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Sample records for acid base regulation

  1. The Kidney and Acid-Base Regulation

    Science.gov (United States)

    Koeppen, Bruce M.

    2009-01-01

    Since the topic of the role of the kidneys in the regulation of acid base balance was last reviewed from a teaching perspective (Koeppen BM. Renal regulation of acid-base balance. Adv Physiol Educ 20: 132-141, 1998), our understanding of the specific membrane transporters involved in H+, HCO , and NH transport, and especially how these…

  2. Regulated acid-base transport in the collecting duct.

    Science.gov (United States)

    Wagner, Carsten A; Devuyst, Olivier; Bourgeois, Soline; Mohebbi, Nilufar

    2009-05-01

    The renal collecting system serves the fine-tuning of renal acid-base secretion. Acid-secretory type-A intercalated cells secrete protons via a luminally expressed V-type H(+)-ATPase and generate new bicarbonate released by basolateral chloride/bicarbonate exchangers including the AE1 anion exchanger. Efficient proton secretion depends both on the presence of titratable acids (mainly phosphate) and the concomitant secretion of ammonia being titrated to ammonium. Collecting duct ammonium excretion requires the Rhesus protein RhCG as indicated by recent KO studies. Urinary acid secretion by type-A intercalated cells is strongly regulated by various factors among them acid-base status, angiotensin II and aldosterone, and the Calcium-sensing receptor. Moreover, urinary acidification by H(+)-ATPases is modulated indirectly by the activity of the epithelial sodium channel ENaC. Bicarbonate secretion is achieved by non-type-A intercalated cells characterized by the luminal expression of the chloride/bicarbonate exchanger pendrin. Pendrin activity is driven by H(+)-ATPases and may serve both bicarbonate excretion and chloride reabsorption. The activity and expression of pendrin is regulated by different factors including acid-base status, chloride delivery, and angiotensin II and may play a role in NaCl retention and blood pressure regulation. Finally, the relative abundance of type-A and non-type-A intercalated cells may be tightly regulated. Dysregulation of intercalated cell function or abundance causes various syndromes of distal renal tubular acidosis underlining the importance of these processes for acid-base homeostasis.

  3. Carbonic anhydrase 5 regulates acid-base homeostasis in zebrafish.

    Directory of Open Access Journals (Sweden)

    Ruben Postel

    Full Text Available The regulation of the acid-base balance in cells is essential for proper cellular homeostasis. Disturbed acid-base balance directly affects cellular physiology, which often results in various pathological conditions. In every living organism, the protein family of carbonic anhydrases regulate a broad variety of homeostatic processes. Here we describe the identification, mapping and cloning of a zebrafish carbonic anhydrase 5 (ca5 mutation, collapse of fins (cof, which causes initially a collapse of the medial fins followed by necrosis and rapid degeneration of the embryo. These phenotypical characteristics can be mimicked in wild-type embryos by acetazolamide treatment, suggesting that CA5 activity in zebrafish is essential for a proper development. In addition we show that CA5 regulates acid-base balance during embryonic development, since lowering the pH can compensate for the loss of CA5 activity. Identification of selective modulators of CA5 activity could have a major impact on the development of new therapeutics involved in the treatment of a variety of disorders.

  4. What is the Ultimate Goal in Acid-Base Regulation?

    Science.gov (United States)

    Balakrishnan, Selvakumar; Gopalakrishnan, Maya; Alagesan, Murali; Prakash, E. Sankaranarayanan

    2007-01-01

    It is common to see chapters on acid-base physiology state that the goal of acid-base regulatory mechanisms is to maintain the pH of arterial plasma and not arterial PCO [subscript 2] (Pa[subscript CO[subscript 2

  5. Regulation of Connexin-Based Channels by Fatty Acids.

    Science.gov (United States)

    Puebla, Carlos; Retamal, Mauricio A; Acuña, Rodrigo; Sáez, Juan C

    2017-01-01

    In this mini-review, we briefly summarize the current knowledge about the effects of fatty acids (FAs) on connexin-based channels, as well as discuss the limited information about the impact FAs may have on pannexins (Panxs). FAs regulate diverse cellular functions, some of which are explained by changes in the activity of channels constituted by connexins (Cxs) or Panxs, which are known to play critical roles in maintaining the functional integrity of diverse organs and tissues. Cxs are transmembrane proteins that oligomerize into hexamers to form hemichannels (HCs), which in turn can assemble into dodecamers to form gap junction channels (GJCs). While GJCs communicate the cytoplasm of contacting cells, HCs serve as pathways for the exchange of ions and small molecules between the intra and extracellular milieu. Panxs, as well as Cx HCs, form channels at the plasma membrane that enable the interchange of molecules between the intra and extracellular spaces. Both Cx- and Panx-based channels are controlled by several post-translational modifications. However, the mechanism of action of FAs on these channels has not been described in detail. It has been shown however that FAs frequently decrease GJC-mediated cell-cell communication. The opposite effect also has been described for HC or Panx-dependent intercellular communication, where, the acute FA effect can be reversed upon washout. Additionally, changes in GJCs mediated by FAs have been associated with post-translational modifications (e.g., phosphorylation), and seem to be directly related to chemical properties of FAs (e.g., length of carbon chain and/or degree of saturation), but this possible link remains poorly understood.

  6. Regulation of Connexin-Based Channels by Fatty Acids

    Science.gov (United States)

    Puebla, Carlos; Retamal, Mauricio A.; Acuña, Rodrigo; Sáez, Juan C.

    2017-01-01

    In this mini-review, we briefly summarize the current knowledge about the effects of fatty acids (FAs) on connexin-based channels, as well as discuss the limited information about the impact FAs may have on pannexins (Panxs). FAs regulate diverse cellular functions, some of which are explained by changes in the activity of channels constituted by connexins (Cxs) or Panxs, which are known to play critical roles in maintaining the functional integrity of diverse organs and tissues. Cxs are transmembrane proteins that oligomerize into hexamers to form hemichannels (HCs), which in turn can assemble into dodecamers to form gap junction channels (GJCs). While GJCs communicate the cytoplasm of contacting cells, HCs serve as pathways for the exchange of ions and small molecules between the intra and extracellular milieu. Panxs, as well as Cx HCs, form channels at the plasma membrane that enable the interchange of molecules between the intra and extracellular spaces. Both Cx- and Panx-based channels are controlled by several post-translational modifications. However, the mechanism of action of FAs on these channels has not been described in detail. It has been shown however that FAs frequently decrease GJC-mediated cell-cell communication. The opposite effect also has been described for HC or Panx-dependent intercellular communication, where, the acute FA effect can be reversed upon washout. Additionally, changes in GJCs mediated by FAs have been associated with post-translational modifications (e.g., phosphorylation), and seem to be directly related to chemical properties of FAs (e.g., length of carbon chain and/or degree of saturation), but this possible link remains poorly understood. PMID:28174541

  7. High capacity for extracellular acid-base regulation in the air-breathing fish Pangasianodon hypophthalmus.

    Science.gov (United States)

    Damsgaard, Christian; Gam, Le Thi Hong; Tuong, Dang Diem; Thinh, Phan Vinh; Huong Thanh, Do Thi; Wang, Tobias; Bayley, Mark

    2015-05-01

    The evolution of accessory air-breathing structures is typically associated with reduction of the gills, although branchial ion transport remains pivotal for acid-base and ion regulation. Therefore, air-breathing fishes are believed to have a low capacity for extracellular pH regulation during a respiratory acidosis. In the present study, we investigated acid-base regulation during hypercapnia in the air-breathing fish Pangasianodon hypophthalmus in normoxic and hypoxic water at 28-30°C. Contrary to previous studies, we show that this air-breathing fish has a pronounced ability to regulate extracellular pH (pHe) during hypercapnia, with complete metabolic compensation of pHe within 72 h of exposure to hypoxic hypercapnia with CO2 levels above 34 mmHg. The high capacity for pHe regulation relies on a pronounced ability to increase levels of HCO3(-) in the plasma. Our study illustrates the diversity in the physiology of air-breathing fishes, such that generalizations across phylogenies may be difficult.

  8. Intracellular pH regulation by acid/base transporters in mammalian neurons

    Directory of Open Access Journals (Sweden)

    Vernon A. Ruffin

    2014-02-01

    Full Text Available Intracellular pH (pHi regulation in the brain is important in both physiological and physiopathological conditions because changes in pHi generally result in altered neuronal excitability. In this review, we will cover 4 major areas: [1] The effect of pHi on cellular processes in the brain, including channel activity and neuronal excitability. [2] pHi homeostasis and how it is determined by the balance between rates of acid loading (JL and extrusion (JE. The balance between JE and JL determine steady-state pHi, as well as the ability of the cell to defend pHi in the face of extracellular acid-base disturbances (e.g. metabolic acidosis. [3] The properties and importance of members of the SLC4 and SLC9 families of acid-base transporters expressed in the brain that contribute to JL (namely the Cl-HCO3 exchanger AE3 and JE (the Na-H exchangers NHE1, NHE3 and NHE5 as well as the Na+- coupled HCO3- transporters NBCe1, NBCn1, NDCBE, and NBCn2. [4] The effect of acid-base disturbances on neuronal function and the roles of acid-base transporters in defending neuronal pHi under physiopathologic conditions.

  9. Effectiveness of growth regulators, based on the heterylcarbon acid, on forcing of Tulips (Tulips HD

    Directory of Open Access Journals (Sweden)

    Derevianko Natalia

    2016-03-01

    Full Text Available The main factor in growing flowers for forcing is their rate of growth, on account of the fact that in short period of time it is necessary to grow quickly a large number of flowers and to cut them simultaneously. The influence of growth regulators (GR based on heterylcarbon acid on the forcing of tulips in greenhouse conditions (winter period was studied. It was determined that the application of GR1 of the basic within tulip’s forcing period reduces in average to 5 days (from all period of forcing. In case of application GR2 the tulip’s forcing period also reduces to 3 days (from all period of forcing compared with a control group of tulips. The ability of the plant growth regulators under research to accelerate growing properties of flowers is associated with the presence of heterylcarbon acid and potassium ions in their structure of substances. These growth regulators relate to non-toxic compounds and possess antioxidant properties.

  10. White sturgeon (Acipenser transmontanus) acid-base regulation differs in response to different types of acidoses.

    Science.gov (United States)

    Shartau, Ryan B; Baker, Dan W; Brauner, Colin J

    2017-03-11

    White sturgeon (Acipenser transmontanus) completely protect intracellular tissue pH (pHi) despite large reductions in extracellular (blood) pH (pHe), termed preferential pHi regulation, in response to elevated environmental PCO2 (hypercarbia) and in general appear to be relatively resilient to stressors. Preferential pHi regulation is thought to be associated with hypercarbia tolerance in general, but has also recently been observed to protect pHi against metabolic acidoses induced by exhaustive exercise and anoxia in a tropical air breathing catfish. We hypothesized that preferential pHi regulation may also be a general strategy of acid-base regulation in sturgeon. To address this hypothesis, severe acidoses were imposed to reduce pHe, and the presence or absence of preferential pHi regulation was assessed in red blood cells (RBC), heart, brain, liver and white muscle. A respiratory acidosis was imposed using hyperoxia, while metabolic acidoses were induced by exhaustive exercise, anoxia or air exposure. Reductions in pHe occurred following hyperoxia (0.15 units), exhaustive exercise (0.30 units), anoxia (0.10 units) and air exposure (0.35 units); all acidoses reduced RBC pHi. Following hyperoxia, heart, brain and liver pHi were preferentially regulated against the reduction in pHe, similar to hypercarbia exposure. Following all metabolic acidoses heart pHi was protected and brain pHi remained unchanged following exhaustive exercise and air exposure, however, brain pHi was reduced following anoxia. Liver and white muscle pHi were reduced following all metabolic acidoses. These results suggest preferential pHi regulation may be a general strategy during respiratory acidoses but during metabolic acidoses, the response differs between source of acidoses and tissues.

  11. Acid-Base Homeostasis.

    Science.gov (United States)

    Hamm, L Lee; Nakhoul, Nazih; Hering-Smith, Kathleen S

    2015-12-07

    Acid-base homeostasis and pH regulation are critical for both normal physiology and cell metabolism and function. The importance of this regulation is evidenced by a variety of physiologic derangements that occur when plasma pH is either high or low. The kidneys have the predominant role in regulating the systemic bicarbonate concentration and hence, the metabolic component of acid-base balance. This function of the kidneys has two components: reabsorption of virtually all of the filtered HCO3(-) and production of new bicarbonate to replace that consumed by normal or pathologic acids. This production or generation of new HCO3(-) is done by net acid excretion. Under normal conditions, approximately one-third to one-half of net acid excretion by the kidneys is in the form of titratable acid. The other one-half to two-thirds is the excretion of ammonium. The capacity to excrete ammonium under conditions of acid loads is quantitatively much greater than the capacity to increase titratable acid. Multiple, often redundant pathways and processes exist to regulate these renal functions. Derangements in acid-base homeostasis, however, are common in clinical medicine and can often be related to the systems involved in acid-base transport in the kidneys.

  12. Acid-base regulation in tadpoles of Rana catesbeiana exposed to environmental hypercapnia

    DEFF Research Database (Denmark)

    Busk, Morten; Larsen, Erik Hviid; Jensen, Frank B.

    1997-01-01

    Tadpoles of Rana catesbeiana were exposed to different levels of environmental hypercapnia. The acid-base regulatory response differed from that in adult amphibians in showing a high degree of pH compensation in the extracellular fluid (65-85%) and complete compensation in the intracellular fluid......). It is suggested that the large bicarbonate efflux from the animal is a consequence of the dissolution of CaCO3 stores and the delayed adjustment of bicarbonate-retaining mechanisms. Re-exposure of tadpoles to hypercapnia after 1-3 weeks of normocapnic recovery only affected transepithelial fluxes of acid-base...

  13. Osmoregulation and acid base regulation of the Asian Horseshoe crab Carcinoscorpius rotundicauda

    DEFF Research Database (Denmark)

    Wetter, M.; Cong, N.; Nielsen, Thomas;

    2008-01-01

    to hypercapnia (5% CO2) was partially restored by increased HC = 3-levels in the haemolymph. The degree of compensation did not differ between individuals that had been held at high or low salinity suggesting that the availability of acid-base relevant ions plays a minor role in this response....

  14. Mitochondrial TCA cycle intermediates regulate body fluid and acid-base balance.

    Science.gov (United States)

    Peti-Peterdi, János

    2013-07-01

    Intrarenal control mechanisms play an important role in the maintenance of body fluid and electrolyte balance and pH homeostasis. Recent discoveries of new ion transport and regulatory pathways in the distal nephron and collecting duct system have helped to better our understanding of these critical kidney functions and identified new potential therapeutic targets and approaches. In this issue of the JCI, Tokonami et al. report on the function of an exciting new paracrine mediator, the mitochondrial the citric acid(TCA) cycle intermediate α-ketoglutarate (αKG), which via its OXGR1 receptor plays an unexpected, nontraditional role in the adaptive regulation of renal HCO(3⁻) secretion and salt reabsorption.

  15. Embryonic common snapping turtles (Chelydra serpentina) preferentially regulate intracellular tissue pH during acid-base challenges.

    Science.gov (United States)

    Shartau, Ryan B; Crossley, Dane A; Kohl, Zachary F; Brauner, Colin J

    2016-07-01

    The nests of embryonic turtles naturally experience elevated CO2 (hypercarbia), which leads to increased blood PCO2  and a respiratory acidosis, resulting in reduced blood pH [extracellular pH (pHe)]. Some fishes preferentially regulate tissue pH [intracellular pH (pHi)] against changes in pHe; this has been proposed to be associated with exceptional CO2 tolerance and has never been identified in amniotes. As embryonic turtles may be CO2 tolerant based on nesting strategy, we hypothesized that they preferentially regulate pHi, conferring tolerance to severe acute acid-base challenges. This hypothesis was tested by investigating pH regulation in common snapping turtles (Chelydra serpentina) reared in normoxia then exposed to hypercarbia (13 kPa PCO2 ) for 1 h at three developmental ages: 70% and 90% of incubation, and yearlings. Hypercarbia reduced pHe but not pHi, at all developmental ages. At 70% of incubation, pHe was depressed by 0.324 pH units while pHi of brain, white muscle and lung increased; heart, liver and kidney pHi remained unchanged. At 90% of incubation, pHe was depressed by 0.352 pH units but heart pHi increased with no change in pHi of other tissues. Yearlings exhibited a pHe reduction of 0.235 pH units but had no changes in pHi of any tissues. The results indicate common snapping turtles preferentially regulate pHi during development, but the degree of response is reduced throughout development. This is the first time preferential pHi regulation has been identified in an amniote. These findings may provide insight into the evolution of acid-base homeostasis during development of amniotes, and vertebrates in general.

  16. New insights into the dynamic regulation of water and acid-base balance by renal epithelial cells.

    Science.gov (United States)

    Brown, Dennis; Bouley, Richard; Păunescu, Teodor G; Breton, Sylvie; Lu, Hua A J

    2012-05-15

    Maintaining tight control over body fluid and acid-base homeostasis is essential for human health and is a major function of the kidney. The collecting duct is a mosaic of two cell populations that are highly specialized to perform these two distinct processes. The antidiuretic hormone vasopressin (VP) and its receptor, the V2R, play a central role in regulating the urinary concentrating mechanism by stimulating accumulation of the aquaporin 2 (AQP2) water channel in the apical membrane of collecting duct principal cells. This increases epithelial water permeability and allows osmotic water reabsorption to occur. An understanding of the basic cell biology/physiology of AQP2 regulation and trafficking has informed the development of new potential treatments for diseases such as nephrogenic diabetes insipidus, in which the VP/V2R/AQP2 signaling axis is defective. Tubule acidification due to the activation of intercalated cells is also critical to organ function, and defects lead to several pathological conditions in humans. Therefore, it is important to understand how these "professional" proton-secreting cells respond to environmental and cellular cues. Using epididymal proton-secreting cells as a model system, we identified the soluble adenylate cyclase (sAC) as a sensor that detects luminal bicarbonate and activates the vacuolar proton-pumping ATPase (V-ATPase) via cAMP to regulate tubular pH. Renal intercalated cells also express sAC and respond to cAMP by increasing proton secretion, supporting the hypothesis that sAC could function as a luminal sensor in renal tubules to regulate acid-base balance. This review summarizes recent advances in our understanding of these fundamental processes.

  17. Selected regulation of gastrointestinal acid-base secretion and tissue metabolism for the diamondback water snake and Burmese python.

    Science.gov (United States)

    Secor, Stephen M; Taylor, Josi R; Grosell, Martin

    2012-01-01

    Snakes exhibit an apparent dichotomy in the regulation of gastrointestinal (GI) performance with feeding and fasting; frequently feeding species modestly regulate intestinal function whereas infrequently feeding species rapidly upregulate and downregulate intestinal function with the start and completion of each meal, respectively. The downregulatory response with fasting for infrequently feeding snakes is hypothesized to be a selective attribute that reduces energy expenditure between meals. To ascertain the links between feeding habit, whole-animal metabolism, and GI function and metabolism, we measured preprandial and postprandial metabolic rates and gastric and intestinal acid-base secretion, epithelial conductance and oxygen consumption for the frequently feeding diamondback water snake (Nerodia rhombifer) and the infrequently feeding Burmese python (Python molurus). Independent of body mass, Burmese pythons possess a significantly lower standard metabolic rate and respond to feeding with a much larger metabolic response compared with water snakes. While fasting, pythons cease gastric acid and intestinal base secretion, both of which are stimulated with feeding. In contrast, fasted water snakes secreted gastric acid and intestinal base at rates similar to those of digesting snakes. We observed no difference between fasted and fed individuals for either species in gastric or intestinal transepithelial potential and conductance, with the exception of a significantly greater gastric transepithelial potential for fed pythons at the start of titration. Water snakes experienced no significant change in gastric or intestinal metabolism with feeding. Fed pythons, in contrast, experienced a near-doubling of gastric metabolism and a tripling of intestinal metabolic rate. For fasted individuals, the metabolic rate of the stomach and small intestine was significantly lower for pythons than for water snakes. The fasting downregulation of digestive function for pythons is

  18. Mechanisms Regulating Acid-Base Transporter Expression in Breast- and Pancreatic Cancer

    DEFF Research Database (Denmark)

    Gorbatenko, Andrej

    , characteristics of which are a shift towards glycolytic metabolism and increased acid production. HER2 receptor overexpression in breast cancer leads to further increased glycolysis, invasion and metastasis, drug resistance and poor prognosis. Increased tumor glycolysis requires acquisition of mechanisms...... for dealing with excess acid production. In this light, evidence accumulates on the importance of pH regulatory proteins to cancer cell survival and motility. Our group previously demonstrated upregulation of the Na+/HCO3 - co-transporter NBCn1 (SLC4A7) by a constitutively active form of HER2 receptor (p95HER...

  19. Acid-base regulation in intensively farmed air-breathing fish

    DEFF Research Database (Denmark)

    Bayley, Mark; Damsgaard, Christian; Thomsen, Mikkel;

    Hypercapnia in slow moving organically loaded tropical waters is a natural occurrence with several records of pCO2 at 60 mm Hg. Despite this, studies on South American air-breathing fish have revealed a low capacity for extracellular pH (pHe) regulation. The two underlying reasons proposed are; 1...

  20. Small-Nucleic-Acid-Based Therapeutic Strategy Targeting the Transcription Factors Regulating the Vascular Inflammation, Remodeling and Fibrosis in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sung Won Youn

    2015-05-01

    Full Text Available Atherosclerosis arises when injury to the arterial wall induces an inflammatory cascade that is sustained by a complex network of cytokines, together with accumulation of lipids and fibrous material. Inflammatory cascades involve leukocyte adherence and chemotaxis, which are coordinated by the local secretion of adhesion molecules, chemotactic factors, and cytokines. Transcription factors are critical to the integration of the various steps of the cascade response to mediators of vascular injury, and are induced in a stimulus-dependent and cell-type-specific manner. Several small-nucleic-acid-based therapeutic strategies have recently been developed to target transcription factors: antisense oligodeoxynucleotides, RNA interference, microRNA, and decoy oligodeoxynucleotides. The aim of this review was to provide an overview of these particular targeted therapeutic strategies, toward regulation of the vascular inflammation, remodeling and fibrosis associated with atherosclerosis.

  1. Preferential intracellular pH regulation represents a general pattern of pH homeostasis during acid-base disturbances in the armoured catfish, Pterygoplichthys pardalis.

    Science.gov (United States)

    Harter, T S; Shartau, R B; Baker, D W; Jackson, D C; Val, A L; Brauner, C J

    2014-08-01

    Preferential intracellular pH (pHi) regulation, where pHi is tightly regulated in the face of a blood acidosis, has been observed in a few species of fish, but only during elevated blood PCO2. To determine whether preferential pHi regulation may represent a general pattern for acid-base regulation during other pH disturbances we challenged the armoured catfish, Pterygoplichthys pardalis, with anoxia and exhaustive exercise, to induce a metabolic acidosis, and bicarbonate injections to induce a metabolic alkalosis. Fish were terminally sampled 2-3 h following the respective treatments and extracellular blood pH, pHi of red blood cells (RBC), brain, heart, liver and white muscle, and plasma lactate and total CO2 were measured. All treatments resulted in significant changes in extracellular pH and RBC pHi that likely cover a large portion of the pH tolerance limits of this species (pH 7.15-7.86). In all tissues other than RBC, pHi remained tightly regulated and did not differ significantly from control values, with the exception of a decrease in white muscle pHi after anoxia and an increase in liver pHi following a metabolic alkalosis. Thus preferential pHi regulation appears to be a general pattern for acid-base homeostasis in the armoured catfish and may be a common response in Amazonian fishes.

  2. Bile acids in regulation of intestinal physiology.

    LENUS (Irish Health Repository)

    Keating, Niamh

    2009-10-01

    In addition to their roles in facilitating lipid digestion and absorption, bile acids are recognized as important regulators of intestinal function. Exposure to bile acids can dramatically influence intestinal transport and barrier properties; in recent years, they have also become appreciated as important factors in regulating cell growth and survival. Indeed, few cells reside within the intestinal mucosa that are not altered to some degree by exposure to bile acids. The past decade saw great advances in the knowledge of how bile acids exert their actions at the cellular and molecular levels. In this review, we summarize the current understanding of the role of bile acids in regulation of intestinal physiology.

  3. EDR2 negatively regulates salicylic acid-based defenses and cell death during powdery mildew infections of Arabidopsis thaliana

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    Nishimura Marc

    2007-07-01

    Full Text Available Abstract Background The hypersensitive necrosis response (HR of resistant plants to avirulent pathogens is a form of programmed cell death in which the plant sacrifices a few cells under attack, restricting pathogen growth into adjacent healthy tissues. In spite of the importance of this defense response, relatively little is known about the plant components that execute the cell death program or about its regulation in response to pathogen attack. Results We isolated the edr2-6 mutant, an allele of the previously described edr2 mutants. We found that edr2-6 exhibited an exaggerated chlorosis and necrosis response to attack by three pathogens, two powdery mildew and one downy mildew species, but not in response to abiotic stresses or attack by the bacterial leaf speck pathogen. The chlorosis and necrosis did not spread beyond inoculated sites suggesting that EDR2 limits the initiation of cell death rather than its spread. The pathogen-induced chlorosis and necrosis of edr2-6 was correlated with a stimulation of the salicylic acid defense pathway and was suppressed in mutants deficient in salicylic acid signaling. EDR2 encodes a novel protein with a pleckstrin homology and a StAR transfer (START domain as well as a plant-specific domain of unknown function, DUF1336. The pleckstrin homology domain binds to phosphatidylinositol-4-phosphate in vitro and an EDR2:HA:GFP protein localizes to endoplasmic reticulum, plasma membrane and endosomes. Conclusion EDR2 acts as a negative regulator of cell death, specifically the cell death elicited by pathogen attack and mediated by the salicylic acid defense pathway. Phosphatidylinositol-4-phosphate may have a role in limiting cell death via its effect on EDR2. This role in cell death may be indirect, by helping to target EDR2 to the appropriate membrane, or it may play a more direct role.

  4. Homology-Based Modeling of Universal Stress Protein from Listeria innocua Up-Regulated under Acid Stress Conditions

    Science.gov (United States)

    Tremonte, Patrizio; Succi, Mariantonietta; Coppola, Raffaele; Sorrentino, Elena; Tipaldi, Luca; Picariello, Gianluca; Pannella, Gianfranco; Fraternali, Franca

    2016-01-01

    An Universal Stress Protein (USP) expressed under acid stress condition by Listeria innocua ATCC 33090 was investigated. The USP was up-regulated not only in the stationary phase but also during the exponential growth phase. The three dimensional (3D) structure of USP was predicted using a combined proteomic and bioinformatics approach. Phylogenetic analysis showed that the USP from Listeria detected in our study was distant from the USPs of other bacteria (such as Pseudomonas spp., Escherichia coli, Salmonella spp.) and clustered in a separate and heterogeneous class including several USPs from Listeria spp. and Lactobacillus spp. An important information on the studied USP was obtained from the 3D-structure established through the homology modeling procedure. In detail, the Model_USP-691 suggested that the investigated USP had a homo-tetrameric quaternary structure. Each monomer presented an architecture analogous to the Rossmann-like α/β-fold with five parallel β-strands, and four α-helices. The analysis of monomer-monomer interfaces and quality of the structure alignments confirmed the model reliability. In fact, the structurally and sequentially conserved hydrophobic residues of the β-strand 5 (in particular the residues V146 and V148) were involved in the inter-chains contact. Moreover, the highly conserved residues I139 and H141 in the region α4 were involved in the dimer association and functioned as hot spots into monomer–monomer interface assembly. The hypothetical assembly of dimers was also supported by the large interface area and by the negative value of solvation free energy gain upon interface interaction. Finally, the structurally conserved ATP-binding motif G-2X-G-9X-G(S/T-N) suggested for a putative role of ATP in stabilizing the tetrameric assembly of the USP. Therefore, the results obtained from a multiple approach, consisting in the application of kinetic, proteomic, phylogenetic and modeling analyses, suggest that Listeria USP could

  5. Bile acid biosynthesis and its regulation

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    Areta Hebanowska

    2010-10-01

    Full Text Available Bile acid biosynthesis is the main pathway of cholesterol catabolism. Bile acids are more soluble than cholesterol so are easier to excrete. As amphipathic molecules they participate in lipid digestion and absorption in the intestine and they help to excrete free cholesterol with bile. They are also ligands for nuclear receptors regulating the expression of genes involved in cholesterol metabolism. Interconversion of cholesterol into bile acids is an important point of its homeostasis. Seventeen enzymes are engaged in this process and many of them are cytochromes P450. Bile acid synthesis initiation may proceed with the “classical” pathway (starting with cholesterol hydroxylation at the C7α position or the “alternative” pathway (starting with cholesterol hydroxylation at the C27 position. Two additional pathways are possible, though their quantitative significance is small (initiated with cholesterol hydroxylations of C24 and C25 positions. Oxysterols produced are not only intermediates of bile acid biosynthesis but also important regulators of metabolism. Bile acid biosynthesis takes place in the liver, but some enzymes are also present in other organs, where they participate in regulation of cholesterol metabolism. Those enzymes are potential targets for new drugs against cholesterol metabolism disturbances. This article is a brief description of the bile acid biosynthesis pathway and participating enzymes.

  6. Nucleic acid based logical systems.

    Science.gov (United States)

    Han, Da; Kang, Huaizhi; Zhang, Tao; Wu, Cuichen; Zhou, Cuisong; You, Mingxu; Chen, Zhuo; Zhang, Xiaobing; Tan, Weihong

    2014-05-12

    Researchers increasingly visualize a significant role for artificial biochemical logical systems in biological engineering, much like digital logic circuits in electrical engineering. Those logical systems could be utilized as a type of servomechanism to control nanodevices in vitro, monitor chemical reactions in situ, or regulate gene expression in vivo. Nucleic acids (NA), as carriers of genetic information with well-regulated and predictable structures, are promising materials for the design and engineering of biochemical circuits. A number of logical devices based on nucleic acids (NA) have been designed to handle various processes for technological or biotechnological purposes. This article focuses on the most recent and important developments in NA-based logical devices and their evolution from in vitro, through cellular, even towards in vivo biological applications.

  7. Regulation of branchial V-H(+)-ATPase, Na(+)/K(+)-ATPase and NHE2 in response to acid and base infusions in the Pacific spiny dogfish (Squalus acanthias).

    Science.gov (United States)

    Tresguerres, Martin; Katoh, Fumi; Fenton, Heather; Jasinska, Edyta; Goss, Greg G

    2005-01-01

    To study the mechanisms of branchial acid-base regulation, Pacific spiny dogfish were infused intravenously for 24 h with either HCl (495+/- 79 micromol kg(-1) h(-1)) or NaHCO(3) (981+/-235 micromol kg(-1) h(-1)). Infusion of HCl produced a transient reduction in blood pH. Despite continued infusion of acid, pH returned to normal by 12 h. Infusion of NaHCO(3) resulted in a new steady-state acid-base status at approximately 0.3 pH units higher than the controls. Immunostained serial sections of gill revealed the presence of separate vacuolar proton ATPase (V-H(+)-ATPase)-rich or sodium-potassium ATPase (Na(+)/K(+)-ATPase)-rich cells in all fish examined. A minority of the cells also labeled positive for both transporters. Gill cell membranes prepared from NaHCO(3)-infused fish showed significant increases in both V-H(+)-ATPase abundance (300+/-81%) and activity. In addition, we found that V-H(+)-ATPase subcellular localization was mainly cytoplasmic in control and HCl-infused fish, while NaHCO(3)-infused fish demonstrated a distinctly basolateral staining pattern. Western analysis in gill membranes from HCl-infused fish also revealed increased abundance of Na(+)/H(+) exchanger 2 (213+/-5%) and Na(+)/K(+)-ATPase (315+/-88%) compared to the control.

  8. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances

    Directory of Open Access Journals (Sweden)

    Je Min Lee

    2016-01-01

    Full Text Available Polyunsaturated fatty acids (PUFAs are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism.

  9. Fatty Acid Desaturases, Polyunsaturated Fatty Acid Regulation, and Biotechnological Advances.

    Science.gov (United States)

    Lee, Je Min; Lee, Hyungjae; Kang, SeokBeom; Park, Woo Jung

    2016-01-04

    Polyunsaturated fatty acids (PUFAs) are considered to be critical nutrients to regulate human health and development, and numerous fatty acid desaturases play key roles in synthesizing PUFAs. Given the lack of delta-12 and -15 desaturases and the low levels of conversion to PUFAs, humans must consume some omega-3 and omega-6 fatty acids in their diet. Many studies on fatty acid desaturases as well as PUFAs have shown that fatty acid desaturase genes are closely related to different human physiological conditions. Since the first front-end desaturases from cyanobacteria were cloned, numerous desaturase genes have been identified and animals and plants have been genetically engineered to produce PUFAs such as eicosapentaenoic acid and docosahexaenoic acid. Recently, a biotechnological approach has been used to develop clinical treatments for human physiological conditions, including cancers and neurogenetic disorders. Thus, understanding the functions and regulation of PUFAs associated with human health and development by using biotechnology may facilitate the engineering of more advanced PUFA production and provide new insights into the complexity of fatty acid metabolism.

  10. Metabolic changes associated with acid-base regulation during hypercarbia in the CO2-tolerant chondrostean, white sturgeon (Acipenser transmontanus).

    Science.gov (United States)

    Baker, Daniel W; Brauner, Colin J

    2012-01-01

    CO(2) tolerance in white sturgeon is associated with the ability to tightly regulate intracellular pH (pHi) despite a large reduction in extracellular pH (pHe) termed preferential pHi regulation. How this regulatory response affects whole animal metabolic rate is unknown. Accordingly, we characterized oxygen consumption rate ( [Formula: see text] ) and metabolically-relevant organismal and cellular responses in white sturgeon during exposure to hypercarbia. White sturgeon were able to protect intracellular pH (pHi) in liver and white muscle as early as 6h (the earliest time period investigated) following exposure to severe (sub-lethal) hypercarbia (45 and 90 mm Hg PCO(2)). Sturgeon exposed to 15 and 30 mm Hg PCO(2) exhibited pHe compensation and significant increases in [Formula: see text] (up to 80% greater than control values). In contrast, severe hypercarbia (≥45 mm Hg PCO(2)) elicited an uncompensated reduction in pHe (up to ~1.0 pH units) and red blood cells (as great as ~0.5 pH units), and was accompanied by 30 and 60% reductions in [Formula: see text] , respectively. While behavioral, respiratory and cellular responses to hypercarbia were observed, none corresponded well with the pattern or magnitude of changes in [Formula: see text] . The findings of this research provide empirical support for the hypothesis that preferential pHi regulation is not metabolically costly, and thus may have been a strategy strongly selected for in fishes encountering short-term hypercarbia.

  11. Preparation of amino acid-based polymer functionalized magnetic nanoparticles as adsorbents for analysis of plant growth regulators in bean sprouts.

    Science.gov (United States)

    Ji, Shilei; Qi, Li; Li, Nan; Wang, Minglin

    2016-09-01

    A novel magnetic solid phase extraction (MSPE) adsorbent has been developed for enriching two plant growth regulators, including 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chlorophenoxyacetic acid (4-CPA), in bean sprouts. For preparing the MSPE adsorbent, poly(N-methacryloyl-L-phenylalanine methyl ester (P(MA-L-Phe-OMe)), amino acid-based polymer, was modified onto the magnetic nanoparticles via "grafting to" method by free radical polymerization. The resultant P(MA-L-Phe-OMe)-functionalized magnetic nanoparticles (Fe3O4@P(MA-L-Phe-OMe)) were characterized by Fourier transform infrared (FT-IR) spectroscopy and elemental analysis. The adsorption amount of Fe3O4@P(MA-L-Phe-OMe) nanoparticles to 2,4-D and 4-CPA were 39.82mgg(-1) and 29.02mgg(-1), respectively. Moreover, the prepared MSPE adsorbents showed good selectivity towards 2,4-D and 4-CPA due to the hydrophobic interactions and electrostatic forces between the target analytes and Fe3O4@P(MA-L-Phe-OMe). The results demonstrated that the proposed MSPE adsorbents have high affinity to the targets 2,4-D and 4-CPA. Under the optimized conditions, the proposed materials were successfully applied to enrich 2,4-D and 4-CPA in bean sprouts samples. The recovery values of the bean sprouts solution spiked the targets were from 90.9% to 96.4% with the relative standard deviations of 2.3-3.9%. Our work proved that the novel Fe3O4@P(MA-L-Phe-OMe) nanoparticles were the good adsorbents of magnetic solid phase extraction (MSPE) and have good potential for the analysis of trace compound in real samples.

  12. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation

    DEFF Research Database (Denmark)

    Dzamko, Nicolas; Schertzer, Jonathan D.; Ryall, James G.;

    2008-01-01

    with rates of fatty acid oxidation. To address this issue we have investigated the requirement for skeletal muscle AMPK in controlling aminoimidazole-4-carboxymide-1-beta-d-ribofuranoside (AICAR) and contraction-stimulated fatty acid oxidation utilizing transgenic mice expressing a muscle-specific kinase......-based approach we identified 18 Ser/Thr protein kinases whose phosphorylation was increased by greater than 25% in contracted KD relative to WT muscle. Utilizing bioinformatics we predicted that extracellular regulated protein-serine kinase (ERK1/2), inhibitor of nuclear factor (NF)-kappaB protein-serine kinase...... beta (IKKbeta) and protein kinase D (PKD) may phosphorylate ACC2 at Ser-221 but during in vitro phosphorylation assays only AMPK phosphorylated ACC2. These data demonstrate that AMPK is not essential for the regulation of fatty acid oxidation by AICAR or muscle contraction....

  13. Acids and bases solvent effects on acid-base strenght

    CERN Document Server

    Cox, Brian G

    2013-01-01

    Acids and bases are ubiquitous in chemistry. Our understanding of them, however, is dominated by their behaviour in water. Transfer to non-aqueous solvents leads to profound changes in acid-base strengths and to the rates and equilibria of many processes: for example, synthetic reactions involving acids, bases and nucleophiles; isolation of pharmaceutical actives through salt formation; formation of zwitter- ions in amino acids; and chromatographic separation of substrates. This book seeks to enhance our understanding of acids and bases by reviewing and analysing their behaviour in non-aqueous solvents. The behaviour is related where possible to that in water, but correlations and contrasts between solvents are also presented.

  14. Valve-regulated lead-acid batteries

    Science.gov (United States)

    Berndt, D.

    Valve-regulated lead-acid (VRLA) batteries with gelled electrolyte appeared as a niche market during the 1950s. During the 1970s, when glass-fiber felts became available as a further method to immobilize the electrolyte, the market for VRLA batteries expanded rapidly. The immobilized electrolyte offers a number of obvious advantages including the internal oxygen cycle which accommodates the overcharging current without chemical change within the cell. It also suppresses acid stratification and thus opens new fields of application. VRLA batteries, however, cannot be made completely sealed, but require a valve for gas escape, since hydrogen evolution and grid corrosion are unavoidable secondary reactions. These reactions result in water loss, and also must be balanced in order to ensure proper charging of both electrodes. Both secondary reactions have significant activation energies, and can reduce the service life of VRLA batteries, operated at elevated temperature. This effect can be aggravated by the comparatively high heat generation caused by the internal oxygen cycle during overcharging. Temperature control of VRLA batteries, therefore, is important in many applications.

  15. Characterization of Na(+) transport to gain insight into the mechanism of acid-base and ion regulation in white sturgeon (Acipenser transmontanus).

    Science.gov (United States)

    Shartau, Ryan B; Brix, Kevin V; Brauner, Colin J

    2017-02-01

    Freshwater fish actively take up ions via specific transporters to counter diffusive losses to their hypotonic environment. While much is known about the specific mechanisms employed by teleosts, almost nothing is known about the basal fishes, such as white sturgeon (Acipenser transmontanus) which may offer insight into the evolution of osmo- and ionoregulation in fishes. We investigated Na(+) uptake in juvenile white sturgeon in the presence and absence of transporter inhibitors. We found that sturgeon acclimated to 100μmoll(-1) Na(+) have Na(+) uptake kinetics typical of teleosts and that a Na(+)/H(+) exchanger (NHE) is the predominant transporter for Na(+) uptake. White sturgeon are tolerant to hypercarbia-induced respiratory acidoses and recover blood pH (pHe) at 1.5kPa PCO2 but not at higher PCO2 (6kPa PCO2) where they preferentially regulate intracellular pH (pHi). It was hypothesized that during exposure to hypercarbia Na(+) uptake would increase at CO2 tensions at which fish were capable of pHe regulation but decrease at higher tensions when they were preferentially regulating pHi. We found that Na(+) uptake did not increase at 1.5kPa PCO2, but at 6kPa PCO2 Na(+) uptake was reduced by 95% while low water pH equivalent to 6kPa PCO2 reduced Na(+) uptake by 71%. Lastly, we measured net acid flux during hypercarbia, which indicates that net acid flux is not associated with Na(+) uptake. These findings indicate Na(+) uptake in sturgeon is not different from freshwater teleosts but is sensitive to hypercarbia and is not associated with pHe compensation during hypercarbia.

  16. PHYSIOLOGY OF ACID BASE BALANCE

    Directory of Open Access Journals (Sweden)

    Awati

    2014-12-01

    Full Text Available Acid-base, electrolyte, and metabolic disturbances are common in the intensive care unit. Almost all critically ill patients often suffer from compound acid-base and electrolyte disorders. Successful evaluation and management of such patients requires recognition of common patterns (e.g., metabolic acidosis and the ability to dissect one disorder from another. The intensivists needs to identify and correct these condition with the easiest available tools as they are the associated with multiorgan failure. Understanding the elements of normal physiology in these areas is very important so as to diagnose the pathological condition and take adequate measures as early as possible. Arterial blood gas analysis is one such tool for early detection of acid base disorder. Physiology of acid base is complex and here is the attempt to simplify it in our day to day application for the benefit of critically ill patients.

  17. Effects of seawater alkalinity on calcium and acid-base regulation in juvenile European lobster (Homarus gammarus) during a moult cycle.

    Science.gov (United States)

    Middlemiss, Karen L; Urbina, Mauricio A; Wilson, Rod W

    2016-03-01

    Fluxes of NH4(+) (acid) and HCO3(-) (base), and whole body calcium content were measured in European lobster (Homarus gammarus) during intermoult (megalopae stage), and during the first 24h for postmoult juveniles under control (~2000 μeq/L) and low seawater alkalinity (~830 μeq/L). Immediately after moulting, animals lost 45% of the total body calcium via the shed exoskeleton (exuvia), and only 11% was retained in the uncalcified body. At 24h postmoult, exoskeleton calcium increased to ~46% of the intermoult stage. Ammonia excretion was not affected by seawater alkalinity. After moulting, bicarbonate excretion was immediately reversed from excretion to uptake (~4-6 fold higher rates than intermoult) over the whole 24h postmoult period, peaking at 3-6h. These data suggest that exoskeleton calcification is not completed by 24h postmoult. Low seawater alkalinity reduced postmoult bicarbonate uptake by 29% on average. Net acid-base flux (equivalent to net base uptake) followed the same pattern as HCO3(-) fluxes, and was 22% lower in low alkalinity seawater over the whole 24h postmoult period. The common occurrence of low alkalinity in intensive aquaculture systems may slow postmoult calcification in juvenile H. gammarus, increasing the risk of mortalities through cannibalism.

  18. Mechanisms of gene regulation by fatty acids

    NARCIS (Netherlands)

    Georgiadi, A.; Kersten, A.H.

    2012-01-01

    Consumption of specific dietary fatty acids has been shown to influence risk and progression of several chronic diseases, such as cardiovascular disease, obesity, cancer, and arthritis. In recent years, insights into the mechanisms underlying the biological effects of fatty acids have improved consi

  19. Effect of dietary cation-anion difference on ruminal metabolism, total apparent digestibility, blood and renal acid-base regulation in lactating dairy cows.

    Science.gov (United States)

    Martins, C M M R; Arcari, M A; Welter, K C; Gonçalves, J L; Santos, M V

    2016-01-01

    The present study aimed to evaluate the effect of dietary cation-anion difference (DCAD) on ruminal fermentation, total apparent digestibility, blood and renal metabolism of lactating dairy cows. Sixteen Holstein cows were distributed in four contemporary 4×4 Latin Square designs, which consisted of four periods of 21 days and four treatments according to DCAD: +290; +192; +98 and -71 milliequivalent (mEq)/kg dry matter (DM). Ruminal pH and concentrations of acetic and butyric acid increased linearly according to the increase of DCAD. Similarly, NDF total apparent digestibility linearly increased by 6.38% when DCAD increased from -71 to 290 mEq/kg DM [Y=65.90 (SE=2.37)+0.0167 (SE=0.0068)×DCAD (mEq/kg DM)]. Blood pH was also increased according to DCAD, which resulted in reduction of serum concentrations of Na, K and ionic calcium (iCa). To maintain the blood acid-base homeostasis, renal metabolism played an important role in controlling serum concentrations of Na and K, since the Na and K urinary excretion increased linearly by 89.69% and 46.06%, respectively, from -71 to 290 mEq/kg DM. Changes in acid-base balance of biological fluids may directly affect the mineral composition of milk, as milk concentrations of Na, K, iCa and chlorides were reduced according to blood pH increased. Thus, it can be concluded that the increase of DCAD raises the pH of ruminal fluid, NDF total apparent digestibility, and blood pH, and decreases the milk concentration of cationic minerals, as well as the efficiency of Na utilization to milk production.

  20. Regulation of intestinal protein metabolism by amino acids.

    Science.gov (United States)

    Bertrand, Julien; Goichon, Alexis; Déchelotte, Pierre; Coëffier, Moïse

    2013-09-01

    Gut homeostasis plays a major role in health and may be regulated by quantitative and qualitative food intake. In the intestinal mucosa, an intense renewal of proteins occurs, at approximately 50% per day in humans. In some pathophysiological conditions, protein turnover is altered and may contribute to intestinal or systemic diseases. Amino acids are key effectors of gut protein turnover, both as constituents of proteins and as regulatory molecules limiting intestinal injury and maintaining intestinal functions. Many studies have focused on two amino acids: glutamine, known as the preferential substrate of rapidly dividing cells, and arginine, another conditionally essential amino acid. The effects of glutamine and arginine on protein synthesis appear to be model and condition dependent, as are the involved signaling pathways. The regulation of gut protein degradation by amino acids has been minimally documented until now. This review will examine recent data, helping to better understand how amino acids regulate intestinal protein metabolism, and will explore perspectives for future studies.

  1. Molten fatty acid based microemulsions.

    Science.gov (United States)

    Noirjean, Cecile; Testard, Fabienne; Dejugnat, Christophe; Jestin, Jacques; Carriere, David

    2016-06-21

    We show that ternary mixtures of water (polar phase), myristic acid (MA, apolar phase) and cetyltrimethylammonium bromide (CTAB, cationic surfactant) studied above the melting point of myristic acid allow the preparation of microemulsions without adding a salt or a co-surfactant. The combination of SANS, SAXS/WAXS, DSC, and phase diagram determination allows a complete characterization of the structures and interactions between components in the molten fatty acid based microemulsions. For the different structures characterized (microemulsion, lamellar or hexagonal phases), a similar thermal behaviour is observed for all ternary MA/CTAB/water monophasic samples and for binary MA/CTAB mixtures without water: crystalline myristic acid melts at 52 °C, and a thermal transition at 70 °C is assigned to the breaking of hydrogen bounds inside the mixed myristic acid/CTAB complex (being the surfactant film in the ternary system). Water determines the film curvature, hence the structures observed at high temperature, but does not influence the thermal behaviour of the ternary system. Myristic acid is partitioned in two "species" that behave independently: pure myristic acid and myristic acid associated with CTAB to form an equimolar complex that plays the role of the surfactant film. We therefore show that myristic acid plays the role of a solvent (oil) and a co-surfactant allowing the fine tuning of the structure of oil and water mixtures. This solvosurfactant behaviour of long chain fatty acid opens the way for new formulations with a complex structure without the addition of any extra compound.

  2. A Carbonic Anhydrase Serves as an Important Acid-Base Regulator in Pacific Oyster Crassostrea gigas Exposed to Elevated CO2: Implication for Physiological Responses of Mollusk to Ocean Acidification.

    Science.gov (United States)

    Wang, Xiudan; Wang, Mengqiang; Jia, Zhihao; Qiu, Limei; Wang, Lingling; Zhang, Anguo; Song, Linsheng

    2017-02-01

    Carbonic anhydrases (CAs) have been demonstrated to play an important role in acid-base regulation in vertebrates. However, the classification and modulatory function of CAs in marine invertebrates, especially their responses to ocean acidification remain largely unknown. Here, a cytosolic α-CA (designated as CgCAII-1) was characterized from Pacific oyster Crassostrea gigas and its molecular activities against CO2 exposure were investigated. CgCAII-1 possessed a conserved CA catalytic domain, with high similarity to invertebrate cytoplasmic or mitochondrial α-CAs. Recombinant CgCAII-1 could convert CO2 to HCO3(-) with calculated activity as 0.54 × 10(3) U/mg, which could be inhibited by acetazolamide (AZ). The mRNA transcripts of CgCAII-1 in muscle, mantle, hepatopancreas, gill, and hemocytes increased significantly after exposure to elevated CO2. CgCAII-1 could interact with the hemocyte membrane proteins and the distribution of CgCAII-1 protein became more concentrated and dense in gill and mantle under CO2 exposure. The intracellular pH (pHi) of hemocytes under CO2 exposure increased significantly (p CO2 exposure. The impact of CO2 exposure on CA activity coupled with the mRNA expression level and protein translocation of CgCAII-1 provided evidences that CgCAII-1 could respond to ocean acidification and participate in acid-base regulation. Such cytoplasmic CA-based physiological regulation mechanism might explain other physiological responses of marine organisms to OA.

  3. Comparative Genomics of Regulation of Fatty Acid and Branched-chain Amino Acid Utilization in Proteobacteria

    Energy Technology Data Exchange (ETDEWEB)

    Kazakov, Alexey E.; Rodionov, Dmitry A.; Arkin, Adam Paul; Dubchak, Inna; Gelfand, Mikhail S.; Alm, Eric

    2008-10-31

    Bacteria can use branched-chain amino acids (ILV, i.e. isoleucine, leucine, valine) and fatty acids (FA) as sole carbon and energy sources convering ILV into acetyl-CoA, propanoyl-CoA and propionyl-CoA, respectively. In this work, we used the comparative genomic approach to identify candidate transcriptional factors and DNA motifs that control ILV and FA utilization pathways in proteobacteria. The metabolic regulons were characterized based on the identification and comparison of candidate transcription factor binding sites in groups of phylogenetically related genomes. The reconstructed ILV/FA regulatory network demonstrates considerable variability and involves six transcriptional factors from the MerR, TetR and GntR families binding to eleven distinct DNA motifs. The ILV degradation genes in gamma- and beta-proteobacteria are mainly regulated by anovel regulator from the MerR family (e.g., LiuR in Pseudomonas aeruginosa) (40 species), in addition, the TetR-type regulator LiuQ was identified in some beta-proteobacteria (8 species). Besides the core set of ILV utilization genes, the LiuR regulon in some lineages is expanded to include genes from other metabolic pathways, such as the glyoxylate shunt and glutamate synthase in the Shewanella species. The FA degradation genes are controlled by four regulators including FadR in gamma-proteobacteria (34 species), PsrA in gamma- and beta-proteobacteria (45 species), FadP in beta-proteobacteria (14 species), and LiuR orthologs in alpha-proteobacteria (22 species). The remarkable variability of the regulatory systems associated with the FA degradation pathway is discussed from the functional and evolutionary points of view.

  4. Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation

    NARCIS (Netherlands)

    Lefebvre, Philippe; Cariou, Bertrand; Lien, Fleur; Kuipers, Folkert; Staels, Bart

    2009-01-01

    Lefebvre P, Cariou B, Lien F, Kuipers F, Staels B. Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation. Physiol Rev 89: 147-191,2009; doi: 10.1152/physrev.00010.2008. - The incidence of the metabolic syndrome has taken epidemic proportions in the past decades, contributing to an incre

  5. GROWTH-REGULATING ACTIVITY OF SOME SALTS OF 1-NAPHTHALENACETIC ACID AND 2-NAPHTHOXYACETIC ACID

    Directory of Open Access Journals (Sweden)

    Maria Laichici

    2001-01-01

    Full Text Available The salts of 1-naphthalene acetic acid and 2-naphthoxyacetic acid with ethanolamine have been synthetized. The two salts have been assessed using Tsibulskaya-Vassiliev biological test using agar-agar as the medium. Statistical processing of the data has been carried out. The good results of the bioassay indicate an auxinic growth-regulating activity of the two salts.

  6. Transcriptional regulation of central amino acid metabolism in Lactococcus lactis

    NARCIS (Netherlands)

    Larsen, Rasmus

    2005-01-01

    This thesis describes the functional characterisation of the transcriptional regulators GlnR, ArgR and AhrC of Lactococcus lactis, which are responsible for the control of genes involved in the metabolism of the amino acids glutamine, glutamate and arginine. A chromosomal glnR deletion mutant was ma

  7. Identification of beer bitter acids regulating mechanisms of gastric acid secretion.

    Science.gov (United States)

    Walker, Jessica; Hell, Johannes; Liszt, Kathrin I; Dresel, Michael; Pignitter, Marc; Hofmann, Thomas; Somoza, Veronika

    2012-02-15

    Beer, one of the most consumed beverages worldwide, has been shown to stimulate gastric acid secretion. Although organic acids, formed by fermentation of glucose, are known to be stimulants of gastric acid secretion, very little is known about the effects of different types of beer or the active constituents thereof. In the present study, we compared the effects of different beers on mechanisms of gastric acid secretion. To investigate compound-specific effects on mechanisms of gastric acid secretion, organic acids and bitter compounds were quantified by HPLC-DAD and UPLC-MS/MS and tested in human gastric cancer cells (HGT-1) by means of a pH-sensitive fluorescent dye which determines the intracellular pH as an indicator of proton secretion. The expression of relevant genes, coding the H(+)/K(+)-ATPase, ATP4A, the histamine receptor, HRH2, the acetylcholine receptor, CHRM3, and the somatostatin receptor, SSTR2, was determined by qPCR. Ethanol and the organic acids succinic acid, malic acid, and citric acid were demonstrated to contribute to some extent to the effect of beer. The bitter acids comprising α-, β-, and iso-α-acids were identified as potential key components promoting gastric acid secretion and up-regulation of CHRM3 gene expression by a maximum factor of 2.01 compared to that of untreated control cells with a correlation to their respective bitterness.

  8. Differential regulation of placental amino acid transport by saturated and unsaturated fatty acids.

    Science.gov (United States)

    Lager, Susanne; Jansson, Thomas; Powell, Theresa L

    2014-10-15

    Fatty acids are critical for normal fetal development but may also influence placental function. We have previously reported that oleic acid (OA) stimulates amino acid transport in primary human trophoblasts (PHTs). In other tissues, saturated and unsaturated fatty acids have distinct effects on cellular signaling, for instance, palmitic acid (PA) but not OA reduces IκBα expression. We hypothesized that saturated and unsaturated fatty acids differentially affect trophoblast amino acid transport and cellular signaling. To test this hypothesis, PHTs were cultured in docosahexaenoic acid (DHA; 50 μM), OA (100 μM), or PA (100 μM). DHA and OA were also combined to test whether DHA could counteract the OA stimulatory effect on amino acid transport. The effects of fatty acids were compared against a vehicle control. Amino acid transport was measured by isotope-labeled tracers. Activation of inflammatory-related signaling pathways and the mechanistic target of rapamycin (mTOR) pathway were determined by Western blot analysis. Exposure of PHTs to DHA for 24 h reduced amino acid transport and phosphorylation of p38 MAPK, STAT3, mTOR, eukaryotic initiation factor 4E-binding protein 1, and ribosomal protein (rp)S6. In contrast, OA increased amino acid transport and phosphorylation of ERK, mTOR, S6 kinase 1, and rpS6. The combination of DHA with OA increased amino acid transport and rpS6 phosphorylation. PA did not affect amino acid transport but reduced IκBα expression. In conclusion, these fatty acids differentially regulated placental amino acid transport and cellular signaling. Taken together, these findings suggest that dietary fatty acids could alter the intrauterine environment by modifying placental function, thereby having long-lasting effects on the developing fetus.

  9. The Acid-Base Titration of a Very Weak Acid: Boric Acid

    Science.gov (United States)

    Celeste, M.; Azevedo, C.; Cavaleiro, Ana M. V.

    2012-01-01

    A laboratory experiment based on the titration of boric acid with strong base in the presence of d-mannitol is described. Boric acid is a very weak acid and direct titration with NaOH is not possible. An auxiliary reagent that contributes to the release of protons in a known stoichiometry facilitates the acid-base titration. Students obtain the…

  10. Kislinsko-bazno ravnovesje: Acid-base balance:

    OpenAIRE

    2002-01-01

    Acids are donors, while bases are acceptors of protons in solutions. Many various acids and bases are incorporated into organisms by everyday alimentation and cell metabolism, while the output routes are the respiratory system, kidneys and gastrointestinal system. The concentration of free protonsin the blood (expressed as pH value) is strictly regulated, as it has agreat impact on cell metabolism. There are many ways in which organisms defend themselves against harmful pH changes. The first ...

  11. Acid-base homeostasis in the human system

    Science.gov (United States)

    White, R. J.

    1974-01-01

    Acid-base regulation is a cooperative phenomena in vivo with body fluids, extracellular and intracellular buffers, lungs, and kidneys all playing important roles. The present account is much too brief to be considered a review of present knowledge of these regulatory systems, and should be viewed, instead, as a guide to the elements necessary to construct a simple model of the mutual interactions of the acid-base regulatory systems of the body.

  12. Regulation of hepatic gene expression by saturated fatty acids.

    Science.gov (United States)

    Vallim, T; Salter, A M

    2010-01-01

    Diets rich in saturated fatty acids have long been associated with increased plasma cholesterol concentrations and hence increased risk of cardiovascular disease. More recently, they have also been suggested to promote the development of non-alcoholic fatty liver disease. While there is now considerable evidence to suggest that polyunsaturated fatty acids exert many of their effects through regulating the activity of transcription factors, including peroxisome proliferator activated receptors, sterol regulatory binding proteins (SREBPs) and liver X receptor, our understanding of how saturated fatty acids act is still limited. Here we review the potential mechanisms whereby saturated fatty acids modulate hepatic lipid metabolism thereby impacting on the synthesis, storage and secretion of lipids. Evidence is presented that their effects are, at least partly, mediated through modulation of the activity of the SREBP family of transcription factors.

  13. Regulating fatty acids in infant formula: critical assessment of U.S. policies and practices

    Science.gov (United States)

    2014-01-01

    Background Fatty acids in breast-milk such as docosahexaenoic acid and arachidonic acid, commonly known as DHA and ARA, contribute to the healthy development of children in various ways. However, the manufactured versions that are added to infant formula might not have the same health benefits as those in breast-milk. There is evidence that the manufactured additives might cause harm to infants’ health, and they might lead to unwarranted increases in the cost of infant formula. The addition of such fatty acids to infant formula needs to be regulated. In the U.S., the Food and Drug Administration has primary responsibility for regulating the composition of infant formula. The central purpose of this study is to assess the FDA’s efforts with regard to the regulation of fatty acids in infant formula. Methods This study is based on critical analysis of policies and practices described in publicly available documents of the FDA, the manufacturers of fatty acids, and other relevant organizations. The broad framework for this work was set out by the author in his book on Regulating Infant Formula, published in 2011. Results The FDA does not assess the safety or the health impacts of fatty acid additives to infant formula before they are marketed, and there is no systematic assessment after marketing is underway. Rather than making its own independent assessments, the FDA accepts the manufacturers’ claims regarding their products’ safety and effectiveness. Conclusions The FDA is not adequately regulating the use of fatty acid additives to infant formula. This results in exposure of infants to potential risks. Adverse reactions are already on record. Also, the additives have led to increasing costs of infant formula despite the lack of proven benefits to normal, full term infants. There is a need for more effective regulation of DHA and ARA additives to infant formula. PMID:24433303

  14. Regulation and limitations to fatty acid oxidation during exercise

    DEFF Research Database (Denmark)

    Jeppesen, Jacob; Kiens, Bente

    2012-01-01

    tissue to deliver sufficient fatty acids to exercising muscle has been proposed, but evidence is emerging that factors within the muscle might be of more importance. The high rate of glycolysis during high intensity exercise might be the "driving force" via the increased production of acetyl CoA which...... in turn is trapped by carnitine. This will lead to less availability of free carnitine for fatty acid transport into mitochondria. This review summarizes our present view on how FA metabolism is regulated during exercise with a special focus on the limitations in FA oxidation in the transition from...

  15. Regulation of intestinal mucosal growth by amino acids.

    Science.gov (United States)

    Ray, Ramesh M; Johnson, Leonard R

    2014-03-01

    Amino acids, especially glutamine (GLN) have been known for many years to stimulate the growth of small intestinal mucosa. Polyamines are also required for optimal mucosal growth, and the inhibition of ornithine decarboxylase (ODC), the first rate-limiting enzyme in polyamine synthesis, blocks growth. Certain amino acids, primarily asparagine (ASN) and GLN stimulate ODC activity in a solution of physiological salts. More importantly, their presence is also required before growth factors and hormones such as epidermal growth factor and insulin are able to increase ODC activity. ODC activity is inhibited by antizyme-1 (AZ) whose synthesis is stimulated by polyamines, thus, providing a negative feedback regulation of the enzyme. In the absence of amino acids mammalian target of rapamycin complex 1 (mTORC1) is inhibited, whereas, mTORC2 is stimulated leading to the inhibition of global protein synthesis but increasing the synthesis of AZ via a cap-independent mechanism. These data, therefore, explain why ASN or GLN is essential for the activation of ODC. Interestingly, in a number of papers, AZ has been shown to inhibit cell proliferation, stimulate apoptosis, or increase autophagy. Each of these activities results in decreased cellular growth. AZ binds to and accelerates the degradation of ODC and other proteins shown to regulate proliferation and cell death, such as Aurora-A, Cyclin D1, and Smad1. The correlation between the stimulation of ODC activity and the absence of AZ as influenced by amino acids is high. Not only do amino acids such as ASN and GLN stimulate ODC while inhibiting AZ synthesis, but also amino acids such as lysine, valine, and ornithine, which inhibit ODC activity, increase the synthesis of AZ. The question remaining to be answered is whether AZ inhibits growth directly or whether it acts by decreasing the availability of polyamines to the dividing cells. In either case, evidence strongly suggests that the regulation of AZ synthesis is the

  16. Retinoic acid signalling in thymocytes regulates T cell development

    DEFF Research Database (Denmark)

    Wendland, Kerstin; Sitnik, Katarzyna Maria; Kotarsky, Knut

    The Vitamin A derivative retinoic acid (RA) has emerged as an important regulator of peripheral T cell responses. However, whether there is endogenous retinoic acid receptor (RAR) signaling in developing thymocytes and the potential impact of such signals in thymocyte development remains unclear...... further enhanced in recently generated CD69+ CD4+ SP cells. To address the potential biological significance of RA signaling in developing thymocytes, we evaluated T cell development in CD4Cre-dnRAR mice, where RA signaling is blocked in thymocytes from the CD4+CD8+ double positive (DP) stage onwards due...... of this cell subset. Collectively, our data suggest a direct role for RA signaling in regulating thymocyte homeostasis and T cell development....

  17. Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay

    NARCIS (Netherlands)

    Schulpen, Sjors H. W.; Pennings, Jeroen L. A.; Piersma, Aldert H.

    2015-01-01

    Differentiating pluripotent stem cells in vitro have proven useful for the study of developmental toxicity. Here, we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC)-based neurodevelopmental toxicity test (hESTn). During neural differentiation the cells were

  18. Amino acids regulate the intracellular trafficking of the general amino acid permease of Saccharomycescerevisiae.

    Science.gov (United States)

    Chen, Esther J; Kaiser, Chris A

    2002-11-12

    The delivery to the plasma membrane of the general amino acid permease, Gap1p, of Saccharomyces cerevisiae is regulated by the quality of the nitrogen source in the growth medium. In an effort to define how different nitrogen sources control Gap1p sorting, we find that mutations in GDH1 and GLN1 that decrease the flux through the glutamate and glutamine synthesis pathways result in increased Gap1p sorting to the plasma membrane. Conversely, deletion of MKS1, which increases glutamate and glutamine synthesis, decreases Gap1p sorting to the plasma membrane. Glutamate and glutamine are not unusual in their ability to regulate Gap1p sorting, because the addition of all natural amino acids and many amino acid analogs to the growth medium results in increased Gap1p sorting to the vacuole. Importantly, amino acids have the capacity to signal Gap1p sorting to the vacuole regardless of whether they can be used as a source of nitrogen. Finally, we show that rapamycin does not affect Gap1p sorting, indicating that Gap1p sorting is not directly influenced by the TOR pathway. Together, these data show that amino acids are a signal for sorting Gap1p to the vacuole and imply that the nitrogen-regulated Gap1p sorting machinery responds to amino acid-like compounds rather than to the overall nutritional status associated with growth on a particular nitrogen source.

  19. Regulation of inflammation by short chain fatty acids.

    Science.gov (United States)

    Vinolo, Marco A R; Rodrigues, Hosana G; Nachbar, Renato T; Curi, Rui

    2011-10-01

    The short chain fatty acids (SCFAs) acetate (C(2)), propionate (C(3)) and butyrate (C(4)) are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI) tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43) and inhibiton of histone deacetylase (HDAC). SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10), eicosanoids and chemokines (e.g., MCP-1 and CINC-2). The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells) and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted.

  20. Regulation of Inflammation by Short Chain Fatty Acids

    Directory of Open Access Journals (Sweden)

    Renato T. Nachbar

    2011-10-01

    Full Text Available The short chain fatty acids (SCFAs acetate (C2, propionate (C3 and butyrate (C4 are the main metabolic products of anaerobic bacteria fermentation in the intestine. In addition to their important role as fuel for intestinal epithelial cells, SCFAs modulate different processes in the gastrointestinal (GI tract such as electrolyte and water absorption. These fatty acids have been recognized as potential mediators involved in the effects of gut microbiota on intestinal immune function. SCFAs act on leukocytes and endothelial cells through at least two mechanisms: activation of GPCRs (GPR41 and GPR43 and inhibiton of histone deacetylase (HDAC. SCFAs regulate several leukocyte functions including production of cytokines (TNF-α, IL-2, IL-6 and IL-10, eicosanoids and chemokines (e.g., MCP-1 and CINC-2. The ability of leukocytes to migrate to the foci of inflammation and to destroy microbial pathogens also seems to be affected by the SCFAs. In this review, the latest research that describes how SCFAs regulate the inflammatory process is presented. The effects of these fatty acids on isolated cells (leukocytes, endothelial and intestinal epithelial cells and, particularly, on the recruitment and activation of leukocytes are discussed. Therapeutic application of these fatty acids for the treatment of inflammatory pathologies is also highlighted.

  1. Cyclic phosphatidic acid and lysophosphatidic acid induce hyaluronic acid synthesis via CREB transcription factor regulation in human skin fibroblasts.

    Science.gov (United States)

    Maeda-Sano, Katsura; Gotoh, Mari; Morohoshi, Toshiro; Someya, Takao; Murofushi, Hiromu; Murakami-Murofushi, Kimiko

    2014-09-01

    Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator and an analog of the growth factor-like phospholipid lysophosphatidic acid (LPA). cPA has a unique cyclic phosphate ring at the sn-2 and sn-3 positions of its glycerol backbone. We showed before that a metabolically stabilized cPA derivative, 2-carba-cPA, relieved osteoarthritis pathogenesis in vivo and induced hyaluronic acid synthesis in human osteoarthritis synoviocytes in vitro. This study focused on hyaluronic acid synthesis in human fibroblasts, which retain moisture and maintain health in the dermis. We investigated the effects of cPA and LPA on hyaluronic acid synthesis in human fibroblasts (NB1RGB cells). Using particle exclusion and enzyme-linked immunosorbent assays, we found that both cPA and LPA dose-dependently induced hyaluronic acid synthesis. We revealed that the expression of hyaluronan synthase 2 messenger RNA and protein is up-regulated by cPA and LPA treatment time dependently. We then characterized the signaling pathways up-regulating hyaluronic acid synthesis mediated by cPA and LPA in NB1RGB cells. Pharmacological inhibition and reporter gene assays revealed that the activation of the LPA receptor LPAR1, Gi/o protein, phosphatidylinositol-3 kinase (PI3K), extracellular-signal-regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding protein (CREB) but not nuclear factor κB induced hyaluronic acid synthesis by the treatment with cPA and LPA in NB1RGB cells. These results demonstrate for the first time that cPA and LPA induce hyaluronic acid synthesis in human skin fibroblasts mainly through the activation of LPAR1-Gi/o followed by the PI3K, ERK, and CREB signaling pathway.

  2. Tebuconazole Regulates Fatty Acid Composition of Etiolated Winter Wheat Seedlings

    Directory of Open Access Journals (Sweden)

    A.V. Korsukova

    2016-05-01

    Full Text Available The fatty acid composition of shoots of unhardened and hardened to cold etiolated winter wheat seedlings grown from seeds treated with tebuconazole-based protectant «Bunker» (content of tebuconazole 60 grams per liter, g/L, and the seedlings frost resistance has been studied. It is shown that treatment of winter wheat seeds by «Bunker» preparation (1,5 microliter per gram of seeds, µl/g is accompanied by an increase of the fatty acids unsaturation in the shoots and increase of the seedlings frost resistance (–8°C, 24 h. The most pronounced decrease in the content of saturated palmitic acid and increase in the content of unsaturated α-linolenic acid were observed during cold hardening of winter wheat seedlings grown from seeds treated by tebuconazole-based protectant. It is concluded that the seeds treatment with tebuconazole-based protectant causes changes of fatty acid composition of winter wheat seedlings to increase their frost resistance.

  3. Arabidopsis YAK1 regulates abscisic acid response and drought resistance

    KAUST Repository

    Kim, Dongjin

    2016-06-06

    Abscisic acid (ABA) is an important phytohormone that controls several plant processes such as seed germination, seedling growth, and abiotic stress response. Here, we report that AtYak1 plays an important role in ABA signaling and postgermination growth in Arabidopsis. AtYak1 knockout mutant plants were hyposensitive to ABA inhibition of seed germination, cotyledon greening, seedling growth, and stomatal movement. atyak1-1 mutant plants display reduced drought stress resistance, as evidenced by water loss rate and survival rate. Molecular genetic analysis revealed that AtYak1 deficiency led to elevated expression of stomatal-related gene, MYB60, and down-regulation of several stress-responsive genes. Altogether, these results indicate that AtYak1 plays a role as a positive regulator in ABA-mediated drought response in Arabidopsis. © 2016 Federation of European Biochemical Societies.

  4. The Conjugate Acid-Base Chart.

    Science.gov (United States)

    Treptow, Richard S.

    1986-01-01

    Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

  5. Acid-base transport in pancreas-new challenges

    DEFF Research Database (Denmark)

    Novak, Ivana; Haanes, Kristian Agmund; Wang, Jing

    2013-01-01

    Along the gastrointestinal tract a number of epithelia contribute with acid or basic secretions in order to aid digestive processes. The stomach and pancreas are the most extreme examples of acid (H+) and base (HCO-3) transporters, respectively. Nevertheless, they share the same challenges...... to consider in pancreas are the proton pumps (H-K-ATPases), as well as the calcium-activated K and Cl channels, such as K3.1 and TMEM16A/ANO1. Local regulators, such as purinergic signaling, fine-tune, and coordinate pancreatic secretion. Lastly, we speculate whether dys-regulation of acid-base transport...... contributes to pancreatic diseases including cystic fibrosis, pancreatitis, and cancer. © 2013 Novak, Haanes and Wang....

  6. Risk-based regulation: Challenges and opportunities

    Energy Technology Data Exchange (ETDEWEB)

    Bari, R.A.

    1995-11-01

    Over the last twenty years, man has witnessed a gradual but steady movement toward increased usage of risk-based methods and results in the regulatory process. The ``risk perspective`` as a supportive view to existing (non-risk-based or deterministic) information used in decision making has a firm foothold now in most countries that regulate nuclear power. Furthermore, in the areas outside the nuclear power field, such as health risk assessment, risk-based information is used increasingly to make decisions on potential impacts of chemical, biological, and radiological exposures. Some of the principal concepts and issues that are pertinent to risk-based regulation are reviewed. There is a growing interest in most countries in the use of risk-based methods and results to facilitate decision-making associated with regulatory processes. A summary is presented of the challenges and opportunities related to expanded use of risk-based regulation.

  7. Human Prostatic Acid Phosphatase: Structure, Function and Regulation

    Directory of Open Access Journals (Sweden)

    William G. Chaney

    2013-05-01

    Full Text Available Human prostatic acid phosphatase (PAcP is a 100 kDa glycoprotein composed of two subunits. Recent advances demonstrate that cellular PAcP (cPAcP functions as a protein tyrosine phosphatase by dephosphorylating ErbB-2/Neu/HER-2 at the phosphotyrosine residues in prostate cancer (PCa cells, which results in reduced tumorigenicity. Further, the interaction of cPAcP and ErbB-2 regulates androgen sensitivity of PCa cells. Knockdown of cPAcP expression allows androgen-sensitive PCa cells to develop the castration-resistant phenotype, where cells proliferate under an androgen-reduced condition. Thus, cPAcP has a significant influence on PCa cell growth. Interestingly, promoter analysis suggests that PAcP expression can be regulated by NF-κB, via a novel binding sequence in an androgen-independent manner. Further understanding of PAcP function and regulation of expression will have a significant impact on understanding PCa progression and therapy.

  8. Peptide nucleic acid (PNA) binding-mediated gene regulation

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    Peptide nucleic acids (PNAs) are synthetic oligonucleotides with chemically modified backbones. PNAs can bind to both DNA and RNA targets in a sequence-specific manner to form PNA/DNA and PNA/RNA duplex structures. When bound to double-stranded DNA (dsDNA) targets, the PNA molecule replaces one DNA strand in the duplex by strand invasion to form a PNA/DNA/PNA [or (PNA)2/DNA] triplex structure and the displaced DNA strand exists as a singlestranded D-loop. PNA has been used in many studies as research tools for gene regulation and gene targeting. The Dloops generated from the PNA binding have also been demonstrated for its potential in initiating transcription and inducing gene expression. PNA provides a powerful tool to study the mechanism of transcription and an innovative strategy to regulate target gene expression. An understanding of the PNA-mediated gene regulation will have important clinical implications in treatment of many human diseases including genetic, cancerous, and age-related diseases.

  9. Acid-base transport in pancreas – new challenges

    Directory of Open Access Journals (Sweden)

    Ivana eNovak

    2013-12-01

    Full Text Available Along the gastrointestinal tract a number of epithelia contribute with acid or basic secretions in order to aid digestive processes. The stomach and pancreas are the most extreme examples of acid (H+ and base (HCO3- transporters, respectively. Nevertheless, they share the same challenges of transporting acid and bases across epithelia and effectively regulating their intracellular pH. In this review, we will make use of comparative physiology to enlighten the cellular mechanisms of pancreatic HCO3- and fluid secretion, which is still challenging physiologists. Some of the novel transporters to consider in pancreas are the proton pumps (H+-K+-ATPases, as well as the calcium-activated K+ and Cl- channels, such as KCa3.1 and TMEM16A/ANO1. Local regulators, such as purinergic signalling, fine-tune and coordinate pancreatic secretion. Lastly, we speculate whether dys-regulation of acid-base transport contributes to pancreatic diseases including cystic fibrosis, pancreatitis and cancer.

  10. Structural insights into the regulation of aromatic amino acid hydroxylation.

    Science.gov (United States)

    Fitzpatrick, Paul F

    2015-12-01

    The aromatic amino acid hydroxylases phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase are homotetramers, with each subunit containing a homologous catalytic domain and a divergent regulatory domain. The solution structure of the regulatory domain of tyrosine hydroxylase establishes that it contains a core ACT domain similar to that in phenylalanine hydroxylase. The isolated regulatory domain of tyrosine hydroxylase forms a stable dimer, while that of phenylalanine hydroxylase undergoes a monomer-dimer equilibrium, with phenylalanine stabilizing the dimer. These solution properties are consistent with the regulatory mechanisms of the two enzymes, in that phenylalanine hydroxylase is activated by phenylalanine binding to an allosteric site, while tyrosine hydroxylase is regulated by binding of catecholamines in the active site.

  11. Boronic acid-based autoligation of nucleic acids

    DEFF Research Database (Denmark)

    Barbeyron, R.; Vasseur, J.-J.; Smietana, M.;

    2013-01-01

    Abstract: The development of synthetic systems displaying dynamic and adaptive characteristics is a formidable challenge with wide applications from biotechnology to therapeutics. Recently, we described a dynamic and programmable nucleic acid-based system relying on the formation of reversible...... boronate internucleosidic linkages. The DNA- or RNA-templated system comprises a 5′-ended boronic acid probe connecting a 3′-ended ribonucleosidic oligonucleotide partner. To explore the dominant factors that control the reversible linkage, we synthesized a series of 3′-end modified ribonucleotidic strands...

  12. Regulation of energy metabolism by long-chain fatty acids.

    Science.gov (United States)

    Nakamura, Manabu T; Yudell, Barbara E; Loor, Juan J

    2014-01-01

    In mammals, excess energy is stored primarily as triglycerides, which are mobilized when energy demands arise. This review mainly focuses on the role of long chain fatty acids (LCFAs) in regulating energy metabolism as ligands of peroxisome proliferator-activated receptors (PPARs). PPAR-alpha expressed primarily in liver is essential for metabolic adaptation to starvation by inducing genes for beta-oxidation and ketogenesis and by downregulating energy expenditure through fibroblast growth factor 21. PPAR-delta is highly expressed in skeletal muscle and induces genes for LCFA oxidation during fasting and endurance exercise. PPAR-delta also regulates glucose metabolism and mitochondrial biogenesis by inducing FOXO1 and PGC1-alpha. Genes targeted by PPAR-gamma in adipocytes suggest that PPAR-gamma senses incoming non-esterified LCFAs and induces the pathways to store LCFAs as triglycerides. Adiponectin, another important target of PPAR-gamma may act as a spacer between adipocytes to maintain their metabolic activity and insulin sensitivity. Another topic of this review is effects of skin LCFAs on energy metabolism. Specific LCFAs are required for the synthesis of skin lipids, which are essential for water barrier and thermal insulation functions of the skin. Disturbance of skin lipid metabolism often causes apparent resistance to developing obesity at the expense of normal skin function.

  13. Salicylic acid 3-hydroxylase regulates Arabidopsis leaf longevity by mediating salicylic acid catabolism.

    Science.gov (United States)

    Zhang, Kewei; Halitschke, Rayko; Yin, Changxi; Liu, Chang-Jun; Gan, Su-Sheng

    2013-09-01

    The plant hormone salicylic acid (SA) plays critical roles in plant defense, stress responses, and senescence. Although SA biosynthesis is well understood, the pathways by which SA is catabolized remain elusive. Here we report the identification and characterization of an SA 3-hydroxylase (S3H) involved in SA catabolism during leaf senescence. S3H is associated with senescence and is inducible by SA and is thus a key part of a negative feedback regulation system of SA levels during senescence. The enzyme converts SA (with a Km of 58.29 µM) to both 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-DHBA in vitro but only 2,3-DHBA in vivo. The s3h knockout mutants fail to produce 2,3-DHBA sugar conjugates, accumulate very high levels of SA and its sugar conjugates, and exhibit a precocious senescence phenotype. Conversely, the gain-of-function lines contain high levels of 2,3-DHBA sugar conjugates and extremely low levels of SA and its sugar conjugates and display a significantly extended leaf longevity. This research reveals an elegant SA catabolic mechanism by which plants regulate SA levels by converting it to 2,3-DHBA to prevent SA overaccumulation. The research also provides strong molecular genetic evidence for an important role of SA in regulating the onset and rate of leaf senescence.

  14. Whole body acid-base modeling revisited.

    Science.gov (United States)

    Ring, Troels; Nielsen, Søren

    2017-04-01

    The textbook account of whole body acid-base balance in terms of endogenous acid production, renal net acid excretion, and gastrointestinal alkali absorption, which is the only comprehensive model around, has never been applied in clinical practice or been formally validated. To improve understanding of acid-base modeling, we managed to write up this conventional model as an expression solely on urine chemistry. Renal net acid excretion and endogenous acid production were already formulated in terms of urine chemistry, and we could from the literature also see gastrointestinal alkali absorption in terms of urine excretions. With a few assumptions it was possible to see that this expression of net acid balance was arithmetically identical to minus urine charge, whereby under the development of acidosis, urine was predicted to acquire a net negative charge. The literature already mentions unexplained negative urine charges so we scrutinized a series of seminal papers and confirmed empirically the theoretical prediction that observed urine charge did acquire negative charge as acidosis developed. Hence, we can conclude that the conventional model is problematic since it predicts what is physiologically impossible. Therefore, we need a new model for whole body acid-base balance, which does not have impossible implications. Furthermore, new experimental studies are needed to account for charge imbalance in urine under development of acidosis.

  15. A Direct, Biomass-Based Synthesis of Benzoic Acid: Formic Acid-Mediated Deoxygenation of the Glucose-Derived Materials Quinic Acid and Shikimic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Arceo, Elena; Ellman, Jonathan; Bergman, Robert

    2010-05-03

    An alternative biomass-based route to benzoic acid from the renewable starting materials quinic acid and shikimic acid is described. Benzoic acid is obtained selectively using a highly efficient, one-step formic acid-mediated deoxygenation method.

  16. Direct block of the cystic fibrosis transmembrane conductance regulator Cl(-) channel by niflumic acid.

    Science.gov (United States)

    Scott-Ward, T S; Li, H; Schmidt, A; Cai, Z; Sheppard, D N

    2004-01-01

    Niflumic acid is widely used to inhibit Ca(2+) -activated Cl(-) channels. However, the chemical structure of niflumic acid resembles that of diphenylamine-2-carboxylate, a drug that inhibits the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. To investigate how niflumic acid inhibits CFTR Cl(-) channel, we studied recombinant wild-type human CFTR in excised inside-out membrane patches. When added to the intracellular solution, niflumic acid caused a concentration- and voltage-dependent decrease of CFTR Cl(-) current with half-maximal inhibitory concentration (K(i)) of 253 microM and Hill co-efficient of approximately 1, at -50 mV. Niflumic acid inhibition of single CFTR Cl(-) channels was characterized by a very fast, flickery block that decreased dramatically current amplitude without altering open-probability. Consistent with these data, spectral analysis of CFTR Cl(-) currents suggested that channel block by niflumic acid was described by the closed open blocked kinetic scheme with blocker on rate (k(on)) = 13.9 x 10(6) M(-1)s(-1), off rate (k(off))=3348 s(-1) and dissociation constant (K(d)) = 241 microM, at -50 mV. Based on these data, we tested the effects of niflumic acid on transepithelial Cl(-) secretion and cyst growth using type I MDCK epithelial cells. Niflumic acid (200 microM) inhibited cAMP-stimulated, bumetanide-sensitive short-circuit current by 55%. Moreover, the drug potently retarded cyst growth. We conclude that niflumic acid is an open-channel blocker of CFTR that inhibits Cl(-) permeation by plugging the channel pore. It or related agents might be of value in the development of new therapies for autosomal dominant polycystic kidney disease.

  17. Low-maintenance, valve-regulated, lead/acid batteries in utility applications

    Science.gov (United States)

    Cook, G. M.; Spindler, W. C.

    Electric power utility companies have various needs for lead/acid batteries, and also are beginning to promote customer-side-of-the meter applications for mutual benefits. Increasing use of lead/acid batteries in the future will depend heavily on improving performance and reliability of sealed, recombination designs, and on their versatility for many applications. Classifying various utility uses could be by cycling requirements, depth-of-discharge, power or energy (ratio of watts to hours), or by site (utility or customer). Deep-cycling examples are energy storage, peak-shaving and electric vehicles. Shallow-cycling examples are frequency regulation and reactive power control. Infrequent discharge examples are stationary service and spinning reserve. (Float service for telecommunications and uninterruptible power sources (UPS) applications are not addressed.) Some present and planned installations of valve-regulated lead/acid batteries are surveyed. Performance characteristics will be discussed, including recent results of testing both gel and absorptive glass mat (AGM) types of deep-cycling batteries. Recommendations for future research and development of valve-regulated cell technology are outlined, based on a recent conference organized by the United States Department of Energy (USDOE) and the Electric Power Research Institute (EPRI).

  18. Metabolic regulation of the plant hormone indole-3-acetic acid

    Energy Technology Data Exchange (ETDEWEB)

    Jerry D. Cohen

    2009-11-01

    The phytohormone indole-3-acetic acid (IAA, auxin) is important for many aspects of plant growth, development and responses to the environment yet the routes to is biosynthesis and mechanisms for regulation of IAA levels remain important research questions. A critical issue concerning the biosynthesis if IAA in plants is that redundant pathways for IAA biosynthesis exist in plants. We showed that these redundant pathways and their relative contribution to net IAA production are under both developmental and environmental control. We worked on three fundamental problems related to how plants get their IAA: 1) An in vitro biochemical approach was used to define the tryptophan dependent pathway to IAA using maize endosperm, where relatively large amounts of IAA are produced over a short developmental period. Both a stable isotope dilution and a protein MS approach were used to identify intermediates and enzymes in the reactions. 2) We developed an in vitro system for analysis of tryptophan-independent IAA biosynthesis in maize seedlings and we used a metabolite profiling approach to isolate intermediates in this reaction. 3) Arabidopsis contains a small family of genes that encode potential indolepyruvate decarboxylase enzymes. We cloned these genes and studied plants that are mutant in these genes and that over-express each member in the family in terms of the level and route of IAA biosynthesis. Together, these allowed further development of a comprehensive picture of the pathways and regulatory components that are involved in IAA homeostasis in higher plants.

  19. Hepatic oleate regulates adipose tissue lipogenesis and fatty acid oxidation.

    Science.gov (United States)

    Burhans, Maggie S; Flowers, Matthew T; Harrington, Kristin R; Bond, Laura M; Guo, Chang-An; Anderson, Rozalyn M; Ntambi, James M

    2015-02-01

    Hepatic steatosis is associated with detrimental metabolic phenotypes including enhanced risk for diabetes. Stearoyl-CoA desaturases (SCDs) catalyze the synthesis of MUFAs. In mice, genetic ablation of SCDs reduces hepatic de novo lipogenesis (DNL) and protects against diet-induced hepatic steatosis and adiposity. To understand the mechanism by which hepatic MUFA production influences adipose tissue stores, we created two liver-specific transgenic mouse models in the SCD1 knockout that express either human SCD5 or mouse SCD3, that synthesize oleate and palmitoleate, respectively. We demonstrate that hepatic de novo synthesized oleate, but not palmitoleate, stimulate hepatic lipid accumulation and adiposity, reversing the protective effect of the global SCD1 knockout under lipogenic conditions. Unexpectedly, the accumulation of hepatic lipid occurred without induction of the hepatic DNL program. Changes in hepatic lipid composition were reflected in plasma and in adipose tissue. Importantly, endogenously synthesized hepatic oleate was associated with suppressed DNL and fatty acid oxidation in white adipose tissue. Regression analysis revealed a strong correlation between adipose tissue lipid fuel utilization and hepatic and adipose tissue lipid storage. These data suggest an extrahepatic mechanism where endogenous hepatic oleate regulates lipid homeostasis in adipose tissues.

  20. Towards bridging the gap between acid-base transporters and neuronal excitability modulation.

    Science.gov (United States)

    Liu, Ying; Chen, Li-Ming

    2014-01-01

    pH homeostasis is a fundamental regulator of the function of the central nervous system. Dysfunction of acid-base transporters often results in disturbance of neuronal excitability. In a latest issue of Journal of Neuroscience, Jones et al. report that increasing intracellular bicarbonate concentration substantially stimulates the excitability of pyramidal neurons from mouse hippocampus by inhibiting KCNQ potassium channel. The finding shed important new light in understanding the molecular mechanism underlying the regulation of neuronal excitability by acid-base transporters.

  1. Regulation of Water Deficit-Induced Abscisic Acid Accumulation by Apoplastic Ascorbic Acid in Maize Seedlings

    Institute of Scientific and Technical Information of China (English)

    Jian-Fang HU; Gui-Fen LI; Zhi-Hui GAO; Lin CHEN; Hui-Bo REN; Wen-Suo JIA

    2005-01-01

    Water deficit-induced abscisic acid (ABA) accumulation is one of the most important stress signaling pathways in plant cells. Redox regulation of cellular signaling has currently attracted particular attention, but much less is known about its roles and mechanisms in plant signaling. Herein, we report that water deficit-induced ABA accumulation could be regulated by ascorbic acid (AA)-controlled redox status in leave apoplast. The AA content in non-stressed leaves was approximately 3 μmol/g FW, corresponding to a mean concentration of 3 mmol/L in a whole cell. Because AA is mainly localized in the cytosol and chloroplasts, the volume of which is much smaller than that of the whole cell, AA content in cytosolic and chloroplast compartments should be much higher than 3 mmol/L. Water deficit-induced ABA accumulation in both leaf and root tissues of maize seedlings was significantly inhibited by AA and reduced glutathione (GSH) at concentrations of 500 μmol/L and was completely blocked by 50 mmol/L AA and GSH. These results suggest that the AA-induced inhibition of ABA accumulation should not occur at sites where AA exists in high concentrations. Although water deficit led to a small increase in the dehydroascorbic acid (DHA) content, no significant changes in AA content were observed in either leaf or root tissues. When compared with the whole leaf cell, the AA content in the apoplastic compartment was much lower (i.e.approximately 70 nmol/g FW, corresponding to 0.7 mmol/L). Water deficit induced a significant decrease (approximately 2.5-fold) in the AA content and an increase (approximately 3.4-fold) in the DHA content in the apoplastic compartment, thus leading to a considerably decreased redox status there, which may have contributed to the relief of AA-induced inhibition of ABA accumulation, alternatively, promoting water deficit-induced ABA accumulation. Reactive oxygen species (ROS) could not mimic water deficit in inducing ABA accumulation, suggesting that

  2. Hypokalemic paralysis and acid-base balance

    Directory of Open Access Journals (Sweden)

    Ivo Casagranda

    2006-10-01

    Full Text Available Three cases of hypokalemic paralysis are reported, presenting to the Emergency Department. The first is a patient with a hypokalemic periodic paralysis with a normal acid-base status, the second is a case of hypokalemic flaccid paralysis of all extremities with a normal anion gap metabolic acidosis, the last is a patient with a hypokalemic distal paralysis of right upper arm with metabolic alkalosis. Afterwards some pathophysiologic principles and the clinical aspects of hypokalemia are discussed and an appropriate approach to do in Emergency Department, to identify the hypokalemic paralysis etiologies in the Emergency Department, is presented, beginning from the evaluation of acid-base status.

  3. Arabidopsis MAP kinase 4 regulates salicylic acid- and jasmonic acid/ethylene-dependent responses via EDS1 and PAD4

    DEFF Research Database (Denmark)

    Brodersen, Klaus Peter; Petersen, Morten; Nielsen, Henrik Bjørn

    2006-01-01

    Arabidopsis MPK4 has been implicated in plant defense regulation because mpk4 knockout plants exhibit constitutive activation of salicylic acid (SA)-dependent defenses, but fail to induce jasmonic acid (JA) defense marker genes in response to JA. We show here that mpk4 mutants are also defective...

  4. Metabolic pathways regulated by abscisic acid, salicylic acid and γ-aminobutyric acid in association with improved drought tolerance in creeping bentgrass (Agrostis stolonifera).

    Science.gov (United States)

    Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

    2017-01-01

    Abscisic acid (ABA), salicylic acid (SA) and γ-aminobutyric acid (GABA) are known to play roles in regulating plant stress responses. This study was conducted to determine metabolites and associated pathways regulated by ABA, SA and GABA that could contribute to drought tolerance in creeping bentgrass (Agrostis stolonifera). Plants were foliar sprayed with ABA (5 μM), GABA (0.5 mM) and SA (10 μM) or water (untreated control) prior to 25 days drought stress in controlled growth chambers. Application of ABA, GABA or SA had similar positive effects on alleviating drought damages, as manifested by the maintenance of lower electrolyte leakage and greater relative water content in leaves of treated plants relative to the untreated control. Metabolic profiling showed that ABA, GABA and SA induced differential metabolic changes under drought stress. ABA mainly promoted the accumulation of organic acids associated with tricarboxylic acid cycle (aconitic acid, succinic acid, lactic acid and malic acid). SA strongly stimulated the accumulation of amino acids (proline, serine, threonine and alanine) and carbohydrates (glucose, mannose, fructose and cellobiose). GABA enhanced the accumulation of amino acids (GABA, glycine, valine, proline, 5-oxoproline, serine, threonine, aspartic acid and glutamic acid) and organic acids (malic acid, lactic acid, gluconic acid, malonic acid and ribonic acid). The enhanced drought tolerance could be mainly due to the enhanced respiration metabolism by ABA, amino acids and carbohydrates involved in osmotic adjustment (OA) and energy metabolism by SA, and amino acid metabolism related to OA and stress-defense secondary metabolism by GABA.

  5. [Regulating acid stress resistance of lactic acid bacteria--a review].

    Science.gov (United States)

    Wu, Chongde; Huang, Jun; Zhou, Rongqing

    2014-07-04

    As cell factories, lactic acid bacteria are widely used in food, agriculture, pharmaceutical and other industries. Acid stress is one the important survival challenges encountered by lactic acid bacteria both in fermentation process and in the gastrointestinal tract. Recently, the development of systems biology and metabolic engineering brings unprecedented opportunity for further elucidating the acid tolerance mechanisms and improving the acid stress resistance of lactic acid bacteria. This review addresses physiological mechanisms of lactic acid bacteria during acid stress. Moreover, strategies to improve the acid stress resistance of lactic acid were proposed.

  6. The effect pathway of retinoic acid through regulation of retinoic acid receptor in gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Su Liu; Qiao Wu; Zheng-Ming Chen; Wen-Jin Su

    2001-01-01

    AIM To evaluate the role of RARa gene in mediating the growth inhibitory effect of ail-trans retinoic acid (ATRA)on gastric cancer cells.``METHODS The expression levels of retinoic acid receptors (RARs) in gastric cancer cells were detected by Northern blot. Transient transfection and chlorophenicol acetyl transferase (CAT) assay were used to show the transcriptional activity of β retinoic acid response element (βRARE) and AP-l activity. Cell growth inhibition was determined by MTT assay and anchorage-independent growth assay, respectively. Stable transfection was performed by the method of Lipofectamine, and the cells were screened by G418.``RESULTS ATRA could induce expression level of RARα in MGC80-3, BGCC8823 and SGC-7901 cells obviously,resulting in growth inhibition of these cell lines. After sense RARa gene was transfected into MKN-45 cells that expressed rather Iow level of RARα and could not be induced by ATRA, the cell growth was inhibited by ATRA markedly. In contrast, when antisense RARα gene was transfected into BGC-825 cells, a little inhibitory effect by ATRA was seen, compared with the parallel BGC-823cells. In transient transfection assay, ATRA effectively induced transcriptional activity of βRARE in MGC80-3,BGC.823, SGC-7902 and MKN/RARa cell lines, but not in MKN-45 and BGC/aRARa cell lines. Similar results were observed in measuring anti-AP-l activity by ATRA in these cancer cell lines.``CONCLUSION ATRA inhibits the growth of gastric cancer cells by up-regulating the level of RARa; RARa is the major mediator of ATRA action in gastric cancer cells; and adequate level of RAPa is required for ATRA effect on gastric cancer cells.``

  7. Fermented probiotic beverages based on acid whey

    Directory of Open Access Journals (Sweden)

    Katarzyna Skryplonek

    2015-12-01

    Full Text Available Background. Production of fermented probiotic beverages can be a good method for acid whey usage. The obtained products combine a high nutritional value of whey with health benefits claimed for probiotic bac- teria. The aim of the study was to define quality properties of beverages based on fresh acid whey and milk with addition of buttermilk powder or sweet whey powder. Material and methods. Samples were inoculated with two strains of commercial probiotic cultures: Lac- tobacillus acidophilus La-5 or Bifidobacterium animalis Bb-12. After fermentation, samples were stored at refrigerated conditions. After 1, 4, 7, 14 and 21 days sensory characteristics, hardness, acetaldehyde content, titratable acidity, pH acidity and count of bacteria cells were evaluated. Results. Throughout all storage period, the number of bacteria was higher than 8 log cfu/ml in the all sam- ples. Beverages with La-5 strain had higher hardness and acidity, whilst samples with Bb-12 contained more acetaldehyde. Samples with buttermilk powder had better sensory properties than with sweet whey powder. Conclusions. Obtained products made of acid whey combined with milk and fortified with buttermilk pow- der or sweet whey powder, are good medium for growth and survival of examined probiotic bacteria strains. The level of bacteria was sufficient to provide health benefits to consumers.

  8. The Magic Sign: Acids, Bases, and Indicators.

    Science.gov (United States)

    Phillips, Donald B.

    1986-01-01

    Presents an approach that is used to introduce elementary and junior high students to a series of activities that will provide concrete experiences with acids, bases, and indicators. Provides instructions and listings of needed solutions and materials for developing this "magic sign" device. Includes background information and several…

  9. Jigsaw Cooperative Learning: Acid-Base Theories

    Science.gov (United States)

    Tarhan, Leman; Sesen, Burcin Acar

    2012-01-01

    This study focused on investigating the effectiveness of jigsaw cooperative learning instruction on first-year undergraduates' understanding of acid-base theories. Undergraduates' opinions about jigsaw cooperative learning instruction were also investigated. The participants of this study were 38 first-year undergraduates in chemistry education…

  10. Glycine/Glycolic acid based copolymers

    NARCIS (Netherlands)

    Veld, in 't Peter J.A.; Shen, Zheng-Rong; Takens, Gijsbert A.J.; Dijkstra, Pieter J.; Feijen, Jan

    1994-01-01

    Glycine/glycolic acid based biodegradable copolymers have been prepared by ring-opening homopolymerization of morpholine-2,5-dione, and ring-opening copolymerization of morpholine-2,5-dione and glycolide. The homopolymerization of morpholine-2,5-dione was carried out in the melt at 200°C for 3 min u

  11. Acid trehalase in yeasts and filamentous fungi: localization, regulation and physiological function.

    Science.gov (United States)

    Parrou, Jean Luc; Jules, Matthieu; Beltran, Gemma; François, Jean

    2005-04-01

    Yeasts and filamentous fungi are endowed with two different trehalose-hydrolysing activities, termed acid and neutral trehalases according to their optimal pH for enzymatic activity. A wealth of information already exists on fungal neutral trehalases, while data on localization, regulation and function of fungal acid trehalases have remained elusive. The gene encoding the latter enzyme has now been isolated from two yeast species and two filamentous fungi, and sequences encoding putative acid trehalase can be retrieved from available public sequences. Despite weak similarities between amino acids sequences, this type of trehalase potentially harbours either a transmembrane segment or a signal peptide at the N-terminal sequence, as deduced from domain prediction algorithms. This feature, together with the demonstration that acid trehalase from yeasts and filamentous fungi is localized at the cell surface, is consistent with its main role in the utilisation of exogenous trehalose as a carbon source. The growth on this disaccharide is in fact pretty effective in most fungi except in Saccharomyces cerevisiae. This yeast species actually exhibits a "Kluyver effect" on trehalose. Moreover, an oscillatory behaviour reminiscent of what is observed in aerobic glucose-limited continuous cultures at low dilution rate is also observed in batch growth on trehalose. Finally, the S. cerevisiae acid trehalase may also participate in the catabolism of endogenous trehalose by a mechanism that likely requires the export of the disaccharide, its extracellular hydrolysis, and the subsequent uptake of the glucose released. Based on these recent findings, we suggest to rename "acid" and "neutral" trehalases as "extracellular" and "cytosolic" trehalases, which is more adequate to describe their localization and function in the fungal cell.

  12. A C-terminal acidic domain regulates degradation of the transcriptional coactivator Bob1.

    Science.gov (United States)

    Lindner, John M; Wong, Christina S F; Möller, Andreas; Nielsen, Peter J

    2013-12-01

    Bob1 (Obf-1 or OCA-B) is a 34-kDa transcriptional coactivator encoded by the Pou2af1 gene that is essential for normal B-cell development and immune responses in mice. During lymphocyte activation, Bob1 protein levels dramatically increase independently of mRNA levels, suggesting that the stability of Bob1 is regulated. We used a fluorescent protein-based reporter system to analyze protein stability in response to genetic and physiological perturbations and show that, while Bob1 degradation is proteasome mediated, it does not require ubiquitination of Bob1. Furthermore, degradation of Bob1 in B cells appears to be largely independent of the E3 ubiquitin ligase Siah. We propose a novel mechanism of Bob1 turnover in B cells, whereby an acidic region in the C terminus of Bob1 regulates the activity of degron signals elsewhere in the protein. Changes that make the C terminus more acidic, including tyrosine phosphorylation-mimetic mutations, stabilize the instable murine Bob1 protein, indicating that B cells may regulate Bob1 stability and activity via signaling pathways. Finally, we show that expressing a stable Bob1 mutant in B cells suppresses cell proliferation and induces changes in surface marker expression commonly seen during B-cell differentiation.

  13. Soluble adenylyl cyclase is an acid-base sensor in epithelial base-secreting cells.

    Science.gov (United States)

    Roa, Jinae N; Tresguerres, Martin

    2016-08-01

    Blood acid-base regulation by specialized epithelia, such as gills and kidney, requires the ability to sense blood acid-base status. Here, we developed primary cultures of ray (Urolophus halleri) gill cells to study mechanisms for acid-base sensing without the interference of whole animal hormonal regulation. Ray gills have abundant base-secreting cells, identified by their noticeable expression of vacuolar-type H(+)-ATPase (VHA), and also express the evolutionarily conserved acid-base sensor soluble adenylyl cyclase (sAC). Exposure of cultured cells to extracellular alkalosis (pH 8.0, 40 mM HCO3 (-)) triggered VHA translocation to the cell membrane, similar to previous reports in live animals experiencing blood alkalosis. VHA translocation was dependent on sAC, as it was blocked by the sAC-specific inhibitor KH7. Ray gill base-secreting cells also express transmembrane adenylyl cyclases (tmACs); however, tmAC inhibition by 2',5'-dideoxyadenosine did not prevent alkalosis-dependent VHA translocation, and tmAC activation by forskolin reduced the abundance of VHA at the cell membrane. This study demonstrates that sAC is a necessary and sufficient sensor of extracellular alkalosis in ray gill base-secreting cells. In addition, this study indicates that different sources of cAMP differentially modulate cell biology.

  14. Strong Relationships in Acid-Base Chemistry – Modeling Protons Based on Predictable Concentrations of Strong Ions, Total Weak Acid Concentrations, and pCO2

    OpenAIRE

    2016-01-01

    Understanding acid-base regulation is often reduced to pigeonholing clinical states into categories of disorders based on arterial blood sampling. An earlier ambition to quantitatively explain disorders by measuring production and elimination of acid has not become standard clinical practice. Seeking back to classical physical chemistry we propose that in any compartment, the requirement of electroneutrality leads to a strong relationship between charged moieties. This relationship is derived...

  15. Molecular mechanisms of acid-base sensing by the kidney.

    Science.gov (United States)

    Brown, Dennis; Wagner, Carsten A

    2012-05-01

    A major function of the kidney is to collaborate with the respiratory system to maintain systemic acid-base status within limits compatible with normal cell and organ function. It achieves this by regulating the excretion and recovery of bicarbonate (mainly in the proximal tubule) and the secretion of buffered protons (mainly in the distal tubule and collecting duct). How proximal tubular cells and distal professional proton transporting (intercalated) cells sense and respond to changes in pH, bicarbonate, and CO(2) status is a question that has intrigued many generations of renal physiologists. Over the past few years, however, some candidate molecular pH sensors have been identified, including acid/alkali-sensing receptors (GPR4, InsR-RR), kinases (Pyk2, ErbB1/2), pH-sensitive ion channels (ASICs, TASK, ROMK), and the bicarbonate-stimulated adenylyl cyclase (sAC). Some acid-sensing mechanisms in other tissues, such as CAII-PDK2L1 in taste buds, might also have similar roles to play in the kidney. Finally, the function of a variety of additional membrane channels and transporters is altered by pH variations both within and outside the cell, and the expression of several metabolic enzymes are altered by acid-base status in parts of the nephron. Thus, it is possible that a master pH sensor will never be identified. Rather, the kidney seems equipped with a battery of molecules that scan the epithelial cell environment to mount a coordinated physiologic response that maintains acid-base homeostasis. This review collates current knowledge on renal acid-base sensing in the context of a whole organ sensing and response process.

  16. Xenobiotic, bile acid, and cholesterol transporters: function and regulation.

    Science.gov (United States)

    Klaassen, Curtis D; Aleksunes, Lauren M

    2010-03-01

    Transporters influence the disposition of chemicals within the body by participating in absorption, distribution, and elimination. Transporters of the solute carrier family (SLC) comprise a variety of proteins, including organic cation transporters (OCT) 1 to 3, organic cation/carnitine transporters (OCTN) 1 to 3, organic anion transporters (OAT) 1 to 7, various organic anion transporting polypeptide isoforms, sodium taurocholate cotransporting polypeptide, apical sodium-dependent bile acid transporter, peptide transporters (PEPT) 1 and 2, concentrative nucleoside transporters (CNT) 1 to 3, equilibrative nucleoside transporter (ENT) 1 to 3, and multidrug and toxin extrusion transporters (MATE) 1 and 2, which mediate the uptake (except MATEs) of organic anions and cations as well as peptides and nucleosides. Efflux transporters of the ATP-binding cassette superfamily, such as ATP-binding cassette transporter A1 (ABCA1), multidrug resistance proteins (MDR) 1 and 2, bile salt export pump, multidrug resistance-associated proteins (MRP) 1 to 9, breast cancer resistance protein, and ATP-binding cassette subfamily G members 5 and 8, are responsible for the unidirectional export of endogenous and exogenous substances. Other efflux transporters [ATPase copper-transporting beta polypeptide (ATP7B) and ATPase class I type 8B member 1 (ATP8B1) as well as organic solute transporters (OST) alpha and beta] also play major roles in the transport of some endogenous chemicals across biological membranes. This review article provides a comprehensive overview of these transporters (both rodent and human) with regard to tissue distribution, subcellular localization, and substrate preferences. Because uptake and efflux transporters are expressed in multiple cell types, the roles of transporters in a variety of tissues, including the liver, kidneys, intestine, brain, heart, placenta, mammary glands, immune cells, and testes are discussed. Attention is also placed upon a variety of

  17. Saturated fatty acids regulate retinoic acid signalling and suppress tumorigenesis by targeting fatty acid-binding protein 5.

    Science.gov (United States)

    Levi, Liraz; Wang, Zeneng; Doud, Mary Kathryn; Hazen, Stanley L; Noy, Noa

    2015-11-23

    Long chain fatty acids (LCFA) serve as energy sources, components of cell membranes and precursors for signalling molecules. Here we show that these biological compounds also regulate gene expression and that they do so by controlling the transcriptional activities of the retinoic acid (RA)-activated nuclear receptors RAR and PPARβ/δ. The data indicate that these activities of LCFA are mediated by FABP5, which delivers ligands from the cytosol to nuclear PPARβ/δ. Both saturated and unsaturated LCFA (SLCFA, ULCFA) bind to FABP5, thereby displacing RA and diverting it to RAR. However, while SLCFA inhibit, ULCFA activate the FABP5/PPARβ/δ pathway. We show further that, by concomitantly promoting the activation of RAR and inhibiting the activation of PPARβ/δ, SLCFA suppress the oncogenic properties of FABP5-expressing carcinoma cells in cultured cells and in vivo. The observations suggest that compounds that inhibit FABP5 may constitute a new class of drugs for therapy of certain types of cancer.

  18. Genetic analysis of pathway regulation for enhancing branched-chain amino acid biosynthesis in plants

    KAUST Repository

    Chen, Hao

    2010-08-01

    The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that play critical roles in animal growth and development. Animals cannot synthesize these amino acids and must obtain them from their diet. Plants are the ultimate source of these essential nutrients, and they synthesize BCAAs through a conserved pathway that is inhibited by its end products. This feedback inhibition has prevented scientists from engineering plants that accumulate high levels of BCAAs by simply over-expressing the respective biosynthetic genes. To identify components critical for this feedback regulation, we performed a genetic screen for Arabidopsis mutants that exhibit enhanced resistance to BCAAs. Multiple dominant allelic mutations in the VALINE-TOLERANT 1 (VAT1) gene were identified that conferred plant resistance to valine inhibition. Map-based cloning revealed that VAT1 encodes a regulatory subunit of acetohydroxy acid synthase (AHAS), the first committed enzyme in the BCAA biosynthesis pathway. The VAT1 gene is highly expressed in young, rapidly growing tissues. When reconstituted with the catalytic subunit in vitro, the vat1 mutant-containing AHAS holoenzyme exhibits increased resistance to valine. Importantly, transgenic plants expressing the mutated vat1 gene exhibit valine tolerance and accumulate higher levels of BCAAs. Our studies not only uncovered regulatory characteristics of plant AHAS, but also identified a method to enhance BCAA accumulation in crop plants that will significantly enhance the nutritional value of food and feed. © 2010 Blackwell Publishing Ltd.

  19. The first proton sponge-based amino acids: synthesis, acid-base properties and some reactivity.

    Science.gov (United States)

    Ozeryanskii, Valery A; Gorbacheva, Anastasia Yu; Pozharskii, Alexander F; Vlasenko, Marina P; Tereznikov, Alexander Yu; Chernov'yants, Margarita S

    2015-08-21

    The first hybrid base constructed from 1,8-bis(dimethylamino)naphthalene (proton sponge or DMAN) and glycine, N-methyl-N-(8-dimethylamino-1-naphthyl)aminoacetic acid, was synthesised in high yield and its hydrobromide was structurally characterised and used to determine the acid-base properties via potentiometric titration. It was found that the basic strength of the DMAN-glycine base (pKa = 11.57, H2O) is on the level of amidine amino acids like arginine and creatine and its structure, zwitterionic vs. neutral, based on the spectroscopic (IR, NMR, mass) and theoretical (DFT) approaches has a strong preference to the zwitterionic form. Unlike glycine, the DMAN-glycine zwitterion is N-chiral and is hydrolytically cleaved with the loss of glycolic acid on heating in DMSO. This reaction together with the mild decarboxylative conversion of proton sponge-based amino acids into 2,3-dihydroperimidinium salts under air-oxygen was monitored with the help of the DMAN-alanine amino acid. The newly devised amino acids are unique as they combine fluorescence, strongly basic and redox-active properties.

  20. Amino acids allosterically regulate the thiamine diphosphate-dependent alpha-keto acid decarboxylase from Mycobacterium tuberculosis.

    Science.gov (United States)

    Werther, Tobias; Spinka, Michael; Tittmann, Kai; Schütz, Anja; Golbik, Ralph; Mrestani-Klaus, Carmen; Hübner, Gerhard; König, Stephan

    2008-02-29

    The gene rv0853c from Mycobacterium tuberculosis strain H37Rv codes for a thiamine diphosphate-dependent alpha-keto acid decarboxylase (MtKDC), an enzyme involved in the amino acid degradation via the Ehrlich pathway. Steady state kinetic experiments were performed to determine the substrate specificity of MtKDC. The mycobacterial enzyme was found to convert a broad spectrum of branched-chain and aromatic alpha-keto acids. Stopped-flow kinetics showed that MtKDC is allosterically activated by alpha-keto acids. Even more, we demonstrate that also amino acids are potent activators of this thiamine diphosphate-dependent enzyme. Thus, metabolic flow through the Ehrlich pathway can be directly regulated at the decarboxylation step. The influence of amino acids on MtKDC catalysis was investigated, and implications for other thiamine diphosphate-dependent enzymes are discussed.

  1. Regulation of uterine and umbilical amino acid uptakes by maternal amino acid concentrations.

    Science.gov (United States)

    Thureen, P J; Anderson, S M; Hay, W W

    2000-09-01

    We tested the hypothesis that decreased fetal amino acid (AA) supply, produced by maternal hypoaminoacidemia (low AA) during hyperglycemia (HG), is reversible with maternal AA infusion and regulates fetal insulin concentration ([I]). We measured net uterine and umbilical AA uptakes during maternal HG/low AA concentration ([AA]) and after maternal intravenous infusion of a mixed AA solution. After 5 days HG, all maternal [AA] except glycine were decreased >50%, particularly essential [AA] (P infusion increased net uterine uptakes of Val, Leu, Ile, Met, and Ser and net umbilical uptakes of Val, Leu, Ile, Met, Phe, and Arg but did not change net uteroplacental uptake of any AA. Fetal [I] increased 55 +/- 14%, P < 0.001, with correction of fetal [AA], despite the lack of change in fetal glucose concentration. Thus generalized maternal hypoaminoacidemia decreases uterine and umbilical uptakes of primarily the essential AA and decreases fetal branched-chain [AA]. These changes are reversed with correction of maternal [AA], which also increases fetal [I].

  2. Bio-based production of organic acids with Corynebacterium glutamicum.

    Science.gov (United States)

    Wieschalka, Stefan; Blombach, Bastian; Bott, Michael; Eikmanns, Bernhard J

    2013-03-01

    The shortage of oil resources, the steadily rising oil prices and the impact of its use on the environment evokes an increasing political, industrial and technical interest for development of safe and efficient processes for the production of chemicals from renewable biomass. Thus, microbial fermentation of renewable feedstocks found its way in white biotechnology, complementing more and more traditional crude oil-based chemical processes. Rational strain design of appropriate microorganisms has become possible due to steadily increasing knowledge on metabolism and pathway regulation of industrially relevant organisms and, aside from process engineering and optimization, has an outstanding impact on improving the performance of such hosts. Corynebacterium glutamicum is well known as workhorse for the industrial production of numerous amino acids. However, recent studies also explored the usefulness of this organism for the production of several organic acids and great efforts have been made for improvement of the performance. This review summarizes the current knowledge and recent achievements on metabolic engineering approaches to tailor C. glutamicum for the bio-based production of organic acids. We focus here on the fermentative production of pyruvate, L- and D-lactate, 2-ketoisovalerate, 2-ketoglutarate, and succinate. These organic acids represent a class of compounds with manifold application ranges, e.g. in pharmaceutical and cosmetics industry, as food additives, and economically very interesting, as precursors for a variety of bulk chemicals and commercially important polymers.

  3. Manufacture and application of valve-regulated lead/acid batteries in China

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z. [Battery Consultants China, Univ. of Science and Technology Beijing, Beijing, BJ (China)

    1998-05-18

    This paper introduces the manufacture and application of valve-regulated lead/acid batteries in China. The contents cover the following topics: (i) background development; (ii) materials; (iii) manufacturing technology and equipment; (iv) application and market prospects. (orig.)

  4. Investigating Students' Reasoning about Acid-Base Reactions

    Science.gov (United States)

    Cooper, Melanie M.; Kouyoumdjian, Hovig; Underwood, Sonia M.

    2016-01-01

    Acid-base chemistry is central to a wide range of reactions. If students are able to understand how and why acid-base reactions occur, it should provide a basis for reasoning about a host of other reactions. Here, we report the development of a method to characterize student reasoning about acid-base reactions based on their description of…

  5. Biogas Production on Demand Regulated by Butyric Acid Addition

    Science.gov (United States)

    Kasper, K.; Schiffels, J.; Krafft, S.; Kuperjans, I.; Elbers, G.; Selmer, T.

    2016-03-01

    Investigating effects of volatile fatty acids on the biogas process it was observed that butyric acid can be used for transient stimulation of the methane production in biogas plants operating with low energy substrates like cattle manure. Upon addition of butyrate the methane output of the reactors doubled within 24 h and reached almost 3-times higher methane yields within 3-4 days. Butyrate was quantitatively eliminated and the reactors returned to the original productivity state within 3 days when application of butyrate was stopped. The opportunity to use butyrate feeding for increased biogas production on demand is discussed.

  6. Organism-adapted specificity of the allosteric regulation of pyruvate kinase in lactic acid bacteria.

    Directory of Open Access Journals (Sweden)

    Nadine Veith

    Full Text Available Pyruvate kinase (PYK is a critical allosterically regulated enzyme that links glycolysis, the primary energy metabolism, to cellular metabolism. Lactic acid bacteria rely almost exclusively on glycolysis for their energy production under anaerobic conditions, which reinforces the key role of PYK in their metabolism. These organisms are closely related, but have adapted to a huge variety of native environments. They include food-fermenting organisms, important symbionts in the human gut, and antibiotic-resistant pathogens. In contrast to the rather conserved inhibition of PYK by inorganic phosphate, the activation of PYK shows high variability in the type of activating compound between different lactic acid bacteria. System-wide comparative studies of the metabolism of lactic acid bacteria are required to understand the reasons for the diversity of these closely related microorganisms. These require knowledge of the identities of the enzyme modifiers. Here, we predict potential allosteric activators of PYKs from three lactic acid bacteria which are adapted to different native environments. We used protein structure-based molecular modeling and enzyme kinetic modeling to predict and validate potential activators of PYK. Specifically, we compared the electrostatic potential and the binding of phosphate moieties at the allosteric binding sites, and predicted potential allosteric activators by docking. We then made a kinetic model of Lactococcus lactis PYK to relate the activator predictions to the intracellular sugar-phosphate conditions in lactic acid bacteria. This strategy enabled us to predict fructose 1,6-bisphosphate as the sole activator of the Enterococcus faecalis PYK, and to predict that the PYKs from Streptococcus pyogenes and Lactobacillus plantarum show weaker specificity for their allosteric activators, while still having fructose 1,6-bisphosphate play the main activator role in vivo. These differences in the specificity of allosteric

  7. Aspects of the regulation of long-chain fatty acid oxidation in bovine liver

    Energy Technology Data Exchange (ETDEWEB)

    Jesse, B.W.; Emery, R.S.; Thomas, J.W.

    1986-09-01

    Factors involved in regulation of bovine hepatic fatty acid oxidation were examined using liver slices. Fatty acid oxidation was measured as the conversion of l-(/sup 14/C) palmitate to /sup 14/CO/sub 2/ and total (/sup 14/C) acid-soluble metabolites. Extended (5 to 7 d) fasting of Holstein cows had relatively little effect on palmitate oxidation to acid-soluble metabolites by liver slices, although oxidation to CO/sup 2/ was decreased. Feeding a restricted roughage, high concentrate ration to lactating cows resulted in inhibition of palmitate oxidation. Insulin, glucose, and acetate inhibited palmitate oxidation by bovine liver slices. The authors suggest the regulation of bovine hepatic fatty acid oxidation may be less dependent on hormonally induced alterations in enzyme activity as observed in rat liver and more dependent upon action of rumen fermentation products or their metabolites on enzyme systems involved in fatty acid oxidation.

  8. Insulin signaling regulates fatty acid catabolism at the level of CoA activation.

    Directory of Open Access Journals (Sweden)

    Xiaojun Xu

    2012-01-01

    Full Text Available The insulin/IGF signaling pathway is a highly conserved regulator of metabolism in flies and mammals, regulating multiple physiological functions including lipid metabolism. Although insulin signaling is known to regulate the activity of a number of enzymes in metabolic pathways, a comprehensive understanding of how the insulin signaling pathway regulates metabolic pathways is still lacking. Accepted knowledge suggests the key regulated step in triglyceride (TAG catabolism is the release of fatty acids from TAG via the action of lipases. We show here that an additional, important regulated step is the activation of fatty acids for beta-oxidation via Acyl Co-A synthetases (ACS. We identify pudgy as an ACS that is transcriptionally regulated by direct FOXO action in Drosophila. Increasing or reducing pudgy expression in vivo causes a decrease or increase in organismal TAG levels respectively, indicating that pudgy expression levels are important for proper lipid homeostasis. We show that multiple ACSs are also transcriptionally regulated by insulin signaling in mammalian cells. In sum, we identify fatty acid activation onto CoA as an important, regulated step in triglyceride catabolism, and we identify a mechanistic link through which insulin regulates lipid homeostasis.

  9. Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures.

    Science.gov (United States)

    Liu, Jie; Lu, Hong; Lu, Yuan-Fu; Lei, Xiaohong; Cui, Julia Yue; Ellis, Ewa; Strom, Stephen C; Klaassen, Curtis D

    2014-10-01

    Bile acids (BAs) are known to regulate their own homeostasis, but the potency of individual bile acids is not known. This study examined the effects of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) on expression of BA synthesis and transport genes in human primary hepatocyte cultures. Hepatocytes were treated with the individual BAs at 10, 30, and 100μM for 48 h, and RNA was extracted for real-time PCR analysis. For the classic pathway of BA synthesis, BAs except for UDCA markedly suppressed CYP7A1 (70-95%), the rate-limiting enzyme of bile acid synthesis, but only moderately (35%) down-regulated CYP8B1 at a high concentration of 100μM. BAs had minimal effects on mRNA of two enzymes of the alternative pathway of BA synthesis, namely CYP27A1 and CYP7B1. BAs increased the two major target genes of the farnesoid X receptor (FXR), namely the small heterodimer partner (SHP) by fourfold, and markedly induced fibroblast growth factor 19 (FGF19) over 100-fold. The BA uptake transporter Na(+)-taurocholate co-transporting polypeptide was unaffected, whereas the efflux transporter bile salt export pump was increased 15-fold and OSTα/β were increased 10-100-fold by BAs. The expression of the organic anion transporting polypeptide 1B3 (OATP1B3; sixfold), ATP-binding cassette (ABC) transporter G5 (ABCG5; sixfold), multidrug associated protein-2 (MRP2; twofold), and MRP3 (threefold) were also increased, albeit to lesser degrees. In general, CDCA was the most potent and effective BA in regulating these genes important for BA homeostasis, whereas DCA and CA were intermediate, LCA the least, and UDCA ineffective.

  10. EFFECT OF CASEIN-BASED SEMISYNTHETIC FOOD ON RENAL ACID EXCRETION AND ACID-BASE STATE OF BLOOD IN DOGS

    NARCIS (Netherlands)

    ZIJLSTRA, WG; LANGBROEK, AJM; KRAAN, J; RISPENS, P; NIJMEIJER, A

    1995-01-01

    Urinary acid excretion and blood acid-base stare were determined in dogs fed a casein-based semi-synthetic food (SSF), to which different amounts of salts had been added, in comparison with feeding normal dog food. Net acid excretion (NAE) and inorganic acid excretion (IAE) increased during SSF feed

  11. New insights into the regulation of plant immunity by amino acid metabolic pathways.

    Science.gov (United States)

    Zeier, Jürgen

    2013-12-01

    Besides defence pathways regulated by classical stress hormones, distinct amino acid metabolic pathways constitute integral parts of the plant immune system. Mutations in several genes involved in Asp-derived amino acid biosynthetic pathways can have profound impact on plant resistance to specific pathogen types. For instance, amino acid imbalances associated with homoserine or threonine accumulation elevate plant immunity to oomycete pathogens but not to pathogenic fungi or bacteria. The catabolism of Lys produces the immune signal pipecolic acid (Pip), a cyclic, non-protein amino acid. Pip amplifies plant defence responses and acts as a critical regulator of plant systemic acquired resistance, defence priming and local resistance to bacterial pathogens. Asp-derived pyridine nucleotides influence both pre- and post-invasion immunity, and the catabolism of branched chain amino acids appears to affect plant resistance to distinct pathogen classes by modulating crosstalk of salicylic acid- and jasmonic acid-regulated defence pathways. It also emerges that, besides polyamine oxidation and NADPH oxidase, Pro metabolism is involved in the oxidative burst and the hypersensitive response associated with avirulent pathogen recognition. Moreover, the acylation of amino acids can control plant resistance to pathogens and pests by the formation of protective plant metabolites or by the modulation of plant hormone activity.

  12. Identification of a fatty acid binding protein4-UCP2 axis regulating microglial mediated neuroinflammation.

    Science.gov (United States)

    Duffy, Cayla M; Xu, Hongliang; Nixon, Joshua P; Bernlohr, David A; Butterick, Tammy A

    2017-02-16

    Hypothalamic inflammation contributes to metabolic dysregulation and the onset of obesity. Dietary saturated fats activate microglia via a nuclear factor-kappa B (NFκB) mediated pathway to release pro-inflammatory cytokines resulting in dysfunction or death of surrounding neurons. Fatty acid binding proteins (FABPs) are lipid chaperones regulating metabolic and inflammatory pathways in response to fatty acids. Loss of FABP4 in peripheral macrophages via either molecular or pharmacologic mechanisms results in reduced obesity-induced inflammation via a UCP2-redox based mechanism. Despite the widespread appreciation for the role of FABP4 in mediating peripheral inflammation, the expression of FABP4 and a potential FABP4-UCP2 axis regulating microglial inflammatory capacity is largely uncharacterized. To that end, we hypothesized that microglial cells express FABP4 and that inhibition would upregulate UCP2 and attenuate palmitic acid (PA)-induced pro-inflammatory response. Gene expression confirmed expression of FABP4 in brain tissue lysate from C57Bl/6J mice and BV2 microglia. Treatment of microglial cells with an FABP inhibitor (HTS01037) increased expression of Ucp2 and arginase in the presence or absence of PA. Moreover, cells exposed to HTS01037 exhibited attenuated expression of inducible nitric oxide synthase (iNOS) compared to PA alone indicating reduced NFκB signaling. Hypothalamic tissue from mice lacking FABP4 exhibit increased UCP2 expression and reduced iNOS, tumor necrosis factor-alpha (TNF-α), and ionized calcium-binding adapter molecule 1 (Iba1; microglial activation marker) expression compared to wild type mice. Further, this effect is negated in microglia lacking UCP2, indicating the FABP4-UCP2 axis is pivotal in obesity induced neuroinflammation. To our knowledge, this is the first report demonstrating a FABP4-UCP2 axis with the potential to modulate the microglial inflammatory response.

  13. Bipolar Membranes for Acid Base Flow Batteries

    Science.gov (United States)

    Anthamatten, Mitchell; Roddecha, Supacharee; Jorne, Jacob; Coughlan, Anna

    2011-03-01

    Rechargeable batteries can provide grid-scale electricity storage to match power generation with consumption and promote renewable energy sources. Flow batteries offer modular and flexible design, low cost per kWh and high efficiencies. A novel flow battery concept will be presented based on acid-base neutralization where protons (H+) and hydroxyl (OH-) ions react electrochemically to produce water. The large free energy of this highly reversible reaction can be stored chemically, and, upon discharge, can be harvested as usable electricity. The acid-base flow battery concept avoids the use of a sluggish oxygen electrode and utilizes the highly reversible hydrogen electrode, thus eliminating the need for expensive noble metal catalysts. The proposed flow battery is a hybrid of a battery and a fuel cell---hydrogen gas storing chemical energy is produced at one electrode and is immediately consumed at the other electrode. The two electrodes are exposed to low and high pH solutions, and these solutions are separated by a hybrid membrane containing a hybrid cation and anion exchange membrane (CEM/AEM). Membrane design will be discussed, along with ion-transport data for synthesized membranes.

  14. Regulation of fatty acid biosynthesis by the global regulator CcpA and the local regulator FabT in Streptococcus mutans

    OpenAIRE

    Faustoferri, R.C.; Hubbard, C.J.; Santiago, B.; Buckley, A.A.; Seifert, T.B.; Quivey, R.G.

    2014-01-01

    SMU.1745c, encoding a putative transcriptional regulator of the MarR family, maps to a location proximal to the fab gene cluster in Streptococcus mutans. Deletion of the SMU.1745c (fabTSm) coding region resulted in a membrane fatty acid composition comprised of longer-chained, unsaturated fatty acids (UFA), compared with the parent strain. Previous reports have indicated a role for FabT in regulation of genes in the fab gene cluster in other organisms, through binding to a palindromic DNA seq...

  15. Structural insights into the regulation of aromatic amino acid hydroxylation

    OpenAIRE

    Fitzpatrick, Paul F.

    2015-01-01

    The aromatic amino acid hydroxylases phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase are homotetramers, with each subunit containing a homologous catalytic domain and a divergent regulatory domain. The solution structure of the regulatory domain of tyrosine hydroxylase establishes that it contains a core ACT domain similar to that in phenylalanine hydroxylase. The isolated regulatory domain of tyrosine hydroxylase forms a stable dimer, while that of phenylalanine h...

  16. Biodegradable polyesters based on succinic acid

    Directory of Open Access Journals (Sweden)

    Nikolić Marija S.

    2003-01-01

    Full Text Available Two series of aliphatic polyesters based on succinic acid were synthesized by copolymerization with adipic acid for the first series of saturated polyesters, and with fumaric acid for the second series. Polyesters were prepared starting from the corresponding dimethyl esters and 1,4-butanediol by melt transesterification in the presence of a highly effective catalyst tetra-n-butyl-titanate, Ti(0Bu4. The molecular structure and composition of the copolyesters was determined by 1H NMR spectroscopy. The effect of copolymer composition on the physical and thermal properties of these random polyesters were investigated using differential scanning calorimetry. The degree of crystallinity was determined by DSC and wide angle X-ray. The degrees of crystallinity of the saturated and unsaturated copolyesters were generally reduced with respect to poly(butylene succinate, PBS. The melting temperatures of the saturated polyesters were lower, while the melting temperatures of the unsaturated copolyesters were higher than the melting temperature of PBS. The biodegradability of the polyesters was investigated by enzymatic degradation tests. The enzymatic degradation tests were performed in a buffer solution with Candida cylindracea lipase and for the unsaturated polyesters with Rhizopus arrhizus lipase. The extent of biodegradation was quantified as the weight loss of polyester films. Also the surface of the polyester films after degradation was observed using optical microscopy. It could be concluded that the biodegradability depended strongly on the degree of crystallinity, but also on the flexibility of the chain backbone. The highest biodegradation was observed for copolyesters containing 50 mol.% of adipic acid units, and in the series of unsaturated polyesters for copolyesters containing 5 and 10 mol.% of fumarate units. Although the degree of crystallinity of the unsaturated polyesters decreased slightly with increasing unsaturation, the biodegradation

  17. Using Willie's Acid-Base Box for Blood Gas Analysis

    Science.gov (United States)

    Dietz, John R.

    2011-01-01

    In this article, the author describes a method developed by Dr. William T. Lipscomb for teaching blood gas analysis of acid-base status and provides three examples using Willie's acid-base box. Willie's acid-base box is constructed using three of the parameters of standard arterial blood gas analysis: (1) pH; (2) bicarbonate; and (3) CO[subscript…

  18. Teaching Acid/Base Physiology in the Laboratory

    Science.gov (United States)

    Friis, Ulla G.; Plovsing, Ronni; Hansen, Klaus; Laursen, Bent G.; Wallstedt, Birgitta

    2010-01-01

    Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory exercise in acid/base physiology that would provide…

  19. FOOD SAFETY REGULATIONS BASED ON REAL SCIENCE

    OpenAIRE

    2015-01-01

    Differences in regulations result in needless destruction of safe food and hamper food trade. The differences are not just the result of the history of food safety regulations, often developed in times before global cooperation, but are also built in new regulations. It may be responses to media hypes or for other reasons, but in most cases the differences cannot be justified scientifically. A major difficulty is that, due to the developments in analytical techniques the number of chemicals t...

  20. New mechanisms that regulate Saccharomyces cerevisiae short peptide transporter achieve balanced intracellular amino acid concentrations.

    Science.gov (United States)

    Melnykov, Artem V

    2016-01-01

    The budding yeast Saccharomyces cerevisiae is able to take up large quantities of amino acids in the form of di- and tripeptides via a short peptide transporter, Ptr2p. It is known that PTR2 can be induced by certain peptides and amino acids, and the mechanisms governing this upregulation are understood at the molecular level. We describe two new opposing mechanisms of regulation that emphasize potential toxicity of amino acids: the first is upregulation of PTR2 in a population of cells, caused by amino acid secretion that accompanies peptide uptake; the second is loss of Ptr2p activity, due to transporter internalization following peptide uptake. Our findings emphasize the importance of proper amino acid balance in the cell and extend understanding of peptide import regulation in yeast.

  1. Effects of glucose, ethanol and acetic acid on regulation of ADH2 gene from Lachancea fermentati

    Science.gov (United States)

    Yaacob, Norhayati; Salleh, Abu Bakar; Abdul Rahman, Nor Aini

    2016-01-01

    Background. Not all yeast alcohol dehydrogenase 2 (ADH2) are repressed by glucose, as reported in Saccharomyces cerevisiae. Pichia stipitis ADH2 is regulated by oxygen instead of glucose, whereas Kluyveromyces marxianus ADH2 is regulated by neither glucose nor ethanol. For this reason, ADH2 regulation of yeasts may be species dependent, leading to a different type of expression and fermentation efficiency. Lachancea fermentati is a highly efficient ethanol producer, fast-growing cells and adapted to fermentation-related stresses such as ethanol and organic acid, but the metabolic information regarding the regulation of glucose and ethanol production is still lacking. Methods. Our investigation started with the stimulation of ADH2 activity from S. cerevisiae and L. fermentati by glucose and ethanol induction in a glucose-repressed medium. The study also embarked on the retrospective analysis of ADH2 genomic and protein level through direct sequencing and sites identification. Based on the sequence generated, we demonstrated ADH2 gene expression highlighting the conserved NAD(P)-binding domain in the context of glucose fermentation and ethanol production. Results. An increase of ADH2 activity was observed in starved L. fermentati (LfeADH2) and S. cerevisiae (SceADH2) in response to 2% (w/v) glucose induction. These suggest that in the presence of glucose, ADH2 activity was activated instead of being repressed. An induction of 0.5% (v/v) ethanol also increased LfeADH2 activity, promoting ethanol resistance, whereas accumulating acetic acid at a later stage of fermentation stimulated ADH2 activity and enhanced glucose consumption rates. The lack in upper stream activating sequence (UAS) and TATA elements hindered the possibility of Adr1 binding to LfeADH2. Transcription factors such as SP1 and RAP1 observed in LfeADH2 sequence have been implicated in the regulation of many genes including ADH2. In glucose fermentation, L. fermentati exhibited a bell-shaped ADH2

  2. Effects of glucose, ethanol and acetic acid on regulation of ADH2 gene from Lachancea fermentati

    Directory of Open Access Journals (Sweden)

    Norhayati Yaacob

    2016-03-01

    Full Text Available Background. Not all yeast alcohol dehydrogenase 2 (ADH2 are repressed by glucose, as reported in Saccharomyces cerevisiae. Pichia stipitis ADH2 is regulated by oxygen instead of glucose, whereas Kluyveromyces marxianus ADH2 is regulated by neither glucose nor ethanol. For this reason, ADH2 regulation of yeasts may be species dependent, leading to a different type of expression and fermentation efficiency. Lachancea fermentati is a highly efficient ethanol producer, fast-growing cells and adapted to fermentation-related stresses such as ethanol and organic acid, but the metabolic information regarding the regulation of glucose and ethanol production is still lacking. Methods. Our investigation started with the stimulation of ADH2 activity from S. cerevisiae and L. fermentati by glucose and ethanol induction in a glucose-repressed medium. The study also embarked on the retrospective analysis of ADH2 genomic and protein level through direct sequencing and sites identification. Based on the sequence generated, we demonstrated ADH2 gene expression highlighting the conserved NAD(P-binding domain in the context of glucose fermentation and ethanol production. Results. An increase of ADH2 activity was observed in starved L. fermentati (LfeADH2 and S. cerevisiae (SceADH2 in response to 2% (w/v glucose induction. These suggest that in the presence of glucose, ADH2 activity was activated instead of being repressed. An induction of 0.5% (v/v ethanol also increased LfeADH2 activity, promoting ethanol resistance, whereas accumulating acetic acid at a later stage of fermentation stimulated ADH2 activity and enhanced glucose consumption rates. The lack in upper stream activating sequence (UAS and TATA elements hindered the possibility of Adr1 binding to LfeADH2. Transcription factors such as SP1 and RAP1 observed in LfeADH2 sequence have been implicated in the regulation of many genes including ADH2. In glucose fermentation, L. fermentati exhibited a bell

  3. Regulation of indole-3-acetic acid biosynthesis by branched-chain amino acids in Enterobacter cloacae UW5.

    Science.gov (United States)

    Parsons, Cassandra V; Harris, Danielle M M; Patten, Cheryl L

    2015-09-01

    The soil bacterium Enterobacter cloacae UW5 produces the rhizosphere signaling molecule indole-3-acetic acid (IAA) via the indolepyruvate pathway. Expression of indolepyruvate decarboxylase, a key pathway enzyme encoded by ipdC, is upregulated by the transcription factor TyrR in response to aromatic amino acids. Some members of the TyrR regulon may also be controlled by branched-chain amino acids and here we show that expression from the ipdC promoter and production of IAA are downregulated by valine, leucine and isoleucine. Regulation of the IAA synthesis pathway by both aromatic and branched-chain amino acids suggests a broader role for this pathway in bacterial physiology, beyond plant interactions.

  4. Liquid Crystalline Furandicarboxylic Acid-based Aaromatic Polyesters

    NARCIS (Netherlands)

    WILSENS, CAROLUS HENRICUS R. MARIA; RASTOGI, SANJAY; VELD, MARTIJN ARNOLDUS JOHANNES; KLOP, ENNO ANTON; NOORDOVER, BART ADRIANUS JOHANNES

    2013-01-01

    The invention pertains to a fully aromatic liquid crystalline furandicarboxylic acid- based aromatic polyester obtainable from a mixture of monomers comprising 2,5- furandicarboxylic acid, p-hydroxybenzoic acid, an aromatic diol, and 5-40 mol% of an aromatic monocarboxylic acid selected from vanilli

  5. Effect of plant growth regulators on fatty acids composition in Jatropha curcas L. callus culture.

    Science.gov (United States)

    Hernandez, Ludwi Rodríguez; Mendiola, Martha A Rodríguez; Castro, Carlos Arias; Gutiérrez-Miceli, Federico A

    2015-01-01

    The influence of Naphtaleneacetic acid (NAA) and 6-Benzylaminopurine (BAP) on callus formation, its morphology and fatty acids profile were examined from Jatropha curcas L. Embryo from seeds of J. curcas L. were sown in Murashige and skoog (MS) medium with NAA and BAP. All treatments induced callus formation, however callus morphology was different in most of the treatments. Higher callus biomass was presented with 1.0 NAA + 0.5 BAP mg/L. Plant growth regulators modifies the fatty acids profile in callus of J. curcas L. BAP was induced linoleic and linolenic acids.

  6. Splenic Immune Response Is Down-Regulated in C57BL/6J Mice Fed Eicosapentaenoic Acid and Docosahexaenoic Acid Enriched High Fat Diet

    Science.gov (United States)

    Soni, Nikul K.; Ross, Alastair B.; Scheers, Nathalie; Savolainen, Otto I.; Nookaew, Intawat; Gabrielsson, Britt G.; Sandberg, Ann-Sofie

    2017-01-01

    Dietary n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with reduction of inflammation, although the mechanisms are poorly understood, especially how the spleen, as a secondary lymphoid organ, is involved. To investigate the effects of EPA and DHA on spleen gene expression, male C57BL/6J mice were fed high fat diets (HFD) differing in fatty acid composition, either based on corn oil (HFD-CO), or CO enriched with 2 g/100 g EPA and DHA (HFD-ED), for eight weeks. Spleen tissue was analyzed using transcriptomics and for fatty acids profiling. Biological processes (BPs) related to the immune response, including T-cell receptor signaling pathway, T-cell differentiation and co-stimulation, myeloid dendritic cell differentiation, antigen presentation and processing, and the toll like receptor pathway were downregulated by HFD-ED compared with control and HFD-CO. These findings were supported by the down-regulation of NF-κB in HFD-ED compared with HFD-CO fed mice. Lower phospholipid arachidonic acid levels in HFD-ED compared with HFD-CO, and control mice suggest attenuation of pathways via prostaglandins and leukotrienes. The HFD-ED also upregulated BPs related to erythropoiesis and hematopoiesis compared with control and HFD-CO fed mice. Our findings suggest that EPA and DHA down-regulate the splenic immune response induced by HFD-CO, supporting earlier work that the spleen is a target organ for the anti-inflammatory effects of these n-3 fatty acids. PMID:28075380

  7. Performance characteristics of a gelled-electrolyte valve-regulated lead-acid battery

    Indian Academy of Sciences (India)

    S K Martha; B Hariprakash; S A Gaffoor; A K Shukla

    2003-08-01

    12 V/25 AH gelled-electrolyte valve-regulated lead-acid batteries have been assembled in-house and their performance studied in relation to the absorptive glass-microfibre valve-regulated and flooded-electrolyte counterparts at various discharge rates and temperatures between –40°C and 40°C. Although the performance of the gelled-electrolyte valve-regulated battery is similar to both the absorptive glass-microfibre valve-regulated and flooded-electrolyte lead-acid batteries at temperatures above 0°C, it is superior to both the flooded-electrolyte and absorptive glass-microfibre valve-regulated lead-acid batteries at temperatures between 0°C and -40°C. The latter characteristic is attractive for expanding the application regime of valve-regulated lead-acid batteries. The corrosion rate for the positive grids in the gelled-electrolyte is also lower than both the flooded-electrolyte and absorptive glass-microfibre configurations.

  8. Retinoic acid from the meninges regulates cortical neuron generation.

    Science.gov (United States)

    Siegenthaler, Julie A; Ashique, Amir M; Zarbalis, Konstantinos; Patterson, Katelin P; Hecht, Jonathan H; Kane, Maureen A; Folias, Alexandra E; Choe, Youngshik; May, Scott R; Kume, Tsutomu; Napoli, Joseph L; Peterson, Andrew S; Pleasure, Samuel J

    2009-10-30

    Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had a cortical phenotype similar to the Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis.

  9. DMPD: Regulation of arachidonic acid release and cytosolic phospholipase A2activation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10080535 Regulation of arachidonic acid release and cytosolic phospholipase A2activation...on of arachidonic acid release and cytosolic phospholipase A2activation. PubmedID 10080535 Title Regulation ...of arachidonic acid release and cytosolic phospholipase A2activation. Authors Gij

  10. Arabidopsis MAP kinase 4 regulates salicylic acid- and jasmonic acid/ethylene-dependent responses via EDS1 and PAD4.

    Science.gov (United States)

    Brodersen, Peter; Petersen, Morten; Bjørn Nielsen, Henrik; Zhu, Shijiang; Newman, Mari-Anne; Shokat, Kevan M; Rietz, Steffen; Parker, Jane; Mundy, John

    2006-08-01

    Arabidopsis MPK4 has been implicated in plant defense regulation because mpk4 knockout plants exhibit constitutive activation of salicylic acid (SA)-dependent defenses, but fail to induce jasmonic acid (JA) defense marker genes in response to JA. We show here that mpk4 mutants are also defective in defense gene induction in response to ethylene (ET), and that they are more susceptible than wild-type (WT) to Alternaria brassicicola that induces the ET/JA defense pathway(s). Both SA-repressing and ET/JA-(co)activating functions depend on MPK4 kinase activity and involve the defense regulators EDS1 and PAD4, as mutations in these genes suppress de-repression of the SA pathway and suppress the block of the ET/JA pathway in mpk4. EDS1/PAD4 thus affect SA-ET/JA signal antagonism as activators of SA but as repressors of ET/JA defenses, and MPK4 negatively regulates both of these functions. We also show that the MPK4-EDS1/PAD4 branch of ET defense signaling is independent of the ERF1 transcription factor, and use comparative microarray analysis of ctr1, ctr1/mpk4, mpk4 and WT to show that MPK4 is required for induction of a small subset of ET-regulated genes. The regulation of some, but not all, of these genes involves EDS1 and PAD4.

  11. TORC1 Inhibits GSK3-Mediated Elo2 Phosphorylation to Regulate Very Long Chain Fatty Acid Synthesis and Autophagy

    Directory of Open Access Journals (Sweden)

    Christine Zimmermann

    2013-11-01

    Full Text Available Very long chain fatty acids (VLCFAs are essential fatty acids with multiple functions, including ceramide synthesis. Although the components of the VLCFA biosynthetic machinery have been elucidated, how their activity is regulated to meet the cell’s metabolic demand remains unknown. The goal of this study was to identify mechanisms that regulate the rate of VLCFA synthesis, and we discovered that the fatty acid elongase Elo2 is regulated by phosphorylation. Elo2 phosphorylation is induced upon inhibition of TORC1 and requires GSK3. Expression of nonphosphorylatable Elo2 profoundly alters the ceramide spectrum, reflecting aberrant VLCFA synthesis. Furthermore, VLCFA depletion results in constitutive activation of autophagy, which requires sphingoid base phosphorylation. This constitutive activation of autophagy diminishes cell survival, indicating that VLCFAs serve to dampen the amplitude of autophagy. Together, our data reveal a function for TORC1 and GSK3 in the regulation of VLCFA synthesis that has important implications for autophagy and cell homeostasis.

  12. Vitamin B12 and omega-3 fatty acids together regulate lipid metabolism in Wistar rats.

    Science.gov (United States)

    Khaire, Amrita; Rathod, Richa; Kale, Anvita; Joshi, Sadhana

    2015-08-01

    Our recent study indicates that maternal vitamin B12 and omega-3 fatty acid status influence plasma and erythrocyte fatty acid profile in dams. The present study examines the effects of prenatal and postnatal vitamin B12 and omega-3 fatty acid status on lipid metabolism in the offspring. Pregnant dams were divided into five groups: Control; Vitamin B12 deficient (BD); Vitamin B12 supplemented (BS); Vitamin B12 deficient group supplemented with omega-3 fatty acids (BDO); Vitamin B12 supplemented group with omega-3 fatty acids (BSO). The offspring were continued on the same diets till 3 month of age. Vitamin B12 deficiency increased cholesterol levels (pomega-3 fatty acids together play a crucial role in regulating the genes involved in lipid metabolism in adult offspring.

  13. Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling.

    Science.gov (United States)

    Packer, Lester; Cadenas, Enrique

    2011-01-01

    The role of R-α-lipoic acid as a cofactor (lipoyllysine) in mitochondrial energy metabolism is well established. Lipoic acid non-covalently bound and exogenously administered to cells or supplemented in the diet is a potent modulator of the cell's redox status. The diversity of beneficial effects of lipoic acid in a variety of tissues can be mechanistically viewed in terms of thiol/disulfide exchange reactions that modulate the environment's redox and energy status. Lipoic acid-driven thiol/disulfide exchange reactions appear critical for the modulation of proteins involved in cell signaling and transcription factors. This review emphasizes the effects of lipoic acid on PI3K and AMPK signaling and related transcriptional pathways that are integrated by PGC-1α, a critical regulator of energy homoestasis. The effects of lipoic acid on the neuronal energy-redox axis are largely reviewed in terms of their outcomes for aging and age-related neurodegenerative diseases.

  14. Whole-body acid-base modeling revisited

    DEFF Research Database (Denmark)

    Ring, Troels; Nielsen, Søren

    2017-01-01

    The textbook account of whole-body acid-base balance in terms of endogenous acid production, renal net acid excretion and gastrointestinal alkali absorption which is the only comprehensive model around, has never been applied in clinical practice or been formally validated. In order to improve...... understanding of acid-base modeling, we managed to write up this conventional model as an expression solely on urine chemistry. Renal net acid excretion and endogenous acid production was already formulated in terms of urine chemistry, and we could from the literature also see gastrointestinal alkali absorption...

  15. High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation

    OpenAIRE

    Maharjan, Anu S; Darrell Pilling; Gomer, Richard H.

    2011-01-01

    BACKGROUND: Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×10(6) Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8-8×10(5) Da). METHODS AND FINDINGS: In this report, we show that HMWHA potentiates the differentiation of human monocytes into ...

  16. Milk fat globules: fatty acid composition, size and in vivo regulation of fat liquidity.

    Science.gov (United States)

    Timmen, H; Patton, S

    1988-07-01

    Populations of large and small milk fat globules were isolated and analyzed to determine differences in fatty acid composition. Globule samples were obtained by centrifugation from milks of a herd and of individual animals produced under both pasture and barn feeding. Triacylglycerols of total globule lipids were prepared by thin layer chromatography and analyzed for fatty acid composition by gas chromatography. Using content of the acids in large globules as 100%, small globules contained fewer short-chain acids, -5.9%, less stearic acid, -22.7%, and more oleic acids, +4.6%, mean values for five trials. These differences are consistent with alternative use of short-chain acids or oleic acid converted from stearic acid to maintain liquidity at body temperature of milk fat globules and their precursors, intracellular lipid droplets. Stearyl-CoA desaturase (EC 1.14.99.5), which maintains fluidity of cellular endoplasmic reticulum membrane, is suggested to play a key role in regulating globule fat liquidity. Possible origins of differences between individual globules in fatty acid composition of their triacylglycerols are discussed.

  17. Amino acid catabolism: a pivotal regulator of innate and adaptive immunity.

    Science.gov (United States)

    McGaha, Tracy L; Huang, Lei; Lemos, Henrique; Metz, Richard; Mautino, Mario; Prendergast, George C; Mellor, Andrew L

    2012-09-01

    Enhanced amino acid catabolism is a common response to inflammation, but the immunologic significance of altered amino acid consumption remains unclear. The finding that tryptophan catabolism helped maintain fetal tolerance during pregnancy provided novel insights into the significance of amino acid metabolism in controlling immunity. Recent advances in identifying molecular pathways that enhance amino acid catabolism and downstream mechanisms that affect immune cells in response to inflammatory cues support the notion that amino acid catabolism regulates innate and adaptive immune cells in pathologic settings. Cells expressing enzymes that degrade amino acids modulate antigen-presenting cell and lymphocyte functions and reveal critical roles for amino acid- and catabolite-sensing pathways in controlling gene expression, functions, and survival of immune cells. Basal amino acid catabolism may contribute to immune homeostasis that prevents autoimmunity, whereas elevated amino acid catalytic activity may reinforce immune suppression to promote tumorigenesis and persistence of some pathogens that cause chronic infections. For these reasons, there is considerable interest in generating novel drugs that inhibit or induce amino acid consumption and target downstream molecular pathways that control immunity. In this review, we summarize recent developments and highlight novel concepts and key outstanding questions in this active research field.

  18. Spherical Nucleic Acids as Intracellular Agents for Nucleic Acid Based Therapeutics

    Science.gov (United States)

    Hao, Liangliang

    Recent functional discoveries on the noncoding sequences of human genome and transcriptome could lead to revolutionary treatment modalities because the noncoding RNAs (ncRNAs) can be applied as therapeutic agents to manipulate disease-causing genes. To date few nucleic acid-based therapeutics have been translated into the clinic due to challenges in the delivery of the oligonucleotide agents in an effective, cell specific, and non-toxic fashion. Unmodified oligonucleotide agents are destroyed rapidly in biological fluids by enzymatic degradation and have difficulty crossing the plasma membrane without the aid of transfection reagents, which often cause inflammatory, cytotoxic, or immunogenic side effects. Spherical nucleic acids (SNAs), nanoparticles consisting of densely organized and highly oriented oligonucleotides, pose one possible solution to circumventing these problems in both the antisense and RNA interference (RNAi) pathways. The unique three dimensional architecture of SNAs protects the bioactive oligonucleotides from unspecific degradation during delivery and supports their targeting of class A scavenger receptors and endocytosis via a lipid-raft-dependent, caveolae-mediated pathway. Owing to their unique structure, SNAs are able to cross cell membranes and regulate target genes expression as a single entity, without triggering the cellular innate immune response. Herein, my thesis has focused on understanding the interactions between SNAs and cellular components and developing SNA-based nanostructures to improve therapeutic capabilities. Specifically, I developed a novel SNA-based, nanoscale agent for delivery of therapeutic oligonucleotides to manipulate microRNAs (miRNAs), the endogenous post-transcriptional gene regulators. I investigated the role of SNAs involving miRNAs in anti-cancer or anti-inflammation responses in cells and in in vivo murine disease models via systemic injection. Furthermore, I explored using different strategies to construct

  19. 1-Acetylpyrene-salicylic acid: photoresponsive fluorescent organic nanoparticles for the regulated release of a natural antimicrobial compound, salicylic acid.

    Science.gov (United States)

    Barman, Shrabani; Mukhopadhyay, Sourav K; Behara, Krishna Kalyani; Dey, Satyahari; Singh, N D Pradeep

    2014-05-28

    Photoresponsive 1-acetylpyrene-salicylic acid (AcPy-SA) nanoparticles (NPs) were developed for the regulated release of a natural antimicrobial compound, salicylic acid. The strong fluorescent properties of AcPy-SA NPs have been extensively used for potential in vitro cell imaging. The phototrigger capability of our newly prepared AcPy-SA NPs was utilized for the efficient release of an antimicrobial compound, salicylic acid. The photoregulated drug release of AcPy-SA NPs has been shown by the subsequent switching off and on of a visible-light source. In vitro biological studies reveal that AcPy-SA NPs of ∼68 nm size deliver the antimicrobial drug salicylic acid into the bacteria cells (Pseudomonas aeruginosa) and efficiently kill the cells upon exposure to visible light (≥410 nm). Such photoresponsive fluorescent organic NPs will be highly beneficial for targeted and regulated antimicrobial drug release because of their biocompatible nature, efficient cellular uptake, and light-induced drug release ability.

  20. Acid-base bifunctional catalytic surfaces for nucleophilic addition reactions.

    Science.gov (United States)

    Motokura, Ken; Tada, Mizuki; Iwasawa, Yasuhiro

    2008-09-01

    This article illustrates the modification of oxide surfaces with organic amine functional groups to create acid-base bifunctional catalysts, summarizing our previous reports and also presenting new data. Immobilization of organic amines as bases on inorganic solid-acid surfaces afforded highly active acid-base bifunctional catalysts, which enabled various organic transformations including C--C coupling reactions, though these reactions did not proceed with either the homogeneous amine precursors or the acidic supports alone. Spectroscopic characterization, such as by solid-state MAS NMR and FTIR, revealed not only the interactions between acidic and basic sites but also bifunctional catalytic reaction mechanisms.

  1. Regulation of skeletal muscle insulin action in relation to dietary fatty acids and gender

    DEFF Research Database (Denmark)

    Høeg, Louise Dalgas

    -rich diet enriched in long-chain saturated fatty acids, whole body insulin sensitivity (19%) and insulin stimulated glucose uptake in skeletal muscle (24%) were also reduced, whereas no changes was observed after a diet enriched in medium-chain saturated fatty acids and carbohydrates. These findings show...... in skeletal muscle could rather be ascribed to attenuated GLUT4 translocation to the plasma surface membrane after the unsaturated (23%) and long-chain saturated fatty acid diet (26%) compared with the control diet (52%)(investigated in rats). Furthermore, the present data suggest that mechanisms regulating...

  2. [Systematic analysis and metabolic regulation of physiological functions for lactic acid bacteria--a review].

    Science.gov (United States)

    Wu, Chongde; Zhang, Juan; Liu, Liming

    2012-01-01

    As cell factories, lactic acid bacteria are widely used in food, agriculture, medicine and other industries, and play a great role in industrial processes. However, lactic acid bacteria encounter various environmental stresses both in industrial processes and in the gastrointestinal tract, which impair their physiological functions and food manufacture efficiency. Recently, the development of metabolic engineering and system biology brings unprecedented opportunity for the physiological modification of lactic acid bacteria. In this review, we addresses the progress of lactic acid bacterium system biology, and based on this, the metabolic engineering strategies for manipulating and optimizing lactic acid bacteria physiological function were summarized.

  3. Distinct amino acid-sensing mTOR pathways regulate skeletal myogenesis.

    Science.gov (United States)

    Yoon, Mee-Sup; Chen, Jie

    2013-12-01

    Signaling through the mammalian target of rapamycin (mTOR) in response to amino acid availability controls many cellular and developmental processes. mTOR is a master regulator of myogenic differentiation, but the pathways mediating amino acid signals in this process are not known. Here we examine the Rag GTPases and the class III phosphoinositide 3-kinase (PI3K) Vps34, two mediators of amino acid signals upstream of mTOR complex 1 (mTORC1) in cell growth regulation, for their potential involvement in myogenesis. We find that, although both Rag and Vps34 mediate amino acid activation of mTORC1 in C2C12 myoblasts, they have opposing functions in myogenic differentiation. Knockdown of RagA/B enhances, whereas overexpression of active RagB/C mutants impairs, differentiation, and this inhibitory function of Rag is mediated by mTORC1 suppression of the IRS1-PI3K-Akt pathway. On the other hand, Vps34 is required for myogenic differentiation. Amino acids activate a Vps34-phospholipase D1 (PLD1) pathway that controls the production of insulin-like growth factor II, an autocrine inducer of differentiation, through the Igf2 muscle enhancer. The product of PLD, phosphatidic acid, activates the enhancer in a rapamycin-sensitive but mTOR kinase-independent manner. Our results uncover amino acid-sensing mechanisms controlling the homeostasis of myogenesis and underline the versatility and context dependence of mTOR signaling.

  4. [Regulation effects of grafting on cinnamic acid and vanillin in eggplant root exudates].

    Science.gov (United States)

    Chen, Shao-li; Zhou, Bao-li; Wang, Ru-hua; Fu, Ya-wen

    2008-11-01

    Cinnamic acid and vanillin are the allelochemicals commonly existed in eggplant root exudates. With pot culture experiment, the regulation effects of grafting on the cinnamic acid and vanillin in eggplant root exudates were studied, and the results showed that grafting decreased the amount of the two substances, especially of vanillin, in eggplants root system. The maximum reduction amount of cinnamic acid reached 68.96%, and that of vanillin reached 100%. Under the stress of exotic cinnamic acid and vanillin, especially of exotic cinnamic acid, grafting relieved the autotoxicity of the two substances on eggplants. Compared with own-rooted eggplant, grafted eggplant had a higher plant height and a larger stem diameter, its leaf chlorophyll content increased by 5.26%-13.12%, root electric conductivity and MDA content decreased, and root SOD activity enhanced.

  5. The Promotion of Erythropoiesis via the Regulation of Reactive Oxygen Species by Lactic Acid.

    Science.gov (United States)

    Luo, Shun-Tao; Zhang, Dong-Mei; Qin, Qing; Lu, Lian; Luo, Min; Guo, Fu-Chun; Shi, Hua-Shan; Jiang, Li; Shao, Bin; Li, Meng; Yang, Han-Shuo; Wei, Yu-Quan

    2017-02-06

    The simultaneous increases in blood lactic acid and erythrocytes after intense exercise could suggest a link between lactate and the erythropoiesis. However, the effects of lactic acid on erythropoiesis remain to be elucidated. Here, we utilized a mouse model to determine the role of lactic acid in this process in parallel with studies using leukaemic K562 cells. Treatment of K562 cells in vitro with lactic acid increased the mRNA and protein expression of haemoglobin genes and the frequency of GPA(+) cells. Also, increases in haematocrit and CD71(-)/Ter119(+) erythroid cells were observed in lactic acid-treated mice, which showed a physiological increase in blood lactate. Mouse bone marrow CD34(+)/CD117(-) cells showed an increase in erythroid burst-forming units after stimulation with lactic acid in vitro. Furthermore, lactic acid increased the intracellular reactive oxygen species (ROS) content in bone marrow and in K562 cells. Erythroid differentiation induced in Haematopoietic Stem Cells (HSCs) and K562 cells by lactic acid was abolished by reducing ROS levels with SOD or 2-mercaptoethanol, which suggests that ROS is a critical regulator of this process. These findings provide a better understanding of the role of lactic acid in cellular metabolism and physiological functions.

  6. ACID-BASE INTERACTIONS BETWEEN POLYMERS AND FILLERS

    Institute of Scientific and Technical Information of China (English)

    WANG Qingguo; CHEN Fute; HUANG Yuanfu; ZHOU Qingli

    1987-01-01

    Inverse gas chromatography(IGC) and Fourier-transform infrared (FT-IR) techniques were applied to determining the relative acid-base strength of polymers and coupling agents. The acid-base characteristics of fillers such as CaCO3 could be altered by treatment with different coupling agents. It was shown that some mechanical properties of filled polymers were obviously associated with acid-base interactions between polymers and fillers.

  7. Excitatory amino acid receptors in the ventral tegmental area regulate dopamine release in the ventral striatum

    NARCIS (Netherlands)

    Karreman, M; Westerink, BHC; Moghaddam, B

    1996-01-01

    The role of excitatory amino acid (EAA) receptors located in the ventral tegmental area (VTA) in tonic and phasic regulation of dopamine release in the ventral striatum was investigated. Microdialysis in conscious rats was used to assess dopamine release primarily from the nucleus accumbens shell re

  8. Regulation of aromatic amino acid biosynthesis in the ribulose monophosphate cycle methylotroph Nocardia sp. 239

    NARCIS (Netherlands)

    Boer, L. de; Vrijbloed, J.W.; Grobben, G.; Dijkhuizen, L.

    1989-01-01

    The regulation of aromatic amino acid biosynthesis in Nocardia sp. 239 was studied. In cell-free extracts 3-deoxy-D-arabinoheptulosonate 7-phosphate (DAHP) synthase activity was inhibited in a cumulative manner by tryptophan, phenylalanine and tyrosine. Chorismate mutase was inhibited by both phenyl

  9. Synthesis and regulation of chlorogenic acid in potato: Rerouting phenylpropanoid flux in HQT silenced lines

    Science.gov (United States)

    Chlorogenic acid (CGA) is the major phenolic sink in potato tubers and can constitute over 90% of total phenylpropanoids. The regulation of CGA biosynthesis in potato and the role of the CGA biosynthetic gene hydroxycinnamoyl-CoA:quinate hydroxycinnamoyl transferase (HQT) was characterized. A sucros...

  10. Acid rain compliance and coordination of state and federal utility regulation

    Energy Technology Data Exchange (ETDEWEB)

    Nordhaus, R.R. [Van Ness, Feldman, and Curtis, P.C., Washington, DC (United States)

    1993-07-01

    The Clean Air Act Amendments of 1990 (CAAA) impose new controls on emissions by electric utilities of the two major precursors of acid rain: sulfur dioxide and oxides of nitrogen. Utilities, and the utility holding company systems and power pools of which they are members, will be subject to extensive and costly compliance obligations under the new stature. Most of these utilities, utility systems, and power pools are regulated by more than one utility regulatory authority. Utility regulators will need to coordinate their policies for ratemaking and for review of acid rain compliance strategies if least-cost solutions are to be implemented without imposing on rate payers and utility shareholders the costs and risks of inconsistent regulatory determinations. This article outlines the scope of the coordination problem and spells out possible approaches that utility regulators may take in dealing with it. Topics covered include the following: the 1990 Clean Air Act Amendments; acid rain (SO2); acid rain (NOx); costs of compliance; implications for utility regulation - federal and state utility regulatory framework; potential jurisdictional conflicts under existing state/federal utility regulatory scheme - single utility, holding companies, power pools; Utility regulatory issues under the 1990 amendments - planning conflicts, operational conflicts; methods for dealing with potential jurisdictional conflicts; coordination mechanisms - informal consultation, rulemaking,coordination of adjudicatory proceedings, FERC rate filings.

  11. NR4A orphan nuclear receptors influence retinoic acid and docosahexaenoic acid signaling via up-regulation of fatty acid binding protein 5

    Energy Technology Data Exchange (ETDEWEB)

    Volakakis, Nikolaos; Joodmardi, Eliza [Ludwig Institute for Cancer Research Ltd., Box 240, S-17177 Stockholm (Sweden); Perlmann, Thomas, E-mail: thomas.perlmann@licr.ki.se [Ludwig Institute for Cancer Research Ltd., Box 240, S-17177 Stockholm (Sweden); The Department of Cell and Molecular Biology, Karolinska Institute, S-17177 Stockholm (Sweden)

    2009-12-25

    The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult nervous system and is also induced as an immediate early gene in a variety of cell types. In silico analysis of human promoters identified fatty acid binding protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated PPAR{beta}/{delta} signaling, as a potential Nurr1 target gene. Nurr1 has previously been implicated in retinoid signaling via its heterodimerization partner RXR. Since NRs are commonly involved in cross-regulatory control we decided to further investigate the regulatory relationship between Nurr1 and FABP5. FABP5 expression was up-regulated by Nurr1 and other NR4A NRs in HEK293 cells, and Nurr1 was shown to activate and bind to the FABP5 promoter, supporting that FABP5 is a direct downstream target of NR4A NRs. We also show that the RXR ligand docosahexaenoic acid (DHA) can induce nuclear translocation of FABP5. Moreover, via up-regulation of FABP5 Nurr1 can enhance retinoic acid-induced signaling of PPAR{beta}/{delta} and DHA-induced activation of RXR. We also found that other members of the NR4A orphan NRs can up-regulate FABP5. Thus, our findings suggest that NR4A orphan NRs can influence signaling events of other NRs via control of FABP5 expression levels.

  12. FOOD SAFETY REGULATIONS BASED ON REAL SCIENCE

    Directory of Open Access Journals (Sweden)

    Huub LELIEVELD

    2015-10-01

    Full Text Available Differences in regulations result in needless destruction of safe food and hamper food trade. The differences are not just the result of the history of food safety regulations, often developed in times before global cooperation, but are also built in new regulations. It may be responses to media hypes or for other reasons, but in most cases the differences cannot be justified scientifically. A major difficulty is that, due to the developments in analytical techniques the number of chemicals that are found in food is increasing rapidly and chemicals are always suspected to be a safety risk. By far most chemicals are of natural origin but could not be detected in the past because the methods available in the past were not sensitive enough. Demanding the absence of chemicals because the risk they present is unknown, however, would eventually make all food unacceptable. The general public should be shown that everything they eat is chemical, and all food components will be toxic if the amount is too high. It should also be shown that many of these chemicals will also cause illness and death if there is not enough of it as is the case with vitamins and minerals.

  13. Regulated acid–base transport in the collecting duct

    OpenAIRE

    2009-01-01

    The renal collecting system serves the fine-tuning of renal acid-base secretion. Acid-secretory type-A intercalated cells secrete protons via a luminally expressed V-type H(+)-ATPase and generate new bicarbonate released by basolateral chloride/bicarbonate exchangers including the AE1 anion exchanger. Efficient proton secretion depends both on the presence of titratable acids (mainly phosphate) and the concomitant secretion of ammonia being titrated to ammonium. Collecting duct ammonium excre...

  14. A study on development of methodology and guidelines of risk based regulation for optimization of regulation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hoon; Chang, Soon Hong; Kang, Kee Sik; Paek, Won Phil; Kim, Han Gon; Chang, Hyeon Seop [Korea Association for Nuclear Technology, Taejon (Korea, Republic of)

    1995-12-15

    This project consists of the three phase as follow : define the RBR(Risk Based Regulation) concept and analysis of state of art to RBR to NRC, EPRI etc., develop the application area and guideline of RBR to the selected area, develop the regulatory guideline with considering the plant specific conditions in detail. For the first year of this study elementary work for risk based regulation concept was analysed and performed as follows : state of the art of RBR research status, methodology establishment for usage of PSA(Probabilistic Safety Assessment), establishment of the methodology of risk based regulation, and application area for RBR.

  15. Phytoagents for Cancer Management: Regulation of Nucleic Acid Oxidation, ROS, and Related Mechanisms

    Directory of Open Access Journals (Sweden)

    Wai-Leng Lee

    2013-01-01

    Full Text Available Accumulation of oxidized nucleic acids causes genomic instability leading to senescence, apoptosis, and tumorigenesis. Phytoagents are known to reduce the risk of cancer development; whether such effects are through regulating the extent of nucleic acid oxidation remains unclear. Here, we outlined the role of reactive oxygen species in nucleic acid oxidation as a driving force in cancer progression. The consequential relationship between genome instability and cancer progression highlights the importance of modulation of cellular redox level in cancer management. Current epidemiological and experimental evidence demonstrate the effects and modes of action of phytoagents in nucleic acid oxidation and provide rationales for the use of phytoagents as chemopreventive or therapeutic agents. Vitamins and various phytoagents antagonize carcinogen-triggered oxidative stress by scavenging free radicals and/or activating endogenous defence systems such as Nrf2-regulated antioxidant genes or pathways. Moreover, metal ion chelation by phytoagents helps to attenuate oxidative DNA damage caused by transition metal ions. Besides, the prooxidant effects of some phytoagents pose selective cytotoxicity on cancer cells and shed light on a new strategy of cancer therapy. The “double-edged sword” role of phytoagents as redox regulators in nucleic acid oxidation and their possible roles in cancer prevention or therapy are discussed in this review.

  16. Small noncoding RNA GcvB is a novel regulator of acid resistance in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Jin Ye

    2009-04-01

    Full Text Available Abstract Background The low pH environment of the human stomach is lethal for most microorganisms; but not Escherichia coli, which can tolerate extreme acid stress. Acid resistance in E. coli is hierarchically controlled by numerous regulators among which are small noncoding RNAs (sncRNA. Results In this study, we individually deleted seventy-nine sncRNA genes from the E. coli K12-MG1655 chromosome, and established a single-sncRNA gene knockout library. By systematically screening the sncRNA mutant library, we show that the sncRNA GcvB is a novel regulator of acid resistance in E. coli. We demonstrate that GcvB enhances the ability of E. coli to survive low pH by upregulating the levels of the alternate sigma factor RpoS. Conclusion GcvB positively regulates acid resistance by affecting RpoS expression. These data advance our understanding of the sncRNA regulatory network involved in modulating acid resistance in E. coli.

  17. Scale-up of α-ketoglutaric acid production based on intracellular metabolic regulation%基于细胞代谢调控的α-酮戊二酸发酵过程放大

    Institute of Scientific and Technical Information of China (English)

    余宗钟; 堵国成; 陈坚; 周景文

    2013-01-01

    基于α-酮戊二酸发酵从7L发酵罐放大到5 m3发酵罐时发现:发酵周期大幅缩短,细胞生长速度加快,丙酮酸大量积累,而α-酮戊二酸的产量降低.为此,考察了不同规模反应器上溶氧控制对细胞生长和产物代谢的影响,发现较高的溶氧水平有利于细胞生长和丙酮酸积累,但细胞容易衰老,影响最终发酵产量;降低溶氧有利于保持细胞活力,有利于丙酮酸进入三羧酸循环转化为α-酮戊二酸的积累.根据这一结果,采用两阶段溶氧控制,同时强化丙酮酸进入三羧酸循环的丙酮酸羧化途径,α-酮戊二酸的产量达到44.1 g/L.为了充分发挥解脂亚洛酵母优越的发酵性能,采用恒速流加甘油策略,α-酮戊二酸产量达到64.2g/L.与7L发酵罐上的相比,周期缩短了24h,生产强度提高了38%.%Abstract When α-ketoglutaric acid(α-KG) production by Yarrowia lipolytica was scaled-up in 5 m3 fermentor from 7 L fermentor,it was found that cell growth rate in 5 m3 fermentor was higher than that of in 7 L fermentor and higher amount of pyruvate was accumulated in the broth.However,α-ketoglutaric acid production decreased.In order to solve this problem,the effect of dissolved oxygen level on α-KG production was investigated.The results showed that the higher dissolved oxygen level could facilitate cell growth and pyruvate accumulation,but was harmful to maintaining cell vitality.Conversely,lower dissolved oxygen level could facilitate the channeling of pyruvate into citric acid cycle to product α-ketoglutaric acid.Therefore,a two-stage control strategy was employed,pyruvate carboxylase activity was improved by feeding CaCO3 from 48 h,α-ketoglutaric acid production reached 44.1 g/L.In order to bring the yeast' s intense secretory ability into full play,constant feeding approach was applied in fed-batch culture.Consequently,the culture time was shortened by 24 h,α-ketoglutaric acid production reached 64.2 g/L with its

  18. Quinoline based receptor in fluorometric discrimination of carboxylic acids

    Directory of Open Access Journals (Sweden)

    2008-12-01

    Full Text Available Quinoline and naphthalene-based fluororeceptors 1 and 2 have been designed and synthesized for detection of hydroxy carboxylic acids in less polar solvents. The receptor 1 shows monomer emission quenching followed by excimer emission upon hydrogen bond-mediated complexation of carboxylic acids. The excimer emission distinguishes aromatic dicarboxylic acids from aliphatic dicarboxylic acids and even long chain aliphatic dicarboxylic acids from short chain aliphatic dicarboxylic acids. The receptor 1 is found to be selective for citric acid with a strong excimer emission in CHCl3. On the contrary, the receptor 2 exhibited less binding constant value and did not form any excimer upon complexation with the same acids under similar conditions. This established the role of quinoline ring nitrogen in binding with the acids.

  19. Gut microbiota, cirrhosis and alcohol regulate bile acid metabolism in the gut

    Science.gov (United States)

    Ridlon, Jason M.; Kang, Dae-Joong; Hylemon, Phillip B.; Bajaj, Jasmohan S

    2015-01-01

    The understanding of the complex role of the bile acid-gut microbiome axis in health and disease processes is evolving rapidly. Our focus revolves around the interaction of the gut microbiota with liver diseases, especially cirrhosis. The bile acid pool size has recently been shown to be a function of microbial metabolism of bile acid and regulation of the microbiota by bile acids is important in the development and progression of several liver diseases. Humans produce a large, conjugated hydrophilic bile acid pool, maintained through positive-feedback antagonism of FXR in intestine and liver. Microbes use bile acids, and via FXR signaling this results in a smaller, unconjugated hydrophobic bile acid pool. This equilibrium is critical to maintain health. The challenge is to examine the manifold functions of gut bile acids as modulators of antibiotic, probiotic and disease progression in cirrhosis, metabolic syndrome and alcohol use. Recent studies have shown potential mechanisms explaining how perturbations in the microbiome affect bile acid pool size and composition. With advancing liver disease and cirrhosis, there is dysbiosis in the fecal, ileal and colonic mucosa, in addition to a decrease in bile acid concentration in the intestine due to the liver problems. This results in a dramatic shift toward the Firmicutes, particularly Clostridium cluster XIVa and increasing production of deoxycholic acid (DCA). Alcohol intake speeds up these processes in the subjects with and without cirrhosis without significant FXR feedback. Taken together, these pathways can impact intestinal and systemic inflammation while worsening dysbiosis. The interaction between bile acids, alcohol, cirrhosis and dysbiosis is an important relationship that influences intestinal and systemic inflammation, which in turn determines progression of the overall disease process. These interactions and the impact of commonly used therapies for liver disease can provide insight into the pathogenesis

  20. Enhanced Acid/Base Catalysis in High Temperature Liquid Water

    Institute of Scientific and Technical Information of China (English)

    Xiu Yang LU; Qi JING; Zhun LI; Lei YUAN; Fei GAO; Xin LIU

    2006-01-01

    Two novel and environmentally benign solvent systems, organic acids-enriched high temperature liquid water (HTLW) and NH3-enriched HTLW, were developed, which can enhance the reaction rate of acid/base-catalyzed organic reactions in HTLW. We investigated the decomposition of fructose in organic acids-enriched HTLW, hydrolysis of cinnamaldehyde and aldol condensation of phenylaldehyde with acetaldehyde in NH3-enriched HTLW. The experimental results demonstrated that organic acids-enriched or NH3-enriched HTLW can greatly accelerate acid/base-catalyzed organic reactions in HTLW.

  1. Acid-base strengths in pyridine

    NARCIS (Netherlands)

    Bos, M.; Dahmen, E.A.M.F.

    1971-01-01

    Although pyridine is a solvent with a low dielectric constant, spectrophotometric determinations show simple dissociation without ion pairs as intermediates for some sulfonphthaleins and polynitrophenols in pyridine. The salts of a number of amines and hydrochloric acid, perchloric acid and picric

  2. [The role of arachidonic acid metabolites in the regulation of renal function and pathogenesis of hypertension].

    Science.gov (United States)

    Certíková Chábová, V

    2008-01-01

    Eicosanoids are twenty-carbon compounds derived from arachidonic acid. Lipoxygenases, cyclooxygenases and cytochrome P-450 enzymes contribute to their synthesis. Our review is focused on prostaglandins, leucotrienes, lipoxins, hepoxilins, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids. Most of these compounds have multiple functions and they also participate in blood pressure regulation and excretion of water and solutes in the kidney. They have some roles in the patogenesis of kidney disease, too. Both experimental models (mainly geneticaly modified mice and rats) and human epidemiological and genetical studies are used in the investigation of eicosanoid physiological and patophysiological functions. New information about their enzymatic regulations and receptors have already resulted in the development of new drugs, mainly antiasthmatics, but further investigation should bring about new results in the treatment of hypertension and other cardiovascular and renal diseases.

  3. Recognition of Nucleic Acid Junctions Using Triptycene-Based Molecules

    OpenAIRE

    Barros, Stephanie A.; Chenoweth, David M.

    2014-01-01

    Nucleic acid modulation by small molecules is an essential process across the kingdoms of life. Targeting nucleic acids with small molecules represents a significant challenge at the forefront of chemical biology. Nucleic acid junctions are ubiquitous structural motifs in nature and in designed materials. Herein, we describe a new class of structure specific nucleic acid junction stabilizers based on a triptycene scaffold. Triptycenes provide significant stabilization of DNA and RNA three-way...

  4. Structure-dependent effects of pyridine derivatives on mechanisms of intestinal fatty acid uptake: regulation of nicotinic acid receptor and fatty acid transporter expression.

    Science.gov (United States)

    Riedel, Annett; Lang, Roman; Rohm, Barbara; Rubach, Malte; Hofmann, Thomas; Somoza, Veronika

    2014-07-01

    Pyridines are widely distributed in foods. Nicotinic acid (NA), a carboxylated pyridine derivative, inhibits lipolysis in adipocytes by activation of the orphan NA receptor (HM74A) and is applied to treat hyperlipidemia. However, knowledge on the impact of pyridine derivatives on intestinal lipid metabolism is scarce. This study was performed to identify the structural determinants of pyridines for their effects on fatty acid uptake in enterocyte-like Caco-2 cells and to elucidate the mechanisms of action. The impact of 17 pyridine derivatives on fatty acid uptake was tested. Multiple regression analysis revealed the presence of a methyl group to be the structural determinant at 0.1 mM, whereas at 1 mM, the presence of a carboxylic group and the N-methylation presented further structural characteristics to affect the fatty acid uptake. NA, showing a stimulating effect on FA uptake, and N-methyl-4-phenylpyridinium (MPP), inhibiting FA uptake, were selected for mechanistic studies. Gene expression of the fatty acid transporters CD36, FATP2 and FATP4, and the lipid metabolism regulating transcription factors peroxisome proliferator-activated receptor (PPAR) α and PPARγ was up-regulated upon NA treatment. Caco-2 cells were demonstrated to express the low-affinity NA receptor HM74 of which the gene expression was up-regulated upon NA treatment. We hypothesize that the NA-induced fatty acid uptake might result from NA receptor activation and related intracellular signaling cascades. In contrast, MPP increased transepithelial electrical resistance. We therefore conclude that NA and MPP, both sharing the pyridine motif core, exhibit their contrary effects on intestinal FA uptake by activation of different mechanisms.

  5. Characterisation of SalRAB a salicylic acid inducible positively regulated efflux system of Rhizobium leguminosarum bv viciae 3841.

    Directory of Open Access Journals (Sweden)

    Adrian J Tett

    Full Text Available Salicylic acid is an important signalling molecule in plant-microbe defence and symbiosis. We analysed the transcriptional responses of the nitrogen fixing plant symbiont, Rhizobium leguminosarum bv viciae 3841 to salicylic acid. Two MFS-type multicomponent efflux systems were induced in response to salicylic acid, rmrAB and the hitherto undescribed system salRAB. Based on sequence similarity salA and salB encode a membrane fusion and inner membrane protein respectively. salAB are positively regulated by the LysR regulator SalR. Disruption of salA significantly increased the sensitivity of the mutant to salicylic acid, while disruption of rmrA did not. A salA/rmrA double mutation did not have increased sensitivity relative to the salA mutant. Pea plants nodulated by salA or rmrA strains did not have altered nodule number or nitrogen fixation rates, consistent with weak expression of salA in the rhizosphere and in nodule bacteria. However, BLAST analysis revealed seventeen putative efflux systems in Rlv3841 and several of these were highly differentially expressed during rhizosphere colonisation, host infection and bacteroid differentiation. This suggests they have an integral role in symbiosis with host plants.

  6. Characterisation of SalRAB a salicylic acid inducible positively regulated efflux system of Rhizobium leguminosarum bv viciae 3841.

    Science.gov (United States)

    Tett, Adrian J; Karunakaran, Ramakrishnan; Poole, Philip S

    2014-01-01

    Salicylic acid is an important signalling molecule in plant-microbe defence and symbiosis. We analysed the transcriptional responses of the nitrogen fixing plant symbiont, Rhizobium leguminosarum bv viciae 3841 to salicylic acid. Two MFS-type multicomponent efflux systems were induced in response to salicylic acid, rmrAB and the hitherto undescribed system salRAB. Based on sequence similarity salA and salB encode a membrane fusion and inner membrane protein respectively. salAB are positively regulated by the LysR regulator SalR. Disruption of salA significantly increased the sensitivity of the mutant to salicylic acid, while disruption of rmrA did not. A salA/rmrA double mutation did not have increased sensitivity relative to the salA mutant. Pea plants nodulated by salA or rmrA strains did not have altered nodule number or nitrogen fixation rates, consistent with weak expression of salA in the rhizosphere and in nodule bacteria. However, BLAST analysis revealed seventeen putative efflux systems in Rlv3841 and several of these were highly differentially expressed during rhizosphere colonisation, host infection and bacteroid differentiation. This suggests they have an integral role in symbiosis with host plants.

  7. Regulation of amino-acid metabolism controls flux to lipid accumulation in Yarrowia lipolytica

    DEFF Research Database (Denmark)

    Kerkhoven, Eduard J.; Pomraning, Kyle R.; Baker, Scott E.

    2016-01-01

    Yarrowia lipolytica is a promising microbial cell factory for the production of lipids to be used as fuels and chemicals, but there are few studies on regulation of its metabolism. Here we performed the first integrated data analysis of Y. lipolytica grown in carbon and nitrogen limited chemostat...... cultures. We first reconstructed a genome-scale metabolic model and used this for integrative analysis of multilevel omics data. Metabolite profiling and lipidomics was used to quantify the cellular physiology, while regulatory changes were measured using RNAseq. Analysis of the data showed that lipid...... accumulation in Y. lipolytica does not involve transcriptional regulation of lipid metabolism but is associated with regulation of amino-acid biosynthesis, resulting in redirection of carbon flux during nitrogen limitation from amino acids to lipids. Lipid accumulation in Y. lipolytica at nitrogen limitation...

  8. Temperature regulated Brønsted acidic ionic liquid-catalyze esterification of oleic acid for biodiesel application

    Science.gov (United States)

    Rafiee, Ezzat; Mirnezami, Fakhrosadat

    2017-02-01

    By combining phosphotungstic acid (PW) and SO3H- functioned zwitterion, heteropoly anion-based Brønsted acidic ionic liquids (HPA-ILs) were successfully obtained. Scanning electron microscopy and energy dispersive X-ray spectroscopy were provided the morphology and composition of the prepared material. Catalytic performance and reusability of the catalysts were evaluated through an esterification reaction between oleic acid and methanol for production of biodiesel. Relationship between catalytic activities and acidity of the catalysts have been discussed by potentiometric titration. The results showed that HPA-ILs had good activity and reusability. HPA-ILs dissolved in the reaction mixture during the reaction process and could be precipitated and separated from products at lower temperature.

  9. Salvianolic acid B inhibits mitochondrial dysfunction by up-regulating mortalin

    Science.gov (United States)

    Liu, Yunxia; Hu, Yingying; E, Qiukai; Zuo, Ji; Yang, Ling; Liu, Wen

    2017-01-01

    Salvianolic acid B is an antioxidative ingredient derived from Radix Salviae miltiorrhizae that has been widely used to treat liver diseases. However, the therapeutic mechanism underlying Salvianolic acid B has remained largely unknown. Our studies verified that Salvianolic acid B efficiently blocked mitochondrial deformation and dysfunction induced by H2O2 in the human hepatocyte cell line HL7702. Mortalin, a mitochondrial molecular chaperone, maintains mitochondrial morphology stabilization and function integrity. Previous results showed that mortalin overexpression has been observed in hematoma carcinoma cells and that mortalin maintains mitochondrial homeostasis and antagonizes oxidative stress damage. We found that Salvianolic acid B significantly up-regulated mortalin protein expression levels. In addition, Salvianolic acid B lost the function of preventing mitochondrial deformation and dysfunction induced by oxidative stress under mortalin knockdown conditions. We further found that mortalin overexpression increases the mRNA expression of mitofusin-related factor Mfn1 and mitofission-related factor hFis1. In conclusion, Salvianolic acid B maintains the mitochondrial structure stabilization and functional integrity by up-regulating mortalin, which may be associated with increased mitofusin factor Mfn1 and reduced mitofission factor hFis1. PMID:28251987

  10. Docosahexaenoic acid regulates gene expression in HUVEC cells treated with polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Gdula-Argasińska, Joanna; Czepiel, Jacek; Totoń-Żurańska, Justyna; Jurczyszyn, Artur; Perucki, William; Wołkow, Paweł

    2015-07-16

    The molecular mechanism of inflammation and carcinogenesis induced by exposure of polycyclic aromatic hydrocarbons (PAHs) is not clearly understood. Our study was undertaken due to the strong pro-carcinogenic potential and reactivity of PAH-metabolites, as well as the susceptibility of polyunsaturated fatty acids to oxidation. The aim of this study was to evaluate the pro- or anti-inflammatory impact of n-3 docosahexaenoic acid on human primary umbilical vein endothelial cells (HUVEC) exposed to polycyclic aromatic hydrocarbons. We analysed the influence of docosahexaenoic acid (DHA) and/or PAHs supplementation on the fatty acid profile of cell membranes, on cyclooxygenase-2 (COX-2), aryl hydrocarbon receptor (AHR), and glutathione S transferase Mu1 (GSTM1) protein expression as well as on the prostaglandin synthase 2 (PTGS2), AHR, GSTM1, PLA2G4A, and cytochrome P450 CYP1A1 gene expression. We observed that COX-2 and AHR protein expression was increased while GSTM1 expression was decreased in cells exposed to DHA and PAHs. Docosahexaenoic acid down-regulated CYP1A1 and up-regulated the AHR and PTGS2 genes. Our findings suggested that DHA contributes significantly to alleviate the harmful effects caused by PAHs in endothelial cells. Moreover, these results suggest that a diet rich in n-3 fatty acids is helpful to reduce the harmful effects of PAHs exposure on human living in heavily polluted areas.

  11. Salvianolic acid B inhibits mitochondrial dysfunction by up-regulating mortalin.

    Science.gov (United States)

    Liu, Yunxia; Hu, Yingying; E, Qiukai; Zuo, Ji; Yang, Ling; Liu, Wen

    2017-03-02

    Salvianolic acid B is an antioxidative ingredient derived from Radix Salviae miltiorrhizae that has been widely used to treat liver diseases. However, the therapeutic mechanism underlying Salvianolic acid B has remained largely unknown. Our studies verified that Salvianolic acid B efficiently blocked mitochondrial deformation and dysfunction induced by H2O2 in the human hepatocyte cell line HL7702. Mortalin, a mitochondrial molecular chaperone, maintains mitochondrial morphology stabilization and function integrity. Previous results showed that mortalin overexpression has been observed in hematoma carcinoma cells and that mortalin maintains mitochondrial homeostasis and antagonizes oxidative stress damage. We found that Salvianolic acid B significantly up-regulated mortalin protein expression levels. In addition, Salvianolic acid B lost the function of preventing mitochondrial deformation and dysfunction induced by oxidative stress under mortalin knockdown conditions. We further found that mortalin overexpression increases the mRNA expression of mitofusin-related factor Mfn1 and mitofission-related factor hFis1. In conclusion, Salvianolic acid B maintains the mitochondrial structure stabilization and functional integrity by up-regulating mortalin, which may be associated with increased mitofusin factor Mfn1 and reduced mitofission factor hFis1.

  12. Acid-Base Pairs in Lewis Acidic Zeolites Promote Direct Aldol Reactions by Soft Enolization.

    Science.gov (United States)

    Lewis, Jennifer D; Van de Vyver, Stijn; Román-Leshkov, Yuriy

    2015-08-17

    Hf-, Sn-, and Zr-Beta zeolites catalyze the cross-aldol condensation of aromatic aldehydes with acetone under mild reaction conditions with near quantitative yields. NMR studies with isotopically labeled molecules confirm that acid-base pairs in the Si-O-M framework ensemble promote soft enolization through α-proton abstraction. The Lewis acidic zeolites maintain activity in the presence of water and, unlike traditional base catalysts, in acidic solutions.

  13. HosA, a MarR Family Transcriptional Regulator, Represses Nonoxidative Hydroxyarylic Acid Decarboxylase Operon and Is Modulated by 4-Hydroxybenzoic Acid.

    Science.gov (United States)

    Roy, Ajit; Ranjan, Akash

    2016-02-23

    Members of the Multiple antibiotic resistance Regulator (MarR) family of DNA binding proteins regulate transcription of a wide array of genes required for virulence and pathogenicity of bacteria. The present study reports the molecular characterization of HosA (Homologue of SlyA), a MarR protein, with respect to its target gene, DNA recognition motif, and nature of its ligand. Through a comparative genomics approach, we demonstrate that hosA is in synteny with nonoxidative hydroxyarylic acid decarboxylase (HAD) operon and is present exclusively within the mutS-rpoS polymorphic region in nine different genera of Enterobacteriaceae family. Using molecular biology and biochemical approach, we demonstrate that HosA binds to a palindromic sequence downstream to the transcription start site of divergently transcribed nonoxidative HAD operon and represses its expression. Furthermore, in silico analysis showed that the recognition motif for HosA is highly conserved in the upstream region of divergently transcribed operon in different genera of Enterobacteriaceae family. A systematic chemical search for the physiological ligand revealed that 4-hydroxybenzoic acid (4-HBA) interacts with HosA and derepresses HosA mediated repression of the nonoxidative HAD operon. Based on our study, we propose a model for molecular mechanism underlying the regulation of nonoxidative HAD operon by HosA in Enterobacteriaceae family.

  14. Synthesis and study on biological activity of nitrogen-containing heterocyclic compounds – regulators of enzymes of nucleic acid biosynthesis

    Directory of Open Access Journals (Sweden)

    Alexeeva I. V.

    2013-07-01

    Full Text Available Results of investigations on the development of new regulators of functional activity of nucleic acid biosynthesis enzymes based on polycyclic nitrogen-containing heterosystems are summarized. Computer design and molecular docking in the catalytic site of target enzyme (T7pol allowed to perform the directed optimization of basic structures. Several series of compounds were obtained and efficient inhibitors of herpes family (simple herpes virus type 2, Epstein-Barr virus, influenza A and hepatitis C viruses were identified, as well as compounds with potent antitumor, antibacterial and antifungal activity. It was established that the use of model test systems based on enzymes participating in nucleic acids synthesis is a promising approach to the primary screening of potential inhibitors in vitro.

  15. Efficient production of free fatty acids from ionic liquid-based acid- or enzyme-catalyzed bamboo hydrolysate.

    Science.gov (United States)

    Mi, Le; Qin, Dandan; Cheng, Jie; Wang, Dan; Li, Sha; Wei, Xuetuan

    2017-03-01

    Two engineered Escherichia coli strains, DQ101 (MG1655 fadD (-))/pDQTES and DQ101 (MG1655 fadD (-))/pDQTESZ were constructed to investigate the free fatty acid production using ionic liquid-based acid- or enzyme-catalyzed bamboo hydrolysate as carbon source in this study. The plasmid, pDQTES, carrying an acyl-ACP thioesterase 'TesA of E. coli in pTrc99A was constructed firstly, and then (3R)-hydroxyacyl-ACP dehydratase was ligated after the TesA to give the plasmid pDQTESZ. These two strains exhibited efficient fatty acid production when glucose was used as the sole carbon source, with a final concentration of 2.45 and 3.32 g/L, respectively. The free fatty acid production of the two strains on xylose is not as efficient as that on glucose, which was 2.32 and 2.96 g/L, respectively. For mixed sugars, DQ101 (MG1655 fadD (-))-based strains utilized glucose and pentose sequentially under the carbon catabolite repression (CCR) regulation. The highest total FFAs concentration from the mixed sugar culture reached 2.81 g/L by DQ101 (MG1655 fadD (-))/pDQTESZ. Furthermore, when ionic liquid-based enzyme-catalyzed bamboo hydrolysate was used as the carbon source, the strain DQ101 (MG1655 fadD (-))/pDQTESZ could produce 1.23 g/L FFAs with a yield of 0.13 g/g, and while it just produced 0.65 g/L free fatty acid with the ionic liquid-based acid-catalyzed bamboo hydrolysate as the feedstock. The results suggested that enzymatic catalyzed bamboo hydrolysate with ionic liquid pretreatment could serve as an efficient feedstock for free fatty acid production.

  16. Chip-based sequencing nucleic acids

    Science.gov (United States)

    Beer, Neil Reginald

    2014-08-26

    A system for fast DNA sequencing by amplification of genetic material within microreactors, denaturing, demulsifying, and then sequencing the material, while retaining it in a PCR/sequencing zone by a magnetic field. One embodiment includes sequencing nucleic acids on a microchip that includes a microchannel flow channel in the microchip. The nucleic acids are isolated and hybridized to magnetic nanoparticles or to magnetic polystyrene-coated beads. Microreactor droplets are formed in the microchannel flow channel. The microreactor droplets containing the nucleic acids and the magnetic nanoparticles are retained in a magnetic trap in the microchannel flow channel and sequenced.

  17. The effects of trans-fatty acids on TAG regulation in mice depend on dietary unsaturated fatty acids.

    Science.gov (United States)

    Saín, Juliana; González, Marcela Aída; Lavandera, Jimena Verónica; Scalerandi, María Victoria; Bernal, Claudio Adrián

    2016-08-01

    The aim of this study was to investigate the effects of trans-fatty acids (TFA) on liver and serum TAG regulation in mice fed diets containing different proportions of n-3, n-6 and n-9 unsaturated fatty acids (UFA) from olive (O), maize (C) or rapeseed (R) oils partially substituted or not with TFA (Ot, Ct and Rt, respectively). Male CF1 mice were fed (30 d) one of these diets. The effects of the partial substitution (1 %, w/w) of different UFA with TFA on the activity and expression of hepatic enzymes involved in lipogenesis and fatty acids oxidation were evaluated, as well as their transcription factor expressions. Some of the mechanisms involved in the serum TAG regulation, hepatic VLDL rich in TAG (VLDL-TAG) secretion rate and lipoprotein lipase (LPL) activity were assessed. In liver, TFA induced an increase in TAG content in the Ot and Rt groups, and this effect was associated with an imbalance between lipogenesis and β-oxidation. In the Ot group, exacerbated lipogenesis may be one of the mechanisms responsible for the liver steatosis induced by TFA, whereas in Rt it has been related to a decreased β-oxidation, compared with their respective controls. The enhanced hepatic VLDL-TAG secretion in the Ot and Rt groups was compensated with a differential removal of TAG by LPL enzyme in extrahepatic tissues, leading to unchanged serum TAG levels. In brief, the effects of low levels of TFA on liver and serum TAG regulation in mice depend on the dietary proportions of n-3, n-6 and n-9 UFA.

  18. Ionisation constants of inorganic acids and bases in aqueous solution

    CERN Document Server

    Perrin, D D

    2013-01-01

    Ionisation Constants of Inorganic Acids and Bases in Aqueous Solution, Second Edition provides a compilation of tables that summarize relevant data recorded in the literature up to the end of 1980 for the ionization constants of inorganic acids and bases in aqueous solution. This book includes references to acidity functions for strong acids and bases, as well as details about the formation of polynuclear species. This text then explains the details of each column of the tables, wherein column 1 gives the name of the substance and the negative logarithm of the ionization constant and column 2

  19. Role of Low-Molecule-Weight Organic Acids and Their Salts in Regulating Soil pH

    Institute of Scientific and Technical Information of China (English)

    LI Zhi-An; ZOU Bi; XIA Han-Ping; DING Yong-Zhen; TAN Wan-Neng; FU Sheng-Lei

    2008-01-01

    The process of organic materials increasing soil pH has not yet been fully understood.This study examined the role of cations and organic anions in regulating soil pH using organic compounds.Calcareous soil,acid soil,and paddy soil were incubated with different simple organic compounds,pH was determined periodically and CO2 emission was also measured.Mixing organic acids with the soil caused an instant decrease of soil pH.The magnitude of pH decrease depended on the initial soil acidity and dissociation degree of the acids.Decomposition of organic acids could only recover the soil pH to about its original level.Mixing organic salts with soil caused an instant increase of soil pH.Decomposition of organic salts of sodium resulted in a steady increase of soil pH,with final soil pH being about 2.7-3.2 pH units over the control.Organic salts with the same anions (citrate) but different cations led to different magnitudes of pH increase,while those having the same cations but different anions led to very similar pH increases.Organic salts of sodium and sodium carbonate caused very similar pH increases of soil when they were added to the acid soil at equimolar concentrations of Na+.The results suggested that cations played a central role in regulating soil pH.Decarboxylation might only consume a limited number of protons.Conversion of organic salts into inorganic salts (carbonate) was possibly responsible for pH increase during their decomposition,suggesting that only those plant residues containing high excess base cations could actually increase soil pH.

  20. Regulation of acid adaptation in Lactic acid bacteria%乳酸菌的适酸性调节

    Institute of Scientific and Technical Information of China (English)

    乔磊; 崔艳华; 曲晓军

    2011-01-01

    The understanding of acid adaptation mechanisms of LAB will benefit screening the acid-tolerance bacteria, the optimization of procedures in the ferment progress and optimization of culture. This will greatly improve the quality of fermented foods. The acid adaptation mechanisms were discussed, including proton pump, the production of alkali, the changes of membrane, protection or repair of macro-molecules and the regulation of acid tolerance.%探讨了乳酸菌适酸机制有助于抗酸菌株的筛选、发酵过程中工序的优化以及培养基的优化等,进而大大提升发酵产品品质.对质子泵、产碱、细胞膜变化、大分子保护修复以及耐酸调节在内的适酸性调节机制进行了一一阐述.

  1. MiRNA-194 Regulates Palmitic Acid-Induced Toll-Like Receptor 4 Inflammatory Responses in THP-1 Cells.

    Science.gov (United States)

    Tian, Huiqun; Liu, Chaoqi; Zou, Xiaohua; Wu, Wei; Zhang, Changcheng; Yuan, Ding

    2015-05-13

    There is strong evidence to suggest that inflammatory responses link obesity and diseases, and the understanding of obesity-induced inflammatory mechanisms is central to the pathogenesis of diseases such asnonalcoholic fatty liver disease(NAFLD) and atherosclerosis that are modified by obesity. Based on this, anti-inflammatory treatments become a potential therapies for obesity-related diseases like NAFLD.A critical role of toll-like receptor (TLR) and its downstream molecules such as tumor necrosis factor receptor-associated factor 6(TRAF6) has been documented in inflammatory response induced by fatty acid. TLR pathway regulation provides a new insight to controlling the inflammatory response induced by fatty acid. Taken together, our study was aimed to understand the mechanism of fatty acid-mediated inflammation and look for an effective target which can prevent the inflammatory response induced by obesity. In this study, we used the saturated fatty acid palmitic acid (PA) to activate TLR4 signal pathway in human monocyte cells THP-1 that established an intracellular inflammatory model. Followed with activated TLR4, downstream molecular TRAF6 was upregulated and ultimately induced proinflammatory cytokine production. Based on this model, we also found that PA downregulated miR-194 expression with TLR4 activation. Moreover, our results showed that key signal molecular TRAF6 is a target of miR-194, overexpression of miR-194 directly decreased TRAF6 expression and attenuated the release of proinflammatory cytokine TNF-α in PA-activated monocyte THP-1. We conclude that miR-194 negatively regulates the TLR4 signal pathway which is activated by PA through directly negative TRAF6 expression.

  2. Pistacia lentiscus resin regulates intestinal damage and inflammation in trinitrobenzene sulfonic acid-induced colitis.

    Science.gov (United States)

    Gioxari, Aristea; Kaliora, Andriana C; Papalois, Apostolos; Agrogiannis, George; Triantafillidis, John K; Andrikopoulos, Nikolaos K

    2011-11-01

    Mastic (Pistacia lentiscus) of the Anacardiaceae family has exhibited anti-inflammatory and antioxidant properties in patients with Crohn's disease. This study was based on the hypothesis that mastic inhibits intestinal damage in inflammatory bowel disease, regulating inflammation and oxidative stress in intestinal epithelium. Four different dosages of P. lentiscus powder in the form of powder were administered orally to trinitrobenzene sulfonic acid-induced colitic rats. Eighty-four male Wistar rats were randomly assigned to seven groups: A, control; B, colitic; C-F, colitic rats daily supplemented with P. lentiscus powder at (C) 50 mg/kg, (D) 100 mg/kg, (E) 200 mg/kg, and (F) 300 mg/kg of body weight; and G, colitic rats treated daily with cortisone (25 μg/kg of body weight). Colonic damage was assessed microscopically. The cytokines tumor necrosis factor-α, intercellular adhesion molecule-1 (ICAM-1), interleukin (IL)-6, IL-8, and IL-10 and malonaldehyde were measured in colonic specimens. Results were expressed as mean ± SE values. Histological amelioration of colitis (P≤.001) and significant differences in colonic indices occurred after 3 days of treatment. Daily administration of 100 mg of P. lentiscus powder/kg of body weight decreased all inflammatory cytokines (P≤.05), whereas 50 mg of P. lentiscus powder/kg of body weight and cortisone treatment reduced only ICAM-1 (P≤.05 and P≤.01, respectively). Malonaldehyde was significantly suppressed in all treated groups (P≤.01). IL-10 remained unchanged. Cytokines and malonaldehyde remained unaltered after 6 days of treatment. Thus P. lentiscus powder could possibly have a therapeutic role in Crohn's disease, regulating oxidant/antioxidant balance and modulating inflammation.

  3. A new representation of acid-base disturbances

    NARCIS (Netherlands)

    M. Hekking (Marcel); E.S. Gelsema; J. Lindemans (Jan)

    1994-01-01

    textabstractThe acid-base status of intensive care patients is monitored on the basis of three quantities. The graphical representation which may be of help for the monitoring task is therefore cumbersome. The classical Siggaard-Andersen acid-base chart is such a representation, but it is only suite

  4. A Closer Look at Acid-Base Olfactory Titrations

    Science.gov (United States)

    Neppel, Kerry; Oliver-Hoyo, Maria T.; Queen, Connie; Reed, Nicole

    2005-01-01

    Olfactory titrations using raw onions and eugenol as acid-base indicators are reported. An in-depth investigation on olfactory titrations is presented to include requirements for potential olfactory indicators and protocols for using garlic, onions, and vanillin as acid-base olfactory indicators are tested.

  5. The Roles of Acids and Bases in Enzyme Catalysis

    Science.gov (United States)

    Weiss, Hilton M.

    2007-01-01

    Many organic reactions are catalyzed by strong acids or bases that protonate or deprotonate neutral reactants leading to reactive cations or anions that proceed to products. In enzyme reactions, only weak acids and bases are available to hydrogen bond to reactants and to transfer protons in response to developing charges. Understanding this…

  6. Inducible gene expression and environmentally regulated genes in lactic acid bacteria.

    Science.gov (United States)

    Kok, J

    1996-10-01

    Relatively recently, a number of genes and operons have been identified in lactic acid bacteria that are inducible and respond to environmental factors. Some of these genes/operons had been isolated and analysed because of their importance in the fermentation industry and, consequently, their transcription was studied and found to be regulatable. Examples are the lactose operon, the operon for nisin production, and genes in the proteolytic pathway of Lactococcus lactis, as well as xylose metabolism in Lactobacillus pentosus. Some other operons were specifically targetted with the aim to compare their mode of regulation with known regulatory mechanisms in other well-studied bacteria. These studies, dealing with the biosynthesis of histidine, tryptophan, and of the branched chain amino acids in L. lactis, have given new insights in gene regulation and in the occurrence of auxotrophy in these bacteria. Also, nucleotide sequence analyses of a number of lactococcal bacteriophages was recently initiated to, among other things, specifically learn more about regulation of the phage life cycle. Yet another approach in the analysis of regulated genes is the 'random' selection of genetic elements that respond to environmental stimuli and the first of such sequences from lactic acid bacteria have been identified and characterized. The potential of these regulatory elements in fundamental research and practical (industrial) applications will be discussed.

  7. Connecting Acids and Bases with Encapsulation... and Chemistry with Nanotechnology

    Science.gov (United States)

    Criswell, Brett

    2007-01-01

    The features and the development of various new acids and bases activity sets that combines chemistry with nanotechnology are being described. These sets lead to the generation of many nanotechnology-based pharmaceuticals for the treatment of various diseases.

  8. The role of thyroid hormones in regulating of fatty acid spectrum of brain lipids: ontogenetic aspect

    Directory of Open Access Journals (Sweden)

    Rodynskiy A.G.

    2016-05-01

    Full Text Available In experiments on rats of three age groups the role of thyroid hormones in the regulation of fatty acid spectrum of cortical and hippocampus lipids was studied. It was found that on the background of decreased thyroid status content of polyunsaturated fractions of free fatty acids, significantly changed depending on the age of the animals. In particular, in juvenile rats hypothyroidism was accompanied by a decrease almost twice the number of pentacodan acid decreased lipids viscosity in neurocortex. In old rats reduce of pentacodan acid in the cortex (38% was supplemented by significant (77% decrease in linoleic and linolenic acids. Unlike the two age groups deficiency of thyroid hormones in young animals caused accumulation of free polyunsatarated fatty acids (C18: 2.3 in the cerebral cortex by 74%, which may be associated with a decrease of this fraction in fatty acid spectrum of lipids and increase of viscosity properties of the membranes. These restruc­turing may be associated with modulation of synaptic transmission of specific neurotransmitter systems in the brain.

  9. Gibberellic acid and cGMP-dependent transcriptional regulation in arabidopsis thaliana

    KAUST Repository

    Bastian, René

    2010-03-01

    An ever increasing amount of transcriptomic data and analysis tools provide novel insight into complex responses of biological systems. Given these resources we have undertaken to review aspects of transcriptional regulation in response to the plant hormone gibberellic acid (GA) and its second messenger guanosine 3\\',5\\'-cyclic monophosphate (cGMP) in Arabidopsis thaliana, both wild type and selected mutants. Evidence suggests enrichment of GA-responsive (GARE) elements in promoters of genes that are transcriptionally upregulated in response to cGMP but downregulated in a GA insensitive mutant (ga1-3). In contrast, in the genes upregulated in the mutant, no enrichment in the GARE is observed suggesting that GARE motifs are diagnostic for GA-induced and cGMP-dependent transcriptional upregulation. Further, we review how expression studies of GA-dependent transcription factors and transcriptional networks based on common promoter signatures derived from ab initio analyses can contribute to our understanding of plant responses at the systems level. © 2010 Landes Bioscience.

  10. Strong Relationships in Acid-Base Chemistry - Modeling Protons Based on Predictable Concentrations of Strong Ions, Total Weak Acid Concentrations, and pCO2

    DEFF Research Database (Denmark)

    Ring, Troels; Kellum, John A

    2016-01-01

    confirmed the relationship between charged species we then examine some of the classical and recent literature concerning the importance of charge balance. We conclude that focusing on the charges which are predictable such as strong ions and total concentrations of weak acids leads to new insights......Understanding acid-base regulation is often reduced to pigeonholing clinical states into categories of disorders based on arterial blood sampling. An earlier ambition to quantitatively explain disorders by measuring production and elimination of acid has not become standard clinical practice....... Seeking back to classical physical chemistry we propose that in any compartment, the requirement of electroneutrality leads to a strong relationship between charged moieties. This relationship is derived in the form of a general equation stating charge balance, making it possible to calculate [H+] and p...

  11. Co-expression Analysis Identifies CRC and AP1 the Regulator of Arabidopsis Fatty Acid Biosynthesis

    Institute of Scientific and Technical Information of China (English)

    Xinxin Han; Linlin Yin; Hongwei Xue

    2012-01-01

    Fatty acids (FAs) play crucial rules in signal transduction and plant development,however,the regulation of FA metabolism is still poorly understood.To study the relevant regulatory network,fifty-eight FA biosynthesis genes including de novo synthases,desaturases and elongases were selected as "guide genes" to construct the co-expression network.Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT)identifies 797 candidate FA-correlated genes.Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism,and function in many processes.Interestingly,63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched.Two TF genes,CRC and AP1,both correlating with 8 FA guide genes,were further characterized.Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds.The contents of palmitoleic acid,stearic acid,arachidic acid and eicosadienoic acid are decreased,whereas that of oleic acid is increased in ap1 and crc seeds,which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes.In addition,yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15,indicating that CRC may directly regulate FA biosynthesis.

  12. Jasmonic acid interacts with abscisic acid to regulate plant responses to water stress conditions

    Science.gov (United States)

    de Ollas, Carlos; Arbona, Vicent; Gómez-Cadenas, Aurelio

    2015-01-01

    Phytohormones are key players in signaling environmental stress conditions. Hormone profiling together with proline accumulation were studied in leaves and roots of different mutant lines of Arabidopsis. Regulation of proline accumulation in this system seems complex and JA-deficient (jar1-1) and JA-insensitive (jai1) lines accumulating high levels of proline despite their very low ABA levels seems to discard an ABA-dependent response. However, the pattern of proline accumulation in jai1 seedlings parallels that of ABA. Under stress conditions, there is an opposite pattern of ABA accumulation in roots of jar1-1/coi1-16 (in which ABA only slightly increase) and jai1 (in which ABA increase is even higher than in WT plants). This also makes JA-ABA crosstalk complex and discards any lineal pathway that could explain this hormonal interaction. PMID:26340066

  13. How Should Risk-Based Regulation Reflect Current Public Opinion?

    Science.gov (United States)

    Pollock, Christopher John

    2016-08-01

    Risk-based regulation of novel agricultural products with public choice manifest via traceability and labelling is a more effective approach than the use of regulatory processes to reflect public concerns, which may not always be supported by evidence.

  14. Structural evolution of differential amino acid effector regulation in plant chorismate mutases.

    Science.gov (United States)

    Westfall, Corey S; Xu, Ang; Jez, Joseph M

    2014-10-10

    Chorismate mutase converts chorismate into prephenate for aromatic amino acid biosynthesis. To understand the molecular basis of allosteric regulation in the plant chorismate mutases, we analyzed the three Arabidopsis thaliana chorismate mutase isoforms (AtCM1-3) and determined the x-ray crystal structures of AtCM1 in complex with phenylalanine and tyrosine. Functional analyses show a wider range of effector control in the Arabidopsis chorismate mutases than previously reported. AtCM1 is activated by tryptophan with phenylalanine and tyrosine acting as negative effectors; however, tryptophan, cysteine, and histidine activate AtCM3. AtCM2 is a nonallosteric form. The crystal structure of AtCM1 in complex with tyrosine and phenylalanine identifies differences in the effector sites of the allosterically regulated yeast enzyme and the other two Arabidopsis isoforms. Site-directed mutagenesis of residues in the effector site reveals key features leading to differential effector regulation in these enzymes. In AtCM1, mutations of Gly-213 abolish allosteric regulation, as observed in AtCM2. A second effector site position, Gly-149 in AtCM1 and Asp-132 in AtCM3, controls amino acid effector specificity in AtCM1 and AtCM3. Comparisons of chorismate mutases from multiple plants suggest that subtle differences in the effector site are conserved in different lineages and may lead to specialized regulation of this branch point enzyme.

  15. Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats.

    Science.gov (United States)

    Zhang, Min; Xie, Zongkai; Gao, Weina; Pu, Lingling; Wei, Jingyu; Guo, Changjiang

    2016-03-01

    Quercetin, a common member of the flavonoid family, is widely present in plant kingdom. Despite that quercetin is implicated in regulating cholesterol metabolism, the molecular mechanism is poorly understood. We hypothesized that quercetin regulates cholesterol homeostasis through regulating the key enzymes involved in hepatic cholesterol metabolism. To test this hypothesis, we compared the profile of key enzymes and transcription factors involved in the hepatic cholesterol metabolism in rats with or without quercetin supplementation. Twenty male Wistar rats were randomly divided into control and quercetin-supplemented groups. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids in feces and bile were measured. Hepatic enzymatic activities were determined by activity assay kit and high-performance liquid chromatography-based analyses. The messenger RNA (mRNA) and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. The results showed that the activity of hepatic cholesterol 7α-hydroxylase, a critical enzyme in the conversion of cholesterol to bile acids, was significantly elevated by quercetin. The expression of cholesterol 7α-hydroxylase, as well as liver X receptor α, an important transcription factor, was also increased at both mRNA and protein levels by quercetin. However, quercetin exposure had no impact on the activity of hepatic HMG-CoA reductase, a rate-limiting enzyme in the biosynthesis of cholesterol. We also found that quercetin treatment significantly increased ATP binding cassette transporter G1 mRNA and protein expression in the liver, suggesting that quercetin may increase hepatic cholesterol efflux. Collectively, the results presented here indicate that quercetin regulates hepatic cholesterol metabolism mainly through the pathways that promote cholesterol-to-bile acid conversion and

  16. General base-general acid catalysis by terpenoid cyclases.

    Science.gov (United States)

    Pemberton, Travis A; Christianson, David W

    2016-07-01

    Terpenoid cyclases catalyze the most complex reactions in biology, in that more than half of the substrate carbon atoms often undergo changes in bonding during the course of a multistep cyclization cascade that proceeds through multiple carbocation intermediates. Many cyclization mechanisms require stereospecific deprotonation and reprotonation steps, and most cyclization cascades are terminated by deprotonation to yield an olefin product. The first bacterial terpenoid cyclase to yield a crystal structure was pentalenene synthase from Streptomyces exfoliatus UC5319. This cyclase generates the hydrocarbon precursor of the pentalenolactone family of antibiotics. The structures of pentalenene synthase and other terpenoid cyclases reveal predominantly nonpolar active sites typically lacking amino acid side chains capable of serving general base-general acid functions. What chemical species, then, enables the Brønsted acid-base chemistry required in the catalytic mechanisms of these enzymes? The most likely candidate for such general base-general acid chemistry is the co-product inorganic pyrophosphate. Here, we briefly review biological and nonbiological systems in which phosphate and its derivatives serve general base and general acid functions in catalysis. These examples highlight the fact that the Brønsted acid-base activities of phosphate derivatives are comparable to the Brønsted acid-base activities of amino acid side chains.

  17. Regulation of intestinal IgA responses by dietary palmitic acid and its metabolism.

    Science.gov (United States)

    Kunisawa, Jun; Hashimoto, Eri; Inoue, Asuka; Nagasawa, Risa; Suzuki, Yuji; Ishikawa, Izumi; Shikata, Shiori; Arita, Makoto; Aoki, Junken; Kiyono, Hiroshi

    2014-08-15

    Enhancement of intestinal IgA responses is a primary strategy in the development of oral vaccine. Dietary fatty acids are known to regulate host immune responses. In this study, we show that dietary palmitic acid (PA) and its metabolites enhance intestinal IgA responses. Intestinal IgA production was increased in mice maintained on a PA-enriched diet. These mice also showed increased intestinal IgA responses against orally immunized Ag, without any effect on serum Ab responses. We found that PA directly stimulates plasma cells to produce Ab. In addition, mice receiving a PA-enriched diet had increased numbers of IgA-producing plasma cells in the large intestine; this effect was abolished when serine palmitoyltransferase was inhibited. These findings suggest that dietary PA regulates intestinal IgA responses and has the potential to be a diet-derived mucosal adjuvant.

  18. Antiepileptic Potential of Matrine via Regulation the Levels of Gamma-Aminobutyric Acid and Glutamic Acid in the Brain

    Directory of Open Access Journals (Sweden)

    Jun Xiang

    2013-12-01

    Full Text Available Our present study aimed to determine the antiepileptic activity of matrine, and explore the possible molecular mechanism. To evaluate the antiepileptic activity of matrine, seizures in mice induced by PTZ and MES were established, then the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests in mice were also carried out. For the molecular mechanism investigations, contents of aspartic acid (Asp, gamma-aminobutyric acid (GABA, glutamic acid (Glu, glycine (Gly in seizures mice were determined; then, the chronic seizures rats induced by PTZ were prepared, and western blotting was used to determine the expressions of GAD 65, GABAA and GABAB in the brains. In the results, matrine showed significant antiepileptic effects on seizures mice induced by MES and PTZ. Moreover, the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests were also demonstrated that matrine had obvious antiepileptic effects. Additionally, our results revealed that after treatment with matrine, contents of GABA can be elevated, and the contents of Glu were obviously decreased. Furthermore, western blotting revealed that the mechanism regarding the antiepileptic effect of may be related to the up-regulations of GAD 65 and GABAA in the brain. Collectively, we suggested that matrine can be developed as an effective antiseptic drug.

  19. Antiepileptic potential of matrine via regulation the levels of gamma-aminobutyric acid and glutamic acid in the brain.

    Science.gov (United States)

    Xiang, Jun; Jiang, Yugang

    2013-12-05

    Our present study aimed to determine the antiepileptic activity of matrine, and explore the possible molecular mechanism. To evaluate the antiepileptic activity of matrine, seizures in mice induced by PTZ and MES were established, then the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests in mice were also carried out. For the molecular mechanism investigations, contents of aspartic acid (Asp), gamma-aminobutyric acid (GABA), glutamic acid (Glu), glycine (Gly) in seizures mice were determined; then, the chronic seizures rats induced by PTZ were prepared, and western blotting was used to determine the expressions of GAD 65, GABAA and GABAB in the brains. In the results, matrine showed significant antiepileptic effects on seizures mice induced by MES and PTZ. Moreover, the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests were also demonstrated that matrine had obvious antiepileptic effects. Additionally, our results revealed that after treatment with matrine, contents of GABA can be elevated, and the contents of Glu were obviously decreased. Furthermore, western blotting revealed that the mechanism regarding the antiepileptic effect of may be related to the up-regulations of GAD 65 and GABAA in the brain. Collectively, we suggested that matrine can be developed as an effective antiseptic drug.

  20. A locked nucleic Acid-based nanocrawler

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Pasternak, Karol; Campbell, Meghan A;

    2013-01-01

    Herein we introduce a novel fluorescent LNA/DNA machine, a nanocrawler, which reversibly moves along a directionally polar complementary road controlled by affinity-enhancing locked nucleic acid (LNA) monomers and additional regulatory strands. Polyaromatic hydrocarbon (PAH) dyes attached to 2...

  1. Carbon-based strong solid acid for cornstarch hydrolysis

    Science.gov (United States)

    Nata, Iryanti Fatyasari; Irawan, Chairul; Mardina, Primata; Lee, Cheng-Kang

    2015-10-01

    Highly sulfonated carbonaceous spheres with diameter of 100-500 nm can be generated by hydrothermal carbonization of glucose in the presence of hydroxyethylsulfonic acid and acrylic acid at 180 °C for 4 h. The acidity of the prepared carbonaceous sphere C4-SO3H can reach 2.10 mmol/g. It was used as a solid acid catalyst for the hydrolysis of cornstarch. Total reducing sugar (TRS) concentration of 19.91 mg/mL could be obtained by hydrolyzing 20 mg/mL cornstarch at 150 °C for 6 h using C4-SO3H as solid acid catalyst. The solid acid catalyst demonstrated good stability that only 9% decrease in TRS concentration was observed after five repeat uses. The as-prepared carbon-based solid acid catalyst can be an environmentally benign replacement for homogeneous catalyst.

  2. Human Gastric Epithelial Cells Contribute to Gastric Immune Regulation by Providing Retinoic Acid to Dendritic Cells

    OpenAIRE

    Bimczok, Diane; John Y. Kao; Zhang, Min; Cochrun, Steven; Mannon, Peter; Peter, Shajan; Wilcox, Charles M.; Mönkemüller, Klaus E; Harris, Paul R.; Grams, Jayleen M.; Stahl, Richard D.; Smith, Phillip D.; Smythies, Lesley E.

    2014-01-01

    Despite the high prevalence of chronic gastritis caused by H. pylori, the gastric mucosa has received little investigative attention as a unique immune environment. Here, we analyzed whether retinoic acid (RA), an important homeostatic factor in the small intestinal mucosa, also contributes to gastric immune regulation. We report that human gastric tissue contains high levels of the RA precursor molecule, retinol, and that gastric epithelial cells express both RA biosynthesis genes and RA res...

  3. Paper-based electroanalytical devices for in situ determination of salicylic acid in living tomato leaves.

    Science.gov (United States)

    Sun, Li-Jun; Feng, Qiu-Mei; Yan, Yong-Feng; Pan, Zhong-Qin; Li, Xiao-Hui; Song, Feng-Ming; Yang, Haibing; Xu, Jing-Juan; Bao, Ning; Gu, Hai-Ying

    2014-10-15

    Detection of phytohormones in situ has gained significant attention due to their critical roles in regulating developmental processes and signaling for defenses in plants at low concentration. As one type of plant hormones, salicylic acid has recently been found to be one of pivotal signal molecules for physiological behaviors of plants. Here we report the application of paper-based electroanalytical devices for sensitively in situ detection of salicylic acid in tomato leaves with the sample volume of several microliters. Specifically, disposable working electrodes were fabricated by coating carbon tape with the mixture of multiwall carbon nanotubes and nafion. We observed that the treatment of the modified carbon tape electrodes with oxygen plasma could significantly improve electrochemical responses of salicylic acid. The tomato leaves had a punched hole of 1.5mm diameter to release salicylic acid with minor influence on continuous growth of tomatoes. By incorporating the tomato leaf with the paper-based analytical device, we were able to perform in situ determination of salicylic acid based on its electrocatalytic oxidation. Our experimental results demonstrated that the amounts of salicylic acid differed statistically in normal, phytoene desaturase (PDS) gene silent and diseased (infected by Botrytis cinerea) tomato leaves. By quantifying salicylic acid at the level of several nanograms in situ, the simple paper-based electroanalytical devices could potentially facilitate the study of defense mechanism of plants under biotic and abiotic stresses. This study might also provide a sensitive method with spatiotemporal resolution for mapping of chemicals released from living organisms.

  4. Reactive Distillation for Esterification of Bio-based Organic Acids

    Energy Technology Data Exchange (ETDEWEB)

    Fields, Nathan; Miller, Dennis J.; Asthana, Navinchandra S.; Kolah, Aspi K.; Vu, Dung; Lira, Carl T.

    2008-09-23

    The following is the final report of the three year research program to convert organic acids to their ethyl esters using reactive distillation. This report details the complete technical activities of research completed at Michigan State University for the period of October 1, 2003 to September 30, 2006, covering both reactive distillation research and development and the underlying thermodynamic and kinetic data required for successful and rigorous design of reactive distillation esterification processes. Specifically, this project has led to the development of economical, technically viable processes for ethyl lactate, triethyl citrate and diethyl succinate production, and on a larger scale has added to the overall body of knowledge on applying fermentation based organic acids as platform chemicals in the emerging biorefinery. Organic acid esters constitute an attractive class of biorenewable chemicals that are made from corn or other renewable biomass carbohydrate feedstocks and replace analogous petroleum-based compounds, thus lessening U.S. dependence on foreign petroleum and enhancing overall biorefinery viability through production of value-added chemicals in parallel with biofuels production. Further, many of these ester products are candidates for fuel (particularly biodiesel) components, and thus will serve dual roles as both industrial chemicals and fuel enhancers in the emerging bioeconomy. The technical report from MSU is organized around the ethyl esters of four important biorenewables-based acids: lactic acid, citric acid, succinic acid, and propionic acid. Literature background on esterification and reactive distillation has been provided in Section One. Work on lactic acid is covered in Sections Two through Five, citric acid esterification in Sections Six and Seven, succinic acid in Section Eight, and propionic acid in Section Nine. Section Ten covers modeling of ester and organic acid vapor pressure properties using the SPEAD (Step Potential

  5. Effect of benzoic acid supplementation on acid-base status and mineralmetabolism in catheterized growing pigs

    DEFF Research Database (Denmark)

    Nørgaard, Jan Værum; Fernández, José Adalberto; Sørensen, Kristina Ulrich;

    2010-01-01

    Benzoic acid (BA) in diets for growing pigs results in urinary acidification and reduced ammonia emission. The objective was to study the impact of BA supplementation on the acid-base status and mineral metabolism in pigs. Eight female 50-kg pigs, fitted with a catheter in the abdominal aorta, were...

  6. Facile syntheses of dissymmetric ferrocene-functionalized Lewis acids and acid-base pairs.

    Science.gov (United States)

    Morgan, Ian R; Di Paolo, Angela; Vidovic, Dragoslav; Fallis, Ian A; Aldridge, Simon

    2009-12-21

    A facile synthetic approach is reported for the synthesis of dissymmetric 1,2-ferrocenediyl Lewis acids and mixed acid-base pairs including the first example of a 1-phosphino-2-borylferrocene; the use of non-racemic electrophiles allows for the isolation of single diastereomer products.

  7. High and low molecular weight hyaluronic acid differentially regulate human fibrocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Anu S Maharjan

    Full Text Available BACKGROUND: Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×10(6 Da. During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8-8×10(5 Da. METHODS AND FINDINGS: In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4, or interleukin-13 (IL-13 to promote fibrocyte differentiation. CONCLUSIONS: We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13.

  8. Carbon-based strong solid acid for cornstarch hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Nata, Iryanti Fatyasari, E-mail: yanti_tkunlam@yahoo.com [Chemical Engineering Study Program, Faculty of Engineering, Lambung Mangkurat University, Jl. A. Yani Km. 36 Banjarbaru, South Kalimantan 70714 (Indonesia); Irawan, Chairul; Mardina, Primata [Chemical Engineering Study Program, Faculty of Engineering, Lambung Mangkurat University, Jl. A. Yani Km. 36 Banjarbaru, South Kalimantan 70714 (Indonesia); Lee, Cheng-Kang, E-mail: cklee@mail.ntust.edu.tw [Department of Chemical Engineering, National Taiwan University of Science and Technology, 43 Keelung Rd. Sec.4, Taipei 106, Taiwan (China)

    2015-10-15

    Highly sulfonated carbonaceous spheres with diameter of 100–500 nm can be generated by hydrothermal carbonization of glucose in the presence of hydroxyethylsulfonic acid and acrylic acid at 180 °C for 4 h. The acidity of the prepared carbonaceous sphere C4-SO{sub 3}H can reach 2.10 mmol/g. It was used as a solid acid catalyst for the hydrolysis of cornstarch. Total reducing sugar (TRS) concentration of 19.91 mg/mL could be obtained by hydrolyzing 20 mg/mL cornstarch at 150 °C for 6 h using C4-SO{sub 3}H as solid acid catalyst. The solid acid catalyst demonstrated good stability that only 9% decrease in TRS concentration was observed after five repeat uses. The as-prepared carbon-based solid acid catalyst can be an environmentally benign replacement for homogeneous catalyst. - Highlights: • Carbon solid acid was successfully prepared by one-step hydrothermal carbonization. • The acrylic acid as monomer was effectively reduce the diameter size of particle. • The solid acid catalyst show good catalytic performance of starch hydrolysis. • The solid acid catalyst is not significantly deteriorated after repeated use.

  9. Complementing the sugar code: role of GAGs and sialic acid in complement regulation

    Directory of Open Access Journals (Sweden)

    Alex eLangford-Smith

    2015-02-01

    Full Text Available Sugar molecules play a vital role on both microbial and mammalian cells, where they are involved in cellular communication, govern microbial virulence and modulate host immunity and inflammatory responses. The complement cascade, as part of a host’s innate immune system, is a potent weapon against invading bacteria but has to be tightly regulated to prevent inappropriate attack and damage to host tissues. A number of complement regulators, such as factor H and properdin, interact with sugar molecules, such as glycosaminoglycans and sialic acid, on host and pathogen membranes and direct the appropriate complement response by either promoting the binding of complement activators or inhibitors. The binding of these complement regulators to sugar molecules can vary from location to location, due to their different specificities and because distinct structural and functional subpopulations of sugars are found in different human organs, such as the brain, kidney and eye. This review will cover recent studies that have provided important new insights into the role of glycosaminoglycans and sialic acid in complement regulation and how sugar recognition may be compromised in disease

  10. Bile acids in regulation of inflammation and immunity: friend or foe?

    Science.gov (United States)

    Zhu, Ci; Fuchs, Claudia D; Halilbasic, Emina; Trauner, Michael

    2016-01-01

    Apart from their pivotal role in dietary lipid absorption and cholesterol homeostasis, bile acids (BAs) are increasingly recognised as important signalling molecules in the regulation of systemic endocrine functions. As such BAs are natural ligands for several nuclear hormone receptors and G-protein-coupled receptors. Through activating various signalling pathways, BAs not only regulate their own synthesis, enterohepatic recirculation and metabolism, but also immune homeostasis. This makes BAs attractive therapeutic agents for managing metabolic and inflammatory liver disorders. Recent experimental and clinical evidence indicates that BAs exert beneficial effects in cholestatic and metabolically driven inflammatory diseases. This review elucidates how different BAs function as pathogenetic factors and potential therapeutic agents for inflammation-driven liver diseases, focusing on their role in regulation of inflammation and immunity.

  11. Dietary Gut Microbial Metabolites, Short-chain Fatty Acids, and Host Metabolic Regulation

    Directory of Open Access Journals (Sweden)

    Mayu Kasubuchi

    2015-04-01

    Full Text Available During feeding, the gut microbiota contributes to the host energy acquisition and metabolic regulation thereby influencing the development of metabolic disorders such as obesity and diabetes. Short-chain fatty acids (SCFAs such as acetate, butyrate, and propionate, which are produced by gut microbial fermentation of dietary fiber, are recognized as essential host energy sources and act as signal transduction molecules via G-protein coupled receptors (FFAR2, FFAR3, OLFR78, GPR109A and as epigenetic regulators of gene expression by the inhibition of histone deacetylase (HDAC. Recent evidence suggests that dietary fiber and the gut microbial-derived SCFAs exert multiple beneficial effects on the host energy metabolism not only by improving the intestinal environment, but also by directly affecting various host peripheral tissues. In this review, we summarize the roles of gut microbial SCFAs in the host energy regulation and present an overview of the current understanding of its physiological functions.

  12. Teaching acid/base physiology in the laboratory

    DEFF Research Database (Denmark)

    Friis, Ulla G; Plovsing, Ronni; Hansen, Klaus;

    2010-01-01

    Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory...... exercise in acid/base physiology that would provide students with unambiguous and reproducible data that clearly would illustrate the theory in practice. The laboratory exercise was developed to include both metabolic acidosis and respiratory alkalosis. Data were collected from 56 groups of medical...

  13. The secretion of organic acids is also regulated by factors other than aluminum.

    Science.gov (United States)

    Ding, Haiyan; Wen, Danni; Fu, Zhengwei; Qian, Haifeng

    2014-02-01

    As a result of natural processes and human activities, aluminum (Al) toxicity is recognized as a major limiting factor for plant productivity, and the secretion of organic acids facilitated by channel proteins is one of the most important Al resistance mechanisms in plants. The objective of this study was to evaluate the effects of several types of stress, including herbicide (imazethapyr (IM) and diclofop-methyl (DM)), heavy metal (Al and Cu), salt stress (NaCl), and proton stress (HCl), on the release of organic acids in rice. The results showed that 0.05 mg/L IM, 0.1 mg/L DM, 4680 mg/L NaCl, 0.5 mg/L CuSO4, and 18 mg/L AlCl3 significantly inhibited rice root elongation and the root fresh weight. In contrast, no significant inhibitory effects on rice growth were found with HCl (pH = 4.5). Similar to the effect of AlCl3 on organic acid induction, treatment with IM, DM, NaCl, and CuSO4 also induced the synthesis of endogenous citric acid and oxalic acid but decreased endogenous malic acid synthesis in the seedlings, though only citric acid was released into the environment after these treatments. We also analyzed the transcripts of three citrate channel proteins and found they were up-regulated by NaCl, CuSO4, and AlCl3 but not by IM or DM. This study clarified that organic acid secretion in plants might be a common phenomenon when plants are exposed to environmental stress other than Al toxicity.

  14. Abscisic Acid, High-Light, and Oxidative Stress Down-Regulate a Photosynthetic Gene via a Promoter Motif Not Involved in Phytochrome-Mediated Transcriptional Regulation

    Institute of Scientific and Technical Information of China (English)

    Roberto J. Staneloni; María José Rodriguez-Batiller; Jorge J. Casal

    2008-01-01

    In etiolated seedlings, light perceived by phytochrome promotes the expression of light-harvesting chlorophyll a/b protein of photosystem Ⅱ (Lhcb) genes. However, excess of photosynthetically active radiation can reduce Lhcb expression. Here, we investigate the convergence and divergence of phytochrome, high-light stress and abscisic acid (ABA)signaling, which could connect these processes. Etiolated Arabidopsis thaliana seedlings bearing an Lhcb promoter fused to a reporter were exposed to continuous far-red light to activate phytochrome and not photosynthesis, and treated with ABA. We identified a cis-acting region of the promoter required for down-regulation by ABA. This region contains a CCAC sequence recently found to be necessary for ABI4-binding to an Lhcb promoter. However, we did not find a G-box-binding core motif often associated with the ABI4-binding site in genes promoted by light and repressed by ABI4. Mutations involving this motif also impaired the responses to reduced water potential, the response to high photosynthetic light and the response to methyl viologen but not the response to low temperature or to Norflurazon. We propose a model based on current and previous findings, in which hydrogen peroxide produced in the chloroplasts under high light conditions interacts with the ABA signaling network to regulate Lhcb expression. Since the mutation that affects high-light and methyl viologen responses does not affect phytochrome-mediated responses, the regulation by retrograde and phytochrome signaling can finally be separated at the target promoter level.

  15. Environmentally Benign Bifunctional Solid Acid and Base Catalysts

    NARCIS (Netherlands)

    Elmekawy, A.; Shiju, N.R.; Rothenberg, G.; Brown, D.R.

    2014-01-01

    Solid bifunctional acid-​base catalysts were prepd. in two ways on an amorphous silica support: (1) by grafting mercaptopropyl units (followed by oxidn. to propylsulfonic acid) and aminopropyl groups to the silica surface (NH2-​SiO2-​SO3H)​, and (2) by grafting only aminopropyl groups and then parti

  16. Nutritional and Hormonal Regulation of Citrate and Carnitine/Acylcarnitine Transporters: Two Mitochondrial Carriers Involved in Fatty Acid Metabolism

    Directory of Open Access Journals (Sweden)

    Anna M. Giudetti

    2016-05-01

    Full Text Available The transport of solutes across the inner mitochondrial membrane is catalyzed by a family of nuclear-encoded membrane-embedded proteins called mitochondrial carriers (MCs. The citrate carrier (CiC and the carnitine/acylcarnitine transporter (CACT are two members of the MCs family involved in fatty acid metabolism. By conveying acetyl-coenzyme A, in the form of citrate, from the mitochondria to the cytosol, CiC contributes to fatty acid and cholesterol synthesis; CACT allows fatty acid oxidation, transporting cytosolic fatty acids, in the form of acylcarnitines, into the mitochondrial matrix. Fatty acid synthesis and oxidation are inversely regulated so that when fatty acid synthesis is activated, the catabolism of fatty acids is turned-off. Malonyl-CoA, produced by acetyl-coenzyme A carboxylase, a key enzyme of cytosolic fatty acid synthesis, represents a regulator of both metabolic pathways. CiC and CACT activity and expression are regulated by different nutritional and hormonal conditions. Defects in the corresponding genes have been directly linked to various human diseases. This review will assess the current understanding of CiC and CACT regulation; underlining their roles in physio-pathological conditions. Emphasis will be placed on the molecular basis of the regulation of CiC and CACT associated with fatty acid metabolism.

  17. NIRS-based noninvasive cerebrovascular regulation assessment

    Science.gov (United States)

    Miller, S.; Richmond, I.; Borgos, J.; Mitra, K.

    2016-03-01

    Alterations to cerebral blood flow (CBF) have been implicated in diverse neurological conditions, including mild traumatic brain injury, microgravity induced intracranial pressure (ICP) increases, mild cognitive impairment, and Alzheimer's disease. Near infrared spectroscopy (NIRS)-measured regional cerebral tissue oxygen saturation (rSO2) provides an estimate of oxygenation of the interrogated cerebral volume that is useful in identifying trends and changes in oxygen supply to cerebral tissue and has been used to monitor cerebrovascular function during surgery and ventilation. In this study, CO2-inhalation-based hypercapnic breathing challenges were used as a tool to simulate CBF dysregulation, and NIRS was used to monitor the CBF autoregulatory response. A breathing circuit for the selective administration of CO2-compressed air mixtures was designed and used to assess CBF regulatory responses to hypercapnia in 26 healthy young adults using non-invasive methods and real-time sensors. After a 5 or 10 minute baseline period, 1 to 3 hypercapnic challenges of 5 or 10 minutes duration were delivered to each subject while rSO2, partial pressure of end tidal CO2 (PETCO2), and vital signs were continuously monitored. Change in rSO2 measurements from pre- to intrachallenge (ΔrSO2) detected periods of hypercapnic challenges. Subjects were grouped into three exercise factor levels (hr/wk), 1: 0, 2:>0 and 10. Exercise factor level 3 subjects showed significantly greater ΔrSO2 responses to CO2 challenges than level 2 and 1 subjects. No significant difference in ΔPETCO2 existed between these factor levels. Establishing baseline values of rSO2 in clinical practice may be useful in early detection of CBF changes.

  18. ABI4 regulates primary seed dormancy by regulating the biogenesis of abscisic acid and gibberellins in arabidopsis.

    Science.gov (United States)

    Shu, Kai; Zhang, Huawei; Wang, Shengfu; Chen, Mingluan; Wu, Yaorong; Tang, Sanyuan; Liu, Chunyan; Feng, Yuqi; Cao, Xiaofeng; Xie, Qi

    2013-06-01

    Seed dormancy is an important economic trait for agricultural production. Abscisic acid (ABA) and Gibberellins (GA) are the primary factors that regulate the transition from dormancy to germination, and they regulate this process antagonistically. The detailed regulatory mechanism involving crosstalk between ABA and GA, which underlies seed dormancy, requires further elucidation. Here, we report that ABI4 positively regulates primary seed dormancy, while negatively regulating cotyledon greening, by mediating the biogenesis of ABA and GA. Seeds of the Arabidopsis abi4 mutant that were subjected to short-term storage (one or two weeks) germinated significantly more quickly than Wild-Type (WT), and abi4 cotyledons greened markedly more quickly than WT, while the rates of germination and greening were comparable when the seeds were subjected to longer-term storage (six months). The ABA content of dry abi4 seeds was remarkably lower than that of WT, but the amounts were comparable after stratification. Consistently, the GA level of abi4 seeds was increased compared to WT. Further analysis showed that abi4 was resistant to treatment with paclobutrazol (PAC), a GA biosynthesis inhibitor, during germination, while OE-ABI4 was sensitive to PAC, and exogenous GA rescued the delayed germination phenotype of OE-ABI4. Analysis by qRT-PCR showed that the expression of genes involved in ABA and GA metabolism in dry and germinating seeds corresponded to hormonal measurements. Moreover, chromatin immunoprecipitation qPCR (ChIP-qPCR) and transient expression analysis showed that ABI4 repressed CYP707A1 and CYP707A2 expression by directly binding to those promoters, and the ABI4 binding elements are essential for this repression. Accordingly, further genetic analysis showed that abi4 recovered the delayed germination phenotype of cyp707a1 and cyp707a2 and further, rescued the non-germinating phenotype of ga1-t. Taken together, this study suggests that ABI4 is a key factor that

  19. 75 FR 79455 - OPEN GOVERNMENT AND EVIDENCE-BASED REGULATION

    Science.gov (United States)

    2010-12-20

    ... government and evidence- based regulation. If regulatory choices are based on careful analysis of the... emphasis on sound analysis and on ensuring a careful accounting of the anticipated consequences of... burdens and innovative solutions. By promoting accountability, open government policies can help to...

  20. Down-regulation of the Caffeic acid O-methyltransferase Gene in Switchgrass Reveals a Novel Monolignol Analog

    Energy Technology Data Exchange (ETDEWEB)

    Tschaplinski, Timothy J [ORNL; Standaert, Robert F [ORNL; Engle, Nancy L [ORNL; Martin, Madhavi Z [ORNL; Sangha, Amandeep K [ORNL; Parks, Jerry M [ORNL; Smith, Jeremy C [ORNL; Samuel, Reichel [ORNL; Pu, Yunqiao [ORNL; Ragauskas, A J [Georgia Institute of Technology; Hamilton, Choo Yieng [ORNL; Fu, Chunxiang [Noble Foundation; Wang, Zeng-Yu [Noble Foundation; Davison, Brian H [ORNL; Dixon, Richard A [Noble Foundation; Mielenz, Jonathan R [ORNL

    2012-01-01

    Down-regulation of the caffeic acid 3-O-methyltransferase (COMT) gene in the lignin biosynthetic pathway of switchgrass (Panicum virgatum) resulted in cell walls of transgenic plants releasing more constituent sugars after pretreatment by dilute acid and treatment with glycosyl hydrolases from an added enzyme preparation and from Clostridium thermocellum. Fermentation of both wild-type and transgenic switchgrass after milder hot water pretreatment with no water washing showed that only the transgenic switchgrass inhibited C. thermocellum. Gas chromatography-mass spectrometry-based metabolomics were undertaken on cell wall aqueous extracts to determine the nature of the microbial inhibitors, confirming the increased concentration of a number of phenolic acids and aldehydes that are known inhibitors of fermentation. Metabolomic analyses of the transgenic biomass additionally revealed the presence of a novel monolignol-like metabolite, identified as trans-3, 4-dimethoxy-5-hydroxycinnamyl alcohol (iso-sinapyl alcohol) in both non-pretreated, as well as hot water pretreated samples. Although there was no indication that iso-sinapyl alcohol was integrated into the cell wall, diversion of substrates from sinapyl alcohol to free iso-sinapyl alcohol, its glucoside, and associated upstream lignin pathway changes, including increased phenolic aldehydes and acids, are associated with more facile cell wall deconstruction, and to the observed inhibitory effect on microbial growth.

  1. Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration.

    Science.gov (United States)

    Jeong, Jae Young; Hong, Eun-Hye; Lee, Song Yi; Lee, Jae-Young; Song, Jae-Hyoung; Ko, Seung-Hak; Shim, Jae-Seong; Choe, Sunghwa; Kim, Dae-Duk; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2017-02-16

    (3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface

  2. Compassion-based emotion regulation up-regulates experienced positive affect and associated neural networks.

    Science.gov (United States)

    Engen, Haakon G; Singer, Tania

    2015-09-01

    Emotion regulation research has primarily focused on techniques that attenuate or modulate the impact of emotional stimuli. Recent evidence suggests that this mode regulation can be problematic in the context of regulation of emotion elicited by the suffering of others, resulting in reduced emotional connectedness. Here, we investigated the effects of an alternative emotion regulation technique based on the up-regulation of positive affect via Compassion-meditation on experiential and neural affective responses to depictions of individuals in distress, and compared these with the established emotion regulation strategy of Reappraisal. Using fMRI, we scanned 15 expert practitioners of Compassion-meditation either passively viewing, or using Compassion-meditation or Reappraisal to modulate their emotional reactions to film clips depicting people in distress. Both strategies effectively, but differentially regulated experienced affect, with Compassion primarily increasing positive and Reappraisal primarily decreasing negative affect. Imaging results showed that Compassion, relative to both passive-viewing and Reappraisal increased activation in regions involved in affiliation, positive affect and reward processing including ventral striatum and medial orbitfrontal cortex. This network was shown to be active prior to stimulus presentation, suggesting that the regulatory mechanism of Compassion is the stimulus-independent endogenous generation of positive affect.

  3. New Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Inhibitors, Nalidixic Acid Linked to Isatin Schiff Bases via Certain l-Amino Acid Bridges.

    Science.gov (United States)

    Naglah, Ahmed M; Ahmed, Atallah F; Wen, Zhi-Hong; Al-Omar, Mohamed A; Amr, Abd El-Galil E; Kalmouch, Atef

    2016-04-15

    A series of new Schiff bases were synthesized by condensation of isatins with the nalidixic acid-l-amino acid hydrazides. Prior to hydrazide formation, a peptide linkage has been prepared via coupling of nalidixic acid with appropriate l-amino acid methyl esters to yield 3a-c. The chemical structures of the new Schiff bases (5b and 5d-h) were confirmed by means of IR, NMR, mass spectroscopic, and elemental analyses. The anti-inflammatory activity of these Schiff bases was evaluated via measurement of the expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells model. The Schiff bases exhibited significant dual inhibitory effect against the induction of the pro-inflammatory iNOS and COX-2 proteins with variable potencies. However, they strongly down-regulated the iNOS expression to the level of 16.5% ± 7.4%-42.2% ± 19.6% compared to the effect on COX-2 expression (bases, relative to that of COX-2, seems to be a reflection of the combined suppressive effects exerted by their nalidixic acid, isatins (4a-c), and l-amino acid moieties against iNOS expression. These synthesized nalidixic acid-l-amino acid-isatin conjugates can be regarded as a novel class of anti-inflammatory antibacterial agents.

  4. Synthesis and catalytic application of amino acid based dendritic macromolecules

    NARCIS (Netherlands)

    Koten, G. van; Gossage, R.A.; Jastrzebski, J.T.B.H.; Ameijde, J. van; Mulders, S.J.E.; Brouwer, Arwin J.; Liskamp, R.M.J.

    1999-01-01

    The use of amino acid based dendrimers as molecular scaffolds for the attachment of catalytically active organometallic Ni ''pincer'' complexes, via a urea functionality, is described; the dendrimer catalysts have comparable activity to their mononuclear (NCN)NiX analogues.

  5. An Olfactory Indicator for Acid-Base Titrations.

    Science.gov (United States)

    Flair, Mark N.; Setzer, William N.

    1990-01-01

    The use of an olfactory acid-base indicator in titrations for visually impaired students is discussed. Potential olfactory indicators include eugenol, thymol, vanillin, and thiophenol. Titrations performed with each indicator with eugenol proved to be successful. (KR)

  6. Towards lactic acid bacteria-based biorefineries.

    Science.gov (United States)

    Mazzoli, Roberto; Bosco, Francesca; Mizrahi, Itzhak; Bayer, Edward A; Pessione, Enrica

    2014-11-15

    Lactic acid bacteria (LAB) have long been used in industrial applications mainly as starters for food fermentation or as biocontrol agents or as probiotics. However, LAB possess several characteristics that render them among the most promising candidates for use in future biorefineries in converting plant-derived biomass-either from dedicated crops or from municipal/industrial solid wastes-into biofuels and high value-added products. Lactic acid, their main fermentation product, is an attractive building block extensively used by the chemical industry, owing to the potential for production of polylactides as biodegradable and biocompatible plastic alternative to polymers derived from petrochemicals. LA is but one of many high-value compounds which can be produced by LAB fermentation, which also include biofuels such as ethanol and butanol, biodegradable plastic polymers, exopolysaccharides, antimicrobial agents, health-promoting substances and nutraceuticals. Furthermore, several LAB strains have ascertained probiotic properties, and their biomass can be considered a high-value product. The present contribution aims to provide an extensive overview of the main industrial applications of LAB and future perspectives concerning their utilization in biorefineries. Strategies will be described in detail for developing LAB strains with broader substrate metabolic capacity for fermentation of cheaper biomass.

  7. Regulation of polyurethane hemocompatibility and endothelialization by tethered hyaluronic acid oligosaccharides.

    Science.gov (United States)

    Chuang, Tzu-Wen; Masters, Kristyn S

    2009-10-01

    Current synthetic vascular grafts possess a significant mechanical mismatch compared to the native vasculature and do not permit endothelialization; both of these deficiencies contribute to the relatively high rate of failure of many synthetic grafts. In this communication, we report the modification of polyurethane (PU)-based materials to impart hemocompatibility, support endothelial growth, and display vascular-appropriate mechanics. This modification was achieved by incorporating branched polyethylenimine (PEI) into the PU backbone, followed by covalent attachment of either hyaluronic acid (HA; 4.7, 64, and 104 kDa), heparin, or poly(ethylene glycol) (PEG; used as a non-adhesive control) to the PEI. This grafting chemistry resulted in comparatively dense immobilization of HA and heparin (0.062 and 2.3 microg/cm(2), respectively) to the PU-PEI surfaces. PU materials modified with HA were more effective than either PEG- or heparin-grafted materials with respect to limiting protein adsorption and platelet adhesion. Confluent, morphologically-healthy cultures of endothelial cells were achieved only on materials grafted with low molecular weight HA, but not high MW HA, heparin, or PEG. These modifications in PU chemistry were performed while retaining material mechanics in the range of native vascular tissue. Thus, this study describes the generation of materials that possess the unique ability to display excellent hemocompatibility while simultaneously supporting extensive endothelialization and retaining vascular-appropriate mechanics. The bioactivity of these materials was regulated by the molecular weight of the grafted HA, and their physical and biological properties make them promising for use as vascular grafts.

  8. Lysophosphatidic Acid Up-Regulates Hexokinase II and Glycolysis to Promote Proliferation of Ovarian Cancer Cells

    Directory of Open Access Journals (Sweden)

    Abir Mukherjee

    2015-09-01

    Full Text Available Lysophosphatidic acid (LPA, a blood-borne lipid mediator, is present in elevated concentrations in ascites of ovarian cancer patients and other malignant effusions. LPA is a potent mitogen in cancer cells. The mechanism linking LPA signal to cancer cell proliferation is not well understood. Little is known about whether LPA affects glucose metabolism to accommodate rapid proliferation of cancer cells. Here we describe that in ovarian cancer cells, LPA enhances glycolytic rate and lactate efflux. A real time PCR-based miniarray showed that hexokinase II (HK2 was the most dramatically induced glycolytic gene to promote glycolysis in LPA-treated cells. Analysis of the human HK2 gene promoter identified the sterol regulatory element-binding protein as the primary mediator of LPA-induced HK2 transcription. The effects of LPA on HK2 and glycolysis rely on LPA2, an LPA receptor subtype overexpressed in ovarian cancer and many other malignancies. We further examined the general role of growth factor-induced glycolysis in cell proliferation. Like LPA, epidermal growth factor (EGF elicited robust glycolytic and proliferative responses in ovarian cancer cells. Insulin-like growth factor 1 (IGF-1 and insulin, however, potently stimulated cell proliferation but only modestly induced glycolysis. Consistent with their differential effects on glycolysis, LPA and EGF-dependent cell proliferation was highly sensitive to glycolytic inhibition while the growth-promoting effect of IGF-1 or insulin was more resistant. These results indicate that LPA- and EGF-induced cell proliferation selectively involves up-regulation of HK2 and glycolytic metabolism. The work is the first to implicate LPA signaling in promotion of glucose metabolism in cancer cells.

  9. Synthesis and antimicrobial activities of new higher amino acid Schiff base derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid

    Science.gov (United States)

    Özdemir (nee Güngör), Özlem; Gürkan, Perihan; Özçelik, Berrin; Oyardı, Özlem

    2016-02-01

    Novel β-lactam derivatives (1c-3c) (1d-3d) were produced by using 6-aminopenicillanic acid (6-APA), 7-aminocephalosporanic acid (7-ACA) and the higher amino acid Schiff bases. The synthesized compounds were characterized by elemental analysis, IR, 1H/13C NMR and UV-vis spectra. Antibacterial activities of all the higher amino acid Schiff bases (1a-3a) (1b-3b) and β-lactam derivatives were screened against three gram negative bacteria (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii RSKK 02026), three gram positive bacteria (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 07005, Bacillus subtilis ATCC 6633) and their drug-resistant isolates by using broth microdilution method. Two fungi (Candida albicans and Candida krusei) were used for antifungal activity.

  10. Aphid amino acid transporter regulates glutamine supply to intracellular bacterial symbionts.

    Science.gov (United States)

    Price, Daniel R G; Feng, Honglin; Baker, James D; Bavan, Selvan; Luetje, Charles W; Wilson, Alex C C

    2014-01-01

    Endosymbiotic associations have played a major role in evolution. However, the molecular basis for the biochemical interdependence of these associations remains poorly understood. The aphid-Buchnera endosymbiosis provides a powerful system to elucidate how these symbioses are regulated. In aphids, the supply of essential amino acids depends on an ancient nutritional symbiotic association with the gamma-proteobacterium Buchnera aphidicola. Buchnera cells are densely packed in specialized aphid bacteriocyte cells. Here we confirm that five putative amino acid transporters are highly expressed and/or highly enriched in Acyrthosiphon pisum bacteriocyte tissues. When expressed in Xenopus laevis oocytes, two bacteriocyte amino acid transporters displayed significant levels of glutamine uptake, with transporter ACYPI001018, LOC100159667 (named here as Acyrthosiphon pisum glutamine transporter 1, ApGLNT1) functioning as the most active glutamine transporter. Transporter ApGLNT1 has narrow substrate selectivity, with high glutamine and low arginine transport capacity. Notably, ApGLNT1 has high binding affinity for arginine, and arginine acts as a competitive inhibitor for glutamine transport. Using immunocytochemistry, we show that ApGLNT1 is localized predominantly to the bacteriocyte plasma membrane, a location consistent with the transport of glutamine from A. pisum hemolymph to the bacteriocyte cytoplasm. On the basis of functional transport data and localization, we propose a substrate feedback inhibition model in which the accumulation of the essential amino acid arginine in A. pisum hemolymph reduces the transport of the precursor glutamine into bacteriocytes, thereby regulating amino acid biosynthesis in the bacteriocyte. Structural similarities in the arrangement of hosts and symbionts across endosymbiotic systems suggest that substrate feedback inhibition may be mechanistically important in other endosymbioses.

  11. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to calcium and potassium and maintenance of normal acid-base balance (ID 400, 407) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to calcium and potassium and maintenance of normal acid-base balance. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from...... stakeholders. The food constituents that are the subject of the health claims are calcium and potassium. The Panel considers that calcium and potassium are sufficiently characterised. The claimed effects are “calcium contributes to acid/base balance within metabolism” and “mineral/potassium: key function...... within metabolism (intracellular cation)”. The target population is assumed to be the general population. In the context of the proposed wordings, the Panel assumes that the claimed effects refer to the maintenance of normal acid-base balance. The Panel considers that maintenance of normal acid...

  12. Abscisic acid and sucrose regulate tomato and strawberry fruit ripening through the abscisic acid-stress-ripening transcription factor.

    Science.gov (United States)

    Jia, Haifeng; Jiu, Songtao; Zhang, Cheng; Wang, Chen; Tariq, Pervaiz; Liu, Zhongjie; Wang, Baoju; Cui, Liwen; Fang, Jinggui

    2016-10-01

    Although great progress has been made towards understanding the role of abscisic acid (ABA) and sucrose in fruit ripening, the mechanisms underlying the ABA and sucrose signalling pathways remain elusive. In this study, transcription factor ABA-stress-ripening (ASR), which is involved in the transduction of ABA and sucrose signalling pathways, was isolated and analysed in the nonclimacteric fruit, strawberry and the climacteric fruit, tomato. We have identified four ASR isoforms in tomato and one in strawberry. All ASR sequences contained the ABA stress- and ripening-induced proteins and water-deficit stress-induced proteins (ABA/WDS) domain and all ASR transcripts showed increased expression during fruit development. The expression of the ASR gene was influenced not only by sucrose and ABA, but also by jasmonic acid (JA) and indole-3-acetic acid (IAA), and these four factors were correlated with each other during fruit development. ASR bound the hexose transporter (HT) promoter, which contained a sugar box that activated downstream gene expression. Overexpression of the ASR gene promoted fruit softening and ripening, whereas RNA interference delayed fruit ripening, as well as affected fruit physiological changes. Change in ASR gene expression influenced the expression of several ripening-related genes such as CHS, CHI, F3H, DFR, ANS, UFGT, PG, PL, EXP1/2, XET16, Cel1/2 and PME. Taken together, this study may provide new evidence on the important role of ASR in cross-signalling between ABA and sucrose to regulate tomato and strawberry fruit ripening. The findings of this study also provide new insights into the regulatory mechanism underlying fruit development.

  13. Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate mTORC1

    Directory of Open Access Journals (Sweden)

    Liufeng Zheng

    2016-09-01

    Full Text Available The mammalian target of rapamycin (mTOR is the central regulator of mammalian cell growth, and is essential for the formation of two structurally and functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple cues such as nutrients, energy status, growth factors and hormones to control cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of the key environmental stimuli, amino acids (AAs, especially leucine, glutamine and arginine, play a crucial role in mTORC1 activation, but where and how AAs are sensed and signal to mTORC1 are not fully understood. Classically, AAs activate mTORC1 by Rag GTPases which recruit mTORC1 to lysosomes, where AA signaling initiates. Plasma membrane transceptor L amino acid transporter 1 (LAT1-4F2hc has dual transporter-receptor function that can sense extracellular AA availability upstream of mTORC1. The lysosomal AA sensors (PAT1 and SLC38A9 and cytoplasmic AA sensors (LRS, Sestrin2 and CASTOR1 also participate in regulating mTORC1 activation. Importantly, AAs can be sensed by plasma membrane receptors, like G protein-coupled receptor (GPCR T1R1/T1R3, and regulate mTORC1 without being transported into the cells. Furthermore, AA-dependent mTORC1 activation also initiates within Golgi, which is regulated by Golgi-localized AA transporter PAT4. This review provides an overview of the research progress of the AA sensing mechanisms that regulate mTORC1 activity.

  14. Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate mTORC1

    Science.gov (United States)

    Zheng, Liufeng; Zhang, Wei; Zhou, Yuanfei; Li, Fengna; Wei, Hongkui; Peng, Jian

    2016-01-01

    The mammalian target of rapamycin (mTOR) is the central regulator of mammalian cell growth, and is essential for the formation of two structurally and functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple cues such as nutrients, energy status, growth factors and hormones to control cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of the key environmental stimuli, amino acids (AAs), especially leucine, glutamine and arginine, play a crucial role in mTORC1 activation, but where and how AAs are sensed and signal to mTORC1 are not fully understood. Classically, AAs activate mTORC1 by Rag GTPases which recruit mTORC1 to lysosomes, where AA signaling initiates. Plasma membrane transceptor L amino acid transporter 1 (LAT1)-4F2hc has dual transporter-receptor function that can sense extracellular AA availability upstream of mTORC1. The lysosomal AA sensors (PAT1 and SLC38A9) and cytoplasmic AA sensors (LRS, Sestrin2 and CASTOR1) also participate in regulating mTORC1 activation. Importantly, AAs can be sensed by plasma membrane receptors, like G protein-coupled receptor (GPCR) T1R1/T1R3, and regulate mTORC1 without being transported into the cells. Furthermore, AA-dependent mTORC1 activation also initiates within Golgi, which is regulated by Golgi-localized AA transporter PAT4. This review provides an overview of the research progress of the AA sensing mechanisms that regulate mTORC1 activity. PMID:27690010

  15. Action of Plant Growth Regulators. IV. Adsorption of Unsubstituted and 2,6-Dichloro-aromatic Acids to Oat Monolayers

    Science.gov (United States)

    Brian, R. C.

    1967-01-01

    The adsorption of chloro-aromatic acids to monomolecular layers of oat squashes is reported in earlier papers but it was not possible by the technique used, to measure unambiguously the adsorption of unsubstituted and 2,6-dichloro-aromatic acids. This has now been achieved by a modification of the earlier method and involves assessments of competitive adsorption between the unknown acid and a standard acid, using measurements of surface potential. Benzoic and phenoxyacetic acids were not adsorbed but phenylacetic acid was weakly adsorbed. The second ring in naphthalene and naphthoxyacetic acids greatly increased adsorption. Substitution of the 2 and 6 positions in the phenyl and phenoxyacetic acids resulted in low adsorption but 2,6-disubstituted phenoxybutyric and benzoic acids were more highly adsorbed. The adsorption values from earlier work are combined and discussed in relation to the growth-regulating activity of the acids. It is conciuded that there is no direct relation embracing all acids between adsorption and activity, notable exceptions being those substituted by chlorine in the 3-position of the aromatic ring. However, for a number of acids it is suggested that activity is limited not only by their ability to interact at enzyme sites but also by the amount of acid immobilised by adsorption when moving to these sites. It is also concluded that the hydrophilic/lipophilic balance of a growth regulator sometimes used as a guide to its activity, is an unreliable indication of interfacial behaviour. PMID:16656642

  16. Speed limits for acid-base chemistry in aqueous solutions.

    Science.gov (United States)

    Donten, Mateusz L; Vandevondele, Joost; Hamm, Peter

    2012-01-01

    Proton transfer reactions, including acid-base recombination, are commonly considered to occur 'nearly instantaneously'. However, their actual time scales may stretch far into the microsecond range, as acid-base reactions are diffusion controlled and the concentrations are low near neutral pH. The interplay of competing bases in the pH relaxation is illustrated using a model acid-base system consisting of o-nitrobenzaldehyde (oNBA) as a proton cage and acetate ions and hydroxyl ions as bases. The kinetically controlled behavior leads to highly counterintuitive states, i.e. acetate ions are transiently protonated for hundreds of nanoseconds despite the presence of a much stronger base OH-.

  17. Dynamic regulation of glutamic acid decarboxylase 65 gene expression in rat testis

    Institute of Scientific and Technical Information of China (English)

    Haixiong Liu; Shifeng Li; Yunbin Zhang; Yuanchang Yan; Yiping Li

    2009-01-01

    Glutamate decarboxylase 65 (GAD65) produces γ-amino-butyric acid,the main inhibitory neurotransmitter in adult mammalian brain.Previous experiments,per-formed in brain,showed that GAD65 gene possesses two TATA-less promoters,although the significance is unknown.Here,by rapid amplification of cDNA ends method,two distinct GAD65 mRNA isoforms transcribed from two independent clusters of transcription start sites were identified in post-natal rat testis.RT-PCR results revealed that the two mRNA isoforms had distinct expression patterns during post-natal testis maturation,suggesting that GAD65 gene expression was regulated by alternative promoters at the transcription level.By using GAD65-speciflc antibodies,western blotting analysis showed that the 58-kDa GAD65,N-terminal 69 amino acids truncated form of full-length GAD65 protein,was developmentally expressed during post-natal testis matu-ration,suggesting that GAD65 gene expression in testis may also be regulated by post-translational processing.Confocal immunofluorescence microscopy revealed that GAD65 protein was presented in Leydig cells of Day 1 testis,primary spermatocytes and spermatids of post-natal of Day 90 testis.The above results suggested that GAD65 gene expression is dynamically regulated at mul-tiple levels during post-natal testis maturation.

  18. Role of Vitamin A/Retinoic Acid in Regulation of Embryonic and Adult Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Ana Cañete

    2017-02-01

    Full Text Available Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA, acting through nuclear retinoic acid receptors (RARs, is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality. RA signaling appears to be essential for expression of genes involved in developmental hematopoiesis, regulating the endothelial/blood cells balance in the yolk sac, promoting the hemogenic program in the aorta-gonad-mesonephros area and stimulating eryrthropoiesis in fetal liver by activating the expression of erythropoietin. In adults, RA signaling regulates differentiation of granulocytes and enhances erythropoiesis. Vitamin A may facilitate iron absorption and metabolism to prevent anemia and plays a key role in mucosal immune responses, modulating the function of regulatory T cells. Furthermore, defective RA/RARα signaling is involved in the pathogenesis of acute promyelocytic leukemia due to a failure in differentiation of promyelocytes. This review focuses on the different roles played by vitamin A/RA signaling in physiological and pathological mouse hematopoiesis duddurring both, embryonic and adult life, and the consequences of vitamin A deficiency for the blood system.

  19. Retinoic acid receptor regulation of epimorphic and homeostatic regeneration in the axolotl.

    Science.gov (United States)

    Nguyen, Matthew; Singhal, Pankhuri; Piet, Judith W; Shefelbine, Sandra J; Maden, Malcolm; Voss, S Randal; Monaghan, James R

    2017-02-15

    Salamanders are capable of regenerating amputated limbs by generating a mass of lineage-restricted cells called a blastema. Blastemas only generate structures distal to their origin unless treated with retinoic acid (RA), which results in proximodistal (PD) limb duplications. Little is known about the transcriptional network that regulates PD duplication. In this study, we target specific retinoic acid receptors (RARs) to either PD duplicate (RA treatment or RARγ agonist) or truncate (RARβ antagonist) regenerating limbs. RARE-EGFP reporter axolotls showed divergent reporter activity in limbs undergoing PD duplication versus truncation, suggesting differences in patterning and skeletal regeneration. Transcriptomics identified expression patterns that explain PD duplication, including upregulation of proximal homeobox gene expression and silencing of distal-associated genes, whereas limb truncation was associated with disrupted skeletal differentiation. RARβ antagonism in uninjured limbs induced a loss of skeletal integrity leading to long bone regression and loss of skeletal turnover. Overall, mechanisms were identified that regulate the multifaceted roles of RARs in the salamander limb including regulation of skeletal patterning during epimorphic regeneration, skeletal tissue differentiation during regeneration, and homeostatic regeneration of intact limbs.

  20. Role of Vitamin A/Retinoic Acid in Regulation of Embryonic and Adult Hematopoiesis

    Science.gov (United States)

    Cañete, Ana; Cano, Elena; Muñoz-Chápuli, Ramón; Carmona, Rita

    2017-01-01

    Vitamin A is an essential micronutrient throughout life. Its physiologically active metabolite retinoic acid (RA), acting through nuclear retinoic acid receptors (RARs), is a potent regulator of patterning during embryonic development, as well as being necessary for adult tissue homeostasis. Vitamin A deficiency during pregnancy increases risk of maternal night blindness and anemia and may be a cause of congenital malformations. Childhood Vitamin A deficiency can cause xerophthalmia, lower resistance to infection and increased risk of mortality. RA signaling appears to be essential for expression of genes involved in developmental hematopoiesis, regulating the endothelial/blood cells balance in the yolk sac, promoting the hemogenic program in the aorta-gonad-mesonephros area and stimulating eryrthropoiesis in fetal liver by activating the expression of erythropoietin. In adults, RA signaling regulates differentiation of granulocytes and enhances erythropoiesis. Vitamin A may facilitate iron absorption and metabolism to prevent anemia and plays a key role in mucosal immune responses, modulating the function of regulatory T cells. Furthermore, defective RA/RARα signaling is involved in the pathogenesis of acute promyelocytic leukemia due to a failure in differentiation of promyelocytes. This review focuses on the different roles played by vitamin A/RA signaling in physiological and pathological mouse hematopoiesis duddurring both, embryonic and adult life, and the consequences of vitamin A deficiency for the blood system. PMID:28230720

  1. Towards bridging the gap between acid-base transporters and neuronal excitability modulation

    OpenAIRE

    2014-01-01

    pH homeostasis is a fundamental regulator of the function of the central nervous system. Dysfunction of acid-base transporters often results in disturbance of neuronal excitability. In a latest issue of Journal of Neuroscience, Jones et al. report that increasing intracellular bicarbonate concentration substantially stimulates the excitability of pyramidal neurons from mouse hippocampus by inhibiting KCNQ potassium channel. The finding shed important new light in understanding the molecular m...

  2. Acid-base and ion balance in fishes with bimodal respiration.

    Science.gov (United States)

    Shartau, R B; Brauner, C J

    2014-03-01

    The evolution of air breathing during the Devonian provided early fishes with bimodal respiration with a stable O2 supply from air. This was, however, probably associated with challenges and trade-offs in terms of acid-base balance and ionoregulation due to reduced gill:water interaction and changes in gill morphology associated with air breathing. While many aspects of acid-base and ionoregulation in air-breathing fishes are similar to water breathers, the specific cellular and molecular mechanisms involved remain largely unstudied. In general, reduced ionic permeability appears to be an important adaptation in the few bimodal fishes investigated but it is not known if this is a general characteristic. The kidney appears to play an important role in minimizing ion loss to the freshwater environment in the few species investigated, and while ion uptake across the gut is probably important, it has been largely unexplored. In general, air breathing in facultative air-breathing fishes is associated with an acid-base disturbance, resulting in an increased partial pressure of arterial CO2 and a reduction in extracellular pH (pHE ); however, several fishes appear to be capable of tightly regulating tissue intracellular pH (pHI ), despite a large sustained reduction in pHE , a trait termed preferential pHI regulation. Further studies are needed to determine whether preferential pHI regulation is a general trait among bimodal fishes and if this confers reduced sensitivity to acid-base disturbances, including those induced by hypercarbia, exhaustive exercise and hypoxia or anoxia. Additionally, elucidating the cellular and molecular mechanisms may yield insight into whether preferential pHI regulation is a trait ultimately associated with the early evolution of air breathing in vertebrates.

  3. Treatment of allergic asthma by targeting transcription factors using nucleic-acid based technologies.

    Science.gov (United States)

    Sel, Serdar; Henke, Wolfgang; Dietrich, Alexander; Herz, Udo; Renz, Harald

    2006-01-01

    There is considerable evidence that T-helper 2 (Th2) cells play a central role in the pathogenesis of allergic diseases such as bronchial asthma, hay fever or food allergy. The differentiation of naïve T cells into Th2 cells producing a specific pattern of cytokines is tightly controlled and regulated by transcription factors. Thus down-regulation of mRNA-levels of a single transcription factor leads to a "knock-down" of several mediators simultaneously, representing an advantage compared to earlier approaches involving down-regulation of one intercellular inflammatory mediator, which is unlikely to influence all pathophysiological aspects of the disease. We review the impact of specific and master transcription factors involved in Th2 cell commitment and evaluate approaches for the down-regulation of these proteins by degradation of their mRNA using nucleic-acid based technologies including antisense oligonucleotides, ribozymes, DNAzymes, decoys oligonucleotides and RNA interference.

  4. One carbon metabolism in anaerobic bacteria: Regulation of carbon and electron flow during organic acid production

    Energy Technology Data Exchange (ETDEWEB)

    Zeikus, J.G.; Jain, M.

    1993-12-31

    The project deals with understanding the fundamental biochemical mechanisms that physiologically control and regulate carbon and electron flow in anaerobic chemosynthetic bacteria that couple metabolism of single carbon compounds and hydrogen to the production of organic acids (formic, acetic, butyric, and succinic) or methane. The authors compare the regulation of carbon dioxide and hydrogen metabolism by fermentation, enzyme, and electron carrier analysis using Butyribacterium methylotrophicum, Anaeroblospirillum succiniciproducens, Methanosarcina barkeri, and a newly isolated tri-culture composed of a syntrophic butyrate degrader strain IB, Methanosarcina mazei and Methanobacterium formicicum as model systems. To understand the regulation of hydrogen metabolism during butyrate production or acetate degradation, hydrogenase activity in B. methylotrophicum or M. barkeri is measured in relation to growth substrate and pH; hydrogenase is purified and characterized to investigate number of hydrogenases; their localization and functions; and, their sequences are determined. To understand the mechanism for catabolic CO{sub 2} fixation to succinate the PEP carboxykinase enzyme and gene of A. succiniciproducens are purified and characterized. Genetically engineered strains of Escherichia coli containing the phosphoenolpyruvate (PEP) carboxykinase gene are examined for their ability to produce succinate in high yield. To understand the mechanism of fatty acid degradation by syntrophic acetogens during mixed culture methanogenesis formate and hydrogen production are characterized by radio tracer studies. It is intended that these studies provide strategies to improve anaerobic fermentations used for the production of organic acids or methane and, new basic understanding on catabolic CO{sub 2} fixation mechanisms and on the function of hydrogenase in anaerobic bacteria.

  5. Effects of lanthanum on abscisic acid regulation of root growth in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    王建荣; 王蕾; 胡婷; 李文超; 薛绍武

    2014-01-01

    Rare earth elements (REEs) were reported to have adverse biology effects on plant growth and production. However, whether REEs are involved in plant hormone abscisic acid signal is not clear. Here we reported that REE lanthanum (La) interacted with abscisic acid (ABA) in the regulation of seed germination and root growth in model plant Arabidopsis. La3+at a concentration of 10 µmol/L alleviated ABA depression of seed germination and reversed ABA inhibition of root elongation growth in Arabidopsis. Previous studies showed that ABA could promote root hair development. In the present study, La3+inhibited root hair development promoted by ABA. Moreover, La3+inhibited H2O2 generation induced by ABA in root cells. Therefore we inferred that La3+might interact with ABA upstream of H2O2 generation.

  6. Acid sphingomyelinase activity is regulated by membrane lipids and facilitates cholesterol transfer by NPC2.

    Science.gov (United States)

    Oninla, Vincent O; Breiden, Bernadette; Babalola, Jonathan O; Sandhoff, Konrad

    2014-12-01

    During endocytosis, membrane components move to intraluminal vesicles of the endolysosomal compartment for digestion. At the late endosomes, cholesterol is sorted out mainly by two sterol-binding proteins, Niemann-Pick protein type C (NPC)1 and NPC2. To study the NPC2-mediated intervesicular cholesterol transfer, we developed a liposomal assay system. (Abdul-Hammed, M., B. Breiden, M. A. Adebayo, J. O. Babalola, G. Schwarzmann, and K. Sandhoff. 2010. Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion. J. Lipid Res. 51: 1747-1760.) Anionic lipids stimulate cholesterol transfer between liposomes while SM inhibits it, even in the presence of anionic bis(monoacylglycero)phosphate (BMP). Preincubation of vesicles containing SM with acid sphingomyelinase (ASM) (SM phosphodiesterase, EC 3.1.4.12) results in hydrolysis of SM to ceramide (Cer), which enhances cholesterol transfer. Besides SM, ASM also cleaves liposomal phosphatidylcholine. Anionic phospholipids derived from the plasma membrane (phosphatidylglycerol and phosphatidic acid) stimulate SM and phosphatidylcholine hydrolysis by ASM more effectively than BMP, which is generated during endocytosis. ASM-mediated hydrolysis of liposomal SM was also stimulated by incorporation of diacylglycerol (DAG), Cer, and free fatty acids into the liposomal membranes. Conversely, phosphatidylcholine hydrolysis was inhibited by incorporation of cholesterol, Cer, DAG, monoacylglycerol, and fatty acids. Our data suggest that SM degradation by ASM is required for physiological secretion of cholesterol from the late endosomal compartment, and is a key regulator of endolysosomal lipid digestion.

  7. The role of membrane fatty-acid transporters in regulating skeletal muscle substrate use during exercise.

    Science.gov (United States)

    Pelsers, Maurice M A L; Stellingwerff, Trent; van Loon, Luc J C

    2008-01-01

    While endogenous carbohydrates form the main substrate source during high-intensity exercise, long-chain fatty acids (LCFA) represent the main substrate source during more prolonged low- to moderate-intensity exercise. Adipose tissue lipolysis is responsible for the supply of LCFA to the contracting muscle. Once taken up by skeletal muscle tissue, LCFA can either serve as a substrate for oxidative phosphorylation or can be directed towards esterification into triacylglycerol. Myocellular uptake of LCFA comprises a complex and incompletely understood process. Although LCFA can enter the cell via passive diffusion, more recent reports indicate that LCFA uptake is tightly regulated by plasma membrane-located transport proteins (fatty acid translocase [FAT/CD36], plasmalemmal-located fatty acid binding protein [FABPpm] and fatty acid transport protein [FATP]). Depending on cardiac and skeletal muscle energy demands, some of these LCFA transporters can translocate rapidly from intracellular pools to the plasma membrane to allow greater LCFA uptake. This translocation process can be induced by insulin and/or muscle contraction. However, the precise signalling pathways responsible for activating the translocation machinery remain to be elucidated. This article will provide an overview on the effects of diet, acute exercise and exercise training on the expression and/or translocation of the various LCFA transporters in skeletal muscle tissue (FAT/CD36, FABPpm, FATP).

  8. NERP-2 regulates gastric acid secretion and gastric emptying via the orexin pathway.

    Science.gov (United States)

    Namkoong, Cherl; Toshinai, Koji; Waise, T M Zaved; Sakoda, Hideyuki; Sasaki, Kazuki; Ueta, Yoichi; Kim, Min-Seon; Minamino, Naoto; Nakazato, Masamitsu

    2017-02-16

    Neuroendocrine regulatory peptide (NERP)-2 is derived from a distinct region of VGF, a neurosecretory protein originally identified as a product of a nerve growth factor-responsive gene in rat PC12 cells. Colocalization of NERP-2 with orexin-A in the lateral hypothalamus increases orexin-A-induced feeding and energy expenditure in both rats and mice. Orexigenic and anorectic peptides in the hypothalamus modulate gastric function. In this study, we investigated the effect of NERP-2 on gastric function in rats. Intracerebroventricular administration of NERP-2 to rats increased gastric acid secretion and gastric emptying, whereas peripheral administration did not affect gastric function. NERP-2-induced gastric acid secretion and gastric emptying were blocked by an orexin 1 receptor antagonist, SB334867. NERP-2 also induced Fos expression in the lateral hypothalamus and the dorsomotor nucleus of the vagus X, which are key sites in the central nervous system for regulation of gastric function. Atropine, a blocker of vagal efferent signal transduction, completely blocked NERP-2-induced gastric acid secretion. These results demonstrate that central administration of NERP-2 activates the orexin pathway, resulting in elevated gastric acid secretion and gastric emptying.

  9. Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag

    Directory of Open Access Journals (Sweden)

    Melanie Friedrich

    2016-04-01

    Full Text Available The HIV-1 Gag p6 protein regulates the final abscission step of nascent virions from the cell membrane by the action of its two late (l- domains, which recruit Tsg101 and ALIX, components of the ESCRT system. Even though p6 consists of only 52 amino acids, it is encoded by one of the most polymorphic regions of the HIV-1 gag gene and undergoes various posttranslational modifications including sumoylation, ubiquitination, and phosphorylation. In addition, it mediates the incorporation of the HIV-1 accessory protein Vpr into budding virions. Despite its small size, p6 exhibits an unusually high charge density. In this study, we show that mutation of the conserved glutamic acids within p6 increases the membrane association of Pr55 Gag followed by enhanced polyubiquitination and MHC-I antigen presentation of Gag-derived epitopes, possibly due to prolonged exposure to membrane bound E3 ligases. The replication capacity of the total glutamic acid mutant E0A was almost completely impaired, which was accompanied by defective virus release that could not be rescued by ALIX overexpression. Altogether, our data indicate that the glutamic acids within p6 contribute to the late steps of viral replication and may contribute to the interaction of Gag with the plasma membrane.

  10. Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag.

    Science.gov (United States)

    Friedrich, Melanie; Setz, Christian; Hahn, Friedrich; Matthaei, Alina; Fraedrich, Kirsten; Rauch, Pia; Henklein, Petra; Traxdorf, Maximilian; Fossen, Torgils; Schubert, Ulrich

    2016-04-25

    The HIV-1 Gag p6 protein regulates the final abscission step of nascent virions from the cell membrane by the action of its two late (L-) domains, which recruit Tsg101 and ALIX, components of the ESCRT system. Even though p6 consists of only 52 amino acids, it is encoded by one of the most polymorphic regions of the HIV-1 gag gene and undergoes various posttranslational modifications including sumoylation, ubiquitination, and phosphorylation. In addition, it mediates the incorporation of the HIV-1 accessory protein Vpr into budding virions. Despite its small size, p6 exhibits an unusually high charge density. In this study, we show that mutation of the conserved glutamic acids within p6 increases the membrane association of Pr55 Gag followed by enhanced polyubiquitination and MHC-I antigen presentation of Gag-derived epitopes, possibly due to prolonged exposure to membrane bound E3 ligases. The replication capacity of the total glutamic acid mutant E0A was almost completely impaired, which was accompanied by defective virus release that could not be rescued by ALIX overexpression. Altogether, our data indicate that the glutamic acids within p6 contribute to the late steps of viral replication and may contribute to the interaction of Gag with the plasma membrane.

  11. New roles for Smad signaling and phosphatidic acid in the regulation of skeletal muscle mass.

    Science.gov (United States)

    Goodman, Craig A; Hornberger, Troy A

    2014-01-01

    Skeletal muscle is essential for normal bodily function and the loss of skeletal muscle (i.e. muscle atrophy/wasting) can have a major impact on mobility, whole-body metabolism, disease resistance, and quality of life. Thus, there is a clear need for the development of therapies that can prevent the loss, or increase, of skeletal muscle mass. However, in order to develop such therapies, we will first have to develop a thorough understanding of the molecular mechanisms that regulate muscle mass. Fortunately, our knowledge is rapidly advancing, and in this review, we will summarize recent studies that have expanded our understanding of the roles that Smad signaling and the synthesis of phosphatidic acid play in the regulation of skeletal muscle mass.

  12. Thyroid hormone and retinoic acid interact to regulate zebrafish craniofacial neural crest development.

    Science.gov (United States)

    Bohnsack, Brenda L; Kahana, Alon

    2013-01-15

    Craniofacial and ocular morphogenesis require proper regulation of cranial neural crest migration, proliferation, survival and differentiation. Although alterations in maternal thyroid hormone (TH) are associated with congenital craniofacial anomalies, the role of TH on the neural crest has not been previously described. Using zebrafish, we demonstrate that pharmacologic and genetic alterations in TH signaling disrupt cranial neural crest migration, proliferation, and survival, leading to craniofacial, extraocular muscle, and ocular developmental abnormalities. In the rostral cranial neural crest that gives rise to the periocular mesenchyme and the frontonasal process, retinoic acid (RA) rescued migratory defects induced by decreased TH signaling. In the caudal cranial neural crest, TH and RA had reciprocal effects on anterior and posterior pharyngeal arch development. The interactions between TH and RA signaling were partially mediated by the retinoid X receptor. We conclude that TH regulates both rostral and caudal cranial neural crest. Further, coordinated interactions of TH and RA are required for proper craniofacial and ocular development.

  13. Role of bile acids in the regulation of the metabolic pathways

    Institute of Scientific and Technical Information of China (English)

    Hiroki; Taoka; Yoko; Yokoyama; Kohkichi; Morimoto; Naho; Kitamura; Tatsuya; Tanigaki; Yoko; Takashina; Kazuo; Tsubota; Mitsuhiro; Watanabe

    2016-01-01

    Recent studies have revealed that bile acids(BAs)are not only facilitators of dietary lipid absorption but also important signaling molecules exerting multiple physiological functions.Some major signaling pathways involving the nuclear BAs receptor farnesoid X receptor and the G protein-coupled BAs receptor TGR5/M-BAR have been identified to be the targets of BAs.BAs regulate their own homeostasis via signaling pathways.BAs also affect diverse metabolic pathways including glucose metabolism,lipid metabolism and energy expenditure.This paper suggests the mechanism of controlling metabolism via BA signaling and demonstrates that BA signaling is an attractive therapeutic target of the metabolic syndrome.

  14. Sugar signaling regulation by Arabidopsis SIZ1-driven sumoylation is independent of salicylic acid

    DEFF Research Database (Denmark)

    Castro, Pedro Humberto; Verde, Nuno; Tavares, Rui Manuel

    2017-01-01

    SUMO is a modifying peptide that regulates protein activity and is essential to eukaryotes. In plants, SUMO plays an important role in both development and the response to environmental stimuli. The best described sumoylation pathway component is the SUMO E3 ligase SIZ1. Its mutant displays...... inefficient responses to nutrient imbalance in phosphate, nitrate and copper. Recently, we reported that siz1 also displays altered responses to exogenous sugar supplementation. The siz1 mutant is a salicylic acid (SA) accumulator, and SA may interfere with sugar-dependent responses and signaling events. Here...

  15. Reliability of valve-regulated lead-acid batteries for stationary applications.

    Energy Technology Data Exchange (ETDEWEB)

    De Anda, Mindi Farber (Energetics Inc., Washington, DC); Butler, Paul Charles; Miller, Jennifer L (Energetics Inc., Washington, DC); Moseley, Patrick T. (International Lead Zinc Research Organization, Research Triangle Park, NC)

    2004-03-01

    A survey has been carried out to quantify the performance and life of over 700,000 valve-regulated lead-acid (VRLA) cells, which have been or are being used in stationary applications across the United States. The findings derived from this study have not identified any fundamental flaws of VRLA battery technology. There is evidence that some cell designs are more successful in float duty than others. A significant number of the VRLA cells covered by the survey were found to have provided satisfactory performance.

  16. Myxostiolide, myxostiol, and clavatoic acid, plant growth regulators from the fungus Myxotrichum stipitatum.

    Science.gov (United States)

    Kimura, Yasuo; Shimada, Atsumi; Kusano, Miyako; Yoshii, Katsunobu; Morita, Akiko; Nishibe, Masahiko; Fujioka, Shozo; Kawano, Tsuyoshi

    2002-04-01

    New plant growth regulators, named myxostiolide (1), myxostiol (2), and clavatoic acid (3), have been isolated from Myxotrichum stipitatum, and their structures have been established by spectroscopic methods including 2D NMR. The biological activities of 1, 2, and 3 have been examined using tea pollen and lettuce seedling bioassay methods. With tea pollen, compound 1 inhibited the pollen tube growth to 14% of control at a concentration of 100 mg/L. With lettuce seedlings, compound 2 accelerated the root growth from 1 mg/L to 100 mg/L and compound 3 inhibited the root growth, to 52% of control, at a concentration of 100 mg/L.

  17. ATAF1 transcription factor directly regulates abscisic acid biosynthetic gene NCED3 in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Jensen, Michael Krogh; Lindemose, Søren; De Masi, Federico

    2013-01-01

    ATAF1, an Arabidopsis thaliana NAC transcription factor, plays important roles in plant adaptation to environmental stress and development. To search for ATAF1 target genes, we used protein binding microarrays and chromatin-immunoprecipitation (ChIP). This identified T[A,C,G]CGT[A,G] and TT[A,C,G...... abscisic acid (ABA) phytohormone biosynthetic gene NCED3. ChIP-qPCR and expression analysis showed that ATAF1 binding to the NCED3 promoter correlated with increased NCED3 expression and ABA hormone levels. These results indicate that ATAF1 regulates ABA biosynthesis....

  18. Characterization and Regulation of the Amino Acid Transporter SNAT2 in the Small Intestine of Piglets.

    Directory of Open Access Journals (Sweden)

    Guangran Li

    Full Text Available The sodium-dependent neutral amino acid transporter 2 (SNAT2, which has dual transport/receptor functions, is well documented in eukaryotes and some mammalian systems, but has not yet been verified in piglets. The objective of this study was to investigate the characteristics and regulation of SNAT2 in the small intestine of piglets. The 1,521-bp porcine full cDNA sequence of SNAT2 (KC769999 from the small intestine of piglets was cloned. The open reading frame of cDNA encodes 506 deduced amino acid residues with a calculated molecular mass of 56.08 kDa and an isoelectric point (pI of 7.16. Sequence alignment and phylogenetic analysis revealed that SNAT2 is highly evolutionarily conserved in mammals. SNAT2 mRNA can be detected in the duodenum, jejunum and ileum by real-time quantitative PCR. During the suckling period from days 1 to 21, the duodenum had the highest abundance of SNAT2 mRNA among the three segments of the small intestine. There was a significant decrease in the expression of SNAT2 mRNA in the duodenal and jejunal mucosa and in the expression of SNAT2 protein in the jejunal and ileal mucosa on day 1 after weaning (P < 0.05. Studies with enterocytes in vitro showed that amino acid starvation and supplementation with glutamate, arginine or leucine enhanced, while supplementation with glutamine reduced, SNAT2 mRNA expression (P < 0.05. These results regarding the characteristics and regulation of SNAT2 should help to provide some information to further clarify its roles in the absorption of amino acids and signal transduction in the porcine small intestine.

  19. Down-regulation of the caffeic acid O-methyltransferase gene in switchgrass reveals a novel monolignol analog

    Directory of Open Access Journals (Sweden)

    Tschaplinski Timothy J

    2012-09-01

    Full Text Available Abstract Background Down-regulation of the caffeic acid 3-O-methyltransferase EC 2.1.1.68 (COMT gene in the lignin biosynthetic pathway of switchgrass (Panicum virgatum resulted in cell walls of transgenic plants releasing more constituent sugars after pretreatment by dilute acid and treatment with glycosyl hydrolases from an added enzyme preparation and from Clostridium thermocellum. Fermentation of both wild-type and transgenic switchgrass after milder hot water pretreatment with no water washing showed that only the transgenic switchgrass inhibited C. thermocellum. Gas chromatography–mass spectrometry (GCMS-based metabolomics were undertaken on cell wall aqueous extracts to determine the nature of the microbial inhibitors. Results GCMS confirmed the increased concentration of a number of phenolic acids and aldehydes that are known inhibitors of microbial fermentation. Metabolomic analyses of the transgenic biomass additionally revealed the presence of a novel monolignol-like metabolite, identified as trans-3, 4-dimethoxy-5-hydroxycinnamyl alcohol (iso-sinapyl alcohol in both non-pretreated, as well as hot water pretreated samples. iso-Sinapyl alcohol and its glucoside were subsequently generated by organic synthesis and the identity of natural and synthetic materials were confirmed by mass spectrometric and NMR analyses. The additional novel presence of iso-sinapic acid, iso-sinapyl aldehyde, and iso-syringin suggest the increased activity of a para-methyltransferase, concomitant with the reduced COMT activity, a strict meta-methyltransferase. Quantum chemical calculations were used to predict the most likely homodimeric lignans generated from dehydration reactions, but these products were not evident in plant samples. Conclusions Down-regulation of COMT activity in switchgrass resulted in the accumulation of previously undetected metabolites resembling sinapyl alcohol and its related metabolites, but that are derived from para

  20. Cationic amino acid transporter-2 regulates immunity by modulating arginase activity.

    Directory of Open Access Journals (Sweden)

    Robert W Thompson

    2008-03-01

    Full Text Available Cationic amino acid transporters (CAT are important regulators of NOS2 and ARG1 activity because they regulate L-arginine availability. However, their role in the development of Th1/Th2 effector functions following infection has not been investigated. Here we dissect the function of CAT2 by studying two infectious disease models characterized by the development of polarized Th1 or Th2-type responses. We show that CAT2(-/- mice are significantly more susceptible to the Th1-inducing pathogen Toxoplasma gondii. Although T. gondii infected CAT2(-/- mice developed stronger IFN-gamma responses, nitric oxide (NO production was significantly impaired, which contributed to their enhanced susceptibility. In contrast, CAT2(-/- mice infected with the Th2-inducing pathogen Schistosoma mansoni displayed no change in susceptibility to infection, although they succumbed to schistosomiasis at an accelerated rate. Granuloma formation and fibrosis, pathological features regulated by Th2 cytokines, were also exacerbated even though their Th2 response was reduced. Finally, while IL-13 blockade was highly efficacious in wild-type mice, the development of fibrosis in CAT2(-/- mice was largely IL-13-independent. Instead, the exacerbated pathology was associated with increased arginase activity in fibroblasts and alternatively activated macrophages, both in vitro and in vivo. Thus, by controlling NOS2 and arginase activity, CAT2 functions as a potent regulator of immunity.

  1. Regulation of basal and oxidative stress-triggered jasmonic acid-related gene expression by glutathione.

    Science.gov (United States)

    Han, Yi; Mhamdi, Amna; Chaouch, Sejir; Noctor, Graham

    2013-06-01

    Glutathione is a determinant of cellular redox state with roles in defence and detoxification. Emerging concepts suggest that this compound also has functions in cellular signalling. Here, we report evidence that glutathione plays potentially important roles in setting signalling strength through the jasmonic acid (JA) pathway. Firstly, we show that basal expression of JA-related genes is correlated with leaf glutathione content when the latter is manipulated either genetically or pharmacologically. Secondly, analyses of an oxidative stress signalling mutant, cat2, reveal that up-regulation of the JA pathway triggered by intracellular oxidation requires accompanying glutathione accumulation. Genetically blocking this accumulation in a cat2 cad2 line largely annuls H2 O2 -induced expression of JA-linked genes, and this effect can be rescued by exogenously supplying glutathione. While most attention on glutathione functions in biotic stress responses has been focused on the thiol-regulated protein NPR1, a comparison of JA-linked gene expression in cat2 cad2 and cat2 npr1 double mutants provides evidence that glutathione acts through other components to regulate the response of this pathway to oxidative stress. Our study provides new information implicating glutathione as a factor determining basal JA gene expression and suggests novel glutathione-dependent control points that regulate JA signalling in response to intracellular oxidation.

  2. Regulation of retinoid receptors by retinoic acid and axonal contact in Schwann cells.

    Directory of Open Access Journals (Sweden)

    Maria-Jesus Latasa

    Full Text Available BACKGROUND: Schwann cells (SCs are the cell type responsible for the formation of the myelin sheath in the peripheral nervous system (PNS. As retinoic acid (RA and other retinoids have a profound effect as regulators of the myelination program, we sought to investigate how their nuclear receptors levels were regulated in this cell type. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, by using Schwann cells primary cultures from neonatal Wistar rat pups, as well as myelinating cocultures of Schwann cells with embryonic rat dorsal root ganglion sensory neurons, we have found that sustained expression of RXR-γ depends on the continuous presence of a labile activator, while axonal contact mimickers produced an increase in RXR-γ mRNA and protein levels, increment that could be prevented by RA. The upregulation by axonal contact mimickers and the transcriptional downregulation by RA were dependent on de novo protein synthesis and did not involve changes in mRNA stability. On the other hand, RAR-β mRNA levels were only slightly modulated by axonal contact mimickers, while RA produced a strong transcriptional upregulation that was independent of de novo protein synthesis without changes in mRNA stability. CONCLUSIONS/SIGNIFICANCE: All together, our results show that retinoid receptors are regulated in a complex manner in Schwann cells, suggesting that they could have a prominent role as regulators of Schwann cell physiology.

  3. cAMP-dependent signaling regulates the adipogenic effect of n-6 polyunsaturated fatty acids

    DEFF Research Database (Denmark)

    Madsen, Lise; Pedersen, Lone Møller; Liaset, Bjørn

    2008-01-01

    The effect of n-6 polyunsaturated fatty acids (n-6 PUFAs) on adipogenesis and obesity is controversial. Using in vitro cell culture models, we show that n-6 PUFAs was pro-adipogenic under conditions with base-line levels of cAMP, but anti-adipogenic when the levels of cAMP were elevated. The anti...

  4. Teaching the Role of Secretin in the Regulation of Gastric Acid Secretion Using a Classic Paper by Johnson and Grossman

    Science.gov (United States)

    Walton, Kristen L. W.

    2009-01-01

    The regulation of gastric acid secretion has been the subject of investigation for over a century. Inhibition of gastrin-induced acid secretion by the intestine-derived hormone secretin provides a classic physiological example of negative feedback in the gastrointestinal tract. A classic paper by Leonard R. Johnson and Morton I. Grossman clearly…

  5. Regulation of hepatic branched-chain alpha-keto acid dehydrogenase complex in rats fed a high-fat diet

    Science.gov (United States)

    Objective: Branched-chain alpha-keto acid dehydrogenase complex (BCKDC) regulates branched-chain amino acid (BCAA) metabolism at the level of branched chain alpha-ketoacid (BCKA) catabolism. It has been demonstrated that the activity of hepatic BCKDC is markedly decreased in type 2 diabetic animal...

  6. Role of acids and bases in nanoparticle growth

    Science.gov (United States)

    Yli-Juuti, Taina; Barsanti, Kelley; Bzdek, Bryan; Hildebrandt Ruiz, Lea; Jokinen, Tuija; Kieloaho, Antti-Jussi; Makkonen, Ulla; Petäjä, Tuukka; Ruuskanen, Taina; Johnston, Murray; Kulmala, Markku; Riipinen, Ilona

    2014-05-01

    Secondary aerosol particles that are formed in atmosphere by gas-to-particle conversion during new particle formation events have potential to affect climate significantly due to their typically high number concentrations. This, however, requires that the freshly formed nanoparticles of about 1 nm in diameter grow tens of nanometers and reach climatically relevant sizes, i.e. sizes where they can act as cloud condensation nuclei. During the growth towards larger sizes the nanoparticles are subject to coagulational losses, and the rate at which the nanoparticles grow by condensation of vapors is a key factor affecting their probability to survive to climatically relevant sizes. Vapors that condense on the nanoparticles can be produced in the atmosphere from volatile compounds through gas phase chemical reactions, and their volatility can also be further lowered by particle phase processes. Therefore, particle composition and particle phase processes may influence nanoparticle growth. We study the growth of atmospheric nanoparticles and especially the role of particle phase salt formation in the nanoparticle growth using MABNAG model (Model for Acid-Base chemistry in NAnoparticle Growth) and by comparing to atmospheric measurements. MABNAG is a condensation growth model for aqueous solution particles. In MABNAG the dynamics of gas phase mass transport of vapors to particle are coupled with thermodynamics of particle phase acid-base chemistry, and both the composition and size dependence of equilibrium vapor pressures are accounted for. The model is applied especially for boreal forest environment. Here nanoparticle growth is modeled with a system of water, two acids (sulfuric acid and an organic acid) and two bases (ammonia and an amine) as condensing vapors. Focus is on the neutralization of acids by the bases and the related effects on the particle growth. According to the model predictions the enhancement of condensation of organic acid due to salt formation is

  7. TdaA Regulates Tropodithietic Acid Synthesis by Binding to the tdaC Promoter Region ▿ †

    OpenAIRE

    Geng, Haifeng; Belas, Robert

    2011-01-01

    Silicibacter sp. TM1040, a member of the marine Roseobacter clade, produces the antibiotic and quorum signaling molecule tropodithietic acid (TDA), encoded by tdaABCDEF. Here, we showed that an LysR-type transcriptional regulator, TdaA, is a positive regulator of tdaCDE gene expression and binds to the tdaC promoter region.

  8. Phosphorylation of KasB regulates virulence and acid-fastness in Mycobacterium tuberculosis.

    Science.gov (United States)

    Vilchèze, Catherine; Molle, Virginie; Carrère-Kremer, Séverine; Leiba, Jade; Mourey, Lionel; Shenai, Shubhada; Baronian, Grégory; Tufariello, Joann; Hartman, Travis; Veyron-Churlet, Romain; Trivelli, Xavier; Tiwari, Sangeeta; Weinrick, Brian; Alland, David; Guérardel, Yann; Jacobs, William R; Kremer, Laurent

    2014-05-01

    -dependent KasB phosphorylation in regulating the later stages of mycolic acid elongation, with important consequences in terms of acid-fast staining and pathogenicity.

  9. Phosphorylation of KasB regulates virulence and acid-fastness in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Catherine Vilchèze

    2014-05-01

    Ser/Thr kinase-dependent KasB phosphorylation in regulating the later stages of mycolic acid elongation, with important consequences in terms of acid-fast staining and pathogenicity.

  10. Acid-base disturbance in patients with cirrhosis

    DEFF Research Database (Denmark)

    Henriksen, Jens H; Bendtsen, Flemming; Møller, Søren

    2015-01-01

    PURPOSE: Acid-base disturbances were investigated in patients with cirrhosis in relation to hemodynamic derangement to analyze the hyperventilatory effects and the metabolic compensation. METHODS: A total of 66 patients with cirrhosis and 44 controls were investigated during a hemodynamic study......, and effects of unidentified ions (all Pacid-base disturbances could not be identified. CONCLUSION: Hypocapnic alkalosis is related to disease severity and hyperdynamic systemic circulation in patients with cirrhosis. The metabolic compensation includes...... alterations in serum albumin and water retention that may result in a delicate acid-base balance in these patients....

  11. Poly (ricinoleic acid) based novel thermosetting elastomer.

    Science.gov (United States)

    Ebata, Hiroki; Yasuda, Mayumi; Toshima, Kazunobu; Matsumura, Shuichi

    2008-01-01

    A novel bio-based thermosetting elastomer was prepared by the lipase-catalyzed polymerization of methyl ricinoleate with subsequent vulcanization. Some mechanical properties of the cured carbon black-filled polyricinoleate compounds were evaluated as a thermosetting elastomer. It was found that the carbon black-filled polyricinoleate compounds were readily cured by sulfur curatives to produce a thermosetting elastomer that formed a rubber-like sheet with a smooth and non-sticky surface. The curing behaviors and mechanical properties were dependent on both the molecular weight of the polyricinoleate and the amount of the sulfur curatives. Cured compounds consisting of polyricinoleate with a molecular weight of 100,800 showed good mechanical properties, such as a hardness of 48 A based on the durometer A measurements, a tensile strength at break of 6.91 MPa and an elongation at break of 350%.

  12. Arachidonic acid has a dominant effect to regulate lipogenic genes in 3T3-L1 adipocytes compared to omega-3 fatty acids

    Directory of Open Access Journals (Sweden)

    Hitesh Vaidya

    2015-03-01

    Full Text Available Background: The effects of long-chain n-3 and n-6 polyunsaturated fatty acids (PUFA on the regulation of adipocytes metabolism are well known. These fatty acids are generally consumed together in our diets; however, the metabolic regulation of adipocytes in the presence of these fatty acids when given together is not known. Objective: To investigate the effects of n-3 PUFA and arachidonic acid (AA, an n-6 PUFA, on the regulation of adipogenic and lipogenic genes in mature 3T3-L1 adipocytes. Methods: 3T3-L1 adipocytes were incubated in the presence or absence of 100 µM of eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA; docosapentaenoic acid, DPA and AA, either alone or AA+n-3 PUFA; control cells received bovine serum albumin alone. The mRNA expression of adipogenic and lipogenic genes was measured. The fatty acid composition of adipocytes was analyzed using gas chromatography. Results: Individual n-3 PUFA or AA had no effect on the mRNA expression of peroxisome-proliferator-activated receptor-γ; however, AA+EPA and AA+DPA significantly increased (P<0.05 the expression compared to control cells (38 and 42%, respectively. AA and AA+EPA increased the mRNA expression of acetyl-CoA carboxylase 1 (P<0.05. AA treatment decreased the mRNA expression of stearoyl-CoA desaturase (SCD1 (P<0.01, while n-3 PUFA, except EPA, had no effect compared to control cells. AA+DHA and AA+DPA inhibited SCD1 gene expression (P<0.05 suggesting a dominant effect of AA. Fatty acids analysis of adipocytes revealed a higher accretion of AA compared to n-3 PUFA. Conclusions: Our findings reveal that AA has a dominant effect on the regulation of lipogenic genes in adipocytes.

  13. Web-Based Expert System for Civil Service Regulations: RCSES

    CERN Document Server

    Hogo, Mofreh; Mousa, Fouad

    2010-01-01

    Internet and expert systems have offered new ways of sharing and distributing knowledge, but there is a lack of researches in the area of web based expert systems. This paper introduces a development of a web-based expert system for the regulations of civil service in the Kingdom of Saudi Arabia named as RCSES. It is the first time to develop such system (application of civil service regulations) as well the development of it using web based approach. The proposed system considers 17 regulations of the civil service system. The different phases of developing the RCSES system are presented, as knowledge acquiring and selection, ontology and knowledge representations using XML format. XML Rule-based knowledge sources and the inference mechanisms were implemented using ASP.net technique. An interactive tool for entering the ontology and knowledge base, and the inferencing was built. It gives the ability to use, modify, update, and extend the existing knowledge base in an easy way. The knowledge was validated by ...

  14. Soil Studies: Applying Acid-Base Chemistry to Environmental Analysis.

    Science.gov (United States)

    West, Donna M.; Sterling, Donna R.

    2001-01-01

    Laboratory activities for chemistry students focus attention on the use of acid-base chemistry to examine environmental conditions. After using standard laboratory procedures to analyze soil and rainwater samples, students use web-based resources to interpret their findings. Uses CBL probes and graphing calculators to gather and analyze data and…

  15. Parallel proton transfer pathways in aqueous acid-base reactions

    NARCIS (Netherlands)

    Cox, M.J.; Bakker, H.J.

    2008-01-01

    We study the mechanism of proton transfer (PT) between the photoacid 8-hydroxy-1,3, 6-pyrenetrisulfonic acid (HPTS) and the base chloroacetate in aqueous solution. We investigate both proton and deuteron transfer reactions in solutions with base concentrations ranging from 0.25M to 4M. Using femtose

  16. A European Acid Rain Program based on the US experience

    DEFF Research Database (Denmark)

    Brandt, U. Steiner; Svendsen, Gert Tinggaard

    2000-01-01

    The paper shows that cost-effective involvement of the source location involves utmost difficulty in practice. Based on the RAINS model, it is recommended that source location should be ignored in a European market for SO2, as is the case in the US Acid Rain Program. Based on the political target...

  17. Physiological and clinical significance of enterochromaffin-like cell activation in the regulation of gastric acid secretion

    Institute of Scientific and Technical Information of China (English)

    Guanglin Cui; Helge L Waldum

    2007-01-01

    Gastric acid plays an important role in digesting food (especially protein), iron absorption, and destroying swallowed micro-organisms. H+ is secreted by the oxyntic parietal cells and its secretion is regulated by endocrine, neurocrine and paracrine mechanisms.Gastrin released from the antral G cell is the principal physiological stimulus of gastric acid secretion. Activation of the enterochromaffin-like (ECL) cell is accepted as the main source of histamine participating in the regulation of acid secretion and is functionally and trophically controlled by gastrin, which is mediated by gastrin/CCK-2 receptors expressed on the ECL cell. However, longterm hypergastrinemia will induce ECL cell hyperplasia and probably carcinoids. Clinically, potent inhibitors of acid secretion have been prescribed widely to patients with acid-related disorders. Long-term potent acid inhibition evokes a marked increase in plasma gastrin levels,leading to enlargement of oxyntic mucosa with ECL cell hyperplasia. Accordingly, the induction of ECL cell hyperplasia and carcinoids remains a topic of considerable concern, especially in long-term use. In addition, the activation of ECL cells also induces another clinical concern, i.e., rebound acid hypersecretion after acid inhibition. Recent experimental and clinical findings indicate that the activation of ECL cells plays a critical role both physiologically and clinically in the regulation of gastric acid secretion.

  18. Regulation of pyruvate dehydrogenase activity and citric acid cycle intermediates during high cardiac power generation.

    Science.gov (United States)

    Sharma, Naveen; Okere, Isidore C; Brunengraber, Daniel Z; McElfresh, Tracy A; King, Kristen L; Sterk, Joseph P; Huang, Hazel; Chandler, Margaret P; Stanley, William C

    2005-01-15

    A high rate of cardiac work increases citric acid cycle (CAC) turnover and flux through pyruvate dehydrogenase (PDH); however, the mechanisms for these effects are poorly understood. We tested the hypotheses that an increase in cardiac energy expenditure: (1) activates PDH and reduces the product/substrate ratios ([NADH]/[NAD(+)] and [acetyl-CoA]/[CoA-SH]); and (2) increases the content of CAC intermediates. Measurements were made in anaesthetized pigs under control conditions and during 15 min of a high cardiac workload induced by dobutamine (Dob). A third group was made hyperglycaemic (14 mm) to stimulate flux through PDH during the high work state (Dob + Glu). Glucose and fatty acid oxidation were measured with (14)C-glucose and (3)H-oleate. Compared with control, the high workload groups had a similar increase in myocardial oxygen consumption ( and cardiac power. Dob increased PDH activity and glucose oxidation above control, but did not reduce the [NADH]/[NAD(+)] and [acetyl-CoA]/[CoA-SH] ratios, and there were no differences between the Dob and Dob + Glu groups. An additional group was treated with Dob + Glu and oxfenicine (Oxf) to inhibit fatty acid oxidation: this increased [CoA-SH] and glucose oxidation compared with Dob; however, there was no further activation of PDH or decrease in the [NADH]/[NAD(+)] ratio. Content of the 4-carbon CAC intermediates succinate, fumarate and malate increased 3-fold with Dob, but there was no change in citrate content, and the Dob + Glu and Dob + Glu + Oxf groups were not different from Dob. In conclusion, compared with normal conditions, at high myocardial energy expenditure (1) the increase in flux through PDH is regulated by activation of the enzyme complex and continues to be partially controlled through inhibition by fatty acid oxidation, and (2) there is expansion of the CAC pool size at the level of 4-carbon intermediates that is largely independent of myocardial fatty acid oxidation.

  19. Ionic liquid supported acid/base-catalyzed production of biodiesel.

    Science.gov (United States)

    Lapis, Alexandre A M; de Oliveira, Luciane F; Neto, Brenno A D; Dupont, Jairton

    2008-01-01

    The transesterification (alcoholysis) reaction was successfully applied to synthesize biodiesel from vegetable oils using imidazolium-based ionic liquids under multiphase acidic and basic conditions. Under basic conditions, the combination of the ionic liquid 1-n-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMINTf2), alcohols, and K2CO3 (40 mol %) results in the production of biodiesel from soybean oil in high yields (>98%) and purity. H2SO4 immobilized in BMINTf2 efficiently promotes the transesterification reaction of soybean oil and various primary and secondary alcohols. In this multiphase process the acid is almost completely retained in the ionic liquid phase, while the biodiesel forms a separate phase. The recovered ionic liquid containing the acid could be reused at least six times without any significant loss in the biodiesel yield or selectivity. In both catalytic processes (acid and base), the reactions proceed as typical multiphasic systems in which the formed biodiesel accumulates as the upper phase and the glycerol by-product is selectively captured by the alcohol-ionic liquid-acid/base phase. Classical ionic liquids such as 1-n-butyl-3-methylimidazolium tetrafluoroborate and hexafluorophosphate are not stable under these acidic or basic conditions and decompose.

  20. A computational study of ultrafast acid dissociation and acid-base neutralization reactions. I. The model.

    Science.gov (United States)

    Maurer, Patrick; Thomas, Vibin; Rivard, Ugo; Iftimie, Radu

    2010-07-28

    Ultrafast, time-resolved investigations of acid-base neutralization reactions have recently been performed using systems containing the photoacid 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) and various Bronsted bases. Two conflicting neutralization mechanisms have been formulated by Mohammed et al. [Science 310, 83 (2005)] and Siwick et al. [J. Am. Chem. Soc. 129, 13412 (2007)] for the same acid-base system. Herein an ab initio molecular dynamics based computational model is formulated, which is able to investigate the validity of the proposed mechanisms in the general context of ground-state acid-base neutralization reactions. Our approach consists of using 2,4,6-tricyanophenol (exp. pKa congruent with 1) as a model for excited-state HPTS( *) (pKa congruent with 1.4) and carboxylate ions for the accepting base. We employ our recently proposed dipole-field/quantum mechanics (QM) treatment [P. Maurer and R. Iftimie, J. Chem. Phys. 132, 074112 (2010)] of the proton donor and acceptor molecules. This approach allows one to tune the free energy of neutralization to any desired value as well as model initial nonequilibrium hydration effects caused by a sudden increase in acidity, making it possible to achieve a more realistic comparison with experimental data than could be obtained via a full-QM treatment of the entire system. It is demonstrated that the dipole-field/QM model reproduces correctly key properties of the 2,4,6-tricyanophenol acid molecule including gas-phase proton dissociation energies and dipole moments, and condensed-phase hydration structure and pKa values.

  1. Tbx1 and Brn4 regulate retinoic acid metabolic genes during cochlear morphogenesis

    Directory of Open Access Journals (Sweden)

    Braunstein Evan M

    2009-05-01

    Full Text Available Abstract Background In vertebrates, the inner ear is comprised of the cochlea and vestibular system, which develop from the otic vesicle. This process is regulated via inductive interactions from surrounding tissues. Tbx1, the gene responsible for velo-cardio-facial syndrome/DiGeorge syndrome in humans, is required for ear development in mice. Tbx1 is expressed in the otic epithelium and adjacent periotic mesenchyme (POM, and both of these domains are required for inner ear formation. To study the function of Tbx1 in the POM, we have conditionally inactivated Tbx1 in the mesoderm while keeping expression in the otic vesicle intact. Results Conditional mutants (TCre-KO displayed malformed inner ears, including a hypoplastic otic vesicle and a severely shortened cochlear duct, indicating that Tbx1 expression in the POM is necessary for proper inner ear formation. Expression of the mesenchyme marker Brn4 was also lost in the TCre-KO. Brn4-;Tbx1+/-embryos displayed defects in growth of the distal cochlea. To identify a potential signal from the POM to the otic epithelium, expression of retinoic acid (RA catabolizing genes was examined in both mutants. Cyp26a1 expression was altered in the TCre-KO, while Cyp26c1 showed reduced expression in both TCre-KO and Brn4-;Tbx1+/- embryos. Conclusion These results indicate that Tbx1 expression in the POM regulates cochlear outgrowth potentially via control of local retinoic acid activity.

  2. PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid -Hydroxylase (CYP4 Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    James P. Hardwick

    2009-01-01

    Full Text Available Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis, due to a decrease in mitochondria -oxidation with an increase in both peroxisomal -oxidation, and microsomal -oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs. How steatosis increases PPAR activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid -oxidation and -oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA, monounsaturated (MUFA, or saturated (SFA may be determined by the interplay of PPARs and HNF4 with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the -oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPAR. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid -hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA CYP4A and long-chain fatty acid (LCFA CYP4F -hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to

  3. Deoxyribonucleic acid base compositions of dermatophytes.

    Science.gov (United States)

    Davison, F D; Mackenzie, D W; Owen, R J

    1980-06-01

    DNA was extracted and purified from 55 dermatophyte isolates representing 34 species of Trichophyton, Microsporum and Epidermophyton. The base compositions of the chromosomal DNA were determined by CsCl density gradient centrifugation and were found to be in the narrow range of 48.7 to 50.3 mol % G + C. A satellite DNA component assumed to be of mitochondrial origin was present in most strains, with a G + C content ranging from 14.7 to 30.8 mol % G + C. Heterogeneity in microscopic and colonial characteristics was not reflected in differences in the mean G + C content of the chromosomal DNAs. Strains varied in the G + C contents of satelite DNA, but these did not correlate with traditional species concepts.

  4. Regulating non audit services: Towards a principles based approach to regulation

    OpenAIRE

    Ojo, Marianne

    2009-01-01

    Based on the argument that the benefits conferred through the provision of non audit services by audit firms outweigh the attributed costs of safeguarding the auditor's independence, this paper will not only seek to justify this argument, advance proposals which do not favour an outright prohibition of the provision of non audit services, but also consider means through which non audit services could be regulated in order to facilitate competition in the audit market. At the same time it will...

  5. Allosteric Regulation in the Ligand Binding Domain of Retinoic Acid Receptorγ

    Science.gov (United States)

    Amal, Ismail; Lutzing, Régis; Stote, Roland H.; Rochette-Egly, Cécile; Rochel, Natacha; Dejaegere, Annick

    2017-01-01

    Retinoic acid (RA) plays key roles in cell differentiation and growth arrest through nuclear retinoic acid receptors (RARs), which are ligand-dependent transcription factors. While the main trigger of RAR activation is the binding of RA, phosphorylation of the receptors has also emerged as an important regulatory signal. Phosphorylation of the RARγ N-terminal domain (NTD) is known to play a functional role in neuronal differentiation. In this work, we investigated the phosphorylation of RARγ ligand binding domain (LBD), and present evidence that the phosphorylation status of the LBD affects the phosphorylation of the NTD region. We solved the X-ray structure of a phospho-mimetic mutant of the LBD (RARγ S371E), which we used in molecular dynamics simulations to characterize the consequences of the S371E mutation on the RARγ structural dynamics. Combined with simulations of the wild-type LBD, we show that the conformational equilibria of LBD salt bridges (notably R387-D340) are affected by the S371E mutation, which likely affects the recruitment of the kinase complex that phosphorylates the NTD. The molecular dynamics simulations also showed that a conservative mutation in this salt bridge (R387K) affects the dynamics of the LBD without inducing large conformational changes. Finally, cellular assays showed that the phosphorylation of the NTD of RARγ is differentially regulated by retinoic acid in RARγWT and in the S371N, S371E and R387K mutants. This multidisciplinary work highlights an allosteric coupling between phosphorylations of the LBD and the NTD of RARγ and supports the importance of structural dynamics involving electrostatic interactions in the regulation of RARs activity. PMID:28125680

  6. TORC1 Inhibits GSK3-Mediated Elo2 Phosphorylation to Regulate Very Long Chain Fatty Acid Synthesis and Autophagy

    DEFF Research Database (Denmark)

    Zimmermann, Christine; Santos, Aline; Gable, Kenneth;

    2013-01-01

    Very long chain fatty acids (VLCFAs) are essential fatty acids with multiple functions, including ceramide synthesis. Although the components of the VLCFA biosynthetic machinery have been elucidated, how their activity is regulated to meet the cell's metabolic demand remains unknown. The goal...... of this study was to identify mechanisms that regulate the rate of VLCFA synthesis, and we discovered that the fatty acid elongase Elo2 is regulated by phosphorylation. Elo2 phosphorylation is induced upon inhibition of TORC1 and requires GSK3. Expression of nonphosphorylatable Elo2 profoundly alters...... of autophagy. Together, our data reveal a function for TORC1 and GSK3 in the regulation of VLCFA synthesis that has important implications for autophagy and cell homeostasis....

  7. Metabolism, gas exchange, and acid-base balance of giant salamanders.

    Science.gov (United States)

    Ultsch, Gordon R

    2012-08-01

    The giant salamanders are aquatic and paedomorphic urodeles including the genera Andrias and Cryptobranchus (Cryptobranchidae), Amphiuma (Amphiumidae), Siren (Sirenidae), and Necturus (Proteidae, of which only N. maculosus is considered 'a giant'). Species in the genera Cryptobranchus and Necturus are considered aquatic salamanders well adapted for breathing water, poorly adapted for breathing air, and with limited abilities to compensate acid-base disturbances. As such, they are water-breathing animals with a somewhat fish-like respiratory and acid-base physiology, whose habitat selection is limited to waters that do not typically become hypoxic or hypercarbic (although this assertion has been questioned for N. maculosus). Siren and Amphiuma species, by contrast, are dependent upon air-breathing, have excellent lungs, inefficient (Siren) or no (Amphiuma) gills, and are obligate air-breathers with an acid-base status more similar to that of terrestrial tetrapods. As such, they can be considered to be air-breathing animals that live in water. Their response to the aquatic hypercarbia that they often encounter is to maintain intracellular pH (pH(i) ) and abandon extracellular pH regulation, a process that has been referred to as preferential pH(i) regulation. The acid-base status of some present-day tropical air-breathing fishes, and of Siren and Amphiuma, suggests that the acid-base transition from a low PCO(2) -low [] system typical of water-breathing fishes to the high PCO(2) -high [] systems of terrestrial tetrapods may have been completed before emergence onto land, and likely occurred in habitats that were typically both hypoxic and hypercarbic.

  8. Characterization and Regulation of the Amino Acid Transporter SNAT2 in the Small Intestine of Piglets.

    Science.gov (United States)

    Li, Guangran; Li, Jianjun; Tan, Bie; Wang, Jing; Kong, Xiangfeng; Guan, Guiping; Li, Fengna; Yin, Yulong

    2015-01-01

    The sodium-dependent neutral amino acid transporter 2 (SNAT2), which has dual transport/receptor functions, is well documented in eukaryotes and some mammalian systems, but has not yet been verified in piglets. The objective of this study was to investigate the characteristics and regulation of SNAT2 in the small intestine of piglets. The 1,521-bp porcine full cDNA sequence of SNAT2 (KC769999) from the small intestine of piglets was cloned. The open reading frame of cDNA encodes 506 deduced amino acid residues with a calculated molecular mass of 56.08 kDa and an isoelectric point (pI) of 7.16. Sequence alignment and phylogenetic analysis revealed that SNAT2 is highly evolutionarily conserved in mammals. SNAT2 mRNA can be detected in the duodenum, jejunum and ileum by real-time quantitative PCR. During the suckling period from days 1 to 21, the duodenum had the highest abundance of SNAT2 mRNA among the three segments of the small intestine. There was a significant decrease in the expression of SNAT2 mRNA in the duodenal and jejunal mucosa and in the expression of SNAT2 protein in the jejunal and ileal mucosa on day 1 after weaning (P absorption of amino acids and signal transduction in the porcine small intestine.

  9. γ-Aminobutyric acid (GABA) homeostasis regulates pollen germination and polarized growth in Picea wilsonii.

    Science.gov (United States)

    Ling, Yu; Chen, Tong; Jing, Yanping; Fan, Lusheng; Wan, Yinglang; Lin, Jinxing

    2013-11-01

    γ-Aminobutyric acid (GABA) is a four-carbon non-protein amino acid found in a wide range of organisms. Recently, GABA accumulation has been shown to play a role in the stress response and cell growth in angiosperms. However, the effect of GABA deficiency on pollen tube development remains unclear. Here, we demonstrated that specific concentrations of exogenous GABA stimulated pollen tube growth in Picea wilsonii, while an overdose suppressed pollen tube elongation. The germination percentage of pollen grains and morphological variations in pollen tubes responded in a dose-dependent manner to treatment with 3-mercaptopropionic acid (3-MP), a glutamate decarboxylase inhibitor, while the inhibitory effects could be recovered in calcium-containing medium supplemented with GABA. Using immunofluorescence labeling, we found that the actin cables were disorganized in 3-MP treated cells, followed by the transition of endo/exocytosis activating sites from the apex to the whole tube shank. In addition, variations in the deposition of cell wall components were detected upon labeling with JIM5, JIM7, and aniline blue. Our results demonstrated that calcium-dependent GABA signaling regulates pollen germination and polarized tube growth in P. wilsonii by affecting actin filament patterns, vesicle trafficking, and the configuration and distribution of cell wall components.

  10. Sugar regulation of plastid reversion in citrus epicarp is mediated through organic acid metabolism.

    Science.gov (United States)

    Ahmed, Omer Khidir

    2009-02-01

    The inhibition by sucrose of chromoplast reversion to chloroplast in citrus epicarp was studied by observing the effects of several sugars, sugar metabolites and 1-iodoacetate on chlorophyll reaccumulation in cultured Citrus paradisi Macf. pericarp segments. Pericarp segments of 1 cm in diameter were cut from yellow fruits and cultured on modified medium plus the indicated metabolites and kept under continuous fluorescent light. Accumulation of chlorophyll in the segments was measured with a spectrophotometer fitted with sphere reflectometer. Respiration was determined via., an infrared gas analyzer. Inhibition of regreening was not specific to a particular sugar. The organic acids malate, citrate, succinate, 2-oxoglutarate and especially malonate elicited effects similar to sucrose, but at much lower concentrations. However, malonate inhibition of chlorophyll accumulation was overcome by increased concentrations of glutamine. At concentrations that usually inhibited chlorophyll, malonate did not reduce CO2 production in the presence of glutamine or KNO3. Sucrose effects on regreening were reduced by 1-iodoacetate. These results indicate that sugar regulation of plastid reversion during regreening in citrus epicarp is not directly due to sugars, but is instead mediated through metabolism of sugars to organic acids, especially malonic acid.

  11. Regulating Inflammation Using Acid-Responsive Electrospun Fibrous Scaffolds for Skin Scarless Healing

    Directory of Open Access Journals (Sweden)

    Ziming Yuan

    2014-01-01

    Full Text Available Skin injury in adult mammals brings about a series of events and inflammation in the wounded area is initiated first and provides lots of inflammatory factors, which is critical for the final scar formation. While the postinjured skin of fetus and nude mice heals scarlessly owing to the absence of inflammation or immunodeficient, we designed a feasible acid-responsive ibuprofen-loaded poly(L-lactide (PLLA fibrous scaffolds via doping sodium bicarbonate to prevent excessive inflammation and achieve scarless healing finally. The morphological results of in vivo experiments revealed that animals treated with acid-responsive ibuprofen-loaded PLLA fibrous scaffolds exhibited alleviative inflammation, accelerated healing process, and regulated collagen deposition via interference in the collagen distribution, the α-smooth muscle actin (α-SMA, and the basic fibroblast growth factor (bFGF expression. The lower ratios of collagen I/collagen III and TGF-β1/TGF-β3 and higher ratio of matrix metalloproteinase-1 (MMP-1/tissue inhibitor of metalloproteinase-1 (TIMP-1 in acid-responsive ibuprofen-loaded PLLA fibrous scaffolds group were confirmed by real-time qPCR as well. These results suggest that inhibiting the excessive inflammation will result in regular collagen distribution and appropriate ratio between the factors, which promote or suppress the scar formation, then decrease the scar area, and finally achieve the scarless healing.

  12. Regulating inflammation using acid-responsive electrospun fibrous scaffolds for skin scarless healing.

    Science.gov (United States)

    Yuan, Ziming; Zhao, Jingwen; Chen, Yigang; Yang, Zhili; Cui, Wenguo; Zheng, Qi

    2014-01-01

    Skin injury in adult mammals brings about a series of events and inflammation in the wounded area is initiated first and provides lots of inflammatory factors, which is critical for the final scar formation. While the postinjured skin of fetus and nude mice heals scarlessly owing to the absence of inflammation or immunodeficient, we designed a feasible acid-responsive ibuprofen-loaded poly(L-lactide) (PLLA) fibrous scaffolds via doping sodium bicarbonate to prevent excessive inflammation and achieve scarless healing finally. The morphological results of in vivo experiments revealed that animals treated with acid-responsive ibuprofen-loaded PLLA fibrous scaffolds exhibited alleviative inflammation, accelerated healing process, and regulated collagen deposition via interference in the collagen distribution, the α-smooth muscle actin (α-SMA), and the basic fibroblast growth factor (bFGF) expression. The lower ratios of collagen I/collagen III and TGF-β1/TGF-β3 and higher ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in acid-responsive ibuprofen-loaded PLLA fibrous scaffolds group were confirmed by real-time qPCR as well. These results suggest that inhibiting the excessive inflammation will result in regular collagen distribution and appropriate ratio between the factors, which promote or suppress the scar formation, then decrease the scar area, and finally achieve the scarless healing.

  13. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    Energy Technology Data Exchange (ETDEWEB)

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-06-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

  14. Vesicles from pH-regulated reversible gemini amino-acid surfactants as nanocapsules for delivery.

    Science.gov (United States)

    Lv, Jing; Qiao, Weihong; Li, Zongshi

    2016-10-01

    Reversible transition from micelles to vesicles by regulating pH were realized by gemini amino-acid surfactants N,N'-dialkyl-N,N'-diacetate ethylenediamine. Measurement results of ζ-potential at different pH and DLS at varying solvents revealed that the protonation between H(+) and double NCH2COO(-) groups (generating NH(+)CH2COO(-)), expressed as pKa1 and pKa2, is the key driving force to control the aggregation behaviors of gemini surfactant molecule. Effect of pH on the bilayer structure was studied in detail by using steady-state fluorescence spectroscopy of hydrophobic pyrene and Coumarin 153 (C153) respectively and fluorescence resonance energy transfer (FRET) from C153 to Rhodamine 6G (R6G). Various pH-regulated and pH-reversible self-assemblies were obtained in one surfactant system. Vitamin D3 was encapsulated in vesicle bilayers to form nano-VD3-capsules as VD3 supplement agent for health care products. By using the electrostatic attraction between Ca(2+) and double -COO(-) groups, nano-VD3-capsules with Ca(2+) coated outermost layers were prepared as a formulation for VD3 and calcium co-supplement agent. DLS and TEM were performed to check stability and morphology of the nano-capsules. It is concluded that the pH-regulated gemini amino-acid surfactants can be used to construct colloidal systems for delivering hydrophobic drugs or nutritions without lipids at human physiological pH level.

  15. ABSCISIC ACID-INSENSITIVE 4 negatively regulates flowering through directly promoting Arabidopsis FLOWERING LOCUS C transcription

    Science.gov (United States)

    Shu, Kai; Chen, Qian; Wu, Yaorong; Liu, Ruijun; Zhang, Huawei; Wang, Shengfu; Tang, Sanyuan; Yang, Wenyu; Xie, Qi

    2016-01-01

    During the life cycle of a plant, one of the major biological processes is the transition from the vegetative to the reproductive stage. In Arabidopsis, flowering time is precisely controlled by extensive environmental and internal cues. Gibberellins (GAs) promote flowering, while abscisic acid (ABA) is considered as a flowering suppressor. However, the detailed mechanism through which ABA inhibits the floral transition is poorly understood. Here, we report that ABSCISIC ACID-INSENSITIVE 4 (ABI4), a key component in the ABA signalling pathway, negatively regulates floral transition by directly promoting FLOWERING LOCUS C (FLC) transcription. The abi4 mutant showed the early flowering phenotype whereas ABI4-overexpressing (OE-ABI4) plants had delayed floral transition. Consistently, quantitative reverse transcription–PCR (qRT–PCR) assay revealed that the FLC transcription level was down-regulated in abi4, but up-regulated in OE-ABI4. The change in FT level was consistent with the pattern of FLC expression. Chromatin immunoprecipitation-qPCR (ChIP-qPCR), electrophoretic mobility shift assay (EMSA), and tobacco transient expression analysis showed that ABI4 promotes FLC expression by directly binding to its promoter. Genetic analysis demonstrated that OE-ABI4::flc-3 could not alter the flc-3 phenotype. OE-FLC::abi4 showed a markedly delayed flowering phenotype, which mimicked OE-FLC::WT, and suggested that ABI4 acts upstream of FLC in the same genetic pathway. Taken together, these findings suggest that ABA inhibits the floral transition by activating FLC transcription through ABI4. PMID:26507894

  16. Multiple-motor based transport and its regulation by Tau

    Science.gov (United States)

    Vershinin, Michael; Carter, Brian C.; Razafsky, David S.; King, Stephen J.; Gross, Steven P.

    2007-01-01

    Motor-based intracellular transport and its regulation are crucial to the functioning of a cell. Disruption of transport is linked to Alzheimer's and other neurodegenerative diseases. However, many fundamental aspects of transport are poorly understood. An important issue is how cells achieve and regulate efficient long-distance transport. Mounting evidence suggests that many in vivo cargoes are transported along microtubules by more than one motor, but we do not know how multiple motors work together or can be regulated. Here we first show that multiple kinesin motors, working in conjunction, can achieve very long distance transport and apply significantly larger forces without the need of additional factors. We then demonstrate in vitro that the important microtubule-associated protein, tau, regulates the number of engaged kinesin motors per cargo via its local concentration on microtubules. This function of tau provides a previously unappreciated mechanism to regulate transport. By reducing motor reattachment rates, tau affects cargo travel distance, motive force, and cargo dispersal. We also show that different isoforms of tau, at concentrations similar to those in cells, have dramatically different potency. These results provide a well defined mechanism for how altered tau isoform levels could impair transport and thereby lead to neurodegeneration without the need of any other pathway. PMID:17190808

  17. Retinoic acid alleviates Con A-induced hepatitis and differentially regulates effector production in NKT cells.

    Science.gov (United States)

    Lee, Kyoo-A; Song, You Chan; Kim, Ga-Young; Choi, Gyeyoung; Lee, Yoon-Sook; Lee, Jung-Mi; Kang, Chang-Yuil

    2012-07-01

    Retinoic acid (RA) is a diverse regulator of immune responses. Although RA promotes natural killer T (NKT) cell activation in vitro by increasing CD1d expression on antigen-presenting cells (APCs), the direct effects of RA on NKT-cell responses in vivo are not known. In the present study, we demonstrated the effect of RA on the severity of Con A-induced hepatitis and molecular changes of NKT cells. First, we demonstrated that Con A-induced liver damage was ameliorated by RA. In correlation with cytokine levels in serum, RA regulated the production of IFN-γ and IL-4 but not TNF-α by NKT cells without influencing the NKT-cell activation status. However, RA did not alleviate α-GalCer-induced liver injury, even though it reduced IFN-γ and IL-4 but not TNF-α levels in serum. This regulation was also detected when liver mononuclear cells (MNCs) or NKT hybridoma cells were treated with RA in vitro. The regulatory effect of RA on NKT cells was mediated by RAR-α, and RA reduced the phosphorylation of MAPK. These results suggest that RA differentially modulates the production of effector cytokines by NKT cells in hepatitis, and the suppressive effect of RA on hepatitis varies with the pathogenic mechanism of liver injury.

  18. Functional analysis of a Lemna gibba rbcS promoter regulated by abscisic acid and sugar

    Indian Academy of Sciences (India)

    Youru Wang

    2013-04-01

    Photosynthesis-associated nuclear genes (PhANGs) are able to respond to multiple environmental and developmental signals, including light, sugar and abscisic acid (ABA). PhANGs have been extensively studied at the level of transcriptional regulation, and several cis-acting elements important for light responsiveness have been identified in their promoter sequences. However, the regulatory elements involved in sugar and ABA regulation of PhANGs have not been completely characterized. A ribulose-1,5-bisphosphate carboxylase small subunit gene (rbcS) promoter (SSU5C promoter) was isolated from duckweed (Lemna gibba). A series of SSU5C promoter 5′ deletion fragments were fused to an intron–gus gene, and transgenic tobacco suspension cell lines were generated. Assay of tobacco suspension cell line harbouring the complete promoter in the fusion construct indicated that SSU5C promoter was negatively regulated by sugar and ABA under the condition of regular photoperiod. 5′ deletion analysis of SSU5C promoter in transgenic tobacco suspension cell lines confirmed that a region between positions $-310$ and $-152$ included the ABA-response region, and that sugar-response cis-acting elements might be located in the region between $-152$ and $-117$. Taken together, our results confirmed that the cis-regulatory region responsible for repression by ABA and sugar in the SSU5C promoter was located between $-310$ and $-117$.

  19. Bile acids are "homeotrophic" sensors of the functional hepatic capacity and regulate adaptive growth during liver regeneration.

    Science.gov (United States)

    Geier, Andreas; Trautwein, Christian

    2007-01-01

    Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor-dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth.

  20. Folic acid protects against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1.

    Science.gov (United States)

    Ma, Yan; Zhang, Chen; Gao, Xiao-Bo; Luo, Hai-Yan; Chen, Yang; Li, Hui-hua; Ma, Xu; Lu, Cai-Ling

    2015-11-05

    As a nutritional factor, folic acid can prevent cardiac and neural defects during embryo development. Our previous study showed that arsenic impairs embryo development by down-regulating Dvr1/GDF1 expression in zebrafish. Here, we investigated whether folic acid could protect against arsenic-mediated embryo toxicity. We found that folic acid supplementation increases hatching and survival rates, decreases malformation rate and ameliorates abnormal cardiac and neural development of zebrafish embryos exposed to arsenite. Both real-time PCR analysis and whole in-mount hybridization showed that folic acid significantly rescued the decrease in Dvr1 expression caused by arsenite. Subsequently, our data demonstrated that arsenite significantly decreased cell viability and GDF1 mRNA and protein levels in HEK293ET cells, while folic acid reversed these effects. Folic acid attenuated the increase in subcellular reactive oxygen species (ROS) levels and oxidative adaptor p66Shc protein expression in parallel with the changes in GDF1 expression and cell viability. P66Shc knockdown significantly inhibited the production of ROS and the down-regulation of GDF1 induced by arsenite. Our data demonstrated that folic acid supplementation protected against arsenic-mediated embryo toxicity by up-regulating the expression of Dvr1/GDF1, and folic acid enhanced the expression of GDF1 by decreasing p66Shc expression and subcellular ROS levels.

  1. Troger's base molecular scaffolds in dicarboxylic acid recognition.

    Science.gov (United States)

    Goswami, S; Ghosh, K; Dasgupta, S

    2000-04-07

    Artificial receptors (1-5) have been designed and synthesized from simple precursors. The chain length selectivity studies of dicarboxylic acids within the cavities of new fluorescent Troger's base molecular frameworks (1-3) have been carried out with a critical examination of their role of rigidity as well as flexibility in selective binding in comparison to receptor 5. The chiral resolution of the racemic Troger's base receptors (1 and 2) by chiral recognition with (+)- camphoric acid using hydrogen-bonding interactions has been studied.

  2. Are Management-Based Regulations Effective? Evidence from State Pollution Prevention Programs

    Science.gov (United States)

    Bennear, Lori Snyder

    2007-01-01

    This paper evaluates a recent innovation in regulating risk called management-based regulation. Traditionally, risk regulation has either specified a particular means of achieving a risk-reduction goal or specified the goal and left the means of achieving that goal up to the regulated entity. In contrast, management-based regulation neither…

  3. A new EPR dosimeter based on sulfanilic acid

    Energy Technology Data Exchange (ETDEWEB)

    Maghraby, A. [Radiation Dosimetry Department, National Institute for Standards (NIS), Ministry of Scientific Research, Haram, Giza, Tersa Street, P.O. Box 136 (Egypt)]. E-mail: maghrabism@yahoo.com; Tarek, E. [Physics Department, Faculty of Science, Fayoum University, Fayoum (Egypt)

    2006-02-15

    A new radiation dosimeter based on sulfanilic acid was suggested and tested. Radiation-induced radical EPR spectrum was recorded and characterized. EPR spectrum of sulfanilic acid is characterized by its simple single signal, which is located at g-factor=2.0053+/-0.00017. Its microwave absorption curve and effect of modulation amplitude on signal intensity and line width were studied. The radiation-induced radical was found to be stable after about 24h following irradiation within +/-1.2%. Energy dependence curves of sulfanilic acid compared to soft tissue and alanine were plotted. Sulfanilic acid is characterized also by its isotropic behavior and its calibration curve in {sup 137}Cs gamma radiation is plotted compared to that of alanine. Its sensitivity is about 85% of alanine, while its detection limit is about 100+/-30mGy.

  4. Carbon Dot Based Sensing of Dopamine and Ascorbic Acid

    Directory of Open Access Journals (Sweden)

    Upama Baruah

    2014-01-01

    Full Text Available We demonstrate carbon dot based sensor of catecholamine, namely, dopamine and ascorbic acid. Carbon dots (CDs were prepared from a green source: commercially available Assam tea. The carbon dots prepared from tea had particle sizes of ∼0.8 nm and are fluorescent. Fluorescence of the carbon dots was found to be quenched in the presence of dopamine and ascorbic acid with greater sensitivity for dopamine. The minimum detectable limits were determined to be 33 μM and 98 μM for dopamine and ascorbic acid, respectively. The quenching constants determined from Stern-Volmer plot were determined to be 5 × 10−4 and 1 × 10−4 for dopamine and ascorbic acid, respectively. A probable mechanism of quenching has been discussed in the paper.

  5. The Heparan and Heparin Metabolism Pathway is Involved in Regulation of Fatty Acid Composition

    Directory of Open Access Journals (Sweden)

    Zhihua Jiang, Jennifer J. Michal, Xiao-Lin Wu, Zengxiang Pan, Michael D. MacNeil

    2011-01-01

    Full Text Available Six genes involved in the heparan sulfate and heparin metabolism pathway, DSEL (dermatan sulfate epimerase-like, EXTL1 (exostoses (multiple-like 1, HS6ST1 (heparan sulfate 6-O-sulfotransferase 1, HS6ST3 (heparan sulfate 6-O-sulfotransferase 3, NDST3 (N-deacetylase/N-sulfotransferase (heparan glucosaminyl 3, and SULT1A1 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 1, were investigated for their associations with muscle lipid composition using cattle as a model organism. Nineteen single nucleotide polymorphisms (SNPs/multiple nucleotide length polymorphisms (MNLPs were identified in five of these six genes. Six of these mutations were then genotyped on 246 Wagyu x Limousin F2 animals, which were measured for 5 carcass, 6 eating quality and 8 fatty acid composition traits. Association analysis revealed that DSEL, EXTL1 and HS6ST1 significantly affected two stearoyl-CoA desaturase activity indices, the amount of conjugated linoleic acid (CLA, and the relative amount of saturated fatty acids (SFA and monounsaturated fatty acids (MUFA in skeletal muscle (P<0.05. In particular, HS6ST1 joined our previously reported SCD1 and UQCRC1 genes to form a three gene network for one of the stearoyl-CoA desaturase activity indices. These results provide evidence that genes involved in heparan sulfate and heparin metabolism are also involved in regulation of lipid metabolism in bovine muscle. Whether the SNPs affected heparan sulfate proteoglycan structure is unknown and warrants further investigation.

  6. Metabolic pathways regulated by γ-aminobutyric acid (GABA) contributing to heat tolerance in creeping bentgrass (Agrostis stolonifera).

    Science.gov (United States)

    Li, Zhou; Yu, Jingjin; Peng, Yan; Huang, Bingru

    2016-07-26

    γ-Aminobutyric acid is a non-protein amino acid involved in various metabolic processes. The objectives of this study were to examine whether increased GABA could improve heat tolerance in cool-season creeping bentgrass through physiological analysis, and to determine major metabolic pathways regulated by GABA through metabolic profiling. Plants were pretreated with 0.5 mM GABA or water before exposed to non-stressed condition (21/19 °C) or heat stress (35/30 °C) in controlled growth chambers for 35 d. The growth and physiological analysis demonstrated that exogenous GABA application significantly improved heat tolerance of creeping bentgrass. Metabolic profiling found that exogenous application of GABA led to increases in accumulations of amino acids (glutamic acid, aspartic acid, alanine, threonine, serine, and valine), organic acids (aconitic acid, malic acid, succinic acid, oxalic acid, and threonic acid), sugars (sucrose, fructose, glucose, galactose, and maltose), and sugar alcohols (mannitol and myo-inositol). These findings suggest that GABA-induced heat tolerance in creeping bentgrass could involve the enhancement of photosynthesis and ascorbate-glutathione cycle, the maintenance of osmotic adjustment, and the increase in GABA shunt. The increased GABA shunt could be the supply of intermediates to feed the tricarboxylic acid cycle of respiration metabolism during a long-term heat stress, thereby maintaining metabolic homeostasis.

  7. Efficient production of optically pure L-lactic acid from food waste at ambient temperature by regulating key enzyme activity.

    Science.gov (United States)

    Li, Xiang; Chen, Yinguang; Zhao, Shu; Chen, Hong; Zheng, Xiong; Luo, Jinyang; Liu, Yanan

    2015-03-01

    Bio-production of optically pure L-lactic acid from food waste has attracted much interest as it can treat organic wastes with simultaneous recovery of valuable by-products. However, the yield of L-lactic acid was very low and no optically pure L-lactic acid was produced in the literature due to (1) the lower activity of enzymes involved in hydrolysis and L-lactic acid generation, and (2) the participation of other enzymes related to D-lactic acid and acetic and propionic acids production. In this paper, a new strategy was reported for effective production of optically pure L-lactic acid from food waste at ambient temperature, i.e. via regulating key enzyme activity by sewage sludge supplement and intermittent alkaline fermentation. It was found that not only optically pure L-lactic acid was produced, but the yield was enhanced by 2.89-fold. The mechanism study showed that the activities of enzymes relevant to food waste hydrolysis and lactic acid production were enhanced, and the key enzymes related to volatile fatty acids and D-lactic acid generations were severally decreased or inhibited. Also, the microbes responsible for L-lactic acid production were selectively proliferated. Finally, the pilot-scale continuous experiment was conducted to testify the feasibility of this new technique.

  8. Strong Relationships in Acid-Base Chemistry – Modeling Protons Based on Predictable Concentrations of Strong Ions, Total Weak Acid Concentrations, and pCO2

    Science.gov (United States)

    Kellum, John A.

    2016-01-01

    Understanding acid-base regulation is often reduced to pigeonholing clinical states into categories of disorders based on arterial blood sampling. An earlier ambition to quantitatively explain disorders by measuring production and elimination of acid has not become standard clinical practice. Seeking back to classical physical chemistry we propose that in any compartment, the requirement of electroneutrality leads to a strong relationship between charged moieties. This relationship is derived in the form of a general equation stating charge balance, making it possible to calculate [H+] and pH based on all other charged moieties. Therefore, to validate this construct we investigated a large number of blood samples from intensive care patients, where both data and pathology is plentiful, by comparing the measured pH to the modeled pH. We were able to predict both the mean pattern and the individual fluctuation in pH based on all other measured charges with a correlation of approximately 90% in individual patient series. However, there was a shift in pH so that fitted pH in general is overestimated (95% confidence interval -0.072–0.210) and we examine some explanations for this shift. Having confirmed the relationship between charged species we then examine some of the classical and recent literature concerning the importance of charge balance. We conclude that focusing on the charges which are predictable such as strong ions and total concentrations of weak acids leads to new insights with important implications for medicine and physiology. Importantly this construct should pave the way for quantitative acid-base models looking into the underlying mechanisms of disorders rather than just classifying them. PMID:27631369

  9. Effects of inhibition gastric acid secretion on arterial acid-base status during digestion in the toad Bufo marinus.

    Science.gov (United States)

    Andersen, Johnnie B; Andrade, Denis V; Wang, Tobias

    2003-07-01

    Digestion affects acid-base status, because the net transfer of HCl from the blood to the stomach lumen leads to an increase in HCO3(-) levels in both extra- and intracellular compartments. The increase in plasma [HCO3(-)], the alkaline tide, is particularly pronounced in amphibians and reptiles, but is not associated with an increased arterial pH, because of a concomitant rise in arterial PCO2 caused by a relative hypoventilation. In this study, we investigate whether the postprandial increase in PaCO2 of the toad Bufo marinus represents a compensatory response to the increased plasma [HCO3(-)] or a state-dependent change in the control of pulmonary ventilation. To this end, we successfully prevented the alkaline tide, by inhibiting gastric acid secretion with omeprazole, and compared the response to that of untreated toads determined in our laboratory during the same period. In addition, we used vascular infusions of bicarbonate to mimic the alkaline tide in fasting animals. Omeprazole did not affect blood gases, acid-base and haematological parameters in fasting toads, but abolished the postprandial increase in plasma [HCO3(-)] and the rise in arterial PCO2 that normally peaks 48 h into the digestive period. Vascular infusion of HCO3(-), that mimicked the postprandial rise in plasma [HCO3(-)], led to a progressive respiratory compensation of arterial pH through increased arterial PCO2. Thus, irrespective of whether the metabolic alkalosis is caused by gastric acid secretion in response to a meal or experimental infusion of bicarbonate, arterial pH is being maintained by an increased arterial PCO2. It seems, therefore, that the elevated PCO2, occuring during the postprandial period, constitutes of a regulated response to maintain pH rather than a state-dependent change in ventilatory control.

  10. A knowledge based advisory system for acid/base titrations in non-aqueous solvents

    NARCIS (Netherlands)

    Bos, M.; Linden, van der W.E.

    1996-01-01

    A computer program was developed that could advice on the choice of solvent and titrant for acid/base titrations in nonaqueous media. It is shown that the feasibility of a titration in a given solvent can be calculated from solvent properties and intrinsic acid/base properties of the sample componen

  11. Ionic and Amino Acid Regulation in Hard Clam (Meretrix lusoria in Response to Salinity Challenges

    Directory of Open Access Journals (Sweden)

    Chia-Hao Lin

    2016-08-01

    Full Text Available Most marine mollusks are osmoconformers, in that, their body fluid osmolality changes in the direction of the change in environmental salinity. Marine mollusks exhibit a number of osmoregulatory mechanisms to cope with either hypo- or hyperosmotic stress. The effects of changes in salinity on the osmoregulatory mechanisms of the hard clam (Meretrix lusoria, an economically important species of marine bivalve for Taiwan have not been determined. In this study, we examined the effect of exposure to hypo (10‰- and hyper (35‰-osmotic salinity on hard clams raised at their natural salinity (20‰. The osmolality, [Na+], and [Cl-] of the hard clam hemolymph were changed in the same direction as the surrounding salinity. Further, the contents of total free amino acids including taurine in the gills and mantles were significantly upregulated in hard clam with increasing salinity. The gill Na+,K+-ATPase (NKA activity, the important enzyme regulating cellular inorganic ions, was not affected by the changed salinity. Mantle NKA activity, however, was stimulated in the 35‰ SW treatment. The taurine transporter (TAUT is related to the regulation of intracellular contents of taurine, the dominant osmolyte. Herein, a TAUT gene of hard clam was cloned and a TAUT antibody was derived for the immunoblotting. The TAUT mRNA expression of the mantle in hard clam was significantly stimulated in 35‰ SW, but protein expression was not modulated by the changed salinity. In gills of the hard clam with 10‰ SW, both TAUT mRNA and protein expressions were significantly stimulated, and it may reflect a feedback regulation from the decreased gills taurine content under long-term hypoosmotic acclimation. These findings suggest that TAUT expression is regulated differently in gills and mantles following exposure to alterations in environmental salinity. Taken together, this study used the physiological, biochemical and molecular approaches to simultaneously explore

  12. Ionic and Amino Acid Regulation in Hard Clam (Meretrix lusoria) in Response to Salinity Challenges.

    Science.gov (United States)

    Lin, Chia-Hao; Yeh, Po-Ling; Lee, Tsung-Han

    2016-01-01

    Most marine mollusks are osmoconformers, in that, their body fluid osmolality changes in the direction of the change in environmental salinity. Marine mollusks exhibit a number of osmoregulatory mechanisms to cope with either hypo- or hyperosmotic stress. The effects of changes in salinity on the osmoregulatory mechanisms of the hard clam (Meretrix lusoria, an economically important species of marine bivalve for Taiwan) have not been determined. In this study, we examined the effect of exposure to hypo (10‰)- and hyper (35‰)-osmotic salinity on hard clams raised at their natural salinity (20‰). The osmolality, [Na(+)], and [Cl(-)] of the hard clam hemolymph were changed in the same direction as the surrounding salinity. Further, the contents of total free amino acids including taurine in the gills and mantles were significantly upregulated in hard clam with increasing salinity. The gill Na(+), K(+)-ATPase (NKA) activity, the important enzyme regulating cellular inorganic ions, was not affected by the changed salinity. Mantle NKA activity, however, was stimulated in the 35‰ SW treatment. The taurine transporter (TAUT) is related to the regulation of intracellular contents of taurine, the dominant osmolyte. Herein, a TAUT gene of hard clam was cloned and a TAUT antibody was derived for the immunoblotting. The TAUT mRNA expression of the mantle in hard clam was significantly stimulated in 35‰ SW, but protein expression was not modulated by the changed salinity. In gills of the hard clam with 10‰ SW, both TAUT mRNA and protein expressions were significantly stimulated, and it may reflect a feedback regulation from the decreased gills taurine content under long-term hypoosmotic acclimation. These findings suggest that TAUT expression is regulated differently in gills and mantles following exposure to alterations in environmental salinity. Taken together, this study used the physiological, biochemical and molecular approaches to simultaneously explore the

  13. Thioredoxin, a master regulator of the tricarboxylic acid cycle in plant mitochondria.

    Science.gov (United States)

    Daloso, Danilo M; Müller, Karolin; Obata, Toshihiro; Florian, Alexandra; Tohge, Takayuki; Bottcher, Alexandra; Riondet, Christophe; Bariat, Laetitia; Carrari, Fernando; Nunes-Nesi, Adriano; Buchanan, Bob B; Reichheld, Jean-Philippe; Araújo, Wagner L; Fernie, Alisdair R

    2015-03-17

    Plant mitochondria have a fully operational tricarboxylic acid (TCA) cycle that plays a central role in generating ATP and providing carbon skeletons for a range of biosynthetic processes in both heterotrophic and photosynthetic tissues. The cycle enzyme-encoding genes have been well characterized in terms of transcriptional and effector-mediated regulation and have also been subjected to reverse genetic analysis. However, despite this wealth of attention, a central question remains unanswered: "What regulates flux through this pathway in vivo?" Previous proteomic experiments with Arabidopsis discussed below have revealed that a number of mitochondrial enzymes, including members of the TCA cycle and affiliated pathways, harbor thioredoxin (TRX)-binding sites and are potentially redox-regulated. We have followed up on this possibility and found TRX to be a redox-sensitive mediator of TCA cycle flux. In this investigation, we first characterized, at the enzyme and metabolite levels, mutants of the mitochondrial TRX pathway in Arabidopsis: the NADP-TRX reductase a and b double mutant (ntra ntrb) and the mitochondrially located thioredoxin o1 (trxo1) mutant. These studies were followed by a comparative evaluation of the redistribution of isotopes when (13)C-glucose, (13)C-malate, or (13)C-pyruvate was provided as a substrate to leaves of mutant or WT plants. In a complementary approach, we evaluated the in vitro activities of a range of TCA cycle and associated enzymes under varying redox states. The combined dataset suggests that TRX may deactivate both mitochondrial succinate dehydrogenase and fumarase and activate the cytosolic ATP-citrate lyase in vivo, acting as a direct regulator of carbon flow through the TCA cycle and providing a mechanism for the coordination of cellular function.

  14. The Pepper CaOSR1 Protein Regulates the Osmotic Stress Response via Abscisic Acid Signaling.

    Science.gov (United States)

    Park, Chanmi; Lim, Chae Woo; Lee, Sung Chul

    2016-01-01

    Plants are sessile organisms, and their growth and development is detrimentally affected by environmental stresses such as drought and high salinity. Defense mechanisms are tightly regulated and complex processes, which respond to changing environmental conditions; however, the precise mechanisms that function under adverse conditions remain unclear. Here, we report the identification and functional characterization of the CaOSR1 gene, which functions in the adaptive response to abiotic stress. We found that CaOSR1 gene expression in pepper leaves was up-regulated after exposure to abscisic acid (ABA), drought, and high salinity. In addition, we demonstrated that the fusion protein of CaOSR1 with green fluorescent protein (GFP) is localized in the nucleus. We used CaOSR1-silenced pepper plants and CaOSR1-OX-overexpressing (OX) transgenic Arabidopsis plants to show that the CaOSR1 protein regulates the osmotic stress response. CaOSR1-silenced pepper plants showed increased drought susceptibility, and this was accompanied by a high transpiration rate. CaOSR1-OX plants displayed phenotypes that were hypersensitive to ABA and hyposensitive to osmotic stress, during the seed germination and seedling growth stages; furthermore, these plants exhibited enhanced drought tolerance at the adult stage, and this was characterized by higher leaf temperatures and smaller stomatal apertures because of ABA hypersensitivity. Taken together, our data indicate that CaOSR1 positively regulates osmotic stress tolerance via ABA-mediated cell signaling. These findings suggest an involvement of a novel protein in ABA and osmotic stress signalings in plants.

  15. Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake

    DEFF Research Database (Denmark)

    Habets, Daphna D J; Luiken, Joost J F P; Ouwens, Margriet;

    2012-01-01

    Aim: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-¿ knockout mice the roles of atypical PKCs (PKC-¿ and PKC-¿) in regulating ca...... to allow optimal stimulation of glucose and fatty acid uptake, indicating that atypical PKCs are necessary but not rate-limiting in the regulation of cardiac substrate uptake and that PKC-¿ and PKC-¿ have interchangeable functions in these processes.......Aim: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-¿ knockout mice the roles of atypical PKCs (PKC-¿ and PKC-¿) in regulating...... cardiac glucose and fatty acid uptake. Results: Neither insulin-stimulated nor AMPK-mediated glucose and fatty acid uptake were inhibited upon genetic PKC-¿ ablation in cardiomyocytes. In contrast, myristoylated PKC-¿ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty...

  16. Glucagon Couples Hepatic Amino Acid Catabolism to mTOR-Dependent Regulation of α-Cell Mass

    Directory of Open Access Journals (Sweden)

    Mark J. Solloway

    2015-07-01

    Full Text Available Understanding the regulation of islet cell mass has important implications for the discovery of regenerative therapies for diabetes. The liver plays a central role in metabolism and the regulation of endocrine cell number, but liver-derived factors that regulate α-cell and β-cell mass remain unidentified. We propose a nutrient-sensing circuit between liver and pancreas in which glucagon-dependent control of hepatic amino acid metabolism regulates α-cell mass. We found that glucagon receptor inhibition reduced hepatic amino acid catabolism, increased serum amino acids, and induced α-cell proliferation in an mTOR-dependent manner. In addition, mTOR inhibition blocked amino-acid-dependent α-cell replication ex vivo and enabled conversion of α-cells into β-like cells in vivo. Serum amino acids and α-cell proliferation were increased in neonatal mice but fell throughout postnatal development in a glucagon-dependent manner. These data reveal that amino acids act as sensors of glucagon signaling and can function as growth factors that increase α-cell proliferation.

  17. Acid-base metabolism: implications for kidney stones formation.

    Science.gov (United States)

    Hess, Bernhard

    2006-04-01

    The physiology and pathophysiology of renal H+ ion excretion and urinary buffer systems are reviewed. The main focus is on the two major conditions related to acid-base metabolism that cause kidney stone formation, i.e., distal renal tubular acidosis (dRTA) and abnormally low urine pH with subsequent uric acid stone formation. Both the entities can be seen on the background of disturbances of the major urinary buffer system, NH3+ NH4+. On the one hand, reduced distal tubular secretion of H+ ions results in an abnormally high urinary pH and either incomplete or complete dRTA. On the other hand, reduced production/availability of NH4+ is the cause of an abnormally low urinary pH, which predisposes to uric acid stone formation. Most recent research indicates that the latter abnormality may be a renal manifestation of the increasingly prevalent metabolic syndrome. Despite opposite deviations from normal urinary pH values, both the dRTA and uric acid stone formation due to low urinary pH require the same treatment, i.e., alkali. In the dRTA, alkali is needed for improving the body's buffer capacity, whereas the goal of alkali treatment in uric acid stone formers is to increase the urinary pH to 6.2-6.8 in order to minimize uric acid crystallization.

  18. Photoresponsive self-assemblies based on fatty acids.

    Science.gov (United States)

    Fameau, A-L; Arnould, A; Lehmann, M; von Klitzing, R

    2015-02-18

    Photoresponsive surfactant system based on fatty acids has been developed by the introduction in aqueous solution of a photoacid generator (PAG). Self-assembly transitions are triggered by UV irradiation due to a pH change induced by the presence of PAG.

  19. A Schiff base formed from sulfanilic acid and dimethylformamide.

    Science.gov (United States)

    Hempel, A; Camerman, N; Mastropaolo, D; Camerman, A

    1999-04-15

    The crystal structure the Schiff base contains one 4-dimethylaminomethyleneaminobenzenesulfonic acid molecule in zwitterionic form [4-(dimethylaminomethyleneammonio)benzenesulfonate], and one water molecule in the asymmetric unit (C9H12N2O3S.H2O). Protonation occurs at nitrogen atom N1, but the charge is delocalized.

  20. Acid-Base Disorders--A Computer Simulation.

    Science.gov (United States)

    Maude, David L.

    1985-01-01

    Describes and lists a program for Apple Pascal Version 1.1 which investigates the behavior of the bicarbonate-carbon dioxide buffer system in acid-base disorders. Designed specifically for the preclinical medical student, the program has proven easy to use and enables students to use blood gas parameters to arrive at diagnoses. (DH)

  1. Interactions between acid- and base-functionalized surfaces

    NARCIS (Netherlands)

    Giesbers, M.; Kleijn, J.M.; Cohen Stuart, M.A.

    2002-01-01

    In this paper we present an AFM force study on interactions between chemically modified surfaces. Surfaces with terminal groups of either NH2 or COOH were obtained by chemisorption of a silane-based compound (3-amino-propyltriethoxysilane) on silica or a thiol compound (11-mercapto undecanoic acid)

  2. Students' Understanding of Acids/Bases in Organic Chemistry Contexts

    Science.gov (United States)

    Cartrette, David P.; Mayo, Provi M.

    2011-01-01

    Understanding key foundational principles is vital to learning chemistry across different contexts. One such foundational principle is the acid/base behavior of molecules. In the general chemistry sequence, the Bronsted-Lowry theory is stressed, because it lends itself well to studying equilibrium and kinetics. However, the Lewis theory of…

  3. Turkish Prospective Chemistry Teachers' Alternative Conceptions about Acids and Bases

    Science.gov (United States)

    Boz, Yezdan

    2009-01-01

    The purpose of this study was to obtain prospective chemistry teachers' conceptions about acids and bases concepts. Thirty-eight prospective chemistry teachers were the participants. Data were collected by means of an open-ended questionnaire and semi-structured interviews. Analysis of data indicated that most prospective teachers did not have…

  4. Asymmetric bipolar membranes in acid-base electrodialysis

    NARCIS (Netherlands)

    Wilhelm, Friedrich G.; Punt, Ineke; Vegt, van der Nico F.A.; Strathmann, H.; Wessling, M.

    2002-01-01

    In this experimental study, the influence of asymmetric bipolar membranes on the salt impurities in the acid and base product is investigated. The thickness of one, the other, or both ion-permeable layers of a bipolar membrane is increased. With increased layer thickness, the current-voltage curves

  5. Abscisic acid is a negative regulator of root gravitropism in Arabidopsis thaliana.

    Science.gov (United States)

    Han, Woong; Rong, Honglin; Zhang, Hanma; Wang, Myeong-Hyeon

    2009-01-23

    The plant hormone abscisic acid (ABA) plays a role in root gravitropism and has led to an intense debate over whether ABA acts similar to auxin by translating the gravitational signal into directional root growth. While tremendous advances have been made in the past two decades in establishing the role of auxin in root gravitropism, little progress has been made in characterizing the role of ABA in this response. In fact, roots of plants that have undetectable levels of ABA and that display a normal gravitropic response have raised some serious doubts about whether ABA plays any role in root gravitropism. Here, we show strong evidence that ABA plays a role opposite to that of auxin and that it is a negative regulator of the gravitropic response of Arabidopsis roots.

  6. Allosteric ACTion: the varied ACT domains regulating enzymes of amino-acid metabolism.

    Science.gov (United States)

    Lang, Eric J M; Cross, Penelope J; Mittelstädt, Gerd; Jameson, Geoffrey B; Parker, Emily J

    2014-12-01

    Allosteric regulation of enzyme activity plays important metabolic roles. Here we review the allostery of enzymes of amino-acid metabolism conferred by a discrete domain known as the ACT domain. This domain of 60-70 residues has a βαββαβ topology leading to a four-stranded β4β1β3β2 antiparallel sheet with two antiparallel helices on one face. Extensive sequence variation requires a combined sequence/structure/function analysis for identification of the ACT domain. Common features include highly varied modes of self-association of ACT domains, ligand binding at domain interfaces, and transmittal of allosteric signals through conformational changes and/or the manipulation of quaternary equilibria. A recent example illustrates the relatively facile adoption of this versatile module of allostery by gene fusion.

  7. Retinoic acid is enriched in Hensen's node and is developmentally regulated in the early chicken embryo.

    Science.gov (United States)

    Chen, Y; Huang, L; Russo, A F; Solursh, M

    1992-11-01

    Retinoic acid (RA) has been considered as a potential morphogen in the chicken limb and has also been suggested to be involved in early embryonic development. On the basis of biological activity, previous reports suggest that Hensen's node, the anatomical equivalent in the chicken of the Spemann's organizer, may contain RA. Here, by using a molecular assay system, we demonstrate that Hensen's node contains retinoids in a concentration approximately 20 times more than that in the neighboring tissues. Furthermore, stage 6 Hensen's node contains approximately 3 times more retinoid than that of stage 4 embryos. These endogenous retinoids may establish a concentration gradient from Hensen's node to adjacent tissues and play a role in establishing the primary embryonic axis in the vertebrate. The results also suggest that the retinoid concentration in Hensen's node is developmentally regulated.

  8. Phosphatidic Acid Regulates BZR1 Activity andBrassinosteroid Signal of Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    Dear Editor, Brassinosteroid (BR) is an important hormone and playscrucial roles in plant growth and development (Kim andWang, 2010). Genetics studies identify many componentsinvolving in BR signaling, including transcript factor BZR1(BRASSINAZOLE RESISTANT 1). BZR1 is dephosphorylated (Heet al., 2005) to regulate expression of target genes. A sin-gle amino acid mutation in BZR1 PEST domain results inenhanced binding and dephosphorylation by PP2A (PROTEINPHOSPHATASE 2A; Tang et al., 2011), leading to constitutivelyactivated BZR1 and enhanced BR signal in gain-of-functionmutant bzr1-1D. Although BR signal is well characterized inArabidopsis, how the components of BR signaling transduc-tion pathway are reclulated needs further illustrations.

  9. Retinoic acid receptor agonists regulate expression of ATP-binding cassette transporter G1 in macrophages.

    Science.gov (United States)

    Ayaori, Makoto; Yakushiji, Emi; Ogura, Masatsune; Nakaya, Kazuhiro; Hisada, Tetsuya; Uto-Kondo, Harumi; Takiguchi, Shunichi; Terao, Yoshio; Sasaki, Makoto; Komatsu, Tomohiro; Iizuka, Maki; Yogo, Makiko; Uehara, Yoshinari; Kagechika, Hiroyuki; Nakanishi, Tsuyoshi; Ikewaki, Katsunori

    2012-04-01

    ABC transporter G1 (ABCG1) plays a pivotal role in HDL-mediated cholesterol efflux and atherogenesis. We investigated whether, and how, retinoic acid receptors (RARs) regulate ABCG1 expression in macrophages. All-trans retinoic acid (ATRA), an RAR ligand, increased ABCG1 protein levels and apoA-I/HDL-mediated cholesterol efflux from the macrophages. Both ATRA and other RAR agonists, TTNPB and Am580, increased major transcripts driven by promoter B upstream of exon 5, though minor transcripts driven by promoter A upstream of exon 1 were only increased by ATRA. The stimulatory effects of ATRA on ABCG1 expression were completely abolished in the presence of RAR/RXR antagonists but were only partially canceled in the presence of an LXR antagonist. Adenovirus with overexpressed oxysterol sulfotransferase abolished the LXR pathway, as previously reported, and ATRA-responsiveness in ABCA1/ABCG1 expressions were respectively attenuated by 38 and 22% compared to the control virus. Promoter assays revealed that ABCG1 levels were regulated more by promoter B than promoter A, and ATRA activated promoter B in a liver X receptor-responsive element (LXRE)-dependent manner. Further, LXRE-B in intron 7, but not LXRE-A in intron 5, enhanced ATRA responsiveness under overexpression of all RAR isoforms-RARα/β/γ. In contrast, the activation of promoter B by TTNPB depended on LXRE-B and RARα, but not on RARβ/γ. Finally, chromatin immunoprecipitation and gel-shift assays revealed a specific and direct repeat 4-dependent binding of RARα to LXRE-B. In conclusion, RAR ligands increase ABCA1/G1 expression and apoA-I/HDL-mediated cholesterol efflux from macrophages, and modulate ABCG1 promoter activity via LXRE-dependent mechanisms.

  10. Lysophosphatidic acid (LPA 18:1 transcriptional regulation of primary human gingival fibroblasts

    Directory of Open Access Journals (Sweden)

    D. Roselyn Cerutis

    2014-12-01

    Full Text Available The pleiotropic, bioactive lipid lysophosphatidic acid [(LPA, 1-acyl-sn-glycerol-3-phosphate] exerts critical regulatory actions in physiology and pathophysiology in many systems. It is present in normal bodily fluids, and is elevated in pathology (1. In vivo, “LPA” exists as distinct molecular species, each having a single fatty acid of varying chain length and degree of unsaturation covalently attached to the glycerol backbone via an acyl, alkyl, or alkenyl link. These species differ in affinities for the individual LPA receptors [(LPARs, LPA1-6] and coupling to G proteins (2. However, LPA 18:1 has been and continues to be the most commonly utilized species in reported studies. The actions of “LPA” remain poorly defined in oral biology and pathophysiology. Our laboratory has addressed this knowledge gap by studying in vitro the actions of the major human salivary LPA species [18:1, 18:0, and 16:0 (3] in human oral cells (4–7. This includes gingival fibroblasts (GF, which our flow cytometry data from multiple donors found that they express LPA1-5 (6. We have also reported that these species are ten-fold elevated to pharmacologic levels in the saliva and gingival crevicular fluid obtained from patients with moderate–severe periodontitis (8. As the potential of LPA to regulate transcriptional activity had not been examined in the oral system, this study used whole human genome microarray analysis to test the hypothesis that LPA 18:1-treated human GF would show significant changes in gene transcripts relevant to their biology, wound-healing, and inflammatory responses. LPA 18:1 was found to significantly regulate a large, complex set of genes critical to GF biology in these categories and to periodontal disease. The raw data has been deposited at NCBI's GEO database as record GSE57496.

  11. Parallel proton transfer pathways in aqueous acid-base reactions

    OpenAIRE

    Cox, M. J.; Bakker, H.J.

    2008-01-01

    We study the mechanism of proton transfer (PT) between the photoacid 8-hydroxy-1,3, 6-pyrenetrisulfonic acid (HPTS) and the base chloroacetate in aqueous solution. We investigate both proton and deuteron transfer reactions in solutions with base concentrations ranging from 0.25M to 4M. Using femtosecond midinfrared spectroscopy, we probe the vibrational responses of HPTS, its conjugate photobase, the hydrated proton/deuteron, and chloroacetate. The measurement of these four resonances allows ...

  12. Nucleic Acid Base Analog FRET-Pair Facilitating Detailed Structural Measurements in Nucleic Acid Containing Systems

    DEFF Research Database (Denmark)

    Börjesson, Karl; Preus, Søren; El-Sagheer, Afaf;

    2009-01-01

    toward detailed studies of the inherent dynamics of nucleic acid structures. Moreover, the placement of FRET-pair chromophores inside the base stack will be a great advantage in studies where other (biomacro)molecules interact with the nucleic acid. Lastly, our study gives possibly the first truly solid...... distances covering up to more than one turn of the DNA duplex. Importantly, we show that the rigid stacking of the two base analogs, and consequently excellent control of their exact positions and orientations, results in a high control of the orientation factor and hence very distinct FRET changes...... as the number of bases separating tCO and tC(nitro) is varied. A set of DNA strands containing the FRET-pair at wisely chosen locations will, thus, make it possible to accurately distinguish distance- from orientation-changes using FRET. In combination with the good nucleobase analog properties, this points...

  13. Regulation of protein degradation pathways by amino acids and insulin in skeletal muscle of neonatal pigs

    Institute of Scientific and Technical Information of China (English)

    Agus Suryawan; Teresa ADavis

    2014-01-01

    Background:The rapid gain in lean mass in neonates requires greater rates of protein synthesis than degradation. We previously delineated the molecular mechanisms by which insulin and amino acids, especially leucine, modulate skeletal muscle protein synthesis and how this changes with development. In the current study, we identified mechanisms involved in protein degradation regulation. In experiment 1, 6-and 26-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic, 2) euinsulinemic-euglycemic-hyperaminoacidemic, and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps for 2 h. In experiment 2, 5-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic-euleucinemic, 2) euinsulinemic-euglycemic-hypoaminoacidemic-hyperleucinemic, and 3) euinsulinemic-euglycemic-euaminoacidemic-hyperleucinemic clamps for 24 h. We determined in muscle indices of ubiquitin-proteasome, i.e., atrogin-1 (MAFbx) and muscle RING-finger protein-1 (MuRF1) and autophagy-lysosome systems, i.e., unc51-like kinase 1 (UKL1), microtubule-associated protein light chain 3 (LC3), and lysosomal-associated membrane protein 2 (Lamp-2). For comparison, we measured ribosomal protein S6 (rpS6) and eukaryotic initiation factor 4E (eIF4E) activation, components of translation initiation. Results:Abundance of atrogin-1, but not MuRF1, was greater in 26-than 6-d-old pigs and was not affected by insulin, amino acids, or leucine. Abundance of ULK1 and LC3 was higher in younger pigs and not affected by treatment. The LC3-II/LC3-I ratio was reduced and ULK1 phosphorylation increased by insulin, amino acids, and leucine. These responses were more profound in younger pigs. Abundance of Lamp-2 was not affected by treatment or development. Abundance of eIF4E, but not rpS6, was higher in 6-than 26-d-old-pigs but unaffected by treatment. Phosphorylation of eIF4E was not affected by treatment, however, insulin, amino acids, and leucine stimulated rpS6 phosphorylation, and the

  14. Regulation of adipogenesis by medium-chain fatty acids in the absence of hormonal cocktail.

    Science.gov (United States)

    Yang, Jeong-Yeh; Della-Fera, Mary Anne; Rayalam, Srujana; Park, Hea Jin; Ambati, Suresh; Hausman, Dorothy B; Hartzell, Diane L; Baile, Clifton A

    2009-07-01

    We report here that octanoate and decanoate, 8-carbon and 10-carbon medium-chain fatty acids (MCFA), decreased adipogenesis in 3T3-L1 preadipocytes when treated with standard hormonal cocktail, but increased adipogenesis in a dose-dependent manner (with decanoate being more effective) when treated with basal media. Addition of dexamethasone to basal medium with either octanoate or decanoate further increased adipogenesis. In order to understand the adipogenic effects of MCFA in the absence of standard hormonal cocktail, postconfluent 3T3-L1 preadipocytes were treated with octanoate or decanoate, and the change in the expression of several adipogenic transcription factors and enzymes was investigated using real-time RT-PCR. Octanoate and decanoate up-regulated the mRNA expression of peroxisome-proliferator-activated receptor (PPAR) gamma, CCAAT/enhancer-binding protein (C/EBP) alpha, fatty-acid-binding protein, sterol-regulatory element binding protein 1c, lipoprotein lipase and hormone-sensitive lipase, and the protein expression of PPARgamma and C/EBPalpha, with decanoate being more effective. Moreover, the PPARgamma antagonist GW9662 inhibited MCFA-induced lipid accumulation by about 50%. Decanoate and octanoate, to a lesser degree, increased lipid accumulation, which was associated with an increase in glycerol-3-phosphate dehydrogenase activity. These results show that octanoate and decanoate may stimulate differentiation of preadipocytes, at least in part, by their influence on the expression of PPARgamma and other adipocyte-specific factors.

  15. Circadian and Dopaminergic Regulation of Fatty Acid Oxidation Pathway Genes in Retina and Photoreceptor Cells

    Science.gov (United States)

    Vancura, Patrick; Wolloscheck, Tanja; Baba, Kenkichi; Tosini, Gianluca; Iuvone, P. Michael; Spessert, Rainer

    2016-01-01

    The energy metabolism of the retina might comply with daily changes in energy demand and is impaired in diabetic retinopathy—one of the most common causes of blindness in Europe and the USA. The aim of this study was to investigate putative adaptation of energy metabolism in healthy and diabetic retina. Hence expression analysis of metabolic pathway genes was performed using quantitative polymerase chain reaction, semi-quantitative western blot and immunohistochemistry. Transcriptional profiling of key enzymes of energy metabolism identified transcripts of mitochondrial fatty acid β-oxidation enzymes, i.e. carnitine palmitoyltransferase-1α (Cpt-1α) and medium chain acyl-CoA dehydrogenase (Acadm) to display daily rhythms with peak values during daytime in preparations of the whole retina and microdissected photoreceptors. The cycling of both enzymes persisted in constant darkness, was dampened in mice deficient for dopamine D4 (D4) receptors and was altered in db/db mice—a model of diabetic retinopathy. The data of the present study are consistent with circadian clock-dependent and dopaminergic regulation of fatty acid oxidation in retina and its putative disturbance in diabetic retina. PMID:27727308

  16. [Catabolism of methylphosphonic acid and its physiological regulation in Escherichia coli].

    Science.gov (United States)

    Matys, S V; Laurinavichius, K S; Nesmeianova, M A

    1996-01-01

    It was found that methyl phosphonic acid (Pn) was degraded by different Escherichia coli strains, which utilized it as the sole phosphorus source with resulting methane formation. This ability was influenced by mutations in the regulatory genes of the pho regulon. Thus, Pn was not degraded by an E. coli mutant defective in the regulatory phoB gene, responsible for the induction of pho-regulon proteins during phosphorus starvation. The intensity of Pn degradation depended on the age and concentration of the inoculum. Preincubation of bacteria in the presence of Pn accelerated subsequent degradation of both methyl phosphonic acid and its esters. Cultures developing from a small amount of inoculum degraded Pn more efficiently than heavily inoculated cultures that underwent only one cell division. However, cultures heavily inoculated with adapted cells degraded Pn as efficiently as cultures developing from a small amount of inoculum. Aeration was an important factor regulating Pn degradation: Pn was degraded more efficiently under anaerobic conditions regardless of the amount of inoculum.

  17. Synthesis and regulation of chlorogenic acid in potato: Rerouting phenylpropanoid flux in HQT-silenced lines.

    Science.gov (United States)

    Payyavula, Raja S; Shakya, Roshani; Sengoda, Venkatesan G; Munyaneza, Joseph E; Swamy, Prashant; Navarre, Duroy A

    2015-05-01

    Chlorogenic acid (CGA) is the major phenolic sink in potato tubers and can constitute over 90% of total phenylpropanoids. The regulation of CGA biosynthesis in potato and the role of the CGA biosynthetic gene hydroxycinnamoyl CoA:quinate hydroxycinnamoyl transferase (HQT) was characterized. A sucrose induced accumulation of CGA correlated with the increased expression of phenylalanine ammonia-lyase (PAL) rather than HQT. Transient expression of the potato MYB transcription factor StAN1 (anthocyanin 1) in tobacco increased CGA. RNAi suppression of HQT resulted in over a 90% reduction in CGA and resulted in early flowering. The reduction in total phenolics and antioxidant capacity was less than the reduction in CGA, suggesting flux was rerouted into other phenylpropanoids. Network analysis showed distinct patterns in different organs, with anthocyanins and phenolic acids showing negative correlations in leaves and flowers and positive in tubers. Some flavonols increased in flowers, but not in leaves or tubers. Anthocyanins increased in flowers and showed a trend to increase in leaves, but not tubers. HQT suppression increased biosynthesis of caffeoyl polyamines, some of which are not previously reported in potato. Decreased PAL expression and enzyme activity was observed in HQT suppressed lines, suggesting the existence of a regulatory loop between CGA and PAL. Electrophysiology detected no effect of CGA suppression on potato psyllid feeding. Collectively, this research showed that CGA in potatoes is synthesized through HQT and HQT suppression altered phenotype and redirected phenylpropanoid flux.

  18. Phase Transformation of Adefovir Dipivoxil/Succinic Acid Cocrystals Regulated by Polymeric Additives

    Directory of Open Access Journals (Sweden)

    Sungyup Jung

    2013-12-01

    Full Text Available The polymorphic phase transformation in the cocrystallization of adefovir dipivoxil (AD and succinic acid (SUC was investigated. Inspired by biological and biomimetic crystallization, polymeric additives were utilized to control the phase transformation. With addition of poly(acrylic acid, the metastable phase newly identified through the analysis of X-ray diffraction was clearly isolated from the previously reported stable form. Without additives, mixed phases were obtained even at the early stage of cocrystallization. Also, infrared spectroscopy analysis verified the alteration of the hydrogen bonding that was mainly responsible for the cocrystal formation between AD and SUC. The hydrogen bonding in the metastable phase was relatively stronger than that in the stable form, which indicated the locally strong AD/SUC coupling in the initial stage of cocrystallization followed by the overall stabilization during the phase transformation. The stronger hydrogen bonding could be responsible for the faster nucleation of the initially observed metastable phase. The present study demonstrated that the polymeric additives could function as effective regulators for the polymorph-selective cocrystallization.

  19. Model for acid-base chemistry in nanoparticle growth (MABNAG

    Directory of Open Access Journals (Sweden)

    T. Yli-Juuti

    2013-03-01

    Full Text Available Climatic effects of newly-formed atmospheric secondary aerosol particles are to a large extent determined by their condensational growth rates. However, all the vapors condensing on atmospheric nanoparticles and growing them to climatically relevant sizes are not identified yet and the effects of particle phase processes on particle growth rates are poorly known. Besides sulfuric acid, organic compounds are known to contribute significantly to atmospheric nanoparticle growth. In this study a particle growth model MABNAG (Model for Acid-Base chemistry in NAnoparticle Growth was developed to study the effect of salt formation on nanoparticle growth, which has been proposed as a potential mechanism lowering the equilibrium vapor pressures of organic compounds through dissociation in the particle phase and thus preventing their evaporation. MABNAG is a model for monodisperse aqueous particles and it couples dynamics of condensation to particle phase chemistry. Non-zero equilibrium vapor pressures, with both size and composition dependence, are considered for condensation. The model was applied for atmospherically relevant systems with sulfuric acid, one organic acid, ammonia, one amine and water in the gas phase allowed to condense on 3–20 nm particles. The effect of dissociation of the organic acid was found to be small under ambient conditions typical for a boreal forest site, but considerable for base-rich environments (gas phase concentrations of about 1010 cm−3 for the sum of the bases. The contribution of the bases to particle mass decreased as particle size increased, except at very high gas phase concentrations of the bases. The relative importance of amine versus ammonia did not change significantly as a function of particle size. While our results give a reasonable first estimate on the maximum contribution of salt formation to nanoparticle growth, further studies on, e.g. the thermodynamic properties of the atmospheric organics

  20. Acid-base thermochemistry of gaseous oxygen and sulfur substituted amino acids (Ser, Thr, Cys, Met).

    Science.gov (United States)

    Riffet, Vanessa; Frison, Gilles; Bouchoux, Guy

    2011-11-07

    Acid-base thermochemistry of isolated amino acids containing oxygen or sulfur in their side chain (serine, threonine, cysteine and methionine) have been examined by quantum chemical computations. Density functional theory (DFT) was used, with B3LYP, B97-D and M06-2X functionals using the 6-31+G(d,p) basis set for geometry optimizations and the larger 6-311++G(3df,2p) basis set for energy computations. Composite methods CBS-QB3, G3B3, G4MP2 and G4 were applied to large sets of neutral, protonated and deprotonated conformers. Conformational analysis of these species, based on chemical approach and AMOEBA force field calculations, has been used to identify the lowest energy conformers and to estimate the population of conformers expected to be present at thermal equilibrium at 298 K. It is observed that G4, G4MP2, G3B3, CBS-QB3 composite methods and M06-2X DFT lead to similar conformer energies. Thermochemical parameters have been computed using either the most stable conformers or equilibrium populations of conformers. Comparison of experimental and theoretical proton affinities and Δ(acid)H shows that the G4 method provides the better agreement with deviations of less than 1.5 kJ mol(-1). From this point of view, a set of evaluated thermochemical quantities for serine, threonine, cysteine and methionine may be proposed: PA = 912, 919, 903, 938; GB = 878, 886, 870, 899; Δ(acid)H = 1393, 1391, 1396, 1411; Δ(acid)G = 1363, 1362, 1367, 1382 kJ mol(-1). This study also confirms that a non-negligible ΔpS° is associated with protonation of methionine and that the most acidic hydrogen of cysteine in the gas phase is that of the SH group. In several instances new conformers were identified thus suggesting a re-examination of several IRMPD spectra.

  1. Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members.

    Directory of Open Access Journals (Sweden)

    Enrique Marcos

    2011-09-01

    Full Text Available Oligomerization is a functional requirement for many proteins. The interfacial interactions and the overall packing geometry of the individual monomers are viewed as important determinants of the thermodynamic stability and allosteric regulation of oligomers. The present study focuses on the role of the interfacial interactions and overall contact topology in the dynamic features acquired in the oligomeric state. To this aim, the collective dynamics of enzymes belonging to the amino acid kinase family both in dimeric and hexameric forms are examined by means of an elastic network model, and the softest collective motions (i.e., lowest frequency or global modes of motions favored by the overall architecture are analyzed. Notably, the lowest-frequency modes accessible to the individual subunits in the absence of multimerization are conserved to a large extent in the oligomer, suggesting that the oligomer takes advantage of the intrinsic dynamics of the individual monomers. At the same time, oligomerization stiffens the interfacial regions of the monomers and confers new cooperative modes that exploit the rigid-body translational and rotational degrees of freedom of the intact monomers. The present study sheds light on the mechanism of cooperative inhibition of hexameric N-acetyl-L-glutamate kinase by arginine and on the allosteric regulation of UMP kinases. It also highlights the significance of the particular quaternary design in selectively determining the oligomer dynamics congruent with required ligand-binding and allosteric activities.

  2. Acid-sensing ion channels (ASICs: therapeutic targets for neurological diseases and their regulation

    Directory of Open Access Journals (Sweden)

    Hae-Jin Kweon

    2013-06-01

    Full Text Available Extracellular acidification occurs not only in pathologicalconditions such as inflammation and brain ischemia, but alsoin normal physiological conditions such as synaptic transmission.Acid-sensing ion channels (ASICs can detect a broadrange of physiological pH changes during pathological andsynaptic cellular activities. ASICs are voltage-independent,proton-gated cation channels widely expressed throughout thecentral and peripheral nervous system. Activation of ASICs isinvolved in pain perception, synaptic plasticity, learning andmemory, fear, ischemic neuronal injury, seizure termination,neuronal degeneration, and mechanosensation. Therefore,ASICs emerge as potential therapeutic targets for manipulatingpain and neurological diseases. The activity of these channelscan be regulated by many factors such as lactate, Zn2+, andPhe-Met-Arg-Phe amide (FMRFamide-like neuropeptides byinteracting with the channel’s large extracellular loop. ASICsare also modulated by G protein-coupled receptors such asCB1 cannabinoid receptors and 5-HT2. This review focuses onthe physiological roles of ASICs and the molecularmechanisms by which these channels are regulated. [BMBReports 2013; 46(6: 295-304

  3. Regulation of Serum Response Factor and Adiponectin by PPARγ Agonist Docosahexaenoic Acid

    Directory of Open Access Journals (Sweden)

    Clayton Johnson

    2011-01-01

    Full Text Available Recent studies indicate that significant health benefits involving the regulation of signaling proteins result from the consumption of omega-3 polyunsaturated fatty acids (ω-3 PUFAs. Serum response factor (SRF is involved in transcriptional regulation of muscle growth and differentiation. SRF levels are increased in the aging heart muscle. It has not been examined whether SRF is made by adipocytes and whether SRF secretion by adipocytes is modulated by PPARγ agonist DHA. Adiponectin is made exclusively by adipocytes. We and others have previously reported that PUFAs such as DHA increase adiponectin levels and secretion in adipocytes. Here we show that DHA downregulates SRF with a simultaneous upregulation of adiponectin and that both these responses are reversible by PPARγ antagonist. Furthermore, there appears to be a direct relationship between DHA exposure and increased levels of membrane-associated high-density adiponectin, as well as lower levels of membrane-associated SRF. Thus, we find that the levels of SRF and adiponectin are inversely related in response to treatment with PPARγ agonist DHA. Decreased levels of SRF along with increase in membrane-associated adiponectin could in part mediate the health benefits of DHA.

  4. Jasmonic acid carboxyl methyltransferase regulates development and herbivory-induced defense response in rice

    Institute of Scientific and Technical Information of China (English)

    Jinfeng Qi; Yonggen Lou; Jiancai Li; Xiu Han; Ran Li; Jianqiang Wu; Haixin Yu; Lingfei Hu; Yutao Xiao; Jing Lu

    2016-01-01

    Jasmonic acid (JA) and related metabolites play a key role in plant defense and growth. JA carboxyl methyltransferase (JMT) may be involved in plant defense and development by methylating JA to methyl jasmonate (MeJA) and thus influencing the concentrations of JA and related metabolites. However, no JMT gene has been well characterized in monocotyledon defense and development at the molecular level. After we cloned a rice JMT gene, OsJMT1, whose encoding protein was localized in the cytosol, we found that the recombinant OsJMT1 protein catalyzed JA to MeJA. OsJMT1 is up-regulated in response to infestation with the brown planthopper (BPH; Nilaparvata lugens). Plants in which OsJMT1 had been overexpressed (oe-JMT plants) showed reduced height and yield. These oe-JMT plants also exhibited increased MeJA levels but reduced levels of herbivore-induced JA and jasmonoyl-isoleucine (JA-Ile). The oe-JMT plants were more attractive to BPH female adults but showed increased resistance to BPH nymphs, probably owing to the different responses of BPH female adults and nymphs to the changes in levels of H2O2 and MeJA in oe-JMT plants. These results indicate that OsJMT1, by altering levels of JA and related metabolites, plays a role in regulating plant development and herbivore-induced defense responses in rice.

  5. Clavulanic acid production by Streptomyces clavuligerus: biogenesis, regulation and strain improvement.

    Science.gov (United States)

    Paradkar, Ashish

    2013-07-01

    Clavulanic acid (CA) is a potent β-lactamase inhibitor produced by Streptomyces clavuligerus and has been successfully used in combination with β-lactam antibiotics (for example, Augmentin) to treat infections caused by β-lactamase-producing pathogens. Since the discovery of CA in the late 1970s, significant information has accumulated on its biosynthesis, and regarding molecular mechanisms involved in the regulation of its production. Notably, the genes directing CA biosynthesis are clustered along with the genes responsible for the biosynthesis of the β-lactam antibiotic, cephamycin C, and co-regulated, which makes this organism unique in that the production of an antibiotic and production of a small molecule to protect the antibiotic from its enzymatic degradation are controlled by shared mechanisms. Traditionally, the industrial strain improvement programs have relied significantly on random mutagenesis and selection approach. However, the recent availability of the genome sequence of S. clavuligerus along with the capability to build metabolic models, and ability to engineer the organism by directed approaches, has created exciting opportunities to improve strain productivity more efficiently. This review will include focus mainly on the gene organization of the CA biosynthetic genes, regulatory mechanisms that affect its production, and will include perspectives on improving strain productivity.

  6. Feature-Based Classification of Amino Acid Substitutions outside Conserved Functional Protein Domains

    Directory of Open Access Journals (Sweden)

    Branislava Gemovic

    2013-01-01

    Full Text Available There are more than 500 amino acid substitutions in each human genome, and bioinformatics tools irreplaceably contribute to determination of their functional effects. We have developed feature-based algorithm for the detection of mutations outside conserved functional domains (CFDs and compared its classification efficacy with the most commonly used phylogeny-based tools, PolyPhen-2 and SIFT. The new algorithm is based on the informational spectrum method (ISM, a feature-based technique, and statistical analysis. Our dataset contained neutral polymorphisms and mutations associated with myeloid malignancies from epigenetic regulators ASXL1, DNMT3A, EZH2, and TET2. PolyPhen-2 and SIFT had significantly lower accuracies in predicting the effects of amino acid substitutions outside CFDs than expected, with especially low sensitivity. On the other hand, only ISM algorithm showed statistically significant classification of these sequences. It outperformed PolyPhen-2 and SIFT by 15% and 13%, respectively. These results suggest that feature-based methods, like ISM, are more suitable for the classification of amino acid substitutions outside CFDs than phylogeny-based tools.

  7. Research needs for risk-informed, performance-based regulation

    Energy Technology Data Exchange (ETDEWEB)

    Cloninger, T.H. [Houston Lighting & Power Company, Wadsworth, TX (United States)

    1997-01-01

    This presentation was made by an executive in the utility which operates the South Texas Project reactors, and summarizes their perspective on probabilistic safety analysis, risk-based operation, and risk-based regulation. They view it as a tool to help them better apply their resources to maintain the level of safety necessary to protect the public health and safety. South Texas served as one of the pilot plants for the application of risk-based regulation to the maintenance rule. The author feels that the process presents opportunities as well as challenges. Among the opportunities is the involvement of more people in the process, and the sense of investment they take in the decisions, in addition to the insight they can offer. In the area of challenges there is the need for better understanding of how to apply what already is known on problems, rather than essentially reinventing the wheel to address problems. Research is needed to better understand when some events are not truly of a significant safety concern. The demarcation between deterministic decisions and the appropriate application of risk-based decisions must be better defined, for the sake of the operator as well as the public observing plant operation.

  8. Transcriptional regulation of genes involved in retinoic acid metabolism in Senegalese sole larvae.

    Science.gov (United States)

    Boglino, Anaïs; Ponce, Marian; Cousin, Xavier; Gisbert, Enric; Manchado, Manuel

    2017-01-01

    The aim of this study was the characterization of transcriptional regulatory pathways mediated by retinoic acid (RA) in Senegalese sole larvae. For this purpose, pre-metamorphic larvae were treated with a low concentration of DEAB, an inhibitor of RALDH enzyme, until the end of metamorphosis. No differences in growth, eye migration or survival were observed. Nevertheless, gene expression analysis revealed a total of 20 transcripts differentially expressed during larval development and only six related with DEAB treatments directly involved in RA metabolism and actions (rdh10a, aldh1a2, crbp1, igf2r, rarg and cyp26a1) to adapt to a low-RA environment. In a second experiment, post-metamorphic larvae were exposed to the all-trans RA (atRA) observing an opposite regulation for those genes involved in RA synthesis and degradation (rdh10a, aldh1a2, crbp1 and cyp26a1) as well as other related with thyroid- (dio2) and IGF-axes (igfbp1, igf2r and igfbp5) to balance RA levels. In a third experiment, DEAB-pretreated post-metamorphic larvae were exposed to atRA and TTNPB (a specific RAR agonist). Both drugs down-regulated rdh10a and aldh1a2 and up-regulated cyp26a1 expression demonstrating their important role in RA homeostasis. Moreover, five retinoic receptors that mediate RA actions, the thyroid receptor thrb, and five IGF binding proteins changed differentially their expression. Overall, this study demonstrates that exogenous RA modulates the expression of some genes involved in the RA synthesis, degradation and cellular transport through RAR-mediated regulatory pathways establishing a negative feedback regulatory mechanism necessary to balance endogenous RA levels and gradients.

  9. Regulation of alpha-1 acid glycoprotein synthesis by porcine hepatocytes in monolayer culture.

    Science.gov (United States)

    Caperna, T J; Shannon, A E; Stoll, M; Blomberg, L A; Ramsay, T G

    2015-07-01

    Alpha-1 acid glycoprotein (AGP, orosomucoid, ORM-1) is a highly glycosylated mammalian acute-phase protein, which is synthesized primarily in the liver and represents the major serum protein in newborn pigs. Recent data have suggested that the pig is unique in that AGP is a negative acute-phase protein in this species, and its circulating concentration appears to be associated with growth rate. The purpose of the present study was to investigate the regulation of AGP synthesis in hepatocytes prepared from suckling piglets and to provide a framework to compare its regulation with that of haptoglobin (HP), a positive acute-phase protein. Hepatocytes were isolated from preweaned piglets and maintained in serum-free monolayer culture for up to 72 h. The influences of hormones, cytokines, and redox modifiers on the expression and secretion of AGP and HP were determined by relative polymerase chain reaction and by measuring the concentration of each protein secreted into culture medium. The messenger RNA abundance and/or secretion of AGP protein was enhanced by interleukin (IL)-17a, IL-1, and resveratrol and inhibited by tumor necrosis factor-α (TNF), oncostatin M, and thyroid hormone (P < 0.05). HP expression and synthesis were upregulated by oncostatin M, IL-6, and dexamethasone and downregulated by TNF (P < 0.01). The overall messenger RNA expression at 24 h was in agreement with the secreted protein patterns confirming that control of these proteins in hepatocytes is largely transcriptional. Moreover, these data support the consideration that AGP is a negative acute-phase reactant and appears to be regulated by cytokines (with the exception of TNF) and hormones primarily in a manner opposite to that of the positive acute-phase protein, HP.

  10. New Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Inhibitors, Nalidixic Acid Linked to Isatin Schiff Bases via Certain l-Amino Acid Bridges

    Directory of Open Access Journals (Sweden)

    Ahmed M. Naglah

    2016-04-01

    Full Text Available A series of new Schiff bases were synthesized by condensation of isatins with the nalidixic acid-l-amino acid hydrazides. Prior to hydrazide formation, a peptide linkage has been prepared via coupling of nalidixic acid with appropriate l-amino acid methyl esters to yield 3a–c. The chemical structures of the new Schiff bases (5b and 5d–h were confirmed by means of IR, NMR, mass spectroscopic, and elemental analyses. The anti-inflammatory activity of these Schiff bases was evaluated via measurement of the expressed inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 in the lipopolysaccharide (LPS-stimulated RAW264.7 macrophage cells model. The Schiff bases exhibited significant dual inhibitory effect against the induction of the pro-inflammatory iNOS and COX-2 proteins with variable potencies. However, they strongly down-regulated the iNOS expression to the level of 16.5% ± 7.4%–42.2% ± 19.6% compared to the effect on COX-2 expression (<56.4% ± 3.1% inhibition at the same concentration (10 μM. The higher iNOS inhibition activity of the tested Schiff bases, relative to that of COX-2, seems to be a reflection of the combined suppressive effects exerted by their nalidixic acid, isatins (4a–c, and l-amino acid moieties against iNOS expression. These synthesized nalidixic acid-l-amino acid-isatin conjugates can be regarded as a novel class of anti-inflammatory antibacterial agents.

  11. Cauliflower mosaic virus protein P6 inhibits signaling responses to salicylic acid and regulates innate immunity.

    Directory of Open Access Journals (Sweden)

    Andrew J Love

    Full Text Available Cauliflower mosaic virus (CaMV encodes a multifunctional protein P6 that is required for translation of the 35S RNA and also acts as a suppressor of RNA silencing. Here we demonstrate that P6 additionally acts as a pathogenicity effector of an unique and novel type, modifying NPR1 (a key regulator of salicylic acid (SA- and jasmonic acid (JA-dependent signaling and inhibiting SA-dependent defence responses We find that that transgene-mediated expression of P6 in Arabidopsis and transient expression in Nicotiana benthamiana has profound effects on defence signaling, suppressing expression of representative SA-responsive genes and increasing expression of representative JA-responsive genes. Relative to wild-type Arabidopsis P6-expressing transgenics had greatly reduced expression of PR-1 following SA-treatment, infection by CaMV or inoculation with an avirulent bacterial pathogen Pseudomonas syringae pv tomato (Pst. Similarly transient expression in Nicotiana benthamiana of P6 (including a mutant form defective in translational transactivation activity suppressed PR-1a transcript accumulation in response to Agrobacterium infiltration and following SA-treatment. As well as suppressing the expression of representative SA-regulated genes, P6-transgenic Arabidopsis showed greatly enhanced susceptibility to both virulent and avirulent Pst (titres elevated 10 to 30-fold compared to non-transgenic controls but reduced susceptibility to the necrotrophic fungus Botrytis cinerea. Necrosis following SA-treatment or inoculation with avirulent Pst was reduced and delayed in P6-transgenics. NPR1 an important regulator of SA/JA crosstalk, was more highly expressed in the presence of P6 and introduction of the P6 transgene into a transgenic line expressing an NPR1:GFP fusion resulted in greatly increased fluorescence in nuclei even in the absence of SA. Thus in the presence of P6 an inactive form of NPR1 is mislocalized in the nucleus even in uninduced plants

  12. Methanol Expression Regulator 1 (Mxr1p) Is Essential for the Utilization of Amino Acids as the Sole Source of Carbon by the Methylotrophic Yeast, Pichia pastoris.

    Science.gov (United States)

    Sahu, Umakant; Rangarajan, Pundi N

    2016-09-23

    Unlike Saccharomyces cerevisiae, the methylotrophic yeast Pichia pastoris can assimilate amino acids as the sole source of carbon and nitrogen. It can grow in media containing yeast extract and peptone (YP), yeast nitrogen base (YNB) + glutamate (YNB + Glu), or YNB + aspartate (YNB + Asp). Methanol expression regulator 1 (Mxr1p), a zinc finger transcription factor, is essential for growth in these media. Mxr1p regulates the expression of several genes involved in the utilization of amino acids as the sole source of carbon and nitrogen. These include the following: (i) GDH2 encoding NAD-dependent glutamate dehydrogenase; (ii) AAT1 and AAT2 encoding mitochondrial and cytosolic aspartate aminotransferases, respectively; (iii) MDH1 and MDH2 encoding mitochondrial and cytosolic malate dehydrogenases, respectively; and (iv) GLN1 encoding glutamine synthetase. Synthesis of all these enzymes is regulated by Mxr1p at the level of transcription except GDH2, whose synthesis is regulated at the level of translation. Mxr1p activates the transcription of AAT1, AAT2, and GLN1 in cells cultured in YP as well as in YNB + Glu media, whereas transcription of MDH1 and MDH2 is activated in cells cultured in YNB + Glu but not in YP. A truncated Mxr1p composed of 400 N-terminal amino acids activates transcription of target genes in cells cultured in YP but not in YNB + Glu. Mxr1p binds to Mxr1p response elements present in the promoters of AAT2, MDH2, and GLN1 We conclude that Mxr1p is essential for utilization of amino acids as the sole source of carbon and nitrogen, and it is a global regulator of multiple metabolic pathways in P. pastoris.

  13. [Blood acid-base balance of sportsmen during physical activity].

    Science.gov (United States)

    Petrushova, O P; Mikulyak, N I

    2014-01-01

    The aim of this study was to investigate the acid-base balance parameters in blood of sportsmen by physical activity. Before exercise lactate concentration in blood was normal. Carbon dioxide pressure (рСО2), bicarbonate concentration (НСО3 -), base excess (BE), were increased immediately after physical activity lactate concentration increased, while pH, BE, НСО3 -, рСО2 decreased in capillary blood of sportsmen. These changes show the development of lactate-acidosis which is partly compensated with bicarbonate buffering system and respiratory alkalosis. During postexercise recovery lactate concentration decreased, while рСО2, НСО3 -, BE increased. The results of this study can be used for diagnostics of acid-base disorders and their medical treatment for preservation of sportsmen physical capacity.

  14. Species-specific mechanisms for cholesterol 7alpha-hydroxylase (CYP7A1) regulation by drugs and bile acids

    OpenAIRE

    C. Handschin.; Gnerre, C; Fraser, D. J.; Martinez-Jimenez, C.; Jover, R; Meyer, U A

    2005-01-01

    The gene encoding cholesterol 7alpha-hydroxylase (CYP7A1) is tightly regulated in order to control intrahepatic cholesterol and bile acid levels. Ligands of the xenobiotic-sensing pregnane X receptor inhibit CYP7A1 expression. To retrace the evolution of the molecular mechanisms underlying CYP7A1 inhibition, we used a chicken hepatoma cell system that retains the ability to be induced by phenobarbital and other drugs. Whereas bile acids regulate CYP7A1 via small heterodimer partner and liver ...

  15. Food composition and acid-base balance: alimentary alkali depletion and acid load in herbivores.

    Science.gov (United States)

    Kiwull-Schöne, Heidrun; Kiwull, Peter; Manz, Friedrich; Kalhoff, Hermann

    2008-02-01

    Alkali-enriched diets are recommended for humans to diminish the net acid load of their usual diet. In contrast, herbivores have to deal with a high dietary alkali impact on acid-base balance. Here we explore the role of nutritional alkali in experimentally induced chronic metabolic acidosis. Data were collected from healthy male adult rabbits kept in metabolism cages to obtain 24-h urine and arterial blood samples. Randomized groups consumed rabbit diets ad libitum, providing sufficient energy but variable alkali load. One subgroup (n = 10) received high-alkali food and approximately 15 mEq/kg ammonium chloride (NH4Cl) with its drinking water for 5 d. Another group (n = 14) was fed low-alkali food for 5 d and given approximately 4 mEq/kg NH4Cl daily for the last 2 d. The wide range of alimentary acid-base load was significantly reflected by renal base excretion, but normal acid-base conditions were maintained in the arterial blood. In rabbits fed a high-alkali diet, the excreted alkaline urine (pH(u) > 8.0) typically contained a large amount of precipitated carbonate, whereas in rabbits fed a low-alkali diet, both pH(u) and precipitate decreased considerably. During high-alkali feeding, application of NH4Cl likewise decreased pH(u), but arterial pH was still maintained with no indication of metabolic acidosis. During low-alkali feeding, a comparably small amount of added NH4Cl further lowered pH(u) and was accompanied by a significant systemic metabolic acidosis. We conclude that exhausted renal base-saving function by dietary alkali depletion is a prerequisite for growing susceptibility to NH4Cl-induced chronic metabolic acidosis in the herbivore rabbit.

  16. Thermodynamics-based models of transcriptional regulation with gene sequence.

    Science.gov (United States)

    Wang, Shuqiang; Shen, Yanyan; Hu, Jinxing

    2015-12-01

    Quantitative models of gene regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation. However, the few models available today have been based on simplistic assumptions about the sequences being modeled or heuristic approximations of the underlying regulatory mechanisms. In this work, we have developed a thermodynamics-based model to predict gene expression driven by any DNA sequence. The proposed model relies on a continuous time, differential equation description of transcriptional dynamics. The sequence features of the promoter are exploited to derive the binding affinity which is derived based on statistical molecular thermodynamics. Experimental results show that the proposed model can effectively identify the activity levels of transcription factors and the regulatory parameters. Comparing with the previous models, the proposed model can reveal more biological sense.

  17. Acid Stability of the Hemagglutinin Protein Regulates H5N1 Influenza Virus Pathogenicity

    Energy Technology Data Exchange (ETDEWEB)

    DuBois, Rebecca M.; Zaraket, Hassan; Reddivari, Muralidhar; Heath, Richard J.; White, Stephen W.; Russell, Charles J. (Tennessee-HSC); (SJCH)

    2012-12-10

    Highly pathogenic avian influenza viruses of the H5N1 subtype continue to threaten agriculture and human health. Here, we use biochemistry and x-ray crystallography to reveal how amino-acid variations in the hemagglutinin (HA) protein contribute to the pathogenicity of H5N1 influenza virus in chickens. HA proteins from highly pathogenic (HP) A/chicken/Hong Kong/YU562/2001 and moderately pathogenic (MP) A/goose/Hong Kong/437-10/1999 isolates of H5N1 were found to be expressed and cleaved in similar amounts, and both proteins had similar receptor-binding properties. However, amino-acid variations at positions 104 and 115 in the vestigial esterase sub-domain of the HA1 receptor-binding domain (RBD) were found to modulate the pH of HA activation such that the HP and MP HA proteins are activated for membrane fusion at pH 5.7 and 5.3, respectively. In general, an increase in H5N1 pathogenicity in chickens was found to correlate with an increase in the pH of HA activation for mutant and chimeric HA proteins in the observed range of pH 5.2 to 6.0. We determined a crystal structure of the MP HA protein at 2.50 {angstrom} resolution and two structures of HP HA at 2.95 and 3.10 {angstrom} resolution. Residues 104 and 115 that modulate the acid stability of the HA protein are situated at the N- and C-termini of the 110-helix in the vestigial esterase sub-domain, which interacts with the B loop of the HA2 stalk domain. Interactions between the 110-helix and the stalk domain appear to be important in regulating HA protein acid stability, which in turn modulates influenza virus replication and pathogenesis. Overall, an optimal activation pH of the HA protein is found to be necessary for high pathogenicity by H5N1 influenza virus in avian species.

  18. Model for acid-base chemistry in nanoparticle growth (MABNAG)

    Science.gov (United States)

    Yli-Juuti, T.; Barsanti, K.; Hildebrandt Ruiz, L.; Kieloaho, A.-J.; Makkonen, U.; Petäjä, T.; Ruuskanen, T.; Kulmala, M.; Riipinen, I.

    2013-12-01

    Climatic effects of newly-formed atmospheric secondary aerosol particles are to a large extent determined by their condensational growth rates. However, all the vapours condensing on atmospheric nanoparticles and growing them to climatically relevant sizes are not identified yet and the effects of particle phase processes on particle growth rates are poorly known. Besides sulfuric acid, organic compounds are known to contribute significantly to atmospheric nanoparticle growth. In this study a particle growth model MABNAG (Model for Acid-Base chemistry in NAnoparticle Growth) was developed to study the effect of salt formation on nanoparticle growth, which has been proposed as a potential mechanism lowering the equilibrium vapour pressures of organic compounds through dissociation in the particle phase and thus preventing their evaporation. MABNAG is a model for monodisperse aqueous particles and it couples dynamics of condensation to particle phase chemistry. Non-zero equilibrium vapour pressures, with both size and composition dependence, are considered for condensation. The model was applied for atmospherically relevant systems with sulfuric acid, one organic acid, ammonia, one amine and water in the gas phase allowed to condense on 3-20 nm particles. The effect of dissociation of the organic acid was found to be small under ambient conditions typical for a boreal forest site, but considerable for base-rich environments (gas phase concentrations of about 1010 cm-3 for the sum of the bases). The contribution of the bases to particle mass decreased as particle size increased, except at very high gas phase concentrations of the bases. The relative importance of amine versus ammonia did not change significantly as a function of particle size. While our results give a reasonable first estimate on the maximum contribution of salt formation to nanoparticle growth, further studies on, e.g. the thermodynamic properties of the atmospheric organics, concentrations of low

  19. Arabidopsis plastid AMOS1/EGY1 integrates abscisic acid signaling to regulate global gene expression response to ammonium stress

    KAUST Repository

    Li, Baohai

    2012-10-12

    Ammonium (NH4 +) is a ubiquitous intermediate of nitrogen metabolism but is notorious for its toxic effects on most organisms. Extensive studies of the underlying mechanisms of NH4 + toxicity have been reported in plants, but it is poorly understood how plants acclimate to high levels of NH4 +. Here, we identified an Arabidopsis (Arabidopsis thaliana) mutant, ammonium overly sensitive1 (amos1), that displays severe chlorosis under NH4 + stress. Map-based cloning shows amos1 to carry a mutation in EGY1 (for ethylene-dependent, gravitropism-deficient, and yellow-green-like protein1), which encodes a plastid metalloprotease. Transcriptomic analysis reveals that among the genes activated in response to NH4 +, 90% are regulated dependent on AMOS1/ EGY1. Furthermore, 63% of AMOS1/EGY1-dependent NH4 +-activated genes contain an ACGTG motif in their promoter region, a core motif of abscisic acid (ABA)-responsive elements. Consistent with this, our physiological, pharmacological, transcriptomic, and genetic data show that ABA signaling is a critical, but not the sole, downstream component of the AMOS1/EGY1-dependent pathway that regulates the expression of NH4 +-responsive genes and maintains chloroplast functionality under NH4 + stress. Importantly, abi4 mutants defective in ABA-dependent and retrograde signaling, but not ABA-deficient mutants, mimic leaf NH4 + hypersensitivity of amos1. In summary, our findings suggest that an NH4 +-responsive plastid retrograde pathway, which depends on AMOS1/EGY1 function and integrates with ABA signaling, is required for the regulation of expression of the presence of high NH4 + levels. © 2012 American Society of Plant Biologists. All Rights Reserved.

  20. Developing nucleic acid-based electrical detection systems

    Directory of Open Access Journals (Sweden)

    Gabig-Ciminska Magdalena

    2006-03-01

    Full Text Available Abstract Development of nucleic acid-based detection systems is the main focus of many research groups and high technology companies. The enormous work done in this field is particularly due to the broad versatility and variety of these sensing devices. From optical to electrical systems, from label-dependent to label-free approaches, from single to multi-analyte and array formats, this wide range of possibilities makes the research field very diversified and competitive. New challenges and requirements for an ideal detector suitable for nucleic acid analysis include high sensitivity and high specificity protocol that can be completed in a relatively short time offering at the same time low detection limit. Moreover, systems that can be miniaturized and automated present a significant advantage over conventional technology, especially if detection is needed in the field. Electrical system technology for nucleic acid-based detection is an enabling mode for making miniaturized to micro- and nanometer scale bio-monitoring devices via the fusion of modern micro- and nanofabrication technology and molecular biotechnology. The electrical biosensors that rely on the conversion of the Watson-Crick base-pair recognition event into a useful electrical signal are advancing rapidly, and recently are receiving much attention as a valuable tool for microbial pathogen detection. Pathogens may pose a serious threat to humans, animal and plants, thus their detection and analysis is a significant element of public health. Although different conventional methods for detection of pathogenic microorganisms and their toxins exist and are currently being applied, improvements of molecular-based detection methodologies have changed these traditional detection techniques and introduced a new era of rapid, miniaturized and automated electrical chip detection technologies into pathogen identification sector. In this review some developments and current directions in

  1. The citric acid production from raw glycerol by Yarrowia lipolytica yeast and its regulation.

    Science.gov (United States)

    Morgunov, Igor G; Kamzolova, Svetlana V; Lunina, Julia N

    2013-08-01

    The optimal cultivation conditions ensuring the maximal rate of citric acid (CA) biosynthesis by glycerol-grown mutant Yarrowia lipolytica NG40/UV7 were found to be as follows: growth limitation by inorganic nutrients (nitrogen, phosphorus, or sulfur), 28 °C, pH 5.0, dissolved oxygen concentration (pO₂) of 50 % (of air saturation), and pulsed addition of glycerol from 20 to 80 g L⁻¹ depending on the rate of medium titration. Under optimal conditions of fed-batch cultivation, in the medium with pure glycerol, strain Y. lipolytica NG40/UV7 produced 115 g L⁻¹ of CA with the mass yield coefficient of 0.64 g g⁻¹ and isocitric acid (ICA) amounted to 4.6 g L⁻¹; in the medium with raw glycerol, CA production was 112 g L⁻¹ with the mass yield coefficient of 0.90 g g⁻¹ and ICA amounted to 5.3 g L⁻¹. Based on the activities of enzymes involved in the initial stages of raw glycerol assimilation, the tricarboxylic acid cycle and the glyoxylate cycle, the mechanism of increased CA yield from glycerol-containing substrates in Y. lipolytica yeast was explained.

  2. Domoic acid toxicokinetics in Dungeness crabs: New insights into mechanisms that regulate bioaccumulation

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Irvin R., E-mail: ir_schultz@pnl.gov; Skillman, Ann; Sloan-Evans, Siobhan; Woodruff, Dana

    2013-09-15

    Highlights: •Domoic acid is retained in the hepatopancreas after oral dosing but not after intravascular dosing. •Localization of domoic acid in the hepatopancreas is extracellular, likely in the lumen of tubules. •Isolated hepatopancreas cells do not absorb domoic acid from culture media. •Domoic acid is eliminated through urinary excretion. -- Abstract: Domoic acid (DA) is an excitatory neurotoxic amino acid produced by several marine algal species and is the causative agent of amnesic shellfish poisoning. Profound differences in the toxicokinetics of DA have been identified in a wide variety of shellfish. We characterized the toxicokinetics of DA in Dungeness crabs (Metacarcinus magister) after oral and intravascular dosing (IV) using a variety of doses ranging from 0.1 to 20 mg/kg. After a 1 mg/kg oral dose, DA disappeared from the foregut within 2 h and largely accumulated in the hepatopancreas, with hemolymph and other tissues having 100–1000 times lower concentrations. After IV dosing, hemolymph concentrations of DA were unexpectedly high and toxicokinetic analysis indicated the steady-state volume of distribution (V{sub ss}) was 123–197 ml/kg, which is well below the hemolymph volume of 350 ml/kg for crabs. This indicated only limited extravascular distribution of DA was occurring after IV injection, which is surprising considering the capacity of the hepatopancreas to sequester DA after oral dosing. Additional studies measured the partitioning of DA in hepatopancreas cellular and subcellular fractions. The subcellular distribution of DA was primarily associated with the S8 fraction and could be filtered through a 30,000 MW cut-off filter, indicating DA was not appreciably bound to macromolecules. Interestingly, very little (<0.4%) of the total hepatopancreas DA tissue content was associated with the cellular fraction isolated after dissociation and separation from tissue fragments. The in vivo and in vitro results led us to hypothesize that DA

  3. Acid and base stress and transcriptomic responses in Bacillus subtilis.

    Science.gov (United States)

    Wilks, Jessica C; Kitko, Ryan D; Cleeton, Sarah H; Lee, Grace E; Ugwu, Chinagozi S; Jones, Brian D; BonDurant, Sandra S; Slonczewski, Joan L

    2009-02-01

    Acid and base environmental stress responses were investigated in Bacillus subtilis. B. subtilis AG174 cultures in buffered potassium-modified Luria broth were switched from pH 8.5 to pH 6.0 and recovered growth rapidly, whereas cultures switched from pH 6.0 to pH 8.5 showed a long lag time. Log-phase cultures at pH 6.0 survived 60 to 100% at pH 4.5, whereas cells grown at pH 7.0 survived acid or base induced adaptation to a more extreme acid or base, respectively. Expression indices from Affymetrix chip hybridization were obtained for 4,095 protein-encoding open reading frames of B. subtilis grown at external pH 6, pH 7, and pH 9. Growth at pH 6 upregulated acetoin production (alsDS), dehydrogenases (adhA, ald, fdhD, and gabD), and decarboxylases (psd and speA). Acid upregulated malate metabolism (maeN), metal export (czcDO and cadA), oxidative stress (catalase katA; OYE family namA), and the SigX extracytoplasmic stress regulon. Growth at pH 9 upregulated arginine catabolism (roc), which generates organic acids, glutamate synthase (gltAB), polyamine acetylation and transport (blt), the K(+)/H(+) antiporter (yhaTU), and cytochrome oxidoreductases (cyd, ctaACE, and qcrC). The SigH, SigL, and SigW regulons were upregulated at high pH. Overall, greater genetic adaptation was seen at pH 9 than at pH 6, which may explain the lag time required for growth shift to high pH. Low external pH favored dehydrogenases and decarboxylases that may consume acids and generate basic amines, whereas high external pH favored catabolism-generating acids.

  4. Acid-base properties of bentonite rocks with different origins.

    Science.gov (United States)

    Nagy, Noémi M; Kónya, József

    2006-03-01

    Five bentonite samples (35-47% montmorillonite) from a Sarmatian sediment series with bentonite sites around Sajóbábony (Hungary) is studied. Some of these samples were tuffogenic bentonite (sedimentary), the others were bentonitized tuff with volcano sedimentary origin. The acid-base properties of the edge sites were studied by potentiometric titrations and surface complexation modeling. It was found that the number and the ratio of silanol and aluminol sites as well as the intrinsic stability constants are different for the sedimentary bentonite and bentonitized tuff. The characteristic properties of the edges sites depend on the origins. The acid-base properties are compared to other commercial and standard bentonites.

  5. An Alternative to Synthetic Acid Base Indicator-Tagetes Erecta Linn

    Directory of Open Access Journals (Sweden)

    *A. Elumalai

    2012-06-01

    Full Text Available The present work highlights the use of the methanolic extract of the flowers of Tagetes erecta as an acid-base indicator in acid-base titrations. This natural indicator is easy to extract as well as easily available. Indicators used in titration show well marked changes of colour in certain intervals of pH. Most of these indicators are organic dyes and are of synthetic origin. Today synthetic indicators are the choice of acid-base titrations. But due to environmental pollution, availability and cost, the search for natural compounds as an acid-base indicator was started. Herbal indicators are evaluated by using strong acid-strong base, strong acid-weak base, weak acid-strong base and weak acid weak base. In all these titrations the methanolic extract of the flowers of Tagetes erecta was found to be very useful, economical, simple and accurate for acid base titration.

  6. Acid-base thermochemistry of gaseous aliphatic α-aminoacids.

    Science.gov (United States)

    Bouchoux, Guy; Huang, Sihua; Inda, Bhawani Singh

    2011-01-14

    Acid-base thermochemistry of isolated aliphatic amino acids (denoted AAA): glycine, alanine, valine, leucine, isoleucine and proline has been examined theoretically by quantum chemical computations at the G3MP2B3 level. Conformational analysis on neutral, protonated and deprotonated species has been used to identify the lowest energy conformers and to estimate the population of conformers expected to be present at thermal equilibrium at 298 K. Comparison of the G3MP2B3 theoretical proton affinities, PA, and ΔH(acid) with experimental results is shown to be correct if experimental thermochemistry is re-evaluated and adapted to the most recent acidity-basicity scales. From this point of view, a set of evaluated proton affinities of 887, 902, 915, 916, 919 and 941 kJ mol(-1), and a set of evaluated ΔH(acid) of 1433, 1430, 1423, 1423, 1422 and 1426 kJ mol(-1), is proposed for glycine, alanine, valine, leucine, isoleucine and proline, respectively. Correlations with structural parameters (Taft's σ(α) polarizability parameter and molecular size) suggest that polarizability of the side chain is the major origin of the increase in PA and decrease in ΔH(acid) along the homologous series glycine, alanine, valine and leucine/isoleucine. Heats of formation of gaseous species AAA, AAAH(+) and [AAA-H](-) were computed at the G3MP2B3 level. The present study provides previously unavailable Δ(f)H°(298) for the ionized species AAAH(+) and [AAA-H](-). Comparison with Benson's estimate, and correlation with molecular size, show that several experimental Δ(f)H°(298) values of neutral or gaseous AAA might be erroneous.

  7. Differential regulation of protein synthesis by amino acids and insulin in peripheral and visceral tissues of neonatal pigs.

    Science.gov (United States)

    Suryawan, Agus; O'Connor, Pamela M J; Bush, Jill A; Nguyen, Hanh V; Davis, Teresa A

    2009-05-01

    The high efficiency of protein deposition during the neonatal period is driven by high rates of protein synthesis, which are maximally stimulated after feeding. In the current study, we examined the individual roles of amino acids and insulin in the regulation of protein synthesis in peripheral and visceral tissues of the neonate by performing pancreatic glucose-amino acid clamps in overnight-fasted 7-day-old pigs. We infused pigs (n = 8-12/group) with insulin at 0, 10, 22, and 110 ng kg(-0.66) min(-1) to achieve approximately 0, 2, 6 and 30 muU ml(-1) insulin so as to simulate below fasting, fasting, intermediate, and fed insulin levels, respectively. At each insulin dose, amino acids were maintained at the fasting or fed level. In conjunction with the highest insulin dose, amino acids were also allowed to fall below the fasting level. Tissue protein synthesis was measured using a flooding dose of L: -[4-(3)H] phenylalanine. Both insulin and amino acids increased fractional rates of protein synthesis in longissimus dorsi, gastrocnemius, masseter, and diaphragm muscles. Insulin, but not amino acids, increased protein synthesis in the skin. Amino acids, but not insulin, increased protein synthesis in the liver, pancreas, spleen, and lung and tended to increase protein synthesis in the jejunum and kidney. Neither insulin nor amino acids altered protein synthesis in the stomach. The results suggest that the stimulation of protein synthesis by feeding in most tissues of the neonate is regulated by the post-prandial rise in amino acids. However, the feeding-induced stimulation of protein synthesis in skeletal muscles is independently mediated by insulin as well as amino acids.

  8. Effects of acid-base imbalance on vascular reactivity

    Directory of Open Access Journals (Sweden)

    A.C. Celotto

    2008-06-01

    Full Text Available Acid-base homeostasis maintains systemic arterial pH within a narrow range. Whereas the normal range of pH for clinical laboratories is 7.35-7.45, in vivo pH is maintained within a much narrower range. In clinical and experimental settings, blood pH can vary in response to respiratory or renal impairment. This altered pH promotes changes in vascular smooth muscle tone with impact on circulation and blood pressure control. Changes in pH can be divided into those occurring in the extracellular space (pHo and those occurring within the intracellular space (pHi, although, extracellular and intracellular compartments influence each other. Consistent with the multiple events involved in the changes in tone produced by altered pHo, including type of vascular bed, several factors and mechanisms, in addition to hydrogen ion concentration, have been suggested to be involved. The scientific literature has many reports concerning acid-base balance and endothelium function, but these concepts are not clear about acid-base disorders and their relations with the three known mechanisms of endothelium-dependent vascular reactivity: nitric oxide (NO/cGMP-dependent, prostacyclin (PGI2/cAMP-dependent and hyperpolarization. During the last decades, many studies have been published and have given rise to confronting data on acid-base disorder and endothelial function. Therefore, the main proposal of this review is to provide a critical analysis of the state of art and incentivate researchers to develop more studies about these issues.

  9. A fully automatic system for acid-base coulometric titrations

    OpenAIRE

    1990-01-01

    An automatic system for acid-base titrations by electrogeneration of H+ and OH- ions, with potentiometric end-point detection, was developed. The system includes a PC-compatible computer for instrumental control, data acquisition and processing, which allows up to 13 samples to be analysed sequentially with no human intervention. The system performance was tested on the titration of standard solutions, which it carried out with low errors and RSD. It was subsequently applied to the analysis o...

  10. Developing nucleic acid-based electrical detection systems

    OpenAIRE

    Gabig-Ciminska Magdalena

    2006-01-01

    Abstract Development of nucleic acid-based detection systems is the main focus of many research groups and high technology companies. The enormous work done in this field is particularly due to the broad versatility and variety of these sensing devices. From optical to electrical systems, from label-dependent to label-free approaches, from single to multi-analyte and array formats, this wide range of possibilities makes the research field very diversified and competitive. New challenges and r...

  11. PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Qiao, Jingbo [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Paul, Pritha; Lee, Sora [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Qiao, Lan; Josifi, Erlena; Tiao, Joshua R. [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Chung, Dai H., E-mail: dai.chung@vanderbilt.edu [Department of Pediatric Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Retinoic acid (RA) induces neuroblastoma cells differentiation, which is accompanied by G0/G1 cell cycle arrest. Black-Right-Pointing-Pointer RA resulted in neuroblastoma cell survival and inhibition of DNA fragmentation; this is regulated by PI3K pathway. Black-Right-Pointing-Pointer RA activates PI3K and ERK1/2 pathway; PI3K pathway mediates RA-induced neuroblastoma cell differentiation. Black-Right-Pointing-Pointer Upregulation of p21 is necessary for RA-induced neuroblastoma cell differentiation. -- Abstract: Neuroblastoma, the most common extra-cranial solid tumor in infants and children, is characterized by a high rate of spontaneous remissions in infancy. Retinoic acid (RA) has been known to induce neuroblastoma differentiation; however, the molecular mechanisms and signaling pathways that are responsible for RA-mediated neuroblastoma cell differentiation remain unclear. Here, we sought to determine the cell signaling processes involved in RA-induced cellular differentiation. Upon RA administration, human neuroblastoma cell lines, SK-N-SH and BE(2)-C, demonstrated neurite extensions, which is an indicator of neuronal cell differentiation. Moreover, cell cycle arrest occurred in G1/G0 phase. The protein levels of cyclin-dependent kinase inhibitors, p21 and p27{sup Kip}, which inhibit cell proliferation by blocking cell cycle progression at G1/S phase, increased after RA treatment. Interestingly, RA promoted cell survival during the differentiation process, hence suggesting a potential mechanism for neuroblastoma resistance to RA therapy. Importantly, we found that the PI3K/AKT pathway is required for RA-induced neuroblastoma cell differentiation. Our results elucidated the molecular mechanism of RA-induced neuroblastoma cellular differentiation, which may be important for developing novel therapeutic strategy against poorly differentiated neuroblastoma.

  12. Neurologic complications of electrolyte disturbances and acid-base balance.

    Science.gov (United States)

    Espay, Alberto J

    2014-01-01

    Electrolyte and acid-base disturbances are common occurrences in daily clinical practice. Although these abnormalities can be readily ascertained from routine laboratory findings, only specific clinical correlates may attest as to their significance. Among a wide phenotypic spectrum, acute electrolyte and acid-base disturbances may affect the peripheral nervous system as arreflexic weakness (hypermagnesemia, hyperkalemia, and hypophosphatemia), the central nervous system as epileptic encephalopathies (hypomagnesemia, dysnatremias, and hypocalcemia), or both as a mixture of encephalopathy and weakness or paresthesias (hypocalcemia, alkalosis). Disabling complications may develop not only when these derangements are overlooked and left untreated (e.g., visual loss from intracranial hypertension in respiratory or metabolic acidosis; quadriplegia with respiratory insufficiency in hypermagnesemia) but also when they are inappropriately managed (e.g., central pontine myelinolisis when rapidly correcting hyponatremia; cardiac arrhythmias when aggressively correcting hypo- or hyperkalemia). Therefore prompt identification of the specific neurometabolic syndromes is critical to correct the causative electrolyte or acid-base disturbances and prevent permanent central or peripheral nervous system injury. This chapter reviews the pathophysiology, clinical investigations, clinical phenotypes, and current management strategies in disorders resulting from alterations in the plasma concentration of sodium, potassium, calcium, magnesium, and phosphorus as well as from acidemia and alkalemia.

  13. Homography-based visual servo regulation of mobile robots.

    Science.gov (United States)

    Fang, Yongchun; Dixon, Warren E; Dawson, Darren M; Chawda, Prakash

    2005-10-01

    A monocular camera-based vision system attached to a mobile robot (i.e., the camera-in-hand configuration) is considered in this paper. By comparing corresponding target points of an object from two different camera images, geometric relationships are exploited to derive a transformation that relates the actual position and orientation of the mobile robot to a reference position and orientation. This transformation is used to synthesize a rotation and translation error system from the current position and orientation to the fixed reference position and orientation. Lyapunov-based techniques are used to construct an adaptive estimate to compensate for a constant, unmeasurable depth parameter, and to prove asymptotic regulation of the mobile robot. The contribution of this paper is that Lyapunov techniques are exploited to craft an adaptive controller that enables mobile robot position and orientation regulation despite the lack of an object model and the lack of depth information. Experimental results are provided to illustrate the performance of the controller.

  14. Spatial and temporal regulation of biosynthesis of the plant immune signal salicylic acid.

    Science.gov (United States)

    Zheng, Xiao-Yu; Zhou, Mian; Yoo, Heejin; Pruneda-Paz, Jose L; Spivey, Natalie Weaver; Kay, Steve A; Dong, Xinnian

    2015-07-28

    The plant hormone salicylic acid (SA) is essential for local defense and systemic acquired resistance (SAR). When plants, such as Arabidopsis, are challenged by different pathogens, an increase in SA biosynthesis generally occurs through transcriptional induction of the key synthetic enzyme isochorismate synthase 1 (ICS1). However, the regulatory mechanism for this induction is poorly understood. Using a yeast one-hybrid screen, we identified two transcription factors (TFs), NTM1-like 9 (NTL9) and CCA1 hiking expedition (CHE), as activators of ICS1 during specific immune responses. NTL9 is essential for inducing ICS1 and two other SA synthesis-related genes, phytoalexin-deficient 4 (PAD4) and enhanced disease susceptibility 1 (EDS1), in guard cells that form stomata. Stomata can quickly close upon challenge to block pathogen entry. This stomatal immunity requires ICS1 and the SA signaling pathway. In the ntl9 mutant, this response is defective and can be rescued by exogenous application of SA, indicating that NTL9-mediated SA synthesis is essential for stomatal immunity. CHE, the second identified TF, is a central circadian clock oscillator and is required not only for the daily oscillation in SA levels but also for the pathogen-induced SA synthesis in systemic tissues during SAR. CHE may also regulate ICS1 through the known transcription activators calmodulin binding protein 60g (CBP60g) and systemic acquired resistance deficient 1 (SARD1) because induction of these TF genes is compromised in the che-2 mutant. Our study shows that SA biosynthesis is regulated by multiple TFs in a spatial and temporal manner and therefore fills a gap in the signal transduction pathway between pathogen recognition and SA production.

  15. RETINOIC ACID DOWN-REGULATES BONE MORPHOGENETIC PROTEIN 7 EXPRESSION IN RAT WITH CLEFT PALATE

    Institute of Scientific and Technical Information of China (English)

    Lei Guo; Yu-yan Zhao; Shi-liang Zhang; Kui Liu; Xiao-yu Gao

    2008-01-01

    Objective To evaluate the effects of retinoic acid (RA) on expression of bone morphogenetic protein 7 (BMP-7)in rat fetus with cleft palate, and the effects of RA on proliferation and apoptosis of osteoblasts. Methods All-trans RA (ATRA) was used to induce congenital cleft palate in Wistar rat. BMP-7 mRNA expres-sion in maxillary bone tissue of fetal rats was measured by Northern blotting analysis. Flow cytometry and MTT assay were used to measure the apoptosis and proliferation of ATRA-treated MC-3T3-E1 cells. BMP-7 mRNA and protein ex-pressions in ATRA-treated MC-3T3-E1 cells were detected by RT-PCR and Western blotting analysis.Results ATRA could induce cleft palate of rat fetus. The incidence rate of cleft palate induced by 100 mg/kg AT-RA (45.5%) was significantly higher than 50 mg/kg ATRA (12.5%, P<0.05). BMP-7 mRNA expression de-creased in maxillary bone tissue of rat fetus with cleft palate. MC-3T3-E1 cells proliferation treated with 1 × 10-6 mol/L ATRA decreased by 60%, the cell apoptosis increased by 2 times. BMP-7 mR.NA and protein levels in MC-3T3-E1cells treated with 1 × 10-6 mol/L ATRA decreased by 60% and 80%, respectively, compared with ATRA-untreated ceils (P<0.05).Conclusions BMP-7 may play an important role in embryonic palate development RA may possess the ability to down-regulate cell proliferation through regulation of BMP-7 gene expression.

  16. Regulation of rat intrapulmonary arterial tone by arachidonic acid and prostaglandin E2 during hypoxia.

    Directory of Open Access Journals (Sweden)

    Gaoliang Yan

    Full Text Available AIMS: Arachidonic acid (AA and its metabolites, prostaglandins (PG are known to be involved in regulation of vascular homeostasis including vascular tone and vessel wall tension, but their potential role in Hypoxic pulmonary vasoconstriction (HPV remains unclear. In this study, we examined the effects of AA and PGE2 on the hypoxic response in isolated rat intrapulmonary arteries (IPAs. METHODS AND RESULTS: We carried out the investigation on IPAs by vessel tension measurement. Isotetrandrine (20 µM significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. Both indomethacin (100 µM and NS398 attenuated KPSS-induced vessel contraction and phase I, phase IIb and phase IIc of HPV, implying that COX-2 plays a primary role in the hypoxic response of rat IPAs. PGE2 alone caused a significant vasoconstriction in isolated rat IPAs. This constriction is mediated by EP4. Blockage of EP4 by L-161982 (1 µM significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. However, AH6809 (3 µM, an antagonist of EP1, EP2, EP3 and DP1 receptors, exerted no effect on KPSS or hypoxia induced vessel contraction. Increase of cellular cAMP by forskolin could significantly reduce KPSS-induced vessel contraction and abolish phase I, phase II b and phase II c of HPV. CONCLUSION: Our results demonstrated a vasoconstrictive effect of PGE2 on rat IPAs and this effect is via activation of EP4. Furthermore, our results suggest that intracellular cAMP plays dual roles in regulation of vascular tone, depending on the spatial distribution of cAMP and its coupling with EP receptor and Ca(2+ channels.

  17. Regulation of the activity of lactate dehydrogenases from four lactic acid bacteria.

    Science.gov (United States)

    Feldman-Salit, Anna; Hering, Silvio; Messiha, Hanan L; Veith, Nadine; Cojocaru, Vlad; Sieg, Antje; Westerhoff, Hans V; Kreikemeyer, Bernd; Wade, Rebecca C; Fiedler, Tomas

    2013-07-19

    Despite high similarity in sequence and catalytic properties, the l-lactate dehydrogenases (LDHs) in lactic acid bacteria (LAB) display differences in their regulation that may arise from their adaptation to different habitats. We combined experimental and computational approaches to investigate the effects of fructose 1,6-bisphosphate (FBP), phosphate (Pi), and ionic strength (NaCl concentration) on six LDHs from four LABs studied at pH 6 and pH 7. We found that 1) the extent of activation by FBP (Kact) differs. Lactobacillus plantarum LDH is not regulated by FBP, but the other LDHs are activated with increasing sensitivity in the following order: Enterococcus faecalis LDH2 ≤ Lactococcus lactis LDH2 < E. faecalis LDH1 < L. lactis LDH1 ≤ Streptococcus pyogenes LDH. This trend reflects the electrostatic properties in the allosteric binding site of the LDH enzymes. 2) For L. plantarum, S. pyogenes, and E. faecalis, the effects of Pi are distinguishable from the effect of changing ionic strength by adding NaCl. 3) Addition of Pi inhibits E. faecalis LDH2, whereas in the absence of FBP, Pi is an activator of S. pyogenes LDH, E. faecalis LDH1, and L. lactis LDH1 and LDH2 at pH 6. These effects can be interpreted by considering the computed binding affinities of Pi to the catalytic and allosteric binding sites of the enzymes modeled in protonation states corresponding to pH 6 and pH 7. Overall, the results show a subtle interplay among the effects of Pi, FBP, and pH that results in different regulatory effects on the LDHs of different LABs.

  18. Mitochondrial complex II participates in normoxic and hypoxic regulation of alpha-keto acids in the murine heart.

    NARCIS (Netherlands)

    Muhling, J.; Tiefenbach, M.; Lopez-Barneo, J.; Piruat, J.I.; Garcia-Flores, P.; Pfeil, U.; Gries, B.; Muhlfeld, C.; Weigand, M.A.; Kummer, W.; Weissmann, N.; Paddenberg, R.

    2010-01-01

    alpha-Keto acids (alpha-KAs) are not just metabolic intermediates but are also powerful modulators of different cellular pathways. Here, we tested the hypothesis that alpha-KA concentrations are regulated by complex II (succinate dehydrogenase=SDH), which represents an intersection between the mitoc

  19. Lewis base activation of Lewis acids: development of a Lewis base catalyzed selenolactonization.

    Science.gov (United States)

    Denmark, Scott E; Collins, William R

    2007-09-13

    The concept of Lewis base activation of Lewis acids has been applied to the selenolactonization reaction. Through the use of substoichiometric amounts of Lewis bases with "soft" donor atoms (S, Se, P) significant rate enhancements over the background reaction are seen. Preliminary mechanistic investigations have revealed the resting state of the catalyst as well as the significance of a weak Brønsted acid promoter.

  20. Crosstalk of Escherichia coli FadR with global regulators in expression of fatty acid transport genes.

    Directory of Open Access Journals (Sweden)

    Youjun Feng

    Full Text Available Escherichia coli FadR plays two regulatory roles in fatty acid metabolism. FadR represses the fatty acid degradation (fad system and activates the unsaturated fatty acid synthetic pathway. Cross-talk between E. coli FadR and the ArcA-ArcB oxygen-responsive two-component system was observed that resulted in diverse regulation of certain fad regulon β-oxidation genes. We have extended such analyses to the fadL and fadD genes, the protein products of which are required for long chain fatty acid transport and have also studied the role of a third global regulator, the CRP-cAMP complex. The promoters of both the fadL and fadD genes contain two experimentally validated FadR-binding sites plus binding sites for ArcA and CRP-cAMP. Despite the presence of dual binding sites FadR only modestly regulates expression of these genes, indicating that the number of binding sites does not determine regulatory strength. We report complementary in vitro and in vivo studies indicating that the CRP-cAMP complex directly activates expression of fadL and fadD as well as the β-oxidation gene, fadH. The physiological relevance of the fadL and fadD transcription data was validated by direct assays of long chain fatty acid transport.

  1. Amplification of electrolyte uptake in the absorptive glass mat (AGM) separator for valve regulated lead acid (VRLA) batteries

    Science.gov (United States)

    Kumar, Vijay; Kameswara Rao, P. V.; Rawal, Amit

    2017-02-01

    Absorptive glass mat (AGM) separators are widely used for valve regulated lead acid (VRLA) batteries due to their remarkable fiber and structural characteristics. Discharge performance and recharge effectiveness of VRLA batteries essentially rely on the distribution and saturation levels of the electrolyte within the AGM separator. Herein, we report an analytical model for predicting the wicking characteristics of AGM battery separators under unconfined and confined states. The model of wicking behavior of AGM is based upon Fries and Dreyer's approach that included the effect of gravity component which was neglected in classic Lucas-Washburn's model. In addition, the predictive model of wicking accounted for realistic structural characteristics of AGM via orientation averaging approach. For wicking under confined state, the structural parameters have been updated under defined level of compressive stresses based upon the constitutive equation derived for a planar network of fibers in AGM under transverse loading conditions. A comparison has been made between the theoretical models and experimental results of wicking behavior under unconfined and confined states. Most importantly, the presented work has highlighted the questionable validity of classic Lucas-Washburn model for predicting the wicking characteristics of AGM separator over longer time duration.

  2. A knowledge based advisory system for acid/base titrations in non-aqueous solvents

    OpenAIRE

    1996-01-01

    A computer program was developed that could advice on the choice of solvent and titrant for acid/base titrations in nonaqueous media. It is shown that the feasibility of a titration in a given solvent can be calculated from solvent properties and intrinsic acid/base properties of the sample components. A consistent set of properties for various solvents and a large number of acidic and basic compounds was calculated from literature data with the use of a genetic algorithm. Test results show t...

  3. Advances in nucleic acid-based diagnostics of bacterial infections

    DEFF Research Database (Denmark)

    Barken, Kim Bundvig; Haagensen, Janus Anders Juul; Tolker-Nielsen, Tim

    2007-01-01

    of these pathogens is important to isolate patients and prevent further spreading of the diseases. Newly developed diagnostic procedures are superior with respect to turnaround time, sensitivity and specificity. Methods like multiplex real time PCR and different array-based technologies offer the possibility......Methods for rapid detection of infectious bacteria and antimicrobial-resistant pathogens have evolved significantly over the last decade. Many of the new procedures are nucleic acid-based and replace conventional diagnostic methods like culturing which is time consuming especially with fastidious...

  4. Acid-base chemistry of frustrated water at protein interfaces.

    Science.gov (United States)

    Fernández, Ariel

    2016-01-01

    Water molecules at a protein interface are often frustrated in hydrogen-bonding opportunities due to subnanoscale confinement. As shown, this condition makes them behave as a general base that may titrate side-chain ammonium and guanidinium cations. Frustration-based chemistry is captured by a quantum mechanical treatment of proton transference and shown to remove same-charge uncompensated anticontacts at the interface found in the crystallographic record and in other spectroscopic information on the aqueous interface. Such observations are untenable within classical arguments, as hydronium is a stronger acid than ammonium or guanidinium. Frustration enables a directed Grotthuss mechanism for proton transference stabilizing same-charge anticontacts.

  5. Synthesis and curing of alkyd enamels based on ricinoleic acid

    Directory of Open Access Journals (Sweden)

    Jovičić Mirjana C.

    2010-01-01

    Full Text Available A combination of an alkyd resin with a melamine-formaldehyde resin gives a cured enamel film with the flexibility of the alkyd constituent and the high chemical resistance and hardness of the melamine resin at the same time. The melamine resin is a minor constituent and plays the role of a crosslinking agent. In this paper, alkyd resins of high hydroxyl numbers based on trimethylolpropane, ricinoleic acid and phthalic anhydride were synthesized. Two alkyds having 30 and 40 wt% of ricinoleic acid were formulated by calculation on alkyd constant. Alkyds were characterized by FTIR and by the determination of acid and hydroxyl numbers. Then synthesized alkyds were made into baking enamels by mixing with melamine-formaldehyde resins (weight ratio of 70:30 based on dried mass. Two types of commercial melamine resins were used: threeisobutoxymethyl melamine-formaldehyde resin (TIMMF and hexamethoxymethyl melamine resin (HMMMF. Prepared alkyd/melamine resin mixtures were cured in a differential scanning calorimeter (DSC under non-isothermal mode. Apparent degree of curing as a function of temperature was calculated from the curing enthalpies. Kinetic parameters of curing were calculated using Freeman-Carroll method. TIMMF resin is more reactive with synthesized alkyds than HMMMF resin what was expected. Alkyd resin with 30 wt% of ricinoleic acid is slightly more reactive than alkyd with 40 wt% of ricinoleic acid, probably because it has the high contents of free hydroxyl and acid groups. The gel content, Tg, thermal stability, hardness, elasticity and impact resistance of coated films cured at 150°C for 60 min were measured. Cured films show good thermal stability since the onset of films thermal degradation determined by thermogravimetric analysis (TGA is observed at the temperatures from 281 to 329°C. Films based on alkyd 30 are more thermal stable than those from alkyd 40, with the same melamine resin. The type of alkyd resin has no significant

  6. Nolz1 promotes striatal neurogenesis through the regulation of retinoic acid signaling

    Directory of Open Access Journals (Sweden)

    Urbán Noelia

    2010-08-01

    Full Text Available Abstract Background Nolz1 is a zinc finger transcription factor whose expression is enriched in the lateral ganglionic eminence (LGE, although its function is still unknown. Results Here we analyze the role of Nolz1 during LGE development. We show that Nolz1 expression is high in proliferating neural progenitor cells (NPCs of the LGE subventricular zone. In addition, low levels of Nolz1 are detected in the mantle zone, as well as in the adult striatum. Similarly, Nolz1 is highly expressed in proliferating LGE-derived NPC cultures, but its levels rapidly decrease upon cell differentiation, pointing to a role of Nolz1 in the control of NPC proliferation and/or differentiation. In agreement with this hypothesis, we find that Nolz1 over-expression promotes cell cycle exit of NPCs in neurosphere cultures and negatively regulates proliferation in telencephalic organotypic cultures. Within LGE primary cultures, Nolz1 over-expression promotes the acquisition of a neuronal phenotype, since it increases the number of β-III tubulin (Tuj1- and microtubule-associated protein (MAP2-positive neurons, and inhibits astrocyte generation and/or differentiation. Retinoic acid (RA is one of the most important morphogens involved in striatal neurogenesis, and regulates Nolz1 expression in different systems. Here we show that Nolz1 also responds to this morphogen in E12.5 LGE-derived cell cultures. However, Nolz1 expression is not regulated by RA in E14.5 LGE-derived cell cultures, nor is it affected during LGE development in mouse models that present decreased RA levels. Interestingly, we find that Gsx2, which is necessary for normal RA signaling during LGE development, is also required for Nolz1 expression, which is lost in Gsx2 knockout mice. These findings suggest that Nolz1 might act downstream of Gsx2 to regulate RA-induced neurogenesis. Keeping with this hypothesis, we show that Nolz1 induces the selective expression of the RA receptor (RARβ without altering

  7. Iron-regulated excretion of alpha-keto acids by Salmonella typhimurium.

    OpenAIRE

    Reissbrodt, R.; Kingsley, R; Rabsch, W.; Beer, W.; Roberts, M.; Williams, P H

    1997-01-01

    Excretion of alpha-keto acids by clinical isolates and laboratory strains of Salmonella typhimurium was determined by high-performance liquid chromatography analysis of culture supernatants. The levels of excretion increased markedly with increasing iron stress imposed by the presence of alpha,alpha'-dipyridyl or conalbumin in the medium. The major product was pyruvic acid, but significant concentrations of alpha-ketoglutaric acid, alpha-ketoisovaleric acid, and alpha-ketoisocaproic acid were...

  8. CitI, a Transcription Factor Involved in Regulation of Citrate Metabolism in Lactic Acid Bacteria†

    Science.gov (United States)

    Martin, Mauricio G.; Magni, Christian; de Mendoza, Diego; López, Paloma

    2005-01-01

    A large variety of lactic acid bacteria (LAB) can utilize citrate under fermentative conditions. Although much information concerning the metabolic pathways leading to citrate utilization by LAB has been gathered, the mechanisms regulating these pathways are obscure. In Weissella paramesenteroides (formerly called Leuconostoc paramesenteroides), transcription of the citMDEFCGRP citrate operon and the upstream divergent gene citI is induced by the presence of citrate in the medium. Although genetic experiments have suggested that CitI is a transcriptional activator whose activity can be modulated in response to citrate availability, specific details of the interaction between CitI and DNA remained unknown. In this study, we show that CitI recognizes two A+T-rich operator sites located between citI and citM and that the DNA-binding affinity of CitI is increased by citrate. Subsequently, this citrate signal propagation leads to the activation of the cit operon through an enhanced recruitment of RNA polymerase to its promoters. Our results indicate that the control of CitI by the cellular pools of citrate provides a mechanism for sensing the availability of citrate and adjusting the expression of the cit operon accordingly. In addition, this is the first reported example of a transcription factor directly functioning as a citrate-activated switch allowing the cell to optimize the generation of metabolic energy. PMID:16030208

  9. Gallic acid regulates skin photoaging in UVB-exposed fibroblast and hairless mice.

    Science.gov (United States)

    Hwang, Eunson; Park, Sang-Yong; Lee, Hyun Ji; Lee, Tae Youp; Sun, Zheng-Wang; Yi, Tae Hoo

    2014-12-01

    Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin-6, and MMP-1 were significantly suppressed, and type I procollagen expression was stimulated in UVB-irradiated and GA-treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP-1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor-β1. Our data indicate that GA is a potential candidate for the prevention of UVB-induced premature skin aging.

  10. The Regulation of Acid Mine Drainage in South Africa: Law and Governance Perspectives

    Directory of Open Access Journals (Sweden)

    Loretta Feris

    2014-12-01

    Full Text Available Acid mine drainage (AMD is arguably one of the most serious environmental concerns in South Africa. AMD is a legacy left behind by abandoned, derelict and defunct mines, and is a continuing by-product of existing mining activities. In addition to its environmental impacts, AMD will also impact on all the parameters of sustainability, including ecological, social and economic concerns. In particular, AMD is set to affect infrastructure, displace people and affect their livelihoods, influence economic activity, impact on the resource extraction industry, and affect South Africa's policies and actions in relation to climate change and its efforts to move towards a low carbon economy; and it will test the efficiency of regulatory interventions emanating from both the private and the public sector to the extreme. Given these pervasive challenges, in this article we provide a survey of the AMD problem in South Africa through the law and governance lens. We commence by highlighting the various issues and challenges that result from AMD in the environmental context on the one hand, and the law and governance context on the other hand. We then describe the many provisions of the regulatory framework that we believe would be instrumental in responding to the threat. We conclude the article with brief remarks on what we believe are important considerations in the future regulation of AMD.

  11. Ursolic acid regulates aging process through enhancing of metabolic sensor proteins level.

    Science.gov (United States)

    Bahrami, Soroush Alaghehband; Bakhtiari, Nuredin

    2016-08-01

    We previously reported that Ursolic Acid (UA) ameliorates skeletal muscle performance through satellite cells proliferation and cellular energy status. In studying the potential role of the hypothalamus in aging, we developed a strategy to pursue UA effects on the hypothalamus anti-aging proteins such as; SIRT1, SIRT6, PGC-1β and α-Klotho. In this study, we used a model of aging animals (C57BL/6). UA dissolved in Corn oil (20mg/ml) and then administrated (200mg/Kg i.p injection) to mice, twice daily for 7days. After treatment times, the mice perfused and the hypothalamus isolated for preparing of tissue to Immunofluorescence microscopy. The data illustrated that UA significantly increased SIRT1 (∼3.5±0.3 folds) and SIRT-6 (∼1.5±0.2 folds) proteins overexpression (Presults showed that UA enhanced α-Klotho (∼3.3±0.3) and PGC-1β (∼2.6±0.2 folds) proteins levels (PUA through enhancing of anti-aging biomarkers (SIRT1 and SIRT6) and PGC-1β in hypothalamus regulates aging-process and attenuates mitochondrial-related diseases. In regard to the key role of α-Klotho in aging, our data indicate that UA may be on the horizon to forestall diseases of aging.

  12. Regulation of Ecto-5´-Nucleotidase by Docosahexaenoic Acid in Human Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Vu Thi Thom

    2013-08-01

    Full Text Available Background/Aims: Modulation of extracellular adenine nucleotide and adenosine concentrations is one potential mechanism by which docosahexaenoic acid (DHA may exert beneficial effects in critically ill patients. This study assessed DHA effects on extracellular adenine purines. Methods: Experiments used human pulmonary endothelial cells (HPMEC and umbilical vein endothelial cells (HUVEC treated with DHA (48 h. mRNA level (real-time PCR, expression (western blot, flow cytometry and activities (hydrolysis of etheno(ε-purines and fluorescence HPLC of CD73 (ecto-5´-nucleotidase and CD39 (ecto-NTPDase-1 were quantified. Results: DHA elevated total CD73 membrane protein expression concentration-dependently but CD73 mRNA level did not change. Increased expression was paralleled by increased enzyme activity. Effects observed on membrane level were reversed in intact cells, in which ε-AMP hydrolysis decreased after DHA. In intact endothelial cells ATP release was enhanced and CD39 activity blunted following DHA treatment. Hence, extracellular ATP and ADP concentrations increased and this inhibited ε-AMP hydrolysis. Conclusion: In human endothelial cells DHA caused 1 up-regulation of CD73 protein content and increased AMP hydrolysis at the cell membrane level, 2 increased cellular ATP release, and 3 decreased extracellular ATP/ADP hydrolysis. Thus, reorganization of the extracellular adenine-nucleotide-adenosine axis in response to DHA resulted in an increased extracellular ATP/adenosine ratio.

  13. Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up-regulation

    Institute of Scientific and Technical Information of China (English)

    Ananya Chatterjee; Sirshendu Chatterjee; Smita Das; Arpita Saha; Subrata Chattopadhyay; Sandip K. Bandyopadhyay

    2012-01-01

    The mechanism of indomethacin-induced gastric ulcer healing by ellagic acid (EA) in experimental mice model is described in our study.Ulcer index (UI) and myeloperoxidase (MPO) activity of the stomach tissues showed maximum ulceration on the third day after indomethacin (18 mg/kg,single dose) administration.Preliminary observation of UI and MPO activity suggests that EA possesses ulcer-healing activity.Other anti-ulcer parameters such as the levels of prostaglandin E2,cyclooxygenase (COX) 1 and 2 enzymes,anti-inflammatory cytokines [interleukin (IL)-4 and -5J,pro-angiogenic factors,e.g.vascular endothelial growth factor,hepatocyte growth factor (HGF),and endothelial growth factor (EGF) were down-regulated by indomethacin.EA (7 mg/kg/day) treatment for 3 days shifted the indomethacin-induced pro-inflammatory biochemical parameters to the healing side.These activities were correlated with the ability of EA to alter the COX-2-dependent healing pathways.The ulcer-healing activity of EA was,however,compromised by pre-administration of the specific COX-2 inhibitor,celecoxib,and NS-398.Taken together,these results suggested that the EA treatment accelerates ulcer healing by inducing IL-4,EGF/HGF levds and enhances COX-2 expression.

  14. Reactive oxygen species, abscisic acid and ethylene interact to regulate sunflower seed germination.

    Science.gov (United States)

    El-Maarouf-Bouteau, Hayat; Sajjad, Yasar; Bazin, Jérémie; Langlade, Nicolas; Cristescu, Simona M; Balzergue, Sandrine; Baudouin, Emmanuel; Bailly, Christophe

    2015-02-01

    Sunflower (Helianthus annuus L.) seed dormancy is regulated by reactive oxygen species (ROS) and can be alleviated by incubating dormant embryos in the presence of methylviologen (MV), a ROS-generating compound. Ethylene alleviates sunflower seed dormancy whereas abscisic acid (ABA) represses germination. The purposes of this study were to identify the molecular basis of ROS effect on seed germination and to investigate their possible relationship with hormone signalling pathways. Ethylene treatment provoked ROS generation in embryonic axis whereas ABA had no effect on their production. The beneficial effect of ethylene on germination was lowered in the presence of antioxidant compounds, and MV suppressed the inhibitory effect of ABA. MV treatment did not alter significantly ethylene nor ABA production during seed imbibition. Microarray analysis showed that MV treatment triggered differential expression of 120 probe sets (59 more abundant and 61 less abundant genes), and most of the identified transcripts were related to cell signalling components. Many transcripts less represented in MV-treated seeds were involved in ABA signalling, thus suggesting an interaction between ROS and ABA signalling pathways at the transcriptional level. Altogether, these results shed new light on the crosstalk between ROS and plant hormones in seed germination.

  15. Regulation of fatty acid metabolism by FadR is essential for Vibrio vulnificus to cause infection of mice.

    Science.gov (United States)

    Brown, Roslyn N; Gulig, Paul A

    2008-12-01

    The opportunistic bacterial pathogen Vibrio vulnificus causes severe wound infection and fatal septicemia. We used alkaline phosphatase insertion mutagenesis in a clinical isolate of V. vulnificus to find genes necessary for virulence, and we identified fadR, which encodes a regulator of fatty acid metabolism. The fadR::mini-Tn5Km2phoA mutant was highly attenuated in a subcutaneously inoculated iron dextran-treated mouse model of V. vulnificus disease, was hypersensitive to the fatty acid synthase inhibitor cerulenin, showed aberrant expression of fatty acid biosynthetic (fab) genes and fatty acid oxidative (fad) genes, produced smaller colonies on agar media, and grew slower in rich broth than did the wild-type parent. Deletion of fadR essentially recapitulated the phenotypes of the insertion mutant, and the DeltafadR mutation was complemented in trans with the wild-type gene. Further characterization of the DeltafadR mutant showed that it was not generally hypersensitive to envelope stresses but had decreased motility and showed an altered membrane lipid profile compared to that of the wild type. Supplementation of broth with the unsaturated fatty acid oleate restored wild-type growth in vitro, and infection with oleate in the inoculum increased the ability of the DeltafadR mutant to infect mice. We conclude that fadR and regulation of fatty acid metabolism are essential for V. vulnificus to be able to cause disease in mammalian hosts.

  16. Age estimation based on aspartic acid racemization in human sclera.

    Science.gov (United States)

    Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie

    2016-01-01

    Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.

  17. How Do Undergraduate Students Conceptualize Acid-Base Chemistry? Measurement of a Concept Progression

    Science.gov (United States)

    Romine, William L.; Todd, Amber N.; Clark, Travis B.

    2016-01-01

    We developed and validated a new instrument, called "Measuring Concept progressions in Acid-Base chemistry" (MCAB) and used it to better understand the progression of undergraduate students' understandings about acid-base chemistry. Items were developed based on an existing learning progression for acid-base chemistry. We used the Rasch…

  18. Down-regulation of malignant potential by alpha linolenic acid in human and mouse colon cancer cells.

    Science.gov (United States)

    Chamberland, John P; Moon, Hyun-Seuk

    2015-03-01

    Omega-3 fatty acids (also called ω-3 fatty acis or n-3 fatty acid) are polyunsaturated fatty acids (PUFAs) with a double bond (C=C) at the third carbon atom from the end of the carbon chain. Numerous test tube and animal studies have shown that omega-3 fatty acids may prevent or inhibit the growth of cancers, suggesting that omega-3 fatty acids are important in cancer physiology. Alpha-linolenic acid (ALA) is one of an essential omega-3 fatty acid and organic compound found in seeds (chia and flaxseed), nuts (notably walnuts), and many common vegetable oils. ALA has also been shown to down-regulate cell proliferation of prostate, breast, and bladder cancer cells. However, direct evidence that ALA suppresses to the development of colon cancer has not been studied. Also, no previous studies have evaluated whether ALA may regulate malignant potential (adhesion, invasion and colony formation) in colon cancer cells. In order to address the questions above, we conducted in vitro studies and evaluated whether ALA may down-regulate malignant potential in human (HT29 and HCT116) and mouse (MCA38) colon cancer cell lines. We observed that treatment with 1-5 mM of ALA inhibits cell proliferation, adhesion and invasion in both human and mouse colon cancer cell lines. Interestingly, we observed that ALA did not decrease total colony numbers when compared to control. By contrast, we found that size of colony was significantly changed by ALA treatment when compared to control in all colon cancer cell lines. We suggest that our data enhance our current knowledge of ALA's mechanism and provide crucial information to further the development of new therapies for the management or chemoprevention of colon cancer.

  19. Acetylsalicylic acid regulates MMP-2 activity and inhibits colorectal invasion of murine B16F0 melanoma cells in C57BL/6J mice: effects of prostaglandin F(2)alpha.

    Science.gov (United States)

    Tsai, Chin-Shaw Stella; Luo, Shue-Fen; Ning, Chung-Chu; Lin, Chien-Liang; Jiang, Ming-Chung; Liao, Ching-Fong

    2009-08-01

    Epidemiological studies indicate that acetylsalicylic acid may reduce the risk of mortality due to colon cancers. Metastasis is the major cause of cancer death. Matrix metalloproteinases (MMPs) play important roles in tumor invasion regulation, and prostaglandin F(2)alpha (PGF(2)alpha) is a key stimulator of MMP production. Thus, we investigated whether acetylsalicylic acid regulated MMP activity and the invasion of cancer cells and whether PGF(2)alpha attenuated acetylsalicylic acid-inhibited invasion of cancer cells. Gelatin-based zymography assays showed that acetylsalicylic acid inhibited the MMP-2 activity of B16F0 melanoma cells. Matrigel-based chemoinvasion assays showed that acetylsalicylic acid inhibited the invasion of B16F0 cells. Acetylsalicylic acid can inhibit PGF(2)alpha synthesis and PGF(2)alpha is a key stimulator of MMP-2 production. Our data showed that PGF(2)alpha treatment attenuated the acetylsalicylic acid-inhibited invasion of B16F0 cells. In animal experiments, acetylsalicylic acid reduced colorectal metastasis of B16F0 cells in C57BL/6J mice by 44%. Our results suggest that PGF(2)alpha is a therapeutic target for metastasis inhibition and acetylsalicylic acid may possess anti-metastasis ability.

  20. Production of Lauric Acid and Pentaerythritol Based Biolubricant

    Directory of Open Access Journals (Sweden)

    Hamizah Ammarah Mahmud

    2014-01-01

    Full Text Available Production of a  biolubricant based on  lauric acid and pentaerythritol (PE was carried out. The esterification reaction at 180°C-200°C for 6-7 hours in the present of sulphuric acid as catalyst. The  end product (PE ester was confirmed through the determination of Fourier Transformation Infrared spectroscopy (FTIR, Nuclear Magnetic Resonance (NMR, GC-FID . The characterization of PE ester's of  viscosity index, pour point, flash point and  oxidative stability . The PE ester showed flash point at 250°C, pour point at 25°C, viscosity index 162 and the oxidative stability at 216°C respectively.The  PE ester produced is plausible to be used as potential  biolubricant.

  1. Acid-Base Balance in Uremic Rats with Vascular Calcification

    Directory of Open Access Journals (Sweden)

    Alan Peralta-Ramírez

    2014-07-01

    Full Text Available Background/Aims: Vascular calcification (VC, a major complication in humans and animals with chronic kidney disease (CKD, is influenced by changes in acid-base balance. The purpose of this study was to describe the acid-base balance in uremic rats with VC and to correlate the parameters that define acid-base equilibrium with VC. Methods: Twenty-two rats with CKD induced by 5/6 nephrectomy (5/6 Nx and 10 nonuremic control rats were studied. Results: The 5/6 Nx rats showed extensive VC as evidenced by a high aortic calcium (9.2 ± 1.7 mg/g of tissue and phosphorus (20.6 ± 4.9 mg/g of tissue content. Uremic rats had an increased pH level (7.57 ± 0.03 as a consequence of both respiratory (PaCO2 = 28.4 ± 2.1 mm Hg and, to a lesser degree, metabolic (base excess = 4.1 ± 1 mmol/l derangements. A high positive correlation between both anion gap (AG and strong ion difference (SID with aortic calcium (AG: r = 0.604, p = 0.02; SID: r = 0.647, p = 0.01 and with aortic phosphorus (AG: r = 0.684, p = 0.007; SID: r = 0.785, p = 0.01 was detected. Conclusions: In an experimental model of uremic rats, VC showed high positive correlation with AG and SID.

  2. Glucose, amino acids and fatty acids directly regulate ghrelin and NUCB2/nesfatin-1 in the intestine and hepatopancreas of goldfish (Carassius auratus) in vitro.

    Science.gov (United States)

    Bertucci, Juan Ignacio; Blanco, Ayelén Melisa; Canosa, Luis Fabián; Unniappan, Suraj

    2017-04-01

    Ghrelin and nesfatin-1 are two peptidyl hormones primarily involved in food intake regulation. We previously reported that the amount of dietary carbohydrates, protein and lipids modulates the expression of these peptides in goldfish in vivo. In the present work, we aimed to characterize the effects of single nutrients on ghrelin and nesfatin-1 in the intestine and hepatopancreas. First, immunolocalization of ghrelin and NUCB2/nesfatin-1 in goldfish hepatopancreas cells was studied by immunohistochemistry. Second, the effects of 2 and 4hour-long exposures of cultured intestine and hepatopancreas sections to glucose, l-tryptophan, oleic acid, linolenic acid (LNA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on ghrelin and nesfatin-1 gene and protein expression were studied. Co-localization of ghrelin and NUCB2/nesfatin-1 in the cytoplasm of goldfish hepatocytes was found. Exposure to glucose led to an upregulation of preproghrelin and a downregulation of nucb2/nesfatin-1 in the intestine. l-Tryptophan mainly decreased the expression of both peptides in the intestine and hepatopancreas. Fatty acids, in general, downregulated NUCB2/nesfatin-1 in the intestine, but only the longer and highly unsaturated fatty acids inhibited preproghrelin. EPA exposure led to a decrease in preproghrelin, and an increase in nucb2/nesfatin-1 expression in hepatopancreas after 2h. These results show that macronutrients exert a dose- and time-dependent, direct regulation of ghrelin and nesfatin-1 in the intestine and hepatopancreas, and suggest a role for these hormones in the digestive process and nutrient metabolism.

  3. Superabsorbent biphasic system based on poly(lactic acid) and poly(acrylic acid)

    Science.gov (United States)

    Sartore, Luciana; Pandini, Stefano; Baldi, Francesco; Bignotti, Fabio

    2016-05-01

    In this research work, biocomposites based on crosslinked particles of poly(acrylic acid), commonly used as superabsorbent polymer (SAP), and poly-L-lactic acid (PLLA) were developed to elucidate the role of the filler (i.e., polymeric crosslinked particles) on the overall physico-mechanical behavior and to obtain superabsorbent thermoplastic products. Samples prepared by melt-blending of components in different ratios showed a biphasic system with a regular distribution of particles, with diameter ranging from 5 to 10 μm, within the PLLA polymeric matrix. The polymeric biphasic system, coded PLASA i.e. superabsorbent poly(lactic acid), showed excellent swelling properties, demonstrating that cross-linked particles retain their superabsorbent ability, as in their free counterparts, even if distributed in a thermoplastic polymeric matrix. The thermal characteristics of the biocomposites evidence enhanced thermal stability in comparison with neat PLLA and also mechanical properties are markedly modified by addition of crosslinked particles which induce regular stiffening effect. Furthermore, in aqueous environments the particles swell and are leached from PLLA matrix generating very high porosity. These new open-pore PLLA foams, produced in absence of organic solvents and chemical foaming agents, with good physico-mechanical properties appear very promising for several applications, for instance in tissue engineering for scaffold production.

  4. Acid-base buffer effect of fulvic acid and barium fulvate from weathered coal

    Energy Technology Data Exchange (ETDEWEB)

    Xiao-feng Guo; Xi-feng Li [Taiyuan University of Science and Technology, Taiyuan (China). Mining Engineering Institute

    2009-12-15

    The acid-base buffer characteristics of fulvic acid (FA) and barium fulvate (BaFA) were analyzed. Each share of the sample or model agents (phthalic acid and salicylic acid) were separately mixed into a series of shares of dilute solutions of HCl or NaOH with a series of concentration. The original pH values of the solutions were arranged from 2 to 13. Final balanced pH of each share was measured. The pH changes show that FA and BaFA possess buffer ability, whereas the model agents do not. The tendency of balanced pH values was 5.4 for FA and 7.4 for BaFA, whereas the original pH was 4.0-8.5; balanced pH changed little. At room temperature, the maximum buffer capacities were as follows: 18.11 mmol hydroxyl per gram FA, 11.25 mmol hydroxyl per gram BaFA, 1.19 mmol proton per gram FA, and 1.45 mmol proton per gram BaFA. Mathematics analysis shows that logarithm of buffer capacities of FA and BaFA is linearly dependent on original pH. Compared with BaFA and model agents, it is concluded that FA buffer capacity against hydroxyl relies not only on its acidic groups, BaFA buffer capacity against hydroxyl does not rely on its acidic groups, and FA buffer capacity against proton is not related with its carboxyl and phenolic hydroxyl group. The pH values of FA-water solutions with different concentrations from 1 to 10 grams per liter were measured. Their pH values were slightly affected by its concentration. Thus, FA possesses a much stronger buffer ability against water dilution than common buffer agent. All the pH values of FA water solutions were very nearly 5.4, just the same as the balanced pH tendency for adding FA. 10 refs., 5 figs., 2 tabs.

  5. Acid-base buffer effect of fulvic acid and barium fulvate from weathered coal

    Institute of Scientific and Technical Information of China (English)

    GUO Xiao-feng; LI Xi-feng

    2009-01-01

    The acid-base buffer characteristics of fulvic acid (FA) and barium fulvate (BaFA) were analyzed. Each share of the sample or model agents (phthalic acid and salicylic acid) were separately mixed into a series of shares of dilute solutions of HCI or NaOH with a series of concentration. The original pH values of the solutions were arranged from 2 to 13. Final balanced pH of each share was measured. The pH changes show that FA and BaFA possess buffer ability, whereas the model agents do not. The tendency of balanced pH values was 5.4 for FA and 7.4 for BaFA, whereas the original pH was 4.0-8.5; balanced pH changed little. At room temperature, the maximum buffer capacities were as follows:18.11 mmol hydroxyl per gram FA, 11.25 mmol hydroxyl per gram BaFA, 1.19 mmol proton per gram FA, and 1.45 mmol proton per gram BaFA. Mathematics analysis shows that logarithm of buffer capacities of FA and BaFA is linearly dependent on original pH. Compared with BaFA and model agents, it is concluded that FA buffer capacity against hydroxyl relies not only on its acidic groups, BaFA buffer capacity against hydroxyl does not rely on its acidic groups, and FA buffer capacity against proton is not related with its carboxyl and phenolic hydroxyl group. The pH values of FA-water solutions with different concentrations from 1 to 10 grams per liter were measured. Their pH values were slightly affected by its concentration. Thus, FA possesses a much stronger buffer ability against water dilution than common buffer agent. All the pH values of FA water solutions were very nearby 5.4,just the same as the balanced pH tendency for adding FA.

  6. The response regulator YycF inhibits expression of the fatty acid biosynthesis repressor FabT in Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Maria Luz Mohedano

    2016-08-01

    Full Text Available The YycFG (also known as WalRK, VicRK, MicAB or TCS02 two-component system (TCS is highly conserved among Gram-positive bacteria with a low G+C content. In Streptococcus pneumoniae the YycF response regulator has been reported to be essential due to its control of pcsB gene expression. Previously we showed that overexpression of yycF in S. pneumoniae TIGR4 altered the transcription of genes involved in cell wall metabolism and fatty acid biosynthesis, giving rise to anomalous cell division and increased chain length of membrane fatty acids. Here, we have overexpressed the yycFG system in TIGR4 wild-type strain and yycF in a TIGR4 mutant depleted of YycG, and analyzed their effects on expression of proteins involved in fatty acid biosynthesis during activation of the TCS. We demonstrate that transcription of the fab genes and levels of their products were only altered in the YycF overexpressing strain, indicating that the unphosphorylated form of YycF is involved in the regulation of fatty acid biosynthesis. In addition, DNA-binding assays and in vitro transcription experiments with purified YycF and the promoter region of the FabTH-acp operon support a direct inhibition of transcription of the FabT repressor by YycF, thus confirming the role of the unphosphorylated form in transcriptional regulation.

  7. The Response Regulator YycF Inhibits Expression of the Fatty Acid Biosynthesis Repressor FabT in Streptococcus pneumoniae

    Science.gov (United States)

    Mohedano, Maria L.; Amblar, Mónica; de la Fuente, Alicia; Wells, Jerry M.; López, Paloma

    2016-01-01

    The YycFG (also known as WalRK, VicRK, MicAB, or TCS02) two-component system (TCS) is highly conserved among Gram-positive bacteria with a low G+C content. In Streptococcus pneumoniae the YycF response regulator has been reported to be essential due to its control of pcsB gene expression. Previously we showed that overexpression of yycF in S. pneumoniae TIGR4 altered the transcription of genes involved in cell wall metabolism and fatty acid biosynthesis, giving rise to anomalous cell division and increased chain length of membrane fatty acids. Here, we have overexpressed the yycFG system in TIGR4 wild-type strain and yycF in a TIGR4 mutant depleted of YycG, and analyzed their effects on expression of proteins involved in fatty acid biosynthesis during activation of the TCS. We demonstrate that transcription of the fab genes and levels of their products were only altered in the YycF overexpressing strain, indicating that the unphosphorylated form of YycF is involved in the regulation of fatty acid biosynthesis. In addition, DNA-binding assays and in vitro transcription experiments with purified YycF and the promoter region of the FabTH-acp operon support a direct inhibition of transcription of the FabT repressor by YycF, thus confirming the role of the unphosphorylated form in transcriptional regulation. PMID:27610104

  8. When acid-base titrations are carried out in unusual conditions

    OpenAIRE

    Domenico De Marco; Rocco De Marco

    2012-01-01

    Uncommon aspects in acid-base titrations are presented, which occur in titrations between both mono- and/or poly-functional acid and bases but are rarely introduced in ordinary analytical chemistry courses.

  9. Lysophosphatidic acid receptor-5 negatively regulates cellular responses in mouse fibroblast 3T3 cells

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Yan; Hirane, Miku; Araki, Mutsumi [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Fukushima, Nobuyuki [Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Tsujiuchi, Toshifumi, E-mail: ttujiuch@life.kindai.ac.jp [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)

    2014-04-04

    Highlights: • LPA{sub 5} inhibits the cell growth and motile activities of 3T3 cells. • LPA{sub 5} suppresses the cell motile activities stimulated by hydrogen peroxide in 3T3 cells. • Enhancement of LPA{sub 5} on the cell motile activities inhibited by LPA{sub 1} in 3T3 cells. • The expression and activation of Mmp-9 were inhibited by LPA{sub 5} in 3T3 cells. • LPA signaling via LPA{sub 5} acts as a negative regulator of cellular responses in 3T3 cells. - Abstract: Lysophosphatidic acid (LPA) signaling via G protein-coupled LPA receptors (LPA{sub 1}–LPA{sub 6}) mediates a variety of biological functions, including cell migration. Recently, we have reported that LPA{sub 1} inhibited the cell motile activities of mouse fibroblast 3T3 cells. In the present study, to evaluate a role of LPA{sub 5} in cellular responses, Lpar5 knockdown (3T3-L5) cells were generated from 3T3 cells. In cell proliferation assays, LPA markedly stimulated the cell proliferation activities of 3T3-L5 cells, compared with control cells. In cell motility assays with Cell Culture Inserts, the cell motile activities of 3T3-L5 cells were significantly higher than those of control cells. The activity levels of matrix metalloproteinases (MMPs) were measured by gelatin zymography. 3T3-L5 cells stimulated the activation of Mmp-2, correlating with the expression levels of Mmp-2 gene. Moreover, to assess the co-effects of LPA{sub 1} and LPA{sub 5} on cell motile activities, Lpar5 knockdown (3T3a1-L5) cells were also established from Lpar1 over-expressing (3T3a1) cells. 3T3a1-L5 cells increased the cell motile activities of 3T3a1 cells, while the cell motile activities of 3T3a1 cells were significantly lower than those of control cells. These results suggest that LPA{sub 5} may act as a negative regulator of cellular responses in mouse fibroblast 3T3 cells, similar to the case for LPA{sub 1}.

  10. Determination of the Acid-Base Dissociation Constant of Acid-Degradable Hexamethylenetetramine by Capillary Zone Electrophoresis.

    Science.gov (United States)

    Takayanagi, Toshio; Shimakami, Natsumi; Kurashina, Masashi; Mizuguchi, Hitoshi; Yabutani, Tomoki

    2016-01-01

    The acid-base equilibrium of hexamethylenetetramine (hexamine) was analyzed with its effective electrophoretic mobility by capillary zone electrophoresis. Although hexamine is degradable in a weakly acidic aqueous solution, and the degraded products of ammonia and formaldehyde can be formed, the effective electrophoretic mobility of hexamine was measured in the pH range between 2.8 and 6.9. An acid-base dissociation equilibrium of the protonated hexamine was analyzed based on the mobility change, and an acid dissociation constant of pKa = 4.93 ± 0.01 (mean ± standard error, ionic strength: 0.020 mol dm(-3)) was determined. The monoprotic acid-base equilibrium of hexamine was confirmed through comparisons of its electrophoretic mobility with the N-ethylquinolinium ion and with the monocationic N-ethyl derivative of hexamine, as well as a slope analysis of the dissociation equilibrium.

  11. Regulation of erucic acid accumulation in oilseed rape (Brassica napus L.). Effects of temperature and abscisic acid.

    NARCIS (Netherlands)

    Wilmer, J.A.

    1997-01-01

    Vegetable oils are an important commodity world-wide with an annual production of about 70 million tonnes. Oilseed rape is one of the four major crops, providing about 10% of the total production. Quality of vegetable oils is determined by the fatty acid composition of the triacylglycerols (TAG) tha

  12. Regulation of adipose branched chain amino acid catabolism enzyme expression and cross-adipose amino acid flux in human obesity

    Science.gov (United States)

    Elevated blood branched chain amino acids (BCAA) are often associated with insulin resistance and type 2 diabetes. One possibility is that under these conditions there is a reduced cellular utilization and/or lower complete oxidation of BCAAs. White adipose tissue (WAT) has become appreciated as a...

  13. Rosmarinic acid is a homoserine lactone mimic produced by plants that activates a bacterial quorum-sensing regulator.

    Science.gov (United States)

    Corral-Lugo, Andrés; Daddaoua, Abdelali; Ortega, Alvaro; Espinosa-Urgel, Manuel; Krell, Tino

    2016-01-05

    Quorum sensing is a bacterial communication mechanism that controls genes, enabling bacteria to live as communities, such as biofilms. Homoserine lactone (HSL) molecules function as quorum-sensing signals for Gram-negative bacteria. Plants also produce previously unidentified compounds that affect quorum sensing. We identified rosmarinic acid as a plant-derived compound that functioned as an HSL mimic. In vitro assays showed that rosmarinic acid bound to the quorum-sensing regulator RhlR of Pseudomonas aeruginosa PAO1 and competed with the bacterial ligand N-butanoyl-homoserine lactone (C4-HSL). Furthermore, rosmarinic acid stimulated a greater increase in RhlR-mediated transcription in vitro than that of C4-HSL. In P. aeruginosa, rosmarinic acid induced quorum sensing-dependent gene expression and increased biofilm formation and the production of the virulence factors pyocyanin and elastase. Because P. aeruginosa PAO1 infection induces rosmarinic acid secretion from plant roots, our results indicate that rosmarinic acid secretion is a plant defense mechanism to stimulate a premature quorum-sensing response. P. aeruginosa is a ubiquitous pathogen that infects plants and animals; therefore, identification of rosmarinic acid as an inducer of premature quorum-sensing responses may be useful in agriculture and inform human therapeutic strategies.

  14. Endogenous excitatory amino acid neurotransmission regulates thyroid-stimulating hormone and thyroid hormone secretion in conscious freely moving male rats.

    Science.gov (United States)

    Arufe, M C; Durán, R; Perez-Vences, D; Alfonso, M

    2002-04-01

    The role of neurotransmission of endogenous excitatory amino acid (EAA) on serum thyroid hormones and thyroid-stimulating hormone (TSH) levels was examined in conscious and freely moving adult male Sprague-Dawley rats. The rats were cannulated at the third ventricle 2 d before the experiments. Several glutamate receptor agonists, such as kainic acid and domoic acid, and antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dizocilpine (MK-801) were administered into the third ventricle. Serum TSH levels were assesed by radioimmunoassay, and serum thyroid hormone levels were assessed by enzyme immunoassay. The results showed that the administration of CNQX and MK-801 produced a decrease in serum levels of TSH and thyroid hormones. The administration of kainic acid and domoic acid increased TSH concentrations, whereas CNQX completely blocked the release of TSH induced by kainic acid and domoic acid. These results suggest the importance of endogenous EAA in the regulation of hormone secretion from the pituitary-thyroid axis, as well as the role of the N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the stimulatory effect of EAAs on the pituitary-thyroid axis.

  15. Acid base catalyzed transesterification kinetics of waste cooking oil

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Siddharth; Sharma, M.P.; Rajvanshi, Shalini [Alternate Hydro Energy Centre, Indian Institute of Technology, Roorkee (India)

    2011-01-15

    The present study reports the results of kinetics study of acid base catalyzed two step transesterification process of waste cooking oil, carried out at pre-determined optimum temperature of 65 C and 50 C for esterification and transesterification process respectively under the optimum condition of methanol to oil ratio of 3:7 (v/v), catalyst concentration 1%(w/w) for H{sub 2}SO{sub 4} and NaOH and 400 rpm of stirring. The optimum temperature was determined based on the yield of ME at different temperature. Simply, the optimum concentration of H{sub 2}SO{sub 4} and NaOH was determined with respect to ME Yield. The results indicated that both esterification and transesterification reaction are of first order rate reaction with reaction rate constant of 0.0031 min{sup -1} and 0.0078 min{sup -1} respectively showing that the former is a slower process than the later. The maximum yield of 21.50% of ME during esterification and 90.6% from transesterification of pretreated WCO has been obtained. This is the first study of its kind which deals with simplified kinetics of two step acid-base catalyzed transesterification process carried under the above optimum conditions and took about 6 h for complete conversion of TG to ME with least amount of activation energy. Also various parameters related to experiments are optimized with respect to ME yield. (author)

  16. Learning in constructivist environments: a research based on the acid-base subject

    Directory of Open Access Journals (Sweden)

    Vera Gouveia

    2004-08-01

    Full Text Available This communication intends to show as a constructivist environment permits a better learning of some concepts related to the acid-base subject, where generally students have some misconceptions at the beginning, as many researches had proved. Based on a long epistemological, psychological and educational reflection, supported by a wide bibliographical research and our own experience, we make some considerations about learning constructivist environments in the classroom, emphasising the cooperative work of students. In the second part, the effects produced in the teaching of the acid-base by such kind of environment are described, according a quasi-experimental study involving 52 students in their 10th year of education, distributed by two equivalent groups, taught by the same teacher. The results indicate clearly that the constructivist environment promoted a better learning of the acid-base subject, as well as improved the educational relationship in the classroom. Furthermore, the students developed positive attitudes regarding themselves and the others.

  17. The plant cuticle is required for osmotic stress regulation of abscisic acid biosynthesis and osmotic stress tolerance in Arabidopsis

    KAUST Repository

    Wang, Zhenyu

    2011-05-01

    Osmotic stress activates the biosynthesis of abscisic acid (ABA). One major step in ABA biosynthesis is the carotenoid cleavage catalyzed by a 9-cis epoxycarotenoid dioxygenase (NCED). To understand the mechanism for osmotic stress activation of ABA biosynthesis, we screened for Arabidopsis thaliana mutants that failed to induce the NCED3 genee xpression in response to osmotic stress treatments. The ced1 (for 9-cis epoxycarotenoid dioxy genase defective 1) mutant isolated in this study showed markedly reduced expression of NCED3 in response to osmotic stress (polyethylene glycol)treatments compared with the wild type. Other ABA biosynthesis genes are also greatly reduced in ced1 under osmotic stress. ced1 mutant plants are very sensitive to even mild osmotic stress. Map-based cloning revealed unexpectedly thatCED1 encodes a putative a/b hydrolase domain-containing protein and is allelic to the BODYGUARD gene that was recently shown to be essential for cuticle biogenesis. Further studies discovered that other cut in biosynthesis mutants are also impaired in osmotic stress induction of ABA biosynthesis genes and are sensitive to osmotic stress. Our work demonstrates that the cuticle functions not merely as a physical barrier to minimize water loss but also mediates osmotic stress signaling and tolerance by regulating ABA biosynthesis and signaling. © 2011 American Society of Plant Biologists. All rights reserved.

  18. Opuntia ficus indica (L.) Fruit Extract as Natural Indicator in Acid-Base Titration

    OpenAIRE

    Manoj A. Suva

    2014-01-01

    In routine experiments synthetic indicators are the choice of acid base titrations. But there are some limitations like environmental pollution, availability and higher cost which leads to search for natural compounds as an acid base indicator was started. The present work highlights theexploit of the methanolic and aqueous extract of the fruit of Opuntia ficus indica plants as a natural acid base indicator in acid base titrations. Opuntia ficus indica plant was identified and fruits were was...

  19. Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake

    Directory of Open Access Journals (Sweden)

    Daphna D.J. Habets

    2012-09-01

    Full Text Available Aim: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/ long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-λ knockout mice the roles of atypical PKCs (PKC-ζ and PKC-λ in regulating cardiac glucose and fatty acid uptake. Results: Neither insulin-stimulated nor AMPK-mediated glucose and fatty acid uptake were inhibited upon genetic PKC-λ ablation in cardiomyocytes. In contrast, myristoylated PKC-ζ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty acid uptake by >80% in both wild-type and PKC-λ-knockout cardiomyocytes. In PKC-λ knockout cardiomyocytes, PKC-ζ is the sole remaining atypical PKC isoform, and its expression level is not different from wild-type cardiomyocytes, in which it contributes to 29% and 17% of total atypical PKC expression and phosphorylation, respectively. Conclusion: Taken together, atypical PKCs are necessary for insulin-stimulated and AMPK-mediated glucose uptake into the heart, as well as for insulin-stimulated and AMPK-mediated fatty acid uptake. However, the residual PKC-ζ activity in PKC-λ-knockout cardiomyocytes is sufficient to allow optimal stimulation of glucose and fatty acid uptake, indicating that atypical PKCs are necessary but not rate-limiting in the regulation of cardiac substrate uptake and that PKC-λ and PKC-ζ have interchangeable functions in these processes.

  20. Born energy, acid-base equilibrium, structure and interactions of end-grafted weak polyelectrolyte layers

    Energy Technology Data Exchange (ETDEWEB)

    Nap, R. J.; Tagliazucchi, M.; Szleifer, I., E-mail: igalsz@northwestern.edu [Department of Biomedical Engineering, Department of Chemistry, and Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3100 (United States)

    2014-01-14

    This work addresses the effect of the Born self-energy contribution in the modeling of the structural and thermodynamical properties of weak polyelectrolytes confined to planar and curved surfaces. The theoretical framework is based on a theory that explicitly includes the conformations, size, shape, and charge distribution of all molecular species and considers the acid-base equilibrium of the weak polyelectrolyte. Namely, the degree of charge in the polymers is not imposed but it is a local varying property that results from the minimization of the total free energy. Inclusion of the dielectric properties of the polyelectrolyte is important as the environment of a polymer layer is very different from that in the adjacent aqueous solution. The main effect of the Born energy contribution on the molecular organization of an end-grafted weak polyacid layer is uncharging the weak acid (or basic) groups and consequently decreasing the concentration of mobile ions within the layer. The magnitude of the effect increases with polymer density and, in the case of the average degree of charge, it is qualitatively equivalent to a small shift in the equilibrium constant for the acid-base equilibrium of the weak polyelectrolyte monomers. The degree of charge is established by the competition between electrostatic interactions, the polymer conformational entropy, the excluded volume interactions, the translational entropy of the counterions and the acid-base chemical equilibrium. Consideration of the Born energy introduces an additional energetic penalty to the presence of charged groups in the polyelectrolyte layer, whose effect is mitigated by down-regulating the amount of charge, i.e., by shifting the local-acid base equilibrium towards its uncharged state. Shifting of the local acid-base equilibrium and its effect on the properties of the polyelectrolyte layer, without considering the Born energy, have been theoretically predicted previously. Account of the Born energy leads

  1. A metabolic-based approach to improve xylose utilization for fumaric acid production from acid pretreated wheat bran by Rhizopus oryzae.

    Science.gov (United States)

    Wang, Guanyi; Huang, Di; Li, Yong; Wen, Jianping; Jia, Xiaoqiang

    2015-03-01

    In this work, wheat bran (WB) was utilized as feedstock to synthesize fumaric acid by Rhizopus oryzae. Firstly, the pretreatment process of WB by dilute sulfuric acid hydrolysis undertaken at 100°C for 30min offered the best performance for fumaric acid production. Subsequently, through optimizing the seed culture medium, a suitable morphology (0.55mm pellets diameter) of R. oryzae was obtained. Furthermore, a metabolic-based approach was developed to profile the differences of intracellular metabolites concentration of R. oryzae between xylose (the abundant sugar in wheat bran hydrolysate (WBH)) and glucose metabolism. The xylitol, sedoheptulose 7-phosphate, ribulose 5-phosphate, glucose 6-phosphate, proline and serine were responsible for fumaric acid biosynthesis limitation in xylose fermentation. Consequently, regulation strategies were proposed, leading to a 149% increase in titer (up to 15.4g/L). Finally, by combinatorial regulation strategies the highest production was 20.2g/L from WBH, 477% higher than that of initial medium.

  2. The comprehensive acid-base characterization of glutathione

    Science.gov (United States)

    Mirzahosseini, Arash; Somlyay, Máté; Noszál, Béla

    2015-02-01

    Glutathione in its thiol (GSH) and disulfide (GSSG) forms, and 4 related compounds were studied by 1H NMR-pH titrations and a case-tailored evaluation method. The resulting acid-base properties are quantified in terms of 128 microscopic protonation constants; the first complete set of such parameters for this vitally important pair of compounds. The concomitant 12 interactivity parameters were also determined. Since biological redox systems are regularly compared to the GSH-GSSG pair, the eight microscopic thiolate basicities determined this way are exclusive means for assessing subtle redox parameters in a wide pH range.

  3. Evidence for a role of free fatty acids in the regulation of somatostatin secretion in normal and alloxan diabetic dogs.

    Science.gov (United States)

    Wasada, T; Howard, B; Dobbs, R E; Unger, R H

    1980-09-01

    To investigate the effect of acute elevation of plasma free fatty acids (FFA) on the secretion of splanchnic somatostatin-like immunoreactivity (SLI), the peripheral venous, pancreatic, and gastric venous effluent levels of SLI were measured in normal and chronic alloxan diabetic dogs before and after the infusion of a fat emulsion supplemented with heparin. In normal conscious dogs heparin injected during the infusion of a fat emulsion elevated FFA levels from a mean (+/-SE) base-line level of 0.7+/-0.1 meq/liter to a peak value of 1.5+/-0.1 meq/liter (P fat emulsion without heparin, of heparin alone nor of saline itself had an effect on either the plasma level of FFA or SLI. In another group of anesthetized dogs with surgically implanted catheters the administration of fat emulsion plus heparin was accompanied by more than a two-fold rise in the concentration of SLI in the venous effluent of the pancreas and of the gastric fundus and antrum in association with an elevation of FFA levels. In a group of conscious diabetic dogs fat emulsion plus heparin raised FFA from a mean base-line level of 1.2+/-0.2 to 1.6+/-0.3 meq/liter (P < 0.05) and SLI rose from a mean base-line level of 185+/-9 pg/ml to a peak value of 310+/-44 pg/ml (P < 0.01). Although SLI levels were significantly greater than in normal dogs at several time points after the rise in FFA, the magnitude of the increment in diabetic dogs did not differ from normal. These results demonstrate that a rise in FFA levels is a potent stimulus for SLI secretion from the pancreas and stomach and raise the possibility that FFA is an important physiological regulator of SLI secretion.

  4. The Role of Sirt1 in Bile Acid Regulation during Calorie Restriction in Mice.

    Directory of Open Access Journals (Sweden)

    Zidong Donna Fu

    Full Text Available Sirtuin 1 (Sirt1 is an NAD+-dependent protein deacetylase that is proposed to mediate many health-promoting effects of calorie restriction (CR. We recently reported that short-term CR increased the bile acid (BA pool size in mice, likely due to increased BA synthesis in liver. Given the important role of Sirt1 in the regulation of glucose, lipid, as well as BA metabolism, we hypothesized that the CR-induced increase in BAs is Sirt1-dependent. To address this, the present study utilized genetically-modified mice that were Sirt1 loss of function (liver knockout, LKO or Sirt1 gain of function (whole body-transgenic, TG. Three genotypes of mice (Sirt1-LKO, wild-type, and Sirt1-TG were each randomly divided into ad libitum or 40% CR feeding for one month. BAs were extracted from various compartments of the enterohepatic circulation, followed by BA profiling by UPLC-MS/MS. CR increased the BA pool size and total BAs in serum, gallbladder, and small intestine. The CR-induced increase in BA pool size correlated with the tendency of increase in the expression of the rate-limiting BA-synthetic enzyme Cyp7a1. However, in contrast to the hypothesis, the CR-induced increase in BA pool size and Cyp7a1 expression was still observed with ablated expression of Sirt1 in liver, and completely suppressed with whole-body overexpression of Sirt1. Furthermore, in terms of BA composition, CR increased the ratio of 12α-hydroxylated BAs regardless of Sirt1 genotypes. In conclusion, the CR-induced alterations in BA pool size, BA profiles, and expression of BA-related genes do not appear to be dependent on Sirt1.

  5. The Role of Sirt1 in Bile Acid Regulation during Calorie Restriction in Mice.

    Science.gov (United States)

    Fu, Zidong Donna; Cui, Julia Yue; Klaassen, Curtis D

    2015-01-01

    Sirtuin 1 (Sirt1) is an NAD+-dependent protein deacetylase that is proposed to mediate many health-promoting effects of calorie restriction (CR). We recently reported that short-term CR increased the bile acid (BA) pool size in mice, likely due to increased BA synthesis in liver. Given the important role of Sirt1 in the regulation of glucose, lipid, as well as BA metabolism, we hypothesized that the CR-induced increase in BAs is Sirt1-dependent. To address this, the present study utilized genetically-modified mice that were Sirt1 loss of function (liver knockout, LKO) or Sirt1 gain of function (whole body-transgenic, TG). Three genotypes of mice (Sirt1-LKO, wild-type, and Sirt1-TG) were each randomly divided into ad libitum or 40% CR feeding for one month. BAs were extracted from various compartments of the enterohepatic circulation, followed by BA profiling by UPLC-MS/MS. CR increased the BA pool size and total BAs in serum, gallbladder, and small intestine. The CR-induced increase in BA pool size correlated with the tendency of increase in the expression of the rate-limiting BA-synthetic enzyme Cyp7a1. However, in contrast to the hypothesis, the CR-induced increase in BA pool size and Cyp7a1 expression was still observed with ablated expression of Sirt1 in liver, and completely suppressed with whole-body overexpression of Sirt1. Furthermore, in terms of BA composition, CR increased the ratio of 12α-hydroxylated BAs regardless of Sirt1 genotypes. In conclusion, the CR-induced alterations in BA pool size, BA profiles, and expression of BA-related genes do not appear to be dependent on Sirt1.

  6. Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E_2 and cytokines

    Institute of Scientific and Technical Information of China (English)

    Mary Ann Cox; James Jackson; Michaela Stanton; Alberto Rojas-Triana; Loretta Bober; Maureen Laverty; Xiaoxin Yang; Feng Zhu; Jianjun Liu; Suke Wang; Frederick Monsma; Galya Vassileva; Maureen Maguire; Eric Gustafson; Marvin Bayne; Chuan-Chu Chou; Daniel Lundell; Chung-Her Jenh

    2009-01-01

    AIM: To investigate the effect of short-chain fatty acids(SCFAs) on production of prostaglandin E_2 (PGE_2),cytokines and chemokines in human monocytes.METHODS: Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtimepolymerase chain reaction. The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells (PBMC) was studied by measuring PGE_2, cytokines and chemokines in the supernatant.The effect of SCFAs in vivo was examined by intraplantar injection into rat paws.RESULTS: Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE_2 and that this effect can be enhanced in the presence of lipopolysaccharide(LPS). In addition, we demonstrate that PGE_2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1(MCP-1) production and LPS-induced interleukin-10(IL-10) production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE_2, MCP-1 and IL-10 after SCFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-γ in human PBMC. Finally, we show that SCFAs and LPS can induce PGE_2 production in vivo by intraplantar injectioninto rat paws ( P < 0.01).CONCLUSION: SCFAs can have distinct antiinflammatory activities due to their regulation of PGE_2, cytokine and chemokine release from human immune

  7. The behaviour of the coup de fouet of valve-regulated lead-acid batteries

    Science.gov (United States)

    Pascoe, Phillip E.; Anbuky, Adnan H.

    This paper presents the results of an investigation into the initial stage of the discharge voltage response of valve-regulated lead-acid (VRLA) batteries. This region is dominated by the phenomenon known as the coup de fouet which manifests itself as a voltage dip followed by a recovery. The research focuses on two parameters found within the coup de fouet region, namely, the trough and the plateau voltage. It is found that these parameters are influenced by the operating conditions and the sate-state-of health (SoH) of the battery. The operating conditions considered are discharge rate, ambient temperature, depth of previous discharge, charge duration, and float voltage. The coup de fouet parameters corresponding to high rate discharges, as well as discharges conducted at low temperatures, have reduced magnitudes compared with those conducted at lower rates or higher temperatures. This behaviour mirrors the availability of capacity when the battery is discharged under the same operating conditions. The float voltage is found to have a direct relationship with the trough and plateau voltages, whereas an indirect relationship between charge duration and the trough and plateau voltages is observed. The influence of variations in discharge depth on the coup de fouet is more complex. For consecutive discharge depths below approximately 10% of rated capacity, the coup de fouet becomes distorted and exhibits a second voltage dip. For consecutive discharges of greater depth, this does not occur. The influence of the degradation in battery SoH due to accelerated thermal ageing, water replenishment post-accelerated thermal ageing, and field ageing is investigated. The coup de fouet parameters associated with the discharge of batteries with low SoH have a reduced magnitude compared with those associated with the discharge of batteries with a high SoH.

  8. A Salmonella Regulator Modulates Intestinal Colonization and Use of Phosphonoacetic Acid

    Science.gov (United States)

    Elfenbein, Johanna R.; Knodler, Leigh A.; Schaeffer, Allison R.; Faber, Franziska; Bäumler, Andreas J.; Andrews-Polymenis, Helene L.

    2017-01-01

    Many microorganisms produce phosphonates, molecules characterized by stable carbon-phosphorus bonds that store phosphorus or act as antimicrobials. The role of phosphonates in the marine biosphere is well characterized but the role of these molecules in the intestine is poorly understood. Salmonella enterica uses its virulence factors to influence the host immune response to compete with the host and normal microflora for nutrients. Salmonella cannot produce phosphonates but encodes the enzymes to use them suggesting that it is exposed to phosphonates during its life cycle. The role of phosphonates during enteric salmonellosis is unexplored. We have previously shown that STM3602, encoding a putative regulator of phosphonate metabolism, is needed for colonization in calves. Here, we report that the necessity of STM3602 in colonization of the murine intestine results from multiple factors. STM3602 is needed for full activation of the type-3 secretion system-1 and for optimal invasion of epithelial cells. The ΔSTM3602 mutant grows poorly in phosphonoacetic acid (PA) as the sole phosphorus source, but can use 2-aminoethylphosphonate. PhnA, an enzyme required for PA breakdown, is not controlled by STM3602 suggesting an additional mechanism for utilization of PA in S. Typhimurium. Finally, the requirement of STM3602 for intestinal colonization differs depending on the composition of the microflora. Our data suggest that STM3602 has multiple regulatory targets that are necessary for survival within the microbial community in the intestine. Determination of the members of the STM3602 regulon may illuminate new pathways needed for colonization of the host. PMID:28361036

  9. Enhancing crop yield with the use of N-based fertilizers co-applied with plant hormones or growth regulators.

    Science.gov (United States)

    Zaman, Mohammad; Kurepin, Leonid V; Catto, Warwick; Pharis, Richard P

    2015-07-01

    Crop yield, vegetative or reproductive, depends on access to an adequate supply of essential mineral nutrients. At the same time, a crop plant's growth and development, and thus yield, also depend on in situ production of plant hormones. Thus optimizing mineral nutrition and providing supplemental hormones are two mechanisms for gaining appreciable yield increases. Optimizing the mineral nutrient supply is a common and accepted agricultural practice, but the co-application of nitrogen-based fertilizers with plant hormones or plant growth regulators is relatively uncommon. Our review discusses possible uses of plant hormones (gibberellins, auxins, cytokinins, abscisic acid and ethylene) and specific growth regulators (glycine betaine and polyamines) to enhance and optimize crop yield when co-applied with nitrogen-based fertilizers. We conclude that use of growth-active gibberellins, together with a nitrogen-based fertilizer, can result in appreciable and significant additive increases in shoot dry biomass of crops, including forage crops growing under low-temperature conditions. There may also be a potential for use of an auxin or cytokinin, together with a nitrogen-based fertilizer, for obtaining additive increases in dry shoot biomass and/or reproductive yield. Further research, though, is needed to determine the potential of co-application of nitrogen-based fertilizers with abscisic acid, ethylene and other growth regulators.

  10. TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy.

    Science.gov (United States)

    Vlahakis, Ariadne; Graef, Martin; Nunnari, Jodi; Powers, Ted

    2014-07-22

    The highly conserved Target of Rapamycin (TOR) kinase is a central regulator of cell growth and metabolism in response to nutrient availability. TOR functions in two structurally and functionally distinct complexes, TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2). Through TORC1, TOR negatively regulates autophagy, a conserved process that functions in quality control and cellular homeostasis and, in this capacity, is part of an adaptive nutrient deprivation response. Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through the conserved TORC2 and its downstream target protein kinase, Ypk1. Under these conditions, TORC2-Ypk1 signaling negatively regulates the Ca(2+)/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing eIF2α kinase, Gcn2, and to promote autophagy. Our work reveals that the TORC2 pathway regulates autophagy in an opposing manner to TORC1 to provide a tunable response to cellular metabolic status.

  11. Acid-base interactions in microbial adhesion to hexadecane and chloroform

    NARCIS (Netherlands)

    Bos, R; Busscher, HJ; Geertsema-Doornbusch, GI; Van Der Mei, HC; Mittal, KL

    2000-01-01

    Acid-base interactions play an important role in adhesion, including microbial adhesion to surfaces. Qualitatively acid-base interactions in microbial adhesion can be demonstrated by comparing adhesion to hexadecane (a negatively charged interface in aqueous solutions, unable to exert acid-base inte

  12. Metabolic reprogramming through fatty acid transport protein 1 (FATP1 regulates macrophage inflammatory potential and adipose inflammation

    Directory of Open Access Journals (Sweden)

    Amy R. Johnson

    2016-07-01

    Conclusion: Our findings provide evidence that FATP1 is a novel regulator of MΦ activation through control of substrate metabolism. Absence of FATP1 exacerbated pro-inflammatory activation in vitro and increased local and systemic components of the metabolic syndrome in HFD-fed Fatp1B−/− mice. In contrast, gain of FATP1 activity in MΦs suggested that Fatp1-mediated activation of fatty acids, substrate switch to glucose, oxidative stress, and lipid mediator synthesis are potential mechanisms. We demonstrate for the first time that FATP1 provides a unique mechanism by which the inflammatory tone of adipose and systemic metabolism may be regulated.

  13. Sources, fates, toxicity, and risks of trifluoroacetic acid and its salts: Relevance to substances regulated under the Montreal and Kyoto Protocols.

    Science.gov (United States)

    Solomon, Keith R; Velders, Guus J M; Wilson, Stephen R; Madronich, Sasha; Longstreth, Janice; Aucamp, Pieter J; Bornman, Janet F

    2016-01-01

    Trifluoroacetic acid (TFA) is a breakdown product of several hydrochlorofluorocarbons (HCFC), regulated under the Montreal Protocol (MP), and hydrofluorocarbons (HFC) used mainly as refrigerants. Trifluoroacetic acid is (1) produced naturally and synthetically, (2) used in the chemical industry, and (3) a potential environmental breakdown product of a large number (>1 million) chemicals, including pharmaceuticals, pesticides, and polymers. The contribution of these chemicals to global amounts of TFA is uncertain, in contrast to that from HCFC and HFC regulated under the MP. TFA salts are stable in the environment and accumulate in terminal sinks such as playas, salt lakes, and oceans, where the only process for loss of water is evaporation. Total contribution to existing amounts of TFA in the oceans as a result of the continued use of HCFCs, HFCs, and hydrofluoroolefines (HFOs) up to 2050 is estimated to be a small fraction (<7.5%) of the approximately 0.2 μg acid equivalents/L estimated to be present at the start of the millennium. As an acid or as a salt TFA is low to moderately toxic to a range of organisms. Based on current projections of future use of HCFCs and HFCs, the amount of TFA formed in the troposphere from substances regulated under the MP is too small to be a risk to the health of humans and environment. However, the formation of TFA derived from degradation of HCFC and HFC warrants continued attention, in part because of a long environmental lifetime and due many other potential but highly uncertain sources.

  14. Applicability of age-based hunting regulations for African leopards.

    Science.gov (United States)

    Balme, Guy Andrew; Hunter, Luke; Braczkowski, Alex Richard

    2012-01-01

    In species in which juvenile survival depends strongly on male tenure, excessive trophy hunting can artificially elevate male turnover and increase infanticide, potentially to unsustainable levels. Simulation models show that the likelihood of safe harvests can be improved by restricting offtakes to males old enough to have reared their first cohort of offspring to independence; in the case of African leopards, males were ≥7 years old. Here, we explore the applicability of an age-based approach for regulating trophy hunting of leopards. We conducted a structured survey comprising photographs of known-age leopards to assess the ability of wildlife practitioners to sex and age leopards. We also evaluated the utility of four phenotypic traits for use by trophy hunters to age male leopards in the field. Our logistic regression models showed that male leopard age affected the likelihood of survey respondents identifying the correct sex; notably, males trophy galleries suggested its wider utility as an aging criterion. Our study demonstrated that an age-based hunting approach is practically applicable for leopards. However, implementation would require major reform within the regulatory framework and the hunting industry.

  15. Transcriptional regulation of abscisic acid signal core components during cucumber seed germination and under Cu²⁺, Zn²⁺, NaCl and simulated acid rain stresses.

    Science.gov (United States)

    Wang, Yanping; Wang, Ya; Kai, Wenbin; Zhao, Bo; Chen, Pei; Sun, Liang; Ji, Kai; Li, Qian; Dai, Shengjie; Sun, Yufei; Wang, Yidong; Pei, Yuelin; Leng, Ping

    2014-03-01

    Abscisic acid (ABA) is an important phytohormone that regulates lots of physiological and biochemical processes in plant life cycle, especially in seed germination and stress responses. For exploring the transcriptional regulation of ABA signal transduction during cucumber (Cucumis sativus L.) seed germination and under Cu(2+), Zn(2+), NaCl and simulated acid rain stresses, nine CsPYLs, three group A CsPP2Cs and two subclass III CsSnRK2s were identified from cucumber genome, which respectively showed high sequence similarities and highly conserved domains with homologous genes in Arabidopsis. Based on Real-time PCR analysis, most of the tested genes' expression decreased during cucumber seed germination, which was in accordance with the ABA level variation. In addition, according to the absolute expression, CsPYL1, CsPYL3, CsPP2C5, CsABI1, CsSnRK2.3 and CsSnRK2.4 were highly expressed, indicating that they may play more important roles in ABA signaling during cucumber seed germination. Moreover, most of these highly expressed genes, except CsPYL3, were up-regulated by ABA treatment. Meanwhile, most of the tested genes' expression dramatically changed at the initial water uptake phase, indicating that this period may be critical in the regulation of ABA on seed germination. Under Cu(2+), Zn(2+), NaCl and simulated acid rain stresses, cucumber seed germination percentage decreased and ABA content increased. Meanwhile, the expression of ABA signal transduction core components genes showed specific response to a particular stress and was not always consist with ABA variation. Generally, the expression of CsPYL1, CsPYL3, CsABI1, CsSnRK2.3 and CsSnRK2.4 was sensitive to 120 mM NaCl and 0.5 mM Cu(2+) treatments.

  16. The Process Model of Group-Based Emotion : Integrating Intergroup Emotion and Emotion Regulation Perspectives

    NARCIS (Netherlands)

    Goldenberg, Amit; Halperin, Eran; van Zomeren, Martijn; Gross, James J.

    2016-01-01

    Scholars interested in emotion regulation have documented the different goals and strategies individuals have for regulating their emotions. However, little attention has been paid to the regulation of group-based emotions, which are based on individuals' self-categorization as a group member and oc

  17. The effects of Energised Greens™ upon blood acid-base balance during resting conditions

    Directory of Open Access Journals (Sweden)

    Mitchell Nigel

    2011-10-01

    Full Text Available Abstract Background The consumption of fresh fruit & vegetable in concentrate form (FVC have recently become an alternative approach to combating excessive renal acid loads often associated with Western Diets. Additionally, these FVC's have been purported to induce metabolic alkalosis, which perhaps may enhance the blood buffering capacity of an individual. Therefore, the aim of this preliminary study was to profile the acid-base response after ingestion of an acute dose of fruit and vegetable extract (Energised Greens™ (EG, Nottingham, UK and compare it to a standard, low dose (0.1 g·kg-1 of sodium bicarbonate (NaHCO3. Findings As part of a randomized, cross over design participants consumed 750 mL of water with either 9 g of EG (manufacturer recommendations, 0.1 g·kg-1 of NaHCO3 or a placebo (plain flour in opaque encapsulated pills following an overnight fast. Capillary samples were obtained and analyzed every 15 min for a period of 120 min following ingestion. Significant interactions (p 3-, BE. Interactions indicated significant elevation in blood alkalosis for only the NaHCO3 condition when compared to both placebo and EG from 15 to 120 minutes. Conclusions Despite previous findings of elevated blood pH following acute mineral supplementation, manufacturer recommended doses of EG do not induce any significant changes in acid-base regulation in resting males.

  18. Comparative bioavailability studies of citric acid and malonic acid based aspirin effervescent tablets

    Directory of Open Access Journals (Sweden)

    Anju Gauniya

    2010-01-01

    Full Text Available Purpose: The present investigation is aimed at comparing the pharmacokinetic profile (Bioavailability of aspirin in tablet formulations, which were prepared by using different effervescent excipients such as citric acid and malonic acid. Materials and Methods: The relative bioavailability and pharmacokinetics of citric acid based aspirin effervescent tablet (Product A and malonic acid based aspirin effervescent tablet (Product B formulations were evaluated for an in-vitro dissolution study and in-vivo bioavailability study, in 10 normal healthy rabbits. The study utilized a randomized, crossover design with a one-week washout period between doses. Blood samples were collected at 0, 1, 2, 4, 6, 8, 12 and 24 hours following a 100 mg/kg dose. Plasma samples were assayed by High Performance Liquid Chromatography. T max , C max , AUC 0-24 , AUC 0- ∞, MRT, K a, and relative bioavailability were estimated using the traditional pharmacokinetic methods and were compared by using the paired t-test. Result: In the present study, Products A and B showed their T max , C max , AUC 0-24 , AUC 0- ∞, MRT, and K a values as 2.5 h, 2589 ± 54.79 ng/ml, 9623 ± 112.87 ng.h/ml, 9586 ± 126.22 ng.h/ml, 3.6 ± 0.10 h, and 0.3698 ± 0.003 h -1 for Product A and 3.0 h, 2054 ± 55.79 ng/ml, 9637 ± 132.87 ng.h/ml, 9870 ± 129.22 ng.h/ml, 4.76 ± 0.10 h, and 0.3812 ± 0.002 h -1 for Product B, respectively. Conclusion: The results of the paired t-test of pharmacokinetics data showed that there was no significant difference between Products A and B. From both the in vitro dissolution studies and in vivo bioavailability studies it was concluded that products A and B had similar bioavailability.

  19. Transcriptomic analysis of Streptomyces clavuligerus ΔccaR::tsr: effects of the cephamycin C-clavulanic acid cluster regulator CcaR on global regulation.

    Science.gov (United States)

    Alvarez-Álvarez, R; Rodríguez-García, A; Santamarta, I; Pérez-Redondo, R; Prieto-Domínguez, A; Martínez-Burgo, Y; Liras, P

    2014-05-01

    Streptomyces clavuligerus ATCC 27064 and S. clavuligerus ΔccaR::tsr cultures were grown in asparagine-starch medium, and samples were taken in the exponential and stationary growth phases. Transcriptomic analysis showed that the expression of 186 genes was altered in the ccaR-deleted mutant. These genes belong to the cephamycin C gene cluster, clavulanic acid gene cluster, clavams, holomycin, differentiation, carbon, nitrogen, amino acids or phosphate metabolism and energy production. All the clavulanic acid biosynthesis genes showed Mc values in the order of -4.23. The blip gene-encoding a β-lactamase inhibitory protein was also controlled by the cephamycin C-clavulanic acid cluster regulator (Mc -2.54). The expression of the cephamycin C biosynthesis genes was greatly reduced in the mutant (Mc values up to -7.1), while the genes involved in putative β-lactam resistance were less affected (Mc average -0.88). Genes for holomycin biosynthesis were upregulated. In addition, the lack of clavulanic acid and cephamycin production negatively affected the expression of genes for the clavulanic acid precursor arginine and of miscellaneous genes involved in nitrogen metabolism (amtB, glnB, glnA3, glnA2, glnA1). The transcriptomic results were validated by quantative reverse transcription polymerase chain reaction and luciferase assay of luxAB-coupled promoters. Transcriptomic analysis of the homologous genes of S. coelicolor validated the results obtained for S. clavuligerus primary metabolism genes.

  20. Regulation of fatty acid oxidation in mouse cumulus-oocyte complexes during maturation and modulation by PPAR agonists.

    Directory of Open Access Journals (Sweden)

    Kylie R Dunning

    Full Text Available Fatty acid oxidation is an important energy source for the oocyte; however, little is known about how this metabolic pathway is regulated in cumulus-oocyte complexes. Analysis of genes involved in fatty acid oxidation showed that many are regulated by the luteinizing hormone surge during in vivo maturation, including acyl-CoA synthetases, carnitine transporters, acyl-CoA dehydrogenases and acetyl-CoA transferase, but that many are dysregulated when cumulus-oocyte complexes are matured under in vitro maturation conditions using follicle stimulating hormone and epidermal growth factor. Fatty acid oxidation, measured as production of ³H₂O from [³H]palmitic acid, occurs in mouse cumulus-oocyte complexes in response to the luteinizing hormone surge but is significantly reduced in cumulus-oocyte complexes matured in vitro. Thus we sought to determine whether fatty acid oxidation in cumulus-oocyte complexes could be modulated during in vitro maturation by lipid metabolism regulators, namely peroxisome proliferator activated receptor (PPAR agonists bezafibrate and rosiglitazone. Bezafibrate showed no effect with increasing dose, while rosiglitazone dose dependently inhibited fatty acid oxidation in cumulus-oocyte complexes during in vitro maturation. To determine the impact of rosiglitazone on oocyte developmental competence, cumulus-oocyte complexes were treated with rosiglitazone during in vitro maturation and gene expression, oocyte mitochondrial activity and embryo development following in vitro fertilization were assessed. Rosiglitazone restored Acsl1, Cpt1b and Acaa2 levels in cumulus-oocyte complexes and increased oocyte mitochondrial membrane potential yet resulted in significantly fewer embryos reaching the morula and hatching blastocyst stages. Thus fatty acid oxidation is increased in cumulus-oocyte complexes matured in vivo and deficient during in vitro maturation, a known model of poor oocyte quality. That rosiglitazone further

  1. The plastidial retrograde signal methyl erythritol cyclopyrophosphate is a regulator of salicylic acid and jasmonic acid crosstalk.

    Science.gov (United States)

    Lemos, Mark; Xiao, Yanmei; Bjornson, Marta; Wang, Jin-Zheng; Hicks, Derrick; Souza, Amancio de; Wang, Chang-Quan; Yang, Panyu; Ma, Shisong; Dinesh-Kumar, Savithramma; Dehesh, Katayoon

    2016-03-01

    The exquisite harmony between hormones and their corresponding signaling pathways is central to prioritizing plant responses to simultaneous and/or successive environmental trepidations. The crosstalk between jasmonic acid (JA) and salicylic acid (SA) is an established effective mechanism that optimizes and tailors plant adaptive responses. However, the underlying regulatory modules of this crosstalk are largely unknown. Global transcriptomic analyses of mutant plants (ceh1) with elevated levels of the stress-induced plastidial retrograde signaling metabolite 2-C-methyl-D-erythritol cyclopyrophosphate (MEcPP) revealed robustly induced JA marker genes, expected to be suppressed by the presence of constitutively high SA levels in the mutant background. Analyses of a range of genotypes with varying SA and MEcPP levels established the selective role of MEcPP-mediated signal(s) in induction of JA-responsive genes in the presence of elevated SA. Metabolic profiling revealed the presence of high levels of the JA precursor 12-oxo-phytodienoic acid (OPDA), but near wild type levels of JA in the ceh1 mutant plants. Analyses of coronatine-insensitive 1 (coi1)/ceh1 double mutant plants confirmed that the MEcPP-mediated induction is JA receptor COI1 dependent, potentially through elevated OPDA. These findings identify MEcPP as a previously unrecognized central regulatory module that induces JA-responsive genes in the presence of high SA, thereby staging a multifaceted plant response within the environmental context.

  2. Role of the multidrug resistance regulator MarA in global regulation of the hdeAB acid resistance operon in Escherichia coli.

    Science.gov (United States)

    Ruiz, Cristian; McMurry, Laura M; Levy, Stuart B

    2008-02-01

    MarA, a transcriptional regulator in Escherichia coli, affects functions such as multiple-antibiotic resistance (Mar) and virulence. Usually an activator, MarA is a repressor of hdeAB and other acid resistance genes. We found that, in wild-type cells grown in LB medium at pH 7.0 or pH 5.5, repression of hdeAB by MarA occurred only in stationary phase and was reduced in the absence of H-NS and GadE, the main regulators of hdeAB. Moreover, repression of hdeAB by MarA was greater in the absence of GadX or Lrp in exponential phase at pH 7.0 and in the absence of GadW or RpoS in stationary phase at pH 5.5. In turn, MarA enhanced repression of hdeAB by H-NS and hindered activation by GadE in stationary phase and also reduced the activity of GadX, GadW, RpoS, and Lrp on hdeAB under some conditions. As a result of its direct and indirect effects, overexpression of MarA prevented most of the induction of hdeAB expression as cells entered stationary phase and made the cells sevenfold more sensitive to acid challenge at pH 2.5. These findings show that repression of hdeAB by MarA depends on pH, growth phase, and other regulators of hdeAB and is associated with reduced resistance to acid conditions.

  3. Post-translational inhibitory regulation of acid invertase induced by fructose and glucose in developing apple fruit

    Institute of Scientific and Technical Information of China (English)

    张大鹏; 王永章

    2002-01-01

    Acid invertase (EC 3.2.1.26) is one of the key enzymes involved in the carbohydrate sink-organ development and the sink strength modulation in crops. The experiment conducted with 'Starkrimson' apple (Malus domestica Borkh) fruit showed that, during the fruit development, the activity of acid invertase gradually declined concomitantly with the progressive accumulation of fructose, glucose and sucrose, while Western blotting assay of acid invertase detected a 30 ku peptide of which the immuno-signal intensity increased during the fruit development. The immuno-localization via immunogold electron microscopy showed that, on the one hand, acid invertase was mainly located on the flesh cell wall with numbers of the immunosignals present in the vacuole at the late stage of fruit development; and on the other hand, the amount of acid invertase increased during fruit development, which was consistent with the results of Western blotting. The in vivo pre-incubation of fruit discs with soluble sugars showed that the activity of extractible acid invertase was inhibited by fructose or glucose, while Western blotting did not detect any changes in apparent quantity of the enzyme nor other peptides than 30 ku one. So it is considered that fructose and glucose induced the post-translational or translocational inhibitory regulation of acid invertase in developing apple fruit. The mechanism of the post-translational inhibition was shown different from both the two previously reported ones that proposed either the inhibition by hexose products in the in vitro chemical reaction equilibrium system or the inhibition by the proteinaceous inhibitors. It was hypothesized that fructose and glucose might induce acid invertase inhibition by modulating the expression of some inhibition-related genes or some structural modification of acid invertase.

  4. Sphingoid bases inhibit acid-induced demineralization of hydroxyapatite.

    Science.gov (United States)

    Valentijn-Benz, Marianne; van 't Hof, Wim; Bikker, Floris J; Nazmi, Kamran; Brand, Henk S; Sotres, Javier; Lindh, Liselott; Arnebrant, Thomas; Veerman, Enno C I

    2015-01-01

    Calcium hydroxyapatite (HAp), the main constituent of dental enamel, is inherently susceptible to the etching and dissolving action of acids, resulting in tooth decay such as dental caries and dental erosion. Since the prevalence of erosive wear is gradually increasing, there is urgent need for agents that protect the enamel against erosive attacks. In the present study we studied in vitro the anti-erosive effects of a number of sphingolipids and sphingoid bases, which form the backbone of sphingolipids. Pretreatment of HAp discs with sphingosine, phytosphingosine (PHS), PHS phosphate and sphinganine significantly protected these against acid-induced demineralization by 80 ± 17%, 78 ± 17%, 78 ± 7% and 81 ± 8%, respectively (p measurement revealed that HAp discs treated with PHS were almost completely and homogeneously covered by patches of PHS. This suggests that PHS and other sphingoid bases form layers on the surface of HAp, which act as diffusion barriers against H(+) ions. In principle, these anti-erosive properties make PHS and related sphingosines promising and attractive candidates as ingredients in oral care products.

  5. Geopolymers Based on Phosphoric Acid and Illito-Kaolinitic Clay

    Directory of Open Access Journals (Sweden)

    S. Louati

    2016-01-01

    Full Text Available New three-dimensional geopolymer materials based on illito-kaolinitic clay and phosphoric acid were synthesized. The effect of Si/P molar ratio on the geopolymers properties was studied. Raw, calcined clay, and geopolymers structures were investigated using XRD, IR spectroscopy, and SEM. The phosphoric acid-based geopolymers mechanical properties were evaluated by measuring the compressive strength. The Si/P molar ratio was found to increase with the increase of the compressive strength of the obtained geopolymers, which attained a maximum value at Si/P equal to 2.75. Beyond this ratio, the mechanical strength decreases. The XRD patterns of these geopolymers samples have proven that when the Si/P molar ratio decreases, the amorphous phase content increases. Besides, the structural analyses have revealed the presence of aluminum phosphate and Si-O-Al-O-P polymeric structure, whatever the Si/P molar ratio is (between 2.25 and 3.5. The obtained results have confirmed that the presence of the associated minerals such as hematite and quartz in the clay does not prevent the geopolymerization reaction, but the presence of illite mineral seems to have a modest contribution in the geopolymerization.

  6. Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes

    Energy Technology Data Exchange (ETDEWEB)

    Lowden, Michael J.; Skorupski, Karen; Pellegrini, Maria; Chiorazzo, Michael G.; Taylor, Ronald K.; Kull, F. Jon (Dartmouth)

    2010-03-04

    Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae. In order for V. cholerae to cause disease, it must produce two virulence factors, the toxin-coregulated pilus (TCP) and cholera toxin (CT), whose expression is controlled by a transcriptional cascade culminating with the expression of the AraC-family regulator, ToxT. We have solved the 1.9 {angstrom} resolution crystal structure of ToxT, which reveals folds in the N- and C-terminal domains that share a number of features in common with AraC, MarA, and Rob as well as the unexpected presence of a buried 16-carbon fatty acid, cis-palmitoleate. The finding that cis-palmitoleic acid reduces TCP and CT expression in V. cholerae and prevents ToxT from binding to DNA in vitro provides a direct link between the host environment of V. cholerae and regulation of virulence gene expression.

  7. Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

    Institute of Scientific and Technical Information of China (English)

    Wang-sheng Duanmu; Liu Cao; Jing-yu Chen; Hong-fei Ge; Rong Hu; Hua Feng

    2016-01-01

    Ischemic postconditioning renders brain tissue tolerant to brain ischemia, thereby alleviating ischemic brain injury. However, the exact mechanism of action is still unclear. In this study, a rat model of global brain ischemia was subjected to ischemic postconditioning treat-ment using the vessel occlusion method. After 2 hours of ischemia, the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds. This procedure was repeated six times. Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia, and up-regulate acid-sensing ion channel 2a expression at the mRNA and protein level. These ifndings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippo-campus after global brain ischemia, which promotes neuronal tolerance to ischemic brain injury.

  8. Transcriptional regulation of the human acid alpha-glucosidase gene. Identification of a repressor element and its transcription factors Hes-1 and YY1.

    Science.gov (United States)

    Yan, B; Heus, J; Lu, N; Nichols, R C; Raben, N; Plotz, P H

    2001-01-19

    Acid alpha-glucosidase, the product of a housekeeping gene, is a lysosomal enzyme that degrades glycogen. A deficiency of this enzyme is responsible for a recessively inherited myopathy and cardiomyopathy, glycogenesis type II. We have previously demonstrated that the human acid alpha-glucosidase gene expression is regulated by a silencer within intron 1, which is located in the 5'-untranslated region. In this study, we have used deletion analysis, electrophoretic mobility shift assay, and footprint analysis to further localize the silencer to a 25-base pair element. The repressive effect on the TK promoter was about 50% in both orientations in expression plasmid, and two transcriptional factors were identified with antibodies binding specifically to the element. Mutagenesis and functional analyses of the element demonstrated that the mammalian homologue 1 of Drosophila hairy and Enhancer of split (Hes-1) binding to an E box (CACGCG) and global transcription factor-YY1 binding to its core site function as a transcriptional repressor. Furthermore, the overexpression of Hes-1 significantly enhanced the repressive effect of the silencer element. The data should be helpful in understanding the expression and regulation of the human acid alpha-glucosidase gene as well as other lysosomal enzyme genes.

  9. Incidence of Postoperative Acid-Base Disturbances in Abdominal Surgery

    Directory of Open Access Journals (Sweden)

    Taghavi Gilani M

    2014-04-01

    Full Text Available Introduction: Respiratory and blood pressure changes as well as fluid administration alter the acid-base balance during the perioperative period which may cause consciousness disturbance and additional hemodynamic disorders. The aim of this study was to identify frequent postoperative acid-base disturbances in order to control postoperative complications. Materials and Methods:This prospective, observational study design was used on patients who underwent abdominal surgery during a six-month period. Gasometry was performed immediately after the patients’ admittion to ICU and six and 12 hours postoperatively. SPSS v13 software was used, and PResults: 213 patients (123 male and 90 female aged 14-85 years (51.7± 22.4 were evaluated. During admission, PH and PaCO2 were (7.29±0.13 and (38.3±11.9, respectively; however, although PH increased gradually (P=0.001, PaCO2 was reduced (P=0.03. Bicarbonate and base excess had opposite effects; bicarbonate initially decreased but increased after 12 hours (P=0.001, whereas base excess initially increased (-6.3±11.6 and then decreased gradually (P=0.003. The arterial oxygen pressure was reduced for 22.5% of the patients throughout the admission period, and this did not significantly change (P=0.57. Conclusion: According to the results, in admission, 65.7% had metabolic acidosis, but metabolic alkalosis was the least. Gradually, metabolic acidosis was modified, but metabolic alkalosis increased. Intraoperative hypotension and fluid infusion may be the main factors of early metabolic acidosis and control of hypotension, or correction of acidosis may increase metabolic alkalosis.

  10. Effects of intravenous solutions on acid-base equilibrium: from crystalloids to colloids and blood components.

    Science.gov (United States)

    Langer, Thomas; Ferrari, Michele; Zazzeron, Luca; Gattinoni, Luciano; Caironi, Pietro

    2014-01-01

    Intravenous fluid administration is a medical intervention performed worldwide on a daily basis. Nevertheless, only a few physicians are aware of the characteristics of intravenous fluids and their possible effects on plasma acid-base equilibrium. According to Stewart's theory, pH is independently regulated by three variables: partial pressure of carbon dioxide, strong ion difference (SID), and total amount of weak acids (ATOT). When fluids are infused, plasma SID and ATOT tend toward the SID and ATOT of the administered fluid. Depending on their composition, fluids can therefore lower, increase, or leave pH unchanged. As a general rule, crystalloids having a SID greater than plasma bicarbonate concentration (HCO₃-) cause an increase in plasma pH (alkalosis), those having a SID lower than HCO₃- cause a decrease in plasma pH (acidosis), while crystalloids with a SID equal to HCO₃- leave pH unchanged, regardless of the extent of the dilution. Colloids and blood components are composed of a crystalloid solution as solvent, and the abovementioned rules partially hold true also for these fluids. The scenario is however complicated by the possible presence of weak anions (albumin, phosphates and gelatins) and their effect on plasma pH. The present manuscript summarises the characteristics of crystalloids, colloids, buffer solutions and blood components and reviews their effect on acid-base equilibrium. Understanding the composition of intravenous fluids, along with the application of simple physicochemical rules best described by Stewart's approach, are pivotal steps to fully elucidate and predict alterations of plasma acid-base equilibrium induced by fluid therapy.

  11. Native SILAC: metabolic labeling of proteins in prototroph microorganisms based on lysine synthesis regulation.

    Science.gov (United States)

    Fröhlich, Florian; Christiano, Romain; Walther, Tobias C

    2013-07-01

    Mass spectrometry (MS)-based quantitative proteomics has matured into a methodology able to detect and quantitate essentially all proteins of model microorganisms, allowing for unprecedented depth in systematic protein analyses. The most accurate quantitation approaches currently require lysine auxotrophic strains, which precludes analysis of most existing mutants, strain collections, or commercially important strains (e.g. those used for brewing or for the biotechnological production of metabolites). Here, we used MS-based proteomics to determine the global response of prototrophic yeast and bacteria to exogenous lysine. Unexpectedly, down-regulation of lysine synthesis in the presence of exogenous lysine is achieved via different mechanisms in different yeast strains. In each case, however, lysine in the medium down-regulates its biosynthesis, allowing for metabolic proteome labeling with heavy-isotope-containing lysine. This strategy of native stable isotope labeling by amino acids in cell culture (nSILAC) overcomes the limitations of previous approaches and can be used for the efficient production of protein standards for absolute SILAC quantitation in model microorganisms. As proof of principle, we have used nSILAC to globally analyze yeast proteome changes during salt stress.

  12. Niflumic acid renders dendritic cells tolerogenic and up-regulates inhibitory molecules ILT3 and ILT4

    OpenAIRE

    Vidmar, Alenka; Švajger, Urban; Jeras, Matjaž

    2015-01-01

    Niflumic acid is a member of non-steroidal anti-inflammatory agents, from which aspirin was recently shown to inhibit maturation of human-monocyte derived dendritic cells (DCs). DCs are crucial regulators of the immune response, capable of inducing immunity as well as tolerance. In our in vitro study we showed a tolerogenic effect of NFA on phenotype and function of LPSmatured monocyte-derived DCs. Different drug concentrations dose-dependently downregulated the expression of co-stimulatory m...

  13. Soybean MAPK, GMK1 Is Dually Regulated by Phosphatidic Acid and Hydrogen Peroxide and Translocated to Nucleus during Salt Stress

    OpenAIRE

    Im, Jong Hee; Lee, Hyoungseok; Kim, Jitae; Kim, Ho Bang; An, Chung Sun

    2012-01-01

    Mitogen-activated protein kinase (MAPK) is activated by various biotic and abiotic stresses. Salt stress induces two well-characterized MAPK activating signaling molecules, phosphatidic acid (PA) via phospholipase D and phospholipase C, and reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase. In our previous study, the activity of soybean MAPK, GMK1 was strongly induced within 5 min of 300 mM NaCl treatment and this early activity was regulated by PA....

  14. Induction of YdeO, a regulator for acid resistance genes, by ultraviolet irradiation in Escherichia coli.

    Science.gov (United States)

    Yamanaka, Yuki; Ishihama, Akira; Yamamoto, Kaneyoshi

    2012-01-01

    YdeO, an AraC-type transcription factor, is an important regulator in the induction of acid-resistance genes in Escherichia coli. In this study, we found that ydeO expression was induced 20 min after exposure to UV irradiation. This required the evgA and gadE genes in vivo. YdeO, induced by UV, controls the expression of a total of 21 genes. This accompanies SOS response in E. coli.

  15. Neurocognitive bases of emotion regulation development in adolescence

    OpenAIRE

    Saz P. Ahmed; Amanda Bittencourt-Hewitt; Sebastian, Catherine L

    2015-01-01

    Emotion regulation is the ability to recruit processes to influence emotion generation. In recent years there has been mounting interest in how emotions are regulated at behavioural and neural levels, as well as in the relevance of emotional dysregulation to psychopathology. During adolescence, brain regions involved in affect generation and regulation, including the limbic system and prefrontal cortex, undergo protracted structural and functional development. Adolescence is also a time of in...

  16. Flow Injection Analysis of Acid and Base using Thermo-Sensitive Resistance Coils

    OpenAIRE

    1995-01-01

    A flow injection analysis of acid-base by detecting neutralization heat is proposed. A injected sample (acid or base), combined with a carrier (deionized water), was mixed with a reagent (base or acid) stream. A change in the solution temperature was detected by passing the solution, immediately after mixing, through a stainless steel capillary tube around which a thermo-sensitive resistance was coiled. The temperature of carrier was used as a reference Hydrochloric acid solutions of 0.003 to...

  17. A study on the relevance and influence of the existing regulation and risk informed/performance based regulation

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, B. J.; Kang, J. M.; Kim, H. S.; Koh, S. H.; Kang, D. H.; Park, C. H. [Cheju Univ., Jeju (Korea, Republic of)

    2003-02-15

    The goal of this study is to estimate the relevance and Influence of the Existing Regulation and the RI-PBR to the institutionalization of the regulatory system. This study reviews the current regulatory system and the status of the RI-PBR implementation of the US NRC and Korea based upon SECY Papers, Risk Informed Regulation Implementation Plan (RIRIP) of the US NRC and other domestic studies. In order to investigate the perceptions, knowledge level, ground for the regulatory change, a survey was performed to Korean nuclear utilities, researchers and regulators on the perception on the RIR. The questionnaire was composed of 50 questions regarding personal details on work experience, level of education and specific field of work ; level of knowledge on the risk informed performance based regulation (RI-PBR); the perception of the current regulation, the effectiveness, level of procedure, flexibility, dependency on the regulator and personal view, and the perception of the RI-PBR such as flexibility of regulation, introduction time and the effect of RI-PBR, safety improvement, public perception, parts of the existing regulatory system that should be changed, etc. 515 answered from all sectors of the nuclear field; utilities, engineering companies, research institutes, and regulatory bodies.

  18. Identification of novel secreted fatty acids that regulate nitrogen catabolite repression in fission yeast

    OpenAIRE

    Xiaoying Sun; Go Hirai; Masashi Ueki; Hiroshi Hirota; Qianqian Wang; Yayoi Hongo; Takemichi Nakamura; Yuki Hitora; Hidekazu Takahashi; Mikiko Sodeoka; Hiroyuki Osada; Makiko Hamamoto; Minoru Yoshida; Yoko Yashiroda

    2016-01-01

    Uptake of poor nitrogen sources such as branched-chain amino acids is repressed in the presence of high-quality nitrogen sources such as NH4 + and glutamate (Glu), which is called nitrogen catabolite repression. Amino acid auxotrophic mutants of the fission yeast Schizosaccharomyces pombe were unable to grow on minimal medium containing NH4Cl or Glu even when adequate amounts of required amino acids were supplied. However, growth of these mutant cells was recovered in the vicinity of colonies...

  19. Active Power Regulation based on Droop for AC Microgrid

    DEFF Research Database (Denmark)

    Li, Chendan; Coelho, Ernane A. A.; Firoozabadi, Mehdi Savaghebi

    2015-01-01

    In this paper, two different control strategies are proposed to address the active power regulation issue in AC microgrids. The principle of power regulation in the droop controller is firstly introduced. Frequency scheduling and droop gain scheduling on top of droop control is proposed to succes......In this paper, two different control strategies are proposed to address the active power regulation issue in AC microgrids. The principle of power regulation in the droop controller is firstly introduced. Frequency scheduling and droop gain scheduling on top of droop control is proposed...

  20. Identification of novel secreted fatty acids that regulate nitrogen catabolite repression in fission yeast.

    Science.gov (United States)

    Sun, Xiaoying; Hirai, Go; Ueki, Masashi; Hirota, Hiroshi; Wang, Qianqian; Hongo, Yayoi; Nakamura, Takemichi; Hitora, Yuki; Takahashi, Hidekazu; Sodeoka, Mikiko; Osada, Hiroyuki; Hamamoto, Makiko; Yoshida, Minoru; Yashiroda, Yoko

    2016-02-19

    Uptake of poor nitrogen sources such as branched-chain amino acids is repressed in the presence of high-quality nitrogen sources such as NH4(+) and glutamate (Glu), which is called nitrogen catabolite repression. Amino acid auxotrophic mutants of the fission yeast Schizosaccharomyces pombe were unable to grow on minimal medium containing NH4Cl or Glu even when adequate amounts of required amino acids were supplied. However, growth of these mutant cells was recovered in the vicinity of colonies of the prototrophic strain, suggesting that the prototrophic cells secrete some substances that can restore uptake of amino acids by an unknown mechanism. We identified the novel fatty acids, 10(R)-acetoxy-8(Z)-octadecenoic acid and 10(R)-hydroxy-8(Z)-octadecenoic acid, as secreted active substances, referred to as Nitrogen Signaling Factors (NSFs). Synthetic NSFs were also able to shift nitrogen source utilization from high-quality to poor nitrogen sources to allow adaptive growth of the fission yeast amino acid auxotrophic mutants in the presence of high-quality nitrogen sources. Finally, we demonstrated that the Agp3 amino acid transporter was involved in the adaptive growth. The data highlight a novel intra-species communication system for adaptation to environmental nutritional conditions in fission yeast.

  1. UNMANNED AIR VEHICLE STABILIZATION BASED ON NEURAL NETWORK REGULATOR

    Directory of Open Access Journals (Sweden)

    S. S. Andropov

    2016-09-01

    Full Text Available A problem of stabilizing for the multirotor unmanned aerial vehicle in an environment with external disturbances is researched. A classic proportional-integral-derivative controller is analyzed, its flaws are outlined: inability to respond to changing of external conditions and the need for manual adjustment of coefficients. The paper presents an adaptive adjustment method for coefficients of the proportional-integral-derivative controller based on neural networks. A neural network structure, its input and output data are described. Neural networks with three layers are used to create an adaptive stabilization system for the multirotor unmanned aerial vehicle. Training of the networks is done with the back propagation method. Each neural network produces regulator coefficients for each angle of stabilization as its output. A method for network training is explained. Several graphs of transition process on different stages of learning, including processes with external disturbances, are presented. It is shown that the system meets stabilization requirements with sufficient number of iterations. Described adjustment method for coefficients can be used in remote control of unmanned aerial vehicles, operating in the changing environment.

  2. Domoic acid toxicokinetics in Dungeness crabs: new insights into mechanisms that regulate bioaccumulation.

    Science.gov (United States)

    Schultz, Irvin R; Skillman, Ann; Sloan-Evans, Siobhan; Woodruff, Dana

    2013-09-15

    Domoic acid (DA) is an excitatory neurotoxic amino acid produced by several marine algal species and is the causative agent of amnesic shellfish poisoning. Profound differences in the toxicokinetics of DA have been identified in a wide variety of shellfish. We characterized the toxicokinetics of DA in Dungeness crabs (Metacarcinus magister) after oral and intravascular dosing (IV) using a variety of doses ranging from 0.1 to 20mg/kg. After a 1mg/kg oral dose, DA disappeared from the foregut within 2h and largely accumulated in the hepatopancreas, with hemolymph and other tissues having 100-1000 times lower concentrations. After IV dosing, hemolymph concentrations of DA were unexpectedly high and toxicokinetic analysis indicated the steady-state volume of distribution (Vss) was 123-197 ml/kg, which is well below the hemolymph volume of 350 ml/kg for crabs. This indicated only limited extravascular distribution of DA was occurring after IV injection, which is surprising considering the capacity of the hepatopancreas to sequester DA after oral dosing. Additional studies measured the partitioning of DA in hepatopancreas cellular and subcellular fractions. The subcellular distribution of DA was primarily associated with the S8 fraction and could be filtered through a 30,000 MW cut-off filter, indicating DA was not appreciably bound to macromolecules. Interestingly, very little (<0.4%) of the total hepatopancreas DA tissue content was associated with the cellular fraction isolated after dissociation and separation from tissue fragments. The in vivo and in vitro results led us to hypothesize that DA uptake and distribution is regulated by crustacean orthologs of ATP-binding cassette (ABC) type transporters. We tested this hypothesis by co-exposing crabs to DA and known inhibitors of ABC transporters (verapamil, cyclosporine A and MK-571) and through in vitro studies using isolated hepatopancreas tissue and mixed cell suspensions prepared from hepatopancreas tissue. The in

  3. Synthesis of bio-based methacrylic acid by decarboxylation of itaconic acid and citric acid catalyzed by solid transition-metal catalysts

    NARCIS (Netherlands)

    Notre, le J.E.L.; Witte-van Dijk, S.C.M.; Haveren, van J.; Scott, E.L.; Sanders, J.P.M.

    2014-01-01

    Methacrylic acid, an important monomer for the plastics industry, was obtained in high selectivity (up to 84%) by the decarboxylation of itaconic acid using heterogeneous catalysts based on Pd, Pt and Ru. The reaction takes place in water at 200–2508C without any external added pressure, conditions

  4. Regulation of LXR by fatty acids, insulin, growth hormone and tumor necrosis factor-α in rainbow trout myocytes.

    Science.gov (United States)

    Cruz-Garcia, Lourdes; Sánchez-Gurmaches, Joan; Gutiérrez, Joaquim; Navarro, Isabel

    2011-10-01

    The liver X receptor (LXR) has recently been described in salmonids. In mammals, this receptor is already known as a transcriptional factor that regulates diverse aspects of cholesterol, fatty acid and carbohydrate metabolism in various tissues, including muscle. Here we examined LXR in trout myocytes. For this purpose, we analyzed LXR target gene expression and gene profile during myocyte development. In addition, we studied the transcriptional regulation of LXR by hormones, a pro-inflammatory mediator and unsaturated fatty acids. Trout myocytes were incubated with LXR agonists (T091317, 22(R)-hydroxycholesterol) and unsaturated fatty acids for 24h. Furthermore, differentiated myocytes were incubated with insulin and growth hormone (GH) for 3h, 6h and 18h, and with tumor necrosis factor-α (TNFα) for 24h. Samples were also obtained in various stages of cell differentiation. Our results demonstrate that lipoprotein lipase (LPL), fatty acid synthase (FAS), ATP-binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor-α and β (PPARα, β) are target genes of LXR in trout muscle. LXR agonists increased LXR expression, thereby indicating that this receptor is autoregulated. Unsaturated fatty acids downregulated LXR gene expression. This observation suggests a regulatory mechanism of these molecules on LXR-mediated fatty acid synthesis and uptake. TNFα did not modulate LXR gene transcription. Expression of the LXR gene was activated by insulin and GH. These results suggest that LXR may play a lipogenic role through insulin stimulation and a tendency to promote anabolic effects through GH on trout myocytes.

  5. Applicability of age-based hunting regulations for African leopards.

    Directory of Open Access Journals (Sweden)

    Guy Andrew Balme

    Full Text Available In species in which juvenile survival depends strongly on male tenure, excessive trophy hunting can artificially elevate male turnover and increase infanticide, potentially to unsustainable levels. Simulation models show that the likelihood of safe harvests can be improved by restricting offtakes to males old enough to have reared their first cohort of offspring to independence; in the case of African leopards, males were ≥7 years old. Here, we explore the applicability of an age-based approach for regulating trophy hunting of leopards. We conducted a structured survey comprising photographs of known-age leopards to assess the ability of wildlife practitioners to sex and age leopards. We also evaluated the utility of four phenotypic traits for use by trophy hunters to age male leopards in the field. Our logistic regression models showed that male leopard age affected the likelihood of survey respondents identifying the correct sex; notably, males <2 years were typically misidentified as females, while mature males (≥4 years were sexed correctly. Mature male leopards were also more likely to be aged correctly, as were portrait photographs. Aging proficiency was also influenced by the profession of respondents, with hunters recording the lowest scores. A discriminant model including dewlap size, the condition of the ears, and the extent of facial scarring accurately discriminated among male leopard age classes. Model classification rates were considerably higher than the respective scores attained by survey respondents, implying that the aging ability of hunters could theoretically improve with appropriate training. Dewlap size was a particularly reliable indicator of males ≥7 years and a review of online trophy galleries suggested its wider utility as an aging criterion. Our study demonstrated that an age-based hunting approach is practically applicable for leopards. However, implementation would require major reform within the regulatory

  6. Index-based reactive power compensation scheme for voltage regulation

    Science.gov (United States)

    Dike, Damian Obioma

    2008-10-01

    Increasing demand for electrical power arising from deregulation and the restrictions posed to the construction of new transmission lines by environment, socioeconomic, and political issues had led to higher grid loading. Consequently, voltage instability has become a major concern, and reactive power support is vital to enhance transmission grid performance. Improved reactive power support to distressed grid is possible through the application of relatively unfamiliar emerging technologies of "Flexible AC Transmission Systems (FACTS)" devices and "Distributed Energy Resources (DERS)." In addition to these infrastructure issues, a lack of situational awareness by system operators can cause major power outages as evidenced by the August 14, 2003 widespread North American blackout. This and many other recent major outages have highlighted the inadequacies of existing power system indexes. In this work, a novel "Index-based reactive compensation scheme" appropriate for both on-line and off-line computation of grid status has been developed. A new voltage stability index (Ls-index) suitable for long transmission lines was developed, simulated, and compared to the existing two-machine modeled L-index. This showed the effect of long distance power wheeling amongst regional transmission organizations. The dissertation further provided models for index modulated voltage source converters (VSC) and index-based load flow analysis of both FACTS and microgrid interconnected power systems using the Newton-Raphson's load flow model incorporated with multi-FACTS devices. The developed package has been made user-friendly through the embodiment of interactive graphical user interface and implemented on the IEEE 14, 30, and 300 bus systems. The results showed reactive compensation has system wide-effect, provided readily accessible system status indicators, ensured seamless DERs interconnection through new islanding modes and enhanced VSC utilization. These outcomes may contribute

  7. The role of putrescine in the regulation of proteins and fatty acids of thylakoid membranes under salt stress.

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    Shu, Sheng; Yuan, Yinghui; Chen, Jie; Sun, Jin; Zhang, Wenhua; Tang, Yuanyuan; Zhong, Min; Guo, Shirong

    2015-10-05

    Polyamines can alleviate the inhibitory effects of salinity on plant growth by regulating photosynthetic efficiency. However, little information is available to explain the specific mechanisms underlying the contribution of polyamines to salt tolerance of the photosynthetic apparatus. Here, we investigated the role of putrescine (Put) on the photosynthetic apparatus of cucumber seedlings under salt stress. We found that NaCl stress resulted in severe ion toxicity and oxidative stress in cucumber chloroplasts. In addition, salinity caused a significant increase in the saturated fatty acid contents of thylakoid membranes. Put altered unsaturated fatty acid content, thereby alleviating the disintegration of thylakoid grana lamellae and reducing the number of plastoglobuli in thylakoid membranes. BN-PAGE revealed Put up-regulated the expression of ATP synthase, CP47, D1, Qb, and psbA proteins and down-regulated CP24, D2, and LHCII type III in NaCl-stressed thylakoid membranes. qRT-PCR analysis of gene expression was used to compare transcript and protein accumulation among 10 candidate proteins. For five of these proteins, induced transcript accumulation was consistent with the pattern of induced protein accumulation. Our results suggest that Put regulates protein expression at transcriptional and translational levels by increasing endogenous polyamines levels in thylakoid membranes, which may stabilise photosynthetic apparatus under salt stress.

  8. Phospholipase D2 specifically regulates TREK potassium channels via direct interaction and local production of phosphatidic acid.

    Science.gov (United States)

    Comoglio, Yannick; Levitz, Joshua; Kienzler, Michael A; Lesage, Florian; Isacoff, Ehud Y; Sandoz, Guillaume

    2014-09-16

    Membrane lipids serve as second messengers and docking sites for proteins and play central roles in cell signaling. A major question about lipid signaling is whether diffusible lipids can selectively target specific proteins. One family of lipid-regulated membrane proteins is the TWIK-related K channel (TREK) subfamily of K2P channels: TREK1, TREK2, and TWIK-related arachdonic acid stimulated K(+) channel (TRAAK). We investigated the regulation of TREK channels by phosphatidic acid (PA), which is generated by phospholipase D (PLD) via hydrolysis of phosphatidylcholine. Even though all three of the channels are sensitive to PA, we found that only TREK1 and TREK2 are potentiated by PLD2 and that none of these channels is modulated by PLD1, indicating surprising selectivity. We found that PLD2, but not PLD1, directly binds to the C terminus of TREK1 and TREK2, but not to TRAAK. The results have led to a model for selective lipid regulation by localization of phospholipid enzymes to specific effector proteins. Finally, we show that regulation of TREK channels by PLD2 occurs natively in hippocampal neurons.

  9. A novel processing system of sterol regulatory element-binding protein-1c regulated by polyunsaturated fatty acid.

    Science.gov (United States)

    Nakakuki, Masanori; Kawano, Hiroyuki; Notsu, Tatsuto; Imada, Kazunori; Mizuguchi, Kiyoshi; Shimano, Hitoshi

    2014-05-01

    The proteolytic cascade is the key step in transactivation of sterol regulatory element-binding proteins (SREBPs), a transcriptional factor of lipid synthesis. Proteolysis of SREBP-2 is strictly regulated by sterols, but that of SREBP-1c was not strongly sterol-regulated, but inhibited by polyunsaturated fatty acids (PUFAs). In this study, the proteolytic processing of SREBP-1 and -2 was examined by transfection studies of cDNA-encoding mutants in which all the known cleavage sites were disrupted. In cultured cells, sterol-regulated SREBP-2 processing was completely eliminated by mutation of cleavage sites. In contrast, the corresponding SREBP-1c mutants as well as wild type exhibited large amounts of cleaved products in the nuclear extracts from culture cells and murine liver in vivo. The nuclear form of the mutant SREBP-1c was induced by delipidated condition and suppressed by eicosapentaenoic acid, an n-3 PUFA, but not by sterols. This novel processing mechanism was affected by neither SREBP cleavage-activating protein (SCAP) nor insulin-induced gene (Insig)-1, unlike SREBP-2, but abolished by a serine protease inhibitor. Through analysis of deletion mutant, a site-2 protease recognition sequence (DRSR) was identified to be involved in this novel processing. These findings suggest that SREBP-1c cleavage could be subjected to a novel PUFA-regulated cleavage system in addition to the sterol-regulatory SCAP/Insig system.

  10. Retinoic acid regulates several genes in bile acid and lipid metabolism via upregulation of small heterodimer partner in hepatocytes.

    Science.gov (United States)

    Mamoon, Abulkhair; Subauste, Angela; Subauste, Maria C; Subauste, Jose

    2014-10-25

    Retinoic acid (RA) affects multiple aspects of development, embryogenesis and cell differentiation processes. The liver is a major organ that stores RA suggesting that retinoids play an important role in the function of hepatocytes. In our previous studies, we have demonstrated the involvement of small heterodimer partner (SHP) in RA-induced signaling in a non-transformed hepatic cell line AML 12. In the present study, we have identified several critical genes in lipid homeostasis (Apoa1, Apoa2 and ApoF) that are repressed by RA-treatment in a SHP dependent manner, in vitro and also in vivo with the use of the SHP null mice. In a similar manner, RA also represses several critical genes involved in bile acid metabolism (Cyp7a1, Cyp8b1, Mdr2, Bsep, Baat and Ntcp) via upregulation of SHP. Collectively our data suggest that SHP plays a major role in RA-induced potential changes in pathophysiology of metabolic disorders in the liver.

  11. Regulation of fruit ascorbic acid concentrations during ripening in high and low vitamin C tomato cultivars

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    Mellidou Ifigeneia

    2012-12-01

    Full Text Available Abstract Background To gain insight into the regulation of fruit ascorbic acid (AsA pool in tomatoes, a combination of metabolite analyses, non-labelled and radiolabelled substrate feeding experiments, enzyme activity measurements and gene expression studies were carried out in fruits of the ‘low-’ and ‘high-AsA’ tomato cultivars ‘Ailsa Craig’ and ‘Santorini’ respectively. Results The two cultivars exhibited different profiles of total AsA (totAsA, AsA + dehydroascorbate and AsA accumulation during ripening, but both displayed a characteristic peak in concentrations at the breaker stage. Substrate feeding experiments demonstrated that the L-galactose pathway is the main AsA biosynthetic route in tomato fruits, but that substrates from alternative pathways can increase the AsA pool at specific developmental stages. In addition, we show that young fruits display a higher AsA biosynthetic capacity than mature ones, but this does not lead to higher AsA concentrations due to either enhanced rates of AsA breakdown (‘Ailsa Craig’ or decreased rates of AsA recycling (‘Santorini’, depending on the cultivar. In the later stages of ripening, differences in fruit totAsA-AsA concentrations of the two cultivars can be explained by differences in the rate of AsA recycling activities. Analysis of the expression of AsA metabolic genes showed that only the expression of one orthologue of GDP-L-galactose phosphorylase (SlGGP1, and of two monodehydroascorbate reductases (SlMDHAR1 and SlMDHAR3 correlated with the changes in fruit totAsA-AsA concentrations during fruit ripening in ‘Ailsa Craig’, and that only the expression of SlGGP1 was linked to the high AsA concentrations found in red ripe ‘Santorini’ fruits. Conclusions Results indicate that ‘Ailsa Craig’ and ‘Santorini’ use complementary mechanisms to maintain the fruit AsA pool. In the low-AsA cultivar (‘Ailsa Craig’, alternative routes of AsA biosynthesis may

  12. Acid-base titrations using microfluidic paper-based analytical devices.

    Science.gov (United States)

    Karita, Shingo; Kaneta, Takashi

    2014-12-16

    Rapid and simple acid-base titration was accomplished using a novel microfluidic paper-based analytical device (μPAD). The μPAD was fabricated by wax printing and consisted of ten reservoirs for reaction and detection. The reaction reservoirs contained various amounts of a primary standard substance, potassium hydrogen phthalate (KHPth), whereas a constant amount of phenolphthalein was added to all the detection reservoirs. A sample solution containing NaOH was dropped onto the center of the μPAD and was allowed to spread to the reaction reservoirs where the KHPth neutralized it. When the amount of NaOH exceeded that of the KHPth in the reaction reservoirs, unneutralized hydroxide ion penetrated the detection reservoirs, resulting in a color reaction from the phenolphthalein. Therefore, the number of the detection reservoirs with no color change determined the concentration of the NaOH in the sample solution. The titration was completed within 1 min by visually determining the end point, which required neither instrumentation nor software. The volumes of the KHPth and phenolphthalein solutions added to the corresponding reservoirs were optimized to obtain reproducible and accurate results for the concentration of NaOH. The μPADs determined the concentration of NaOH at orders of magnitude ranging from 0.01 to 1 M. An acid sample, HCl, was also determined using Na2CO3 as a primary standard substance instead of KHPth. Furthermore, the μPAD was applicable to the titrations of nitric acid, sulfuric acid, acetic acid, and ammonia solutions. The μPADs were stable for more than 1 month when stored in darkness at room temperature, although this was reduced to only 5 days under daylight conditions. The analysis of acidic hot spring water was also demonstrated in the field using the μPAD, and the results agreed well with those obtained by classic acid-base titration.

  13. Sialic acid transport and catabolism are cooperatively regulated by SiaR and CRP in nontypeable Haemophilus influenzae

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    Johnston Jason W

    2010-09-01

    Full Text Available Abstract Background The transport and catabolism of sialic acid, a critical virulence factor for nontypeable Haemophilus influenzae, is regulated by two transcription factors, SiaR and CRP. Results Using a mutagenesis approach, glucosamine-6-phosphate (GlcN-6P was identified as a co-activator for SiaR. Evidence for the cooperative regulation of both the sialic acid catabolic and transport operons suggested that cooperativity between SiaR and CRP is required for regulation. cAMP was unable to influence the expression of the catabolic operon in the absence of SiaR but was able to induce catabolic operon expression when both SiaR and GlcN-6P were present. Alteration of helical phasing supported this observation by uncoupling SiaR and CRP regulation. The insertion of one half-turn of DNA between the SiaR and CRP operators resulted in the loss of SiaR-mediated repression of the transport operon while eliminating cAMP-dependent induction of the catabolic operon when GlcN-6P was present. SiaR and CRP were found to bind to their respective operators simultaneously and GlcN-6P altered the interaction of SiaR with its operator. Conclusions These results suggest multiple novel features for the regulation of these two adjacent operons. SiaR functions as both a repressor and an activator and SiaR and CRP interact to regulate both operons from a single set of operators.

  14. Kinetics of acid base catalyzed transesterification of Jatropha curcas oil.

    Science.gov (United States)

    Jain, Siddharth; Sharma, M P

    2010-10-01

    Out of various non-edible oil resources, Jatropha curcas oil (JCO) is considered as future feedstock for biodiesel production in India. Limited work is reported on the kinetics of transesterification of high free fatty acids containing oil. The present study reports the results of kinetic study of two-step acid base catalyzed transesterification process carried out at an optimum temperature of 65 °C and 50 °C for esterification and transesterification respectively under the optimum methanol to oil ratio of 3:7 (v/v), catalyst concentration 1% (w/w) for H₂SO₄ and NaOH. The yield of methyl ester (ME) has been used to study the effect of different parameters. The results indicate that both esterification and transesterification reaction are of first order with reaction rate constant of 0.0031 min⁻¹ and 0.008 min⁻¹ respectively. The maximum yield of 21.2% of ME during esterification and 90.1% from transesterification of pretreated JCO has been obtained.

  15. Eicosapentaenoic acid regulation of muscle lipid metabolism in vivo and in vitro

    Science.gov (United States)

    Eicosapentaenoic acid (EPA), an omega 3 fatty acids exerts potent anti-inflammatory and hypolipidemic effects. We previously reported that mice fed high fat diets supplemented with EPA (HF-EPA) were resistant to diet-induced obesity, inflammation and insulin resistance. Here we further investigate b...

  16. The Arachidonic Acid Metabolome Serves as a Conserved Regulator of Cholesterol Metabolism

    NARCIS (Netherlands)

    Demetz, Egon; Schroll, Andrea; Auer, Kristina; Heim, Christiane; Patsch, Josef R.; Eller, Philipp; Theurl, Markus; Theurl, Igor; Theurl, Milan; Seifert, Markus; Lener, Daniela; Stanzl, Ursula; Haschka, David; Asshoff, Malte; Dichtl, Stefanie; Nairz, Manfred; Huber, Eva; Stadlinger, Martin; Moschen, Alexander R.; Li, Xiaorong; Pallweber, Petra; Scharnagl, Hubert; Stojakovic, Tatjana; Maerz, Winfried; Kleber, Marcus E.; Garlaschelli, Katia; Uboldi, Patrizia; Catapano, Alberico L.; Stellaard, Frans; Rudling, Mats; Kuba, Keiji; Imai, Yumiko; Arita, Makoto; Schuetz, John D.; Pramstaller, Peter P.; Tietge, Uwe J. F.; Trauner, Michael; Norata, Giuseppe D.; Claudel, Thierry; Hicks, Andrew A.; Weiss, Guenter; Tancevski, Ivan

    2014-01-01

    Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By co

  17. Chlorophyll-derived fatty acids regulate expression of lipid metabolizing enzymes in liver - a nutritional opportunity

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    Wolfrum Christian

    2001-01-01

    Full Text Available Nutritional values of fatty acid classes are normally discussed on the basis of their saturated, monounsaturated and polyunsaturated structures with implicit understanding that they are straight-chain. Here we focus on chlorophyll-derived phytanic and pristanic acids that are minor isoprenoid branched-chain lipid constituents in food, but of unknown nutritional value. After describing the enzyme machinery that degrades these nutrient fatty acids in the peroxisome, we show by the criteria of a mouse model and of a human cell culture model that they induce with high potency expression of enzymes responsible for beta-oxidation of straight-chain fatty acids in the peroxisome. We summarize present mechanistic knowledge on fatty acid signaling to the nucleus, which involves protein/protein contacts between peroxisome proliferator activated receptor (PPAR and fatty acid binding protein (FABP. In this signaling event the branched-chain fatty acids are the most effective ones. Finally, on the basis of this nutrient-gene interaction we discuss nutritional opportunities and therapeutic aspects of the chlorophyll-derived fatty acids.

  18. Transcriptional regulation of chlorogenic acid biosynthesis in carrot root slices exposed to UV-B light

    Science.gov (United States)

    Orange carrots are well known for their nutritional value as producers of ß-carotene, a Vitamin A precursor. Lesser known, is their ability to accumulate antioxidants such as chlorogenic acid. Chlorogenic acid is produced through the same biosynthetic pathway that produces lignins, anthocyanins, f...

  19. Alpha-2-glycoprotein 1(AZGP1 regulates biological behaviors of LoVo cells by down-regulating mTOR signaling pathway and endogenous fatty acid synthesis.

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    Ligong Chang

    Full Text Available AZGP1 is a multifaceted protein associated with lipid mobilization, a process that is regulated by FASN and other metabolic pathways such as mTOR signaling. The active mTOR signaling pathway has been found to be involved in a variety of tumors. However, it remains unclear whether it is involved in the regulation of AZGP1 and FASN. An AZGP1-expressing plasmid was transfected into a human colorectal cancer cell line (LoVo with a low expression of AZGP1. The expression of AZGP1, FASN, eIF4E, p-mTOR, p-S6,and S6K1 were measured by Western blot analysis, and target genes were detected by RT-PCR. Cell proliferation was studied using the MTT and colony formation assays. The analysis of apoptosis and the cell cycle phase were assessed by flow cytometry. The capacity of cell migration was investigated using the transwell migration assay. We found that the expression of AZGP1 was up-regulated while the expression of FASN, eIF4E, p-mTOR, p-S6, and S6K1 were down-regulated in LoVo cells after AZGP1 was expressed. The proliferation of malignant cells was reduced in AZGP1-overexpression cells, which is consistent with an increased in the G2-arrest and apoptosis rate. Furthermore, the migration of AZGP1-overexpression cells was decreased. The overexpression of AZGP1 suppressed the activation of the mTOR pathway and endogenous FASN-regulated fatty acid synthesis, mitigating the malignant phenotype of LoVo cells. Herein, we provide evidence that AZGP1 may constitute a novel tumor suppressor for LoVo colorectal cancer cells.

  20. Alpha-2-glycoprotein 1(AZGP1) regulates biological behaviors of LoVo cells by down-regulating mTOR signaling pathway and endogenous fatty acid synthesis.

    Science.gov (United States)

    Chang, Ligong; Tian, Xiaoqiang; Lu, Yinghui; Jia, Min; Wu, Peng; Huang, Peilin

    2014-01-01

    AZGP1 is a multifaceted protein associated with lipid mobilization, a process that is regulated by FASN and other metabolic pathways such as mTOR signaling. The active mTOR signaling pathway has been found to be involved in a variety of tumors. However, it remains unclear whether it is involved in the regulation of AZGP1 and FASN. An AZGP1-expressing plasmid was transfected into a human colorectal cancer cell line (LoVo) with a low expression of AZGP1. The expression of AZGP1, FASN, eIF4E, p-mTOR, p-S6,and S6K1 were measured by Western blot analysis, and target genes were detected by RT-PCR. Cell proliferation was studied using the MTT and colony formation assays. The analysis of apoptosis and the cell cycle phase were assessed by flow cytometry. The capacity of cell migration was investigated using the transwell migration assay. We found that the expression of AZGP1 was up-regulated while the expression of FASN, eIF4E, p-mTOR, p-S6, and S6K1 were down-regulated in LoVo cells after AZGP1 was expressed. The proliferation of malignant cells was reduced in AZGP1-overexpression cells, which is consistent with an increased in the G2-arrest and apoptosis rate. Furthermore, the migration of AZGP1-overexpression cells was decreased. The overexpression of AZGP1 suppressed the activation of the mTOR pathway and endogenous FASN-regulated fatty acid synthesis, mitigating the malignant phenotype of LoVo cells. Herein, we provide evidence that AZGP1 may constitute a novel tumor suppressor for LoVo colorectal cancer cells.

  1. Role of gluconic acid production in the regulation of biocontrol traits of Pseudomonas fluorescens CHA0.

    Science.gov (United States)

    de Werra, Patrice; Péchy-Tarr, Maria; Keel, Christoph; Maurhofer, Monika

    2009-06-01

    The rhizobacterium Pseudomonas fluorescens CHA0 promotes the growth of various crop plants and protects them against root diseases caused by pathogenic fungi. The main mechanism of disease suppression by this strain is the production of the antifungal compounds 2,4-diacetylphloroglucinol (DAPG) and pyoluteorin (PLT). Direct plant growth promotion can be achieved through solubilization of inorganic phosphates by the production of organic acids, mainly gluconic acid, which is one of the principal acids produced by Pseudomonas spp. The aim of this study was to elucidate the role of gluconic acid production in CHA0. Therefore, mutants were created with deletions in the genes encoding glucose dehydrogenase (gcd) and gluconate dehydrogenase (gad), required for the conversion of glucose to gluconic acid and gluconic acid to 2-ketogluconate, respectively. These enzymes should be of predominant importance for rhizosphere-colonizing biocontrol bacteria, as major carbon sources provided by plant root exudates are made up of glucose. Our results show that the ability of strain CHA0 to acidify its environment and to solubilize mineral phosphate is strongly dependent on its ability to produce gluconic acid. Moreover, we provide evidence that the formation of gluconic acid by CHA0 completely inhibits the production of PLT and partially inhibits that of DAPG. In the Deltagcd mutant, which does not produce gluconic acid, the enhanced production of antifungal compounds was associated with improved biocontrol activity against take-all disease of wheat, caused by Gaeumannomyces graminis var. tritici. This study provides new evidence for a close association of gluconic acid metabolism with antifungal compound production and biocontrol activity in P. fluorescens CHA0.

  2. Nucleic Acid-Based Therapy Approaches for Huntington's Disease

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    Tatyana Vagner

    2012-01-01

    Full Text Available Huntington's disease (HD is caused by a dominant mutation that results in an unstable expansion of a CAG repeat in the huntingtin gene leading to a toxic gain of function in huntingtin protein which causes massive neurodegeneration mainly in the striatum and clinical symptoms associated with the disease. Since the mutation has multiple effects in the cell and the precise mechanism of the disease remains to be elucidated, gene therapy approaches have been developed that intervene in different aspects of the condition. These approaches include increasing expression of growth factors, decreasing levels of mutant huntingtin, and restoring cell metabolism and transcriptional balance. The aim of this paper is to outline the nucleic acid-based therapeutic strategies that have been tested to date.

  3. Neurocognitive bases of emotion regulation development in adolescence

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    Saz P. Ahmed

    2015-10-01

    Full Text Available Emotion regulation is the ability to recruit processes to influence emotion generation. In recent years there has been mounting interest in how emotions are regulated at behavioural and neural levels, as well as in the relevance of emotional dysregulation to psychopathology. During adolescence, brain regions involved in affect generation and regulation, including the limbic system and prefrontal cortex, undergo protracted structural and functional development. Adolescence is also a time of increasing vulnerability to internalising and externalising psychopathologies associated with poor emotion regulation, including depression, anxiety and antisocial behaviour. It is therefore of particular interest to understand how emotion regulation develops over this time, and how this relates to ongoing brain development. However, to date relatively little research has addressed these questions directly. This review will discuss existing research in these areas in both typical adolescence and in adolescent psychopathology, and will highlight opportunities for future research. In particular, it is important to consider the social context in which adolescent emotion regulation develops. It is possible that while adolescence may be a time of vulnerability to emotional dysregulation, scaffolding the development of emotion regulation during this time may be a fruitful preventative target for psychopathology.

  4. Neurocognitive bases of emotion regulation development in adolescence.

    Science.gov (United States)

    Ahmed, Saz P; Bittencourt-Hewitt, Amanda; Sebastian, Catherine L

    2015-10-01

    Emotion regulation is the ability to recruit processes to influence emotion generation. In recent years there has been mounting interest in how emotions are regulated at behavioural and neural levels, as well as in the relevance of emotional dysregulation to psychopathology. During adolescence, brain regions involved in affect generation and regulation, including the limbic system and prefrontal cortex, undergo protracted structural and functional development. Adolescence is also a time of increasing vulnerability to internalising and externalising psychopathologies associated with poor emotion regulation, including depression, anxiety and antisocial behaviour. It is therefore of particular interest to understand how emotion regulation develops over this time, and how this relates to ongoing brain development. However, to date relatively little research has addressed these questions directly. This review will discuss existing research in these areas in both typical adolescence and in adolescent psychopathology, and will highlight opportunities for future research. In particular, it is important to consider the social context in which adolescent emotion regulation develops. It is possible that while adolescence may be a time of vulnerability to emotional dysregulation, scaffolding the development of emotion regulation during this time may be a fruitful preventative target for psychopathology.

  5. The effects of bud load and regulated deficit irrigation on sugar, organic acid, phenolic compounds and antioxidant activity of Razakı table grape berries

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    Tangolar Semih

    2015-01-01

    Full Text Available This study aims at assessing the effects of increased bud load and irrigation applications on berry quality of the Razakı table grape. Two Regulated Deficit Irrigation (RDI having different irrigation levels (RDI-I and RDI-II based on the growth stages, in addition to a non-irrigated control treatment together with two different bud load practices (K-normal and 2K-two-fold buds of the normal were examined for their effects on quality attributes such as sugar and organic acids contents, phenolic compounds as well as antioxidant capacity of the berries. The non-irrigated vines had highest sugar level (198.86 g/kg in the first year (2013 of the experiment whilst the sugar content of the berries was increased with irrigation (RDI-II in 2014. However the highest organic acid (7.10 g/kg was recorded from the RDI-II treatment in 2013 whereas those of from non-irrigated vines were highest (7.81 g/kg in 2014. Considering the sugar and organic acid content of the berries, bud load effects were not significant. The total phenolic acids were higher under non-irrigated and 2K bud load conditions. Antioxidant activity of berries was increased with RDI-I irrigation and 2K practices in the first year (2013 although no significant effect was recorded in the second year of the experiment. In all applications, glucose among the sugars, tartaric acid among the organic acids, catechin and epicatechin among the phenolic compounds were detected to be higher compared to other components in berries.

  6. Susceptibility of podocytes to palmitic acid is regulated by stearoyl-CoA desaturases 1 and 2.

    Science.gov (United States)

    Sieber, Jonas; Weins, Astrid; Kampe, Kapil; Gruber, Stefan; Lindenmeyer, Maja T; Cohen, Clemens D; Orellana, Jana M; Mundel, Peter; Jehle, Andreas W

    2013-09-01

    Type 2 diabetes mellitus is characterized by dyslipidemia with elevated free fatty acids (FFAs). Loss of podocytes is a hallmark of diabetic nephropathy, and podocytes are highly susceptible to saturated FFAs but not to protective, monounsaturated FFAs. We report that patients with diabetic nephropathy develop alterations in glomerular gene expression of enzymes involved in fatty acid metabolism, including induction of stearoyl-CoA desaturase (SCD)-1, which converts saturated to monounsaturated FFAs. By IHC of human renal biopsy specimens, glomerular SCD-1 induction was observed in podocytes of patients with diabetic nephropathy. Functionally, the liver X receptor agonists TO901317 and GW3965, two known inducers of SCD, increased Scd-1 and Scd-2 expression in cultured podocytes and reduced palmitic acid-induced cell death. Similarly, overexpression of Scd-1 attenuated palmitic acid-induced cell death. The protective effect of TO901317 was associated with a reduction of endoplasmic reticulum stress. It was lost after gene silencing of Scd-1/-2, thereby confirming that the protective effect of TO901317 is mediated by Scd-1/-2. TO901317 also shifted palmitic acid-derived FFAs into biologically inactive triglycerides. In summary, SCD-1 up-regulation in diabetic nephropathy may be part of a protective mechanism against saturated FFA-derived toxic metabolites that drive endoplasmic reticulum stress and podocyte death.

  7. Improved physical stability of amorphous state through acid base interactions.

    Science.gov (United States)

    Telang, Chitra; Mujumdar, Siddharthya; Mathew, Michael

    2009-06-01

    To investigate role of specific interactions in aiding formation and stabilization of amorphous state in ternary and binary dispersions of a weakly acidic drug. Indomethacin (IMC), meglumine (MU), and polyvinyl pyrollidone (PVP) were the model drug, base, and polymer, respectively. Dispersions were prepared using solvent evaporation. Physical mixtures were cryogenically coground. XRPD, PLM, DSC, TGA, and FTIR were used for characterization. MU has a high crystallization tendency and is characterized by a low T(g) (17 degrees C). IMC crystallization was inhibited in ternary dispersion with MU compared to IMC/PVP alone. An amorphous state formed readily even in coground mixtures. Spectroscopic data are indicative of an IMC-MU amorphous salt and supports solid-state proton transfer. IMC-MU salt displays a low T(g) approximately 50 degrees C, but is more physically stable than IMC, which in molecular mixtures with MU, resisted crystallization even when present in stoichiometric excess of base. This is likely due to a disrupted local structure of amorphous IMC due to specific interactions. IMC showed improved physical stability on incorporating MU in polymer, in spite of low T(g) of the base indicating that chemical interactions play a dominant role in physical stabilization. Salt formation could be induced thermally and mechanically.

  8. TyrR, the regulator of aromatic amino acid metabolism, is required for mice infection of Yersinia pestis

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    Zhongliang eDeng

    2015-02-01

    Full Text Available Yersinia pestis, the causative agent of plague, poses a serious health threat to rodents and human beings. TyrR is a transcriptional regulator that controls the metabolism of aromatic amino acids in Escherichia coli. In this paper, TyrR played an important role in Y. pestis virulence. Inactivation of tyrR did not seem to affect the in vitro growth of this organism, but resulted in at least 10,000-fold attenuation compared with the wild-type (WT strain upon subcutaneous infection to mice. In addition, loads of tyrR mutant within mice livers and spleens significantly decreased compared with the WT strain. Transcriptome analysis revealed that TyrR, directly or indirectly, regulated 29 genes encoded on Y. pestis chromosome or plasmids under in vitro growth condition. Similar to the regulatory function of this protein in E. coli, five aromatic-pathway genes (aroF-tyrA, aroP, aroL, and tyrP were significantly reduced upon deletion of the tyrR gene. Two genes (glnL and glnG that encode sensory histidine kinase and regulator in a two-component regulatory system involved in nitrogen assimilation were downregulated in the tyrR mutant. Several genes encoding type III secretion proteins were transcribed by 2.0- to 4.2-fold in a tyrR mutant relative to the WT strain. Interestingly, the acid-stressed genes, hdeB and hdeD, were downregulated, and such downregulation partly accounted for the decrease in tolerance of the tyrR mutant under acidic conditions. In conclusion, regulation of TyrR in Y. pestis is similar to, but distinct from, that in E. coli. TyrR is a metabolic virulence determinant in Y. pestis that is important for extracellular survival and/or proliferation.

  9. Structural Bases for the Regulation of CO Binding in the Archaeal Protoglobin from Methanosarcina acetivorans.

    Directory of Open Access Journals (Sweden)

    Lesley Tilleman

    Full Text Available Studies of CO ligand binding revealed that two protein states with different ligand affinities exist in the protoglobin from Methanosarcina acetivorans (in MaPgb*, residue Cys(E20101 was mutated to Ser. The switch between the two states occurs upon the ligation of MaPgb*. In this work, site-directed mutagenesis was used to explore the role of selected amino acids in ligand sensing and stabilization and in affecting the equilibrium between the "more reactive" and "less reactive" conformational states of MaPgb*. A combination of experimental data obtained from electronic and resonance Raman absorption spectra, CO ligand-binding kinetics, and X-ray crystallography was employed. Three amino acids were assigned a critical role: Trp(60B9, Tyr(61B10, and Phe(93E11. Trp(60B9 and Tyr(61B10 are involved in ligand stabilization in the distal heme pocket; the strength of their interaction was reflected by the spectra of the CO-ligated MaPgb* and by the CO dissociation rate constants. In contrast, Phe(93E11 is a key player in sensing the heme-bound ligand and promotes the rotation of the Trp(60B9 side chain, thus favoring ligand stabilization. Although the structural bases of the fast CO binding rate constant of MaPgb* are still unclear, Trp(60B9, Tyr(61B10, and Phe(93E11 play a role in regulating heme/ligand affinity.

  10. Methylene-bis[(aminomethyl)phosphinic acids]: synthesis, acid-base and coordination properties.

    Science.gov (United States)

    David, Tomáš; Procházková, Soňa; Havlíčková, Jana; Kotek, Jan; Kubíček, Vojtěch; Hermann, Petr; Lukeš, Ivan

    2013-02-21

    Three symmetrical methylene-bis[(aminomethyl)phosphinic acids] bearing different substituents on the central carbon atom, (NH(2)CH(2))PO(2)H-C(R(1))(R(2))-PO(2)H(CH(2)NH(2)) where R(1) = OH, R(2) = Me (H(2)L(1)), R(1) = OH, R(2) = Ph (H(2)L(2)) and R(1),R(2) = H (H(2)L(3)), were synthesized. Acid-base and complexing properties of the ligands were studied in solution as well as in the solid state. The ligands show unusually high basicity of the nitrogen atoms (log K(1) = 9.5-10, log K(2) = 8.5-9) if compared with simple (aminomethyl)phosphinic acids and, consequently, high stability constants of the complexes with studied divalent metal ions. The study showed the important role of the hydroxo group attached to the central carbon atom of the geminal bis(phosphinate) moiety. Deprotonation of the hydroxo group yields the alcoholate anion which tends to play the role of a bridging ligand and induces formation of polynuclear complexes. Solid-state structures of complexes [H(2)N=C(NH(2))(2)][Cu(2)(H(-1)L(2))(2)]CO(3)·10H(2)O and Li(2)[Co(4)(H(-1)L(1))(3)(OH)]·17.5H(2)O were determined by X-ray diffraction. The complexes show unexpected geometries forming dinuclear and cubane-like structures, respectively. The dinuclear copper(II) complex contains a bridging μ(2)-alcoholate group with the (-)O-P(=O)-CH(2)-NH(2) fragments of each ligand molecule chelated to the different central ion. In the cubane cobalt(II) complex, one μ(3)-hydroxide and three μ(3)-alcoholate anions are located in the cube vertices and both phosphinate groups of one ligand molecule are chelating the same cobalt(II) ion while each of its amino groups are bound to different neighbouring metal ions. All such three metal ions are bridged by the alcoholate group of a given ligand.

  11. Possible roles for folic acid in the regulation of trophoblast invasion and placental development in normal early human pregnancy.

    Science.gov (United States)

    Williams, Paula J; Bulmer, Judith N; Innes, Barbara A; Broughton Pipkin, Fiona

    2011-06-01

    In addition to its role in the prevention of neural tube defects, folic acid has many other physiological functions, including cell proliferation, DNA replication, and antioxidant protection. The aim of this study was to determine the role that folic acid has in regulating placental trophoblast development. Placental explants from placentae at gestational age 7 wk (n = 3) were cultured in folic acid at concentrations of 10(-6) M, 10(-8) M, and 10(-10) M. Extravillous trophoblast (EVT) invasion was assessed following 6-day culture, and explants were used for immunohistochemical evaluation of proliferation (MKI67) and apoptosis (active caspase 3). In addition, an array was performed on cell culture supernatants to examine a range of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). Folic acid increased the invasion of EVT cells in this explant model by between 83% and 19% (P = 0.005), and this was associated with increased MKI67 positivity and decreased active caspase 3 positivity; this effect was concentration dependent and showed a biphasic response. In addition, culture in folic acid increased vascular density, as determined by anti-CD31 immunostaining (P = 0.05). The increase in EVT invasion correlated with increased placental explant secretion of MMP2 (P = 0.01), MMP3 (P = 0.01), and MMP9 (P = 0.02). This study demonstrates that folic acid is potentially important in a number of crucial early stages of placental development, including EVT invasion, angiogenesis, and secretion of MMPs, and highlights the need for further studies to address the benefit of longer-term folic acid supplementation throughout pregnancy to prevent pregnancy disorders associated with deficient placental development, including preeclampsia.

  12. Folic Acid Is Able to Polarize the Inflammatory Response in LPS Activated Microglia by Regulating Multiple Signaling Pathways

    Science.gov (United States)

    Salvatore, Rosaria; Porro, Chiara; Trotta, Teresa

    2016-01-01

    We investigated the ability of folic acid to modulate the inflammatory responses of LPS activated BV-2 microglia cells and the signal transduction pathways involved. To this aim, the BV-2 cell line was exposed to LPS as a proinflammatory response inducer, in presence or absence of various concentrations of folic acid. The production of nitric oxide (NO) was determined by the Griess test. The levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-10 were determined by ELISA. Inducible NO synthase (iNOS), nuclear transcription factor-kappa B (NF-κB) p65, MAPKs protein, and suppressors of cytokine signaling (SOCS)1 and SOCS3 were analyzed by western blotting. TNF-α and IL-1β, as well as iNOS dependent NO production, resulted significantly inhibited by folic acid pretreatment in LPS-activated BV-2 cells. We also observed that folic acid dose-dependently upregulated both SOCS1 and SOCS3 expression in BV-2 cells, leading to an increased expression of the anti-inflammatory cytokine IL-10. Finally, p-IκBα, which indirectly reflects NF-κB complex activation, and JNK phosphorylation resulted dose-dependently downregulated by folic acid pretreatment of LPS-activated cells, whereas p38 MAPK phosphorylation resulted significantly upregulated by folic acid treatment. Overall, these results demonstrated that folic acid was able to modulate the inflammatory response in microglia cells, shifting proinflammatory versus anti-inflammatory responses through regulating multiple signaling pathways.

  13. 78 FR 42430 - Revisions to the Export Administration Regulations Based on the 2012 Missile Technology Control...

    Science.gov (United States)

    2013-07-16

    ... (Definitions of Terms as Used in the Export Administration Regulations) by amending the definition of the term... Definitions of terms as used in the Export Administration Regulations (EAR). * * * * * Payload... Administration Regulations Based on the 2012 Missile Technology Control Regime Plenary Agreements AGENCY:...

  14. The metabolic flux regulation of Klebsiella pneumoniae based on quorum sensing system

    Science.gov (United States)

    Sun, Shujing; Zhang, Haiyang; Lu, Shuyi; Lai, Chunfen; Liu, Huijun; Zhu, Hu

    2016-01-01

    Quorum-sensing (QS) systems exist universally in bacteria to regulate multiple biological functions. Klebsiella pneumoniae, an industrially important bacterium that produces bio-based chemicals such as 2,3-butanediol and acetoin, can secrete a furanosyl borate diester (AI-2) as the signalling molecule mediating a QS system, which plays a key regulatory role in the biosynthesis of secondary metabolites. In this study, the molecular regulation and metabolic functions of a QS system in K. pneumoniae were investigated. The results showed that after the disruption of AI-2-mediated QS by the knockout of luxS, the production of acetoin, ethanol and acetic acid were relatively lower in the K. pneumoniae mutant than in the wild type bacteria. However, 2,3-butanediol production was increased by 23.8% and reached 54.93 g/L. The observed enhancement may be attributed to the improvement of the catalytic activity of 2,3-butanediol dehydrogenase (BDH) in transforming acetoin to 2,3-butanediol. This possibility is consistent with the RT-PCR-verified increase in the transcriptional level of budC, which encodes BDH. These results also demonstrated that the physiological metabolism of K. pneumoniae was adversely affected by a QS system. This effect was reversed through the addition of synthetic AI-2. This study provides the basis for a QS-modulated metabolic engineering study of K. pneumoniae. PMID:27924940

  15. RNA-guided transcriptional regulation in planta via synthetic dCas9-based transcription factors

    KAUST Repository

    Piatek, Agnieszka Anna

    2014-11-14

    Targeted genomic regulation is a powerful approach to accelerate trait discovery and development in agricultural biotechnology. Bacteria and archaea use clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) regulatory systems for adaptive molecular immunity against foreign nucleic acids introduced by invading phages and conjugative plasmids. The type II CRISPR/Cas system has been adapted for genome editing in many cell types and organisms. A recent study used the catalytically inactive Cas9 (dCas9) protein combined with guide-RNAs (gRNAs) as a DNA-targeting platform to modulate gene expression in bacterial, yeast, and human cells. Here, we modified this DNA-targeting platform for targeted transcriptional regulation in planta by developing chimeric dCas9-based transcriptional activators and repressors. To generate transcriptional activators, we fused the dCas9 C-terminus with the activation domains of EDLL and TAL effectors. To generate a transcriptional repressor, we fused the dCas9 C-terminus with the SRDX repression domain. Our data demonstrate that dCas9 fusion with the EDLL activation domain (dCas9:EDLL) and the TAL activation domain (dCas9:TAD), guided by gRNAs complementary to selected promoter elements, induce strong transcriptional activation on Bs3

  16. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to linoleic acid (LA) in combination with gamma-linolenic acid (GLA) and reduction of ocular dryness (ID 4274) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... claims in relation to linoleic acid (LA) in combination with gamma-linolenic acid (GLA) and reduction of ocular dryness. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from...... Member States or directly from stakeholders. The food that is the subject of the health claims is linoleic acid in combination with gamma-linolenic acid. The Panel considers that the food constituents, linoleic acid and gamma-linolenic acid, are sufficiently characterised. The claimed effect is “ocular...

  17. Amino acid-bile acid based molecules: extremely narrow surfactant nanotubes formed by a phenylalanine-substituted cholic acid.

    Science.gov (United States)

    Travaglini, Leana; D'Annibale, Andrea; Schillén, Karin; Olsson, Ulf; Sennato, Simona; Pavel, Nicolae V; Galantini, Luciano

    2012-12-21

    An amino acid-substituted bile acid forms tubular aggregates with inner and outer diameters of about 3 and 6 nm. The diameters are unusually small for surfactant self-assembled tubes. The results enhance the spectrum of applications of supramolecular tubules and open up possibilities for investigating a novel class of biological amphiphiles.

  18. Salvianolic acid B regulates gene expression and promotes cell viability in chondrocytes.

    Science.gov (United States)

    Yang, Xiaohong; Liu, Shaojie; Li, Siming; Wang, Pengzhen; Zhu, Weicong; Liang, Peihong; Tan, Jianrong; Cui, Shuliang

    2017-02-28

    Articular chondrocytes reside in lacunae distributed in cartilage responsible for the remodelling of the tissue with limited ability of damage repairing. The in vitro expanded chondrocytes enhanced by factors/agents to obtain large numbers of cells with strengthened phenotype are essential for successful repair of cartilage lesions by clinical cell implantation therapies. Because the salvianolic acid B (Sal B), a major hydrophilic therapeutic agent isolated from Salvia miltiorrhiza, has been widely used to treat diseases and able to stimulate activity of cells, this study examines the effects of Sal B on passaged chondrocytes. Chondrocytes were treated with various concentrations of Sal B in monolayer culture, their morphological properties and changes, and mitochondrial membrane potential were analysed using microscopic analyses, including cellular biochemical staining and confocal laser scanning microscopy. The proteins were quantified by BCA and Western blotting, and the transcription of genes was detected by qRT-PCR. The passaged chondrocytes treated with Sal B showed strengthened cellular synthesis and stabilized mitochondrial membrane potential with upregulated expression of the marker genes for chondrocyte phenotype, Col2-α1, Acan and Sox9, the key Wnt signalling molecule β-catenin and paracrine cytokine Cytl-1. The treatments using CYTL-1 protein significantly increased expression of Col2-α1 and Acan with no effect on Sox9, indicating the paracrine cytokine acts on chondrocytes independent of SOX9. Sal B has ultimately promoted cell growth and enhanced chondrocyte phenotype. The chondrocytes treated with pharmaceutical agent and cytokine in the formulated medium for generating large number of differentiated chondrocytes would facilitate the cell-based therapies for cartilage repair.

  19. Human ketone body production and utilization studied using tracer techniques: Regulation by free fatty acids, insulin, catecholamines, and thyroid hormones

    Energy Technology Data Exchange (ETDEWEB)

    Keller, U.; Lustenberger, M.; Mueller-Brand, J.G.; Gerber, P.P.; Stauffacher, W.

    1989-05-01

    Ketone body concentrations fluctuate markedly during physiological and pathological conditions. Tracer techniques have been developed in recent years to study production, utilization, and the metabolic clearance rate of ketone bodies. This review describes data on the roles of insulin, catecholamines, and thyroid hormones in the regulation of ketone body kinetics. The data indicate that insulin lowers ketone body concentrations by three independent mechanisms: first, it inhibits lipolysis, and thus lowers free fatty acid availability for ketogenesis; second, it restrains ketone body production within the liver; third, it enhances peripheral ketone body utilization. To assess these effects in humans in vivo, experimental models were developed to study insulin effects with controlled concentrations of free fatty acids, insulin, glucagon, and ketone bodies. Presently available data also support an important role of catecholamines in increasing ketone body concentrations. Evidence was presented that norepinephrine increases ketogenesis not only by stimulating lipolysis, and