity of gel structure was determined by X-ray diffraction analysis (XRD). On the basis of structural changes during the conditioning in water a mechanism of their formation was proposed.

  11. Evidence against a physiological role of prostaglandins in the regulation of noradrenaline release in the cat spleen.

    PubMed Central

    Dubocovich, M L; Langer, S Z

    1975-01-01

    1. The effects of prostaglandins E2 (PGE2) and indomethacin on responses and on noradrenaline overflow elicited by nerve stimulation were studied in the perfused cat's spleen, at different calcium concentrations in the perfusion medium: 0-26, 0-65 and 2-6 mve stimulation and in the overflow of the transmitter. PGE2 was more effective in reducing transmitter overflow at 5 than at 30 Hz. 3. Indomethacin, 14-0 muM, prevented the release of PGE-like material in the venous effluent of the spleen elicited by either nerve stimulation or by exogenous noradrenaline. 4. During exposure to 14-0 muM indomethacin there was no increase in responses to nerve stimulation or in the overflow of noradrenaline elicited by nerve stimulation at 5 or at 30 Hz. 5. Similar results to those obtained with exogenous PGE2 and with indomethacin in the presence of 2-6 mM calcium, were observed when the experiments were carried out in the presence of either 0-65 or 0-26 mM calcium. 6. In the presence of the alpha-adrenoceptor blocking agents, phenoxybenzamine (2-9 muM) or phentolamine (3-1 muM), the increase in transmitter overflow obtained during stimulation was 6-5 and 8-3-fold respectively. 7. Since inhibition of the synthesis of PGE did not increase transmitter overflow during nerve stimulation, it appears that the proposed negative feed-back mechanism mediated by endogenous prostaglandins does not play an important physiological role in the regulation of adrenergic neurotransmission in the cat spleen. In this tissue the major endogenous negative feed-back regulatory mechanism is triggered by the neurotransmitter through the activation of prejunctional alpha-adrenoceptors. PMID:171381

  12. Physiological roles of trehalose in Leptinotarsa larvae revealed by RNA interference of trehalose-6-phosphate synthase and trehalase genes.

    PubMed

    Shi, Ji-Feng; Xu, Qing-Yu; Sun, Qiang-Kun; Meng, Qing-Wei; Mu, Li-Li; Guo, Wen-Chao; Li, Guo-Qing

    2016-10-01

    Trehalose is proposed to serve multiple physiological roles in insects. However, its importance remains largely unconfirmed. In the present paper, we knocked down either a trehalose biosynthesis gene (trehalose-6-phosphate synthase, LdTPS) or each of three degradation genes (soluble trehalases LdTRE1a, LdTRE1b or membrane-bound LdTRE2) in Leptinotarsa decemlineata by RNA interference (RNAi). Knockdown of LdTPS decreased trehalose content and caused larval and pupal lethality. The LdTPS RNAi survivors consumed a greater amount of foliage, obtained a heavier body mass, accumulated more glycogen, lipid and proline, and had a smaller amount of chitin compared with the controls. Ingestion of trehalose but not glucose rescued the food consumption increase and larval mass rise, increased survivorship, and recovered glycogen, lipid and chitin to the normal levels. In contrast, silencing of LdTRE1a increased trehalose content and resulted in larval and pupal lethality. The surviving LdTRE1a RNAi hypomorphs fed a smaller quantity of food, had a lighter body weight, depleted lipid and several glucogenic amino acids, and contained a smaller amount of chitin. Neither trehalose nor glucose ingestion rescued these LdTRE1a RNAi defects. Silencing of LdTRE1b caused little effects. Knockdown of LdTRE2 caused larval death, increased trehalose contents in several tissues and diminished glycogen in the brain-corpora cardiaca-corpora allata complex (BCC). Feeding glucose but not trehalose partially rescued the high mortality rate and recovered glycogen content in the BCC. It seems that trehalose is involved in feeding regulation, sugar absorption, brain energy supply and chitin biosynthesis in L. decemlineata larvae. PMID:27524277

  13. Different Physiological Roles of ATP- and PPi-Dependent Phosphofructokinase Isoenzymes in the Methylotrophic Actinomycete Amycolatopsis methanolica

    PubMed Central

    Alves, A. M. C. R.; Euverink, G. J. W.; Santos, H.; Dijkhuizen, L.

    2001-01-01

    Cells of the actinomycete Amycolatopsis methanolica grown on glucose possess only a single, exclusively PPi-dependent phosphofructokinase (PPi-PFK) (A. M. C. R. Alves, G. J. W. Euverink, H. J. Hektor, J. van der Vlag, W. Vrijbloed, D.H.A. Hondmann, J. Visser, and L. Dijkhuizen, J. Bacteriol. 176:6827–6835, 1994). When this methylotrophic bacterium is grown on one-carbon (C1) compounds (e.g., methanol), an ATP-dependent phosphofructokinase (ATP-PFK) activity is specifically induced, completely replacing the PPi-PFK. The two A. methanolica PFK isoenzymes have very distinct functions, namely, in the metabolism of C6 and C1 carbon substrates. This is the first report providing biochemical evidence for the presence and physiological roles of PPi-PFK and ATP-PFK isoenzymes in a bacterium. The novel ATP-PFK enzyme was purified to homogeneity and characterized in detail at the biochemical and molecular levels. The A. methanolica ATP-PFK and PPi-PFK proteins possess a low level of amino acid sequence similarity (24%), clearly showing that the two proteins are not the result of a gene duplication event. PPi-PFK is closely related to other (putative) actinomycete PFK enzymes. Surprisingly, the A. methanolica ATP-PFK is most similar to ATP-PFK from the protozoon Trypanosoma brucei and PPi-PFK proteins from the bacteria Borrelia burgdorferi and Treponema pallidum, both spirochetes, very distinct from actinomycetes. The data thus suggest that A. methanolica obtained the ATP-PFK-encoding gene via a lateral gene transfer event. PMID:11717283

  14. Established and potential physiological roles of bicarbonate-sensing soluble adenylyl cyclase (sAC) in aquatic animals

    PubMed Central

    Tresguerres, Martin; Barott, Katie L.; Barron, Megan E.; Roa, Jinae N.

    2014-01-01

    Soluble adenylyl cyclase (sAC) is a recently recognized source of the signaling molecule cyclic AMP (cAMP) that is genetically and biochemically distinct from the classic G-protein-regulated transmembrane adenylyl cyclases (tmACs). Mammalian sAC is distributed throughout the cytoplasm and it may be present in the nucleus and inside mitochondria. sAC activity is directly stimulated by HCO3−, and sAC has been confirmed to be a HCO3− sensor in a variety of mammalian cell types. In addition, sAC can functionally associate with carbonic anhydrases to act as a de facto sensor of pH and CO2. The two catalytic domains of sAC are related to HCO3−-regulated adenylyl cyclases from cyanobacteria, suggesting the cAMP pathway is an evolutionarily conserved mechanism for sensing CO2 levels and/or acid/base conditions. Reports of sAC in aquatic animals are still limited but are rapidly accumulating. In shark gills, sAC senses blood alkalosis and triggers compensatory H+ absorption. In the intestine of bony fishes, sAC modulates NaCl and water absorption. And in sea urchin sperm, sAC may participate in the initiation of flagellar movement and in the acrosome reaction. Bioinformatics and RT-PCR results reveal that sAC orthologs are present in most animal phyla. This review summarizes the current knowledge on the physiological roles of sAC in aquatic animals and suggests additional functions in which sAC may be involved. PMID:24574382

  15. Established and potential physiological roles of bicarbonate-sensing soluble adenylyl cyclase (sAC) in aquatic animals.

    PubMed

    Tresguerres, Martin; Barott, Katie L; Barron, Megan E; Roa, Jinae N

    2014-03-01

    Soluble adenylyl cyclase (sAC) is a recently recognized source of the signaling molecule cyclic AMP (cAMP) that is genetically and biochemically distinct from the classic G-protein-regulated transmembrane adenylyl cyclases (tmACs). Mammalian sAC is distributed throughout the cytoplasm and it may be present in the nucleus and inside mitochondria. sAC activity is directly stimulated by HCO3(-), and sAC has been confirmed to be a HCO3(-) sensor in a variety of mammalian cell types. In addition, sAC can functionally associate with carbonic anhydrases to act as a de facto sensor of pH and CO2. The two catalytic domains of sAC are related to HCO3(-)-regulated adenylyl cyclases from cyanobacteria, suggesting the cAMP pathway is an evolutionarily conserved mechanism for sensing CO2 levels and/or acid/base conditions. Reports of sAC in aquatic animals are still limited but are rapidly accumulating. In shark gills, sAC senses blood alkalosis and triggers compensatory H(+) absorption. In the intestine of bony fishes, sAC modulates NaCl and water absorption. And in sea urchin sperm, sAC may participate in the initiation of flagellar movement and in the acrosome reaction. Bioinformatics and RT-PCR results reveal that sAC orthologs are present in most animal phyla. This review summarizes the current knowledge on the physiological roles of sAC in aquatic animals and suggests additional functions in which sAC may be involved. PMID:24574382

  16. Sulfuric acid-induced changes in the physiology and structure of the tracheobronchial airways.

    PubMed

    Gearhart, J M; Schlesinger, R B

    1989-02-01

    Sulfuric acid aerosols occur in the ambient particulate mode due to atmospheric conversion from sulfur dioxide (SO2). This paper describes the response of the rabbit tracheobronchial tree to daily exposures to sulfuric acid (H2SO4) aerosol, relating physiological and morphological parameters. Rabbits were exposed to filtered air (sham control) or to submicrometer-sized H2SO4 at 250 micrograms/m3 H2SO4, for 1 hr/day, 5 days/week, with sacrifices after 4, 8, and 12 months of acid (or sham) exposure; some rabbits were allowed a 3-month recovery after all exposures ended. H2SO4 produced a slowing of tracheobronchial mucociliary clearance during the first weeks of exposure; this change became significantly greater with continued exposures and did not improve after exposures ended. Airway hyperresponsiveness was evident by 4 months of acid exposure; the condition worsened by 8 months of exposure and appeared to stabilize after this time. Standard pulmonary mechanics parameters showed no significant trends with repeated acid exposure, except for a decline in dynamic lung compliance in animals exposed to acid for 12 months. Lung tissue samples obtained from exposed animals showed a shift toward a greater frequency of smaller airways compared to control, an increase in epithelial secretory cell density in smaller airways, and a shift from neutral to acidic glycoproteins in the secretory cells. The effect on airway diameter resolved after the exposures ceased, but the secretory cell response did not return to normal within the recovery period. No evidence of inflammatory cell infiltration was found due to H2SO4 exposure. Thus, significant alterations in the physiology of the tracheobronchial tree have been demonstrated due to repeated 1-hr exposures to a concentration of H2SO4 that is one-fourth the current 8-hr threshold limit value for exposure in the work environment. The cumulative dose inhaled by the rabbits is similar to current peak daily doses from ambient exposure

  17. Physiological stress reactivity and physical and relational aggression: the moderating roles of victimization, type of stressor, and child gender.

    PubMed

    Murray-Close, Dianna; Crick, Nicki R; Tseng, Wan-Ling; Lafko, Nicole; Burrows, Casey; Pitula, Clio; Ralston, Peter

    2014-08-01

    The purpose of the present investigation was to examine the association between physiological reactivity to peer stressors and physical and relational aggression. Potential moderation by actual experiences of peer maltreatment (i.e., physical and relational victimization) and gender were also explored. One hundred ninety-six children (M = 10.11 years, SD = 0.64) participated in a laboratory stress protocol during which their systolic blood pressure, diastolic blood pressure, and skin conductance reactivity to recounting a relational stressor (e.g., threats to relationships) and an instrumental stressor (e.g., threats to physical well-being, dominance, or property) were assessed. Teachers provided reports of aggression and victimization. In both boys and girls, physical aggression was associated with blunted physiological reactivity to relational stress and heightened physiological reactivity to instrumental stress, particularly among youth higher in victimization. In girls, relational aggression was most robustly associated with blunted physiological reactivity to relational stressors, particularly among girls exhibiting higher levels of relational victimization. In boys, relational aggression was associated with heightened physiological reactivity to both types of stressors at higher levels of peer victimization and blunted physiological reactivity to both types of stressors at lower levels of victimization. Results underscore the shared and distinct emotional processes underlying physical and relational aggression in boys and girls.

  18. The roles of vegetation structure and composition in terrestrial ecosystem responses to climate change

    NASA Astrophysics Data System (ADS)

    Weng, E.; Lichstein, J. W.; Malyshev, S.; Shevliakova, E.; Pacala, S. W.

    2011-12-01

    Vegetation structure, species compositions, and interactions among individuals change with the development of ecosystems. The sensitivity of ecosystems to climate change is therefore differed. However, current dynamic global vegetation models treat vegetation as a couple of compartmentalized pools and neglect the details of vegetation dynamics with only explicitly representations of physiological and biogeochemical processes. These may lead to bias in the predictions of ecosystem dynamics in response to climate change. We incorporated a vegetation structure model, perfect plasticity approximation model (PPA), into a land model, LM3V, the land component of GFDL ESM, and explored the sensitivity and uncertainty induced by the structure of forest ecosystems in Northeastern USA, where the PPA model explicitly describes the competition of light and resources from soil (water or nitrogen) among plant species and the resulted vegetation structure with different environmental conditions and LM3V is a biogeochemical model describing carbon and water fluxes and storage in ecosystems and their feedback to atmosphere. We employed the rules of PPA to represent the vegetation dynamics (species composition, competition for light and water, and vegetation structure) in LM3V. The simulations showed that vegetation structure and the interactions between species could substantially affect the sensitivity of ecosystem carbon cycle to multi-factorial changes of climate. With changes in vegetation compositions and structure, ecosystem responses were less sensitive than those when only plant physiological and biogeochemical responses were considered. Our study shows that the processes at plant community level play a key role in mid- to long term ecosystem responses to climate change.

  19. Human ABCG2: structure, function, and its role in multidrug resistance

    PubMed Central

    Mo, Wei; Zhang, Jian-Ting

    2012-01-01

    Human ABCG2 is a member of the ATP-binding cassette (ABC) transporter superfamily and is known to contribute to multidrug resistance (MDR) in cancer chemotherapy. Among ABC transporters that are known to cause MDR, ABCG2 is particularly interesting for its potential role in protecting cancer stem cells and its complex oligomeric structure. Recent studies have also revealed that the biogenesis of ABCG2 could be modulated by small molecule compounds. These modulators, upon binding to ABCG2, accelerate the endocytosis and trafficking to lysosome for degradation and effectively reduce the half-life of ABCG2. Hence, targeting ABCG2 stability could be a new venue for therapeutic discovery to sensitize drug resistant human cancers. In this report, we review recent progress on understanding the structure, function, biogenesis, as well as physiological and pathophysiological functions of ABCG2. PMID:22509477

  20. Role of structural holes in containing spreading processes.

    PubMed

    Li, Ping; Sun, Xian; Zhang, Kai; Zhang, Jie; Kurths, Jürgen

    2016-03-01

    Structural holes are channels or paths spanned by a group of indirectly connected nodes and their intermediary in a network. In this work we emphasize the interesting role of structural holes as brokers for information propagation. Based on the distribution of the structural hole numbers associated with each node, we propose a simple yet effective approach for choosing the most influential nodes to immunize in containing the spreading processes. Using a wide spectrum of large real-world networks, we demonstrate that the proposed approach outperforms conventional methods in a remarkable way. In particular, we find that the performance gains of our approach are particularly prominent for networks with high transitivity and assortativity, which verifies the vital role of structural holes in information diffusion on networked systems. PMID:27078371

  1. α-Glucosidases and α-1,4-glucan lyases: structures, functions, and physiological actions.

    PubMed

    Okuyama, Masayuki; Saburi, Wataru; Mori, Haruhide; Kimura, Atsuo

    2016-07-01

    α-Glucosidases (AGases) and α-1,4-glucan lyases (GLases) catalyze the degradation of α-glucosidic linkages at the non-reducing ends of substrates to release α-glucose and anhydrofructose, respectively. The AGases belong to glycoside hydrolase (GH) families 13 and 31, and the GLases belong to GH31 and share the same structural fold with GH31 AGases. GH13 and GH31 AGases show diverse functions upon the hydrolysis of substrates, having linkage specificities and size preferences, as well as upon transglucosylation, forming specific α-glucosidic linkages. The crystal structures of both enzymes were determined using free and ligand-bound forms, which enabled us to understand the important structural elements responsible for the diverse functions. A series of mutational approaches revealed features of the structural elements. In particular, amino-acid residues in plus subsites are of significance, because they regulate transglucosylation, which is used in the production of industrially valuable oligosaccharides. The recently solved three-dimensional structure of GLase from red seaweed revealed the amino-acid residues essential for lyase activity and the strict recognition of the α-(1 → 4)-glucosidic substrate linkage. The former was introduced to the GH31 AGase, and the resultant mutant displayed GLase activity. GH13 and GH31 AGases hydrate anhydrofructose to produce glucose, suggesting that AGases are involved in the catabolic pathway used to salvage unutilized anhydrofructose. PMID:27137181

  2. Perspective: Role of structure prediction in materials discovery and design

    NASA Astrophysics Data System (ADS)

    Needs, Richard J.; Pickard, Chris J.

    2016-05-01

    Materials informatics owes much to bioinformatics and the Materials Genome Initiative has been inspired by the Human Genome Project. But there is more to bioinformatics than genomes, and the same is true for materials informatics. Here we describe the rapidly expanding role of searching for structures of materials using first-principles electronic-structure methods. Structure searching has played an important part in unraveling structures of dense hydrogen and in identifying the record-high-temperature superconducting component in hydrogen sulfide at high pressures. We suggest that first-principles structure searching has already demonstrated its ability to determine structures of a wide range of materials and that it will play a central and increasing part in materials discovery and design.

  3. Physiological roles of the light, oxygen, or voltage domains of phototropin 1 and phototropin 2 in Arabidopsis.

    PubMed

    Cho, Hae-Young; Tseng, Tong-Seung; Kaiserli, Eirini; Sullivan, Stuart; Christie, John M; Briggs, Winslow R

    2007-01-01

    Phototropins (phot1 and phot2) are plant blue-light receptors that mediate phototropism, chloroplast movement, stomatal opening, rapid inhibition of growth of etiolated seedlings, and leaf expansion in Arabidopsis (Arabidopsis thaliana). Their N-terminal region contains two light, oxygen, or voltage (LOV) domains, which bind flavin mononucleotide and form a covalent adduct between a conserved cysteine and the flavin mononucleotide chromophore upon photoexcitation. The C-terminal region contains a serine/threonine kinase domain that catalyzes blue-light-activated autophosphorylation. Here, we have transformed the phot1 phot2 (phot1-5 phot2-1) double mutant with PHOT expression constructs driven by the cauliflower mosaic virus 35S promoter. These constructs encode either wild-type phototropin or phototropin with one or both LOV-domain cysteines mutated to block their photochemistry. We selected multiple lines in each of the eight resulting categories of transformants for further physiological analyses. Specifically, we investigated whether LOV1 and LOV2 serve the same or different functions for phototropism and leaf expansion. Our results show that the LOV2 domain of phot1 plays a major role in phototropism and leaf expansion, as does the LOV2 domain of phot2. No complementation of phototropism or leaf expansion was observed for the LOV1 domain of phot1. However, phot2 LOV1 was unexpectedly found to complement phototropism to a considerable level. Similarly, transformants carrying a PHOT transgene with both LOV domains inactivated developed strong curvatures toward high fluence rate blue light. However, we found that the phot2-1 mutant is leaky and produces a small level of full-length phot2 protein. In vitro experiments indicate that cross phosphorylation can occur between functional phot2 and inactivated phot1 molecules. Such a mechanism may occur in vivo and therefore account for the functional activities observed in the PHOT transgenics with both lov domains

  4. Listening to music and physiological and psychological functioning: the mediating role of emotion regulation and stress reactivity.

    PubMed

    Thoma, M V; Scholz, U; Ehlert, U; Nater, U M

    2012-01-01

    Music listening has been suggested to have short-term beneficial effects. The aim of this study was to investigate the association and potential mediating mechanisms between various aspects of habitual music-listening behaviour and physiological and psychological functioning. An internet-based survey was conducted in university students, measuring habitual music-listening behaviour, emotion regulation, stress reactivity, as well as physiological and psychological functioning. A total of 1230 individuals (mean = 24.89 ± 5.34 years, 55.3% women) completed the questionnaire. Quantitative aspects of habitual music-listening behaviour, i.e. average duration of music listening and subjective relevance of music, were not associated with physiological and psychological functioning. In contrast, qualitative aspects, i.e. reasons for listening (especially 'reducing loneliness and aggression', and 'arousing or intensifying specific emotions') were significantly related to physiological and psychological functioning (all p = 0.001). These direct effects were mediated by distress-augmenting emotion regulation and individual stress reactivity. The habitual music-listening behaviour appears to be a multifaceted behaviour that is further influenced by dispositions that are usually not related to music listening. Consequently, habitual music-listening behaviour is not obviously linked to physiological and psychological functioning.

  5. Biochemistry and control of the reductive tricarboxylic acid pathway of CO2 fixation and physiological role of the Rubis CO-like protein

    SciTech Connect

    Tabita, F. Robert

    2008-12-04

    During the past years of this project we have made progress relative to the two major goals of the proposal: (1) to study the biochemistry and regulation of the reductive TCA cycle of CO2 fixation and (2) to probe the physiological role of a RubisCO-like protein (RLP). Both studies primarily employ the green sulfur bacterium Chlorobium tepidum as well as other photosynthetic bacteria including Rhodospirillum rubrum and Rhodopseudomonas palustris.

  6. Organizational Structuring of Sex Roles in a Nonstereotyped Industry

    ERIC Educational Resources Information Center

    Mennerick, Lewis A.

    1975-01-01

    Examines the occupation of travel agent, an occupation that is not sex-role stereotyped. Six measures were developed, revealing the existence of sex structuring of men and women in management and sales positions both among and within New York City travel agencies. (Author)

  7. Narrating Data Structures: The Role of Context in CS2

    ERIC Educational Resources Information Center

    Yarosh, Svetlana; Guzdial, Mark

    2008-01-01

    Learning computing with respect to the context of its use has been linked in previous reports to student motivation in introductory Computer Science (CS) courses. In this report, we consider the role of context in a second course. We present a case study of a CS2 data structures class that uses a media computation context. In this course, students…

  8. Coping with Unemployment: Personality, Role Demands, and Time Structure

    ERIC Educational Resources Information Center

    Van Hoye, Greet; Lootens, Hanne

    2013-01-01

    Time structure has been found to be an important coping mechanism for dealing with the negative effects of unemployment on psychological well-being. This study extends the literature by investigating personality (openness to experience, conscientiousness, extraversion, neuroticism, and proactivity) and role demands (marital status, being the only…

  9. Interactions of drought and shade effects on seedlings of four Quercus species: physiological and structural leaf responses.

    PubMed

    Quero, José Luis; Villar, Rafael; Marañón, Teodoro; Zamora, Regino

    2006-01-01

    Here, we investigated the physiological and structural leaf responses of seedlings of two evergreen and two deciduous Quercus species, grown in a glasshouse and subjected to contrasted conditions of light (low, medium and high irradiance) and water (continuous watering vs 2-months drought). The impact of drought on photosynthetic rate was strongest in high irradiance, while the impact of shade on photosynthetic rate was strongest with high water supply, contradicting the hypothesis of allocation trade-off. Multivariate causal models were evaluated using d-sep method. The model that best fitted the dataset proposed that the variation in specific leaf area affects photosynthetic rate and leaf nitrogen concentration, and this trait determines stomatal conductance, which also affects photosynthetic rate. Shade conditions seemed to ameliorate, or at least not aggravate, the drought impact on oak seedlings, therefore, the drought response on leaf performance depended on the light environment. PMID:16684241

  10. Genotypic Variation in Growth and Physiological Response to Drought Stress and Re-Watering Reveals the Critical Role of Recovery in Drought Adaptation in Maize Seedlings.

    PubMed

    Chen, Daoqian; Wang, Shiwen; Cao, Beibei; Cao, Dan; Leng, Guohui; Li, Hongbing; Yin, Lina; Shan, Lun; Deng, Xiping

    2015-01-01

    Non-irrigated crops in temperate climates and irrigated crops in arid climates are subjected to continuous cycles of water stress and re-watering. Thus, fast and efficient recovery from water stress may be among the key determinants of plant drought adaptation. The present study was designed to comparatively analyze the roles of drought resistance and drought recovery in drought adaptation and to investigate the physiological basis of genotypic variation in drought adaptation in maize (Zea mays) seedlings. As the seedlings behavior in growth associate with yield under drought, it could partly reflect the potential of drought adaptability. Growth and physiological responses to progressive drought stress and recovery were observed in seedlings of 10 maize lines. The results showed that drought adaptability is closely related to drought recovery (r = 0.714(**)), but not to drought resistance (r = 0.332). Drought induced decreases in leaf water content, water potential, osmotic potential, gas exchange parameters, chlorophyll content, Fv/Fm and nitrogen content, and increased H2O2 accumulation and lipid peroxidation. After recovery, most of these physiological parameters rapidly returned to normal levels. The physiological responses varied between lines. Further correlation analysis indicated that the physiological bases of drought resistance and drought recovery are definitely different, and that maintaining higher chlorophyll content (r = 0.874(***)) and Fv/Fm (r = 0.626(*)) under drought stress contributes to drought recovery. Our results suggest that both drought resistance and recovery are key determinants of plant drought adaptation, and that drought recovery may play a more important role than previously thought. In addition, leaf water potential, chlorophyll content and Fv/Fm could be used as efficient reference indicators in the selection of drought-adaptive genotypes. PMID:26793218

  11. Genotypic Variation in Growth and Physiological Response to Drought Stress and Re-Watering Reveals the Critical Role of Recovery in Drought Adaptation in Maize Seedlings

    PubMed Central

    Chen, Daoqian; Wang, Shiwen; Cao, Beibei; Cao, Dan; Leng, Guohui; Li, Hongbing; Yin, Lina; Shan, Lun; Deng, Xiping

    2016-01-01

    Non-irrigated crops in temperate climates and irrigated crops in arid climates are subjected to continuous cycles of water stress and re-watering. Thus, fast and efficient recovery from water stress may be among the key determinants of plant drought adaptation. The present study was designed to comparatively analyze the roles of drought resistance and drought recovery in drought adaptation and to investigate the physiological basis of genotypic variation in drought adaptation in maize (Zea mays) seedlings. As the seedlings behavior in growth associate with yield under drought, it could partly reflect the potential of drought adaptability. Growth and physiological responses to progressive drought stress and recovery were observed in seedlings of 10 maize lines. The results showed that drought adaptability is closely related to drought recovery (r = 0.714**), but not to drought resistance (r = 0.332). Drought induced decreases in leaf water content, water potential, osmotic potential, gas exchange parameters, chlorophyll content, Fv/Fm and nitrogen content, and increased H2O2 accumulation and lipid peroxidation. After recovery, most of these physiological parameters rapidly returned to normal levels. The physiological responses varied between lines. Further correlation analysis indicated that the physiological bases of drought resistance and drought recovery are definitely different, and that maintaining higher chlorophyll content (r = 0.874***) and Fv/Fm (r = 0.626*) under drought stress contributes to drought recovery. Our results suggest that both drought resistance and recovery are key determinants of plant drought adaptation, and that drought recovery may play a more important role than previously thought. In addition, leaf water potential, chlorophyll content and Fv/Fm could be used as efficient reference indicators in the selection of drought-adaptive genotypes. PMID:26793218

  12. Structures and functions of insect arylalkylamine N-acetyltransferase (iaaNAT); a key enzyme for physiological and behavioral switch in arthropods

    PubMed Central

    Hiragaki, Susumu; Suzuki, Takeshi; Mohamed, Ahmed A. M.; Takeda, Makio

    2015-01-01

    The evolution of N-acetyltransfeases (NATs) seems complex. Vertebrate arylalkylamine N-acetyltransferase (aaNAT) has been extensively studied since it leads to the synthesis of melatonin, a multifunctional neurohormone prevalent in photoreceptor cells, and is known as a chemical token of the night. Melatonin also serves as a scavenger for reactive oxygen species. This is also true with invertebrates. NAT therefore has distinct functional implications in circadian function, as timezymes (aaNAT), and also xenobiotic reactions (arylamine NAT or simply NAT). NATs belong to a broader enzyme group, the GCN5-related N-acetyltransferase superfamily. Due to low sequence homology and a seemingly fast rate of structural differentiation, the nomenclature for NATs can be confusing. The advent of bioinformatics, however, has helped to classify this group of enzymes; vertebrates have two distinct subgroups, the timezyme type and the xenobiotic type, which has a wider substrate range including imidazolamine, pharmacological drugs, environmental toxicants and even histone. Insect aaNAT (iaaNAT) form their own clade in the phylogeny, distinct from vertebrate aaNATs. Arthropods are unique, since the phylum has exoskeleton in which quinones derived from N-acetylated monoamines function in coupling chitin and arthropodins. Monoamine oxidase (MAO) activity is limited in insects, but NAT-mediated degradation prevails. However, unexpectedly iaaNAT occurs not only among arthropods but also among basal deuterostomia, and is therefore more apomorphic. Our analyses illustrate that iaaNATs has unique physiological roles but at the same time it plays a role in a timezyme function, at least in photoperiodism. Photoperiodism has been considered as a function of circadian system but the detailed molecular mechanism is not well understood. We propose a molecular hypothesis for photoperiodism in Antheraea pernyi based on the transcription regulation of NAT interlocked by the circadian system

  13. Specificity and Ligand Affinities of the Cocaine Aptamer: Impact of Structural Features and Physiological NaCl.

    PubMed

    Sachan, Ashish; Ilgu, Muslum; Kempema, Aaron; Kraus, George A; Nilsen-Hamilton, Marit

    2016-08-01

    The cocaine aptamer has been seen as a good candidate for development as a probe for cocaine in many contexts. Here, we demonstrate that the aptamer binds cocaine, norcocaine, and cocaethylene with similar affinities and aminoglycosides with similar or higher affinities in a mutually exclusive manner with cocaine. Analysis of its affinities for a series of cocaine derivatives shows that the aptamer specificity is the consequence of its interaction with all faces of the cocaine molecule. Circular dichroism spectroscopy and 2-aminopurine (2AP) fluorescence studies show no evidence of large structural rearrangement of the cocaine aptamer upon ligand binding, which is contrary to the general view of this aptamer. The aptamer's affinity for cocaine and neomycin-B decreases with the inclusion of physiological NaCl. The substitution of 2AP for A in position 6 (2AP6) of the aptamer sequence eliminated the effect of NaCl on its affinities for cocaine and analogues, but not for neomycin-B, showing a selective effect of 2AP substitution on cocaine binding. The affinity for cocaine also decreased with increasing concentrations of serum or urine, with the 2AP6 substitution blunting the effect of urine. Its low affinities for cocaine and metabolites and its ability to bind irrelevant compounds limit the opportunities for application of this aptamer in its current form as a selective and reliable sensor for cocaine. However, these studies also show that a small structural adjustment to the aptamer (2AP exchanged for adenine) can increase its specificity for cocaine in physiological NaCl relative to an off-target ligand.

  14. Specificity and Ligand Affinities of the Cocaine Aptamer: Impact of Structural Features and Physiological NaCl.

    PubMed

    Sachan, Ashish; Ilgu, Muslum; Kempema, Aaron; Kraus, George A; Nilsen-Hamilton, Marit

    2016-08-01

    The cocaine aptamer has been seen as a good candidate for development as a probe for cocaine in many contexts. Here, we demonstrate that the aptamer binds cocaine, norcocaine, and cocaethylene with similar affinities and aminoglycosides with similar or higher affinities in a mutually exclusive manner with cocaine. Analysis of its affinities for a series of cocaine derivatives shows that the aptamer specificity is the consequence of its interaction with all faces of the cocaine molecule. Circular dichroism spectroscopy and 2-aminopurine (2AP) fluorescence studies show no evidence of large structural rearrangement of the cocaine aptamer upon ligand binding, which is contrary to the general view of this aptamer. The aptamer's affinity for cocaine and neomycin-B decreases with the inclusion of physiological NaCl. The substitution of 2AP for A in position 6 (2AP6) of the aptamer sequence eliminated the effect of NaCl on its affinities for cocaine and analogues, but not for neomycin-B, showing a selective effect of 2AP substitution on cocaine binding. The affinity for cocaine also decreased with increasing concentrations of serum or urine, with the 2AP6 substitution blunting the effect of urine. Its low affinities for cocaine and metabolites and its ability to bind irrelevant compounds limit the opportunities for application of this aptamer in its current form as a selective and reliable sensor for cocaine. However, these studies also show that a small structural adjustment to the aptamer (2AP exchanged for adenine) can increase its specificity for cocaine in physiological NaCl relative to an off-target ligand. PMID:27348073

  15. MBBS student perceptions about physiology subject teaching and objective structured practical examination based formative assessment for improving competencies.

    PubMed

    Lakshmipathy, K

    2015-09-01

    The objectives of the present study were to 1) assess student attitudes to physiology, 2) evaluate student opinions about the influence of an objective structured practical examination (OSPE) on competence, and 3) assess the validity and reliability of an indigenously designed feedback questionnaire. A structured questionnaire containing 16 item statements, 8 items on an Osgood's 5-point semantic differential scale and 8 items on a Likert's 5-point scale, was used. Options were assigned scores of 1-5 according to weightage. For Osgood's semantic differential scale items, a χ(2)-test was done to analyze student attitudes toward the subject. For Likert scale items, mean score and SD were calculated to analyze student opinions of the OSPE. Item validity was assessed by item analysis, and reliability was assessed by calculating Crohnbach's α. The subject as a whole was interesting to 82% of the students (n = 135). The theory was interesting to 75% of the students (n = 132) but complex to 42% (n = 118). The practical was interesting to 93% of the students (n = 134); 76% of the students (n = 104) felt that the practical was simple, whereas 4% felt it was complex. The OSPE was interesting to 79% of the students (n = 131); 57% of the students (n = 116) felt it was simple, whereas 24% found it complex. Components of the subject, intricateness, and student interests were strongly associated. Students chose options on a higher weight scale, favoring the OSPE. Items were found to be valid and reliable. In conclusion, the subject of physiology was interesting but not simple to understand. Student interests varied with the components of the subject, and the components of the subject had varied intricateness. Students were in favor of the OSPE for assessment. The questionnaire used for the study was valid and reliable.

  16. Acyl Carrier Protein Synthases from Gram-Negative, Gram-Positive, and Atypical Bacterial Species: Biochemical and Structural Properties and Physiological Implications

    PubMed Central

    McAllister, Kelly A.; Peery, Robert B.; Zhao, Genshi

    2006-01-01

    Acyl carrier protein (ACP) synthase (AcpS) catalyzes the transfer of the 4′-phosphopantetheine moiety from coenzyme A (CoA) onto a serine residue of apo-ACP, resulting in the conversion of apo-ACP to the functional holo-ACP. The holo form of bacterial ACP plays an essential role in mediating the transfer of acyl fatty acid intermediates during the biosynthesis of fatty acids and phospholipids. AcpS is therefore an attractive target for therapeutic intervention. In this study, we have purified and characterized the AcpS enzymes from Escherichia coli, Streptococcus pneumoniae, and Mycoplasma pneumoniae, which exemplify gram-negative, gram-positive, and atypical bacteria, respectively. Our gel filtration column chromatography and cross-linking studies demonstrate that the AcpS enzyme from M. pneumoniae, like E. coli enzyme, exhibits a homodimeric structure, but the enzyme from S. pneumoniae exhibits a trimeric structure. Our biochemical studies show that the AcpS enzymes from M. pneumoniae and S. pneumoniae can utilize both short- and long-chain acyl CoA derivatives but prefer long-chain CoA derivatives as substrates. On the other hand, the AcpS enzyme from E. coli can utilize short-chain CoA derivatives but not the long-chain CoA derivatives tested. Finally, our biochemical studies show that M. pneumoniae AcpS is kinetically a very sluggish enzyme compared with those from E. coli and S. pneumoniae. Together, the results of these studies show that the AcpS enzymes from different bacterial species exhibit different native structures and substrate specificities with regard to the utilization of CoA and its derivatives. These findings suggest that AcpS from different microorganisms plays a different role in cellular physiology. PMID:16788183

  17. The urea transporter family (SLC14): physiological, pathological and structural aspects.

    PubMed

    Shayakul, Chairat; Clémençon, Benjamin; Hediger, Matthias A

    2013-01-01

    Urea transporters (UTs) belonging to the solute carrier 14 (SLC14) family comprise two genes with a total of eight isoforms in mammals, UT-A1 to -A6 encoded by SLC14A2 and UT-B1 to -B2 encoded by SLC14A1. Recent efforts have been directed toward understanding the molecular and cellular mechanisms involved in the regulation of UTs using transgenic mouse models and heterologous expression systems, leading to important new insights. Urea uptake by UT-A1 and UT-A3 in the kidney inner medullary collecting duct and by UT-B1 in the descending vasa recta for the countercurrent exchange system are chiefly responsible for medullary urea accumulation in the urinary concentration process. Vasopressin, an antidiuretic hormone, regulates UT-A isoforms via the phosphorylation and trafficking of the glycosylated transporters to the plasma membrane that occurs to maintain equilibrium with the exocytosis and ubiquitin-proteasome degradation pathways. UT-B isoforms are also important in several cellular functions, including urea nitrogen salvaging in the colon, nitric oxide pathway modulation in the hippocampus, and the normal cardiac conduction system. In addition, genomic linkage studies have revealed potential additional roles for SLC14A1 and SLC14A2 in hypertension and bladder carcinogenesis. The precise role of UT-A2 and presence of the urea recycling pathway in normal kidney are issues to be further explored. This review provides an update of these advances and their implications for our current understanding of the SLC14 UTs. PMID:23506873

  18. A new role for structures technology in aircraft configuration development

    NASA Technical Reports Server (NTRS)

    Nisbet, J. W.; Hoy, J. M.

    1976-01-01

    It is pointed out that decisions made during configuration development determine nearly 60% of the total program cost. The key to the new Structures Technology role considered is the development of integrated computer systems for structural design and analysis. Such systems make it possible to include structural sizing within the scope of preliminary configuration development. Analysis models are discussed, taking into account approaches used to determine the structural weight of an aircraft in the preliminary design stage, a finite element representation for a supersonic arrow wing transport, and the aerodynamic model. Attention is given to automated design considerations and a study which was conducted to reduce the aerodynamic drag of a supersonic transport by blending the structure of the wing and fuselage.

  19. Physiological tolerances account for range limits and abundance structure in an invasive slug.

    PubMed

    Lee, Jennifer E; Janion, Charlene; Marais, Elrike; Jansen van Vuuren, Bettine; Chown, Steven L

    2009-04-22

    Despite the importance of understanding the mechanisms underlying range limits and abundance structure, few studies have sought to do so. Here we use a terrestrial slug species, Deroceras panormitanum, that has invaded a remote, largely predator-free, Southern Ocean island as a model system to do so. Across Marion Island, slug density does not conform to an abundant centre distribution. Rather, abundance structure is characterized by patches and gaps. These are associated with this desiccation-sensitive species' preference for biotic and drainage line habitats that share few characteristics except for their high humidity below the vegetation surface. The coastal range margin has a threshold form, rapidly rising from zero to high density. Slugs do not occur where soil-exchangeable Na values are higher than 3000 mg kg(-1), and in laboratory experiments, survival is high below this value but negligible above it. Upper elevation range margins are a function of the inability of this species to survive temperatures below an absolute limit of -6.4 degrees C, which is regularly exceeded at 200 m altitude, above which slug density declines to zero. However, the linear decline in density from the coastal peak is probably also a function of a decline in performance or time available for activity. This is probably associated with an altitudinal decline in mean annual soil temperature. These findings support previous predictions made regarding the form of density change when substrate or climatic factors set range limits.

  20. Physiological tolerances account for range limits and abundance structure in an invasive slug

    PubMed Central

    Lee, Jennifer E.; Janion, Charlene; Marais, Elrike; Jansen van Vuuren, Bettine; Chown, Steven L.

    2009-01-01

    Despite the importance of understanding the mechanisms underlying range limits and abundance structure, few studies have sought to do so. Here we use a terrestrial slug species, Deroceras panormitanum, that has invaded a remote, largely predator-free, Southern Ocean island as a model system to do so. Across Marion Island, slug density does not conform to an abundant centre distribution. Rather, abundance structure is characterized by patches and gaps. These are associated with this desiccation-sensitive species' preference for biotic and drainage line habitats that share few characteristics except for their high humidity below the vegetation surface. The coastal range margin has a threshold form, rapidly rising from zero to high density. Slugs do not occur where soil-exchangeable Na values are higher than 3000 mg kg−1, and in laboratory experiments, survival is high below this value but negligible above it. Upper elevation range margins are a function of the inability of this species to survive temperatures below an absolute limit of −6.4°C, which is regularly exceeded at 200 m altitude, above which slug density declines to zero. However, the linear decline in density from the coastal peak is probably also a function of a decline in performance or time available for activity. This is probably associated with an altitudinal decline in mean annual soil temperature. These findings support previous predictions made regarding the form of density change when substrate or climatic factors set range limits. PMID:19324817

  1. Inspiratory muscle training in patients with chronic obstructive pulmonary disease: structural adaptation and physiologic outcomes.

    PubMed

    Ramirez-Sarmiento, Alba; Orozco-Levi, Mauricio; Guell, Rosa; Barreiro, Esther; Hernandez, Nuria; Mota, Susana; Sangenis, Merce; Broquetas, Joan M; Casan, Pere; Gea, Joaquim

    2002-12-01

    The present study was aimed at evaluating the effects of a specific inspiratory muscle training protocol on the structure of inspiratory muscles in patients with chronic obstructive pulmonary disease. Fourteen patients (males, FEV1, 24 +/- 7% predicted) were randomized to either inspiratory muscle or sham training groups. Supervised breathing using a threshold inspiratory device was performed 30 minutes per day, five times a week, for 5 consecutive weeks. The inspiratory training group was subjected to inspiratory loading equivalent to 40 to 50% of their maximal inspiratory pressure. Biopsies from external intercostal muscles and vastus lateralis (control muscle) were taken before and after the training period. Muscle samples were processed for morphometric analyses using monoclonal antibodies against myosin heavy chain isoforms I and II. Increases in both the strength and endurance of the inspiratory muscles were observed in the inspiratory training group. This improvement was associated with increases in the proportion of type I fibers (by approximately 38%, p < 0.05) and in the size of type II fibers (by approximately 21%, p < 0.05) in the external intercostal muscles. No changes were observed in the control muscle. The study demonstrates that inspiratory training induces a specific functional improvement of the inspiratory muscles and adaptive changes in the structure of external intercostal muscles. PMID:12406842

  2. A Prospective Examination of the Role of Childhood Sexual Abuse and Physiological Asymmetry in the Development of Psychopathology

    ERIC Educational Resources Information Center

    Shenk, Chad E.; Noll, Jennie G.; Putnam, Frank W.; Trickett, Penelope K.

    2010-01-01

    Objective: Recent literature has emphasized the simultaneous assessment of multiple physiological stress response systems in an effort to identify biobehavioral risk factors of psychopathology in maltreated populations. The current study assessed whether an asymmetrical stress response, marked by activation in one system and a blunted response in…

  3. Biogeographical Survey Identifies Consistent Alternative Physiological Optima and a Minor Role for Environmental Drivers in Maintaining a Polymorphism

    PubMed Central

    Iserbyt, Arne; Van Gossum, Hans; Stoks, Robby

    2012-01-01

    The contribution of adaptive mechanisms in maintaining genetic polymorphisms is still debated in many systems. To understand the contribution of selective factors in maintaining polymorphism, we investigated large-scale (>1000 km) geographic variation in morph frequencies and fitness-related physiological traits in the damselfly Nehalennia irene. As fitness-related physiological traits, we investigated investment in immune function (phenoloxidase activity), energy storage and fecundity (abdomen protein and lipid content), and flight muscles (thorax protein content). In the first part of the study, our aim was to identify selective agents maintaining the large-scale spatial variation in morph frequencies. Morph frequencies varied considerably among populations, but, in contrast to expectation, in a geographically unstructured way. Furthermore, frequencies co-varied only weakly with the numerous investigated ecological parameters. This suggests that spatial frequency patterns are driven by stochastic processes, or alternatively, are consequence of highly variable and currently unidentified ecological conditions. In line with this, the investigated ecological parameters did not affect the fitness-related physiological traits differently in both morphs. In the second part of the study, we aimed at identifying trade-offs between fitness-related physiological traits that may contribute to the local maintenance of both colour morphs by defining alternative phenotypic optima, and test the spatial consistency of such trade-off patterns. The female morph with higher levels of phenoloxidase activity had a lower thorax protein content, and vice versa, suggesting a trade-off between investments in immune function and in flight muscles. This physiological trade-off was consistent across the geographical scale studied and supports widespread correlational selection, possibly driven by male harassment, favouring alternative trait combinations in both female morphs. PMID:22384278

  4. Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor

    PubMed Central

    Brown, Jacquelyn A.; Pensabene, Virginia; Markov, Dmitry A.; Allwardt, Vanessa; Neely, M. Diana; Shi, Mingjian; Britt, Clayton M.; Hoilett, Orlando S.; Yang, Qing; Brewer, Bryson M.; Samson, Philip C.; McCawley, Lisa J.; May, James M.; Webb, Donna J.; Li, Deyu; Bowman, Aaron B.; Reiserer, Ronald S.; Wikswo, John P.

    2015-01-01

    The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier. PMID:26576206

  5. Three-dimensional nuclear magnetic resonance structures of mouse epidermal growth factor in acidic and physiological pH solutions.

    PubMed

    Kohda, D; Inagaki, F

    1992-12-01

    The three-dimensional structures of epidermal growth factors (EGF) previously reported were all in acidic solutions (pH 2.0-3.2), at which pHs EGF cannot bind to the receptor. Here we studied the structure of mouse EGF at pH 6.8, where EGF is physiologically active, and compared it with the structure at pH 2.0 by CD and NMR. From pH dependence of CD spectra and a comparison between the chemical shifts of the proton resonances at pH 6.8 and 2.0, the conformations at two pHs were found to be nearly identical except for the C-terminal tail region. The three-dimensional structures at pH 6.8 and 2.0 were determined independently by a combination of two-dimensional 1H NMR and stimulated annealing calculations using the program XPLOR. The calculations were based on 261 distance constraints at pH 6.8 and 355 distance and 24 torsion angle constraints at pH 2.0. The conformational difference of the C-terminal domain (residues 33-50) was detected between the two structures, which were supported by CD and the chemical shift comparison. The positions of the side chains of Leu47, Arg48, Trp49, and Trp50 are changed probably by the effect of the deprotonation of Asp46. Considering the fact that Leu47 is essential in EGF binding to the receptor, this conformational difference may be important in receptor recognition.

  6. The role of structural parameters in DNA cyclization

    DOE PAGESBeta

    Alexandrov, Ludmil B.; Bishop, Alan R.; Rasmussen, Kim O.; Alexandrov, Boian S.

    2016-02-04

    The intrinsic bendability of DNA plays an important role with relevance for myriad of essential cellular mechanisms. The flexibility of a DNA fragment can be experimentally and computationally examined by its propensity for cyclization, quantified by the Jacobson-Stockmayer J factor. In this paper, we use a well-established coarse-grained three-dimensional model of DNA and seven distinct sets of experimentally and computationally derived conformational parameters of the double helix to evaluate the role of structural parameters in calculating DNA cyclization.

  7. Where the woodland ends: How edges affect landscape structure and physiological responses of Quercus agrifolia

    NASA Astrophysics Data System (ADS)

    de Chant, Timothy Paul

    Forests and woodlands are integral parts of ecosystems across the globe, but they are threatened by a variety of factors, including urbanization and introduced forest pathogens. These two forces are fundamentally altering ecosystems, both by removing forest cover and reshaping landscapes. Comprehending how these two processes have changed forest ecosystems is an important step toward understanding how the affected systems will function in the future. I investigated the range of edge effects that result from disturbance brought about by forest pathogens and urbanization in two coastal oak woodlands in Marin County, California. Oak woodlands are a dynamic part of California's landscape, reacting to changes in their biotic and abiotic environments across a range of spatial and temporal scales. Sudden Oak Death, caused by the introduced forest pathogen Phytophthora ramorum, has led to widespread mortality of many tree species in California's oak woodlands. I investigated how the remaining trees respond to such rapid changes in canopy structure (Chapter 2), and my results revealed a forest canopy quick to respond to the new openings. Urbanization, another disturbance regime, operates on a longer time scale. Immediately following urban development, forest edges are strikingly linear, but both forest processes and homeowner actions likely work in concert to disrupt the straight edge (Chapter 3). Forest edges grew more sinuous within 14 years of the initial disturbance, and continued to do so for the remainder of the study, another 21 years. Individual Quercus agrifolia trees also respond to urban edges decades after disturbance (Chapter 4), and their reaction is reflected in declining stable carbon isotope values (delta13C). This change suggests trees may have increased their stomatal conductance in response to greater water availability, reduced their photosynthetic rate as a result of stress, or some combination of both. Edges have far reaching and long lasting effects

  8. Role of optimization in interdisciplinary analyses of naval structures

    NASA Technical Reports Server (NTRS)

    Dhir, S. K.; Hurwitz, M. M.

    1984-01-01

    The need for numerical design optimization of naval structures is discussed. The complexity of problems that arise due to the significant roles played by three major disciplines, i.e., structural mechanics, acoustics, and hydrodynamics are discussed. A major computer software effort that has recently begun at the David W. Taylor Naval Ship R&D Center to accommodate large multidisciplinary analyses is also described. In addition to primarily facilitating, via the use of data bases, interdisciplinary analyses for predicting the response of the Navy's ships and related structures, this software effort is expected to provide the analyst with a convenient numerical workbench for performing large numbers of analyses that may be necessary for optimizing the design performance. Finally, an example is included that investigates several aspects of optimizing a typical naval structure from the viewpoints of strength, hydrodynamic form, and acoustic characteristics.

  9. Role of an elliptical structure in photosynthetic energy transfer: Collaboration between quantum entanglement and thermal fluctuation.

    PubMed

    Oka, Hisaki

    2016-05-13

    Recent experiments have revealed that the light-harvesting complex 1 (LH1) in purple photosynthetic bacteria has an elliptical structure. Generally, symmetry lowering in a structure leads to a decrease in quantum effects (quantum coherence and entanglement), which have recently been considered to play a role in photosynthetic energy transfer, and hence, elliptical structure seems to work against efficient photosynthetic energy transfer. Here we analyse the effect of an elliptical structure on energy transfer in a purple photosynthetic bacterium and reveal that the elliptical distortion rather enhances energy transfer from peripheral LH2 to LH1 at room temperature. Numerical results show that quantum entanglement between LH1 and LH2 is formed over a wider range of high energy levels than would have been the case with circular LH1. Light energy absorbed by LH2 is thermally pumped via thermal fluctuation and is effectively transferred to LH1 through the entangled states at room temperature rather than at low temperature. This result indicates the possibility that photosynthetic systems adopt an elliptical structure to effectively utilise both quantum entanglement and thermal fluctuation at physiological temperature.

  10. Role of an elliptical structure in photosynthetic energy transfer: Collaboration between quantum entanglement and thermal fluctuation

    NASA Astrophysics Data System (ADS)

    Oka, Hisaki

    2016-05-01

    Recent experiments have revealed that the light-harvesting complex 1 (LH1) in purple photosynthetic bacteria has an elliptical structure. Generally, symmetry lowering in a structure leads to a decrease in quantum effects (quantum coherence and entanglement), which have recently been considered to play a role in photosynthetic energy transfer, and hence, elliptical structure seems to work against efficient photosynthetic energy transfer. Here we analyse the effect of an elliptical structure on energy transfer in a purple photosynthetic bacterium and reveal that the elliptical distortion rather enhances energy transfer from peripheral LH2 to LH1 at room temperature. Numerical results show that quantum entanglement between LH1 and LH2 is formed over a wider range of high energy levels than would have been the case with circular LH1. Light energy absorbed by LH2 is thermally pumped via thermal fluctuation and is effectively transferred to LH1 through the entangled states at room temperature rather than at low temperature. This result indicates the possibility that photosynthetic systems adopt an elliptical structure to effectively utilise both quantum entanglement and thermal fluctuation at physiological temperature.

  11. Role of an elliptical structure in photosynthetic energy transfer: Collaboration between quantum entanglement and thermal fluctuation

    PubMed Central

    Oka, Hisaki

    2016-01-01

    Recent experiments have revealed that the light-harvesting complex 1 (LH1) in purple photosynthetic bacteria has an elliptical structure. Generally, symmetry lowering in a structure leads to a decrease in quantum effects (quantum coherence and entanglement), which have recently been considered to play a role in photosynthetic energy transfer, and hence, elliptical structure seems to work against efficient photosynthetic energy transfer. Here we analyse the effect of an elliptical structure on energy transfer in a purple photosynthetic bacterium and reveal that the elliptical distortion rather enhances energy transfer from peripheral LH2 to LH1 at room temperature. Numerical results show that quantum entanglement between LH1 and LH2 is formed over a wider range of high energy levels than would have been the case with circular LH1. Light energy absorbed by LH2 is thermally pumped via thermal fluctuation and is effectively transferred to LH1 through the entangled states at room temperature rather than at low temperature. This result indicates the possibility that photosynthetic systems adopt an elliptical structure to effectively utilise both quantum entanglement and thermal fluctuation at physiological temperature. PMID:27173144

  12. Response of Organ Structure and Physiology to Autotetraploidization in Early Development of Energy Willow Salix viminalis.

    PubMed

    Dudits, Dénes; Török, Katalin; Cseri, András; Paul, Kenny; Nagy, Anna V; Nagy, Bettina; Sass, László; Ferenc, Györgyi; Vankova, Radomira; Dobrev, Petre; Vass, Imre; Ayaydin, Ferhan

    2016-03-01

    The biomass productivity of the energy willow Salix viminalis as a short-rotation woody crop depends on organ structure and functions that are under the control of genome size. Colchicine treatment of axillary buds resulted in a set of autotetraploid S. viminalis var. Energo genotypes (polyploid Energo [PP-E]; 2n = 4x = 76) with variation in the green pixel-based shoot surface area. In cases where increased shoot biomass was observed, it was primarily derived from larger leaf size and wider stem diameter. Autotetraploidy slowed primary growth and increased shoot diameter (a parameter of secondary growth). The duplicated genome size enlarged bark and wood layers in twigs sampled in the field. The PP-E plants developed wider leaves with thicker midrib and enlarged palisade parenchyma cells. Autotetraploid leaves contained significantly increased amounts of active gibberellins, cytokinins, salicylic acid, and jasmonate compared with diploid individuals. Greater net photosynthetic CO2 uptake was detected in leaves of PP-E plants with increased chlorophyll and carotenoid contents. Improved photosynthetic functions in tetraploids were also shown by more efficient electron transport rates of photosystems I and II. Autotetraploidization increased the biomass of the root system of PP-E plants relative to diploids. Sections of tetraploid roots showed thickening with enlarged cortex cells. Elevated amounts of indole acetic acid, active cytokinins, active gibberellin, and salicylic acid were detected in the root tips of these plants. The presented variation in traits of tetraploid willow genotypes provides a basis to use autopolyploidization as a chromosome engineering technique to alter the organ development of energy plants in order to improve biomass productivity. PMID:26729798

  13. Nickel has biochemical, physiological, and structural effects on the green microalga Ankistrodesmus falcatus: An integrative study.

    PubMed

    Martínez-Ruiz, Erika Berenice; Martínez-Jerónimo, Fernando

    2015-12-01

    In recent years, the release of chemical pollutants to water bodies has increased due to anthropogenic activities. Ni(2+) is an essential metal that causes damage to aquatic biota at high concentrations. Phytoplankton are photosynthesizing microscopic organisms that constitute a fundamental community in aquatic environments because they are primary producers that sustain the aquatic food web. Nickel toxicity has not been characterized in all of the affected levels of biological organization. For this reason, the present study evaluated the toxic effects of nickel on the growth of a primary producer, the green microalga Ankistrodesmus falcatus, and on its biochemical, enzymatic, and structural levels. The IC50 (96h) was determined for Ni(2+). Based on this result, five concentrations were determined for additional tests, in which cell density was evaluated daily. At the end of the assay, pigments and six biomarkers, including antioxidant enzymes (catalase [CAT], glutathione peroxidase [GPx], superoxide dismutase [SOD]), and macromolecules (proteins, carbohydrates and lipids), were quantified; the integrated biomarker response (IBR) was determined also. The microalgae were observed by SEM and TEM. Population growth was affected starting at 7.5 μg L(-1) (0.028 μM), and at 120 μg L(-1) (0.450 μM), growth was inhibited completely; the determined IC50 was 17 μg L(-1). Exposure to nickel reduced the concentration of pigments, decreased the content of all of the macromolecules, inhibited of SOD activity, and increased CAT and GPx activities. The IBR revealed that Ni(2+) increased the antioxidant response and diminished the macromolecules concentration. A. falcatus was affected by nickel at very low concentrations; negative effects were observed at the macromolecular, enzymatic, cytoplasmic, and morphological levels, as well as in population growth. Ni(2+) toxicity could result in environmental impacts with consequences on the entire aquatic community. Current

  14. Nickel has biochemical, physiological, and structural effects on the green microalga Ankistrodesmus falcatus: An integrative study.

    PubMed

    Martínez-Ruiz, Erika Berenice; Martínez-Jerónimo, Fernando

    2015-12-01

    In recent years, the release of chemical pollutants to water bodies has increased due to anthropogenic activities. Ni(2+) is an essential metal that causes damage to aquatic biota at high concentrations. Phytoplankton are photosynthesizing microscopic organisms that constitute a fundamental community in aquatic environments because they are primary producers that sustain the aquatic food web. Nickel toxicity has not been characterized in all of the affected levels of biological organization. For this reason, the present study evaluated the toxic effects of nickel on the growth of a primary producer, the green microalga Ankistrodesmus falcatus, and on its biochemical, enzymatic, and structural levels. The IC50 (96h) was determined for Ni(2+). Based on this result, five concentrations were determined for additional tests, in which cell density was evaluated daily. At the end of the assay, pigments and six biomarkers, including antioxidant enzymes (catalase [CAT], glutathione peroxidase [GPx], superoxide dismutase [SOD]), and macromolecules (proteins, carbohydrates and lipids), were quantified; the integrated biomarker response (IBR) was determined also. The microalgae were observed by SEM and TEM. Population growth was affected starting at 7.5 μg L(-1) (0.028 μM), and at 120 μg L(-1) (0.450 μM), growth was inhibited completely; the determined IC50 was 17 μg L(-1). Exposure to nickel reduced the concentration of pigments, decreased the content of all of the macromolecules, inhibited of SOD activity, and increased CAT and GPx activities. The IBR revealed that Ni(2+) increased the antioxidant response and diminished the macromolecules concentration. A. falcatus was affected by nickel at very low concentrations; negative effects were observed at the macromolecular, enzymatic, cytoplasmic, and morphological levels, as well as in population growth. Ni(2+) toxicity could result in environmental impacts with consequences on the entire aquatic community. Current

  15. Response of Organ Structure and Physiology to Autotetraploidization in Early Development of Energy Willow Salix viminalis.

    PubMed

    Dudits, Dénes; Török, Katalin; Cseri, András; Paul, Kenny; Nagy, Anna V; Nagy, Bettina; Sass, László; Ferenc, Györgyi; Vankova, Radomira; Dobrev, Petre; Vass, Imre; Ayaydin, Ferhan

    2016-03-01

    The biomass productivity of the energy willow Salix viminalis as a short-rotation woody crop depends on organ structure and functions that are under the control of genome size. Colchicine treatment of axillary buds resulted in a set of autotetraploid S. viminalis var. Energo genotypes (polyploid Energo [PP-E]; 2n = 4x = 76) with variation in the green pixel-based shoot surface area. In cases where increased shoot biomass was observed, it was primarily derived from larger leaf size and wider stem diameter. Autotetraploidy slowed primary growth and increased shoot diameter (a parameter of secondary growth). The duplicated genome size enlarged bark and wood layers in twigs sampled in the field. The PP-E plants developed wider leaves with thicker midrib and enlarged palisade parenchyma cells. Autotetraploid leaves contained significantly increased amounts of active gibberellins, cytokinins, salicylic acid, and jasmonate compared with diploid individuals. Greater net photosynthetic CO2 uptake was detected in leaves of PP-E plants with increased chlorophyll and carotenoid contents. Improved photosynthetic functions in tetraploids were also shown by more efficient electron transport rates of photosystems I and II. Autotetraploidization increased the biomass of the root system of PP-E plants relative to diploids. Sections of tetraploid roots showed thickening with enlarged cortex cells. Elevated amounts of indole acetic acid, active cytokinins, active gibberellin, and salicylic acid were detected in the root tips of these plants. The presented variation in traits of tetraploid willow genotypes provides a basis to use autopolyploidization as a chromosome engineering technique to alter the organ development of energy plants in order to improve biomass productivity.

  16. Metallothionein: structure/antigenicity and detection/quantitation in normal physiological fluids.

    PubMed Central

    Garvey, J S

    1984-01-01

    Recent experiments in the application of radioimmunoassay (RIA) in the detection and quantitation of metallothionein (MT) in human sera and urines demonstrate that it is possible to extend the lower limit of practical quantitation from the previous limit of 50-100 pg to 1 pg.RIA of normal sera indicates that the typical range of concentrations of MT is from less than 0.01 ng/mL to about 1 ng/mL, and that concentrations above 2 ng/mL should be considered abnormal. The typical range for normal urines is from less than 1 ng/mL to 10 ng/mL; concentrations above 10 ng/mL should be considered abnormal. A complementary assay, the enzyme-linked immunosorbent assay (ELISA), is under development. The ELISA is a competitive binding assay, detection and quantitation of MT being either by colorimetric or fluorimetric methods. The present useful range for MT quantitation in the ELISA is from about 50-50000 pg (fluorimetric) or 500-5000 pg (colorimetric). Recent experiments using the RIA have identified the principal antigenic determinants of vertebrate MTs as involving the immediate amino terminal residues (-MDPNC-) and the segment including residues 20-25 (-KCKECK- in human MT). Theoretical predictions of secondary structure based on hydrophilicity and sequence analysis indicate that the conformational profile is dominated by tetrapeptide candidates for beta turns (reverse turns) with 2-3 hexapeptide sequences being candidates for helical conformation and 4-5 short sequences (3-5 residues) being candidates for beta chain conformation. The helical candidates are predicted to be unstable and the analysis favors reverse turns for both determinants of vertebrate MT and a sequestered location for the joining region between clusters A and B. PMID:6203731

  17. Physiological and proteomic changes suggest an important role of cell walls in the high tolerance to metals of Elodea nuttallii.

    PubMed

    Larras, Floriane; Regier, Nicole; Planchon, Sébastien; Poté, John; Renaut, Jenny; Cosio, Claudia

    2013-12-15

    Macrophytes bioaccumulate metals, the suggestion being made that they be considered for phytoremediation. However, a thorough understanding of the mechanisms of metal tolerance in these plants is necessary to allow full optimization of this approach. The present study was undertaken to gain insight into Hg and Cd accumulation and their effects in a representative macrophyte, Elodea nuttallii. Exposure to methyl-Hg (23 ng dm(-3)) had no significant effect while inorganic Hg (70 ng dm(-3)) and Cd (281 μg dm(-3)) affected root growth but did not affect shoots growth, photosynthesis, or antioxidant enzymes. Phytochelatins were confirmed as having a role in Cd tolerance in this plant while Hg tolerance seems to rely on different mechanisms. Histology and subcellular distribution revealed a localized increase in lignification, and an increased proportion of metal accumulation in cell wall over time. Proteomics further suggested that E. nuttallii was able to efficiently adapt its energy sources and the structure of its cells during Hg and Cd exposure. Storage in cell walls to protect cellular machinery is certainly predominant at environmental concentrations of metals in this plant resulting in a high tolerance highlighted by the absence of toxicity symptoms in shoots despite the significant accumulation of metals.

  18. Physiological and proteomic approaches to address the active role of ozone in kiwifruit post-harvest ripening

    PubMed Central

    Minas, Ioannis S.; Tanou, Georgia; Belghazi, Maya; Job, Dominique; Manganaris, George A.; Molassiotis, Athanassios; Vasilakakis, Miltiadis

    2012-01-01

    Post-harvest ozone application has recently been shown to inhibit the onset of senescence symptoms on fleshy fruit and vegetables; however, the exact mechanism of action is yet unknown. To characterize the impact of ozone on the post-harvest performance of kiwifruit (Actinidia deliciosa cv. ‘Hayward’), fruits were cold stored (0 °C, 95% relative humidity) in a commercial ethylene-free room for 1, 3, or 5 months in the absence (control) or presence of ozone (0.3 μl l−1) and subsequently were allowed to ripen at a higher temperature (20 °C), herein defined as the shelf-life period, for up to 12 days. Ozone blocked ethylene production, delayed ripening, and stimulated antioxidant and anti-radical activities of fruits. Proteomic analysis using 1D-SDS-PAGE and mass spectrometry identified 102 kiwifruit proteins during ripening, which are mainly involved in energy, protein metabolism, defence, and cell structure. Ripening induced protein carbonylation in kiwifruit but this effect was depressed by ozone. A set of candidate kiwifruit proteins that are sensitive to carbonylation was also discovered. Overall, the present data indicate that ozone improved kiwifruit post-harvest behaviour, thus providing a first step towards understanding the active role of this molecule in fruit ripening. PMID:22268155

  19. In search for a common denominator for the diverse functions of arthropod corazonin: a role in the physiology of stress?

    PubMed

    Boerjan, Bart; Verleyen, Peter; Huybrechts, Jurgen; Schoofs, Liliane; De Loof, Arnold

    2010-04-01

    Corazonin (Crz) is an 11 amino acid C-terminally amidated neuropeptide that has been identified in most arthropods examined with the notable exception of beetles and an aphid. The Crz-receptor shares sequence similarity to the GnRH-AKH receptor family thus suggesting an ancestral function related to the control of reproduction and metabolism. In 1989, Crz was purified and identified as a potent cardioaccelerating agent in cockroaches (hence the Crz name based on "corazon", the Spanish word for "heart"). Since the initial assignment as a cardioacceleratory peptide, additional functions have been discovered, ranging from pigment migration in the integument of crustaceans and in the eye of locusts, melanization of the locust cuticle, ecdysis initiation and in various aspects of gregarization in locusts. The high degree of structural conservation of Crz, its well-conserved (immuno)-localization, mainly in specific neurosecretory cells in the pars lateralis, and its many functions, suggest that Crz is vital. Yet, Crz-deficient insects develop normally. Upon reexamining all known effects of Crz, a hypothesis was developed that the evolutionary ancient function of Crz may have been "to prepare animals for coping with the environmental stressors of the day". This function would then complement the role of pigment-dispersing factor (PDF), the prime hormonal effector of the clock, which is thought "to set a coping mechanism for the night".

  20. Physiological and proteomic approaches to address the active role of ozone in kiwifruit post-harvest ripening.

    PubMed

    Minas, Ioannis S; Tanou, Georgia; Belghazi, Maya; Job, Dominique; Manganaris, George A; Molassiotis, Athanassios; Vasilakakis, Miltiadis

    2012-04-01

    Post-harvest ozone application has recently been shown to inhibit the onset of senescence symptoms on fleshy fruit and vegetables; however, the exact mechanism of action is yet unknown. To characterize the impact of ozone on the post-harvest performance of kiwifruit (Actinidia deliciosa cv. 'Hayward'), fruits were cold stored (0 °C, 95% relative humidity) in a commercial ethylene-free room for 1, 3, or 5 months in the absence (control) or presence of ozone (0.3 μl l(-1)) and subsequently were allowed to ripen at a higher temperature (20 °C), herein defined as the shelf-life period, for up to 12 days. Ozone blocked ethylene production, delayed ripening, and stimulated antioxidant and anti-radical activities of fruits. Proteomic analysis using 1D-SDS-PAGE and mass spectrometry identified 102 kiwifruit proteins during ripening, which are mainly involved in energy, protein metabolism, defence, and cell structure. Ripening induced protein carbonylation in kiwifruit but this effect was depressed by ozone. A set of candidate kiwifruit proteins that are sensitive to carbonylation was also discovered. Overall, the present data indicate that ozone improved kiwifruit post-harvest behaviour, thus providing a first step towards understanding the active role of this molecule in fruit ripening.

  1. Starch Granule Re-Structuring by Starch Branching Enzyme and Glucan Water Dikinase Modulation Affects Caryopsis Physiology and Metabolism.

    PubMed

    Shaik, Shahnoor S; Obata, Toshihiro; Hebelstrup, Kim H; Schwahn, Kevin; Fernie, Alisdair R; Mateiu, Ramona V; Blennow, Andreas

    2016-01-01

    Starch is of fundamental importance for plant development and reproduction and its optimized molecular assembly is potentially necessary for correct starch metabolism. Re-structuring of starch granules in-planta can therefore potentially affect plant metabolism. Modulation of granule micro-structure was achieved by decreasing starch branching and increasing starch-bound phosphate content in the barley caryopsis starch by RNAi suppression of all three Starch Branching Enzyme (SBE) isoforms or overexpression of potato Glucan Water Dikinase (GWD). The resulting lines displayed Amylose-Only (AO) and Hyper-Phosphorylated (HP) starch chemotypes, respectively. We studied the influence of these alterations on primary metabolism, grain composition, starch structural features and starch granule morphology over caryopsis development at 10, 20 and 30 days after pollination (DAP) and at grain maturity. While HP showed relatively little effect, AO showed significant reduction in starch accumulation with re-direction to protein and β-glucan (BG) accumulation. Metabolite profiling indicated significantly higher sugar accumulation in AO, with re-partitioning of carbon to accumulate amino acids, and interestingly it also had high levels of some important stress-related metabolites and potentially protective metabolites, possibly to elude deleterious effects. Investigations on starch molecular structure revealed significant increase in starch phosphate and amylose content in HP and AO respectively with obvious differences in starch granule morphology at maturity. The results demonstrate that decreasing the storage starch branching resulted in metabolic adjustments and re-directions, tuning to evade deleterious effects on caryopsis physiology and plant performance while only little effect was evident by increasing starch-bound phosphate as a result of overexpressing GWD.

  2. Starch Granule Re-Structuring by Starch Branching Enzyme and Glucan Water Dikinase Modulation Affects Caryopsis Physiology and Metabolism.

    PubMed

    Shaik, Shahnoor S; Obata, Toshihiro; Hebelstrup, Kim H; Schwahn, Kevin; Fernie, Alisdair R; Mateiu, Ramona V; Blennow, Andreas

    2016-01-01

    Starch is of fundamental importance for plant development and reproduction and its optimized molecular assembly is potentially necessary for correct starch metabolism. Re-structuring of starch granules in-planta can therefore potentially affect plant metabolism. Modulation of granule micro-structure was achieved by decreasing starch branching and increasing starch-bound phosphate content in the barley caryopsis starch by RNAi suppression of all three Starch Branching Enzyme (SBE) isoforms or overexpression of potato Glucan Water Dikinase (GWD). The resulting lines displayed Amylose-Only (AO) and Hyper-Phosphorylated (HP) starch chemotypes, respectively. We studied the influence of these alterations on primary metabolism, grain composition, starch structural features and starch granule morphology over caryopsis development at 10, 20 and 30 days after pollination (DAP) and at grain maturity. While HP showed relatively little effect, AO showed significant reduction in starch accumulation with re-direction to protein and β-glucan (BG) accumulation. Metabolite profiling indicated significantly higher sugar accumulation in AO, with re-partitioning of carbon to accumulate amino acids, and interestingly it also had high levels of some important stress-related metabolites and potentially protective metabolites, possibly to elude deleterious effects. Investigations on starch molecular structure revealed significant increase in starch phosphate and amylose content in HP and AO respectively with obvious differences in starch granule morphology at maturity. The results demonstrate that decreasing the storage starch branching resulted in metabolic adjustments and re-directions, tuning to evade deleterious effects on caryopsis physiology and plant performance while only little effect was evident by increasing starch-bound phosphate as a result of overexpressing GWD. PMID:26891365

  3. Starch Granule Re-Structuring by Starch Branching Enzyme and Glucan Water Dikinase Modulation Affects Caryopsis Physiology and Metabolism

    PubMed Central

    Shaik, Shahnoor S.; Obata, Toshihiro; Hebelstrup, Kim H.; Schwahn, Kevin; Fernie, Alisdair R.; Mateiu, Ramona V.; Blennow, Andreas

    2016-01-01

    Starch is of fundamental importance for plant development and reproduction and its optimized molecular assembly is potentially necessary for correct starch metabolism. Re-structuring of starch granules in-planta can therefore potentially affect plant metabolism. Modulation of granule micro-structure was achieved by decreasing starch branching and increasing starch-bound phosphate content in the barley caryopsis starch by RNAi suppression of all three Starch Branching Enzyme (SBE) isoforms or overexpression of potato Glucan Water Dikinase (GWD). The resulting lines displayed Amylose-Only (AO) and Hyper-Phosphorylated (HP) starch chemotypes, respectively. We studied the influence of these alterations on primary metabolism, grain composition, starch structural features and starch granule morphology over caryopsis development at 10, 20 and 30 days after pollination (DAP) and at grain maturity. While HP showed relatively little effect, AO showed significant reduction in starch accumulation with re-direction to protein and β-glucan (BG) accumulation. Metabolite profiling indicated significantly higher sugar accumulation in AO, with re-partitioning of carbon to accumulate amino acids, and interestingly it also had high levels of some important stress-related metabolites and potentially protective metabolites, possibly to elude deleterious effects. Investigations on starch molecular structure revealed significant increase in starch phosphate and amylose content in HP and AO respectively with obvious differences in starch granule morphology at maturity. The results demonstrate that decreasing the storage starch branching resulted in metabolic adjustments and re-directions, tuning to evade deleterious effects on caryopsis physiology and plant performance while only little effect was evident by increasing starch-bound phosphate as a result of overexpressing GWD. PMID:26891365

  4. Physiological mechanisms that underlie the effects of interactional unfairness on deviant behavior: the role of cortisol activity.

    PubMed

    Yang, Liu-Qin; Bauer, Jeremy; Johnson, Russell E; Groer, Maureen W; Salomon, Kristen

    2014-03-01

    Although experiencing unfairness is a primary source of stress, there are surprisingly few studies that have examined the physiological underpinnings of unfairness. Drawing from social self-preservation theory, we derive predictions regarding the effects of interactional unfairness on activity in the hypothalamic-pituitary-adrenocortical (HPA) axis, which is one of the body's primary hormonal systems for responding to stress. Using an experimental design with objective physiological measures, we found support for our hypothesis that interactional unfairness triggers the release of cortisol by the HPA axis. This cortisol activity in turn mediated the effects of interactional unfairness on deviant behavior. This indirect effect remained significant after controlling for established attitudinal and self-construal mediators of the justice-deviance relationship. We discuss the theoretical and practical implications of these findings for the occupational stress and organizational justice literatures. PMID:24099347

  5. High adenylyl cyclase activity and in vivo cAMP fluctuations in corals suggest central physiological role

    PubMed Central

    Barott, K. L.; Helman, Y.; Haramaty, L.; Barron, M. E.; Hess, K. C.; Buck, J.; Levin, L. R.; Tresguerres, M.

    2013-01-01

    Corals are an ecologically and evolutionarily significant group, providing the framework for coral reef biodiversity while representing one of the most basal of metazoan phyla. However, little is known about fundamental signaling pathways in corals. Here we investigate the dynamics of cAMP, a conserved signaling molecule that can regulate virtually every physiological process. Bioinformatics revealed corals have both transmembrane and soluble adenylyl cyclases (AC). Endogenous cAMP levels in live corals followed a potential diel cycle, as they were higher during the day compared to the middle of the night. Coral homogenates exhibited some of the highest cAMP production rates ever to be recorded in any organism; this activity was inhibited by calcium ions and stimulated by bicarbonate. In contrast, zooxanthellae or mucus had >1000-fold lower AC activity. These results suggest that cAMP is an important regulator of coral physiology, especially in response to light, acid/base disturbances and inorganic carbon levels. PMID:23459251

  6. Physiological mechanisms that underlie the effects of interactional unfairness on deviant behavior: the role of cortisol activity.

    PubMed

    Yang, Liu-Qin; Bauer, Jeremy; Johnson, Russell E; Groer, Maureen W; Salomon, Kristen

    2014-03-01

    Although experiencing unfairness is a primary source of stress, there are surprisingly few studies that have examined the physiological underpinnings of unfairness. Drawing from social self-preservation theory, we derive predictions regarding the effects of interactional unfairness on activity in the hypothalamic-pituitary-adrenocortical (HPA) axis, which is one of the body's primary hormonal systems for responding to stress. Using an experimental design with objective physiological measures, we found support for our hypothesis that interactional unfairness triggers the release of cortisol by the HPA axis. This cortisol activity in turn mediated the effects of interactional unfairness on deviant behavior. This indirect effect remained significant after controlling for established attitudinal and self-construal mediators of the justice-deviance relationship. We discuss the theoretical and practical implications of these findings for the occupational stress and organizational justice literatures.

  7. Hallmarks in the study of respiratory physiology and the crucial role of Antoine-Laurent de Lavoisier (1743-1794).

    PubMed

    Karamanou, Marianna; Tsoucalas, Gregory; Androutsos, George

    2013-11-01

    From the early 17th century the advent of physical and chemical sciences developed two important movements toward the explanation of all vital phenomena: the Iatrochemical and Iatromechanical Schools. The important research of their representatives such as Jan Baptist van Helmont, John Mayow, Robert Boyle, Gian Alfonso Borelli, Richard Lower, and Albrecht von Haller, followed by the discovery of the atmospheric gases, provided a fecund soil for the leading work of Lavoisier in respiratory physiology. PMID:24039254

  8. Hallmarks in the study of respiratory physiology and the crucial role of Antoine-Laurent de Lavoisier (1743-1794).

    PubMed

    Karamanou, Marianna; Tsoucalas, Gregory; Androutsos, George

    2013-11-01

    From the early 17th century the advent of physical and chemical sciences developed two important movements toward the explanation of all vital phenomena: the Iatrochemical and Iatromechanical Schools. The important research of their representatives such as Jan Baptist van Helmont, John Mayow, Robert Boyle, Gian Alfonso Borelli, Richard Lower, and Albrecht von Haller, followed by the discovery of the atmospheric gases, provided a fecund soil for the leading work of Lavoisier in respiratory physiology.

  9. Beyond physiological hypoarousal: the role of life stress and callous-unemotional traits in incarcerated adolescent males.

    PubMed

    Gostisha, Andrew J; Vitacco, Michael J; Dismukes, Andrew R; Brieman, Chelsea; Merz, Jenna; Shirtcliff, Elizabeth A

    2014-05-01

    The development of antisocial behavior in youth has been examined with neurobiological theories that suggest that adolescents who are less responsive to their environments are less likely to develop empathy in the absence of extant physiological arousal. However, little attention is paid to these individuals' social context. Individuals with adverse early experiences can also exhibit attenuated physiological arousal. The current investigation examines whether psychopathic symptoms or life stress exposure is associated with cortisol and its diurnal rhythm within 50 incarcerated adolescent boys (14-18years old). Ten saliva cortisol samples were collected 1-2weeks after admission to a maximum-security juvenile facility. Hierarchical Linear Modeling distinguished waking cortisol levels, the awakening response (CAR) and the diurnal rhythm. Multiple interviews and self-report measures of CU traits and stressor exposure were collected. Boys with higher levels of CU traits or greater life stress exposure had flat diurnal rhythms and a steeper awakening response in analyses with lifetime stress exposure specifically. Nonetheless, boys who were elevated on both CU traits and prior stress exposure had steeper diurnal rhythms. These results extend neurobiological theories of cortisol and illustrate that boys with the combination of severe stress with CU traits have a unique physiological profile. PMID:24726789

  10. Beyond Physiological Hypoarousal: The Role of Life Stress and Callous-Unemotional Traits in Incarcerated Adolescent Males

    PubMed Central

    Gostisha, Andrew J.; Vitacco, Michael J.; Dismukes, Andrew R.; Brieman, Chelsea; Merz, Jenna; Shirtcliff, Elizabeth A.

    2015-01-01

    The development of antisocial behavior in youth has been examined with neurobiological theories that suggest adolescents who are less responsive to their environments are less likely to develop empathy in the absence of extant physiological arousal. However, little attention is paid to these individuals’ social context. Individuals with adverse early experiences can also exhibit attenuated physiological arousal. The current investigation examines whether psychopathic symptoms or life stress exposure is associated with cortisol and its diurnal rhythm within 50 incarcerated adolescent boys (14–18 years old). Ten saliva cortisol samples were collected 1–2 weeks after admission to a maximum-security juvenile facility. Hierarchical Linear Modeling distinguished waking cortisol levels, the awakening response (CAR) and the diurnal rhythm. Multiple interviews and self-report measures of CU traits and stressor exposure were collected. Boys with higher levels of CU traits or greater life stress exposure had flat diurnal rhythms and a steeper awakening response in analyses with lifetime stress exposure specifically. Nonetheless, boys who were elevated on both CU traits and prior stress exposure had steeper diurnal rhythms. These results extend neurobiological theories of cortisol and illustrate that boys with the combination of severe stress with CU traits have a unique physiological profile. PMID:24726789

  11. Analysis of Experts’ Quantitative Assessment of Adolescent Basketball Players and the Role of Anthropometric and Physiological Attributes

    PubMed Central

    Štrumbelj, Erik; Erčulj, Frane

    2014-01-01

    In this paper, we investigated two questions: (1) can measurements of anthropometric and physiological attributes substitute for expert assessment of adolescent basketball players, and (2) how much does the quantitative assessment of a player vary among experts? The first question is relevant to the potential simplification of the player selection process. The second question pertains directly to the validity of expert quantitative assessment. Our research was based on data from 148 U14 female and male basketball players. For each player, an array of anthropometric and physiological attributes was recorded, including body height, body mass, BMI, and several motor skill tests. Furthermore, each player’s current ability and potential ability were quantitatively evaluated by two different experts from a group of seven experts. Analysis of the recorded data showed that the anthropometric and physiological attributes explained between 15% and 40% of the variance in experts’ scores. The primary predictive attributes were speed and agility (for predicting current ability) and body height and growth potential (for predicting potential ability). We concluded that these attributes were not sufficiently informative to act as a substitute for expert assessment of the players’ current or potential ability. There is substantial variability in different experts’ scores of the same player’s ability. However, the differences between experts are mostly in scale, and the relationships between experts’ scores are monotonic. That is, different experts rank players on ability very similarly, but their scores are not well calibrated. PMID:25414759

  12. [Physiological processes in organism: nanomechanism].

    PubMed

    Chekman, I S

    2010-01-01

    Physiologically active substances by nanosizes are divided into 4 groups. The first group includes substances up to 100 nm: leukocytes, erythrocytes, cell components (nucleus, mitochondria), cancer cells, bacteria and bacteriophages. The second group consists of nanoparticles with size from 10 to 100 nm. These are antibody, ribosomes, glycogen granules, liposomes, and others. The third group of substances has sizes from 10 to 1 nm. This group includes: albumin, hemoglobin, membrane cells, fibrixogen, receptors (serotonin, beta-adrenergic receptor and others), insulin, fat soluble vitamins (ergocalciferol, retinol), folic acid, drugs (digoxin, quetcitin), chlorophyll plants, fullerenes. The fourth group consists of matter smaller than 1 nm, in particular: ATP, fructose, mediators (acetyl-choline, adrenaline, noradrenaline), phenylephrine, amino acids, water molecules, CO2, NO, oxygen atoms, hydrogen. The existence in the body of physiological processes based on natural nanotechnology may be proved by the following facts. 1. Physiologically active substances have nanosizes. 2. Cell membranes, the capillary wall have also nanosizes, promoting effective physiological processes involving biologically active substances with nanosizes. 3. Due to the small size of nanoparticles can penetrate through cell membranes and be distributed in the body. 4. From the position of modern nanoscience functioning organs, cells, subcellular structures, calcium channels, sodium-potassium pump is under the laws of natural nanomechanisms. 5. Summarising the literature data and own research, we can argue that the body's physiological processes based on natural nanomechanisms require more detailed, in-depth research. Nanophysiology studies peculiarities of the physiological processes in the body from the position of nanoscience and the impact of nanoparticles on the function of cells and organs. The author accepts the fact that not all ideas reported in this article have experimental

  13. Biosilicification: the role of the organic matrix in structure control.

    PubMed

    Perry, C C; Keeling-Tucker, T

    2000-10-01

    Silicon (although never in the elemental form) is present in all living organisms and is required for the production of structural materials in single-celled organisms through to higher plants and animals. Hydrated amorphous silica is a mineral of infinite functionality and yet it is formed into structures with microscopic and macroscopic form. Research into the mechanisms controlling the process have highlighted proteins and proteoglycans as possible control molecules. Such molecules are suggested to play a critical role in the catalysis of silica polycondensation reactions and in structure direction. This article reviews information on silica form and function, silica condensation chemistry, the role of macromolecules in structure control and in vitro studies of silica formation using biomolecules extracted from biological silicas. An understanding of the mechanisms by which biological organisms regulate mineral formation will assist in our understanding of the essentiality of silicon to life processes and in the generation of new materials with specific form and function for industrial application in the 21st century.

  14. Mannan structural complexity is decreased when Candida albicans is cultivated in blood or serum at physiological temperature

    PubMed Central

    Lowman, Douglas W.; Ensley, Harry E.; Greene, Rachel R.; Knagge, Kevin J.; Williams, David L.; Kruppa, Michael D.

    2011-01-01

    The Candida albicans cell wall provides an architecture that allows for the organism to survive environmental stresses as well as interaction with host tissues. Previous work has focused on growing C. albicans on media such as Sabouraud or YPD at 30 °C. Because C. albicans normally colonizes a host, we hypothesized that cultivation on blood or serum at 37 °C would result in structural changes in cell wall mannan. C. albicans SC5314 was inoculated onto YPD, 5% blood, or 5% serum agar media three successive times at 30 °C and 37 °C, then cultivated overnight at 30 °C in YPD. The mannan was extracted and characterized using 1D and 2D 1H NMR techniques. At 30 °C cells grown in blood and serum contain less acid-stable terminal β-(1→2)-linked D-mannose and α-(1→2)-linked D-mannose-containing side chains, while the acid-labile side chains of mannan grown in blood and serum contain fewer β-Man-(1→2)-α-Man-(1→ side chains. The decrement in acid-stable mannan side chains is greater at 37 °C than at 30 °C. Cells grown on blood at 37 °C show fewer →6)-α-Man-(1→ structural motifs in the acid-stable polymer backbone. The data indicate that C. albicans, grown on media containing host derived components, produces less complex mannan. This is accentuated when the cells are cultured at 37 °C. This study demonstrates that the C. albicans cell wall is a dynamic and adaptive organelle, which alters its structural phenotype in response to growth in host-derived media at physiological temperature. PMID:22030461

  15. A dominant role for mechanical resonance in physiological finger tremor revealed by selective minimization of voluntary drive and movement.

    PubMed

    Vernooij, Carlijn A; Reynolds, Raymond F; Lakie, Martin

    2013-05-01

    There is a debate in the literature about whether the low- and high-frequency peaks of physiological finger tremor are caused by resonance or central drive. One way to address this issue is to examine the consequences of eliminating, as far as possible, the resonant properties or the voluntary drive. To study the effect of minimizing resonance, finger tremor was recorded under isometric conditions and compared with normal isotonic tremor. To minimize central drive, finger tremor was generated artificially by broad-band electrical stimulation. When resonance was minimized, tremor size declined almost monotonically with increasing frequency. There was no consistent large peak at a frequency characteristic of tremor. Although there was sometimes a peak around the tremor frequency during some isometric conditions, it was extremely small and variable; therefore, any contribution of central drive was minimal. In contrast, there was always a prominent peak in the isotonic frequency spectra. Resonance was, therefore, necessary to produce the characteristic tremor peaks. When central drive was minimized by replacing voluntary muscle activation with artificial stimulation, a realistic tremor spectrum was observed. Central drive is, therefore, not required to generate a characteristic physiological tremor spectrum. In addition, regardless of the nature of the driving input (voluntary or artificial), increasing the size of the input considerably reduced isotonic tremor frequency. We attribute the frequency reduction to a movement-related thixotropic change in muscle stiffness. From these results we conclude that physiological finger tremor across a large range of frequencies is produced by natural broad-band forcing of a nonlinear resonant system, and that synchronous central input is not required.

  16. Sloth biology: an update on their physiological ecology, behavior and role as vectors of arthropods and arboviruses.

    PubMed

    Gilmore, D P; Da Costa, C P; Duarte, D P

    2001-01-01

    This is a review of the research undertaken since 1971 on the behavior and physiological ecology of sloths. The animals exhibit numerous fascinating features. Sloth hair is extremely specialized for a wet tropical environment and contains symbiotic algae. Activity shows circadian and seasonal variation. Nutrients derived from the food, particularly in Bradypus, only barely match the requirements for energy expenditure. Sloths are hosts to a fascinating array of commensal and parasitic arthropods and are carriers of various arthropod-borne viruses. Sloths are known reservoirs of the flagellate protozoan which causes leishmaniasis in humans, and may also carry trypanosomes and the protozoan Pneumocystis carinii.

  17. On the role of numerical simulations in studies of reduced gravity-induced physiological effects in humans. Results from NELME.

    NASA Astrophysics Data System (ADS)

    Perez-Poch, Antoni

    Computer simulations are becoming a promising research line of work, as physiological models become more and more sophisticated and reliable. Technological advances in state-of-the-art hardware technology and software allow nowadays for better and more accurate simulations of complex phenomena, such as the response of the human cardiovascular system to long-term exposure to microgravity. Experimental data for long-term missions are difficult to achieve and reproduce, therefore the predictions of computer simulations are of a major importance in this field. Our approach is based on a previous model developed and implemented in our laboratory (NELME: Numercial Evaluation of Long-term Microgravity Effects). The software simulates the behaviour of the cardiovascular system and different human organs, has a modular archi-tecture, and allows to introduce perturbations such as physical exercise or countermeasures. The implementation is based on a complex electrical-like model of this control system, using inexpensive development frameworks, and has been tested and validated with the available experimental data. The objective of this work is to analyse and simulate long-term effects and gender differences when individuals are exposed to long-term microgravity. Risk probability of a health impairement which may put in jeopardy a long-term mission is also evaluated. . Gender differences have been implemented for this specific work, as an adjustment of a number of parameters that are included in the model. Women versus men physiological differences have been therefore taken into account, based upon estimations from the physiology bibliography. A number of simulations have been carried out for long-term exposure to microgravity. Gravity varying continuosly from Earth-based to zero, and time exposure are the two main variables involved in the construction of results, including responses to patterns of physical aerobic ex-ercise and thermal stress simulating an extra

  18. Homogalacturonan-modifying enzymes: structure, expression, and roles in plants

    PubMed Central

    Sénéchal, Fabien; Wattier, Christopher; Rustérucci, Christine; Pelloux, Jérôme

    2014-01-01

    Understanding the changes affecting the plant cell wall is a key element in addressing its functional role in plant growth and in the response to stress. Pectins, which are the main constituents of the primary cell wall in dicot species, play a central role in the control of cellular adhesion and thereby of the rheological properties of the wall. This is likely to be a major determinant of plant growth. How the discrete changes in pectin structure are mediated is thus a key issue in our understanding of plant development and plant responses to changes in the environment. In particular, understanding the remodelling of homogalacturonan (HG), the most abundant pectic polymer, by specific enzymes is a current challenge in addressing its fundamental role. HG, a polymer that can be methylesterified or acetylated, can be modified by HGMEs (HG-modifying enzymes) which all belong to large multigenic families in all species sequenced to date. In particular, both the degrees of substitution (methylesterification and/or acetylation) and polymerization can be controlled by specific enzymes such as pectin methylesterases (PMEs), pectin acetylesterases (PAEs), polygalacturonases (PGs), or pectate lyases-like (PLLs). Major advances in the biochemical and functional characterization of these enzymes have been made over the last 10 years. This review aims to provide a comprehensive, up to date summary of the recent data concerning the structure, regulation, and function of these fascinating enzymes in plant development and in response to biotic stresses. PMID:25056773

  19. The Structural Determinants behind the Epigenetic Role of Histone Variants

    PubMed Central

    Cheema, Manjinder S.; Ausió, Juan

    2015-01-01

    Histone variants are an important part of the histone contribution to chromatin epigenetics. In this review, we describe how the known structural differences of these variants from their canonical histone counterparts impart a chromatin signature ultimately responsible for their epigenetic contribution. In terms of the core histones, H2A histone variants are major players while H3 variant CenH3, with a controversial role in the nucleosome conformation, remains the genuine epigenetic histone variant. Linker histone variants (histone H1 family) haven’t often been studied for their role in epigenetics. However, the micro-heterogeneity of the somatic canonical forms of linker histones appears to play an important role in maintaining the cell-differentiated states, while the cell cycle independent linker histone variants are involved in development. A picture starts to emerge in which histone H2A variants, in addition to their individual specific contributions to the nucleosome structure and dynamics, globally impair the accessibility of linker histones to defined chromatin locations and may have important consequences for determining different states of chromatin metabolism. PMID:26213973

  20. Structural and physiological responses of two invasive weeds, Mikania micrantha and Chromolaena odorata, to contrasting light and soil water conditions.

    PubMed

    Zhang, Ling-Ling; Wen, Da-Zhi

    2009-01-01

    To better understand the requirement of light and soil water conditions in the invasion sites of two invasive weeds, Mikania micrantha and Chromolaena odorata, we investigated their structural and physiological traits in response to nine combined treatments of light [full, medium and low irradiance (LI)] and soil water (full, medium and low field water content) conditions in three glasshouses. Under the same light conditions, most variables for both species did not vary significantly among different water treatments. Irrespective of water treatment, both species showed significant decreases in maximum light saturated photosynthetic rate (P (max)), photosynthetic nitrogen-use efficiency, and relative growth rate under LI relative to full irradiance; specific leaf area, however, increased significantly from full to LI though leaf area decreased significantly, indicating that limited light availability under extreme shade was the critical factor restricting the growth of both species. Our results also indicated that M. micrantha performed best under a high light and full soil water combination, while C. odorata was more efficient in growth under a high light and medium soil water combination.

  1. Zinc stress induces physiological, ultra-structural and biochemical changes in mandarin orange (Citrus reticulata Blanco) seedlings.

    PubMed

    Subba, Pratap; Mukhopadhyay, Mainaak; Mahato, Suresh Kumar; Bhutia, Karma Diki; Mondal, Tapan Kumar; Ghosh, Swapan Kumar

    2014-10-01

    Zinc (Zn) is an essential micronutrient for higher plants; yet, at higher concentrations it is toxic. In order to explore the effect of Zn stress on growth, biochemical, physiological and ultra-structural changes, 1 year old mandarin plants were grown under various Zn concentrations (1, 2, 3, 4, 5, 10 15 and 20 mM) for 14 weeks. The biomass of the plants increased with increasing Zn concentrations and finally declined under excess Zn concentration but the prime increase was observed at 4 and 5 mM Zn. Zn stress reduced the photosynthetic rate, stomatal conductance, and transpiration along with reduction of chlorophyll a, chlorophyll b, and carotenoids content in leaf. Superoxide anion, malondialdehyde, hydrogen peroxide and electrolyte leakage were elevated in Zn stressed plants. The activities of ascorbate peroxidase (EC 1.11.1.11), catalase (EC 1.11.1.6), superoxide dismutase (EC 1.15.1.1) and peroxidase (EC 1.11.1.7) enzymes were increased in both Zn-deficient and Zn-excess plants. Therefore it is suggested that antioxidant defense system did not sufficiently protect the plants under rigorous Zn stress which was also corroborated by the alteration in cell ultrastructure as revealed by transmission electron microscopy. PMID:25320469

  2. Physiological roles of asialoglycoprotein receptors (ASGPRs) variants and recent advances in hepatic-targeted delivery of therapeutic molecules via ASGPRs.

    PubMed

    Hu, Jing; Liu, Jia; Yang, Dongliang; Lu, Mengji; Yin, Jian

    2014-01-01

    The asialoglycoprotein receptor (ASGPR) is a high-capacity C-type lectin receptor mainly expressed on mammalian hepatic cells. The physiological function of ASGPR has not been completely clarified and is thought to be specific binding and internalization of galactose (Gal) or N-acetylgalactosamine (GalNAc)-terminating glycoproteins by hepatocytes. The human ASGPR is comprised of two homologous polypeptides, H1 and H2. ASGPR H1 has two splice variants (H1a and H1b) and ASGPR H2 has three splice variants (H2a, H2b, and H2c). These variants have been discovered to exist both in human liver tissues and in human hepatoma cells. Variant H1b, which has an in-frame deletion of exon 2 resulting in the loss of the transmembrane domain and is secreted as a soluble protein, encodes functional soluble ASGPR (s- ASGPR). Based on our previous results, we proposed the possible physiological function of s-ASGPR, which is well interpreted in the Galactosyl Homeostasis Hypothesis proposed by Weigel. ASGPR is one of the most promising targets for hepatic delivery. In this review, the recent progresses of cationic polysomes and liposomes as effective non-viral delivery system via ASGPR are also presented.

  3. Unraveling the role of dark septate endophyte (DSE) colonizing maize (Zea mays) under cadmium stress: physiological, cytological and genic aspects.

    PubMed

    Wang, Jun-ling; Li, Tao; Liu, Gao-yuan; Smith, Joshua M; Zhao, Zhi-wei

    2016-01-01

    A growing body of evidence suggests that plant root-associated fungi such as dark septate endophytes (DSE) can help plants overcome many biotic and abiotic stresses, of great interest is DSE-plant metal tolerance and alleviation capabilities on contaminated soils. However, the tolerance and alleviation mechanisms involved have not yet been elucidated. In the current study, the regulation and physiological response of Zea mays to its root-associated DSE, Exophiala pisciphila was analyzed under increased soil Cd stress (0, 10, 50, 100 mg kg(-1)). Under Cd stress, DSE inoculation significantly enhanced the activities of antioxidant enzymes and low-molecular weight antioxidants, while also inducing increased Cd accumulation in the cell wall and conversion of Cd into inactive forms by shoot and root specific regulation of genes related to metal uptake, translocation and chelation. Our results showed that DSE colonization resulted in a marked tolerance to Cd, with a significant decrease in cadmium phytotoxicity and a significant increase in maize growth by triggering antioxidant systems, altering metal chemical forms into inactive Cd, and repartitioning subcellular Cd into the cell wall. These results provide comprehensive evidence for the mechanisms by which DSE colonization bioaugments Cd tolerance in maize at physiological, cytological and molecular levels. PMID:26911444

  4. Unraveling the role of dark septate endophyte (DSE) colonizing maize (Zea mays) under cadmium stress: physiological, cytological and genic aspects

    PubMed Central

    Wang, Jun-ling; Li, Tao; Liu, Gao-yuan; Smith, Joshua M.; Zhao, Zhi-wei

    2016-01-01

    A growing body of evidence suggests that plant root-associated fungi such as dark septate endophytes (DSE) can help plants overcome many biotic and abiotic stresses, of great interest is DSE-plant metal tolerance and alleviation capabilities on contaminated soils. However, the tolerance and alleviation mechanisms involved have not yet been elucidated. In the current study, the regulation and physiological response of Zea mays to its root-associated DSE, Exophiala pisciphila was analyzed under increased soil Cd stress (0, 10, 50, 100 mg kg−1). Under Cd stress, DSE inoculation significantly enhanced the activities of antioxidant enzymes and low-molecular weight antioxidants, while also inducing increased Cd accumulation in the cell wall and conversion of Cd into inactive forms by shoot and root specific regulation of genes related to metal uptake, translocation and chelation. Our results showed that DSE colonization resulted in a marked tolerance to Cd, with a significant decrease in cadmium phytotoxicity and a significant increase in maize growth by triggering antioxidant systems, altering metal chemical forms into inactive Cd, and repartitioning subcellular Cd into the cell wall. These results provide comprehensive evidence for the mechanisms by which DSE colonization bioaugments Cd tolerance in maize at physiological, cytological and molecular levels. PMID:26911444

  5. Unraveling the role of dark septate endophyte (DSE) colonizing maize (Zea mays) under cadmium stress: physiological, cytological and genic aspects.

    PubMed

    Wang, Jun-ling; Li, Tao; Liu, Gao-yuan; Smith, Joshua M; Zhao, Zhi-wei

    2016-01-01

    A growing body of evidence suggests that plant root-associated fungi such as dark septate endophytes (DSE) can help plants overcome many biotic and abiotic stresses, of great interest is DSE-plant metal tolerance and alleviation capabilities on contaminated soils. However, the tolerance and alleviation mechanisms involved have not yet been elucidated. In the current study, the regulation and physiological response of Zea mays to its root-associated DSE, Exophiala pisciphila was analyzed under increased soil Cd stress (0, 10, 50, 100 mg kg(-1)). Under Cd stress, DSE inoculation significantly enhanced the activities of antioxidant enzymes and low-molecular weight antioxidants, while also inducing increased Cd accumulation in the cell wall and conversion of Cd into inactive forms by shoot and root specific regulation of genes related to metal uptake, translocation and chelation. Our results showed that DSE colonization resulted in a marked tolerance to Cd, with a significant decrease in cadmium phytotoxicity and a significant increase in maize growth by triggering antioxidant systems, altering metal chemical forms into inactive Cd, and repartitioning subcellular Cd into the cell wall. These results provide comprehensive evidence for the mechanisms by which DSE colonization bioaugments Cd tolerance in maize at physiological, cytological and molecular levels.

  6. The Many Roles of Lagrangian Coherent Structures in Fluid Mixing

    NASA Astrophysics Data System (ADS)

    Ouellette, N. T.

    2014-12-01

    Understanding, characterizing, and modeling hydrodynamic mixing and transport in unsteady and turbulent flows remains a tremendous challenge despite decades of work. A wide array of techniques have been applied to mixing, ranging from statistical mechanics to stochastic modeling to decompositions of the flow field into discrete coherent structures. Recent years have seen significant progress in applying the tools and methods of dynamical systems theory to turbulent mixing. Such methods are usually applied in the Lagrangian framework, and are based on studying advection directly. Using data from quasi-two-dimensional laboratory experiments and numerical simulations, I will discuss the roles played by one particular mixing diagnostic: so-called Lagrangian Coherent Structures (LCSs). LCSs are defined to be distinguished material lines that are the dominant barriers to fluid transport and that organize advection. Here, I will demonstrate that they also play other roles. In particular, I will show that they separate regions of the flow field with distinct spectral dynamics, that they act as aligning structures for transported anisotropic particles, and that they can be attractors for self-motile particles.

  7. Androgen receptor: structure, role in prostate cancer and drug discovery

    PubMed Central

    Tan, MH Eileen; Li, Jun; Xu, H Eric; Melcher, Karsten; Yong, Eu-leong

    2015-01-01

    Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2–3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein. PMID:24909511

  8. Androgen receptor: structure, role in prostate cancer and drug discovery.

    PubMed

    Tan, M H Eileen; Li, Jun; Xu, H Eric; Melcher, Karsten; Yong, Eu-leong

    2015-01-01

    Androgens and androgen receptors (AR) play a pivotal role in expression of the male phenotype. Several diseases, such as androgen insensitivity syndrome (AIS) and prostate cancer, are associated with alterations in AR functions. Indeed, androgen blockade by drugs that prevent the production of androgens and/or block the action of the AR inhibits prostate cancer growth. However, resistance to these drugs often occurs after 2-3 years as the patients develop castration-resistant prostate cancer (CRPC). In CRPC, a functional AR remains a key regulator. Early studies focused on the functional domains of the AR and its crucial role in the pathology. The elucidation of the structures of the AR DNA binding domain (DBD) and ligand binding domain (LBD) provides a new framework for understanding the functions of this receptor and leads to the development of rational drug design for the treatment of prostate cancer. An overview of androgen receptor structure and activity, its actions in prostate cancer, and how structural information and high-throughput screening have been or can be used for drug discovery are provided herein. PMID:24909511

  9. Voltage behavior along the irregular dendritic structure of morphologically and physiologically characterized vagal motoneurons in the guinea pig.

    PubMed

    Nitzan, R; Segev, I; Yarom, Y

    1990-02-01

    1. Intracellular recordings from neurons in the dorsal motor nucleus of the vagus (vagal motoneurons, VMs) obtained in the guinea pig brain stem slice preparation were used for both horseradish peroxidase (HRP) labeling of the neurons and for measurements of their input resistance (RN) and time constant (tau 0). Based on the physiological data and on the morphological reconstruction of the labeled cells, detailed steady-state and compartmental models of VM were built and utilized to estimate the range of membrane resistivity, membrane capacitance, and cytoplasm resistivity values (Rm, Cm, and Ri, respectively) and to explore the integrative properties of these cells. 2. VMs are relatively small cells with a simple dendritic structure. Each cell has an average of 5.3 smooth (nonspiny), short (251 microns) dendrites with a low order (2) of branching. The average soma-dendritic surface area of VMs is 9,876 microns 2. 3. Electrically, VMs show remarkably linear membrane properties in the hyperpolarizing direction; they have an average RN of 67 +/- 23 (SD) M omega and a tau 0 of 9.4 +/- 4.1 ms. Several unfavorable experimental conditions precluded the possibility of faithfully recovering ("peeling") the first equalizing time constant (tau 1) and, thereby, of estimating the electrotonic length (Lpeel) of VMs. 4. Reconciling VM morphology with the measured RN and tau 0 through the models, assuming an Ri of 70 omega.cm and a spatially uniform Rm, yielded an Rm estimate of 5,250 omega.cm2 and a Cm of 1.8 microF/cm2. Peeling theoretical transients produced by these models result in an Lpeel of 1.35. Because of marked differences in the length of dendrites within a single cell, this value is larger than the maximal cable length of the dendrites and is twice as long as their average cable length. 5. The morphological and physiological data could be matched indistinguishably well if a possible soma shunt (i.e., Rm, soma less than Rm, dend) was included in the model. Although

  10. Hfqs in Bacillus anthracis: Role of protein sequence variation in the structure and function of proteins in the Hfq family.

    PubMed

    Vrentas, Catherine; Ghirlando, Rodolfo; Keefer, Andrea; Hu, Zonglin; Tomczak, Aurelie; Gittis, Apostolos G; Murthi, Athulaprabha; Garboczi, David N; Gottesman, Susan; Leppla, Stephen H

    2015-11-01

    Hfq proteins in Gram-negative bacteria play important roles in bacterial physiology and virulence, mediated by binding of the Hfq hexamer to small RNAs and/or mRNAs to post-transcriptionally regulate gene expression. However, the physiological role of Hfqs in Gram-positive bacteria is less clear. Bacillus anthracis, the causative agent of anthrax, uniquely expresses three distinct Hfq proteins, two from the chromosome (Hfq1, Hfq2) and one from its pXO1 virulence plasmid (Hfq3). The protein sequences of Hfq1 and 3 are evolutionarily distinct from those of Hfq2 and of Hfqs found in other Bacilli. Here, the quaternary structure of each B. anthracis Hfq protein, as produced heterologously in Escherichia coli, was characterized. While Hfq2 adopts the expected hexamer structure, Hfq1 does not form similarly stable hexamers in vitro. The impact on the monomer-hexamer equilibrium of varying Hfq C-terminal tail length and other sequence differences among the Hfqs was examined, and a sequence region of the Hfq proteins that was involved in hexamer formation was identified. It was found that, in addition to the distinct higher-order structures of the Hfq homologs, they give rise to different phenotypes. Hfq1 has a disruptive effect on the function of E. coli Hfq in vivo, while Hfq3 expression at high levels is toxic to E. coli but also partially complements Hfq function in E. coli. These results set the stage for future studies of the roles of these proteins in B. anthracis physiology and for the identification of sequence determinants of phenotypic complementation.

  11. Disentangling the role of structure and friction in shear jamming

    NASA Astrophysics Data System (ADS)

    Vinutha, H. A.; Sastry, Srikanth

    2016-06-01

    Amorphous sphere packings have been intensely investigated to understand mechanical and flow behaviour of dense granular matter and to explore universal aspects of the jamming transition, from fluid to structurally arrested states. Considerable recent research has focused on anisotropic packings of frictional grains generated by shear deformation leading to shear jamming, occurring below the jamming density for isotropic packings of frictionless grains. Here, with the aim of disentangling the role of shear-deformation-induced structures and friction in generating shear jamming, we computationally study sheared assemblies of frictionless spheres, over a wide range of densities. We demonstrate that shear deformation alone leads to the emergence of geometric features characteristic of jammed packings, with the increase of shear strain. We also show that such emergent geometry, together with friction, leads to mechanically stable, shear-jammed, packings above a threshold density that lies well below the isotropic jamming point.

  12. Volutin granules of Eimeria parasites are acidic compartments and have physiological and structural characteristics similar to acidocalcisomes

    PubMed Central

    Medeiros, Lia Carolina Soares; Gomes, Fabio; Maciel, Luis Renato Maia; Seabra, Sergio Henrique; Docampo, Roberto; Moreno, Silvia; Plattner, Helmut; Hentschel, Joachim; Kawazoe, Urara; Barrabin, Hector; de Souza, Wanderley; DaMatta, Renato Augusto; Miranda, Kildare

    2012-01-01

    The structural organization of parasites has been the subject of investigation by many groups and has lead to the identification of structures and metabolic pathways that may represent targets for anti-parasitic drugs. A specific group of organelles named acidocalcisomes has been identified in a number of organisms, including the apicomplexan parasites such as Toxoplasma and Plasmodium, where they have been shown to be involved in cation homeostasis, polyphosphate metabolism, and osmoregulation. Their structural counterparts in the apicomplexan parasite Eimeria have not been fully characterized. In this work, the ultrastructural and chemical properties of acidocalcisomes in Eimeria were characterized. Electron microscopy analysis of Eimeria parasites showed the dense organelles called volutin granules similar to acidocalcisomes. Immunolocalization of the vacuolar proton pyrophosphatase, considered as a marker for acidocalcisomes, showed labeling in vesicles of size and distribution similar to the dense organelles seen by electron microscopy. Spectrophotometric measurements of the kinetics of proton uptake showed a vacuolar proton pyrophosphatase activity. X-ray mapping revealed significant amounts of Na, Mg, P, K, Ca, and Zn in their matrix. The results suggest that volutin granules of Eimeria parasites are acidic, dense organelles and possess structural and chemical properties analogous to those of other acidocalcisomes, suggesting a similar functional role in these parasites. PMID:21699625

  13. Identification of 7alpha-hydroxypregnenolone, a novel bioactive amphibian neurosteroid stimulating locomotor activity, and its physiological roles in the regulation of locomotion.

    PubMed

    Tsutsui, Kazuyoshi; Haraguchi, Shogo; Matsunaga, Masahiro; Koyama, Teppei; Do Rego, Jean-Luc; Vaudry, Hubert

    2010-09-01

    We now know that steroids can be synthesized de novo by the brain and the peripheral nervous system. Such steroids are called neurosteroids and de novo neurosteroidogenesis from cholesterol is a conserved property of vertebrate brains. Our studies over the past decade have demonstrated that the brain expresses several kinds of steroidogenic enzymes and produces a variety of neurosteroids in sub-mammalian species. However, neurosteroid biosynthetic pathways in amphibians, as well as other vertebrates may still not be fully mapped. We first found that the newt brain actively produces 7alpha-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. We then demonstrated that 7alpha-hydroxypregnenolone acts as a novel bioactive neurosteroid to stimulate locomotor activity of newt by means of the dopaminergic system. Subsequently, we analyzed the physiological roles of 7alpha-hydroxypregnenolone in the regulation of locomotor activity of newt. This paper summarizes the advances made in our understanding of 7alpha-hydroxypregnenolone, a newly discovered bioactive amphibian neurosteroid stimulating locomotor activity, and its physiological roles in the regulation of locomotion in newt.

  14. Molecular and physiological evidences for the role in appetite regulation of apelin and its receptor APJ in Ya-fish (Schizothorax prenanti).

    PubMed

    Lin, Fangjun; Wu, Hongwei; Chen, Hu; Xin, Zhiming; Yuan, Dengyue; Wang, Tao; Liu, Ju; Gao, Yundi; Zhang, Xin; Zhou, Chaowei; Wei, Rongbin; Chen, Defang; Yang, Shiyong; Wang, Yan; Pu, Yundan; Li, Zhiqiong

    2014-10-01

    Apelin is a recently discovered peptide produced by several tissues with diverse physiological actions mediated by its receptor APJ. In order to better understand the role of apelin in the regulation of appetite in fish, we cloned the cDNAs encoding apelin and APJ, and investigated their mRNA distributions in Ya-fish (Schizothorax prenanti) tissues. We also assessed the effects of different nutritional status on apelin and APJ mRNAs abundance. Apelin and APJ mRNAs were ubiquitously expressed in all tissues tested, relatively high expression levels were detected in the heart, spleen, hypothalamus and kidney. Short-term fasting significant increased APJ mRNA expression, but no significant difference between fasted fish and fed control on 5- and 7-day. Meanwhile, apelin mRNA expression consistently increased during the 7-day food deprivation. In order to further characterize apelin in fish, we performed intraperitoneal (i.p.) injection of apelin-13 and examined food intake of the injected fish. Apelin injected at a dose of 100 ng/g body weight induced a significant increase in food intake compared to saline injected fish. Our results suggest that apelin acts as an orexigenic factor in Ya-fish. Their widespread distributions also suggest that apelin and APJ might play multiple physiological regulating roles in fish.

  15. Physiological Waterfalls

    ERIC Educational Resources Information Center

    Leith, David E.

    1976-01-01

    Provides background information, defining areas within organ systems where physiological waterfalls exist. Describes pressure-flow relationships of elastic tubes (blood vessels, airways, renal tubules, various ducts). (CS)

  16. Swimming physiology.

    PubMed

    Holmér, I

    1992-05-01

    Swimming takes place in a medium, that presents different gravitational and resistive forces, respiratory conditions and thermal stress compared to air. The energy cost of propulsion in swimming is high, but a considerable reduction occurs at a given velocity as result of regular swim training. In medley swimmers the energy cost is lowest for front crawl, followed by backstroke, butterfly and breast-stroke. Cardiac output is probably not limiting for performance since swimmers easily achieve higher values during running. Maximal heart rate, however, is lowered by approx. 10 beats/min during swimming compared to running. Most likely active muscle mass is smaller and rate of power production lesser in swimming. Local factors, such as peripheral circulation, capillary density, perfusion pressure and metabolic capacity of active muscles, are important determinants of the power production capacity and emphasize the role of swim specific training movements. Improved swimming technique and efficiency are likely to explain much of the continuous progress in performance. Rational principles based on improved understanding of the biomechanics and physiology of swimming should be guidelines for swimmers and coaches in their efforts to explore the limits of human performance. PMID:1642724

  17. AN EXAMPLE OF MODEL STRUCTURE DIFFERENCES USING SENSITIVITY ANALYSES IN PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELS OF TRICHLOROETHYLENE IN HUMANS

    EPA Science Inventory

    Abstract Trichloroethylene (TCE) is an industrial chemical and an environmental contaminant. TCE and its metabolites may be carcinogenic and affect human health. Physiologically based pharmacokinetic (PBPK) models that differ in compartmentalization are developed for TCE metabo...

  18. Physiological and biochemical responses and microscopic structure changes of Populus tomentosa Carr seedlings to 4-BDE exposure.

    PubMed

    Cai, Man; Li, Yuling; Li, Yanling; Du, Kejiu

    2015-09-01

    Populus species are very effective in remediation of contaminants. Polybrominated diphenyl ethers (PBDEs) are commonly used as flame retardants and are known to be persistent environmental pollutants. Numerous studies have shown that PBDEs are rising in human tissues and biota. 4-Monobrominated diphenyl ether (4-BDE), one of the less brominated PBDEs, was served as a model compound for biodegradation of lower brominated congeners. The present study was designed to clarify the effects of 4-BDE stress on morphological, physiological, and biochemical impacts of Populus tomentosa Carr in a tissue culture condition. Different concentrations of 4-BDE (3 and 30 mg L(-1)) were supplied alone or together with 0.5 mg L(-1) IBA in tissue culture media. With the concentration increased, 4-BDE caused negative effects on the microscopic structure of roots, stem, and leaves. The leaf color became shallow in low concentration of 4-BDE treatments and appeared albinism with 4-BDE concentration increased. The chlorophyll content and the leaf mass per area of albino leaves reduced significantly. 4-BDE also caused positive effects on the adventitious root differentiation and the biomass below 30 mg L(-1). With the 4-BDE treatment time increased (23, 47, and 58 days), the peroxidase (POD) activity displayed the decreasing trend. The proline content decreased first and then increased. Exposure to 4-BDE induced the malondialdehyde (MDA) to increase in leaves. Application of 4-BDE affected the endogenous hormone levels of cuttings in their adventitious roots inducing media. Below 0.3 mg L(-1), 4-BDE caused the faint expression of auxin-sensitive DR5::GUS reporter gene in Arabidopsis thaliana. Additionally, P. tomentosa Carr exhibited the better tolerance against 4-BDE in the range of less than 30 mg L(-1). PMID:25971809

  19. Interactions of cationic polystyrene nanoparticles with marine bivalve hemocytes in a physiological environment: Role of soluble hemolymph proteins.

    PubMed

    Canesi, Laura; Ciacci, Caterina; Fabbri, Rita; Balbi, Teresa; Salis, Annalisa; Damonte, Gianluca; Cortese, Katia; Caratto, Valentina; Monopoli, Marco P; Dawson, Kenneth; Bergami, Elisa; Corsi, Ilaria

    2016-10-01

    The bivalve Mytilus galloprovincialis has proven as a suitable model invertebrate for evaluating the potential impact of nanoparticles (NPs) in the marine environment. In particular, in mussels, the immune system represents a sensitive target for different types of NPs. In environmental conditions, both NP intrinsic properties and those of the receiving medium will affect particle behavior and consequent bioavailability/uptake/toxicity. However, the evaluation of the biological effects of NPs requires additional understanding of how, once within the organism, NPs interact at the molecular level with cells in a physiological environment. In mammalian systems, different NPs associate with serum soluble components, organized into a "protein corona", which affects particle interactions with target cells. However, no information is available so far on the interactions of NPs with biological fluids of aquatic organisms. In this work, the influence of hemolymph serum (HS) on the in vitro effects of amino modified polystyrene NPs (PS-NH2) on Mytilus hemocytes was investigated. Hemocytes were incubated with PS-NH2 suspensions in HS (1, 5 and 50µg/mL) and the results were compared with those obtained in ASW medium. Cell functional parameters (lysosomal membrane stability, oxyradical production, phagocytosis) were evaluated, and morphological changes were investigated by TEM. The activation state of the signalling components involved in Mytilus immune response (p38 MAPK and PKC) was determined. The results show that in the presence of HS, PS-NH2 increased cellular damage and ROS production with respect to ASW medium. The effects were apparently mediated by disregulation of p38 MAPK signalling. The formation of a PS-NH2-protein corona in HS was investigated by centrifugation, and 1D- gel electrophoresis and nano-HPLC-ESI-MS/MS. The results identified the Putative C1q domain containing protein (MgC1q6) as the only component of the PS-NH2 hard protein corona in Mytilus

  20. Rowing Physiology.

    ERIC Educational Resources Information Center

    Spinks, W. L.

    This review of the literature discusses and examines the methods used in physiological assessment of rowers, results of such assessments, and future directions emanating from research in the physiology of rowing. The first section discusses the energy demands of rowing, including the contribution of the energy system, anaerobic metabolism, and the…

  1. Hydrogeologic role of geologic structures. Part 2: analytical models

    NASA Astrophysics Data System (ADS)

    Levens, Russell L.; Williams, Roy E.; Ralston, Dale R.

    1994-04-01

    This paper is the second of two papers that address the influence of geologic structures on ground water flow at various scales in fractured rocks. The ultimate purpose of this research is to investigate the feasibility of grouting preferentially permeable zones as a strategy to minimize the production of acid mine drainage in underground hard rock mines in which the major permeability is structure and fracture controlled. The aim of grouting is to reduce permeability around mined-out openings, to minimize the rate of inflow of ground water into such openings via the structurally controlled preferentially permeable pathways. A series of hydraulic stress tests were conducted to help characterize the role of geologic structures in controlling the ground water flow system in the vicinity of the Bunker Hill Mine in north Idaho. The results of these tests indicate that most of the ground water that flows from the underground drillholes used for hydraulic stress testing is derived from a few discrete, structurally produced fracture zones that are more or less connected through smaller-scale fractures. Four types of analytical models are considered as a means of analyzing the results of multiple drillhole hydraulic stress tests, as follows: cross-hole equivalent porous media; double-porosity equivalent porous media; a solution to flow in and around a single vertical fracture; leaky equivalent porous media, partial penetration. The estimation of hydraulic coefficients in complex fractured rock environments involves the combined application of a number of deterministic analytical models. The models to be used are selected dependent on the location of the drawdown observations relative to the water-producing zone and the length of the test. The result of the tests can be related to the permeability hierarchy discussed in our first paper.

  2. The role of ontogeny in physiological tolerance: decreasing hydrostatic pressure tolerance with development in the northern stone crab Lithodes maja.

    PubMed

    Munro, Catriona; Morris, James P; Brown, Alastair; Hauton, Chris; Thatje, Sven

    2015-06-22

    Extant deep-sea invertebrate fauna represent both ancient and recent invasions from shallow-water habitats. Hydrostatic pressure may present a significant physiological challenge to organisms seeking to colonize deeper waters or migrate ontogenetically. Pressure may be a key factor contributing to bottlenecks in the radiation of taxa and potentially drive speciation. Here, we assess shifts in the tolerance of hydrostatic pressure through early ontogeny of the northern stone crab Lithodes maja, which occupies a depth range of 4-790 m in the North Atlantic. The zoea I, megalopa and crab I stages were exposed to hydrostatic pressures up to 30.0 MPa (equivalent of 3000 m depth), and the relative fold change of genes putatively coding for the N-methyl-D-aspartate receptor-regulated protein 1 (narg gene), two heat-shock protein 70 kDa (HSP70) isoforms and mitochondrial Citrate Synthase (CS gene) were measured. This study finds a significant increase in the relative expression of the CS and hsp70a genes with increased hydrostatic pressure in the zoea I stage, and an increase in the relative expression of all genes with increased hydrostatic pressure in the megalopa and crab I stages. Transcriptional responses are corroborated by patterns in respiratory rates in response to hydrostatic pressure in all stages. These results suggest a decrease in the acute high-pressure tolerance limit as ontogeny advances, as reflected by a shift in the hydrostatic pressure at which significant differences are observed.

  3. Physiological Regulation of Isocitrate Dehydrogenase and the Role of 2-Oxoglutarate in Prochlorococcus sp. Strain PCC 9511

    PubMed Central

    Diez, Jesús; Gómez-Baena, Guadalupe; Rangel-Zúñiga, Oriol Alberto; García-Fernández, José Manuel

    2014-01-01

    The enzyme isocitrate dehydrogenase (ICDH; EC 1.1.1.42) catalyzes the oxidative decarboxylation of isocitrate, to produce 2-oxoglutarate. The incompleteness of the tricarboxylic acids cycle in marine cyanobacteria confers a special importance to isocitrate dehydrogenase in the C/N balance, since 2-oxoglutarate can only be metabolized through the glutamine synthetase/glutamate synthase pathway. The physiological regulation of isocitrate dehydrogenase was studied in cultures of Prochlorococcus sp. strain PCC 9511, by measuring enzyme activity and concentration using the NADPH production assay and Western blotting, respectively. The enzyme activity showed little changes under nitrogen or phosphorus starvation, or upon addition of the inhibitors DCMU, DBMIB and MSX. Azaserine, an inhibitor of glutamate synthase, induced clear increases in the isocitrate dehydrogenase activity and icd gene expression after 24 h, and also in the 2-oxoglutarate concentration. Iron starvation had the most significant effect, inducing a complete loss of isocitrate dehydrogenase activity, possibly mediated by a process of oxidative inactivation, while its concentration was unaffected. Our results suggest that isocitrate dehydrogenase responds to changes in the intracellular concentration of 2-oxoglutarate and to the redox status of the cells in Prochlorococcus. PMID:25061751

  4. Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions.

    PubMed

    Lefebvre, Hervé; Thomas, Michaël; Duparc, Céline; Bertherat, Jérôme; Louiset, Estelle

    2016-01-01

    In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions. PMID:27489549

  5. The role of ontogeny in physiological tolerance: decreasing hydrostatic pressure tolerance with development in the northern stone crab Lithodes maja

    PubMed Central

    Munro, Catriona; Morris, James P.; Brown, Alastair; Hauton, Chris; Thatje, Sven

    2015-01-01

    Extant deep-sea invertebrate fauna represent both ancient and recent invasions from shallow-water habitats. Hydrostatic pressure may present a significant physiological challenge to organisms seeking to colonize deeper waters or migrate ontogenetically. Pressure may be a key factor contributing to bottlenecks in the radiation of taxa and potentially drive speciation. Here, we assess shifts in the tolerance of hydrostatic pressure through early ontogeny of the northern stone crab Lithodes maja, which occupies a depth range of 4–790 m in the North Atlantic. The zoea I, megalopa and crab I stages were exposed to hydrostatic pressures up to 30.0 MPa (equivalent of 3000 m depth), and the relative fold change of genes putatively coding for the N-methyl-d-aspartate receptor-regulated protein 1 (narg gene), two heat-shock protein 70 kDa (HSP70) isoforms and mitochondrial Citrate Synthase (CS gene) were measured. This study finds a significant increase in the relative expression of the CS and hsp70a genes with increased hydrostatic pressure in the zoea I stage, and an increase in the relative expression of all genes with increased hydrostatic pressure in the megalopa and crab I stages. Transcriptional responses are corroborated by patterns in respiratory rates in response to hydrostatic pressure in all stages. These results suggest a decrease in the acute high-pressure tolerance limit as ontogeny advances, as reflected by a shift in the hydrostatic pressure at which significant differences are observed. PMID:26041343

  6. A New Insight into the Physiological Role of Bile Salt Hydrolase among Intestinal Bacteria from the Genus Bifidobacterium

    PubMed Central

    Jarocki, Piotr; Podleśny, Marcin; Glibowski, Paweł; Targoński, Zdzisław

    2014-01-01

    This study analyzes the occurrence of bile salt hydrolase in fourteen strains belonging to the genus Bifidobacterium. Deconjugation activity was detected using a plate test, two-step enzymatic reaction and activity staining on a native polyacrylamide gel. Subsequently, bile salt hydrolases from B. pseudocatenulatum and B. longum subsp. suis were purified using a two-step chromatographic procedure. Biochemical characterization of the bile salt hydrolases showed that the purified enzymes hydrolyzed all of the six major human bile salts under the pH and temperature conditions commonly found in the human gastrointestinal tract. Next, the dynamic rheometry was applied to monitor the gelation process of deoxycholic acid under different conditions. The results showed that bile acids displayed aqueous media gelating properties. Finally, gel-forming abilities of bifidobacteria exhibiting bile salt hydrolase activity were analyzed. Our investigations have demonstrated that the release of deconjugated bile acids led to the gelation phenomenon of the enzymatic reaction solution containing purified BSH. The presented results suggest that bile salt hydrolase activity commonly found among intestinal microbiota increases hydrogel-forming abilities of certain bile salts. To our knowledge, this is the first report showing that bile salt hydrolase activity among Bifidobacterium is directly connected with the gelation process of bile salts. In our opinion, if such a phenomenon occurs in physiological conditions of human gut, it may improve bacterial ability to colonize the gastrointestinal tract and their survival in this specific ecological niche. PMID:25470405

  7. Role of ACTH in the Interactive/Paracrine Regulation of Adrenal Steroid Secretion in Physiological and Pathophysiological Conditions

    PubMed Central

    Lefebvre, Hervé; Thomas, Michaël; Duparc, Céline; Bertherat, Jérôme; Louiset, Estelle

    2016-01-01

    In the normal human adrenal gland, steroid secretion is regulated by a complex network of autocrine/paracrine interactions involving bioactive signals released by endothelial cells, nerve terminals, chromaffin cells, immunocompetent cells, and adrenocortical cells themselves. ACTH can be locally produced by medullary chromaffin cells and is, therefore, a major mediator of the corticomedullary functional interplay. Plasma ACTH also triggers the release of angiogenic and vasoactive agents from adrenocortical cells and adrenal mast cells and, thus, indirectly regulates steroid production through modulation of the adrenal blood flow. Adrenocortical neoplasms associated with steroid hypersecretion exhibit molecular and cellular defects that tend to reinforce the influence of paracrine regulatory loops on corticosteroidogenesis. Especially, ACTH has been found to be abnormally synthesized in bilateral macronodular adrenal hyperplasia responsible for hypercortisolism. In these tissues, ACTH is detected in a subpopulation of adrenocortical cells that express gonadal markers. This observation suggests that ectopic production of ACTH may result from impaired embryogenesis leading to abnormal maturation of the adrenogonadal primordium. Globally, the current literature indicates that ACTH is a major player in the autocrine/paracrine processes occurring in the adrenal gland in both physiological and pathological conditions. PMID:27489549

  8. The relative role of patient physiology and device optimisation in cardiac resynchronisation therapy: A computational modelling study.

    PubMed

    Crozier, Andrew; Blazevic, Bojan; Lamata, Pablo; Plank, Gernot; Ginks, Matthew; Duckett, Simon; Sohal, Manav; Shetty, Anoop; Rinaldi, Christopher A; Razavi, Reza; Smith, Nicolas P; Niederer, Steven A

    2016-07-01

    Cardiac resynchronisation therapy (CRT) is an established treatment for heart failure, however the effective selection of patients and optimisation of therapy remain controversial. While extensive research is ongoing, it remains unclear whether improvements in patient selection or therapy planning offers a greater opportunity for the improvement of clinical outcomes. This computational study investigates the impact of both physiological conditions that guide patient selection and the optimisation of pacing lead placement on CRT outcomes. A multi-scale biophysical model of cardiac electromechanics was developed and personalised to patient data in three patients. These models were separated into components representing cardiac anatomy, pacing lead location, myocardial conductivity and stiffness, afterload, active contraction and conduction block for each individual, and recombined to generate a cohort of 648 virtual patients. The effect of these components on the change in total activation time of the ventricles (ΔTAT) and acute haemodynamic response (AHR) was analysed. The pacing site location was found to have the largest effect on ΔTAT and AHR. Secondary effects on ΔTAT and AHR were found for functional conduction block and cardiac anatomy. The simulation results highlight a need for a greater emphasis on therapy optimisation in order to achieve the best outcomes for patients.

  9. The physiology of salinity tolerance in larvae of two species of Culex mosquitoes: the role of compatible solutes.

    PubMed

    Patrick, M L; Bradley, T J

    2000-02-01

    We investigated the physiological basis for differences in salinity tolerance ranges in mosquito larvae of the genus Culex. We examined the response of larvae of C. quinquefasciatus, a freshwater obligate, and C. tarsalis, a euryhaline osmoconformer, following transfer from fresh water to 34% sea water. Hemolymph Na(+) and Cl(-) levels increased similarly in both species, indicating that ion regulation does not differ under these conditions. C. quinquefasciatus responded to increased environmental salinity with increased hemolymph levels of serine, but suffered a significant reduction in levels of trehalose. C. tarsalis responded to increased environmental salinity with increased hemolymph levels of both proline and trehalose. When C. tarsalis larvae were held in 64% sea water, which C. quinquefasciatus larvae cannot tolerate, hemolymph proline and trehalose were accumulated approximately 50-fold and twofold, respectively, relative to freshwater values. We found that proline serves as both an intra- and extracellular compatible solute in C. tarsalis, the first such circumstance documented in an animal in response to increased environmental salinity. Analyses of the acute responses of the two species to an increase in salinity (from 30% to 50% sea water) indicate that larvae of C. tarsalis are able to volume-regulate via drinking and to attenuate increases in hemolymph NaCl concentration using unknown mechanisms during large, rapid increases in salinity. PMID:10648224

  10. Identification of a group of Haemophilus influenzae penicillin-binding proteins that may have complementary physiological roles

    SciTech Connect

    Malouin, F.; Parr, T.R. Jr.; Bryan, L.E. )

    1990-02-01

    (35S)penicillin bound to different Haemophilus influenzae proteins in assays performed at 20, 37, or 42{degrees}C. Penicillin-binding proteins 3a, 3b, 4, and 4' formed a group characterized by their affinity for moxalactam, cefotaxime, and piperacillin. Penicillin-binding protein 4' showed specific properties that may reflect its complementary role in septation.

  11. Endocrine factors in the hypothalamic regulation of food intake in females: a review of the physiological roles and interactions of ghrelin, leptin, thyroid hormones, oestrogen and insulin.

    PubMed

    Somogyi, V; Gyorffy, A; Scalise, T J; Kiss, D S; Goszleth, G; Bartha, T; Frenyo, V L; Zsarnovszky, A

    2011-06-01

    Controlling energy homeostasis involves modulating the desire to eat and regulating energy expenditure. The controlling machinery includes a complex interplay of hormones secreted at various peripheral endocrine endpoints, such as the gastrointestinal tract, the adipose tissue, thyroid gland and thyroid hormone-exporting organs, the ovary and the pancreas, and, last but not least, the brain itself. The peripheral hormones that are the focus of the present review (ghrelin, leptin, thyroid hormones, oestrogen and insulin) play integrated regulatory roles in and provide feedback information on the nutritional and energetic status of the body. As peripheral signals, these hormones modulate central pathways in the brain, including the hypothalamus, to influence food intake, energy expenditure and to maintain energy homeostasis. Since the growth of the literature on the role of various hormones in the regulation of energy homeostasis shows a remarkable and dynamic expansion, it is now becoming increasingly difficult to understand the individual and interactive roles of hormonal mechanisms in their true complexity. Therefore, our goal is to review, in the context of general physiology, the roles of the five best-known peripheral trophic hormones (ghrelin, leptin, thyroid hormones, oestrogen and insulin, respectively) and discuss their interactions in the hypothalamic regulation of food intake.

  12. Role of Endogenous Sulfur Dioxide in Regulating Vascular Structural Remodeling in Hypertension

    PubMed Central

    Chen, Selena; Tang, Chaoshu

    2016-01-01

    Sulfur dioxide (SO2), an emerging gasotransmitter, was discovered to be endogenously generated in the cardiovascular system. Recently, the physiological effects of endogenous SO2 were confirmed. Vascular structural remodeling (VSR), an important pathological change in many cardiovascular diseases, plays a crucial role in the pathogenesis of the diseases. Here, the authors reviewed the research progress of endogenous SO2 in regulating VSR by searching the relevant data from PubMed and Medline. In spontaneously hypertensive rats (SHRs) and pulmonary hypertensive rats, SO2/aspartate aminotransferase (AAT) pathway was significantly altered. SO2 inhibited vascular smooth muscle cell (VSMC) proliferation, promoted apoptosis, inhibited the synthesis of extracellular collagen but promoted its degradation, and enhanced antioxidative capacity, thereby playing a significant role in attenuating VSR. However, the detailed mechanisms needed to be further explored. Further studies in this field would be important for the better understanding of the pathogenesis of systemic hypertension and pulmonary hypertension. Also, clinical trials are needed to demonstrate if SO2 would be a potential therapeutic target in cardiovascular diseases. PMID:27721913

  13. Neuropeptide physiology in helminths.

    PubMed

    Mousley, Angela; Novozhilova, Ekaterina; Kimber, Michael J; Day, Tim A

    2010-01-01

    Parasitic worms come from two distinct, distant phyla, Nematoda (roundworms) and Platyhelminthes (flatworms). The nervous systems of worms from both phyla are replete with neuropeptides and there is ample physiological evidence that these neuropeptides control vital aspects of worm biology. In each phyla, the physiological evidence for critical roles for helminth neuropeptides is derived from both parasitic and free-living members. In the nematodes, the intestinal parasite Ascaris suum and the free-living Caenorhabditis elegans have yielded most of the data; in the platyhelminths, the most physiological data has come from the blood fluke Schistosoma mansoni. FMRFamide-like peptides (FLPs) have many varied effects (excitation, relaxation, or a combination) on somatic musculature, reproductive musculature, the pharynx and motor neurons in nematodes. Insulin-like peptides (INSs) play an essential role in nematode dauer formation and other developmental processes. There is also some evidence for a role in somatic muscle control for the somewhat heterogeneous grouping ofpeptides known as neuropeptide-like proteins (NLPs). In platyhelminths, as in nematodes, FLPs have a central role in somatic muscle function. Reports of FLP physiological action in platyhelminths are limited to a potent excitation of the somatic musculature. Platyhelminths are also abundantly endowed with neuropeptide Fs (NPFs), which appear absent from nematodes. There is not yet any data linking platyhelminth NPF to any particular physiological outcome, but this neuropeptide does potently and specifically inhibit cAMP accumulation in schistosomes. In nematodes and platyhelminths, there is an abundance of physiological evidence demonstrating that neuropeptides play critical roles in the biology of both free-living and parasitic helminths. While it is certainly true that there remains a great deal to learn about the biology of neuropeptides in both phyla, physiological evidence presently available points

  14. Hydathode trichomes actively secreting water from leaves play a key role in the physiology and evolution of root-parasitic rhinanthoid Orobanchaceae

    PubMed Central

    Světlíková, Petra; Hájek, Tomáš; Těšitel, Jakub

    2015-01-01

    Background and Aims Root hemiparasites from the rhinanthoid clade of Orobanchaceae possess metabolically active glandular trichomes that have been suggested to function as hydathode trichomes actively secreting water, a process that may facilitate resource acquisition from the host plant’s root xylem. However, no direct evidence relating the trichomes to water secretion exists, and carbon budgets associated with this energy-demanding process have not been determined. Methods Macro- and microscopic observations of the leaves of hemiparasitic Rhinanthus alectorolophus were conducted and night-time gas exchange was measured. Correlations were examined among the intensity of guttation, respiration and transpiration, and analysis of these correlations allowed the carbon budget of the trichome activity to be quantified. We examined the intensity of guttation, respiration and transpiration, correlations among which indicate active water secretion. Key Results Guttation was observed on the leaves of 50 % of the young, non-flowering plants that were examined, and microscopic observations revealed water secretion from the glandular trichomes present on the abaxial leaf side. Night-time rates of respiration and transpiration and the presence of guttation drops were positively correlated, which is a clear indicator of hydathode trichome activity. Subsequent physiological measurements on older, flowering plants indicated neither intense guttation nor the presence of correlations, which suggests that the peak activity of hydathodes is in the juvenile stage. Conclusions This study provides the first unequivocal evidence for the physiological role of the hydathode trichomes in active water secretion in the rhinanthoid Orobanchaceae. Depending on the concentration of organic elements calculated to be in the host xylem sap, the direct effect of water secretion on carbon balance ranges from close to neutral to positive. However, it is likely to be positive in the xylem-only feeding

  15. Role of environmental pollutants in liver physiology: special references to peoples living in the oil drilling sites of Assam.

    PubMed

    Dey, Tapan; Gogoi, Kabita; Unni, Balagopalan; Bharadwaz, Moonmee; Kalita, Munmi; Ozah, Dibyajyoti; Kalita, Manoj; Kalita, Jatin; Baruah, Pranab Kumar; Bora, Thaneswar

    2015-01-01

    The populations residing near polluted sites are more prone to various types of diseases. The important causes of air pollution are the suspended particulate matter, respirable suspended particulate matter, sulfur dioxide and nitrogen dioxide. As limited information is available enumerating the effect of these pollutants on liver physiology of the population living near the polluted sites; in the present study, we tried to investigate their effect on liver of the population residing near the oil drilling sites since birth. In this study, a randomly selected 105 subjects (46 subjects from oil drilling site and 61 subjects from control site) aged above 30 years were taken under consideration. The particulate matter as well as the gaseous pollutants, sulfur dioxide and nitrogen dioxide, were analyzed through a respirable dust sampler. The level of alkaline phosphatase, alanine transaminase and aspartate transaminase enzymes in serum were measured by spectrophotometer. The generalized regression model studies suggests a higher concentration of respirable suspended particulate matter, suspended particulate matter and nitrogen dioxide lowers the alkaline phosphatase level (p<0.0001) by 3.5 times (95% CI 3.1-3.9), 1.5 times (95% CI 1.4-1.6) and 12 times (95% CI 10.74-13.804), respectively in the exposed group. The higher concentration of respirable suspended particulate matter and nitrogen dioxide in air was associated with increase in alanine transaminase level (p<0.0001) by 0.8 times (95% CI 0.589-1.049) and by 2.8 times (95% CI 2.067-3.681) respectively in the exposed group. The increase in nitrogen dioxide level was also associated with increase in aspartate transaminase level (p<0.0001) by 2.5 times (95% CI 1.862-3.313) in the exposed group as compared to control group. Thus, the study reveals that long-term exposure to the environmental pollutants may lead to liver abnormality or injury of populations living in polluted sites.

  16. Structure and function of gap junction proteins: role of gap junction proteins in embryonic heart development.

    PubMed

    Ahir, Bhavesh K; Pratten, Margaret K

    2014-01-01

    Intercellular (cell-to-cell) communication is a crucial and complex mechanism during embryonic heart development. In the cardiovascular system, the beating of the heart is a dynamic and key regulatory process, which is functionally regulated by the coordinated spread of electrical activity through heart muscle cells. Heart tissues are composed of individual cells, each bearing specialized cell surface membrane structures called gap junctions that permit the intercellular exchange of ions and low molecular weight molecules. Gap junction channels are essential in normal heart function and they assist in the mediated spread of electrical impulses that stimulate synchronized contraction (via an electrical syncytium) of cardiac tissues. This present review describes the current knowledge of gap junction biology. In the first part, we summarise some relevant biochemical and physiological properties of gap junction proteins, including their structure and function. In the second part, we review the current evidence demonstrating the role of gap junction proteins in embryonic development with particular reference to those involved in embryonic heart development. Genetics and transgenic animal studies of gap junction protein function in embryonic heart development are considered and the alteration/disruption of gap junction intercellular communication which may lead to abnormal heart development is also discussed.

  17. The role of structural inheritance in continental rifting

    NASA Astrophysics Data System (ADS)

    Buiter, Susanne; Tetreault, Joya

    2015-04-01

    In nature we observe that passive margins tend to originate on continental collision zones. This is not surprising as continents are long-lived and therefore have undergone multiple deformation phases, producing many regions with inherited structures. Collision zones can act as intrinsic rift-localizers for several reasons: rifting at a suture may be initiated by extensional collapse of the orogen, the thicker crustal root of orogens and their associated increase in heat producing elements makes orogens thermally weak, and inherited thrust faults form large-scale heterogeneities. When investigating continental extension geodynamically, numerical experiments often simplify such inheritance and start from laterally homogeneous crustal layers with a prescribed inhomogeneity that initiates deformation. These inhomogeneities represent thermal or structural remnants from previous deformation phases and are imposed as a thermal anomaly, a variation in Moho geometry, or an inherited weak region. However, imposed initial heterogeneities do not fully capture the structural and thermal complexities of continental sutures. Here we present 2-D numerical experiments that investigate the role of inherited crustal structures in continental rifting and passive margin formation. We first examine a series of experiments in which we explicitly prescribe collisional structures in the initial setup, such as increased Moho depth and inherited thrust faults. Different prescribed collisional structures result in different rift to break-up durations, crustal shear zone patterns, and margin symmetry. Our second series of experiments actually creates an inherited collision zone through subduction and closure of an ocean. We use this set-up to investigate how extension localizes on a former continental collision zone. Passive margin architecture strongly depends on the duration of post-collision thermal equilibration time, with a long pause between collision and initiation of extension

  18. Heme and erythropoieis: more than a structural role

    PubMed Central

    Chiabrando, Deborah; Mercurio, Sonia; Tolosano, Emanuela

    2014-01-01

    Erythropoiesis is the biological process that consumes the highest amount of body iron for heme synthesis. Heme synthesis in erythroid cells is finely coordinated with that of alpha (α) and beta (β)-globin, resulting in the production of hemoglobin, a tetramer of 2α- and 2β-globin chains, and heme as the prosthetic group. Heme is not only the structural component of hemoglobin, but it plays multiple regulatory roles during the differentiation of erythroid precursors since it controls its own synthesis and regulates the expression of several erythroid-specific genes. Heme is synthesized in developing erythroid progenitors by the stage of proerythroblast, through a series of eight enzymatic reactions divided between mitochondria and cytosol. Defects of heme synthesis in the erythroid lineage result in sideroblastic anemias, characterized by microcytic anemia associated to mitochondrial iron overload, or in erythropoietic porphyrias, characterized by porphyrin deposition in erythroid cells. Here, we focus on the heme biosynthetic pathway and on human erythroid disorders due to defective heme synthesis. The regulatory role of heme during erythroid differentiation is discussed as well as the heme-mediated regulatory mechanisms that allow the orchestration of the adaptive cell response to heme deficiency. PMID:24881043

  19. The role of sympathetic and parasympathetic nerve systems on the smooth muscle of rat seminal vesicles - experimental results and speculation for physiological implication on ejaculation.

    PubMed

    Hsieh, J-T; Kuo, Y-C; Chang, H-C; Liu, S-P; Chen, J-H; Tsai, V F S

    2014-01-01

    Ejaculation is a process involving sympathetic and parasympathetic effects during different stages - emission and ejection. Some conditions of ejaculation dysfunction are associated with autonomic nerves. However, the exact effects of autonomic nerves on ejaculation are not well defined. Autonomic agonists induce different recorded trace patterns of seminal vesicular contraction. The different traces contain different components of phasic and tonic contraction, which may have physiological implications. In this study, we examined isolated rat seminal vesicle (SV) contraction by phenylephrine (PE), acetylcholine, and their respective antagonists and then speculated upon physiological roles of sympathetic and parasympathetic nerves on SV during ejaculation. We found that PE and Ach both achieved good contraction of rat SV. Compared to α1b for sympathetic and M1, M2 for parasympathetic receptors, α1a and M3 are the relatively dominant subtypes on rat SV. Adrenergic and cholinergic agonists cause different trace patterns of SV contraction. We speculated that the sympathetic effect is dominant during emission to squeeze seminal fluid out and that the parasympathetic effect is dominant during ejection to provide an anti-reflux effect on the ejaculatory duct.

  20. An experimental test of the role of environmental temperature variability on ectotherm molecular, physiological and life-history traits: implications for global warming.

    PubMed

    Folguera, Guillermo; Bastías, Daniel A; Caers, Jelle; Rojas, José M; Piulachs, Maria-Dolors; Bellés, Xavier; Bozinovic, Francisco

    2011-07-01

    Global climate change is one of the greatest threats to biodiversity; one of the most important effects is the increase in the mean earth surface temperature. However, another but poorly studied main characteristic of global change appears to be an increase in temperature variability. Most of the current analyses of global change have focused on mean values, paying less attention to the role of the fluctuations of environmental variables. We experimentally tested the effects of environmental temperature variability on characteristics associated to the fitness (body mass balance, growth rate, and survival), metabolic rate (VCO(2)) and molecular traits (heat shock protein expression, Hsp70), in an ectotherm, the terrestrial woodlouse Porcellio laevis. Our general hypotheses are that higher values of thermal amplitude may directly affect life-history traits, increasing metabolic cost and stress responses. At first, results supported our hypotheses showing a diversity of responses among characters to the experimental thermal treatments. We emphasize that knowledge about the cellular and physiological mechanisms by which animals cope with environmental changes is essential to understand the impact of mean climatic change and variability. Also, we consider that the studies that only incorporate only mean temperatures to predict the life-history, ecological and evolutionary impact of global temperature changes present important problems to predict the diversity of responses of the organism. This is because the analysis ignores the complexity and details of the molecular and physiological processes by which animals cope with environmental variability, as well as the life-history and demographic consequences of such variability.

  1. The role of inheritance in structuring hyperextended rift systems

    NASA Astrophysics Data System (ADS)

    Manatschal, Gianreto; Lavier, Luc; Chenin, Pauline

    2015-04-01

    A long-standing question in Earth Sciences is related to the importance of inheritance in controlling tectonic processes. In contrast to physical processes that are generally applicable, assessing the role of inheritance suffers from two major problems: firstly, it is difficult to appraise without having insights into the history of a geological system; and secondly all inherited features are not reactivated during subsequent deformation phases. Therefore, the aim of our presentation is to give some conceptual framework about how inheritance may control the architecture and evolution of hyperextended rift systems. We use the term inheritance to refer to the difference between an "ideal" layer-cake type lithosphere and a "real" lithosphere containing heterogeneities and we define 3 types of inheritance, namely structural, compositional and thermal inheritance. Moreover, we assume that the evolution of hyperextended rift systems reflects the interplay between their inheritance (innate/"genetic code") and the physical processes at play (acquired/external factors). Thus, by observing the architecture and evolution of hyperextended rift systems and integrating the physical processes, one my get hints on what may have been the original inheritance of a system. Using this approach, we focus on 3 well-studied rift systems that are the Alpine Tethys, Pyrenean-Bay of Biscay and Iberia-Newfoundland rift systems. For the studied examples we can show that: 1) strain localization on a local scale and during early stages of rifting is controlled by inherited structures and weaknesses 2) the architecture of the necking zone seems to be influenced by the distribution and importance of ductile layers during decoupled deformation and is consequently controlled by the thermal structure and/or the inherited composition of the curst 3) the location of breakup in the 3 examples is not significantly controlled by the inherited structures 4) inherited mantle composition and rift

  2. Movement dynamics reflect a functional role for weak coupling and role structure in dyadic problem solving.

    PubMed

    Abney, Drew H; Paxton, Alexandra; Dale, Rick; Kello, Christopher T

    2015-11-01

    Successful interaction requires complex coordination of body movements. Previous research has suggested a functional role for coordination and especially synchronization (i.e., time-locked movement across individuals) in different types of human interaction contexts. Although such coordination has been shown to be nearly ubiquitous in human interaction, less is known about its function. One proposal is that synchrony supports and facilitates communication (Topics Cogn Sci 1:305-319, 2009). However, questions still remain about what the properties of coordination for optimizing communication might look like. In the present study, dyads worked together to construct towers from uncooked spaghetti and marshmallows. Using cross-recurrence quantification analysis, we found that dyads with loosely coupled gross body movements performed better, supporting recent work suggesting that simple synchrony may not be the key to effective performance (Riley et al. 2011). We also found evidence that leader-follower dynamics-when sensitive to the specific role structure of the interaction-impact task performance. We discuss our results with respect to the functional role of coordination in human interaction.

  3. Role of Environmental Pollutants in Liver Physiology: Special References to Peoples Living in the Oil Drilling Sites of Assam

    PubMed Central

    Dey, Tapan; Gogoi, Kabita; Unni, Balagopalan; Bharadwaz, Moonmee; Kalita, Munmi; Ozah, Dibyajyoti; Kalita, Manoj; Kalita, Jatin; Baruah, Pranab Kumar; Bora, Thaneswar

    2015-01-01

    The populations residing near polluted sites are more prone to various types of diseases. The important causes of air pollution are the suspended particulate matter, respirable suspended particulate matter, sulfur dioxide and nitrogen dioxide. As limited information is available enumerating the effect of these pollutants on liver physiology of the population living near the polluted sites; in the present study, we tried to investigate their effect on liver of the population residing near the oil drilling sites since birth. In this study, a randomly selected 105 subjects (46 subjects from oil drilling site and 61 subjects from control site) aged above 30 years were taken under consideration. The particulate matter as well as the gaseous pollutants, sulfur dioxide and nitrogen dioxide, were analyzed through a respirable dust sampler. The level of alkaline phosphatase, alanine transaminase and aspartate transaminase enzymes in serum were measured by spectrophotometer. The generalized regression model studies suggests a higher concentration of respirable suspended particulate matter, suspended particulate matter and nitrogen dioxide lowers the alkaline phosphatase level (p<0.0001) by 3.5 times (95% CI 3.1-3.9), 1.5 times (95% CI 1.4 - 1.6) and 12 times (95% CI 10.74 -13.804), respectively in the exposed group. The higher concentration of respirable suspended particulate matter and nitrogen dioxide in air was associated with increase in alanine transaminase level (p<0.0001) by 0.8 times (95% CI 0.589-1.049) and by 2.8 times (95% CI 2.067-3.681) respectively in the exposed group. The increase in nitrogen dioxide level was also associated with increase in aspartate transaminase level (p<0.0001) by 2.5 times (95% CI 1.862 – 3.313) in the exposed group as compared to control group. Thus, the study reveals that long-term exposure to the environmental pollutants may lead to liver abnormality or injury of populations living in polluted sites. PMID:25874634

  4. Role of physiological ClC-1 Cl− ion channel regulation for the excitability and function of working skeletal muscle

    PubMed Central

    Riisager, Anders; de Paoli, Frank Vincenzo; Chen, Tsung-Yu; Nielsen, Ole Bækgaard

    2016-01-01

    /or oxidation. The present review summarizes the current knowledge of the physiological factors that control ClC-1 function in active muscle. PMID:27022190

  5. Role of environmental pollutants in liver physiology: special references to peoples living in the oil drilling sites of Assam.

    PubMed

    Dey, Tapan; Gogoi, Kabita; Unni, Balagopalan; Bharadwaz, Moonmee; Kalita, Munmi; Ozah, Dibyajyoti; Kalita, Manoj; Kalita, Jatin; Baruah, Pranab Kumar; Bora, Thaneswar

    2015-01-01

    The populations residing near polluted sites are more prone to various types of diseases. The important causes of air pollution are the suspended particulate matter, respirable suspended particulate matter, sulfur dioxide and nitrogen dioxide. As limited information is available enumerating the effect of these pollutants on liver physiology of the population living near the polluted sites; in the present study, we tried to investigate their effect on liver of the population residing near the oil drilling sites since birth. In this study, a randomly selected 105 subjects (46 subjects from oil drilling site and 61 subjects from control site) aged above 30 years were taken under consideration. The particulate matter as well as the gaseous pollutants, sulfur dioxide and nitrogen dioxide, were analyzed through a respirable dust sampler. The level of alkaline phosphatase, alanine transaminase and aspartate transaminase enzymes in serum were measured by spectrophotometer. The generalized regression model studies suggests a higher concentration of respirable suspended particulate matter, suspended particulate matter and nitrogen dioxide lowers the alkaline phosphatase level (p<0.0001) by 3.5 times (95% CI 3.1-3.9), 1.5 times (95% CI 1.4-1.6) and 12 times (95% CI 10.74-13.804), respectively in the exposed group. The higher concentration of respirable suspended particulate matter and nitrogen dioxide in air was associated with increase in alanine transaminase level (p<0.0001) by 0.8 times (95% CI 0.589-1.049) and by 2.8 times (95% CI 2.067-3.681) respectively in the exposed group. The increase in nitrogen dioxide level was also associated with increase in aspartate transaminase level (p<0.0001) by 2.5 times (95% CI 1.862-3.313) in the exposed group as compared to control group. Thus, the study reveals that long-term exposure to the environmental pollutants may lead to liver abnormality or injury of populations living in polluted sites. PMID:25874634

  6. Role of physiological ClC-1 Cl- ion channel regulation for the excitability and function of working skeletal muscle.

    PubMed

    Pedersen, Thomas Holm; Riisager, Anders; de Paoli, Frank Vincenzo; Chen, Tsung-Yu; Nielsen, Ole Bækgaard

    2016-04-01

    /or oxidation. The present review summarizes the current knowledge of the physiological factors that control ClC-1 function in active muscle. PMID:27022190

  7. Effect of vegetation physiology and structure on thermal and hydrological state in a coupled terrestrial system model

    NASA Astrophysics Data System (ADS)

    Lu, Yen-Sen; Rihani, Jehan; Langensiepen, Matthias; Simmer, Clemens

    2015-04-01

    When simulating the circulation of energy and moisture in the terrestrial system, vegetation is one of the key factors which affect energy and water fluxes at land surface and in the subsurface. Vegetation physiology in the terrestrial system includes transpiration, respiration, and root water uptake. One of the main vegetation schemes controlling transpiration in Land Surface Models is the empirical parameterization for stomatal conductance. There are two main types of stomatal conductance used in land surface models: the Jarvis-Stewart type based on environmental factors such as light use efficiency, temperature, vapor pressure deficit, and soil moisture limit: and the Ball-Berry type based on photosynthesis schemes with a semi-mechanistic parameterization. Moreover, the interconnection between soil moisture and stomatal conductance is not fully understood and needs further investigation. Alongside stomatal conductance, Leaf area index (LAI) also has a significant effect on the modelling system and thereby can impact the calculation of latent heat and sensible heat fluxes, ground temperature, and soil moisture. LAI represents the vegetation structure effects on the hydrological and thermal state of land surface by interception, albedo, and shading, and therefore altering transpiration and leaf surface evaporation. LAI can be obtained from observations such as field and satellite measurement; or estimated using parameterization in Land Surface Models and Dynamic Vegetation Models.. This study focuses on how different vegetation schemes of stomatal conductance and LAI input effect land surface energy fluxes and groundwater flow, and how the uncertainty of different schemes propagates to the calculation of thermal and hydrologic state of land surface and soil moisture. To reach the research aims of this study, land surface simulations and coupled land surface-groundwater simulations are performed and compared. In this numerical experiment, the modelling platform

  8. Role of coherent structures in supersonic impinging jetsa)

    NASA Astrophysics Data System (ADS)

    Kumar, Rajan; Wiley, Alex; Venkatakrishnan, L.; Alvi, Farrukh

    2013-07-