Sample records for export pump bsep

  1. Genetics Home Reference: benign recurrent intrahepatic cholestasis

    MedlinePlus

    ... for making a protein called the bile salt export pump (BSEP). This protein is found in the ... progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic ...

  2. Short-chain ubiquitination is associated with the degradation rate of a cell-surface-resident bile salt export pump (BSEP/ABCB11).

    PubMed

    Hayashi, Hisamitsu; Sugiyama, Yuichi

    2009-01-01

    The reduced expression of the bile salt export pump (BSEP/ABCB11) at the canalicular membrane is associated with cholestasis-induced hepatotoxicity due to the accumulation of bile acids in hepatocytes. We demonstrated previously that 4-phenylbutyrate (4PBA) treatment, a U.S. Food and Drug Administration-approved drug for the treatment of urea cycle disorders, induces the cell-surface expression of BSEP by prolonging the degradation rate of cell-surface-resident BSEP. On the other hand, BSEP mutations, E297G and D482G, found in progressive familial intrahepatic cholestasis type 2 (PFIC2), reduced it by shortening the degradation rate of cell-surface-resident BSEP. Therefore, to help the development of the medical treatment of cholestasis, we investigated the underlying mechanism by which 4PBA and PFIC2-type mutations affect the BSEP degradation from cell surface, focusing on short-chain ubiquitination. In Madin-Darby canine kidney II (MDCK II) cells expressing BSEP and rat canalicular membrane vesicles, the molecular mass of the mature form of BSEP/Bsep shifted from 170 to 190 kDa after ubiquitin modification (molecular mass, 8 kDa). Ubiquitination susceptibility of BSEP/Bsep was reduced in vitro and in vivo by 4PBA treatment and, conversely, was enhanced by BSEP mutations E297G and D482G. Moreover, biotin-labeling studies using MDCK II cells demonstrated that the degradation of cell-surface-resident chimeric protein fusing ubiquitin to BSEP was faster than that of BSEP itself. In conclusion, BSEP/Bsep is modified with two to three ubiquitins, and its ubiquitination is modulated by 4PBA treatment and PFIC2-type mutations. Modulation of short-chain ubiquitination can regulate the change in the degradation rate of cell-surface-resident BSEP by 4PBA treatment and PFIC2-type mutations.

  3. Structure based classification for bile salt export pump (BSEP) inhibitors using comparative structural modeling of human BSEP

    NASA Astrophysics Data System (ADS)

    Jain, Sankalp; Grandits, Melanie; Richter, Lars; Ecker, Gerhard F.

    2017-06-01

    The bile salt export pump (BSEP) actively transports conjugated monovalent bile acids from the hepatocytes into the bile. This facilitates the formation of micelles and promotes digestion and absorption of dietary fat. Inhibition of BSEP leads to decreased bile flow and accumulation of cytotoxic bile salts in the liver. A number of compounds have been identified to interact with BSEP, which results in drug-induced cholestasis or liver injury. Therefore, in silico approaches for flagging compounds as potential BSEP inhibitors would be of high value in the early stage of the drug discovery pipeline. Up to now, due to the lack of a high-resolution X-ray structure of BSEP, in silico based identification of BSEP inhibitors focused on ligand-based approaches. In this study, we provide a homology model for BSEP, developed using the corrected mouse P-glycoprotein structure (PDB ID: 4M1M). Subsequently, the model was used for docking-based classification of a set of 1212 compounds (405 BSEP inhibitors, 807 non-inhibitors). Using the scoring function ChemScore, a prediction accuracy of 81% on the training set and 73% on two external test sets could be obtained. In addition, the applicability domain of the models was assessed based on Euclidean distance. Further, analysis of the protein-ligand interaction fingerprints revealed certain functional group-amino acid residue interactions that could play a key role for ligand binding. Though ligand-based models, due to their high speed and accuracy, remain the method of choice for classification of BSEP inhibitors, structure-assisted docking models demonstrate reasonably good prediction accuracies while additionally providing information about putative protein-ligand interactions.

  4. The role of bile salt export pump mutations in progressive familial intrahepatic cholestasis type II

    PubMed Central

    Wang, Lin; Soroka, Carol J.; Boyer, James L.

    2002-01-01

    PFIC II is a subtype of progressive familial intrahepatic cholestasis (PFIC) that is associated with mutations in the ABCB11 gene encoding the bile salt export pump (BSEP). However it is not known how these mutations cause this disease. To evaluate these mechanisms, we introduced seven PFIC II–associated missense mutations into rat Bsep and assessed their effects on Bsep membrane localization and transport function in MDCK and Sf9 cells, respectively. Five mutations, G238V, E297G, G982R, R1153C, and R1268Q, prevented the protein from trafficking to the apical membrane, and E297G, G982R, R1153C, and R1268Q also abolished taurocholate transport activity, possibly by causing Bsep to misfold. Mutation C336S affected neither Bsep transport activity nor the apical trafficking of Bsep, suggesting that this mutation alone may not cause this disease. D482G did not affect the apical expression but partially decreased the transport activity of Bsep. Mutant G238V was rapidly degraded in both MDCK and Sf9 cells, and proteasome inhibitor resulted in intracellular accumulation of this and other mutants, suggesting proteasome-mediated degradation plays an important role in expression of these PFIC II mutants. Our studies highlight the heterogeneous nature of PFIC II mutations and illustrate the significance of these mutations in the function and expression of Bsep. PMID:12370274

  5. AP2 adaptor complex mediates bile salt export pump internalization and modulates its hepatocanalicular expression and transport function.

    PubMed

    Hayashi, Hisamitsu; Inamura, Kaori; Aida, Kensuke; Naoi, Sotaro; Horikawa, Reiko; Nagasaka, Hironori; Takatani, Tomozumi; Fukushima, Tamio; Hattori, Asami; Yabuki, Takashi; Horii, Ikuo; Sugiyama, Yuichi

    2012-06-01

    The bile salt export pump (BSEP) mediates the biliary excretion of bile salts and its dysfunction induces intrahepatic cholestasis. Reduced canalicular expression of BSEP resulting from the promotion of its internalization is one of the causes of this disease state. However, the molecular mechanism underlying BSEP internalization from the canalicular membrane (CM) remains unknown. We have shown previously that 4-phenylbutyrate (4PBA), a drug used for ornithine transcarbamylase deficiency (OTCD), inhibited internalization and subsequent degradation of cell-surface-resident BSEP. The current study found that 4PBA treatment decreased significantly the expression of α- and μ2-adaptin, both of which are subunits of the AP2 adaptor complex (AP2) that mediates clathrin-dependent endocytosis, in liver specimens from rats and patients with OTCD, and that BSEP has potential AP2 recognition motifs in its cytosolic region. Based on this, the role of AP2 in BSEP internalization was explored further. In vitro analysis with 3×FLAG-human BSEP-expressing HeLa cells and human sandwich-culture hepatocytes indicates that the impairment of AP2 function by RNA interference targeting of α-adaptin inhibits BSEP internalization from the plasma membrane and increases its cell-surface expression and transport function. Studies using immunostaining, coimmunoprecipitation, glutathione S-transferase pulldown assay, and time-lapse imaging show that AP2 interacts with BSEP at the CM through a tyrosine motif at the carboxyl terminus of BSEP and mediates BSEP internalization from the CM of hepatocytes. AP2 mediates the internalization and subsequent degradation of CM-resident BSEP through direct interaction with BSEP and thereby modulates the canalicular expression and transport function of BSEP. This information should be useful for understanding the pathogenesis of severe liver diseases associated with intrahepatic cholestasis. Copyright © 2012 American Association for the Study of Liver Diseases.

  6. Biliary excretion of pravastatin and taurocholate in rats with bile salt export pump (Bsep) impairment.

    PubMed

    Cheng, Yaofeng; Freeden, Chris; Zhang, Yueping; Abraham, Pamela; Shen, Hong; Wescott, Debra; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2016-07-01

    The bile salt export pump (BSEP) is expressed on the canalicular membrane of hepatocytes regulating liver bile salt excretion, and impairment of BSEP function may lead to cholestasis in humans. This study explored drug biliary excretion, as well as serum chemistry, individual bile acid concentrations and liver transporter expressions, in the SAGE Bsep knockout (KO) rat model. It was observed that the Bsep protein in KO rats was decreased to 15% of that in the wild type (WT), as quantified using LC-MS/MS. While the levels of Ntcp and Mrp2 were not significantly altered, Mrp3 expression increased and Oatp1a1 decreased in KO animals. Compared with the WT rats, the KO rats had similar serum chemistry and showed normal liver transaminases. Although the total plasma bile salts and bile flow were not significantly changed in Bsep KO rats, individual bile acids in plasma and liver demonstrated variable changes, indicating the impact of Bsep KO. Following an intravenous dose of deuterium labeled taurocholic acid (D4-TCA, 2 mg/kg), the D4-TCA plasma exposure was higher and bile excretion was delayed by approximately 0.5 h in the KO rats. No differences were observed for the pravastatin plasma concentration-time profile or the biliary excretion after intravenous administration (1 mg/kg). Collectively, the results revealed that these rats have significantly lower Bsep expression, therefore affecting the biliary excretion of endogenous bile acids and Bsep substrates. However, these rats are able to maintain a relatively normal liver function through the remaining Bsep protein and via the regulation of other transporters. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Vectorial transport of bile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump.

    PubMed

    Mita, Sachiko; Suzuki, Hiroshi; Akita, Hidetaka; Stieger, Bruno; Meier, Peter J; Hofmann, Alan F; Sugiyama, Yuichi

    2005-01-01

    Bile salts are predominantly taken up by hepatocytes via the basolateral Na(+)-taurocholate cotransporting polypeptide (NTCP/SLC10A1) and secreted into the bile by the bile salt export pump (BSEP/ABCB11). In the present study, we transfected rat Ntcp and rat Bsep into polarized Madin-Darby canine kidney cells and characterized the transport properties of these cells for eight bile salts. Immunohistochemical staining demonstrated that Ntcp was expressed at the basolateral domains, whereas Bsep was expressed at the apical domains. Basal-to-apical transport of taurocholate across the monolayer expressing only Ntcp and that coexpressing Ntcp/Bsep was observed, whereas the flux across the monolayer of control and Bsep-expressing cells was symmetrical. Basal-to-apical transport of taurocholate across Ntcp/Bsep-coexpressing monolayers was significantly higher than that across monolayers expressing only Ntcp. Kinetic analysis of this vectorial transport of taurocholate gave an apparent K(m) value of 13.9 +/- 4.7 microM for cells expressing Ntcp alone, which is comparable with 22.2 +/- 4.5 microM for cells expressing both Ntcp and Bsep and V(max) values of 15.8 +/- 4.2 and 60.8 +/- 9.0 pmol.min(-1).mg protein(-1) for Ntcp alone and Ntcp and Bsep-coexpressing cells, respectively. Transcellular transport of cholate, glycocholate, taurochenodeoxycholate, chenodeoxycholate, glycochenodeoxycholate, tauroursodeoxycholate, ursodeoxycholate, and glycoursodeoxycholate, but not that of lithocholate was also observed across the double transfectant. This double-expressing system can be used as a model to clarify vectorial transport of bile salts across hepatocytes under physiological conditions.

  8. Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells.

    PubMed

    Imagawa, Kazuo; Takayama, Kazuo; Isoyama, Shigemi; Tanikawa, Ken; Shinkai, Masato; Harada, Kazuo; Tachibana, Masashi; Sakurai, Fuminori; Noguchi, Emiko; Hirata, Kazumasa; Kage, Masayoshi; Kawabata, Kenji; Sumazaki, Ryo; Mizuguchi, Hiroyuki

    2017-02-02

    Bile salt export pump (BSEP) plays an important role in hepatic secretion of bile acids and its deficiency results in severe cholestasis and liver failure. Mutation of the ABCB11 gene encoding BSEP induces BSEP deficiency and progressive familial intrahepatic cholestasis type 2 (PFIC2). Because liver transplantation remains standard treatment for PFIC2, the development of a novel therapeutic option is desired. However, a well reproducible model, which is essential for the new drug development for PFIC2, has not been established. Therefore, we attempted to establish a PFIC2 model by using iPSC technology. Human iPSCs were generated from patients with BSEP-deficiency (BD-iPSC), and were differentiated into hepatocyte-like cells (HLCs). In the BD-iPSC derived HLCs (BD-HLCs), BSEP was not expressed on the cell surface and the biliary excretion capacity was significantly impaired. We also identified a novel mutation in the 5'-untranslated region of the ABCB11 gene that led to aberrant RNA splicing in BD-HLCs. Furthermore, to evaluate the drug efficacy, BD-HLCs were treated with 4-phenylbutyrate (4PBA). The membrane BSEP expression level and the biliary excretion capacity in BD-HLCs were rescued by 4PBA treatment. In summary, we succeeded in establishing a PFIC2 model, which may be useful for its pathophysiological analysis and drug development.

  9. Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells

    PubMed Central

    Imagawa, Kazuo; Takayama, Kazuo; Isoyama, Shigemi; Tanikawa, Ken; Shinkai, Masato; Harada, Kazuo; Tachibana, Masashi; Sakurai, Fuminori; Noguchi, Emiko; Hirata, Kazumasa; Kage, Masayoshi; Kawabata, Kenji; Sumazaki, Ryo; Mizuguchi, Hiroyuki

    2017-01-01

    Bile salt export pump (BSEP) plays an important role in hepatic secretion of bile acids and its deficiency results in severe cholestasis and liver failure. Mutation of the ABCB11 gene encoding BSEP induces BSEP deficiency and progressive familial intrahepatic cholestasis type 2 (PFIC2). Because liver transplantation remains standard treatment for PFIC2, the development of a novel therapeutic option is desired. However, a well reproducible model, which is essential for the new drug development for PFIC2, has not been established. Therefore, we attempted to establish a PFIC2 model by using iPSC technology. Human iPSCs were generated from patients with BSEP-deficiency (BD-iPSC), and were differentiated into hepatocyte-like cells (HLCs). In the BD-iPSC derived HLCs (BD-HLCs), BSEP was not expressed on the cell surface and the biliary excretion capacity was significantly impaired. We also identified a novel mutation in the 5′-untranslated region of the ABCB11 gene that led to aberrant RNA splicing in BD-HLCs. Furthermore, to evaluate the drug efficacy, BD-HLCs were treated with 4-phenylbutyrate (4PBA). The membrane BSEP expression level and the biliary excretion capacity in BD-HLCs were rescued by 4PBA treatment. In summary, we succeeded in establishing a PFIC2 model, which may be useful for its pathophysiological analysis and drug development. PMID:28150711

  10. 4-phenylbutyrate enhances the cell surface expression and the transport capacity of wild-type and mutated bile salt export pumps.

    PubMed

    Hayashi, Hisamitsu; Sugiyama, Yuichi

    2007-06-01

    Progressive familial intrahepatic cholestasis type 2 (PFIC2) is caused by a mutation in the bile salt export pump (BSEP/ABCB11) gene. We previously reported that E297G and D482G BSEP, which are frequently found mutations in European patients, result in impaired membrane trafficking, whereas both mutants retain their transport function. The dysfunctional localization is probably attributable to the retention of BSEP in endoplasmic reticulum (ER) followed by proteasomal degradation. Because sodium 4-phenylbutyrate (4PBA) has been shown to restore the reduced cell surface expression of mutated plasma membrane proteins, in the current study, we investigated the effect of 4PBA treatment on E297G and D482G BSEP. Transcellular transport and cell surface biotinylation studies using Madin-Darby canine kidney (MDCK) II cells demonstrated that 4PBA treatment increased functional cell surface expression of wild-type (WT), E297G, and D482G BSEP. The prolonged half-life of cell surface-resident BSEP with 4PBA treatment was responsible for this result. Moreover, treatment of Sprague-Dawley rats with 4PBA resulted in an increase in BSEP expression at the canalicular membrane, which was accompanied by an increase in the biliary excretion of [(3)H]taurocholic acid (TC). 4PBA treatment with a clinically achievable concentration enhances the cell surface expression and the transport capacity of WT, E297G, and D482G BSEP in MDCK II cells, and also induces functional BSEP expression at the canalicular membrane and bile acid transport via canalicular membrane in vivo. 4PBA is a potential pharmacological agent for treating not only PFIC2 patients with E297G and D482G mutations but also other cholestatic patients, in whom the BSEP expression at the canalicular membrane is reduced.

  11. Short- and medium-chain fatty acids enhance the cell surface expression and transport capacity of the bile salt export pump (BSEP/ABCB11).

    PubMed

    Kato, Takuya; Hayashi, Hisamitsu; Sugiyama, Yuichi

    2010-09-01

    The reduced expression of the bile salt export pump (BSEP/ABCB11) at the canalicular membrane is associated with cholestasis-induced hepatotoxicity due to the accumulation of bile acids in hepatocytes. We previously reported that 4-phenylbutyrate (4PBA), an approved drug for urea cycle disorders, is a promising agent for intrahepatic cholestasis because it increases both the cell surface expression and the transport capacity of BSEP. In the present study, we searched for effective compounds other than 4PBA by focusing on short- and medium-chain fatty acids, which have similar characteristics to 4PBA such as their low-molecular-weight and a carboxyl group. In transcellular transport studies using Madin-Darby canine kidney (MDCK) II cells, all short- and medium-chain fatty acids tested except for formate, acetate, and hexanoic acid showed more potent effects on wild type (WT) BSEP-mediated [3H]taurocholate transport than did 4PBA. The increase in WT BSEP transport with butyrate and octanoic acid treatment correlated with an increase in its expression at the cell surface. Two PFIC2-type variants, E297G and D482G BSEP, were similarly affected with both compounds treatment. The prolonged half-life of cell surface-resident WT BSEP was responsible for this increased octanoic acid-stimulated transport, but not for that of butyrate. In conclusion, short- and medium-chain fatty acids have potent effects on the increase in WT and PFIC2-type BSEP-mediated transport in MDCK II cells. Although both short- and medium-chain fatty acids enhance the transport capacity of WT and PFIC2-type BSEP by inducing those expressions at the cell surface, the underlying mechanism seems to differ between fatty acids. 2010 Elsevier B.V. All rights reserved.

  12. Regulation of hepatic bile acid transporters Ntcp and Bsep expression.

    PubMed

    Cheng, Xingguo; Buckley, David; Klaassen, Curtis D

    2007-12-03

    Sodium-taurocholate cotransporting polypeptide (Ntcp) and bile salt export pump (Bsep) are two key transporters for hepatic bile acid uptake and excretion. Alterations in Ntcp and Bsep expression have been reported in pathophysiological conditions. In the present study, the effects of age, gender, and various chemicals on the regulation of these two transporters were characterized in mice. Ntcp and Bsep mRNA levels in mouse liver were low in the fetus, but increased to its highest expression at parturition. After birth, mouse Ntcp and Bsep mRNA decreased by more than 50%, and then gradually increased to adult levels by day 30. Expression of mouse Ntcp mRNA and protein exhibit higher levels in female than male livers. No gender difference exists in BSEP/Bsep expression in human and mouse livers. Hormone replacements conducted in gonadectomized, hypophysectomized, and lit/lit mice indicate that female-predominant Ntcp expression in mouse liver is due to the inhibitory effect of male-pattern GH secretion, but not sex hormones. Ntcp and Bsep expression are in general resistant to induction by a large battery of microsomal enzyme inducers. Administration of cholestyramine increased Ntcp, whereas chenodeoxycholic acid (CDCA) increased Bsep mRNA expression. In conclusion, mouse Ntcp and Bsep are regulated by age, gender, cholestyramine, and bile acid, but resistant to induction by most microsomal enzyme inducers.

  13. Sustained repression and translocation of Ntcp and expression of Mrp4 for cholestasis after rat 90% partial hepatectomy.

    PubMed

    Miura, Takuya; Kimura, Norihisa; Yamada, Toshiyuki; Shimizu, Takeshi; Nanashima, Naoki; Yamana, Daisuke; Hakamada, Kenichi; Tsuchida, Shigeki

    2011-08-01

    To clarify the mechanism of persistent cholestasis after massive hepatectomy, the relationship between such cholestasis and the expression and localization of organic anion transporters for bile acids was examined in a rat model. Male Sprague-Dawley rats were subjected to 90% hepatectomy, and tissues were harvested at 0, 1, 3, and 7 days for microarray analysis, quantitative real-time polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry to examine the expression of multidrug resistance protein 4 (Mrp4), bile salt export pump (Bsep), and sodium-dependent taurocholate cotransporting polypeptide (Ntcp). Persistently elevated levels of serum bile acids were observed at days 3 and 7. RT-PCR and Western blotting indicated that the expression of Mrp4, a bile acid export pump located in the basolateral membrane, was increased at day 3. The expression of Ntcp, a transporter used to uptake bile acids from the sinusoids, was significantly decreased throughout the period. The levels of Bsep, an export pump localized to the canalicular membrane, were unchanged. Immunohistochemistry revealed the localization of Mrp4 and Bsep in the basolateral and canalicular membranes, respectively. On the other hand, at days 3 and 7, Ntcp was localized in the cytoplasm and was hardly detected in the basolateral membrane. These results suggested that the sustained repression and translocation of Ntcp and the expression of Mrp4 at the basolateral membrane seem to be responsible for the high blood bile acids levels after massive hepatectomy. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  14. Vectorial transport of unconjugated and conjugated bile salts by monolayers of LLC-PK1 cells doubly transfected with human NTCP and BSEP or with rat Ntcp and Bsep.

    PubMed

    Mita, Sachiko; Suzuki, Hiroshi; Akita, Hidetaka; Hayashi, Hisamitsu; Onuki, Reiko; Hofmann, Alan F; Sugiyama, Yuichi

    2006-03-01

    Na(+)-taurocholate-cotransporting peptide (NTCP)/SLC10A1 and bile salt export pump (BSEP)/ABCB11 synergistically play an important role in the transport of bile salts by the hepatocyte. In this study, we transfected human NTCP and BSEP or rat Ntcp and Bsep into LLC-PK1 cells, a cell line devoid of bile salts transporters. Transport by these cells was characterized with a focus on substrate specificity between rats and humans. The basal to apical flux of taurocholate across NTCP- and BSEP-expressing LLC-PK1 monolayers was 10 times higher than that in the opposite direction, whereas the flux across the monolayer of control and NTCP or BSEP single-expressing cells did not show any vectorial transport. The basal to apical flux of taurocholate was saturated with a K(m) value of 20 microM. Vectorial transcellular transport was also observed for cholate, chenodeoxycholate, ursodeoxycholate, their taurine and glycine conjugates, and taurodeoxycholate and glycodeoxycholate, whereas no transport of lithocholate was detected. To evaluate the respective functions of NTCP and BSEP and to compare them with those of rat Ntcp and Bsep, we calculated the clearance by each transporter in this system. A good correlation in the clearance of the examined bile salts (cholate, chenodeoxycholate, ursodeoxycholate, and their taurine or glycine conjugates) was observed between transport by human and that of rat transporters in terms of their rank order: for NTCP, taurine conjugates > glycine conjugates > unconjugated bile salts, and for BSEP, unconjugated bile salts and glycine conjugates > taurine conjugates. In conclusion, the substrate specificity of human and rat NTCP and BSEP appear to be very similar at least for monovalent bile salts under physiological conditions.

  15. [Development of new therapeutic strategy for transporter-related diseases].

    PubMed

    Hayashi, Hisamitsu

    2014-01-01

    Significant technological advances in gene sequence analysis and construction of genetically-modified animals during the last two decades made it possible to reveal that many transporters are associated with diseases. The bile salt export pump (BSEP/ABCB11), a member of the family of ATP-binding cassette transporters, is localized on the canalicular membrane of hepatocytes and predominantly mediates the biliary excretion of bile salts. A hereditary defect of BSEP results in severe cholestasis called progressive familial intrahepatic cholestasis type 2 (PFIC2). Without liver transplantation, this disease progresses to liver failure and death before adulthood; therefore the development of new, less invasive medical therapy for PFIC2 is of the highest priority. We have previously shown that in many cases of PFIC2 patients, the dysfunction of BSEP is attributable to decreased BSEP expression on the hepatocanalicular membrane and that 4-phenylbutyrate (4PB), an approved drug for urea cycle disorder, may be a compound with potential to restore BSEP expression. This drug inhibits ubiquitination of cell surface-resident BSEP and thereby its clathrin-mediated endocytosis through the AP2 adaptor complex, leading to increase in BSEP expression on the canalicular membrane. Clinical studies to investigate the efficacy of 4PB in the treatment of PFIC2 revealed that 4PB therapy biochemically and histologically improved liver function without any side effect. Therefore, 4PB therapy may become the preferred choice, instead of liver transplantation, for PFIC2 patients. The strategy employed and findings in this study would be valuable for the drug development of transporter-related disorders.

  16. Detergent Screening and Purification of the Human Liver ABC Transporters BSEP (ABCB11) and MDR3 (ABCB4) Expressed in the Yeast Pichia pastoris

    PubMed Central

    Stindt, Jan; Smits, Sander H. J.; Schmitt, Lutz

    2013-01-01

    The human liver ATP-binding cassette (ABC) transporters bile salt export pump (BSEP/ABCB11) and the multidrug resistance protein 3 (MDR3/ABCB4) fulfill the translocation of bile salts and phosphatidylcholine across the apical membrane of hepatocytes. In concert with ABCG5/G8, these two transporters are responsible for the formation of bile and mutations within these transporters can lead to severe hereditary diseases. In this study, we report the heterologous overexpression and purification of human BSEP and MDR3 as well as the expression of the corresponding C-terminal GFP-fusion proteins in the yeast Pichia pastoris. Confocal laser scanning microscopy revealed that BSEP-GFP and MDR3-GFP are localized in the plasma membrane of P. pastoris. Furthermore, we demonstrate the first purification of human BSEP and MDR3 yielding ∼1 mg and ∼6 mg per 100 g of wet cell weight, respectively. By screening over 100 detergents using a dot blot technique, we found that only zwitterionic, lipid-like detergents such as Fos-cholines or Cyclofos were able to extract both transporters in sufficient amounts for subsequent functional analysis. For MDR3, fluorescence-detection size exclusion chromatography (FSEC) screens revealed that increasing the acyl chain length of Fos-Cholines improved monodispersity. BSEP purified in n-dodecyl-β-D-maltoside or Cymal-5 after solubilization with Fos-choline 16 from P. pastoris membranes showed binding to ATP-agarose. Furthermore, detergent-solubilized and purified MDR3 showed a substrate-inducible ATPase activity upon addition of phosphatidylcholine lipids. These results form the basis for further biochemical analysis of human BSEP and MDR3 to elucidate the function of these clinically relevant ABC transporters. PMID:23593265

  17. Hepatobiliary transporter expression and post-operative jaundice in patients undergoing partial hepatectomy.

    PubMed

    Bernhardt, Gerwin A; Zollner, Gernot; Cerwenka, Herwig; Kornprat, Peter; Fickert, Peter; Bacher, Heinz; Werkgartner, Georg; Müller, Gabriele; Zatloukal, Kurt; Mischinger, Hans-Jörg; Trauner, Michael

    2012-01-01

    Post-operative hyperbilirubinaemia in patients undergoing liver resections is associated with high morbidity and mortality. Apart from different known factors responsible for the development of post-operative jaundice, little is known about the role of hepatobiliary transport systems in the pathogenesis of post-operative jaundice in humans after liver resection. Two liver tissue samples were taken from 14 patients undergoing liver resection before and after Pringle manoeuvre. Patients were retrospectively divided into two groups according to post-operative bilirubin serum levels. The two groups were analysed comparing the results of hepatobiliary transporter [Na-taurocholate cotransporter (NTCP); multidrug resistance gene/phospholipid export pump(MDR3); bile salt export pump (BSEP); canalicular bile salt export pump (MRP2)], heat shock protein 70 (HSP70) expression as well as the results of routinely taken post-operative liver chemistry tests. Patients with low post-operative bilirubin had lower levels of NTCP, MDR3 and BSEP mRNA compared to those with high bilirubin after Pringle manoeuvre. HSP70 levels were significantly higher after ischaemia-reperfusion (IR) injury in both groups resulting in 4.5-fold median increase. Baseline median mRNA expression of all four transporters prior to Pringle manoeuvre tended to be lower in the low bilirubin group whereas expression of HSP70 was higher in the low bilirubin group compared to the high bilirubin group. Higher mRNA levels of HSP70 in the low bilirubin group could indicate a possible protective effect of high HSP70 levels against IR injury. Although the exact role of hepatobiliary transport systems in the development of post-operative hyper bilirubinemia is not yet completely understood, this study provides new insights into the molecular aspects of post-operative jaundice after liver surgery. © 2011 John Wiley & Sons A/S.

  18. In Vitro Drug-Induced Liver Injury Prediction: Criteria Optimization of Efflux Transporter IC50 and Physicochemical Properties.

    PubMed

    Yucha, Robert W; He, Kan; Shi, Qin; Cai, Lining; Nakashita, Yukie; Xia, Cindy Q; Liao, Mingxiang

    2017-06-01

    Drug-induced liver injury (DILI) is a severe drug adverse response, which cannot always be reliably predicted in preclinical or clinical studies. Lack of observation of DILI during preclinical and clinical drug development has led to DILI being a leading cause of drug withdrawal from the market. As DILI is potentially fatal, pharmaceutical companies have been developing in vitro tools to screen for potential liver injury. Screens for physicochemical properties, mitochondrial function, and transport protein inhibition have all been employed to varying degrees of success. In vitro inhibition of the bile salt export pump (BSEP) has become a major risk factor for in vivo DILI predictions, yet discrepancies exist in which methods to use and the extent to which BSEP inhibition predicts clinical DILI. The presented work focuses on optimizing DILI predictions by comparing BSEP inhibition via the membrane vesicle assay and the hepatocyte-based BSEPcyte assay, as well as dual and triple liabilities. BSEP transport inhibition of taurcholic acids and glycocholic acids were similar for up to 29 drugs tested, in both the vesicle and hepatocyte-based assays. Positive and negative DILI predictions were optimized at a 50-µM cutoff value for 50 drugs using both NIH Livertox and PharmaPendium databases. Additionally, dual inhibition of BSEP and other efflux transporters (multidrug resistance-associated protein [MRP]2, MRP3, or MRP4) provided no observable predictive benefit compared with BSEP inhibition alone. Eighty-five percent of drugs with high molecular weight (>600 Da), high cLogP (>3), or a daily dose >100 mg and BSEP inhibition were associated with DILI. Triple liability of BSEP inhibition, high molecular weight, and high cLogP attained a 100% positive prediction rate. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Preliminary study on Emodin alleviating alpha-naphthylisothiocyanate-induced intrahepatic cholestasis by regulation of liver farnesoid X receptor pathway.

    PubMed

    Ding, Yan; Xiong, Xiao-Li; Zhou, Li-Shan; Yan, Su-Qi; Qin, Huan; Li, Hua-Rong; Zhang, Ling-Ling; Chen, Peng; Yao, Cong; Jiang, Zhi-Xia; Zhao, Lei

    2016-12-01

    The aim of this study is to investigate Emodin on alleviating intrahepatic cholestasis by regulation of liver farnesoid X receptor (FXR) pathway. Cell and animal models of intrahepatic cholestatis were established. Biochemical tests and histomorphology were performed. The messenger RNA (mRNA) and protein expression of FXR, small heterodimer partner (SHP), uridine diphosphate glucuronosyltransferase 2 family polypeptide B4 (UGT2B4), and bile salt export pump (BSEP) was detected. As a result, compared with the model group, the serum levels of biochemical test were significantly lower in the Emodin group (P <0.01). The histopathological changes were remitted significantly by Emodin treatment. In the model group, the mRNA and protein expression of FXR, SHP, UGT2B4, and BSEP was significantly lower than in the normal group in cell models (P <0.05). With Emodin intervention, the expression of FXR, SHP, UGT2B4, and BSEP was notably increased (P <0.05). In conclusion, Emodin plays a protective role in intrahepatic cholestasis by promoting FXR signal pathways. © The Author(s) 2016.

  20. Evaluation of the endothelin receptor antagonists ambrisentan, darusentan, bosentan, and sitaxsentan as substrates and inhibitors of hepatobiliary transporters in sandwich-cultured human hepatocytes.

    PubMed

    Hartman, J Craig; Brouwer, Kenneth; Mandagere, Arun; Melvin, Lawrence; Gorczynski, Richard

    2010-06-01

    To evaluate potential mechanisms of clinical hepatotoxicity, 4 endothelin receptor antagonists (ERAs) were examined for substrate activity and inhibition of hepatic uptake and efflux transporters in sandwich-cultured human hepatocytes. The 4 transporters studied were sodium-dependent taurocholate cotransporter (NTCP), organic anion transporter (OATP), bile salt export pump (BSEP), and multidrug resistance-associated protein 2 (MRP2). ERA transporter inhibition was examined using the substrates taurocholate (for NTCP and BSEP), [(3)H]estradiol-17beta-D-glucuronide (for OATP), and [2-D-penicillamine, 5-D-penicillamine]enkephalin (for MRP2). ERA substrate activity was evaluated using probe inhibitors ritonavir (OATP and BSEP), bromosulfalein (OATP), erythromycin (P-glycoprotein), probenecid (MRP2 and OATP), and cyclosporin (NTCP). ERAs were tested at 2, 20, and 100 micromol*L-1 for inhibition and at 2 micromol*L-1 as substrates. OATP, NTCP, or BSEP transport activity was not reduced by ambrisentan or darusentan. Bosentan and sitaxsentan attenuated NTCP transport at higher concentrations. Only sitaxsentan decreased OATP transport (52%), and only bosentan reduced BSEP transport (78%). MRP2 transport activity was unaltered. OATP inhibitors decreased influx of all ERAs. Darusentan influx was least affected (84%-100% of control), whereas bosentan was most affected (32%-58% of control). NTCP did not contribute to influx of ERAs. Only bosentan and darusentan were shown as substrates for both BSEP and P-glycoprotein efflux. All ERAs tested were substrates for at least one hepatic transporter. Bosentan and sitaxsentan, but not ambrisentan and darusentan, inhibited human hepatic transporters, which provides a potential mechanism for the increased hepatotoxicity observed for these agents in the clinical setting.

  1. The inhibition of hepatic bile acids transporters Ntcp and Bsep is involved in the pathogenesis of isoniazid/rifampicin-induced hepatotoxicity.

    PubMed

    Guo, Yao Xue; Xu, Xue Fei; Zhang, Qi Zhi; Li, Chun; Deng, Ye; Jiang, Pei; He, Lei Yan; Peng, Wen Xing

    2015-01-01

    Co-treatment of isoniazid (INH) and rifampicin (RFP) is well known for clinically apparent liver injury. However, the mechanism of INH/RFP-induced liver injury is controversial. Emerging evidence shows links between inhibition of bile acids transporters and drug-induced liver injury (DILI). The present study investigates whether sodium taurocholate cotransporting polypeptide (NTCP/Ntcp; SLC10A1) and bile salt export pump (BSEP/Bsep; ABCB11) are involved in the anti-tuberculosis medicines induced liver injury. ICR female mice were intragastrically treated with INH (50 or 100 mg/kg), RFP (100 or 200 mg/kg), or the combination of INH/RFP (50 + 100 mg/kg or 100 + 200 mg/kg) for 14 consecutive days. Liver histopathological examination, serum biochemical and liver malondialdehyde tests were evaluated. Apparent histopathological alterations and hepatic oxidative stress showed in INH (100 mg/kg), RFP (200 mg/kg) and their combination group. The hepatoxic effect was also indicated by increased serum biomarkers, such as aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin (DBil), total bilirubin (TBil) and total bile acids (TBA). Both doses of INH/RFP administration significantly down-regulated the expression of Ntcp and Bsep in liver. Furthermore, the combination of INH and RFP displayed stronger effect on the expression of Ntcp compared with the corresponding dose of INH or RFP alone. In conclusion, down-regulated expression of hepatic Ntcp and Bsep might play an important role in the development of INH and RFP induced liver injury.

  2. Bipolar and Related Disorders Induced by Sodium 4-Phenylbutyrate in a Male Adolescent with Bile Salt Export Pump Deficiency Disease.

    PubMed

    Vitale, Giovanni; Simonetti, Giulia; Pirillo, Martina; Taruschio, Gianfranco; Andreone, Pietro

    2016-09-01

    Bile Salt Export Pump (BSEP) Deficiency disease, including Progressive Familial Intrahepatic Cholestasis type 2 (PFIC2), is a rare disease, usually leading within the first ten years to portal hypertension, liver failure, hepatocellular carcinoma. Often liver transplantation is needed. Sodium 4-phenylbutyrate (4-PB) seems to be a potential therapeutic compound for PFIC2. Psychiatric side effects in the adolescent population are little known and little studied since the drug used to treat children and infants. So we described a case of Caucasian boy, suffering from a late onset PFIC2, listed for a liver transplant when he was sixteen and treated with 4-FB (200 mg per kilogram of body weight per day). The drug was discontinued for the onset of bipolar and related disorders. This case illustrates possible psychiatric side effects of the drug.

  3. Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

    PubMed

    Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2017-09-01

    The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  4. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Aijie, E-mail: zhangaijie1986@163.com

    Alpha-naphthylisothiocyanate (ANIT) is a toxicant that is widely used in rodents to model human intrahepatic cholestasis. The aim of the study is to investigate whether effects of dioscin on ANIT-induced cholestasis are related to changes in expression of hepatic transporters in rats. Effects of dioscin on cholestasis were examined by histology and biochemical marker levels. The functional changes of hepatic transporters were determined by in vitro, in situ and in vivo. qRT-PCR and western blot were used to assess the expression of hepatic transporters in cholestatic rats. Dioscin administration could ameliorate cholestasis, as evidenced by reduced biochemical markers as wellmore » as improved liver pathology. The uptakes of organic anion transporting polypeptide (Oatp) substrates were altered in liver uptake index in vivo, perfused rat liver in situ and isolated rat hepatocytes in vitro in cholestasis rats. qRT-PCR and western blot analysis indicated co-treatment of ANIT with dioscin prevented the adaptive down-regulation of Oatp1a1, 1b2, and prompted the up-regulation of Oatp1a4, multidrug resistance-associated protein (Mrp) 2 and bile salt export pump (Bsep). In addition, concerted effects on Mrp2 and Bsep occurred through up-regulation of small heterodimer partner by activating farnesoid X receptor. Dioscin might prevent impairment of hepatic function by restoring hepatic transporter expression. - Highlights: • Cholestasis was improved by dioscin via up-regulating the expression of Oatps, Mrp2 and Bsep. • Dioscin regulated Mrp2 and Bsep via activating FXR. • Dioscin may be a candidate drug for the prevention of intrahepatic cholestasis.« less

  5. Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11-/- mouse: transport and gene expression studies.

    PubMed

    Wang, Renxue; Liu, Lin; Sheps, Jonathan A; Forrest, Dana; Hofmann, Alan F; Hagey, Lee R; Ling, Victor

    2013-08-15

    The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice (abcb11-/-) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11-/- mice. Feeding UDCA to abcb11-/- mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11-/- mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11-/- mice. UDCA fed to abcb11-/- mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11-/- mice.

  6. Feline hepatic biotransformation of diazepam: Differences between cats and dogs.

    PubMed

    van Beusekom, Cyrina D; van den Heuvel, Jeroen J M W; Koenderink, Jan B; Russel, Frans G M; Schrickx, Johannes A

    2015-12-01

    In contrast to humans and dogs, diazepam has been reported to induce severe hepatic side effects in cats, particularly after repeated dosing. With the aim to elucidate the mechanisms underlying this apparent sensitivity of cats to drug-induced liver injury, in a series of in vitro experiments, the feline-specific biotransformation of diazepam was studied with liver microsomes obtained from cats and dogs and the possible inhibition of the bile salt export pump (Bsep) was measured in isolated membrane vesicles overexpressing feline and canine Bsep. In line with previous in vivo studies, the phase I metabolites nordiazepam, temazepam and oxazepam were measurable in microsomal incubations, although enzyme velocity of demethylases and hydroxylases differed significantly between cats and dogs. In cats, the main metabolite was temazepam, which also could be glucuronidated. In contrast to dogs, no other glucuronidated metabolites could be observed. In addition, in the membrane vesicles an inhibition of the transport of the Bsep substrate taurocholic acid could be observed in the presence of diazepam and its metabolites. It was concluded that both mechanisms, the slow biotransformation of diazepam as well the inhibition of the bile acid efflux that results in an accumulation of bile acids in the hepatocytes, seem to contribute to the liver injury observed in cats following repetitive treatment with diazepam. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Effect of Yin-Zhi-Huang on up-regulation of Oatp2, Ntcp, and Mrp2 proteins in estrogen-induced rat cholestasis.

    PubMed

    Zhang, Guoqiang; Zhou, Yan; Rao, Zhi; Qin, Hongyan; Wei, Yuhui; Ren, Jiangxia; Zhou, Liting; Wu, Xin'an

    2015-03-01

    Yin-Zhi-Huang (YZH), a prescription of traditional Chinese medicine, is widely used to treat neonatal jaundice or cholestasis. This study investigates the regulatory effect of YZH on the localization and expression of organic anion transporting polypeptides 2 (Oatp2), Na(+)-taurocholate co-transporting polypeptide (Ntcp), multidrug-resistance-associated protein 2 (Mrp2), and bile salt export pump (Bsep) in estrogen-induced cholestasis rats. Cholestasis model rats were induced via subcutaneous injection of estradiol benzoate (EB, 5 mg/kg/d) for 5 d. Other EB-induced rats were treated with saline (2 ml) or YZH (1.5 g/kg, two times a day) for 7, 14, and 21 d. The biochemical and pathologic examinations were performed. Moreover, the localization and expression of Oatp2, Ntcp, Mrp2, and Bsep were determined by immunohistochemisty and Western blotting, respectively. YZH treatment could significantly decrease the serum total bile acids (TBA) (4.9 ± 0.6-2.8 ± 0.8) and direct bilirubin (DBIL) (2.6 ± 0.7-1.0 ± 0.1) levels, improve the histological disorganization, and, respectively, increase the expression of Oatp2 and Ntcp by 46% and 28% compared with saline-treated (p < 0.05) rats at 14 d. The expression of Mrp2 increased by 45% was observed in YZH treated compared with saline-treated (p < 0.05) rats at 7 d. However, there was a little change in the expression of Bsep (p > 0.05) after YZH treatment for 7, 14, and 21 d. In conclusion, the therapeutic effect of YZH to cholestasis could be attributed to the regulation of Oatp2, Ntcp, Mrp2, and Bsep.

  8. A novel ABCB11 mutation in an Iranian girl with progressive familial intrahepatic cholestasis

    PubMed Central

    Saber, Sassan; Vazifehmand, Reza; Bagherizadeh, Iman; Kasiri, Mahbubeh

    2013-01-01

    Progressive familial intrahepatic cholestasis is an autosomal recessive liver disorder caused by (biallelic) mutations in the ATP8B1 of ABCB11 gene. A nine-year-old girl with cholestasis was referred for genetic counseling. She had a family history of cholestasis in two previous expired siblings. Genetic analysis of the ABCB11 gene led to the identification of a novel homozygous mutation in exon 25. The mutation 3593- A > G lead to a missense mutation at the amino acid level (His1198Arg). This mutation caused PFIC2 due to abnormal function in the bile salt export pump protein (BSEP). PMID:24339557

  9. Ku proteins function as corepressors to regulate farnesoid X receptor-mediated gene expression

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohno, Masae; Kunimoto, Masaaki; Nishizuka, Makoto

    2009-12-18

    The farnesoid X receptor (FXR; NR1H4) is a member of the nuclear receptor superfamily and regulates the expression of genes involved in enterohepatic circulation and the metabolism of bile acids. Based on functional analyses, nuclear receptors are divided into regions A-F. To explore the cofactors interacting with FXR, we performed a pull-down assay using GST-fused to the N-terminal A/B region and the C region, which are required for the ligand-independent transactivation and DNA-binding, respectively, of FXR, and nuclear extracts from HeLa cells. We identified DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Ku80, and Ku70 as FXR associated factors. These proteins aremore » known to have an important role in DNA repair, recombination, and transcription. DNA-PKcs mainly interacted with the A/B region of FXR, whereas the Ku proteins interacted with the C region and with the D region (hinge region). Chromatin immunoprecipitation assays revealed that the Ku proteins associated with FXR on the bile salt export pump (BSEP) promoter. Furthermore, we demonstrated that ectopic expression of the Ku proteins decreased the promoter activity and expression of BSEP gene mediated by FXR. These results suggest that the Ku proteins function as corepressors for FXR.« less

  10. Paeoniflorin ameliorates cholestasis via regulating hepatic transporters and suppressing inflammation in ANIT-fed rats.

    PubMed

    Zhao, Yanling; He, Xuan; Ma, Xiao; Wen, Jianxia; Li, Pengyan; Wang, Jiabo; Li, Ruisheng; Zhu, Yun; Wei, Shizhang; Li, Haotian; Zhou, Xuelin; Li, Kun; Liu, Honghong; Xiao, Xiaohe

    2017-05-01

    Paeoniflorin has shown the obvious effect on cholestasis according to our previous research. However, its mechanism has not been absolutely explored yet. This study aims at evaluating the potential effect of paeoniflorin on alpha-naphthylisothiocyanate (ANIT) -induced cholestasis by inhibiting nuclear factor kappa-B (NF-κB) and simultaneously regulating hepatocyte transporters. Cholestasis was induced by administration of ANIT. The effect of paeoniflorin on serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GT), total bile acid (TBA) and histopathology of liver were determined. Liver protein levels of NF-κB, interleukin 1β (IL-1β) and the hepatocyte transporters such as Na + /taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2) and cholesterol 7α-hydroxylase (Cyp7a1) were investigated by western blotting. The results demonstrated that paeoniflorin could decrease serum ALT, AST, ALP, γ-GT, TBIL, DBIL and TBA in ANIT-treated rats. Histological examination revealed that rats treated with paeoniflorin represented fewer neutrophils infiltration, edema and necrosis in liver tissue compared with ANIT rats. Moreover, paeoniflorin significantly reduced the over expressions of NF-κB and IL-1β induced by ANIT in liver tissue. In addition, the relative protein expressions of NTCP, BSEP, MRP2 but not Cyp7a1 were also restored by paeoniflorin. The potential mechanism of paeoniflorin in alleviating ANIT-induced cholestasis seems to be related to reduce the over expressions of NF-κB and hepatocyte transporters such as NTCP, BSEP as well as MRP2. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Direct methylation of FXR by Set7/9, a lysine methyltransferase, regulates the expression of FXR target genes

    PubMed Central

    Balasubramaniyan, Natarajan; Ananthanarayanan, Meena

    2012-01-01

    The farnesoid X receptor (FXR) is a ligand (bile acid)-dependent nuclear receptor that regulates target genes involved in every aspect of bile acid homeostasis. Upon binding of ligand, FXR recruits an array of coactivators and associated proteins, some of which have intrinsic enzymatic activity that modify histones or even components of the transcriptional complex. In this study, we show chromatin occupancy by the Set7/9 methyltransferase at the FXR response element (FXRE) and direct methylation of FXR in vivo and in vitro at lysine 206. siRNA depletion of Set7/9 in the Huh-7 liver cell line decreased endogenous mRNAs of the FXR target genes, the short heterodimer partner (SHP) and bile salt export pump (BSEP). Mutation of the methylation site at K206 of FXR to an arginine prevented methylation by Set7/9. A pan-methyllysine antibody recognized the wild-type FXR but not the K206R mutant form. An electromobility shift assay showed that methylation by Set7/9 enhanced binding of FXR/retinoic X receptor-α to the FXRE. Interaction between hinge domain of FXR (containing K206) and Set7/9 was confirmed by coimmunoprecipitation, GST pull down, and mammalian two-hybrid experiments. Set7/9 overexpression in Huh-7 cells significantly enhanced transactivation of the SHP and BSEP promoters in a ligand-dependent fashion by wild-type FXR but not the K206R mutant FXR. A Set7/9 mutant deficient in methyltransferase activity was also not effective in increasing transactivation of the BSEP promoter. These studies demonstrate that posttranslational methylation of FXR by Set7/9 contributes to the transcriptional activation of FXR-target genes. PMID:22345554

  12. Multiple alterations of canalicular membrane transport activities in rats with CCl(4)-induced hepatic injury.

    PubMed

    Song, Im-Sook; Lee, Young-Mi; Chung, Suk-Jae; Shim, Chang-Koo

    2003-04-01

    The influence of CCl(4)-induced experimental hepatic injury (CCl(4)-EHI) on the expression and transport activities of primary active transporters on the canalicular membrane, including P-glycoprotein (P-gp), a bile salt export pump (Bsep) and a multidrug resistance associated protein2 (Mrp2), was assessed. CCl(4)-EHI was induced by an intraperitoneal injection of CCl(4) to rats at a dose of 1 ml/kg 24 h prior to the preparation of canalicular liver plasma membrane (cLPM) vesicles and pharmacokinetic studies. The expression of each transporter was measured for the vesicles via Western blot analysis at 6, 12, 24, 36, and 48 h after the injection of CCl(4). The in vivo canalicular excretion clearance (CL(exc)) of [(3)H]daunomycin, [(3)H]taurocholate and [(3)H]17beta-estradiol-17beta-D-glucuronide (E(2)17betaG), representative substrates of P-gp, Bsep, and Mrp2, respectively, was determined following an i.v. infusion to rats. The uptake of each substrate into cLPM vesicles in the presence of ATP was also measured by a rapid filtration technique. As the result of the CCl(4)-EHI, the protein level of transporters was altered as a function of time in multiple manners; it was increased by 3.6-fold for P-gp, unchanged for Bsep, and decreased by 73% for Mrp2 at 24 h. The in vivo CL(exc) and the intrinsic uptake clearance into cLPM vesicles (CL(int)) at 24 h after the CCl(4) injection (CCl(4)-EHI(24 h)) were also influenced by the EHI in a similar manner; they were increased by 1.8- and 1.9-fold for daunomycin, unchanged for taurocholate, and decreased by 41 and 39% for E(2)17betaG, respectively, consistent with multiple alterations in the expression of the relevant transporters.

  13. [A 22-year-old mother with severe pruritus and increasing jaundice two weeks after starting hormonal contraception].

    PubMed

    Guth, C; Beuers, U; Beckh, K

    2016-09-01

    Intermittent cholestatic liver disease may indicate an inherited deficiency of bile salt transport proteins. Episodes of cholestasis may start during pregnancy or during use of oral contraceptives or other medication. We describe the case of a 22-year-old mother with increasing jaundice and severe pruritus two weeks after starting hormonal contraception. A few months before she was suffering from intrahepatic cholestasis of pregnancy (ICP). Liver biopsy showed bland cholestasis with canalicular bile plugs. Treatment with ursodeoxycholic acid was not effective. Finally, rifampicin induced a complete remission of the cholestasis. Genetic testing showed a heterozygous mutation in the ABCB11 gene encoding the bile salt export pump (BSEP). Rifampicin activates nuclear receptors and may induce alternative pathways for the excretion of bile salts in patients with ABCB11 deficiency. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals.

    PubMed

    Aleo, Michael D; Shah, Falgun; He, Kan; Bonin, Paul D; Rodrigues, A David

    2017-05-15

    The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most-DILI-concern and 55 of No-DILI-concern). Of these tested, 41% of Most-DILI-concern and 47% of No-DILI-concern drugs had MDR3 IC 50 values of <50 μM. A better distinction across DILI classifications occurred when systemic exposure was considered where safety margins of 50-fold had low sensitivity (0.29), but high specificity (0.96). Analysis of physical chemical property space showed that basic compounds were twice as likely to be MDR3 inhibitors as acids, neutrals, and zwitterions and that inhibitors were more likely to have polar surface area (PSA) values of <100 Å 2 and cPFLogD values between 1.5 and 5. These descriptors, with different cutoffs, also highlighted a group of compounds that shared dual potency as MDR3 and BSEP inhibitors. Nine drugs classified as Most-DILI-concern compounds (four withdrawn, four boxed warning, and one liver injury warning in their approved label) had intrinsic potency features of <20 μM in both assays, thereby reinforcing the notion that multiple inhibitory mechanisms governing bile formation (bile acid and phospholipid efflux) may confer additional risk factors that play into more severe forms of DILI as shown by others for BSEP inhibitors combined with multidrug resistance-associated protein (MRP2, MRP3, MRP4) inhibitory properties. Avoiding physical property descriptors that highlight dual BSEP and MDR3 inhibition or testing drug candidates for inhibition of multiple efflux transporters (e.g., BSEP, MDR3, and MRPs) may be an effective strategy for prioritizing drug candidates with less likelihood of causing clinical DILI.

  15. Differential inhibition of rat and human Na+-dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1)by bosentan: a mechanism for species differences in hepatotoxicity.

    PubMed

    Leslie, Elaine M; Watkins, Paul B; Kim, Richard B; Brouwer, Kim L R

    2007-06-01

    Bile acid accumulation in hepatocytes due to inhibition of the canalicular bile salt export pump (BSEP/ABCB11) has been proposed as a mechanism for bosentan-induced hepatotoxicity. The observation that bosentan does not induce hepatotoxicity in rats, although bosentan has been reported to inhibit rat Bsep and cause elevated serum bile acids, challenges this mechanism. The lack of hepatotoxicity could be explained if bosentan inhibited hepatocyte uptake as well as canalicular efflux of bile acids. In the current study, bosentan was found to be a more potent inhibitor of Na(+)-dependent taurocholate uptake in rat (IC(50) 5.4 microM) than human (IC(50) 30 microM) suspended hepatocytes. In addition, bosentan was a more potent inhibitor of taurocholate uptake by rat Na(+)-dependent taurocholate co-transporting polypeptide (Ntcp/Slc10a1) (IC(50) 0.71 microM) than human NTCP (SLC10A1) (IC(50) 24 microM) expressed in HEK293 cells. Thus, bosentan is a more potent inhibitor of Ntcp than NTCP, and this should result in less intrahepatocyte accumulation of bile acids in rats during bosentan treatment. To begin characterization of this species difference, two chimeric molecules were generated and expressed in HEK293 cells; NTCP(1-140)/Ntcp(141-362) and Ntcp(1-140)/NTCP(141-349). The mode of bosentan inhibition was noncompetitive for Ntcp, and competitive for NTCP (K(i) 18 microM) and NTCP(1-140)/Ntcp(141-362) (K(i) 1.7 microM); bosentan affected both the K(m) and V(max) of Ntcp(1-140)/NTCP(141-349) (K(i) 7.0 microM). The carboxyl portions of NTCP and Ntcp were found to confer species differences in basal taurocholate transport V(max). In conclusion, differential inhibition of Ntcp and NTCP may represent a novel mechanism for species differences in bosentan-induced hepatotoxicity.

  16. Transporter Expression in Liver Tissue from Subjects with Alcoholic or Hepatitis C Cirrhosis Quantified by Targeted Quantitative Proteomics

    PubMed Central

    Wang, Li; Collins, Carol; Kelly, Edward J.; Chu, Xiaoyan; Ray, Adrian S.; Salphati, Laurent; Xiao, Guangqing; Lee, Caroline; Lai, Yurong; Liao, Mingxiang; Mathias, Anita; Evers, Raymond; Humphreys, William; Hop, Cornelis E. C. A.; Kumer, Sean C.

    2016-01-01

    Although data are available on the change of expression/activity of drug-metabolizing enzymes in liver cirrhosis patients, corresponding data on transporter protein expression are not available. Therefore, using quantitative targeted proteomics, we compared our previous data on noncirrhotic control livers (n = 36) with the protein expression of major hepatobiliary transporters, breast cancer resistance protein (BCRP), bile salt export pump (BSEP), multidrug and toxin extrusion protein 1 (MATE1), multidrug resistance–associated protein (MRP)2, MRP3, MRP4, sodium taurocholate–cotransporting polypeptide (NTCP), organic anion–transporting polypeptides (OATP)1B1, 1B3, 2B1, organic cation transporter 1 (OCT1), and P-glycoprotein (P-gp) in alcoholic (n = 27) and hepatitis C cirrhosis (n = 30) livers. Compared with control livers, the yield of membrane protein from alcoholic and hepatitis C cirrhosis livers was significantly reduced by 56 and 67%, respectively. The impact of liver cirrhosis on transporter protein expression was transporter-dependent. Generally, reduced protein expression (per gram of liver) was found in alcoholic cirrhosis livers versus control livers, with the exception that the expression of MRP3 was increased, whereas no change was observed for MATE1, MRP2, OATP2B1, and P-gp. In contrast, the impact of hepatitis C cirrhosis on protein expression of transporters (per gram of liver) was diverse, showing an increase (MATE1), decrease (BSEP, MRP2, NTCP, OATP1B3, OCT1, and P-gp), or no change (BCRP, MRP3, OATP1B1, and 2B1). The expression of hepatobiliary transporter protein differed in different diseases (alcoholic versus hepatitis C cirrhosis). Finally, incorporation of protein expression of OATP1B1 in alcoholic cirrhosis into the Simcyp physiologically based pharmacokinetics cirrhosis module improved prediction of the disposition of repaglinide in liver cirrhosis patients. These transporter expression data will be useful in the future to predict transporter-mediated drug disposition in liver cirrhosis patients. PMID:27543206

  17. ABCB4 missense mutations D243A, K435T, G535D, I490T, R545C, and S978P significantly impair the lipid floppase and likely predispose to secondary pathologies in the human population.

    PubMed

    Andress, Edward J; Nicolaou, Michael; McGeoghan, Farrell; Linton, Kenneth J

    2017-07-01

    Bile salts are natural detergents required to solubilise dietary fat and lipid soluble vitamins. They are synthesised in hepatocytes and secreted into the luminal space of the biliary tree by the bile salt export pump (BSEP), an ATP-binding cassette (ABC) transporter in the canalicular membrane. BSEP deficiency causes cytotoxic accumulation of bile salts in the hepatocyte that results in mild-to-severe forms of cholestasis. The resulting inflammation can also progress to hepatocellular cancer via a novel mechanism involving upregulation of proliferative signalling pathways. A second ABC transporter of the canalicular membrane is also critical for bile formation. ABCB4 flops phosphatidylcholine into the outer leaflet of the membrane to be extracted by bile salts in the canalicular space. These mixed micelles reduce the detergent action of the bile salts and protect the biliary tree from their cytotoxic activity. ABCB4 deficiency also causes cholestasis, and might be expected to cause cholangitis and predispose to liver cancer. Non-synonymous SNPs in ABCB4 have now been described in patients with liver cancer or with inflammatory liver diseases that are known to predispose to cancer, but data showing that the SNPs are sufficiently deleterious to be an etiological factor are lacking. Here, we report the first characterisation at the protein level of six ABCB4 variants (D243A, K435T, G535D, I490T, R545C, and S978P) previously found in patients with inflammatory liver diseases or liver cancer. All significantly impair the transporter with a range of phenotypes exhibited, including low abundance, intracellular retention, and reduced floppase activity, suggesting that ABCB4 deficiency is the root cause of the pathology in these cases.

  18. Regulation of Plasma Membrane Localization of the Na+-Taurocholate Cotransporting Polypeptide (Ntcp) by Hyperosmolarity and Tauroursodeoxycholate*

    PubMed Central

    Sommerfeld, Annika; Mayer, Patrick G. K.; Cantore, Miriam; Häussinger, Dieter

    2015-01-01

    In perfused rat liver, hepatocyte shrinkage induces a Fyn-dependent retrieval of the bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2) from the canalicular membrane (Cantore, M., Reinehr, R., Sommerfeld, A., Becker, M., and Häussinger, D. (2011) J. Biol. Chem. 286, 45014–45029) leading to cholestasis. However little is known about the effects of hyperosmolarity on short term regulation of the Na+-taurocholate cotransporting polypeptide (Ntcp), the major bile salt uptake system at the sinusoidal membrane of hepatocytes. The aim of this study was to analyze hyperosmotic Ntcp regulation and the underlying signaling events. Hyperosmolarity induced a significant retrieval of Ntcp from the basolateral membrane, which was accompanied by an activating phosphorylation of the Src kinases Fyn and Yes but not of c-Src. Hyperosmotic internalization of Ntcp was sensitive to SU6656 and PP-2, suggesting that Fyn mediates Ntcp retrieval from the basolateral membrane. Hyperosmotic internalization of Ntcp was also found in livers from wild-type mice but not in p47phox knock-out mice. Tauroursodeoxycholate (TUDC) and cAMP reversed hyperosmolarity-induced Fyn activation and triggered re-insertion of the hyperosmotically retrieved Ntcp into the membrane. This was associated with dephosphorylation of the Ntcp on serine residues. Insertion of Ntcp by TUDC was sensitive to the integrin inhibitory hexapeptide GRGDSP and inhibition of protein kinase A. TUDC also reversed the hyperosmolarity-induced retrieval of bile salt export pump from the canalicular membrane. These findings suggest a coordinated and oxidative stress- and Fyn-dependent retrieval of sinusoidal and canalicular bile salt transport systems from the corresponding membranes. Ntcp insertion was also identified as a novel target of β1-integrin-dependent TUDC action, which is frequently used in the treatment of cholestatic liver disease. PMID:26306036

  19. Regulation of plasma membrane localization of the Na+-taurocholate cotransporting polypeptide (Ntcp) by hyperosmolarity and tauroursodeoxycholate.

    PubMed

    Sommerfeld, Annika; Mayer, Patrick G K; Cantore, Miriam; Häussinger, Dieter

    2015-10-02

    In perfused rat liver, hepatocyte shrinkage induces a Fyn-dependent retrieval of the bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2) from the canalicular membrane (Cantore, M., Reinehr, R., Sommerfeld, A., Becker, M., and Häussinger, D. (2011) J. Biol. Chem. 286, 45014-45029) leading to cholestasis. However little is known about the effects of hyperosmolarity on short term regulation of the Na(+)-taurocholate cotransporting polypeptide (Ntcp), the major bile salt uptake system at the sinusoidal membrane of hepatocytes. The aim of this study was to analyze hyperosmotic Ntcp regulation and the underlying signaling events. Hyperosmolarity induced a significant retrieval of Ntcp from the basolateral membrane, which was accompanied by an activating phosphorylation of the Src kinases Fyn and Yes but not of c-Src. Hyperosmotic internalization of Ntcp was sensitive to SU6656 and PP-2, suggesting that Fyn mediates Ntcp retrieval from the basolateral membrane. Hyperosmotic internalization of Ntcp was also found in livers from wild-type mice but not in p47(phox) knock-out mice. Tauroursodeoxycholate (TUDC) and cAMP reversed hyperosmolarity-induced Fyn activation and triggered re-insertion of the hyperosmotically retrieved Ntcp into the membrane. This was associated with dephosphorylation of the Ntcp on serine residues. Insertion of Ntcp by TUDC was sensitive to the integrin inhibitory hexapeptide GRGDSP and inhibition of protein kinase A. TUDC also reversed the hyperosmolarity-induced retrieval of bile salt export pump from the canalicular membrane. These findings suggest a coordinated and oxidative stress- and Fyn-dependent retrieval of sinusoidal and canalicular bile salt transport systems from the corresponding membranes. Ntcp insertion was also identified as a novel target of β1-integrin-dependent TUDC action, which is frequently used in the treatment of cholestatic liver disease. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Hepatic 3D spheroid models for the detection and study of compounds with cholestatic liability

    PubMed Central

    Hendriks, Delilah F. G.; Fredriksson Puigvert, Lisa; Messner, Simon; Mortiz, Wolfgang; Ingelman-Sundberg, Magnus

    2016-01-01

    Drug-induced cholestasis (DIC) is poorly understood and its preclinical prediction is mainly limited to assessing the compound’s potential to inhibit the bile salt export pump (BSEP). Here, we evaluated two 3D spheroid models, one from primary human hepatocytes (PHH) and one from HepaRG cells, for the detection of compounds with cholestatic liability. By repeatedly co-exposing both models to a set of compounds with different mechanisms of hepatotoxicity and a non-toxic concentrated bile acid (BA) mixture for 8 days we observed a selective synergistic toxicity of compounds known to cause cholestatic or mixed cholestatic/hepatocellular toxicity and the BA mixture compared to exposure to the compounds alone, a phenomenon that was more pronounced after extending the exposure time to 14 days. In contrast, no such synergism was observed after both 8 and 14 days of exposure to the BA mixture for compounds that cause non-cholestatic hepatotoxicity. Mechanisms behind the toxicity of the cholestatic compound chlorpromazine were accurately detected in both spheroid models, including intracellular BA accumulation, inhibition of ABCB11 expression and disruption of the F-actin cytoskeleton. Furthermore, the observed synergistic toxicity of chlorpromazine and BA was associated with increased oxidative stress and modulation of death receptor signalling. Combined, our results demonstrate that the hepatic spheroid models presented here can be used to detect and study compounds with cholestatic liability. PMID:27759057

  1. Pinelliae Rhizoma Praeparatum Involved in the Regulation of Bile Acids Metabolism in Hepatic Injury.

    PubMed

    Guo, Shun; Zhang, Song; Liu, Linna; Yang, Peng; Dang, Xueliang; Wei, Huamei; Hu, Na; Shi, Lei; Zhang, Yan

    2018-06-01

    Pinelliae Rhizoma Praeparatum (PRP) as traditional Chinese medicine had been used for hepatic diseases in combinative forms. However, the effect of PRP was not clear when used alone. So to explore the hepatoprotective/hepatotoxin of PRP is necessary. The activities of PRP were investigated in acetaminophen-induced hepatic injury mice. Liver function markers, hepatic oxidative stress markers were evaluated. Bile acids metabolic transports and nuclear factor erythroid 2-related factor 2 (Nrf2) were detected. As a drug for the treatment of liver diseases, PRP slightly restored the parameters towards normal in model mice only in low dosage, and also had no antioxidant activity and regulate Nrf2. Cholestasis was significantly elevated in model mice when pretreatment with routine or high dosage of PRP, but had no effect on normal mice. Bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2) in model mice were markedly increased when pretreatment with low dose PRP, but significantly decreased when pretreatment in routine or high dosage. Mrp3 was significantly induced in model mice after pretreatment of PRP. But the adjustment effect to bile acids transporters by PRP was not significant in normal mice. These results reveal that PRP has the different effects on bile acids transporter in hepatic injury mice, and therefore, the dosage of PRP need to be paid attention to when it is used in clinical hepatic injury.

  2. Minimizing DILI risk in drug discovery - A screening tool for drug candidates.

    PubMed

    Schadt, S; Simon, S; Kustermann, S; Boess, F; McGinnis, C; Brink, A; Lieven, R; Fowler, S; Youdim, K; Ullah, M; Marschmann, M; Zihlmann, C; Siegrist, Y M; Cascais, A C; Di Lenarda, E; Durr, E; Schaub, N; Ang, X; Starke, V; Singer, T; Alvarez-Sanchez, R; Roth, A B; Schuler, F; Funk, C

    2015-12-25

    Drug-induced liver injury (DILI) is a leading cause of acute hepatic failure and a major reason for market withdrawal of drugs. Idiosyncratic DILI is multifactorial, with unclear dose-dependency and poor predictability since the underlying patient-related susceptibilities are not sufficiently understood. Because of these limitations, a pharmaceutical research option would be to reduce the compound-related risk factors in the drug-discovery process. Here we describe the development and validation of a methodology for the assessment of DILI risk of drug candidates. As a training set, 81 marketed or withdrawn compounds with differing DILI rates - according to the FDA categorization - were tested in a combination of assays covering different mechanisms and endpoints contributing to human DILI. These include the generation of reactive metabolites (CYP3A4 time-dependent inhibition and glutathione adduct formation), inhibition of the human bile salt export pump (BSEP), mitochondrial toxicity and cytotoxicity (fibroblasts and human hepatocytes). Different approaches for dose- and exposure-based calibrations were assessed and the same parameters applied to a test set of 39 different compounds. We achieved a similar performance to the training set with an overall accuracy of 79% correctly predicted, a sensitivity of 76% and a specificity of 82%. This test system may be applied in a prospective manner to reduce the risk of idiosyncratic DILI of drug candidates. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Lipid flopping in the liver.

    PubMed

    Linton, Kenneth J

    2015-10-01

    Bile is synthesized in the liver and is essential for the emulsification of dietary lipids and lipid-soluble vitamins. It is a complex mixture of amphiphilic bile acids (BAs; which act as detergent molecules), the membrane phospholipid phosphatidylcholine (PC), cholesterol and a variety of endogenous metabolites and waste products. Over the last 20 years, the combined effort of clinicians, geneticists, physiologists and biochemists has shown that each of these bile components is transported across the canalicular membrane of the hepatocyte by its own specific ATP-binding cassette (ABC) transporter. The bile salt export pump (BSEP) ABCB11 transports the BAs and drives bile flow from the liver, but it is now clear that two lipid transporters, ABCB4 (which flops PC into the bile) and the P-type ATPase ATP8B1/CDC50 (which flips a different phospholipid in the opposite direction) play equally critical roles that protect the biliary tree from the detergent activity of the bile acids. Understanding the interdependency of these lipid floppases and flippases has allowed the development of an assay to measure ABCB4 function. ABCB4 harbours numerous mis-sense mutations which probably reflects the spectrum of liver disease rooted in ABCB4 aetiology. Characterization of the effect of these mutations at the protein level opens the possibility for the development of personalized prognosis and treatment. © 2015 Authors; published by Portland Press Limited.

  4. Bistable electroactive polymer for refreshable Braille display with improved actuation stability

    NASA Astrophysics Data System (ADS)

    Niu, Xiaofan; Brochu, Paul; Stoyanov, Hristiyan; Yun, Sung Ryul; Pei, Qibing

    2012-04-01

    Poly(t-butyl acrylate) is a bistable electroactive polymer (BSEP) capable of rigid-to-rigid actuation. The BSEP combines the large-strain actuation of dielectric elastomers with shape memory property. We have introduced a material approach to overcome pull-in instability in poly(t-butyl acrylate) that significantly improves the actuation lifetime at strains greater than 100%. Refreshable Braille display devices with size of a smartphone screen have been fabricated to manifest a potential application of the BSEP. We will report the testing results of the devices by a Braille user.

  5. Quantifying the Physical Response to a Contemporary Amateur Boxing Simulation.

    PubMed

    Finlay, Mitchell J; Greig, Matt; Page, Richard M

    2018-04-01

    Finlay, MJ, Greig, M, and Page, RM. Quantifying the physical response to a contemporary amateur boxing simulation. J Strength Cond Res 32(4): 1005-1012, 2018-This study examined the physical response to a contemporary boxing-specific exercise protocol (BSEP), based on notational analysis of amateur boxing. Nine male senior elite amateur boxers completed a 3 × 3-minute BSEP, with a 1-minute passive recovery period interspersing each round. Average (HRave) and peak (HRpeak) heart rates, average (V[Combining Dot Above]O2ave) and peak oxygen consumptions (V[Combining Dot Above]O2peak), blood lactate (BLa) concentrations, rating of perceived exertion, and both triaxial and uniaxial PlayerLoad metrics were recorded during the completion of the BSEP. Blood lactate concentration increased significantly in each round (Round 1 = 2.4 ± 1.3 mmol·L; Round 2 = 3.3 ± 1.7 mmol·L; Round 3 = 4.3 ± 2.6 mmol·L). Significantly lower HRave and HRpeak values were found in the first round (HRave: 150 ± 15 b·min; HRpeak: 162 ± 12 b·min) when compared with the second (HRave: 156 ± 16 b·min; HRpeak: 166 ± 13 b·min) and third (HRave: 150 ± 15 b·min; HRpeak: 169 ± 14 b·min). No significant differences were found in any of the V[Combining Dot Above]O2 or PlayerLoad metrics recorded during the BSEP. The BSEP based on notational analysis elicited a fatigue response across rounds, confirming its validity. The BSEP can be used as a training tool for boxing-specific conditioning with implications for reduced injury risk, and to assess the physical response to boxing-specific interventions. Moreover, the BSEP can also be manipulated to suit all levels of participants or training phases, with practical applications in performance monitoring and microcycle periodization.

  6. Bistable electroactive polymers (BSEP): large-strain actuation of rigid polymers

    NASA Astrophysics Data System (ADS)

    Yu, Zhibin; Niu, Xiaofan; Brochu, Paul; Yuan, Wei; Li, Huafeng; Chen, Bin; Pei, Qibing

    2010-04-01

    Reversible, large-strain, bistable actuation has been a lasting puzzle in the pursuit of smart materials and structures. Conducting polymers are bistable, but the achievable strain is small. Large deformations have been achieved in dielectric elastomers at the expense of mechanical strength. The gel or gel-like soft polymers generally have elastic moduli around or less than 10 MPa. The deformed polymer relaxes to its original shape once the applied electric field is removed. We report new, bistable electroactive polymers (BSEP) that are capable of electrically actuated strains as high as 335% area strain. The BSEP could be useful for constructing rigid structures. The structures can support high mechanical loads, and be actuated to large-strain deformations. We will present one unique application of the BSEP for Braille displays that can be quickly refreshed and maintain the displayed contents without a bias voltage.

  7. Refreshable tactile displays based on bistable electroactive polymer

    NASA Astrophysics Data System (ADS)

    Niu, Xiaofan; Brochu, Paul; Salazar, Brandon; Pei, Qibing

    2011-04-01

    Refreshable tactile displays can significantly improve the education of blind children and the quality of life of people with severe vision impairment. A number of actuator technologies have been investigated. Bistable Electroactive Polymer (BSEP) appears to be well suited for this application. The BSEP exhibits a bistable electrically actuated strain as large as 335%. We present improved refreshable tactile display devices fabricated on thin plastic sheets. Stacked BSEP films were employed to meet the requirements in raised dot height and supporting force. The bistable nature of the actuation reduces the power consumption and simplifies the device operation.

  8. Mechanisms of canalicular transporter endocytosis in the cholestatic rat liver.

    PubMed

    Miszczuk, Gisel S; Barosso, Ismael R; Larocca, María Cecilia; Marrone, Julieta; Marinelli, Raúl A; Boaglio, Andrea C; Sánchez Pozzi, Enrique J; Roma, Marcelo G; Crocenzi, Fernando A

    2018-04-01

    Impaired canalicular secretion due to increased endocytosis and intracellular retention of canalicular transporters such as BSEP and MRP2 is a main, common pathomechanism of cholestasis. Nevertheless, the mechanisms governing this process are unknown. We characterized this process in estradiol 17 β-d-glucuronide (E17G)-induced cholestasis, an experimental model which partially mimics pregnancy-induced cholestasis. Inhibitors of clathrin-mediated endocytosis (CME) such as monodansylcadaverine (MDC) or K + depletion, but not the caveolin-mediated endocytosis inhibitors filipin and genistein, prevented E17G-induced endocytosis of BSEP and MRP2, and the associated impairment of activity of these transporters in isolated rat hepatocyte couplets (IRHC). Immunofluorescence and confocal microscopy studies showed that, in E17G-treated IRHC, there was a significant increase in the colocalization of MRP2 with clathrin, AP2, and Rab5, three essential members of the CME machinery. Knockdown of AP2 by siRNA in sandwich-cultured rat hepatocytes completely prevented E17G-induced endocytosis of BSEP and MRP2. MDC significantly prevented this endocytosis, and the impairment of bile flow and biliary secretion of BSEP and MRP2 substrates, in isolated and perfused livers. BSEP and MRP2, which were mostly present in raft (caveolin-enriched) microdomains in control rats, were largely found in non-raft (clathrin-enriched) microdomains in livers from E17G-treated animals, from where they can be readily recruited for CME. In conclusion, our findings show that CME is the mechanism responsible for the internalization of the canalicular transporters BSEP and MRP2 in E17G-induced cholestasis. The shift of these transporters from raft to non-raft microdomains could be a prerequisite for the transporters to be endocytosed under cholestatic conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Xenobiotic Nuclear Receptor Signaling Determines Molecular Pathogenesis of Progressive Familial Intrahepatic Cholestasis.

    PubMed

    Kim, Kang Ho; Choi, Jong Min; Li, Feng; Arizpe, Armando; Wooton-Kee, Clavia Ruth; Anakk, Sayeepriyadarshini; Jung, Sung Yun; Finegold, Milton J; Moore, David D

    2018-06-01

    Progressive familial intrahepatic cholestasis (PFIC) is a genetically heterogeneous disorder of bile flow disruption due to abnormal canalicular transport or impaired bile acid (BA) metabolism, causing excess BA accumulation and liver failure. We previously reported an intrahepatic cholestasis mouse model based on loss of function of both farnesoid X receptor (FXR; NR1H4) and a small heterodimer partner (SHP; NR0B2) [double knockout (DKO)], which has strong similarities to human PFIC5. We compared the pathogenesis of DKO livers with that of another intrahepatic cholestasis model, Bsep-/-, which represents human PFIC2. Both models exhibit severe hepatomegaly and hepatic BA accumulation, but DKO showed greater circulating BA and liver injury, and Bsep-/- had milder phenotypes. Molecular profiling of BAs uncovered specific enrichment of cholic acid (CA)-derived BAs in DKO livers but chenodeoxycholate-derived BAs in Bsep-/- livers. Transcriptomic and proteomic analysis revealed specific activation of CA synthesis and alternative basolateral BA transport in DKO but increased chenodeoxycholic acid synthesis and canalicular transport in Bsep-/-. The constitutive androstane receptor (CAR)/pregnane X receptor (PXR)-CYP2B/CYP2C axis is activated in DKO livers but not in other cholestasis models. Loss of this axis in Fxr:Shp:Car:Pxr quadruple knockouts blocked Cyp2b/Cyp2c gene induction, impaired bilirubin conjugation/elimination, and increased liver injury. Differential CYP2B expression in DKO and Bsep-/- was recapitulated in human PFIC5 and PFIC2 livers. In conclusion, loss of FXR/SHP results in distinct molecular pathogenesis and CAR/PXR activation, which promotes Cyp2b/Cyp2c gene transcription and bilirubin clearance. CAR/PXR activation was not observed in Bsep-/- mice or PFIC2 patients. These findings provide a deeper understanding of the heterogeneity of intrahepatic cholestasis.

  10. Enhancing Young Graduates' Intention towards Entrepreneurship Development in Malaysia

    ERIC Educational Resources Information Center

    Mohamed, Zainalabidin; Rezai, Golnaz; Shamsudin, Mad Nasir; Mahmud, Muhammad Mu'az

    2012-01-01

    Purpose: The purpose of this paper is to evaluate the effectiveness of the Basic Student Entrepreneurial Programme (BSEP) among local university graduates who have undergone the training programme in entrepreneurship development. Design/methodology/approach: In total, 410 respondents who had participated in BSEP were interviewed with a structural…

  11. Zooplankton fecal pellets, marine snow, phytodetritus and the ocean's biological pump

    NASA Astrophysics Data System (ADS)

    Turner, Jefferson T.

    2015-01-01

    The 'biological pump' is the process by which photosynthetically-produced organic matter in the ocean descends from the surface layer to depth by a combination of sinking particles, advection or vertical mixing of dissolved organic matter, and transport by animals. Particulate organic matter that is exported downward from the euphotic zone is composed of combinations of fecal pellets from zooplankton and fish, organic aggregates known as 'marine snow' and phytodetritus from sinking phytoplankton. Previous reviews by Turner and Ferrante (1979) and Turner (2002) focused on publications that appeared through late 2001. Since that time, studies of the biological pump have continued, and there have been >300 papers on vertical export flux using sediment traps, large-volume filtration systems and other techniques from throughout the global ocean. This review will focus primarily on recent studies that have appeared since 2001. Major topics covered in this review are (1) an overview of the biological pump, and its efficiency and variability, and the role of dissolved organic carbon in the biological pump; (2) zooplankton fecal pellets, including the contribution of zooplankton fecal pellets to export flux, epipelagic retention of zooplankton fecal pellets due to zooplankton activities, zooplankton vertical migration and fecal pellet repackaging, microbial ecology of fecal pellets, sinking velocities of fecal pellets and aggregates, ballasting of sinking particles by mineral contents, phytoplankton cysts, intact cells and harmful algae toxins in fecal pellets, importance of fecal pellets from various types of zooplankton, and the role of zooplankton fecal pellets in picoplankton export; (3) marine snow, including the origins, abundance, and distributions of marine snow, particles and organisms associated with marine snow, consumption and fragmentation of marine snow by animals, pathogens associated with marine snow; (4) phytodetritus, including pulsed export of phytodetritus, phytodetritus from Phaeocystis spp., picoplankton in phytodetritus, the summer export pulse (SEP) of phytodetritus in the subtropical North Pacific, benthic community responses to phytodetritus; (5) other components of the biological pump, including fish fecal pellets and fish-mediated export, sinking carcasses of animals and macrophytes, feces from marine mammals, transparent exopolymer particles (TEP); (6) the biological pump and climate, including origins of the biological pump, the biological pump and glacial/interglacial cycles, the biological pump and contemporary climate variations, and the biological pump and anthropogenic climate change. The review concludes with potential future modifications in the biological pump due to climate change.

  12. New Directions in the Army's Basic Skills Education Program (BSEP).

    ERIC Educational Resources Information Center

    Pilgrim, Mark T.

    The Army has given to the Training and Doctrine Command the task of developing four Basic Skills Education Program (BSEP) curricula to provide functional, job-related basic skills training. These would be Military Occupational Specialty (MOS) Baseline Skills, English-as-a-Second Language (ESL), Military Life Coping Skills, and Learning Strategies.…

  13. Progressive familial intrahepatic cholestasis type 1.

    PubMed

    Paulusma, Coen C; Elferink, Ronald P J Oude; Jansen, Peter L M

    2010-05-01

    Progressive familial intrahepatic cholestasis type 1 is a rare genetic liver disease that presents in the first year of life. Bile salts are elevated and these patients are often jaundiced. Despite the cholestasis, serum gamma-glutamyltransferase activity is normal or reduced. Pruritus is a major symptom in these patients. Partial external biliary diversion is helpful in several patients as it reduces the pruritus and postpones or even avoids liver transplantation. The disease is caused by mutations in the gene ATP8B1 that preclude the normal expression of ATP8B1. ATP8B1 is a protein that acts as a lipid flippase, transporting phosphatidylserine from the exoplasmic to the cytoplasmic leaflet of the canalicular membrane of hepatocytes. The authors have shown that the canalicular membrane of ATP8B1-deficient hepatocytes is less stable as evidenced by enhanced extraction of membrane constituents by bile salts. Recent evidence suggests membrane instability in ATP8B1-deficient hair cells of the ear, providing an explanation for hearing loss in ATP8B1 deficiency. Although the exact etiology of cholestasis is incompletely understood, it is hypothesized that ATP8B1 deficiency results in enhanced cholesterol extraction from the canalicular membrane, which impairs the function of the bile salt export pump (BSEP), resulting in cholestasis. Mutations in ATP8B1 also cause benign recurrent intrahepatic cholestasis, a milder variant of the disease characterized by episodes of cholestasis. The onset and resolution of the cholestatic episodes in these patients is still not well understood.

  14. Spatial Patterns in the Efficiency of the Biological Pump: What Controls Export Ratios at the Global Scale?

    NASA Astrophysics Data System (ADS)

    Moore, J. K.

    2016-02-01

    The efficiency of the biological pump is influenced by complex interactions between chemical, biological, and physical processes. The efficiency of export out of surface waters and down through the water column to the deep ocean has been linked to a number of factors including biota community composition, production of mineral ballast components, physical aggregation and disaggregation processes, and ocean oxygen concentrations. I will examine spatial patterns in the export ratio and the efficiency of the biological pump at the global scale using the Community Earth System Model (CESM). There are strong spatial variations in the export efficiency as simulated by the CESM, which are strongly correlated with new nutrient inputs to the euphotic zone and their impacts on phytoplankton community structure. I will compare CESM simulations that include dynamic, variable export ratios driven by the phytoplankton community structure, with simulations that impose a near-constant export ratio to examine the effects of export efficiency on nutrient and surface chlorophyll distributions. The model predicted export ratios will also be compared with recent satellite-based estimates.

  15. The export and fate of organic matter in the ocean: New constraints from combining satellite and oceanographic tracer observations

    NASA Astrophysics Data System (ADS)

    DeVries, Tim; Weber, Thomas

    2017-03-01

    The ocean's biological pump transfers carbon from the surface euphotic zone into the deep ocean, reducing the atmospheric CO2 concentration. Despite its climatic importance, there are large uncertainties in basic metrics of the biological pump. Previous estimates of the strength of the biological pump, as measured by the amount of organic carbon exported from the euphotic zone, range from about 4 to 12 Pg C yr-1. The fate of exported carbon, in terms of how efficiently it is transferred into the deep ocean, is even more uncertain. Here we present a new model of the biological pump that assimilates satellite and oceanographic tracer observations to constrain rates and patterns of organic matter production, export, and remineralization in the ocean. The data-assimilated model predicts a global particulate organic carbon (POC) flux out of the euphotic zone of ˜9 Pg C yr-1. The particle export ratio (the ratio of POC export to net primary production) is highest at high latitudes and lowest at low latitudes, but low-latitude export is greater than predicted by previous models, in better agreement with observed patterns of long-term carbon export. Particle transfer efficiency (Teff) through the mesopelagic zone is controlled by temperature and oxygen, with highest Teff for high-latitude regions and oxygen minimum zones. In contrast, Teff in the deep ocean (below 1000 m) is controlled by particle sinking speed, with highest deep ocean Teff below the subtropical gyres. These results emphasize the utility of both remote sensing and oceanographic tracer observations for constraining the operation of the biological pump.

  16. Use and engineering of efflux pumps for the export of olefins in microbes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mukhopadhyay, Aindrila

    2016-07-14

    The scope of the project is to investigate efflux pump systems in engineered host microorganisms, such as E. coli, and develop a pump engineered to export a target compound. To initiate the project in coordination with other TOTAL driven projects, the first target compound to be studied was 1-hexene. However, we were investigating other chemicals as Styrene. The main goal of the project was to generate a set of optimized efflux pump systems for microorganisms (E. coli and Streptomyces or other host) engineered to contain biosynthetic pathways to export large titers of target compounds that are toxic (or accumulate andmore » push back biosynthesis) to the host cell. An optimized microbial host will utilize specific and efficient cell wall located pumps to extrude harmful target compounds and enable greater production of these compounds.« less

  17. Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine

    PubMed Central

    Weerachayaphorn, Jittima; Mennone, Albert; Soroka, Carol J.; Harry, Kathy; Hagey, Lee R.; Kensler, Thomas W.

    2012-01-01

    The transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a key regulator for induction of hepatic detoxification and antioxidant mechanisms, as well as for certain hepatobiliary transporters. To examine the role of Nrf2 in bile acid homeostasis and cholestasis, we assessed the determinants of bile secretion and bile acid synthesis and transport before and after bile duct ligation (BDL) in Nrf2−/− mice. Our findings indicate reduced rates of biliary bile acid and GSH excretion, higher levels of intrahepatic bile acids, and decreased expression of regulators of bile acid synthesis, Cyp7a1 and Cyp8b1, in Nrf2−/− compared with wild-type control mice. The mRNA expression of the bile acid transporters bile salt export pump (Bsep) and organic solute transporter (Ostα) were increased in the face of impaired expression of the multidrug resistance-associated proteins Mrp3 and Mrp4. Deletion of Nrf2 also decreased ileal apical sodium-dependent bile acid transporter (Asbt) expression, leading to reduced bile acid reabsorption and increased loss of bile acid in feces. Finally, when cholestasis is induced by BDL, liver injury was not different from that in wild-type BDL mice. These Nrf2−/− mice also had increased pregnane X receptor (Pxr) and Cyp3a11 mRNA expression in association with enhanced hepatic bile acid hydroxylation. In conclusion, this study finds that Nrf2 plays a major role in the regulation of bile acid homeostasis in the liver and intestine. Deletion of Nrf2 results in a cholestatic phenotype but does not augment liver injury following BDL. PMID:22345550

  18. Synthesizing A Phase Changing Bistable Electroactive Polymer And Silver Nanoparticles Coated Fabric As A Resistive Heating Element

    NASA Astrophysics Data System (ADS)

    Ren, Zhi

    Transducer technologies that convert energy from one form to another (e.g. electrical energy to mechanical energy or thermal energy and vise versa) are considered as the basic building blocks of robots and wearable electronics, two of the rapidly emerging technologies that impact our daily life. With an emphasis on developing the essential smart materials, this dissertation focuses on two specific transducer technologies, bistable large-strain electro-mechanical actuation and resistive Joule heating, in pursuit of refreshable Braille electronic displays and wearable thermal management element, respectively. Dielectric elastomers (DEs) have been intensively studied for their promising ability to mimic human muscles in providing efficient electro-mechanical actuation. They exhibit a unique combination of properties, including large strain, fast response, high energy density, mechanical compliancy, lightweight, and low cost. However, the softness of the DE materials, which is a prerequisite for electrically induced large actuation strain, has been hindering their application in adaptive structures. In these applications such as braille displays, a certain amount of mechanical support is necessary in addition to large strains for the device or system to function. Bistable electroactive polymers (BSEP) that leverage the electrically induced large-strain actuation of DE actuators and the bi-stable rigid-to-rigid deformation of shape memory polymers are innovated to provide large electrical actuation strain in their rubbery state and fix the deformation by cooling down to room temperature to incorporate mechanical rigidity. BSEP materials that can suppress electromechanical instability and exhibit stable mechanical properties in the rubbery state are desired. A bimodal BSEP material with a glass transition temperature right above room temperature has been synthesized employing simple UV curing process. The BSEP has a large storage modulus over 1GPa at room temperature that decreases to several MPa at above 70°C after a rigid-to-rubbery transition via glass transition. The rubbery BSEP possesses a stable storage modulus regardless of temperature fluctuations, which is beneficial to stable electrical actuation performances under an electric field. The bimodal structure creates a framework involving both long chain crosslinkers and small molecular crosslinkers. Due to the limited chain extensibility of this bimodal framework, the rubbery BSEP can self-stiffen at modest strains to suppress electromechanical instability, which is responsible for the premature electrical breakdown of the previous BSEP materials in their rubbery states. A BSEP actuator with a braille dot size exhibits steadily increased actuation height with increasing electric field at 70 °C. A stable actuation with a cycle lifetime of over 2000 cycles at a raised dot height of 0.4 mm was demonstrated. A fabrication process for a page-size braille paper using the BSEP has been developed. A selective heating strategy has been investigated based on a 2-cell device to provide a selective actuation strategy of BSEP braille dots. Wearable thermal management strategy has presented itself recently as a new challenge to offer an optimal thermal experience for the occupant as well as to reduce building energy usage for heating, ventilation and air conditioning (HVAC). Joule heating based on silver nanoparticles (AgNPs) coated non-woven fabric can provide a wearable localized heating element.A sheet resistance of <0.3 ohm/square can be achieved for AgNPs-coated polyester fabrics upon thermal annealing. Multistep electroless deposition creates chemical bonding between oxygen groups on the fabrics' surface and AgNPs. As a result, the bonding between the AgNPs layer and the polyester fabrics is strong enough to resist sonication damage. The resistance only increased slightly after an 80minutes of sonication and therefore the AgNPs-polyester fabrics composite are regarded as washable. The AgNPs coated polyester fabrics was employed as a heating element. A voltage as low as 1volt is adequate to heat up the AgNPs-polyester fabrics to 60 °C in 2 seconds. The heat can be dissipated away fast after turning off the heating voltage, due to the mesh structure of the AgNPs-polyester fabrics. The strategy of the wearable heater can potentially play influential roles in energy saving and consumer experience in a localized thermal management system. (Abstract shortened by ProQuest.).

  19. Mesoscale eddies drive increased silica export in the subtropical Pacific Ocean.

    PubMed

    Benitez-Nelson, Claudia R; Bidigare, Robert R; Dickey, Tommy D; Landry, Michael R; Leonard, Carrie L; Brown, Susan L; Nencioli, Francesco; Rii, Yoshimi M; Maiti, Kanchan; Becker, Jamie W; Bibby, Thomas S; Black, Wil; Cai, Wei-Jun; Carlson, Craig A; Chen, Feizhou; Kuwahara, Victor S; Mahaffey, Claire; McAndrew, Patricia M; Quay, Paul D; Rappé, Michael S; Selph, Karen E; Simmons, Melinda P; Yang, Eun Jin

    2007-05-18

    Mesoscale eddies may play a critical role in ocean biogeochemistry by increasing nutrient supply, primary production, and efficiency of the biological pump, that is, the ratio of carbon export to primary production in otherwise nutrient-deficient waters. We examined a diatom bloom within a cold-core cyclonic eddy off Hawaii. Eddy primary production, community biomass, and size composition were markedly enhanced but had little effect on the carbon export ratio. Instead, the system functioned as a selective silica pump. Strong trophic coupling and inefficient organic export may be general characteristics of community perturbation responses in the warm waters of the Pacific Ocean.

  20. TRADOC Evaluation - Basic Skills Education Program. Phase I, BSEP I. Revised

    DTIC Science & Technology

    1980-06-11

    typographical errors. The original text (blue cover) should be de- stroyed. o-!3 3 C )>4 FOR THE COMMANDER: E N_ R 1 Incl R. N. WA. as. Colonel, GS...Summary. . . i I. Purpose 1 - 1I. Historical Background ................. 2 I1. Identification of BSEP I Eligibles .... ........... 4 IV. Program...a’ Avail aid/or Dist spec & I FOReMM Since World War 1 , differing standards have been used at various times in determining eligibility for enlistment

  1. Formative Evaluation of an Adaptation of the Feuerstein Instrumental Enrichment Program in the US Army Basic Skills Education Program (BSEP II)

    DTIC Science & Technology

    1984-10-01

    87 ix CONTENTS (Continued) Page APPENDIX D. COGNITIVE SKILLS TEST ....... ................... .. 98 E. CLASSROOM OBSERVATION FORM...You arrzive ac tine, but nobody is at the c2ub. Vhy? (Give a possible explanaztion.) APPENDIX E Classroom Observation Form 106 B.&SIC ERLLS ED-:UCA1O...gains to be expected, researchers observed classroom instruction in each IE BSEP cycle at Fort Knox. (See Appendix E for a copy of the Classroom

  2. Plankton networks driving carbon export in the oligotrophic ocean

    PubMed Central

    Larhlimi, Abdelhalim; Roux, Simon; Darzi, Youssef; Audic, Stephane; Berline, Léo; Brum, Jennifer; Coelho, Luis Pedro; Espinoza, Julio Cesar Ignacio; Malviya, Shruti; Sunagawa, Shinichi; Dimier, Céline; Kandels-Lewis, Stefanie; Picheral, Marc; Poulain, Julie; Searson, Sarah; Stemmann, Lars; Not, Fabrice; Hingamp, Pascal; Speich, Sabrina; Follows, Mick; Karp-Boss, Lee; Boss, Emmanuel; Ogata, Hiroyuki; Pesant, Stephane; Weissenbach, Jean; Wincker, Patrick; Acinas, Silvia G.; Bork, Peer; de Vargas, Colomban; Iudicone, Daniele; Sullivan, Matthew B.; Raes, Jeroen; Karsenti, Eric; Bowler, Chris; Gorsky, Gabriel

    2015-01-01

    The biological carbon pump is the process by which CO2 is transformed to organic carbon via photosynthesis, exported through sinking particles, and finally sequestered in the deep ocean. While the intensity of the pump correlates with plankton community composition, the underlying ecosystem structure driving the process remains largely uncharacterised. Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve our understanding of carbon export in the oligotrophic ocean. We show that specific plankton communities, from the surface and deep chlorophyll maximum, correlate with carbon export at 150 m and highlight unexpected taxa such as Radiolaria, alveolate parasites, as well as Synechococcus and their phages, as lineages most strongly associated with carbon export in the subtropical, nutrient-depleted, oligotrophic ocean. Additionally, we show that the relative abundance of just a few bacterial and viral genes can predict most of the variability in carbon export in these regions. PMID:26863193

  3. Plankton networks driving carbon export in the oligotrophic ocean

    NASA Astrophysics Data System (ADS)

    2016-04-01

    The biological carbon pump is the process by which CO2 is transformed to organic carbon via photosynthesis, exported through sinking particles, and finally sequestered in the deep ocean. While the intensity of the pump correlates with plankton community composition, the underlying ecosystem structure driving the process remains largely uncharacterized. Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve our understanding of carbon export in the oligotrophic ocean. We show that specific plankton communities, from the surface and deep chlorophyll maximum, correlate with carbon export at 150 m and highlight unexpected taxa such as Radiolaria and alveolate parasites, as well as Synechococcus and their phages, as lineages most strongly associated with carbon export in the subtropical, nutrient-depleted, oligotrophic ocean. Additionally, we show that the relative abundance of a few bacterial and viral genes can predict a significant fraction of the variability in carbon export in these regions.

  4. Plankton networks driving carbon export in the oligotrophic ocean

    NASA Astrophysics Data System (ADS)

    Guidi, L.; Chaffron, S.; Bittner, L.; Eveillard, D.; Raes, J.; Karsenti, E.; Bowler, C.; Gorsky, G.

    2016-02-01

    The biological carbon pump is the process by which CO2 is transformed to organic carbon via photosynthesis that sinks to the deep ocean as particles where it is sequestered. While the intensity of the pump correlates with plankton community composition, the underlying ecosystem structure and interactions driving the process remain largely uncharacterised. Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve our understanding of the underlying processes. We show that specific plankton communities correlate with carbon export and highlight unexpected and overlooked taxa such as Radiolaria, alveolate parasites, as well as Synechococcus and their phages, as lineages most strongly associated with carbon export in the subtropical oligotrophic ocean. Additionally, we show that the relative abundance of just a few bacterial and viral genes can predict most of the variability in carbon export in these regions. Together these results help elucidate ecosystem drivers of the biological carbon pump and present a case study for scaling from genes-to-ecosystems.

  5. Engineering microbial biofuel tolerance and export using efflux pumps

    PubMed Central

    Dunlop, Mary J; Dossani, Zain Y; Szmidt, Heather L; Chu, Hou Cheng; Lee, Taek Soon; Keasling, Jay D; Hadi, Masood Z; Mukhopadhyay, Aindrila

    2011-01-01

    Many compounds being considered as candidates for advanced biofuels are toxic to microorganisms. This introduces an undesirable trade-off when engineering metabolic pathways for biofuel production because the engineered microbes must balance production against survival. Cellular export systems, such as efflux pumps, provide a direct mechanism for reducing biofuel toxicity. To identify novel biofuel pumps, we used bioinformatics to generate a list of all efflux pumps from sequenced bacterial genomes and prioritized a subset of targets for cloning. The resulting library of 43 pumps was heterologously expressed in Escherichia coli, where we tested it against seven representative biofuels. By using a competitive growth assay, we efficiently distinguished pumps that improved survival. For two of the fuels (n-butanol and isopentanol), none of the pumps improved tolerance. For all other fuels, we identified pumps that restored growth in the presence of biofuel. We then tested a beneficial pump directly in a production strain and demonstrated that it improved biofuel yields. Our findings introduce new tools for engineering production strains and utilize the increasingly large database of sequenced genomes. PMID:21556065

  6. Investigations of the total flavonoids extracted from flowers of Abelmoschus manihot (L.) Medic against α-naphthylisothiocyanate-induced cholestatic liver injury in rats.

    PubMed

    Yan, Jia-Yin; Ai, Guo; Zhang, Xiao-Jian; Xu, Hai-Jiang; Huang, Zheng-Ming

    2015-08-22

    The decoction of the flowers of Abelmoschus manihot (L.) Medic was traditionally used for the treatment of jaundice and various types of chronic and acute hepatitis in Anhui and Jiangsu Provinces of China for hundreds of years. Phytochemical studies have indicated that total flavonoids extracted from flowers of A. manihot (L.) Medic (TFA) were the major constituents of the flowers. Our previous studies have investigated the hepatoprotective effects of the TFA against carbon tetrachloride (CCl4) induced hepatocyte damage in vitro and liver injury in vivo. This study aimed to investigate the protective effects and mechanisms of TFA on α-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury in rats. The hepatoprotective activities of TFA (125, 250 and 500mg/kg) were investigated on ANIT-induced cholestatic liver injury in rats. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were used as indices of hepatic cell damage and measured. Meanwhile, the serum levels of alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA) were used as indices of biliary cell damage and cholestasis and evaluated. Hepatic malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione transferase (GST), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were measured in the liver homogenates. The bile flow in 4h was estimated and the histopathology of the liver tissue was evaluated. Furthermore, the expression of transporters, bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and Na(+)-taurocholate cotransporting polypeptide (NTCP) were studied by western blot and reverse transcription-quantitative real-time polymerase chain reaction (RT-PCR) to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. The oral administration of TFA to ANIT-treated rats could reduce the increases in serum levels of ALT, AST, LDH, ALP, GGT, TBIL, DBIL and TBA. Decreased bile flow by ANIT was restored with TFA treatment. Concurrent administration of TFA reduced the severity of polymorphonuclear neutrophil infiltration and other histological damages, which were consistent with the serological tests. Hepatic MDA and GSH contents in liver tissue were reduced, while SOD and GST activities, which had been suppressed by ANIT, were elevated in the groups pretreated with TFA. With TFA intervention, levels of TNF-α and NO in liver were decreased. Additionally, TFA was found to increase the expression of liver BSEP, MRP2, and NTCP in both protein and mRNA levels in ANIT-induced liver injury with cholestasis. TFA exerted protective effects against ANIT-induced liver injury. The possible mechanisms could be related to anti-oxidative damage, anti-inflammation and regulating the expression of hepatic transporters. It layed the foundation for the further research on the mechanisms of cholestasis as well as the therapeutic effects of A. manihot (L.) Medic for the treatment of jaundice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Large-strain, rigid-to-rigid deformation of bistable electroactive polymers

    NASA Astrophysics Data System (ADS)

    Yu, Zhibin; Yuan, Wei; Brochu, Paul; Chen, Bin; Liu, Zhitian; Pei, Qibing

    2009-11-01

    Thermoplastic poly(tert-butyl acrylate) (PTBA) is reported as an electroactive polymer that is rigid at ambient conditions and turns into a dielectric elastomer above a transition temperature. In the rubbery state, a PTBA thin film can be electrically actuated to strains up to 335% in area expansion. The calculated actuation pressure is 3.2 MPa. The actuation is made bistable by cooling to below glass transition temperature. The PTBA represents the bistable electroactive polymer (BSEP) that can be actuated to various largely strained, rigid shapes. The application of the BSEP for refreshable Braille display, an active tactile display, is also demonstrated.

  8. Dielectric Actuation of Polymers

    NASA Astrophysics Data System (ADS)

    Niu, Xiaofan

    Dielectric polymers are widely used in a plurality of applications, such as electrical insulation, dielectric capacitors, and electromechanical actuators. Dielectric polymers with large strain deformations under an electric field are named dielectric elastomers (DE), because of their relative low modulus, high elongation at break, and outstanding resilience. Dielectric elastomer actuators (DEA) are superior to traditional transducers as a muscle-like technology: large strains, high energy densities, high coupling efficiency, quiet operation, and light weight. One focus of this dissertation is on the design of DE materials with high performance and easy processing. UV radiation curing of reactive species is studied as a generic synthesis methodology to provide a platform for material scientists to customize their own DE materials. Oligomers/monomers, crosslinkers, and other additives are mixed and cured at appropriate ratios to control the stress-strain response, suppress electromechanical instability of the resulting polymers, and provide stable actuation strains larger than 100% and energy densities higher than 1 J/g. The processing is largely simplified in the new material system by removal of the prestretching step. Multilayer stack actuators with 11% linear strain are demonstrated in a procedure fully compatible with industrial production. A multifunctional DE derivative material, bistable electroactive polymer (BSEP), is invented enabling repeatable rigid-to-rigid deformation without bulky external structures. Bistable actuation allows the polymer actuator to have two distinct states that can support external load without device failure. Plasticizers are used to lower the glass transition temperature to 45 °C. Interpenetrating polymer network structure is established inside the BSEP to suppress electromechanical instability, providing a breakdown field of 194 MV/m and a stable bistable strain as large as 228% with a 97% strain fixity. The application of BSEP in tactile display is investigated by the prototyping of a large scale refreshable Braille display device. Braille is a critical way for the vision impaired community to learn literacy and improve life quality. Current piezoelectrics-based refreshable Braille display technologies are limited to up to 1 line of Braille text, due to the bulky size of bimorph actuators. Based on the unique actuation feature of BSEP, refreshable Braille display devices up to smartphone-size have been demonstrated by polymer sheet laminates. Dots in the devices can be individually controlled via incorporated field-driven BSEP actuators and Joule heater units. A composite material consisting of silver nanowires (AgNW) embedded in a polymer substrate is brought up as a compliant electrode candidate for BSEP application. The AgNW composite is highly conductive (Rs: 10 Ω/sq) and remains conductive at strains as high as 140% (Rs: <10 3 Ω/sq). The baseline conductivity has only small changes up to 90% strain, which makes it low enough for both field driving and stretchable Joule heating. An out-of-plane bistable area strain up to 68% under Joule heating is achieved.

  9. A new bistable electroactive polymer for prolonged cycle lifetime of refreshable Braille displays

    NASA Astrophysics Data System (ADS)

    Ren, Zhi; Niu, Xiaofan; Chen, Dustin; Hu, Wei; Pei, Qibing

    2014-03-01

    ABSTRACT: Bistable electroactive polymers (BSEP) amalgamating electrically induced large-strain actuation and shape memory effect present a unique opportunity for refreshable Braille displays. A new BSEP material with long-chain crosslinkers to achieve prolonged cycle lifetime of refreshable Braille displays is reported here. The modulus of the BSEP material decreases by more than three orders of magnitude from a rigid, plastic state to a rubbery state when heated above the polymer's glass transition temperature. In its rubbery state, the polymer film can be electrically actuated to buckle convexly when a high voltage is applied across a circular active area. Modifying the concentration of long-chain crosslinkers in the polymer allows not only for fine-tuning of the polymer's glass transition temperature and elasticity in the rubbery state, but also enhancement of the actuation stability. For a raised height of 0.4 mm by a Braille dot with a 1.3 mm diameter, actuation can be repeated over 2000 cycles at 70°C in the rubbery state. The actuated dome shape can be fixed by cooling the polymer below the glass transition temperature. This refreshable rigid-to-rigid actuation simultaneously provides large-strain actuation and large force support. Devices capable of displaying Braille characters over a page-size area consisting of 324 Braille cells have been fabricated.

  10. The dynamic ocean biological pump: Insights from a global compilation of particulate organic carbon, CaCO3, and opal concentration profiles from the mesopelagic

    NASA Astrophysics Data System (ADS)

    Lam, Phoebe J.; Doney, Scott C.; Bishop, James K. B.

    2011-09-01

    We have compiled a global data set of 62 open ocean profiles of particulate organic carbon (POC), CaCO3, and opal concentrations collected by large volume in situ filtration in the upper 1000 m over the last 30 years. We define concentration-based metrics for the strength (POC concentration at depth) and efficiency (attenuation of POC with depth in the mesopelagic) of the biological pump. We show that the strength and efficiency of the biological pump are dynamic and are characterized by a regime of constant and high transfer efficiency at low to moderate surface POC and a bloom regime where the height of the bloom is characterized by a weak deep biological pump and low transfer efficiency. The variability in POC attenuation length scale manifests in a clear decoupling between the strength of the shallow biological pump (e.g., POC at the export depth) and the strength of the deep biological pump (POC at 500 m). We suggest that the paradigm of diatom-driven export production is driven by a too restrictive perspective on upper mesopelagic dynamics. Indeed, our full mesopelagic analysis suggests that large, blooming diatoms have low transfer efficiency and thus may not export substantially to depth; rather, our analysis suggests that ecosystems characterized by smaller cells and moderately high %CaCO3 have a high mesopelagic transfer efficiency and can have higher POC concentrations in the deep mesopelagic even with relatively low surface or near-surface POC. This has negative implications for the carbon sequestration prospects of deliberate iron fertilization.

  11. 76 FR 16842 - Request for a License To Export Reactor Components

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ... NUCLEAR REGULATORY COMMISSION Request for a License To Export Reactor Components Pursuant to 10.... Mechanical Corporation. coolant pump 1000 (design) maintenance, and systems, related reactors. operation of AP- equipment, and 1000 (design) spare parts. nuclear reactors. February 10, 2011 February 23, 2011...

  12. Antibiotic Resistance Mediated by the MacB ABC Transporter Family: A Structural and Functional Perspective.

    PubMed

    Greene, Nicholas P; Kaplan, Elise; Crow, Allister; Koronakis, Vassilis

    2018-01-01

    The MacB ABC transporter forms a tripartite efflux pump with the MacA adaptor protein and TolC outer membrane exit duct to expel antibiotics and export virulence factors from Gram-negative bacteria. Here, we review recent structural and functional data on MacB and its homologs. MacB has a fold that is distinct from other structurally characterized ABC transporters and uses a unique molecular mechanism termed mechanotransmission. Unlike other bacterial ABC transporters, MacB does not transport substrates across the inner membrane in which it is based, but instead couples cytoplasmic ATP hydrolysis with transmembrane conformational changes that are used to perform work in the extra-cytoplasmic space. In the MacAB-TolC tripartite pump, mechanotransmission drives efflux of antibiotics and export of a protein toxin from the periplasmic space via the TolC exit duct. Homologous tripartite systems from pathogenic bacteria similarly export protein-like signaling molecules, virulence factors and siderophores. In addition, many MacB-like ABC transporters do not form tripartite pumps, but instead operate in diverse cellular processes including antibiotic sensing, cell division and lipoprotein trafficking.

  13. Global patterns of organic carbon export and sequestration in the ocean (Arne Richter Award for Outstanding Young Scientists)

    NASA Astrophysics Data System (ADS)

    Henson, S.; Sanders, R.; Madsen, E.; Le Moigne, F.; Quartly, G.

    2012-04-01

    A major term in the global carbon cycle is the ocean's biological carbon pump which is dominated by sinking of small organic particles from the surface ocean to its interior. Here we examine global patterns in particle export efficiency (PEeff), the proportion of primary production that is exported from the surface ocean, and transfer efficiency (Teff), the fraction of exported organic matter that reaches the deep ocean. This is achieved through extrapolating from in situ estimates of particulate organic carbon export to the global scale using satellite-derived data. Global scale estimates derived from satellite data show, in keeping with earlier studies, that PEeff is high at high latitudes and low at low latitudes, but that Teff is low at high latitudes and high at low latitudes. However, in contrast to the relationship observed for deep biomineral fluxes in previous studies, we find that Teff is strongly negatively correlated with opal export flux from the upper ocean, but uncorrelated with calcium carbonate export flux. We hypothesise that the underlying factor governing the spatial patterns observed in Teff is ecosystem function, specifically the degree of recycling occurring in the upper ocean, rather than the availability of calcium carbonate for ballasting. Finally, our estimate of global integrated carbon export is only 50% of previous estimates. The lack of consensus amongst different methodologies on the strength of the biological carbon pump emphasises that our knowledge of a major planetary carbon flux remains incomplete.

  14. Impact of the natural Fe-fertilization on the magnitude, stoichiometry and efficiency of particulate biogenic silica, nitrogen and iron export fluxes

    NASA Astrophysics Data System (ADS)

    Lemaitre, N.; Planquette, H.; Dehairs, F.; van der Merwe, P.; Bowie, A. R.; Trull, T. W.; Laurenceau-Cornec, E. C.; Davies, D.; Bollinger, C.; Le Goff, M.; Grossteffan, E.; Planchon, F.

    2016-11-01

    The Kerguelen Plateau is characterized by a naturally Fe-fertilized phytoplankton bloom that extends more than 1000 km downstream in the Antarctic Circumpolar Current. During the KEOPS2 study, in austral spring, we measured particulate nitrogen (PN), biogenic silica (BSi) and particulate iron (PFe) export fluxes in order to investigate how the natural fertilization impacts the stoichiometry and the magnitude of export fluxes and therefore the efficiency of the biological carbon pump. At 9 stations, we estimated elemental export fluxes based on element concentration to 234Th activity ratios for particulate material collected with in-situ pumps and 234Th export fluxes (Planchon et al., 2015). This study revealed that the natural Fe-fertilization increased export fluxes but to variable degrees. Export fluxes for the bloom impacted area were compared with those of a high-nutrient, low-chlorophyll (HNLC), low-productive reference site located to the south-west of Kerguelen and which had the lowest BSi and PFe export fluxes (2.55 mmol BSi m-2 d-1 and 1.92 μmol PFem-2 d-1) and amongst the lowest PN export flux (0.73 mmol PN m-2 d-1). The impact of the Fe fertilization was the greatest within a meander of the polar front (PF), to the east of Kerguelen, with fluxes reaching 1.26 mmol PN m-2 d-1; 20.4 mmol BSi m-2 d-1 and 22.4 μmol PFe m-2 d-1. A highly productive site above the Kerguelen Plateau, on the contrary, was less impacted by the fertilization with export fluxes reaching 0.72 mmol PN m-2 d-1; 4.50 mmol BSi m-2 d-1 and 21.4 μmol PFe m-2 d-1. Our results suggest that ecosystem features (i.e. type of diatom community) could play an important role in setting the magnitude of export fluxes of these elements. Indeed, for the PF meander, the moderate productivity was sustained by the presence of large and strongly silicified diatom species while at the higher productivity sites, smaller and slightly silicified diatoms dominated. Interestingly, our results suggest that PFe export fluxes can be driven by the lithogenic pool of particles, especially over the Plateau where such inputs from the sediments are important. Finally, for the Plateau and the PF meander, the comparison between PFe export and the particulate PFe stock integrated over the mixed layer depth revealed an efficient PFe export out of the mixed layer at these sites. Export efficiencies (i.e. the ratio between export and uptake) exhibit a very efficient silica pump especially at the HNLC reference station where heavily silicified diatoms were present. On the contrary, the increase with depth of the C:N ratio and the low nitrogen export efficiencies support the idea of a strong remineralization and nitrification activity.

  15. 77 FR 39521 - Application for a License To Export Nuclear Reactor Major Components and Equipment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    ... LLC reactor coolant equipment for four constructing four plant May 14, 2012 pumps with motors, APR1400... Emirates. XR176 monitoring and plant in Braka. 110060011 control equipment, auxiliary equipment and... NUCLEAR REGULATORY COMMISSION Application for a License To Export Nuclear Reactor Major Components...

  16. Antibiotic Resistance Mediated by the MacB ABC Transporter Family: A Structural and Functional Perspective

    PubMed Central

    Greene, Nicholas P.; Kaplan, Elise; Crow, Allister; Koronakis, Vassilis

    2018-01-01

    The MacB ABC transporter forms a tripartite efflux pump with the MacA adaptor protein and TolC outer membrane exit duct to expel antibiotics and export virulence factors from Gram-negative bacteria. Here, we review recent structural and functional data on MacB and its homologs. MacB has a fold that is distinct from other structurally characterized ABC transporters and uses a unique molecular mechanism termed mechanotransmission. Unlike other bacterial ABC transporters, MacB does not transport substrates across the inner membrane in which it is based, but instead couples cytoplasmic ATP hydrolysis with transmembrane conformational changes that are used to perform work in the extra-cytoplasmic space. In the MacAB-TolC tripartite pump, mechanotransmission drives efflux of antibiotics and export of a protein toxin from the periplasmic space via the TolC exit duct. Homologous tripartite systems from pathogenic bacteria similarly export protein-like signaling molecules, virulence factors and siderophores. In addition, many MacB-like ABC transporters do not form tripartite pumps, but instead operate in diverse cellular processes including antibiotic sensing, cell division and lipoprotein trafficking. PMID:29892271

  17. JPRS Report, Near East & South Asia

    DTIC Science & Technology

    1988-01-28

    Israel’s peace in first instance. Having guar - anteed the Jewish state the separate peace it wanted with Egypt, the United States paid no attention to...plant gums , marine prod- ucts, wool and yarn have decreased. This decrease has been compensated by the great increase in the export of dried goods...mentioned session, the requests of the "Tuli Pers" company to export 3,000 tons of powdered detergent and the Pars pump company to export 1,500

  18. Carbon fluxes in the Arabian Sea: Export versus recycling

    NASA Astrophysics Data System (ADS)

    Rixen, Tim; Gaye, Birgit; Ramaswamy, Venkitasubramani

    2016-04-01

    The organic carbon pump strongly influences the exchange of carbon between the ocean and the atmosphere. It is known that it responds to global change but the magnitude and the direction of change are still unpredictable. Sediment trap experiments carried out at various sites in the Arabian Sea between 1986 and 1998 have shown differences in the functioning of the organic carbon pump (OCP). An OCP driven by eukaryotic phytoplankton operated in the upwelling region off Oman and during the spring bloom in the northern Arabian Sea. Cyanobacteria capable of fixing nitrogen seem to dominate the phytoplankton community during all other seasons. The export driven by cyanobacteria was much lower than the export driven by eukaryotic phytoplankton. Productivity and nutrient availability seems to be a main factor controlling fluxes during blooms of eukaryotic phytoplankton. The ballast effect caused by inputs of dust into the ocean and its incorporation into sinking particles seems to be the main factor controlling the export during times when cyanobacteria dominate the phytoplankton community. C/N ratios of organic matter exported from blooms dominated by nitrogen fixing cyanobacteria are enhanced and, furthermore, indicate a more efficient recycling of nutrients at shallower water depth. This implies that the bacterial-driven OCP operates more in a recycling mode that keeps nutrients closer to the euphotic zone whereas the OCP driven by eukaryotic phytoplankton reduces the recycling of nutrients by exporting them into greater water-depth.

  19. Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse

    PubMed Central

    Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F.; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

    2018-01-01

    Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time– and bile-acid-concentration–dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values <50 μM), but only about 20% of the non-sDILI drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. PMID:27000539

  20. Inhibition of bile salt transport by drugs associated with liver injury in primary hepatocytes from human, monkey, dog, rat, and mouse.

    PubMed

    Zhang, Jie; He, Kan; Cai, Lining; Chen, Yu-Chuan; Yang, Yifan; Shi, Qin; Woolf, Thomas F; Ge, Weigong; Guo, Lei; Borlak, Jürgen; Tong, Weida

    2016-08-05

    Interference of bile salt transport is one of the underlying mechanisms for drug-induced liver injury (DILI). We developed a novel bile salt transport activity assay involving in situ biosynthesis of bile salts from their precursors in primary human, monkey, dog, rat, and mouse hepatocytes in suspension as well as LC-MS/MS determination of extracellular bile salts transported out of hepatocytes. Glycine- and taurine-conjugated bile acids were rapidly formed in hepatocytes and effectively transported into the extracellular medium. The bile salt formation and transport activities were time‒ and bile-acid-concentration‒dependent in primary human hepatocytes. The transport activity was inhibited by the bile salt export pump (BSEP) inhibitors ketoconazole, saquinavir, cyclosporine, and troglitazone. The assay was used to test 86 drugs for their potential to inhibit bile salt transport activity in human hepatocytes, which included 35 drugs associated with severe DILI (sDILI) and 51 with non-severe DILI (non-sDILI). Approximately 60% of the sDILI drugs showed potent inhibition (with IC50 values <50 μM), but only about 20% of the non-sDILI drugs showed this strength of inhibition in primary human hepatocytes and these drugs are associated only with cholestatic and mixed hepatocellular cholestatic (mixed) injuries. The sDILI drugs, which did not show substantial inhibition of bile salt transport activity, are likely to be associated with immune-mediated liver injury. Twenty-four drugs were also tested in monkey, dog, rat and mouse hepatocytes. Species differences in potency were observed with mouse being less sensitive than other species to inhibition of bile salt transport. In summary, a novel assay has been developed using hepatocytes in suspension from human and animal species that can be used to assess the potential for drugs and/or drug-derived metabolites to inhibit bile salt transport and/or formation activity. Drugs causing sDILI, except those by immune-mediated mechanism, are highly associated with potent inhibition of bile salt transport. Published by Elsevier Ireland Ltd.

  1. 78 FR 42753 - Materials Technical Advisory Committee; Notice of Partially Closed Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-17

    ... BIS senior management and export control reform update including the proposed Routed Export....'' 4. Report of Composite Working Group and discussion on (1) feasibility of universal test for modulus... values for 1C008-10,1C210, and 1C990. 5. Report of Biological and Pump/Valves Working Group. 6. Report on...

  2. Spatial variability of upper ocean POC export in the Bay of Bengal and the Indian Ocean determined using particle-reactive 234Th

    NASA Astrophysics Data System (ADS)

    Subha Anand, S.; Rengarajan, R.; Sarma, V. V. S. S.; Sudheer, A. K.; Bhushan, R.; Singh, S. K.

    2017-05-01

    The northern Indian Ocean is globally significant for its seasonally reversing winds, upwelled nutrients, high biological production, and expanding oxygen minimum zones. The region acts as sink and source for atmospheric CO2. However, the efficiency of the biological carbon pump to sequester atmospheric CO2 and export particulate organic carbon from the surface is not well known. To quantify the upper ocean carbon export flux and to estimate the efficiency of biological carbon pump in the Bay of Bengal and the Indian Ocean, seawater profiles of total 234Th were measured from surface to 300 m depth at 13 stations from 19.9°N to 25.3°S in a transect along 87°E, during spring intermonsoon period (March-April 2014). Results showed enhanced in situ primary production in the equatorial Indian Ocean and the central Bay of Bengal and varied from 13.2 to 173.8 mmol C m-2 d-1. POC export flux in this region varied from 0 to 7.7 mmol C m-2 d-1. Though high carbon export flux was found in the equatorial region, remineralization of organic carbon in the surface and subsurface waters considerably reduced organic carbon export in the Bay of Bengal. Annually recurring anticyclonic eddies enhanced organic carbon utilization and heterotrophy. Oxygen minimum zone developed due to stratification and poor ventilation was intensified by subsurface remineralization. 234Th-based carbon export fluxes were not comparable with empirical statistical model estimates based on primary production and temperature. Region-specific refinement of model parameters is required to accurately predict POC export fluxes.

  3. Obeticholic acid, a selective farnesoid X receptor agonist, regulates bile acid homeostasis in sandwich-cultured human hepatocytes.

    PubMed

    Zhang, Yuanyuan; Jackson, Jonathan P; St Claire, Robert L; Freeman, Kimberly; Brouwer, Kenneth R; Edwards, Jeffrey E

    2017-08-01

    Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes. Gene expression was determined by measuring mRNA levels. OCA dose-dependently increased fibroblast growth factor-19 (FGF-19) and small heterodimer partner (SHP) which, in turn, suppress mRNA levels of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme for de novo synthesis of bile acids. Consistent with CYP7A1 suppression, total bile acid content was decreased by OCA (1 μmol/L) to 42.7 ± 20.5% relative to control. In addition to suppressing de novo bile acids synthesis, OCA significantly increased the mRNA levels of transporters involved in bile acid homeostasis. The bile salt excretory pump (BSEP), a canalicular efflux transporter, increased by 6.4 ± 0.8-fold, and the basolateral efflux heterodimer transporters, organic solute transporter α (OST α ) and OST β increased by 6.4 ± 0.2-fold and 42.9 ± 7.9-fold, respectively. The upregulation of BSEP and OST α and OST β, by OCA reduced the intracellular concentrations of d 8 -TCA, a model bile acid, to 39.6 ± 8.9% relative to control. These data demonstrate that OCA does suppress bile acid synthesis and reduce hepatocellular bile acid levels, supporting the use of OCA to treat bile acid-induced toxicity observed in cholestatic diseases. © 2017 Intercept Pharmaceuticals. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

  4. Programmed cell death in the marine cyanobacterium Trichodesmium mediates carbon and nitrogen export

    PubMed Central

    Bar-Zeev, Edo; Avishay, Itamar; Bidle, Kay D; Berman-Frank, Ilana

    2013-01-01

    The extent of carbon (C) and nitrogen (N) export to the deep ocean depends upon the efficacy of the biological pump that transports primary production to depth, thereby preventing its recycling in the upper photic zone. The dinitrogen-fixing (diazotrophic) Trichodesmium spp. contributes significantly to oceanic C and N cycling by forming extensive blooms in nutrient-poor tropical and subtropical regions. These massive blooms generally collapse several days after forming, but the cellular mechanism responsible, along with the magnitude of associated C and N export processes, are as yet unknown. Here, we used a custom-made, 2-m high water column to simulate a natural bloom and to specifically test and quantify whether the programmed cell death (PCD) of Trichodesmium mechanistically regulates increased vertical flux of C and N. Our findings demonstrate that extremely rapid development and abrupt, PCD-induced demise (within 2–3 days) of Trichodesmium blooms lead to greatly elevated excretions of transparent exopolymers and a massive downward pulse of particulate organic matter. Our results mechanistically link autocatalytic PCD and bloom collapse to quantitative C and N export fluxes, suggesting that PCD may have an impact on the biological pump efficiency in the oceans. PMID:23887173

  5. Complementary stimulation of hepatobiliary transport and detoxification systems by rifampicin and ursodeoxycholic acid in humans.

    PubMed

    Marschall, Hanns-Ulrich; Wagner, Martin; Zollner, Gernot; Fickert, Peter; Diczfalusy, Ulf; Gumhold, Judith; Silbert, Dagmar; Fuchsbichler, Andrea; Benthin, Lisbet; Grundström, Rosita; Gustafsson, Ulf; Sahlin, Staffan; Einarsson, Curt; Trauner, Michael

    2005-08-01

    Rifampicin (RIFA) and ursodeoxycholic acid (UDCA) improve symptoms and biochemical markers of liver injury in cholestatic liver diseases by largely unknown mechanisms. We aimed to study the molecular mechanisms of action of these drugs in humans. Thirty otherwise healthy gallstone patients scheduled for cholestectomy were randomized to RIFA (600 mg/day for 1 week) or UDCA (1 g/day for 3 weeks) or no medication before surgery. Routine biochemistry, lipids, and surrogate markers for P450 activity (4beta-hydroxy cholesterol, 4beta-OH-C) and bile acid synthesis (7alpha-hydroxy-4-cholesten-3-one, C-4) were measured in serum. Bile acids were analyzed in serum, urine, and bile. A wedge liver biopsy specimen was taken to study expression of hepatobiliary ABC transporters as well as detoxification enzymes and regulatory transcription factors. RIFA enhanced bile acid detoxification as well as bilirubin conjugation and excretion as reflected by enhanced expression of CYP3A4, UGT1A1, and MRP2. These molecular effects were paralleled by decreased bilirubin and deoxycholic acid concentrations in serum and decreased lithocholic and deoxycholic acid concentrations in bile. UDCA on the other hand stimulated the expression of BSEP, MDR3, and MRP4. UDCA became the predominant bile acid after UDCA treatment and lowered the biliary cholesterol saturation index. RIFA enhances bile acid detoxification as well as bilirubin conjugation and export systems, whereas UDCA stimulates the expression of transporters for canalicular and basolateral bile acid export as well as the canalicular phospholipid flippase. These independent but complementary effects may justify a combination of both agents for the treatment of cholestatic liver diseases.

  6. Quantification of the lithogenic carbon pump following a dust deposition event

    NASA Astrophysics Data System (ADS)

    Bressac, M.; Guieu, C.; Doxaran, D.; Bourrin, F.; Desboeufs, K.; Leblond, N.; Ridame, C.

    2013-08-01

    Lithogenic particles, such as desert dust, have been postulated to influence particulate organic carbon (POC) export to the deep ocean by acting as mineral ballasts. However, an accurate understanding and quantification of the POC-dust association that occurs within the upper ocean is required in order to affine the "ballast hypothesis". In the framework of the DUNE project, two artificial seedings were performed seven days apart within large mesocosms. A suite of optical and biogeochemical measurements were used to quantify surface POC export following simulated dust events within a low-nutrient low-chlorophyll ecosystem. The two successive seedings led to a 2.3-6.7 fold higher POC flux as compared to the POC flux observed in controlled mesocosms. A simple linear regression analysis revealed that the lithogenic fluxes explained more than 85% of the variance in POC fluxes. At the scale of a dust deposition event, we estimated that 42-50% of POC fluxes were strictly associated with lithogenic particles through an aggregation process. Lithogenic ballasting also likely impacted the remaining POC fraction which resulted from the fertilization effect. The observations support the "ballast hypothesis" and provide a quantitative estimation of the surface POC export abiotically triggered by dust deposition. In this work, we demonstrate that the strength of such a "lithogenic carbon pump" depends on the biogeochemical conditions of the water column at the time of deposition. Based on these observations, we suggest that this "lithogenic carbon pump" could represent a major component of the biological pump in oceanic areas subjected to intense atmospheric forcing.

  7. All0809/8/7 is a DevBCA-like ABC-type efflux pump required for diazotrophic growth in Anabaena sp. PCC 7120.

    PubMed

    Staron, Peter; Maldener, Iris

    2012-10-01

    Efflux pumps export a wide variety of proteinaceous and non-proteinaceous substrates across the Gram-negative cell wall. For the filamentous cyanobacterium Anabaena sp. strain PCC 7120, the ATP-driven glycolipid efflux pump DevBCA-TolC has been shown to be crucial for the differentiation of N(2)-fixing heterocysts from photosynthetically active vegetative cells. In this study, a homologous system was described. All0809/8/7-TolC form a typical ATP-driven efflux pump as shown by surface plasmon resonance. This putative exporter is also involved in diazotrophic growth of Anabaena sp. PCC 7120. A mutant in all0809 encoding the periplasmic membrane fusion protein of the pump was not able to grow without combined nitrogen. Although heterocysts of this mutant were not distinguishable from those of the wild-type in light and electron micrographs, they were impaired in providing the microoxic environment necessary for N(2) fixation. RT-PCR of all0809 transcripts and localization studies on All0807-GFP revealed that All0809/8/7 was initially downregulated during heterocyst maturation and upregulated at later stages of heterocyst formation in all cells of the filament. A substrate of the efflux pump could not be identified in ATP hydrolysis assays. We discuss a role for All0809/8/7-TolC in maintaining the continuous periplasm and how this would be of special importance for heterocyst differentiation.

  8. Influence of diatom diversity on the ocean biological carbon pump

    NASA Astrophysics Data System (ADS)

    Tréguer, Paul; Bowler, Chris; Moriceau, Brivaela; Dutkiewicz, Stephanie; Gehlen, Marion; Aumont, Olivier; Bittner, Lucie; Dugdale, Richard; Finkel, Zoe; Iudicone, Daniele; Jahn, Oliver; Guidi, Lionel; Lasbleiz, Marine; Leblanc, Karine; Levy, Marina; Pondaven, Philippe

    2018-01-01

    Diatoms sustain the marine food web and contribute to the export of carbon from the surface ocean to depth. They account for about 40% of marine primary productivity and particulate carbon exported to depth as part of the biological pump. Diatoms have long been known to be abundant in turbulent, nutrient-rich waters, but observations and simulations indicate that they are dominant also in meso- and submesoscale structures such as fronts and filaments, and in the deep chlorophyll maximum. Diatoms vary widely in size, morphology and elemental composition, all of which control the quality, quantity and sinking speed of biogenic matter to depth. In particular, their silica shells provide ballast to marine snow and faecal pellets, and can help transport carbon to both the mesopelagic layer and deep ocean. Herein we show that the extent to which diatoms contribute to the export of carbon varies by diatom type, with carbon transfer modulated by the Si/C ratio of diatom cells, the thickness of the shells and their life strategies; for instance, the tendency to form aggregates or resting spores. Model simulations project a decline in the contribution of diatoms to primary production everywhere outside of the Southern Ocean. We argue that we need to understand changes in diatom diversity, life cycle and plankton interactions in a warmer and more acidic ocean in much more detail to fully assess any changes in their contribution to the biological pump.

  9. Quantification of the lithogenic carbon pump following a simulated dust-deposition event in large mesocosms

    NASA Astrophysics Data System (ADS)

    Bressac, M.; Guieu, C.; Doxaran, D.; Bourrin, F.; Desboeufs, K.; Leblond, N.; Ridame, C.

    2014-02-01

    Lithogenic particles, such as desert dust, have been postulated to influence particulate organic carbon (POC) export to the deep ocean by acting as mineral ballasts. However, an accurate understanding and quantification of the POC-dust association that occurs within the upper ocean is required in order to refine the "ballast hypothesis". In the framework of the DUNE (a DUst experiment in a low-Nutrient, low-chlorophyll Ecosystem) project, two artificial seedings were performed seven days apart within large mesocosms. A suite of optical and biogeochemical measurements were used to quantify surface POC export following simulated dust events within a low-nutrient, low-chlorophyll ecosystem. The two successive seedings led to a 2.3-6.7-fold higher POC flux than the POC flux observed in controlled mesocosms. A simple linear regression analysis revealed that the lithogenic fluxes explained more than 85% of the variance in POC fluxes. On the scale of a dust-deposition event, we estimated that 42-50% of POC fluxes were strictly associated with lithogenic particles (through aggregation and most probably sorption processes). Lithogenic ballasting also likely impacted the remaining POC fraction which resulted from the fertilization effect. The observations support the "ballast hypothesis" and provide a quantitative estimation of the surface POC export abiotically triggered by dust deposition. In this work, we demonstrate that the strength of such a "lithogenic carbon pump" depends on the biogeochemical conditions of the water column at the time of deposition. Based on these observations, we suggest that this lithogenic carbon pump could represent a major component of the biological pump in oceanic areas subjected to intense atmospheric forcing.

  10. Global assessment of ocean carbon export by combining satellite observations and food-web models

    NASA Astrophysics Data System (ADS)

    Siegel, D. A.; Buesseler, K. O.; Doney, S. C.; Sailley, S. F.; Behrenfeld, M. J.; Boyd, P. W.

    2014-03-01

    The export of organic carbon from the surface ocean by sinking particles is an important, yet highly uncertain, component of the global carbon cycle. Here we introduce a mechanistic assessment of the global ocean carbon export using satellite observations, including determinations of net primary production and the slope of the particle size spectrum, to drive a food-web model that estimates the production of sinking zooplankton feces and algal aggregates comprising the sinking particle flux at the base of the euphotic zone. The synthesis of observations and models reveals fundamentally different and ecologically consistent regional-scale patterns in export and export efficiency not found in previous global carbon export assessments. The model reproduces regional-scale particle export field observations and predicts a climatological mean global carbon export from the euphotic zone of 6 Pg C yr-1. Global export estimates show small variation (typically < 10%) to factor of 2 changes in model parameter values. The model is also robust to the choices of the satellite data products used and enables interannual changes to be quantified. The present synthesis of observations and models provides a path for quantifying the ocean's biological pump.

  11. Measured flow and tracer-dye data for spring 1996 and 1997 for the south Sacramento-San Joaquin Delta, California

    USGS Publications Warehouse

    Oltmann, Richard N.

    1999-01-01

    During the spring of years when the flow of the San Joaquin River is less than 7,000 cubic feet per second (ft3/s) a temporary rock barrier is installed by the California Department of Water Resources (DWR) at the head of Old River (HOR) in the south Sacramento-San Joaquin Delta to prevent out migrating salmon in the San Joaquin River from entering Old River and being drawn to the State and federal pumping facilities (Figure 1). The export rate of the pumping facilities also is reduced during these migration periods to minimize the draw of fish to the export facilities through the other channels connected to the San Joaquin River north of the HOR such as Turner Cut, Columbia Cut, and Middle River.

  12. The impact on atmospheric CO2 of iron fertilization induced changes in the ocean's biological pump

    NASA Astrophysics Data System (ADS)

    Jin, X.; Gruber, N.; Frenzel, H.; Doney, S. C.; McWilliams, J. C.

    2008-03-01

    Using numerical simulations, we quantify the impact of changes in the ocean's biological pump on the air-sea balance of CO2 by fertilizing a small surface patch in the high-nutrient, low-chlorophyll region of the eastern tropical Pacific with iron. Decade-long fertilization experiments are conducted in a basin-scale, eddy-permitting coupled physical/biogeochemical/ecological model. In contrast to previous studies, we find that most of the dissolved inorganic carbon (DIC) removed from the euphotic zone by the enhanced biological export is replaced by uptake of CO2 from the atmosphere. Atmospheric uptake efficiencies, the ratio of the perturbation in air-sea CO2 flux to the perturbation in export flux across 100 m, integrated over 10 years, are 0.75 to 0.93 in our patch size-scale experiments. The atmospheric uptake efficiency is insensitive to the duration of the experiment. The primary factor controlling the atmospheric uptake efficiency is the vertical distribution of the enhanced biological production and export. Iron fertilization at the surface tends to induce production anomalies primarily near the surface, leading to high efficiencies. In contrast, mechanisms that induce deep production anomalies (e.g. altered light availability) tend to have a low uptake efficiency, since most of the removed DIC is replaced by lateral and vertical transport and mixing. Despite high atmospheric uptake efficiencies, patch-scale iron fertilization of the ocean's biological pump tends to remove little CO2 from the atmosphere over the decadal timescale considered here.

  13. Influence of a Decaying Cyclonic Eddy on Biogenic Silica and Particulate Organic Carbon in the Tropical South China Sea Based on 234Th-238U Disequilibrium.

    PubMed

    Yang, Weifeng; Chen, Min; Zheng, Minfang; He, Zhigang; Zhang, Xinxing; Qiu, Yusheng; Xu, Wangbin; Ma, Lili; Lin, Zhiyu; Hu, Wangjiang; Zeng, Jian

    2015-01-01

    Eddies play a critical role in regulating the biological pump by pumping new nutrients to the euphotic zone. However, the effects of cyclonic eddies on particle export are not well understood. Here, biogenic silica (BSi) and particulate organic carbon (POC) exports were examined inside and outside a decaying cyclonic eddy using 234Th-238U disequilibria in the tropical South China Sea. For the eddy and outside stations, the average concentrations of BSi in the euphotic zone were 0.17±0.09 μmol L-1 (mean±sd, n = 20) and 0.21±0.06 μmol L-1 (n = 34). The POC concentrations were 1.42±0.56 μmol L-1 (n = 34) and 1.30±0.46 μmol L-1 (n = 51). Both BSi and POC abundances did not show change at the 95% confidence level. Based on the 234Th-238U model, BSi export fluxes in the eddy averaged 0.18±0.15 mmol Si m-2 d-1, which was comparable with the 0.40±0.20 mmol Si m-2 d-1 outside the eddy. Similarly, the average POC export fluxes were 1.5±1.4 mmol C m-2 d-1 and 1.9±1.3 mmol C m-2 d-1 for the eddy and outside stations. From these results we concluded that cyclonic eddies in their decaying phase have little effect on the abundance and export of biogenic particles.

  14. Influence of a Decaying Cyclonic Eddy on Biogenic Silica and Particulate Organic Carbon in the Tropical South China Sea Based on 234Th-238U Disequilibrium

    PubMed Central

    Yang, Weifeng; Chen, Min; Zheng, Minfang; He, Zhigang; Zhang, Xinxing; Qiu, Yusheng; Xu, Wangbin; Ma, Lili; Lin, Zhiyu; Hu, Wangjiang; Zeng, Jian

    2015-01-01

    Eddies play a critical role in regulating the biological pump by pumping new nutrients to the euphotic zone. However, the effects of cyclonic eddies on particle export are not well understood. Here, biogenic silica (BSi) and particulate organic carbon (POC) exports were examined inside and outside a decaying cyclonic eddy using 234Th-238U disequilibria in the tropical South China Sea. For the eddy and outside stations, the average concentrations of BSi in the euphotic zone were 0.17±0.09 μmol L-1 (mean±sd, n = 20) and 0.21±0.06 μmol L-1 (n = 34). The POC concentrations were 1.42±0.56 μmol L-1 (n = 34) and 1.30±0.46 μmol L-1 (n = 51). Both BSi and POC abundances did not show change at the 95% confidence level. Based on the 234Th-238U model, BSi export fluxes in the eddy averaged 0.18±0.15 mmol Si m-2 d-1, which was comparable with the 0.40±0.20 mmol Si m-2 d-1 outside the eddy. Similarly, the average POC export fluxes were 1.5±1.4 mmol C m-2 d-1 and 1.9±1.3 mmol C m-2 d-1 for the eddy and outside stations. From these results we concluded that cyclonic eddies in their decaying phase have little effect on the abundance and export of biogenic particles. PMID:26317555

  15. Ocean Biological Pump Sensitivities and Implications for Climate Change Impacts

    NASA Technical Reports Server (NTRS)

    Romanou, Anastasia

    2013-01-01

    The ocean is one of the principal reservoirs of CO2, a greenhouse gas, and therefore plays a crucial role in regulating Earth's climate. Currently, the ocean sequesters about a third of anthropogenic CO2 emissions, mitigating the human impact on climate. At the same time, the deeper ocean represents the largest carbon pool in the Earth System and processes that describe the transfer of carbon from the surface of the ocean to depth are intimately linked to the effectiveness of carbon sequestration.The ocean biological pump (OBP), which involves several biogeochemical processes, is a major pathway for transfer of carbon from the surface mixed layer into the ocean interior. About 75 of the carbon vertical gradient is due to the carbon pump with only 25 attributed to the solubility pump. However, the relative importance and role of the two pumps is poorly constrained. OBP is further divided to the organic carbon pump (soft tissue pump) and the carbonate pump, with the former exporting about 10 times more carbon than the latter through processes like remineralization.Major uncertainties about OBP, and hence in the carbon uptake and sequestration, stem from uncertainties in processes involved in OBP such as particulate organicinorganic carbon sinkingsettling, remineralization, microbial degradation of DOC and uptakegrowth rate changes of the ocean biology. The deep ocean is a major sink of atmospheric CO2 in scales of hundreds to thousands of years, but how the export efficiency (i.e. the fraction of total carbon fixation at the surface that is transported at depth) is affected by climate change remains largely undetermined. These processes affect the ocean chemistry (alkalinity, pH, DIC, particulate and dissolved organic carbon) as well as the ecology (biodiversity, functional groups and their interactions) in the ocean. It is important to have a rigorous, quantitative understanding of the uncertainties involved in the observational measurements, the models and the projections of future changes.

  16. Role of eddy pumping in enhancing primary production in the ocean

    NASA Technical Reports Server (NTRS)

    Falkowski, Paul G.; Kolber, Zbigniew; Ziemann, David; Bienfang, Paul K.

    1991-01-01

    Eddy pumping is considered to explain the disparity between geochemical estimates and biological measurements of exported production. Episodic nutrient injections from the ocean into the photic zone can be generated by eddy pumping, which biological measurements cannot sample accurately. The enhancement of production is studied with respect to a cyclonic eddy in the subtropical Pacific. A pump-and-probe fluorimeter generates continuous vertical profiles of primary productivity from which the contributions of photochemical and nonphotochemical processes to fluorescence are derived. A significant correlation is observed between the fluorescence measurements and radiocarbon measurements. The results indicate that eddy pumping has an important effect on phytoplankton production and that this production is near the maximum relative specific growth rates. Based on the production enhancement observed in this case, eddy pumping increases total primary production by only 20 percent and does not account for all enhancement.

  17. Section 7 reactor incident file general information from 1945

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1969-01-10

    At 0308 on January 10, 1966, both B and C Reactors ``scrammed`` due to an electrical fault on Line C2-L8 caused by a raccoon coming in contact with the 13-8 KV line on top of transformer No. 2 at 182-B Building. Line C2-L8 relayed out at the 151-B Building. Details of the occurrence at 151-B are covered in the attachment. C-Reactor scrammed due to reduced voltage on the pressure monitor system. The reduction in voltage caused the auxiliary relays of the pressure monitor ground detector to open, de-energizing the end result relays PSR and PSRA. The safety circuit trip identificationmore » system displayed ``Pressure Monitor`` and ``Ground Detector.`` B-Reactor scrammed by a power failure signal from 190-B Building. The power failure relays for pump numbers 1 and 3 opened due to these pumps contributing power to the fault. The power failure relays at 190-B remained open long enough for the end result relays PF and PFA to open. Since these relays are timed delayed, 0.26 seconds, the power failure relays must have remained open at least that long. At the 190-B Building the steam turbines started due to the power failure relays for pump numbers 1 and 3 opening. The main process pumps remained stable and continued to supply normal flow to the reactor. Pumps were tripped from the line at 182-B and 183-B Buildings. The surge suppressors cycled normally and the turbine export pumps started as a result of low export line pressure. No power equipment was affected in C Area.« less

  18. 78 FR 65265 - Materials Technical Advisory Committee; Notice of Open Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... BIS senior management and export control reform update. 3. Presentation from DuPont on the challenges... friendly. 4. Report of Composite Working Group. 5. Report of Biological and Pump/Valves Working Group. 6...

  19. Annual Cycles of Deep-ocean, Biogeochemical Export Fluxes and Biological Pump Processes in Subtropical and Subantarctic Waters, Southwest Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Nodder, S.; Chiswell, S.; Northcote, L.

    2016-02-01

    One of the key aspects of the global carbon cycle is the efficiency and spatio-temporal variability of the biological pump. In this paper, the annual cycles of particle fluxes, derived from moored sediment trap data collected from 2000-12 in subtropical (STW) and subantarctic waters (SAW), east of New Zealand, are presented. These observations are the most comprehensive export flux time-series from temperate Southern Hemisphere latitudes to date. With high levels of variability, fluxes in SAW were markedly lower than in STW, reflecting the picophytoplankton-dominated communities in the iron-limited, high nutrient-low chlorophyll SAW. Austral spring chlorophyll blooms in surface STW were near-synchronous with elevated fluxes of bio-siliceous, carbonate and organic carbon-rich materials to the deep ocean, probably facilitated by diatom sedimentation. Lithogenic fluxes were also high in STW, compared to SAW, reflecting proximity to the New Zealand landmass. In contrast, the highest biogenic fluxes in SAW occurred in spring when surface chlorophyll concentrations were low, while highest annual chlorophyll concentrations were in summer with no associated flux increase. We hypothesize that the high spring export in SAW occurs from subsurface chlorophyll accumulations that are not evident from remote-sensing satellites. This material was also rich in biogenic silica, perhaps related to the preferential export of diatoms and other silica-producing organisms, such as silicoflagellates and radiolarians. Particle fluxes in STW are similar to that of other mesotrophic to oligotrophic waters ( 6-7 mgC m-2 d-1), whereas export from SAW is below global averages ( 3 mgC m-2 d-1), and is characterized by carbonate-dominated and prominent bio-siliceous deposition.

  20. Planktic foraminifer and coccolith contribution to carbonate export fluxes over the central Kerguelen Plateau

    NASA Astrophysics Data System (ADS)

    Rembauville, M.; Meilland, J.; Ziveri, P.; Schiebel, R.; Blain, S.; Salter, I.

    2016-05-01

    We report the contribution of planktic foraminifers and coccoliths to the particulate inorganic carbon (PIC) export fluxes collected over an annual cycle (October 2011/September 2012) on the central Kerguelen Plateau in the Antarctic Zone (AAZ) south of the Polar Front (PF). The seasonality of PIC flux was decoupled from surface chlorophyll a concentration and particulate organic carbon (POC) fluxes and was characterized by a late summer (February) maximum. This peak was concomitant with the highest satellite-derived sea surface PIC and corresponded to a Emiliania huxleyi coccoliths export event that accounted for 85% of the annual PIC export. The foraminifer contribution to the annual PIC flux was much lower (15%) and dominated by Turborotalita quinqueloba and Neogloboquadrina pachyderma. Foraminifer export fluxes were closely related to the surface chlorophyll a concentration, suggesting food availability as an important factor regulating the foraminifer's biomass. We compared size-normalized test weight (SNW) of the foraminifers with previously published SNW from the Crozet Islands using the same methodology and found no significant difference in SNW between sites for a given species. However, the SNW was significantly species-specific with a threefold increase from T. quinqueloba to Globigerina bulloides. The annual PIC:POC molar ratio of 0.07 was close to the mean ratio for the global ocean and lead to a low carbonate counter pump effect (~5%) compared to a previous study north of the PF (6-32%). We suggest that lowers counter pump effect south of the PF despite similar productivity levels is due to a dominance of coccoliths in the PIC fluxes and a difference in the foraminifers species assemblage with a predominance of polar species with lower SNW.

  1. Boldine enhances bile production in rats via osmotic and Farnesoid X receptor dependent mechanisms

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cermanova, Jolana; Kadova, Zuzana; Deparment of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove

    Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that themore » effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. - Highlights: • Boldine may increase bile production by direct as well as indirect mechanisms. • Biliary concentrations of boldine above 10 μM directly stimulate bile production. • Long-term oral boldine administration increases bile acid (BA) biliary secretion. • Boldine induces Bsep-mediated transport of BA by FXR receptor stimulation.« less

  2. The Novel Helicobacter pylori CznABC Metal Efflux Pump Is Required for Cadmium, Zinc, and Nickel Resistance, Urease Modulation, and Gastric Colonization

    PubMed Central

    Stähler, Frank Nils; Odenbreit, Stefan; Haas, Rainer; Wilrich, Julia; Vliet, Arnoud H. M. Van; Kusters, Johannes G.; Kist, Manfred; Bereswill, Stefan

    2006-01-01

    Maintaining metal homeostasis is crucial for the adaptation of Helicobacter pylori to the gastric environment. Iron, copper, and nickel homeostasis has recently been demonstrated to be required for the establishment of H. pylori infection in animal models. Here we demonstrate that the HP0969-0971 gene cluster encoding the Czc-type metal export pump homologs HP0969, HP0970, and the H. pylori-specific protein HP0971 forms part of a novel H. pylori metal resistance determinant, which is required for gastric colonization and for the modulation of urease activity. Insertional mutagenesis of the HP0971, HP0970, or HP0969 genes in H. pylori reference strain 26695 resulted in increased sensitivity to cadmium, zinc, and nickel (czn), suggesting that the encoded proteins constitute a metal-specific export pump. Accordingly, the genes were designated cznC (HP0971), cznB (HP0970), and cznA (HP0969). The CznC and CznA proteins play a predominant role in nickel homeostasis, since only the cznC and cznA mutants but not the cznB mutant displayed an 8- to 10-fold increase in urease activity. Nickel-specific affinity chromatography demonstrated that recombinant versions of CznC and CznB can bind to nickel and that the purified CznB protein interacted with cadmium and zinc, since both metals competitively inhibited nickel binding. Finally, single cznA, cznB, and cznC mutants did not colonize the stomach in a Mongolian gerbil-based animal model. This demonstrates that the metal export functions of H. pylori cznABC are essential for gastric colonization and underlines the extraordinary importance of metal ion homeostasis for the survival of H. pylori in the gastric environment. PMID:16790756

  3. Replumbing of the Biological Pump caused by Millennial Climate Variability

    NASA Astrophysics Data System (ADS)

    Galbraith, E.; Sarmiento, J.

    2008-12-01

    It has been hypothesized that millennial-timescale variability in the biological pump was a critical instigator of glacial-interglacial cycles. However, even in the absence of changes in ecosystem function (e.g. due to iron fertilization), determining the mechanisms by which physical climate variability alters the biological pump is not simple. Changes in upper ocean circulation and deep water formation have previously been shown to alter both the downward flux of organic matter and the mass of respired carbon in the ocean interior, often in non- intuitive ways. For example, a reduced upward flux of nutrients at the global scale will decrease the global rate of export production, but it could either increase or decrease the respired carbon content of the ocean interior, depending on where the reduced upward flux of nutrients occurs. Furthermore, viable candidates for physical climate forcing are numerous, including changes in the westerly winds, changes in the depth of the thermocline, and changes in the formation rate of North Atlantic Deep Water, among others. We use a simple, prognostic, light-and temperature-dependent model of biogeochemical cycling within a state-of-the- art global coupled ocean-atmosphere model to examine the response of the biological pump to changes in the coupled Earth system over multiple centuries. The biogeochemical model explicitly distinguishes respired carbon from preformed and saturation carbon, allowing the activity of the biological pump to be clearly quantified. Changes are forced in the model by altering the background climate state, and by manipulating the flux of freshwater to the North Atlantic region. We show how these changes in the physical state of the coupled ocean-atmosphere system impact the distribution and mass of respired carbon in the ocean interior, and the relationship these changes bear to global patterns of export production via the redistribution of nutrients.

  4. Revealing and analyzing networks of environmental systems

    NASA Astrophysics Data System (ADS)

    Eveillard, D.; Bittner, L.; Chaffron, S.; Guidi, L.; Raes, J.; Karsenti, E.; Bowler, C.; Gorsky, G.

    2015-12-01

    Understanding the interactions between microbial communities and their environment well enough to be able to predict diversity on the basis of physicochemical parameters is a fundamental pursuit of microbial ecology that still eludes us. However, modeling microbial communities is a complicated task, because (i) communities are complex, (ii) most are described qualitatively, and (iii) quantitative understanding of the way communities interacts with their surroundings remains incomplete. Within this seminar, we will illustrate two complementary approaches that aim to overcome these points in different manners. First, we will present a network analysis that focus on the biological carbon pump in the global ocean. The biological carbon pump is the process by which photosynthesis transforms CO2 to organic carbon sinking to the deep-ocean as particles where it is sequestered. While the intensity of the pump correlate to plankton community composition, the underlying ecosystem structure and interactions driving this process remain largely uncharacterized Here we use environmental and metagenomic data gathered during the Tara Oceans expedition to improve understanding of these drivers. We show that specific plankton communities correlate with carbon export and highlight unexpected and overlooked taxa such as Radiolaria, alveolate parasites and bacterial pathogens, as well as Synechococcus and their phages, as key players in the biological pump. Additionally, we show that the abundances of just a few bacterial and viral genes predict most of the global ocean carbon export's variability. Together these findings help elucidate ecosystem drivers of the biological carbon pump and present a case study for scaling from genes-to-ecosystems. Second, we will show preliminary results on a probabilistic modeling that predicts microbial community structure across observed physicochemical data, from a putative network and partial quantitative knowledge. This modeling shows that, despite distinct quantitative environmental perturbations, the constraints on community structure could remain stable.

  5. Carbonate counter pump stimulated by natural iron fertilization in the Polar Frontal Zone

    NASA Astrophysics Data System (ADS)

    Salter, Ian; Schiebel, Ralf; Ziveri, Patrizia; Movellan, Aurore; Lampitt, Richard; Wolff, George A.

    2014-12-01

    The production of organic carbon in the ocean's surface and its subsequent downward export transfers carbon dioxide to the deep ocean. This CO2 drawdown is countered by the biological precipitation of carbonate, followed by sinking of particulate inorganic carbon, which is a source of carbon dioxide to the surface ocean, and hence the atmosphere over 100-1,000 year timescales. The net transfer of CO2 to the deep ocean is therefore dependent on the relative amount of organic and inorganic carbon in sinking particles. In the Southern Ocean, iron fertilization has been shown to increase the export of organic carbon, but it is unclear to what degree this effect is compensated by the export of inorganic carbon. Here we assess the composition of sinking particles collected from sediment traps located in the Polar Frontal Zone of the Southern Ocean. We find that in high-nutrient, low-chlorophyll regions that are characterized by naturally high iron concentrations, fluxes of both organic and inorganic carbon are higher than in regions with no iron fertilization. However, the excess flux of inorganic carbon is greater than that of organic carbon. We estimate that the production and flux of carbonate in naturally iron-fertilized waters reduces the overall amount of CO2 transferred to the deep ocean by 6-32%, compared to 1-4% at the non-fertilized site. We suggest that an increased export of organic carbon, stimulated by iron availability in the glacial sub-Antarctic oceans, may have been accompanied by a strengthened carbonate counter pump.

  6. A Multi-Faceted Approach for the Development of the Army's Functional Basic Skills Education Program (BSEP).

    ERIC Educational Resources Information Center

    Begland, Robert R.

    In reviewing the Army Continuing Education System in 1979, the Assistant Secretary of the Army found a basic skills program based on traditional academic level goals was inadequate to meet the Army's requirement to provide functional, job-related basic skill education. Combining the shrinking manpower pool and projected basic skill deficiencies of…

  7. Modelling the regulation effects of lowland polder with pumping station on hydrological processes and phosphorus loads.

    PubMed

    Yan, Renhua; Li, Lingling; Gao, Junfeng

    2018-05-08

    Exploring the hydrological regulation of a lowland polder is essential for increasing knowledge regarding the role of polders associated with pumping stations in lowlands. In this study, the Lowland Polder Hydrology and Phosphorus modelling System (PHPS) was applied to the Jianwei polder as a case study for quantifying the regulation effects of a lowland polder with pumping on discharge and phosphorus loads. The results indicate that the polder significantly affected the temporal distribution and annual amount of catchment discharge. Compared with a no-pumping scenario, an agricultural polder with pumping stations generated a sharper discharge hydrograph with higher peak-values and lower minimum-values, as well as an 8.6% reduction in average annual discharge. It also decreased the phosphorus export to downstream water bodies by 5.33 kg/hm 2 /yr because of widespread ditches and ponds, a lower hydraulic gradient, and increased retention times of surface water in ponds. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Multidrug efflux pumps: the structures of prokaryotic ATP-binding cassette transporter efflux pumps and implications for our understanding of eukaryotic P-glycoproteins and homologues.

    PubMed

    Kerr, Ian D; Jones, Peter M; George, Anthony M

    2010-02-01

    One of the Holy Grails of ATP-binding cassette transporter research is a structural understanding of drug binding and transport in a eukaryotic multidrug resistance pump. These transporters are front-line mediators of drug resistance in cancers and represent an important therapeutic target in future chemotherapy. Although there has been intensive biochemical research into the human multidrug pumps, their 3D structure at atomic resolution remains unknown. The recent determination of the structure of a mouse P-glycoprotein at subatomic resolution is complemented by structures for a number of prokaryotic homologues. These structures have provided advances into our knowledge of the ATP-binding cassette exporter structure and mechanism, and have provided the template data for a number of homology modelling studies designed to reconcile biochemical data on these clinically important proteins.

  9. Enhanced open ocean storage of CO2 from shelf sea pumping.

    PubMed

    Thomas, Helmuth; Bozec, Yann; Elkalay, Khalid; de Baar, Hein J W

    2004-05-14

    Seasonal field observations show that the North Sea, a Northern European shelf sea, is highly efficient in pumping carbon dioxide from the atmosphere to the North Atlantic Ocean. The bottom topography-controlled stratification separates production and respiration processes in the North Sea, causing a carbon dioxide increase in the subsurface layer that is ultimately exported to the North Atlantic Ocean. Globally extrapolated, the net uptake of carbon dioxide by coastal and marginal seas is about 20% of the world ocean's uptake of anthropogenic carbon dioxide, thus enhancing substantially the open ocean carbon dioxide storage.

  10. Menadione metabolism to thiodione in hepatoblastoma by scanning electrochemical microscopy

    PubMed Central

    Mauzeroll, Janine; Bard, Allen J.; Owhadian, Omeed; Monks, Terrence J.

    2004-01-01

    The cytotoxicity of menadione on hepatocytes was studied by using the substrate generation/tip collection mode of scanning electrochemical microscopy by exposing the cells to menadione and detecting the menadione-S-glutathione conjugate (thiodione) that is formed during the cellular detoxication process and is exported from the cell by an ATP-dependent pump. This efflux was electrochemically detected and allowed scanning electrochemical microscopy monitoring and imaging of single cells and groups of highly confluent live cells. Based on a constant flux model, ≈6 × 106 molecules of thiodione per cell per second are exported from monolayer cultures of Hep G2 cells. PMID:15601769

  11. Abstracts of ARI Research Publications FY 1983

    DTIC Science & Technology

    1983-10-01

    and the relationship between SM usage and the soldier’s ability to perform his or her job skills , as measured by 2 SQT scores. Questionnaire data were...System (ACES) on soldier performance. Four -’ ACES programs were selected for evaluation: Basic Skills Education Program I, Literacy Phase (BSEP I...the prototype system was operated at Fort Carson, CO, the relationships among maintenance workload, efficiency, and skill were studied. As workload

  12. Efflux systems in bacteria and their metabolic engineering applications.

    PubMed

    Jones, Christopher M; Hernández Lozada, Néstor J; Pfleger, Brian F

    2015-11-01

    The production of valuable chemicals from metabolically engineered microbes can be limited by excretion from the cell. Efflux is often overlooked as a bottleneck in metabolic pathways, despite its impact on alleviating feedback inhibition and product toxicity. In the past, it has been assumed that endogenous efflux pumps and membrane porins can accommodate product efflux rates; however, there are an increasing number of examples wherein overexpressing efflux systems is required to improve metabolite production. In this review, we highlight specific examples from the literature where metabolite export has been studied to identify unknown transporters, increase tolerance to metabolites, and improve the production capabilities of engineered bacteria. The review focuses on the export of a broad spectrum of valuable chemicals including amino acids, sugars, flavins, biofuels, and solvents. The combined set of examples supports the hypothesis that efflux systems can be identified and engineered to confer export capabilities on industrially relevant microbes.

  13. Quantifying export production in the Southern Ocean: Implications for the Baxs proxy

    NASA Astrophysics Data System (ADS)

    Hernandez-Sanchez, Maria T.; Mills, Rachel A.; Planquette, HéLèNe; Pancost, Richard D.; Hepburn, Laura; Salter, Ian; Fitzgeorge-Balfour, Tania

    2011-12-01

    The water column and sedimentary Baxs distribution around the Crozet Plateau is used to decipher the controls and timing of barite formation and to evaluate how export production signals are recorded in sediments underlying a region of natural Fe fertilization within the Fe limited Southern Ocean. Export production estimated from preserved, vertical sedimentary Baxs accumulation rates are compared with published export fluxes assessed from an integrated study of the biological carbon pump to determine the validity of Baxs as a quantitative proxy under different Fe supply conditions typical of the Southern Ocean. Detailed assessment of the geochemical partitioning of Ba in sediments and the lithogenic end-member allows appropriate correction of the bulk Ba content and determination of the Baxs content of sediments and suspended particles. The upper water column distribution of Baxs is extremely heterogeneous spatially and temporally. Organic carbon/Baxs ratios in deep traps from the Fe fertilized region are similar to other oceanic settings allowing quantification of the inferred carbon export based on established algorithms. There appears to be some decoupling of POC and Ba export in the Fe limited region south of the Plateau. The export production across the Crozet Plateau inferred from the Baxs sedimentary proxy indicates that the Fe fertilized area to the north of the Plateau experiences enhanced export relative to equivalent Southern Ocean settings throughout the Holocene and that this influence may also have impacted the site to the south for significant periods. This interpretation is corroborated by alternative productivity proxies (opal accumulation, 231Paxs/230Thxs). Baxs can be used to quantify export production in complex settings such as naturally Fe-fertilized (volcanoclastic) areas, providing appropriate lithogenic correction is undertaken, and sediment focusing is corrected for along with evaluation of barite preservation.

  14. Structures of the TetR-like simocyclinone efflux pump repressor, SimR, and the mechanism of ligand-mediated derepression.

    PubMed

    Le, Tung B K; Stevenson, Clare E M; Fiedler, Hans-Peter; Maxwell, Anthony; Lawson, David M; Buttner, Mark J

    2011-04-22

    Simocyclinone D8 (SD8), a potent DNA gyrase inhibitor made by Streptomyces antibioticus, is exported from the producing organism by the SimX efflux pump. The expression of simX is under the control of SimR, a member of the TetR family of transcriptional regulators. SimR represses simX transcription by binding to operators in the intergenic region between simR and simX. Previously, we have shown that the mature antibiotic SD8 or its biosynthetic intermediate, simocyclinone C4, can dissociate SimR from its operators, leading to derepression of simX and export of SD8 from the cell. This provides a mechanism that couples the biosynthesis of the antibiotic to its export. Here, we report the crystal structures of SimR alone and in complex with either SD8 or simocyclinone C4. The ligand-binding pocket is unusual compared to those of other characterized TetR-family transcriptional regulators: the structures show an extensive ligand-binding pocket spanning both monomers in the functional dimeric unit, with the aminocoumarin moiety of SD8 buried in the protein core, while the angucyclic polyketide moiety is partially exposed to bulk solvent. Through comparisons of the structures, we postulate a derepression mechanism for SimR that invokes rigid-body motions of the subunits relative to one another, coupled with a putative locking mechanism to restrict further conformational change. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Estimates of micro-, nano-, and picoplankton contributions to particle export in the northeast Pacific

    NASA Astrophysics Data System (ADS)

    Mackinson, B. L.; Moran, S. B.; Lomas, M. W.; Stewart, G. M.; Kelly, R. P.

    2015-06-01

    The contributions of micro-, nano-, and picoplankton to particle export were estimated from measurements of size-fractionated particulate 234Th, organic carbon, and phytoplankton indicator pigments obtained during five cruises between 2010 and 2012 along Line P in the subarctic northeast Pacific Ocean. Sinking fluxes of particulate organic carbon (POC) and indicator pigments were calculated from 234Th-238U disequilibria and, during two cruises, measured by a sediment trap at Ocean Station Papa. POC fluxes at 100 m ranged from 0.65 to 7.95 mmol m-2 d-1, similar in magnitude to previous results at Line P. Microplankton pigments dominate indicator pigment fluxes (averaging 69 ± 19% of total pigment flux), while nanoplankton pigments comprised the majority of pigment standing stocks (averaging 64 ± 23% of total pigment standing stocks). Indicator pigment loss rates (the ratio of pigment export flux to pigment standing stocks) point to preferential export of larger microplankton relative to smaller nano- and picoplankton. However, indicator pigments do not quantitatively trace particle export resulting from zooplankton grazing, which may be an important pathway for the export of small phytoplankton. These results have important implications for understanding the magnitude and mechanisms controlling the biological pump at Line P in particular, and more generally in oligotrophic gyres and high-nutrient, low-chlorophyll (HNLC) regions where small phytoplankton represent a major component of the autotrophic community.

  16. Estimates of micro-, nano-, and picoplankton contributions to particle export in the northeast Pacific

    NASA Astrophysics Data System (ADS)

    Mackinson, B. L.; Moran, S. B.; Lomas, M. W.; Stewart, G. M.; Kelly, R. P.

    2014-08-01

    The contributions of micro-, nano-, and picoplankton to particle export were estimated from measurements of size-fractionated particulate 234Th, organic carbon, and phytoplankton indicator pigments obtained during five cruises between 2010 and 2012 along Line P in the subarctic northeast Pacific Ocean. Sinking fluxes of particulate organic carbon (POC) and indicator pigments were calculated from 234Th-238U disequilibria and, during two cruises, measured by sediment trap at Ocean Station Papa. POC fluxes at 100 m ranged from 0.65-7.95 mmol m-2 d-1, similar in magnitude to previous results at Line P. Microplankton pigments dominate indicator pigment fluxes (averaging 69 ± 19% of total pigment flux), while nanoplankton pigments comprised the majority of pigment standing stocks (averaging 64 ± 23% of total pigment standing stock). Indicator pigment loss rates (the ratio of pigment export flux to pigment standing stock) point to preferential export of larger microplankton relative to smaller nano- and picoplankton. However, indicator pigments do not quantitatively trace particle export resulting from zooplankton grazing, which may be an important pathway for the export of small phytoplankton. These results have important implications for understanding the magnitude and mechanisms controlling the biological pump at Line P in particular, and more generally in oligotrophic gyres and high-nutrient, low-chlorophyll regions where small phytoplankton represent a major component of the autotrophic community.

  17. High-frequency monitoring reveals nutrient sources and transport processes in an agriculture-dominated lowland water system

    NASA Astrophysics Data System (ADS)

    van der Grift, Bas; Broers, Hans Peter; Berendrecht, Wilbert; Rozemeijer, Joachim; Osté, Leonard; Griffioen, Jasper

    2016-05-01

    Many agriculture-dominated lowland water systems worldwide suffer from eutrophication caused by high nutrient loads. Insight in the hydrochemical functioning of embanked polder catchments is highly relevant for improving the water quality in such areas or for reducing export loads to downstream water bodies. This paper introduces new insights in nutrient sources and transport processes in a polder in the Netherlands situated below sea level using high-frequency monitoring technology at the outlet, where the water is pumped into a higher situated lake, combined with a low-frequency water quality monitoring programme at six locations within the drainage area. Seasonal trends and short-scale temporal dynamics in concentrations indicated that the NO3 concentration at the pumping station originated from N loss from agricultural lands. The NO3 loads appear as losses via tube drains after intensive rainfall events during the winter months due to preferential flow through the cracked clay soil. Transfer function-noise modelling of hourly NO3 concentrations reveals that a large part of the dynamics in NO3 concentrations during the winter months can be related to rainfall. The total phosphorus (TP) concentration and turbidity almost doubled during operation of the pumping station, which points to resuspension of particulate P from channel bed sediments induced by changes in water flow due to pumping. Rainfall events that caused peaks in NO3 concentrations did not results in TP concentration peaks. The rainfall induced and NO3 enriched quick interflow, may also be enriched in TP but retention of TP due to sedimentation of particulate P then results in the absence of rainfall induced TP concentration peaks. Increased TP concentrations associated with run-off events is only observed during a rainfall event at the end of a freeze-thaw cycle. All these observations suggest that the P retention potential of polder water systems is primarily due to the artificial pumping regime that buffers high flows. As the TP concentration is affected by operation of the pumping station, timing of sampling relative to the operating hours of the pumping station should be accounted for when calculating P export loads, determining trends in water quality, or when judging water quality status of polder water systems.

  18. Structures and transport dynamics of a Campylobacter jejuni multidrug efflux pump

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Su, Chih-Chia; Yin, Linxiang; Kumar, Nitin

    2017-08-01

    Resistance-nodulation-cell division efflux pumps are integral membrane proteins that catalyze the export of substrates across cell membranes. Within the hydrophobe-amphiphile efflux subfamily, these resistance-nodulation-cell division proteins largely form trimeric efflux pumps. The drug efflux process has been proposed to entail a synchronized motion between subunits of the trimer to advance the transport cycle, leading to the extrusion of drug molecules. Here we use X-ray crystallography and single-molecule fluorescence resonance energy transfer imaging to elucidate the structures and functional dynamics of the Campylobacter jejuni CmeB multidrug efflux pump. We find that the CmeB trimer displays a very unique conformation. A directmore » observation of transport dynamics in individual CmeB trimers embedded in membrane vesicles indicates that each CmeB subunit undergoes conformational transitions uncoordinated and independent of each other. On the basis of our findings and analyses, we propose a model for transport mechanism where CmeB protomers function independently within the trimer.« less

  19. The impact on atmospheric CO2 of iron fertilization induced changes in the ocean's biological pump

    NASA Astrophysics Data System (ADS)

    Jin, X.; Gruber, N.; Frenzel, H.; Doney, S. C.; McWilliams, J. C.

    2007-10-01

    Using numerical simulations, we quantify the impact of changes in the ocean's biological pump on the air-sea balance of CO2 by fertilizing a small surface patch in the high-nutrient, low-chlorophyll region of the eastern tropical Pacific with iron. Decade-long fertilization experiments are conducted in a basin-scale, eddy-permitting coupled physical biogeochemical ecological model. In contrast to previous studies, we find that most of the dissolved inorganic carbon (DIC) removed from the euphotic zone by the enhanced biological export is replaced by uptake of CO2 from the atmosphere. Atmospheric uptake efficiencies, the ratio of the perturbation in air-sea CO2 flux to the perturbation in export flux across 100 m, are 0.75 to 0.93 in our patch size-scale experiments. The atmospheric uptake efficiency is insensitive to the duration of the experiment. The primary factor controlling the atmospheric uptake efficiency is the vertical distribution of the enhanced biological production. Iron fertilization at the surface tends to induce production anomalies primarily near the surface, leading to high efficiencies. In contrast, mechanisms that induce deep production anomalies (e.g. altered light availability) tend to have a low uptake efficiency, since most of the removed DIC is replaced by lateral and vertical transport and mixing. Despite high atmospheric uptake efficiencies, patch-scale iron fertilization of the ocean's biological pump tends to remove little CO2 from the atmosphere over the decadal timescale considered here.

  20. Multidrug resistance: prospects for clinical management.

    PubMed

    Mansouri, A; Henle, K J; Nagle, W A

    1992-01-01

    Clinical success in the treatment of tumors with chemotherapy has significantly improved over the past several years. However, treatment failures due to drug resistance of cancer cells has remained a major problem. The classical form of multiple drug resistance is perhaps also the most common type of drug resistance, and represents the overexpression of a transmembrane glycoprotein pump (P-170) that mediates the efflux of a spectrum of structurally and functionally unrelated drugs. Here, we discuss recent evidence that support the concept that the total phenomenon of multiple drug resistance (MDR) involves several other mechanisms in addition to that underlying "classical" MDR. These include the action of other energy-dependent membrane efflux pumps, elevated levels of GSH for drug conjugation and detoxification to facilitate export, enhanced DNA repair facility, gene amplification and oncogene activation. The combination of mechanisms used by any particular cell line is variable and suggests that many of these mechanisms are independent. Successful reversal of drug resistance appears to require the identification of relevant operative resistance mechanisms. An example is the competitive inhibition of P-170 with verapamil, quinine and tamoxifen. A broadly successful strategy for killing drug-resistant cancer cells, however, could be based on either selective energy depletion of cancer cells or the permeabilization of tumor cells with an effective bypass of efflux pumps, since many mechanisms of drug resistance entail the energy-dependent export of toxins. The latter approach may be achieved via membrane lipid modifications or the introduction of membrane pores by biological or physical (electroporation) means.

  1. 10 CFR Appendix K to Part 110 - Illustrative List of Equipment and Components Under NRC Export Licensing Authority for Use in a...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... from synthesis gas through contact with liquid ammonia in the presence of a catalyst. The systhesis gas... contactors which promote intimate gas/liquid contact. Stage pumps include especially designed submersible... down the towers while the hydrogen sulphide gas circulates from the bottom to the top of the towers. A...

  2. 10 CFR Appendix K to Part 110 - Illustrative List of Equipment and Components Under NRC Export Licensing Authority for Use in a...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... from synthesis gas through contact with liquid ammonia in the presence of a catalyst. The systhesis gas... contactors which promote intimate gas/liquid contact. Stage pumps include especially designed submersible... down the towers while the hydrogen sulphide gas circulates from the bottom to the top of the towers. A...

  3. 10 CFR Appendix K to Part 110 - Illustrative List of Equipment and Components Under NRC Export Licensing Authority for Use in a...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... from synthesis gas through contact with liquid ammonia in the presence of a catalyst. The systhesis gas... contactors which promote intimate gas/liquid contact. Stage pumps include especially designed submersible... down the towers while the hydrogen sulphide gas circulates from the bottom to the top of the towers. A...

  4. 10 CFR Appendix K to Part 110 - Illustrative List of Equipment and Components Under NRC Export Licensing Authority for Use in a...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... from synthesis gas through contact with liquid ammonia in the presence of a catalyst. The systhesis gas... contactors which promote intimate gas/liquid contact. Stage pumps include especially designed submersible... down the towers while the hydrogen sulphide gas circulates from the bottom to the top of the towers. A...

  5. 10 CFR Appendix K to Part 110 - Illustrative List of Equipment and Components Under NRC Export Licensing Authority for Use in a...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... from synthesis gas through contact with liquid ammonia in the presence of a catalyst. The systhesis gas... contactors which promote intimate gas/liquid contact. Stage pumps include especially designed submersible... down the towers while the hydrogen sulphide gas circulates from the bottom to the top of the towers. A...

  6. The role of diatom resting spores in pelagic-benthic coupling in the Southern Ocean

    NASA Astrophysics Data System (ADS)

    Rembauville, Mathieu; Blain, Stéphane; Manno, Clara; Tarling, Geraint; Thompson, Anu; Wolff, George; Salter, Ian

    2018-05-01

    Natural iron fertilization downstream of Southern Ocean island plateaus supports large phytoplankton blooms and promotes carbon export from the mixed layer. In addition to sequestering atmospheric CO2, the biological carbon pump also supplies organic matter (OM) to deep-ocean ecosystems. Although the total flux of OM arriving at the seafloor sets the energy input to the system, the chemical nature of OM is also of significance. However, a quantitative framework linking ecological flux vectors to OM composition is currently lacking. In the present study we report the lipid composition of export fluxes collected by five moored sediment traps deployed in contrasting productivity regimes of Southern Ocean island systems (Kerguelen, Crozet and South Georgia) and compile them with quantitative data on diatom and faecal pellet fluxes. At the three naturally iron-fertilized sites, the relative contribution of labile lipids (mono- and polyunsaturated fatty acids, unsaturated fatty alcohols) is 2-4 times higher than at low productivity sites. There is a strong attenuation of labile components as a function of depth, irrespective of productivity. The three island systems also display regional characteristics in lipid export. An enrichment of zooplankton dietary sterols, such as C27Δ5, at South Georgia is consistent with high zooplankton and krill biomass in the region and the importance of faecal pellets to particulate organic carbon (POC) flux. There is a strong association of diatom resting spore fluxes that dominate productive flux regimes with energy-rich unsaturated fatty acids. At the Kerguelen Plateau we provide a statistical framework to link seasonal variation in ecological flux vectors and lipid composition over a complete annual cycle. Our analyses demonstrate that ecological processes in the upper ocean, e.g. resting spore formation and grazing, not only impact the magnitude and stoichiometry of the Southern Ocean biological pump, but also regulate the composition of exported OM and the nature of pelagic-benthic coupling.

  7. Influence of top-down control in the plankton food web on vertical carbon flux: a mesocosm study in the Chesapeake Bay

    NASA Astrophysics Data System (ADS)

    Stone, J.; Steinberg, D. K.

    2016-02-01

    The effects of predation on carbon export in planktonic food webs are poorly known, but likely play a key role in the biological pump. Gelatinous zooplankton (GZ) dominate the zooplankton community in the Chesapeake Bay during summer months, exerting considerable top-down control on the planktonic food web. The medusa Chrysaora quinquecirrha preys upon the ctenophore Mnemiopsis leidyi, which in turn is a major predator of the omnivorous copepod Acartia tonsa. This trophic cascade is known to significantly affect copepod abundance in Chesapeake Bay, but the resulting changes to particulate organic carbon (POC) flux are unknown. We hypothesized that additions or exclusions of GZ predators would result in changes in both total POC flux and the composition of exported particles (e.g., phytoplankton aggregates, fecal pellets). We conducted mesocosm experiments in the York River tributary of Chesapeake Bay during summer and fall, 2015 to quantify the cascading effects of GZ blooms on POC flux. The mesocosms contained a natural assemblage of phytoplankton and microzooplankton, and A. tonsa copepods, and received one of four treatments of GZ: 1) a control with no GZ added, 2) addition of ctenophores, 3) addition of medusae, and 4) addition of both ctenophores and medusae. POC flux from each mesocosm was measured over multiple 2-day experimental runs and grazing rates of GZ on each other and on copepods were calculated. There were no significant differences in total POC flux between treatments, but the composition of both the final zooplankton assemblage and exported organic matter differed between treatments. As a result of grazing on copepods by ctenophores, treatments which included GZ had lower final copepod abundances and a corresponding decrease in flux of copepod fecal pellets. We discuss how this change in composition of exported material as a result of cascading trophic interactions may affect the efficiency of the biological pump and benthic processes.

  8. Management System for Integrating Basic Skills 2 Training and Unit Training Programs

    DTIC Science & Technology

    1983-09-01

    Social Sciences. NOTEs The findings in this report are not to be construed as en official Department of the Army position, unless so designated by other...This report describes methods used and results obtained in the design , development, and field test of a management system and curriculum components...for integrating the Army’s Basic Skills Education Program, Phase II (BSEP II) and unit training programs. The curriculum components are designed to

  9. Safe intravenous administration in pediatrics: A 5-year Pediatric Intensive Care Unit experience with smart pumps.

    PubMed

    Manrique-Rodríguez, S; Sánchez-Galindo, A C; Fernández-Llamazares, C M; Calvo-Calvo, M M; Carrillo-Álvarez, Á; Sanjurjo-Sáez, M

    2016-10-01

    To estimate the impact of smart pump implementation in a pediatric intensive care unit in terms of number and type of administration errors intercepted. Observational, prospective study carried out from January 2010 to March 2015 with syringe and great volumen infusion pumps available in the hospital. A tertiary level hospital pediatric intensive care unit. Infusions delivered with infusion pumps in all pediatric intensive care unit patients. Design of a drug library with safety limits for all intravenous drugs prescribed. Users' compliance with drug library as well as number and type of errors prevented were analyzed. Two hundred and eighty-three errors were intercepted during 62 months of study. A high risk drug was involved in 58% of prevented errors, such as adrenergic agonists and antagonists, sedatives, analgesics, neuromuscular blockers, opioids, potassium and insulin. Users' average compliance with the safety software was 84%. Smart pumps implementation has proven effective in intercepting high risk drugs programming errors. These results might be exportable to other critical care units, involving pediatric or adult patients. Interdisciplinary colaboration is key to succeed in this process. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  10. Biological and physical controls in the Southern Ocean on past millennial-scale atmospheric CO2 changes.

    PubMed

    Gottschalk, Julia; Skinner, Luke C; Lippold, Jörg; Vogel, Hendrik; Frank, Norbert; Jaccard, Samuel L; Waelbroeck, Claire

    2016-05-17

    Millennial-scale climate changes during the last glacial period and deglaciation were accompanied by rapid changes in atmospheric CO2 that remain unexplained. While the role of the Southern Ocean as a 'control valve' on ocean-atmosphere CO2 exchange has been emphasized, the exact nature of this role, in particular the relative contributions of physical (for example, ocean dynamics and air-sea gas exchange) versus biological processes (for example, export productivity), remains poorly constrained. Here we combine reconstructions of bottom-water [O2], export production and (14)C ventilation ages in the sub-Antarctic Atlantic, and show that atmospheric CO2 pulses during the last glacial- and deglacial periods were consistently accompanied by decreases in the biological export of carbon and increases in deep-ocean ventilation via southern-sourced water masses. These findings demonstrate how the Southern Ocean's 'organic carbon pump' has exerted a tight control on atmospheric CO2, and thus global climate, specifically via a synergy of both physical and biological processes.

  11. Biological and physical controls in the Southern Ocean on past millennial-scale atmospheric CO2 changes

    PubMed Central

    Gottschalk, Julia; Skinner, Luke C.; Lippold, Jörg; Vogel, Hendrik; Frank, Norbert; Jaccard, Samuel L.; Waelbroeck, Claire

    2016-01-01

    Millennial-scale climate changes during the last glacial period and deglaciation were accompanied by rapid changes in atmospheric CO2 that remain unexplained. While the role of the Southern Ocean as a 'control valve' on ocean–atmosphere CO2 exchange has been emphasized, the exact nature of this role, in particular the relative contributions of physical (for example, ocean dynamics and air–sea gas exchange) versus biological processes (for example, export productivity), remains poorly constrained. Here we combine reconstructions of bottom-water [O2], export production and 14C ventilation ages in the sub-Antarctic Atlantic, and show that atmospheric CO2 pulses during the last glacial- and deglacial periods were consistently accompanied by decreases in the biological export of carbon and increases in deep-ocean ventilation via southern-sourced water masses. These findings demonstrate how the Southern Ocean's 'organic carbon pump' has exerted a tight control on atmospheric CO2, and thus global climate, specifically via a synergy of both physical and biological processes. PMID:27187527

  12. Natural ocean carbon cycle sensitivity to parameterizations of the recycling in a climate model

    NASA Astrophysics Data System (ADS)

    Romanou, A.; Romanski, J.; Gregg, W. W.

    2014-02-01

    Sensitivities of the oceanic biological pump within the GISS (Goddard Institute for Space Studies ) climate modeling system are explored here. Results are presented from twin control simulations of the air-sea CO2 gas exchange using two different ocean models coupled to the same atmosphere. The two ocean models (Russell ocean model and Hybrid Coordinate Ocean Model, HYCOM) use different vertical coordinate systems, and therefore different representations of column physics. Both variants of the GISS climate model are coupled to the same ocean biogeochemistry module (the NASA Ocean Biogeochemistry Model, NOBM), which computes prognostic distributions for biotic and abiotic fields that influence the air-sea flux of CO2 and the deep ocean carbon transport and storage. In particular, the model differences due to remineralization rate changes are compared to differences attributed to physical processes modeled differently in the two ocean models such as ventilation, mixing, eddy stirring and vertical advection. GISSEH(GISSER) is found to underestimate mixed layer depth compared to observations by about 55% (10%) in the Southern Ocean and overestimate it by about 17% (underestimate by 2%) in the northern high latitudes. Everywhere else in the global ocean, the two models underestimate the surface mixing by about 12-34%, which prevents deep nutrients from reaching the surface and promoting primary production there. Consequently, carbon export is reduced because of reduced production at the surface. Furthermore, carbon export is particularly sensitive to remineralization rate changes in the frontal regions of the subtropical gyres and at the Equator and this sensitivity in the model is much higher than the sensitivity to physical processes such as vertical mixing, vertical advection and mesoscale eddy transport. At depth, GISSER, which has a significant warm bias, remineralizes nutrients and carbon faster thereby producing more nutrients and carbon at depth, which eventually resurfaces with the global thermohaline circulation especially in the Southern Ocean. Because of the reduced primary production and carbon export in GISSEH compared to GISSER, the biological pump efficiency, i.e., the ratio of primary production and carbon export at 75 m, is half in the GISSEH of that in GISSER, The Southern Ocean emerges as a key region where the CO2 flux is as sensitive to biological parameterizations as it is to physical parameterizations. The fidelity of ocean mixing in the Southern Ocean compared to observations is shown to be a good indicator of the magnitude of the biological pump efficiency regardless of physical model choice.

  13. Natural Ocean Carbon Cycle Sensitivity to Parameterizations of the Recycling in a Climate Model

    NASA Technical Reports Server (NTRS)

    Romanou, A.; Romanski, J.; Gregg, W. W.

    2014-01-01

    Sensitivities of the oceanic biological pump within the GISS (Goddard Institute for Space Studies ) climate modeling system are explored here. Results are presented from twin control simulations of the air-sea CO2 gas exchange using two different ocean models coupled to the same atmosphere. The two ocean models (Russell ocean model and Hybrid Coordinate Ocean Model, HYCOM) use different vertical coordinate systems, and therefore different representations of column physics. Both variants of the GISS climate model are coupled to the same ocean biogeochemistry module (the NASA Ocean Biogeochemistry Model, NOBM), which computes prognostic distributions for biotic and abiotic fields that influence the air-sea flux of CO2 and the deep ocean carbon transport and storage. In particular, the model differences due to remineralization rate changes are compared to differences attributed to physical processes modeled differently in the two ocean models such as ventilation, mixing, eddy stirring and vertical advection. GISSEH(GISSER) is found to underestimate mixed layer depth compared to observations by about 55% (10 %) in the Southern Ocean and overestimate it by about 17% (underestimate by 2%) in the northern high latitudes. Everywhere else in the global ocean, the two models underestimate the surface mixing by about 12-34 %, which prevents deep nutrients from reaching the surface and promoting primary production there. Consequently, carbon export is reduced because of reduced production at the surface. Furthermore, carbon export is particularly sensitive to remineralization rate changes in the frontal regions of the subtropical gyres and at the Equator and this sensitivity in the model is much higher than the sensitivity to physical processes such as vertical mixing, vertical advection and mesoscale eddy transport. At depth, GISSER, which has a significant warm bias, remineralizes nutrients and carbon faster thereby producing more nutrients and carbon at depth, which eventually resurfaces with the global thermohaline circulation especially in the Southern Ocean. Because of the reduced primary production and carbon export in GISSEH compared to GISSER, the biological pump efficiency, i.e., the ratio of primary production and carbon export at 75 m, is half in the GISSEH of that in GISSER, The Southern Ocean emerges as a key region where the CO2 flux is as sensitive to biological parameterizations as it is to physical parameterizations. The fidelity of ocean mixing in the Southern Ocean compared to observations is shown to be a good indicator of the magnitude of the biological pump efficiency regardless of physical model choice.

  14. Classroom Materials for Job-Related BSEP 2 Program

    DTIC Science & Technology

    1983-09-01

    gathered D. gathered, combined, camoufl age 10. The greedy man was happy to take the money. A. greedy C. was *B. was happy D. take 11. The banana ...tastes good with peanut butter on it. A. tastes C. tastes good B. on D. banana III. Instructions: You are given a choice of two verbs in the following...previously o.- before. (The M16 had ALREADY been fired.) 162 peel Grammar Activity Sheet 36A Good Usage of English Name 6. ALL RIGHT - "ALRIGHT" ALL RIGHT

  15. Proceedings of the TRADOC Chiefs of Analysis Seminar (3rd) held 15-17 January 1980, Hampton, Virginia.

    DTIC Science & Technology

    1980-01-25

    11:00 Functional Literacy COL Merrick TRADOC BSEP DR Spangenberg Task Force 11:45 Lunch 13:00 Skill Knowledge Survey Data CMDR Hawrysh Canadian Forces... PSYCHOMOTOR WE HAVE TO TRAIN PEOPLE TO DO MOTOR SKILLS , RIGHT? (ONLY FINE MOTOR!) FOR EXAMPLE ..... IT WOULD BE NICE IF A GIVEN TASK ONLY INVOLVED...GENERALIZATION IS NEEDED REASONS "WHY" MUST BE GIVEN *USER IS NOT FAMILIAR WITH THE TERMINOLOGY *FINE PSYCHOMOTOR SKILLS ARE REQUIRED. THIS JOB AID HELPS YOU

  16. Needs Assessment to Define the Training Requirements for a Basic Skills Education Program (BSEP) Curriculum Development. Revision.

    DTIC Science & Technology

    1984-04-01

    compounds time, understanding and coordination problems. Just too many people in the process. In fact, there are numerous versions of a task with the...sometimes -his caused interruptions. Nhis was further compounded by the fact that the cnalyss * voas toarted ar-d +hen t~opped, when the first cnaiyst...productive. Discrepancies - The major discrepancy was ’he use of Anti-Seize Compound . It is applied to components as a light, thin coat to prevent i..re, any

  17. Evaluation of the McFann, Gray & Associates’ BSEP (Basic Skills Education Program) 2. Curriculum

    DTIC Science & Technology

    1985-08-01

    167 APPENDIX A - Tables APPENDIX B - Student Record Sheets, Module Record Sheets, Classroom Observation Form, and Questionnaires iv LIST OF...course data and demographic data about students, and classroom observation forms for recording classroom activities), * attended teacher-training...5.3% 27.5% (29) (7) (36) >=9.0 18.3% 54.2% 72.5% (24) (71) (95) Total 40.5% 59.5% 100% (53) (78) (131) ell APPENDIX B 4., ’-o CLASSROOM OBSERVATION SHEET

  18. Amino acid stable isotope applications to deep-sea corals: A molecular geochemistry approach to reconstructing past ocean conditions

    NASA Astrophysics Data System (ADS)

    McMahon, K.; McCarthy, M. D.; Guilderson, T. P.; Sherwood, O.; Williams, B.; Larsen, T.; Glynn, D. S.

    2017-12-01

    Future climate change is predicted to alter ocean productivity, food web dynamics, biogeochemical cycling, and the efficacy of the biological pump. Proteinaceous deep-sea corals act as "living sediment traps," providing long-term, high-resolution records of exported surface ocean production and a window into past changes in ocean condition as a historical context for potential future changes. Here, we present recent work developing the application of compound-specific stable isotope analysis of individual amino acids to proteinaceous deep-sea corals to reconstruct past changes in phytoplankton community composition and biogeochemical cycling. We present new calibrations for molecular isotope comparisons between metabolically active coral polyp tissue and bioarchival proteinaceous skeleton. We then applied these techniques to deep-sea corals from the North Pacific Subtropical Gyre (NPSG) to reconstruct centennial to millennial time scale changes in phytoplankton community composition and biogeochemical cycling as a function of regional climate change. This work suggests that the NPSG has undergone multiple major phytoplankton regime shifts over the last millennium between prokaryotic and eukaryotic phytoplankton communities and associated sources of nitrogen fueling production. The most recent regime, which started around the end of the Little Ice Age and the onset of the Industrial era, is unprecedented in the last 1000 years and resulted in a 30-50% increase in diazotrophic cyanobacteria contribution to export production and an associated 17-27% increase in N2-fixation in the NPSG over last century. By offering the first direct phylogenetic context for long-term shifts in isotopic records of exported particulate organic matter, our data represent a major step forward in understanding the evolution of marine plankton community dynamics, food web architecture, biogeochemical cycling, and the climate feedback loops through the biological pump.

  19. The Southern Ocean biogeochemical divide.

    PubMed

    Marinov, I; Gnanadesikan, A; Toggweiler, J R; Sarmiento, J L

    2006-06-22

    Modelling studies have demonstrated that the nutrient and carbon cycles in the Southern Ocean play a central role in setting the air-sea balance of CO(2) and global biological production. Box model studies first pointed out that an increase in nutrient utilization in the high latitudes results in a strong decrease in the atmospheric carbon dioxide partial pressure (pCO2). This early research led to two important ideas: high latitude regions are more important in determining atmospheric pCO2 than low latitudes, despite their much smaller area, and nutrient utilization and atmospheric pCO2 are tightly linked. Subsequent general circulation model simulations show that the Southern Ocean is the most important high latitude region in controlling pre-industrial atmospheric CO(2) because it serves as a lid to a larger volume of the deep ocean. Other studies point out the crucial role of the Southern Ocean in the uptake and storage of anthropogenic carbon dioxide and in controlling global biological production. Here we probe the system to determine whether certain regions of the Southern Ocean are more critical than others for air-sea CO(2) balance and the biological export production, by increasing surface nutrient drawdown in an ocean general circulation model. We demonstrate that atmospheric CO(2) and global biological export production are controlled by different regions of the Southern Ocean. The air-sea balance of carbon dioxide is controlled mainly by the biological pump and circulation in the Antarctic deep-water formation region, whereas global export production is controlled mainly by the biological pump and circulation in the Subantarctic intermediate and mode water formation region. The existence of this biogeochemical divide separating the Antarctic from the Subantarctic suggests that it may be possible for climate change or human intervention to modify one of these without greatly altering the other.

  20. Coarse-grained Simulations of Substrate Export through Multidrug Efflux Transporter AcrB

    NASA Astrophysics Data System (ADS)

    Jewel, Yead; Dutta, Prashanta; Liu, Jin

    2017-11-01

    The treatment of bacterial infectious diseases hampered by the overexpression of multidrug resistance (MDR) systems. The MDR system actively pumps the antibiotic drugs as well as other toxic compounds out of the cells. During the pumping, AcrB (one of the key MDR components) undergoes a series of large-scale proton/substrate dependent conformational changes. In this work, we implement a hybrid coarse-grained PACE force field that couples the united-atom protein model with the coarse-grained MARTINI water/lipid, to investigate the conformational changes of AcrB. We first develop the substrate force field which is compatible with PACE, then we implement the force field to explore large scale structural changes of AcrB in microsecond simulations. The effects of the substrate and the protonation states of two key residues: Asp407 and Asp408, are investigated. Our results show that the drug export through AcrB is proton as well as substrate dependent. Our simulations explain molecular mechanisms of substrate transport through AcrB complex, as well as provide valuable insights for designing proper antibiotic drugs. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R01GM122081.

  1. Electricity for groundwater use: constraints and opportunities for adaptive response to climate change

    NASA Astrophysics Data System (ADS)

    Scott, Christopher A.

    2013-09-01

    Globally, groundwater use is intensifying to meet demands for irrigation, urban supply, industrialization, and, in some instances, electrical power generation. In response to hydroclimatic variability, surface water is being substituted with groundwater, which must be viewed as a strategic resource for climate adaptation. In this sense, the supply of electricity for pumping is an adaptation policy tool. Additionally, planning for climate-change mitigation must consider CO2 emissions resulting from pumping. This paper examines the influence of electricity supply and pricing on groundwater irrigation and resulting emissions, with specific reference to Mexico—a climate-water-energy ‘perfect storm’. Night-time power supply at tariffs below the already-subsidized rates for agricultural groundwater use has caused Mexican farmers to increase pumping, reversing important water and electricity conservation gains achieved. Indiscriminate groundwater pumping, including for virtual water exports of agricultural produce, threatens the long-term sustainability of aquifers, non-agricultural water uses, and stream-aquifer interactions that sustain riparian ecosystems. Emissions resulting from agricultural groundwater pumping in Mexico are estimated to be 3.6% of total national emissions and are equivalent to emissions from transporting the same agricultural produce to market. The paper concludes with an assessment of energy, water, and climate trends coupled with policy futures to address these challenges.

  2. Biological production in the Indian Ocean upwelling zones - Part 1: refined estimation via the use of a variable compensation depth in ocean carbon models

    NASA Astrophysics Data System (ADS)

    Geethalekshmi Sreeush, Mohanan; Valsala, Vinu; Pentakota, Sreenivas; Venkata Siva Rama Prasad, Koneru; Murtugudde, Raghu

    2018-04-01

    Biological modelling approach adopted by the Ocean Carbon-Cycle Model Intercomparison Project (OCMIP-II) provided amazingly simple but surprisingly accurate rendition of the annual mean carbon cycle for the global ocean. Nonetheless, OCMIP models are known to have seasonal biases which are typically attributed to their bulk parameterisation of compensation depth. Utilising the criteria of surface Chl a-based attenuation of solar radiation and the minimum solar radiation required for production, we have proposed a new parameterisation for a spatially and temporally varying compensation depth which captures the seasonality in the production zone reasonably well. This new parameterisation is shown to improve the seasonality of CO2 fluxes, surface ocean pCO2, biological export and new production in the major upwelling zones of the Indian Ocean. The seasonally varying compensation depth enriches the nutrient concentration in the upper ocean yielding more faithful biological exports which in turn leads to accurate seasonality in the carbon cycle. The export production strengthens by ˜ 70 % over the western Arabian Sea during the monsoon period and achieves a good balance between export and new production in the model. This underscores the importance of having a seasonal balance in the model export and new productions for a better representation of the seasonality of the carbon cycle over upwelling regions. The study also implies that both the biological and solubility pumps play an important role in the Indian Ocean upwelling zones.

  3. Tdp studies and tests for C. A. Energia Electrica de Venezuela (enelven) at planta ramon laguna, units RL-17 and RL-10. Volume 3. Unit RL-10 turbine generator condition assessment report and units RL-10 and RL-11 boiler feed pump conditon assessment report. Export trade information

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1991-03-28

    The study, conducted by Babcock and Wilcox, was funded by the U.S. Trade and Development agency on behalf of Enelven. In order to maximize generated power output and minimize operating costs at Planta Ramon Laguna, tests were done to evaluate the condition of equipment at the plant. In order to identify any damage and determine the operating output of each unit, assessments were done of the furnaces, boilers, generators and boiler feed pumps being used in the plant. The report presents the results of these tests. This is the last of three volumes and it is divided into the followingmore » sections: (1) Condition Assessment of Unit RL-10 Turbine-Generator; (2) Condition Assessment of Unit RL-10 and RL-11 Boiler Feed Pumps.« less

  4. Scanning electrochemical microscopy of menadione-glutathione conjugate export from yeast cells

    PubMed Central

    Mauzeroll, Janine; Bard, Allen J.

    2004-01-01

    The uptake of menadione (2-methyl-1,4-naphthoquinone), which is toxic to yeast cells, and its expulsion as a glutathione complex were studied by scanning electrochemical microscopy. The progression of the in vitro reaction between menadione and glutathione was monitored electrochemically by cyclic voltammetry and correlated with the spectroscopic (UV–visible) behavior. By observing the scanning electrochemical microscope tip current of yeast cells suspended in a menadione-containing solution, the export of the conjugate from the cells with time could be measured. Similar experiments were performed on immobilized yeast cell aggregates stressed by a menadione solution. From the export of the menadione-glutathione conjugate detected at a 1-μm-diameter electrode situated 10 μm from the cells, a flux of about 30,000 thiodione molecules per second per cell was extracted. Numerical simulations based on an explicit finite difference method further revealed that the observation of a constant efflux of thiodione from the cells suggested the rate was limited by the uptake of menadione and that the efflux through the glutathione-conjugate pump was at least an order of magnitude faster. PMID:15148374

  5. Short communication: Massive erosion in monsoonal central India linked to late Holocene land cover degradation

    NASA Astrophysics Data System (ADS)

    Giosan, Liviu; Ponton, Camilo; Usman, Muhammed; Blusztajn, Jerzy; Fuller, Dorian Q.; Galy, Valier; Haghipour, Negar; Johnson, Joel E.; McIntyre, Cameron; Wacker, Lukas; Eglinton, Timothy I.

    2017-12-01

    Soil erosion plays a crucial role in transferring sediment and carbon from land to sea, yet little is known about the rhythm and rates of soil erosion prior to the most recent few centuries. Here we reconstruct a Holocene erosional history from central India, as integrated by the Godavari River in a sediment core from the Bay of Bengal. We quantify terrigenous fluxes, fingerprint sources for the lithogenic fraction and assess the age of the exported terrigenous carbon. Taken together, our data show that the monsoon decline in the late Holocene significantly increased soil erosion and the age of exported organic carbon. This acceleration of natural erosion was later exacerbated by the Neolithic adoption and Iron Age extensification of agriculture on the Deccan Plateau. Despite a constantly elevated sea level since the middle Holocene, this erosion acceleration led to a rapid growth of the continental margin. We conclude that in monsoon conditions aridity boosts rather than suppresses sediment and carbon export, acting as a monsoon erosional pump modulated by land cover conditions.

  6. Variable C : N : P stoichiometry of dissolved organic matter cycling in the Community Earth System Model

    DOE PAGES

    Letscher, R. T.; Moore, J. K.; Teng, Y. -C.; ...

    2014-06-16

    Dissolved organic matter (DOM) plays an important role in the ocean's biological carbon pump by providing an advective/mixing pathway for ~ 20% of export production. DOM is known to have a stoichiometry depleted in nitrogen (N) and phosphorus (P) compared to the particulate organic matter pool, a~fact that is often omitted from biogeochemical-ocean general circulation models. However the variable C : N : P stoichiometry of DOM becomes important when quantifying carbon export from the upper ocean and linking the nutrient cycles of N and P with that of carbon. Here we utilize recent advances in DOM observational data coveragemore » and offline tracer-modeling techniques to objectively constrain the variable production and remineralization rates of the DOM C / N / P pools in a simple biogeochemical-ocean model of DOM cycling. The optimized DOM cycling parameters are then incorporated within the Biogeochemical Elemental Cycling (BEC) component of the Community Earth System Model and validated against the compilation of marine DOM observations. The optimized BEC simulation including variable DOM C : N : P cycling was found to better reproduce the observed DOM spatial gradients than simulations that used the canonical Redfield ratio. Global annual average export of dissolved organic C, N, and P below 100 m was found to be 2.28 Pg C yr -1 (143 Tmol C yr -1), 16.4 Tmol N yr -1, and 1 Tmol P yr -1, respectively with an average export C : N : P stoichiometry of 225 : 19 : 1 for the semilabile (degradable) DOM pool. DOC export contributed ~ 25% of the combined organic C export to depths greater than 100 m.« less

  7. Variable C : N : P stoichiometry of dissolved organic matter cycling in the Community Earth System Model

    DOE PAGES

    Letscher, R. T.; Moore, J. K.; Teng, Y. -C.; ...

    2015-01-12

    Dissolved organic matter (DOM) plays an important role in the ocean's biological carbon pump by providing an advective/mixing pathway for ~ 20% of export production. DOM is known to have a stoichiometry depleted in nitrogen (N) and phosphorus (P) compared to the particulate organic matter pool, a fact that is often omitted from biogeochemical ocean general circulation models. However the variable C : N : P stoichiometry of DOM becomes important when quantifying carbon export from the upper ocean and linking the nutrient cycles of N and P with that of carbon. Here we utilize recent advances in DOM observationalmore » data coverage and offline tracer-modeling techniques to objectively constrain the variable production and remineralization rates of the DOM C : N : P pools in a simple biogeochemical-ocean model of DOM cycling. The optimized DOM cycling parameters are then incorporated within the Biogeochemical Elemental Cycling (BEC) component of the Community Earth System Model (CESM) and validated against the compilation of marine DOM observations. The optimized BEC simulation including variable DOM C : N : P cycling was found to better reproduce the observed DOM spatial gradients than simulations that used the canonical Redfield ratio. Global annual average export of dissolved organic C, N, and P below 100 m was found to be 2.28 Pg C yr -1 (143 Tmol C yr -1, 16.4 Tmol N yr -1, and 1 Tmol P yr -1, respectively, with an average export C : N : P stoichiometry of 225 : 19 : 1 for the semilabile (degradable) DOM pool. Dissolved organic carbon (DOC) export contributed ~ 25% of the combined organic C export to depths greater than 100 m.« less

  8. Boldine enhances bile production in rats via osmotic and farnesoid X receptor dependent mechanisms.

    PubMed

    Cermanova, Jolana; Kadova, Zuzana; Zagorova, Marie; Hroch, Milos; Tomsik, Pavel; Nachtigal, Petr; Kudlackova, Zdenka; Pavek, Petr; Dubecka, Michaela; Ceckova, Martina; Staud, Frantisek; Laho, Tomas; Micuda, Stanislav

    2015-05-15

    Boldine, the major alkaloid from the Chilean Boldo tree, is used in traditional medicine to support bile production, but evidence to support this function is controversial. We analyzed the choleretic potential of boldine, including its molecular background. The acute- and long-term effects of boldine were evaluated in rats either during intravenous infusion or after 28-day oral treatment. Infusion of boldine instantly increased the bile flow 1.4-fold in healthy rats as well as in animals with Mrp2 deficiency or ethinylestradiol induced cholestasis. This effect was not associated with a corresponding increase in bile acid or glutathione biliary excretion, indicating that the effect is not related to stimulation of either bile acid dependent or independent mechanisms of bile formation and points to the osmotic activity of boldine itself. We subsequently analyzed bile production under conditions of changing biliary excretion of boldine after bolus intravenous administration and found strong correlations between both parameters. HPLC analysis showed that bile concentrations of boldine above 10 μM were required for induction of choleresis. Importantly, long-term pretreatment, when the bile collection study was performed 24-h after the last administration of boldine, also accelerated bile formation despite undetectable levels of the compound in bile. The effect paralleled upregulation of the Bsep transporter and increased biliary clearance of its substrates, bile acids. We consequently confirmed the ability of boldine to stimulate the Bsep transcriptional regulator, FXR receptor. In conclusion, our study clarified the mechanisms and circumstances surrounding the choleretic activity of boldine. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Different effects of ursodeoxycholic acid on intrahepatic cholestasis in acute and recovery stages induced by alpha-naphthylisothiocyanate in mice.

    PubMed

    Zhang, Linlin; Su, Huizong; Li, Yue; Fan, Yujuan; Wang, Qian; Jiang, Jian; Hu, Yiyang; Chen, Gaofeng; Tan, Bo; Qiu, Furong

    2018-03-01

    The aim of this study was to determine the effect of ursodeoxycholic acid (UDCA) on the alpha-naphthylisothiocyanate (ANIT)-induced acute and recovery stage of cholestasis model mice. In the acute stage of model mice, pretreatment with UDCA (25, 50, and 100 mg·kg -1 , ig) for 12 days prior to ANIT administration (50 mg·kg -1 , ig) resulted in the dramatic increase in serum biochemistry, with aggrevation of bile infarcts and hepatocyte necrosis. The elevation of beta-muricholic acid (β-MCA), cholic acid (CA), and taurocholic acid (TCA) in serum and liver, and reduction of these bile acids (BAs) in bile was observed. In contrast, in the recovery stage of model mice, treatment with UDCA (25, 50, and 100 mg·kg -1 , ig) for 7 days after ANIT administration (50 mg·kg -1 , ig) resulted in the significant decrease in levels of serum alanine aminotransferase (ALT) and total bile acid (TBA). Liver injury was attenuated, and the levels of TBA, CA, TCA, and β-MCA in the liver were significantly decreased. Additionally, UDCA can upregulate expression of BSEP, but it cannot upregulate expression of AE2. UDCA, which induced BSEP to increase bile acid-dependent bile flow, aggravated cholestasis and liver injury when the bile duct was obstructed in the acute stage of injury in model mice. In contrast, UDCA alleviated cholestasis and liver injury induced by ANIT when the obstruction was improved in the recovery stage. Copyright © 2018. Published by Elsevier Inc.

  10. Simulated ground-water flow for a pond-dominated aquifer system near Great Sandy Bottom Pond, Pembroke, Massachusetts

    USGS Publications Warehouse

    Carlson, Carl S.; Lyford, Forest P.

    2005-01-01

    A ground-water flow simulation for a 66.4-square-mile area around Great Sandy Bottom (GSB) Pond (105 acres) near Pembroke, Massachusetts, was developed for use by local and State water managers to assess the yields for public water supply of local ponds and wells for average climatic and drought conditions and the effects of water withdrawals on nearby water levels and streamflows. Wetlands and ponds cover about 30 percent of the study area and the aquifer system is dominated by interactions between ground water and the ponds. The three largest surface-water bodies in the study area are Silver Lake (640 acres), Monponsett Pond (590 acres), and Oldham Pond (236 acres). The study area is drained by tributaries of the Taunton River to the southwest, the South and North Rivers to the northeast, and the Jones River to the southeast. In 2002, 10.8 million gallons per day of water was exported from ponds and 3.5 million gallons per day from wells was used locally for public supply. A transient ground-water-flow model with 69 monthly stress periods spanning the period from January 1998 through September 2003 was calibrated to stage at GSB Pond and nearby Silver Lake and streamflow and water levels collected from September 2002 through September 2003. The calibrated model was used to assess hydrologic responses to a variety of water-use and climatic conditions. Simulation of predevelopment (no pumping or export) average monthly (1949-2002) water-level conditions caused the GSB Pond level to increase by 6.3 feet from the results of a simulation using average 2002 pumping for all wells, withdrawals, and exports. Most of this decline can be attributed to pumping, withdrawals, and exports of water from sites away from GSB Pond. The effects of increasing the export rate from GSB Pond by 1.25 and 1.5 times the 2002 rate were a lowering of pond levels by a maximum of 1.6 and 2.8 feet, respectively. Simulated results for two different drought conditions, one mild drought similar to that of 1979-82 and a more severe drought similar to that of 1963-66, but with current (2002) pumping, were compared to results for average monthly recharge conditions (1949-2002). Simulated mild drought conditions showed a reduction of GSB Pond level of about 1.3 feet and a lower streamflow of about 1.7 percent in the nearby stream. Simulated severe drought conditions reduced the pond level at GSB Pond by almost 7 feet and lowered streamflow by about 37 percent. Varying cranberry-irrigation practices had little effect on simulated GSB Pond water levels, but may be important in other ponds. The model was most sensitive to changes in areal recharge. An increase and decrease of 22 percent in recharge produced changes in the GSB Pond water level of +1.4 feet and -2.4 feet, respectively. The accuracy of simulation results was best in the central portion of the study area in the immediate location of GSB Pond. The model was developed with the study-area boundary far enough away from the GSB Pond area that the boundary would have minimal effect on the water levels in GSB Pond, nearby ponds, and the underlying aquifer system. The model is best suited for use by local and State water managers to assess the effects of different withdrawal scenarios for wells and ponds near GSB Pond and for general delineation of areas contributing recharge to wells and ponds in the vicinity of GSB Pond. The model in its current form may not be well suited to detailed analyses of water budgets and flow patterns for parts of the study area farther from GSB Pond without further investigation, calibration, and data collection.

  11. Sustaining nutrient supply and carbon export in a seasonally-stratifying shelf sea through inconsistent production and remineralisation stoichiometry

    NASA Astrophysics Data System (ADS)

    Humphreys, Matthew; Moore, Mark; Achterberg, Eric; Chowdhury, Mohammed; Griffiths, Alex; Hartman, Susan; Hopkins, Joanne; Hull, Tom; Kivimäe, Caroline; Sivyer, Dave; Smilenova, Angelina; Wihsgott, Juliane; Woodward, Malcolm

    2017-04-01

    Continental shelf seas support 15-20% of global primary productivity despite covering only about 5% of the Earth's ocean surface area. As a result, they may have a significant role in oceanic uptake and storage of carbon dioxide (CO2) from the atmosphere, through the 'continental shelf pump' mechanism. The northwest European continental shelf, in particular the Celtic Sea (50°N 8°W), was the target of extensive biogeochemical sampling from March 2014 to September 2015, as part of the UK Shelf Sea Biogeochemistry research programme (UK-SSB). Here, we use the UK-SSB carbonate chemistry and macronutrient measurements to investigate the biogeochemical seasonality in the temperate, seasonally-stratifying Celtic Sea. During the spring-summer, near-surface biological activity removed dissolved inorganic carbon and nutrients, some of which were then exported into the deeper layer. We calculated vertical inventories of these variables throughout 1.5 seasonal cycles and attempted to correct these for air-sea CO2 exchange, advection and denitrification, thus isolating the combined effect of net community production and remineralisation on the inorganic macronutrient inventories, and revealing fluctuating deviations from Redfield stoichiometry. Here, we discuss the capacity of these stoichiometric inconsistencies to sustain the Celtic Sea nutrient supply, and thus examine whether an effective continental shelf pump for CO2 could operate in this region.

  12. Substantial energy input to the mesopelagic ecosystem from the seasonal mixed-layer pump

    PubMed Central

    Dall’Olmo, Giorgio; Dingle, James; Polimene, Luca; Brewin, Robert J.W.; Claustre, Hervé

    2016-01-01

    The “mesopelagic” is the region of the ocean between about 100 and 1000 m that harbours one of the largest ecosystems and fish stocks on the planet1,2. This vastly unexplored ecosystem is believed to be mostly sustained by chemical energy, in the form of fast-sinking particulate organic carbon, supplied by the biological carbon pump3. Yet, this supply appears insufficient to match mesopelagic metabolic demands4–6. The mixed-layer pump is a physically-driven biogeochemical process7–11 that could further contribute to meet these energetic requirements. However, little is known about the magnitude and spatial distribution of this process at the global scale. Here we show that the mixed-layer pump supplies an important seasonal flux of organic carbon to the mesopelagic. By combining mixed-layer depths from Argo floats with satellite retrievals of particulate organic carbon, we estimate that this pump exports a global flux of about 0.3 Pg C yr−1 (range 0.1 – 0.5 Pg C yr−1). In high-latitude regions where mixed-layers are deep, this flux is on average 23%, but can be greater than 100% of the carbon supplied by fast sinking particles. Our results imply that a relatively large flux of organic carbon is missing from current energy budgets of the mesopelagic. PMID:27857779

  13. High particulate organic carbon export during the decline of a vast diatom bloom in the Atlantic sector of the Southern Ocean

    NASA Astrophysics Data System (ADS)

    Roca-Martí, Montserrat; Puigcorbé, Viena; Iversen, Morten H.; van der Loeff, Michiel Rutgers; Klaas, Christine; Cheah, Wee; Bracher, Astrid; Masqué, Pere

    2017-04-01

    Carbon fixation by phytoplankton plays a key role in the uptake of atmospheric CO2 in the Southern Ocean. Yet, it still remains unclear how efficiently the particulate organic carbon (POC) is exported and transferred from ocean surface waters to depth during phytoplankton blooms. In addition, little is known about the processes that control the flux attenuation within the upper twilight zone. Here, we present results of downward POC and particulate organic nitrogen fluxes during the decline of a vast diatom bloom in the Atlantic sector of the Southern Ocean in summer 2012. We used thorium-234 (234Th) as a particle tracer in combination with drifting sediment traps (ST). Their simultaneous use evidenced a sustained high export rate of 234Th at 100 m depth in the weeks prior to and during the sampling period. The entire study area, of approximately 8000 km2, showed similar vertical export fluxes in spite of the heterogeneity in phytoplankton standing stocks and productivity, indicating a decoupling between production and export. The POC fluxes at 100 m were high, averaging 26±15 mmol C m-2 d-1, although the strength of the biological pump was generally low. Only <20% of the daily primary production reached 100 m, presumably due to an active recycling of carbon and nutrients. Pigment analyses indicated that direct sinking of diatoms likely caused the high POC transfer efficiencies ( 60%) observed between 100 and 300 m, although faecal pellets and transport of POC linked to zooplankton vertical migration might have also contributed to downward fluxes.

  14. Do Continental Shelves Act as an Atmospheric CO2 Sink?

    NASA Astrophysics Data System (ADS)

    Cai, W.

    2003-12-01

    Recent air-to-sea CO2 flux measurements at several major continental shelves (European Atlantic Shelves, East China Sea and U.S. Middle Atlantic Bight) suggest that shelves may act as a one-way pump and absorb atmospheric CO2 into the ocean. These observations also favor the argument that continental shelves are autotrophic (i.e., net production of organic carbon, OC). The U.S. South Atlantic Bight (SAB) contrasts these findings in that it acts as a strong source of CO2 to the atmosphere while simultaneously exporting dissolved inorganic carbon (DIC) to the open ocean. We report pCO2, DIC, and alkalinity data from the SAB collected in 8 cruises along a transect from the shore to the shelf break in the central SAB. The shelf-wide net heterotrophy and carbon exports in the SAB are subsidized by the export of OC from the abundant intertidal marshes, which are a sink for atmospheric CO2. It is proposed here that the SAB represents a marsh-dominated heterotrophic ocean margin as opposed to river-dominated autotrophic margins. To further investigate why margins may behave differently in term of CO2 sink/source, the physical and biological conditions of several western boundary current margins are compared. Based on this and other studies, DIC export flux from margins to the open ocean must be significant in the overall global ocean carbon budget.

  15. Iron defecation by sperm whales stimulates carbon export in the Southern Ocean

    PubMed Central

    Lavery, Trish J.; Roudnew, Ben; Gill, Peter; Seymour, Justin; Seuront, Laurent; Johnson, Genevieve; Mitchell, James G.; Smetacek, Victor

    2010-01-01

    The iron-limited Southern Ocean plays an important role in regulating atmospheric CO2 levels. Marine mammal respiration has been proposed to decrease the efficiency of the Southern Ocean biological pump by returning photosynthetically fixed carbon to the atmosphere. Here, we show that by consuming prey at depth and defecating iron-rich liquid faeces into the photic zone, sperm whales (Physeter macrocephalus) instead stimulate new primary production and carbon export to the deep ocean. We estimate that Southern Ocean sperm whales defecate 50 tonnes of iron into the photic zone each year. Molar ratios of Cexport ∶Feadded determined during natural ocean fertilization events are used to estimate the amount of carbon exported to the deep ocean in response to the iron defecated by sperm whales. We find that Southern Ocean sperm whales stimulate the export of 4 × 105 tonnes of carbon per year to the deep ocean and respire only 2 × 105 tonnes of carbon per year. By enhancing new primary production, the populations of 12 000 sperm whales in the Southern Ocean act as a carbon sink, removing 2 × 105 tonnes more carbon from the atmosphere than they add during respiration. The ability of the Southern Ocean to act as a carbon sink may have been diminished by large-scale removal of sperm whales during industrial whaling. PMID:20554546

  16. Individual bile acids have differential effects on bile acid signaling in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Song, Peizhen, E-mail: songacad@gmail.com; Rockwell, Cheryl E., E-mail: rockwelc@msu.edu; Cui, Julia Yue, E-mail: juliacui@uw.edu

    2015-02-15

    Bile acids (BAs) are known to regulate BA synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). However, the relative importance of individual BAs in regulating these processes is not known. Therefore, mice were fed various doses of five individual BAs, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxoycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) in their diets at various concentrations for one week to increase the concentration of one BA in the enterohepatic circulation. The mRNA of BA synthesis and transporting genes in liver and ileum were quantified. In themore » liver, the mRNA of SHP, which is the prototypical target gene of FXR, increased in mice fed all concentrations of BAs. In the ileum, the mRNA of the intestinal FXR target gene Fgf15 was increased at lower doses and to a higher extent by CA and DCA than by CDCA and LCA. Cyp7a1, the rate-limiting enzyme in BA synthesis, was decreased more by CA and DCA than CDCA and LCA. Cyp8b1, the enzyme that 12-hydroxylates BAs and is thus responsible for the synthesis of CA, was decreased much more by CA and DCA than CDCA and LCA. Surprisingly, neither a decrease in the conjugated BA uptake transporter (Ntcp) nor increase in BA efflux transporter (Bsep) was observed by FXR activation, but an increase in the cholesterol efflux transporter (Abcg5/Abcg8) was observed with FXR activation. Thus in conclusion, CA and DCA are more potent FXR activators than CDCA and LCA when fed to mice, and thus they are more effective in decreasing the expression of the rate limiting gene in BA synthesis Cyp7a1 and the 12-hydroxylation of BAs Cyp8b1, and are also more effective in increasing the expression of Abcg5/Abcg8, which is responsible for biliary cholesterol excretion. However, feeding BAs do not alter the mRNA or protein levels of Ntcp or Bsep, suggesting that the uptake or efflux of BAs is not regulated by FXR at physiological and pharmacological concentrations of BAs. - Highlights: • All four major bile acids in humans activate the FXR in liver and intestine. • These bile acids decreased the mRNA of the bile acid synthetic enzymes Cyp7a1 and Cyp8b1. • These BAs did not alter the mRNA or protein of the conjugated BA transporters (Ntcp and Bsep). • Cholic acid and deoxycholic acid are more potent activators of FXR than chenodeoxycholic acid and lithocholic acid.« less

  17. Feasibility study for the construction of a new LNG receiving terminal, turkey. Volume 2. Appendix. Export trade information. [LNG (liquified natural gas)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1993-06-01

    The report was prepared by The M. W. Kellogg Co. for BOTAS Petroleum Pipeline Corporation of Ankara, Turkey. The study was undertaken to evaluate the cost and economics of constructing a second liquified natural gas (LNG) terminal in Turkey to meet future requirements for natural gas. Volume 2 contains the following appendices: LNG Storage Tanks; Vaporizers; Compressors; Pumps; Loading Arms; Marine Installations; Shipping; and Seismic Study.

  18. Longtime variation of phytoplankton in the South China Sea from the perspective of carbon fixation

    NASA Astrophysics Data System (ADS)

    Li, Teng; Bai, Yan; Chen, Xiaoyan; Zhu, Qiankun; Gong, Fang; Wang, Difeng

    2017-10-01

    The ocean is a huge carbon pool in the earth, and about half of the anthropogenic emissions of carbon dioxide are absorbed by the ocean each year. By converting inorganic carbon into organic carbon, the photosynthesis process of phytoplankton affords an important way for carbon sequestration in the ocean. According to previous researches, primary production (NPP) and the structure of phytoplankton community are important in regulate the efficiency of biological carbon pump. This study examined the spatiotemporal variability of satellite remote sensing derived chlorophyll a concentration (Chla), phytoplankton carbon biomass (Carbon), composition ratio of micro-, nano- and pico- phytoplankton, NPP and integrated particulate organic carbon (IPOC) during 1998-2007 in the South China Sea (SCS). Micro-, nano-phytoplankton and NPP showed similar seasonal variation with highest values in winter (January) (especially in the western ocean of Luzon Strait) and lowest values in summer (July) in SCS. Chla, phytoplankton carbon biomass, and IPOC showed different seasonal trends with one peak values occurred in winter and lowest in spring. Two sampling areas (A, N:17-21°, E:117.5-120° and B, N:12.5-15°, E:112-119°) in SCS were selected based on spatial distribution of the standard deviation of research parameters mentioned above. Compared to Chla, phytoplankton carbon biomass, NPP and IPOC, the interannual changes of phytoplankton community structure were remarkable in the two areas. The fraction of micro- and nano- phytoplankton in SCS tend to rise when La Nina events occur. Our results contribute to an understanding of the response of phytoplankton to climate change in the marginal sea. To quantify the efficiency of biological carbon pump in this area, more attention should be paid to the development of remote sensing algorithms of export NPP (or POC export flux) as well as the regulate mechanism of export NPP.

  19. Zooplankton diel vertical migration and contribution to deep active carbon flux in the NW Mediterranean

    NASA Astrophysics Data System (ADS)

    Isla, Alejandro; Scharek, Renate; Latasa, Mikel

    2015-03-01

    The diel vertical migration (DVM) of zooplankton contributes to the biological pump transporting material from surface to deep waters. We examined the DVM of the zooplankton community in different size fractions (53-200 μm, 200-500 μm, 500-1000 μm, 1000-2000 μm and > 2000 μm) during three cruises carried out in the open NW Mediterranean Sea. We assessed their metabolic rates from empirical published relationships and estimated the active fluxes of dissolved carbon to the mesopelagic zone driven by migrant zooplankton. Within the predominantly oligotrophic Mediterranean Sea, the NW region is one of the most productive ones, with a seasonal cycle characterized by a prominent spring bloom. The study area was visited at three different phases of the seasonal cycle: during the spring bloom, the post-bloom, and strongly stratified oligotrophic conditions. We found seasonal differences in DVM, less evident during the bloom. Changes in DVM intensity were related to the composition of the zooplanktonic assemblage, which also varied between cruises. Euphausiids appeared as the most active migrants in all seasons, and their life cycle conditioned the observed pattern. Immature stages, which are unable to perform large diel vertical movements, dominated during the bloom, in contrast to the higher relative importance of migrating adults in the other two sampling periods. The amount of dissolved carbon exported was determined by the migrant zooplankton biomass, being highest during the post-bloom (2.2 mmol C respired m- 2 d- 1, and up to 3.1 mmol C exported m- 2 d- 1 when DOC release estimations are added). The active transport by diel migrants represented a substantial contribution to total carbon export to deep waters, especially under stratified oligotrophic conditions, revealing the importance of zooplankton in the biological pump operating in the study area.

  20. The simulated climate of the Last Glacial Maximum and insights into the global marine carbon cycle

    NASA Astrophysics Data System (ADS)

    Buchanan, Pearse J.; Matear, Richard J.; Lenton, Andrew; Phipps, Steven J.; Chase, Zanna; Etheridge, David M.

    2016-12-01

    The ocean's ability to store large quantities of carbon, combined with the millennial longevity over which this reservoir is overturned, has implicated the ocean as a key driver of glacial-interglacial climates. However, the combination of processes that cause an accumulation of carbon within the ocean during glacial periods is still under debate. Here we present simulations of the Last Glacial Maximum (LGM) using the CSIRO Mk3L-COAL (Carbon-Ocean-Atmosphere-Land) earth system model to test the contribution of physical and biogeochemical processes to ocean carbon storage. For the LGM simulation, we find a significant global cooling of the surface ocean (3.2 °C) and the expansion of both minimum and maximum sea ice cover broadly consistent with proxy reconstructions. The glacial ocean stores an additional 267 Pg C in the deep ocean relative to the pre-industrial (PI) simulation due to stronger Antarctic Bottom Water formation. However, 889 Pg C is lost from the upper ocean via equilibration with a lower atmospheric CO2 concentration and a global decrease in export production, causing a net loss of carbon relative to the PI ocean. The LGM deep ocean also experiences an oxygenation ( > 100 mmol O2 m-3) and deepening of the calcite saturation horizon (exceeds the ocean bottom) at odds with proxy reconstructions. With modifications to key biogeochemical processes, which include an increased export of organic matter due to a simulated release from iron limitation, a deepening of remineralisation and decreased inorganic carbon export driven by cooler temperatures, we find that the carbon content of the glacial ocean can be sufficiently increased (317 Pg C) to explain the reduction in atmospheric and terrestrial carbon at the LGM (194 ± 2 and 330 ± 400 Pg C, respectively). Assuming an LGM-PI difference of 95 ppm pCO2, we find that 55 ppm can be attributed to the biological pump, 28 ppm to circulation changes and the remaining 12 ppm to solubility. The biogeochemical modifications also improve model-proxy agreement in export production, carbonate chemistry and dissolved oxygen fields. Thus, we find strong evidence that variations in the oceanic biological pump exert a primary control on the climate.

  1. A feedback regulatory model for RifQ-mediated repression of rifamycin export in Amycolatopsis mediterranei.

    PubMed

    Lei, Chao; Wang, Jingzhi; Liu, Yuanyuan; Liu, Xinqiang; Zhao, Guoping; Wang, Jin

    2018-01-29

    Due to the important role of rifamycin in curing tuberculosis infection, the study on rifamycin has never been stopped. Although RifZ, which locates within the rifamycin biosynthetic cluster, has recently been characterized as a pathway-specific regulator for rifamycin biosynthesis, little is known about the regulation of rifamycin export. In this work, we proved that the expression of the rifamycin efflux pump (RifP) was regulated by RifQ, a TetR-family transcriptional regulator. Deletion of rifQ had little impact on bacterial growth, but resulted in improved rifamycin production, which was consistent with the reverse transcription PCR results that RifQ negatively regulated rifP's transcription. With electrophoretic mobility shift assay and DNase I Footprinting assay, RifQ was found to directly bind to the promoter region of rifP, and a typical inverted repeat was identified within the RifQ-protected sequences. The transcription initiation site of rifP was further characterized and found to be upstream of the RifQ binding sites, well explaining the RifQ-mediated repression of rifP's transcription in vivo. Moreover, rifamycin B (the end product of rifamycin biosynthesis) remarkably decreased the DNA binding affinity of RifQ, which led to derepression of rifamycin export, reducing the intracellular concentration of rifamycin B as well as its toxicity against the host. Here, we proved that the export of rifamycin B was repressed by RifQ in Amycolatopsis mediterranei, and the RifQ-mediated repression could be specifically relieved by rifamycin B, the end product of rifamycin biosynthesis, based on which a feedback model was proposed for regulation of rifamycin export. With the findings here, one could improve the antibiotic yield by simply inactivating the negative regulator of the antibiotic transporter.

  2. Amazon River carbon dioxide outgassing fuelled by wetlands.

    PubMed

    Abril, Gwenaël; Martinez, Jean-Michel; Artigas, L Felipe; Moreira-Turcq, Patricia; Benedetti, Marc F; Vidal, Luciana; Meziane, Tarik; Kim, Jung-Hyun; Bernardes, Marcelo C; Savoye, Nicolas; Deborde, Jonathan; Souza, Edivaldo Lima; Albéric, Patrick; Landim de Souza, Marcelo F; Roland, Fabio

    2014-01-16

    River systems connect the terrestrial biosphere, the atmosphere and the ocean in the global carbon cycle. A recent estimate suggests that up to 3 petagrams of carbon per year could be emitted as carbon dioxide (CO2) from global inland waters, offsetting the carbon uptake by terrestrial ecosystems. It is generally assumed that inland waters emit carbon that has been previously fixed upstream by land plant photosynthesis, then transferred to soils, and subsequently transported downstream in run-off. But at the scale of entire drainage basins, the lateral carbon fluxes carried by small rivers upstream do not account for all of the CO2 emitted from inundated areas downstream. Three-quarters of the world's flooded land consists of temporary wetlands, but the contribution of these productive ecosystems to the inland water carbon budget has been largely overlooked. Here we show that wetlands pump large amounts of atmospheric CO2 into river waters in the floodplains of the central Amazon. Flooded forests and floating vegetation export large amounts of carbon to river waters and the dissolved CO2 can be transported dozens to hundreds of kilometres downstream before being emitted. We estimate that Amazonian wetlands export half of their gross primary production to river waters as dissolved CO2 and organic carbon, compared with only a few per cent of gross primary production exported in upland (not flooded) ecosystems. Moreover, we suggest that wetland carbon export is potentially large enough to account for at least the 0.21 petagrams of carbon emitted per year as CO2 from the central Amazon River and its floodplains. Global carbon budgets should explicitly address temporary or vegetated flooded areas, because these ecosystems combine high aerial primary production with large, fast carbon export, potentially supporting a substantial fraction of CO2 evasion from inland waters.

  3. Estimates of Gelatinous Zooplankton Carbon Flux in the Global Oceans

    NASA Astrophysics Data System (ADS)

    Luo, J. Y.; Condon, R.; Cowen, R. K.

    2016-02-01

    Gelatinous zooplankton (GZ), which include the cnidarians, ctenophores, and pelagic tunicates, are a common feature of marine ecosystems worldwide, but their contribution to global biogeochemical fluxes has never been assessed. We constructed a carbon-cycle model with a single, annual time-step and resolved to a 5° spatial grid for the three major GZ groups in order to evaluate the GZ-mediated carbon fluxes and export to depth. Biomass inputs (totaling 0.149 Pg C) were based off of Lucas et al. (2014) and updated using the JeDI database (Condon et al. 2015). From the upper ocean, biomass export flux from cnidarians, ctenophores, and tunicates totaled 2.96 ± 2.82 Pg C y-1, though only 0.199 ± 0.023 Pg C y-1 of GZ carbon were transferred to upper trophic levels, roughly amounting to one-quarter of all mesozooplankton production flux. In contrast, GZ fluxes to DOC only comprised ca. 2% of labile DOC flux. Egestion flux from the upper ocean totaled 2.56 ± 3.35 Pg C y-1, with over 80% being fast-sinking tunicate fecal pellets. Due to fast sinking rates of carcasses and fecal pellets, 26% of all C export from the upper ocean reached the seafloor, such that GZ fecal matter is estimated to comprise between 20-30% of global POC surface export and 11-30% of POC seafloor deposition. Finally, results from sensitivity analyses showed no increase in cnidarian and ctenophore export fluxes with increased temperature and jelly biomass, though tunicate export fluxes showed some increase with both temperature and biomass. These results suggest that current estimates of global POC flux from the surface oceans, which range between 8.6 - 12.9 Pg C y-1, may be underestimated by as much as 20 - 25%, implying a definite need to incorporate GZ mediated flux in estimating the biological pump transfer efficiency. Our study represents the first effort to quantify the role of gelatinous zooplankton in the global marine carbon cycle.

  4. Effect of heme oxygenase-1 on the protection of ischemia reperfusion injury of bile duct in rats after liver transplantation.

    PubMed

    Zhan, Xi; Zhang, Zhiqing; Huang, Hanfei; Zhang, Yujun; Zeng, Zhong

    2018-06-01

    To investigate the effect of heme oxygenase-1 (HO-1) on the ischemic reperfusion injury (IRI) of bile duct in rat models after liver transplantation. 320 SD rats were equally and randomly divided into 5 groups, which were group A receiving injection of 3×10 8 /pfu/ml adenovirus (adv), group B with donor receiving Adv-HO-1 and recipient receiving Adv-HO-1-siRNA, group C with donor and recipient both receiving Adv-HO-1, group D with donor receiving Adv-HO-1-siRNA and recipient receiving Adv-HO-1, and group E with donor and recipient both receiving Adv-HO-1-siRNA at 24h before liver transplantation. Donor liver was stored in UW liquid at 4°C followed by measuring HO-1 level by western blot before transplantation. On d1, d3, d7 and d14, serum and liver was isolated for analysis of liver function, inflammatory cell infiltration by H&E staining, ultrastructure of liver by transmission electron microscopy as well as the expression of HO-1, Bsep, Mrp2 and Ntcp by western blot. Compared with group D and E, group B and C displayed improved liver function as demonstrated by lower level of ALT, AST, LDH, TBIL, ALP and GGT, increased secretion of TBA and PL as well as expression of transporter proteins (Bsep, Mrp2 and Ntcp), reduced inflammatory cells infiltration and liver injury. Our study demonstrated that overexpression of HO-1 in donor liver can ameliorate the damage to bile duct and liver, and improved liver function, suggesting HO-1 might be a new therapeutic target in the treatment of IRI after liver transplantation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Effects of flow diversions on water and habitat quality: Examples from California's highly manipulated Sacramento–San Joaquin Delta

    USGS Publications Warehouse

    Monsen, Nancy E.; Cloern, James E.; Burau, Jon R.

    2007-01-01

    We use selected monitoring data to illustrate how localized water diversions from seasonal barriers, gate operations, and export pumps alter water quality across the Sacramento-San Joaquin Delta (California). Dynamics of water-quality variability are complex because the Delta is a mixing zone of water from the Sacramento and San Joaquin Rivers, agricultural return water, and the San Francisco Estuary. Each source has distinct water-quality characteristics, and the contribution of each source varies in response to natural hydrologic variability and water diversions. We use simulations with a tidal hydrodynamic model to reveal how three diversion events, as case studies, influence water quality through their alteration of Delta-wide water circulation patterns and flushing time. Reduction of export pumping decreases the proportion of Sacramento- to San Joaquin-derived fresh water in the central Delta, leading to rapid increases in salinity. Delta Cross Channel gate operations control salinity in the western Delta and alter the freshwater source distribution in the central Delta. Removal of the head of Old River barrier, in autumn, increases the flushing time of the Stockton Ship Channel from days to weeks, contributing to a depletion of dissolved oxygen. Each shift in water quality has implications either for habitat quality or municipal drinking water, illustrating the importance of a systems view to anticipate the suite of changes induced by flow manipulations, and to minimize the conflicts inherent in allocations of scarce resources to meet multiple objectives.

  6. Stress Introduction Rate Alters the Benefit of AcrAB-TolC Efflux Pumps.

    PubMed

    Langevin, Ariel M; Dunlop, Mary J

    2018-01-01

    Stress tolerance studies are typically conducted in an all-or-none fashion. However, in realistic settings-such as in clinical or metabolic engineering applications-cells may encounter stresses at different rates. Therefore, how cells tolerate stress may depend on its rate of appearance. To address this, we studied how the rate of stress introduction affects bacterial stress tolerance by focusing on a key stress response mechanism. Efflux pumps, such as AcrAB-TolC of Escherichia coli , are membrane transporters well known for the ability to export a wide variety of substrates, including antibiotics, signaling molecules, and biofuels. Although efflux pumps improve stress tolerance, pump overexpression can result in a substantial fitness cost to the cells. We hypothesized that the ideal pump expression level would involve a rate-dependent trade-off between the benefit of pumps and the cost of their expression. To test this, we evaluated the benefit of the AcrAB-TolC pump under different rates of stress introduction, including a step, a fast ramp, and a gradual ramp. Using two chemically diverse stresses, the antibiotic chloramphenicol and the jet biofuel precursor pinene, we assessed the benefit provided by the pumps. A mathematical model describing these effects predicted the benefit as a function of the rate of stress introduction. Our findings demonstrate that as the rate of introduction is lowered, stress response mechanisms provide a disproportionate benefit to pump-containing strains, allowing cells to survive beyond the original inhibitory concentrations. IMPORTANCE Efflux pumps are ubiquitous in nature and provide stress tolerance in the cells of species ranging from bacteria to mammals. Understanding how pumps provide tolerance has far-reaching implications for diverse fields, from medicine to biotechnology. Here, we investigated how the rate of stressor appearance impacts tolerance. We focused on two distinct substrates of AcrAB-TolC efflux pumps, the antibiotic chloramphenicol and the biofuel precursor pinene. Interestingly, tolerance is highly dependent on the rate of stress introduction. Therefore, it is important to consider not only the total quantity of a stressor but also the rate at which it is applied. The implications of this work are significant because environments are rarely static; antibiotic concentrations change during dosing, and metabolic engineering processes change with time. Copyright © 2017 American Society for Microbiology.

  7. The Novel Mouse Mutation Oblivion Inactivates the PMCA2 Pump and Causes Progressive Hearing Loss

    PubMed Central

    de Angelis, Martin Hrabé; Fuchs, Helmut; Lim, Dmitry; Ortolano, Saida; Ingham, Neil J.; Brini, Marisa; Carafoli, Ernesto; Mammano, Fabio; Steel, Karen P.

    2008-01-01

    Progressive hearing loss is common in the human population, but we have few clues to the molecular basis. Mouse mutants with progressive hearing loss offer valuable insights, and ENU (N-ethyl-N-nitrosourea) mutagenesis is a useful way of generating models. We have characterised a new ENU-induced mouse mutant, Oblivion (allele symbol Obl), showing semi-dominant inheritance of hearing impairment. Obl/+ mutants showed increasing hearing impairment from post-natal day (P)20 to P90, and loss of auditory function was followed by a corresponding base to apex progression of hair cell degeneration. Obl/Obl mutants were small, showed severe vestibular dysfunction by 2 weeks of age, and were completely deaf from birth; sensory hair cells were completely degenerate in the basal turn of the cochlea, although hair cells appeared normal in the apex. We mapped the mutation to Chromosome 6. Mutation analysis of Atp2b2 showed a missense mutation (2630C→T) in exon 15, causing a serine to phenylalanine substitution (S877F) in transmembrane domain 6 of the PMCA2 pump, the resident Ca2+ pump of hair cell stereocilia. Transmembrane domain mutations in these pumps generally are believed to be incompatible with normal targeting of the protein to the plasma membrane. However, analyses of hair cells in cultured utricular maculae of Obl/Obl mice and of the mutant Obl pump in model cells showed that the protein was correctly targeted to the plasma membrane. Biochemical and biophysical characterisation showed that the pump had lost a significant portion of its non-stimulated Ca2+ exporting ability. These findings can explain the progressive loss of auditory function, and indicate the limits in our ability to predict mechanism from sequence alone. PMID:18974863

  8. Mechanistic determinants of the directionality and energetics of active export by a heterodimeric ABC transporter

    DOE PAGES

    Grossmann, Nina; Vakkasoglu, Ahmet S.; Hulpke, Sabine; ...

    2014-11-07

    The ATP-binding cassette (ABC) transporter associated with antigen processing (TAP) participates in immune surveillance by moving proteasomal products into the endoplasmic reticulum (ER) lumen for major histocompatibility complex class I loading and cell surface presentation to cytotoxic T cells. Here we delineate the mechanistic basis for antigen translocation. Notably, TAP works as a molecular diode, translocating peptide substrates against the gradient in a strict unidirectional way. We reveal the importance of the D-loop at the dimer interface of the two nucleotide-binding domains (NBDs) in coupling substrate translocation with ATP hydrolysis and defining transport vectoriality. Substitution of the converved aspartate, whichmore » coordinates the ATP-binding site, decreases NBD dimerization affinity and turns the unidirectional primary active pump into a passive bidirectional nucleotide-gated facilitator. Thus, ATP hydrolysis is not required for translocation per se, but is essential for both active and unidirectional transport. As a result, our data provide detailed mechanistic insight into how heterodimeric ABC exporters operate.« less

  9. Shallow Carbon Export from an Iron fertilised Plankton Bloom in the Southern Ocean

    NASA Astrophysics Data System (ADS)

    Sanders, R.; Pollard, R.; Morris, P.; Statham, P.; Moore, C. M. M.; Lucas, M.

    2009-04-01

    Some regions of the global ocean, notably the Southern Ocean, have high levels of macronutrients yet low levels of chlorophyll (the high nutrient, low chlorophyll or HNLC condition). Numerous artificial iron fertilization experiments conducted in the Southern Ocean have resulted in enhanced phytoplankton biomass and macronutrient drawdown. However the subsequent long-term biogeochemical consequences of such iron fertilization are unclear due in part to the limited size and duration of such experiments. An alternative way to assess the affect of iron over the Southern Ocean biological carbon pump is to observe the evolution of plankton production in regions of the Southern Ocean where shallow topography and Ocean currents interact to promote to release terrestrial iron into HNLC waters. During 2004-5 RRS Discovery conduced a complex programme of observations in such a region around the Crozet Islands in the SW Indian Ocean. The results of this programme, focussing on a quantitative estimate of carbon export per unit iron addition, will be presented.

  10. Millennial-scale variability in dust deposition, marine export production, and nutrient consumption in the glacial subantarctic ocean (Invited)

    NASA Astrophysics Data System (ADS)

    Martinez-Garcia, A.; Sigman, D. M.; Anderson, R. F.; Ren, H. A.; Hodell, D. A.; Straub, M.; Jaccard, S.; Eglinton, T. I.; Haug, G. H.

    2013-12-01

    Based on the limitation of modern Southern Ocean phytoplankton by iron and the evidence of higher iron-bearing dust fluxes to the ocean during ice ages, it has been proposed that iron fertilization of Southern Ocean phytoplankton contributed to the reduction in atmospheric CO2 during ice ages. In the Subantarctic zone of the Atlantic Southern Ocean, glacial increases in dust flux and export production have been documented, supporting the iron fertilization hypothesis. However, these observations could be interpreted alternatively as resulting from the equatorward migration of Southern Ocean fronts during ice ages if the observed productivity rise was not accompanied by an increase in major nutrient consumption. Here, new 230Th-normalized lithogenic and opal fluxes are combined with high-resolution biomarker measurements to reconstruct millennial-scale changes in dust deposition and marine export production in the subantarctic Atlantic over the last glacial cycle. In the same record foraminifera-bound nitrogen isotopes are used to reconstruct ice age changes in surface nitrate utilization, providing a comprehensive test of the iron fertilization hypothesis. Elevation in foraminifera-bound δ15N, indicating more complete nitrate consumption, coincides with times of surface cooling and greater dust flux and export production. These observations indicate that the ice age Subantarctic was characterized by iron fertilized phytoplankton growth. The resulting strengthening of the Southern Ocean's biological pump can explain the ~40 ppm lowering of CO2 that characterizes the transitions from mid-climate states to full ice age conditions as well as the millennial-scale atmospheric CO2 fluctuations observed within the last ice age

  11. Polyamines cause plasma membrane depolarization, activate Ca2+-, and modulate H+-ATPase pump activity in pea roots.

    PubMed

    Pottosin, Igor; Velarde-Buendía, Ana María; Bose, Jayakumar; Fuglsang, Anja T; Shabala, Sergey

    2014-06-01

    Polyamines regulate a variety of cation and K(+) channels, but their potential effects on cation-transporting ATPases are underexplored. In this work, noninvasive microelectrode ion flux estimation and conventional microelectrode techniques were applied to study the effects of polyamines on Ca(2+) and H(+) transport and membrane potential in pea roots. Externally applied spermine or putrescine (1mM) equally activated eosin yellow (EY)-sensitive Ca(2+) pumping across the root epidermis and caused net H(+) influx or efflux. Proton influx induced by spermine was suppressed by EY, supporting the mechanism in which Ca(2+) pump imports 2 H(+) per each exported Ca(2+). Suppression of the Ca(2+) pump by EY diminished putrescine-induced net H(+) efflux instead of increasing it. Thus, activities of Ca(2+) and H(+) pumps were coupled, likely due to the H(+)-pump inhibition by intracellular Ca(2+). Additionally, spermine but not putrescine caused a direct inhibition of H(+) pumping in isolated plasma membrane vesicles. Spermine, spermidine, and putrescine (1mM) induced membrane depolarization by 70, 50, and 35 mV, respectively. Spermine-induced depolarization was abolished by cation transport blocker Gd(3+), was insensitive to anion channels' blocker niflumate, and was dependent on external Ca(2+). Further analysis showed that uptake of polyamines but not polyamine-induced cationic (K(+)+Ca(2+)+H(+)) fluxes were a main cause of membrane depolarization. Polyamine increase is a common component of plant stress responses. Activation of Ca(2+) efflux by polyamines and contrasting effects of polyamines on net H(+) fluxes and membrane potential can contribute to Ca(2+) signalling and modulate a variety of transport processes across the plasma membrane under stress. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. The Importance of Subsurface Production for Carbon Export - Evidence from Past Oceans

    NASA Astrophysics Data System (ADS)

    Kemp, A. E. S.

    2016-02-01

    The maxim of the geological concept of uniformitarianism is "the present is the key to the past", but in the context of our temporally and spatially minimal observational record of modern ocean biogeochemical processes, ancient ocean sediments may provide critical evidence of the key species involved in carbon flux. Specifically, laminated marine sediments that preserve the seasonal flux cycle represent "palaeo-sediment traps" that vastly expand our knowledge of the operations of the marine biological carbon pump. Several key subsurface-dwelling diatom taxa, hitherto thought to be biogeochemically insignificant, are dominant components of ancient marine sediments. For example, the sapropels and equivalent horizons that have accumulated in the Mediterranean over the past 5 million years, contain abundant rhizosolenid and hemiaulid diatoms. These deposits contain the highest concentrations of organic carbon and there is extensive evidence that this was produced by subsurface production in a deep chlorophyll maximum. The highly stratified conditions that led to this subsurface production and carbon flux are in contrast to prevailing views that have held upwelling systems as those with the highest potential for export in the global ocean. Similarly, studies of ancient "greenhouse" periods such as the Cretaceous, with highly stratified oceans and which are potential analogues for future climate change, show evidence for extensive subsurface production. Together with emerging evidence from stratified regions of the modern ocean, such as the subtropical gyres, insights from these ancient oceans suggest that a reappraisal is required of current views on key phytoplankton producers and their role the operation of the marine biological carbon pump.

  13. Adaptation of H+-pumping and plasma membrane H+ ATPase activity in proteoid roots of white lupin under phosphate deficiency.

    PubMed

    Yan, Feng; Zhu, Yiyong; Müller, Caroline; Zörb, Christian; Schubert, Sven

    2002-05-01

    White lupin (Lupinus albus) is able to adapt to phosphorus deficiency by producing proteoid roots that release a huge amount of organic acids, resulting in mobilization of sparingly soluble soil phosphate in rhizosphere. The mechanisms responsible for the release of organic acids by proteoid root cells, especially the trans-membrane transport processes, have not been elucidated. Because of high cytosolic pH, the release of undissociated organic acids is not probable. In the present study, we focused on H+ export by plasma membrane H+ ATPase in active proteoid roots. In vivo, rhizosphere acidification of active proteoid roots was vanadate sensitive. Plasma membranes were isolated from proteoid roots and lateral roots from P-deficient and -sufficient plants. In vitro, in comparison with two types of lateral roots and proteoid roots of P-sufficient plants, the following increase of the various parameters was induced in active proteoid roots of P-deficient plants: (a) hydrolytic ATPase activity, (b) Vmax and Km, (c) H+ ATPase enzyme concentration of plasma membrane, (d) H+-pumping activity, (e) pH gradient across the membrane of plasmalemma vesicles, and (f) passive H+ permeability of plasma membrane. In addition, lower vanadate sensitivity and more acidic pH optimum were determined for plasma membrane ATPase of active proteoid roots. Our data support the hypothesis that in active proteoid root cells, H+ and organic anions are exported separately, and that modification of plasma membrane H+ ATPase is essential for enhanced rhizosphere acidification by active proteoid roots.

  14. Marine phytoplankton stoichiometry mediates nonlinear interactions between nutrient supply, temperature, and atmospheric CO2

    NASA Astrophysics Data System (ADS)

    Moreno, Allison R.; Hagstrom, George I.; Primeau, Francois W.; Levin, Simon A.; Martiny, Adam C.

    2018-05-01

    Marine phytoplankton stoichiometry links nutrient supply to marine carbon export. Deviations of phytoplankton stoichiometry from Redfield proportions (106C : 1P) could therefore have a significant impact on carbon cycling, and understanding which environmental factors drive these deviations may reveal new mechanisms regulating the carbon cycle. To explore the links between environmental conditions, stoichiometry, and carbon cycling, we compared four different models of phytoplankton C : P: a fixed Redfield model, a model with C : P given as a function of surface phosphorus concentration (P), a model with C P given as a function of temperature, and a new multi-environmental model that predicts C : P as a function of light, temperature, and P. These stoichiometric models were embedded into a five-box ocean circulation model, which resolves the three major ocean biomes (high-latitude, subtropical gyres, and tropical upwelling regions). Contrary to the expectation of a monotonic relationship between surface nutrient drawdown and carbon export, we found that lateral nutrient transport from lower C : P tropical waters to high C : P subtropical waters could cause carbon export to decrease with increased tropical nutrient utilization. It has been hypothesized that a positive feedback between temperature and pCO2, atm will play an important role in anthropogenic climate change, with changes in the biological pump playing at most a secondary role. Here we show that environmentally driven shifts in stoichiometry make the biological pump more influential, and may reverse the expected positive relationship between temperature and pCO2, atm. In the temperature-only model, changes in tropical temperature have more impact on the Δ pCO2, atm (˜ 41 ppm) compared to subtropical temperature changes (˜ 4.5 ppm). Our multi-environmental model predicted a decline in pCO2, atm of ˜ 46 ppm when temperature spanned a change of 10 °C. Thus, we find that variation in marine phytoplankton stoichiometry and its environmental controlling factors can lead to nonlinear controls on pCO2, atm, suggesting the need for further studies of ocean C : P and the impact on ocean carbon cycling.

  15. Influence of particulates on phosphorus loading exported from farm drainage during a storm event in the Everglades Agricultural Area

    NASA Astrophysics Data System (ADS)

    Bhadha, J. H.; Lang, T. A.; Daroub, S. H.

    2015-12-01

    The purpose of this study was to evaluate the influence of particulates on P loading captured during a single storm event. The Everglades Agricultural Area of Florida comprises 280,000 hectares of organic soil farmland artificially drained by ditches, canals and pumps. Phosphorus (P)-enriched suspended particulates in canals are susceptible to transport and can contribute significantly to the overall P loads in drainage water. A settling tank experiment was conducted to capture particulates during tropical storm Isaac in 2012 from three farms approximately 2.4 to 3.6 km2 in size. Farm canal discharge water was collected in a series of two 200 liter settling tanks over a seven-day drainage period, during tropical storm Isaac. Water from the settling tanks was siphoned through Imhoff settling cones, where the particulates were allowed to settle and collected for P-fractionation analyses, and compared to intact sediment cores collected from the bottom of the canals. The discharged particulates contained higher organic matter content (OM), total P, and labile P fractions compared to the canal bottom sediments. Based on the equilibrium P concentrations, surface sediments behave as a source of P to the water column. A seven-day continuous drainage event exported 4.7 to 11.1 metric tons of suspended solids per farm, corresponding to 32 to 63 kg of particulate P being lost to downstream ecosystems. Drainage associated to a single seven-day storm event exported up to 61% of the total annual farm P load. It is evident from this study that short-term, high-intensity storm events can skew annual P loads due to the export of significantly higher particulate matter from farm canals. Exported particulates rich in P can provide a supplemental source of nutrients if captured and replenished back into the farmlands, as a sustainable farming practice.

  16. Nutrient availability and the ultimate control of the biological carbon pump in the western tropical South Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Moutin, Thierry; Wagener, Thibaut; Caffin, Mathieu; Fumenia, Alain; Gimenez, Audrey; Baklouti, Melika; Bouruet-Aubertot, Pascale; Pujo-Pay, Mireille; Leblanc, Karine; Lefevre, Dominique; Helias Nunige, Sandra; Leblond, Nathalie; Grosso, Olivier; de Verneil, Alain

    2018-05-01

    Surface waters (0-200 m) of the western tropical South Pacific (WTSP) were sampled along a longitudinal 4000 km transect (OUTPACE cruise, DOI: 10.17600/15000900) during the austral summer (stratified) period (18 February to 3 April 2015) between the Melanesian Archipelago (MA) and the western part of the SP gyre (WGY). Two distinct areas were considered for the MA, the western MA (WMA), and the eastern MA (EMA). The main carbon (C), nitrogen (N), and phosphorus (P) pools and fluxes provide a basis for the characterization of the expected trend from oligotrophy to ultra-oligotrophy, and the building of first-order budgets at the daily and seasonal timescales (using climatology). Sea surface chlorophyll a well reflected the expected oligotrophic gradient with higher values obtained at WMA, lower values at WGY, and intermediate values at EMA. As expected, the euphotic zone depth, the deep chlorophyll maximum, and nitracline depth deepen from west to east. Nevertheless, phosphaclines and nitraclines did not match. The decoupling between phosphacline and nitracline depths in the MA allows for excess P to be locally provided in the upper water by winter mixing. We found a significant biological soft tissue carbon pump in the MA sustained almost exclusively by dinitrogen (N2) fixation and essentially controlled by phosphate availability in this iron-rich environment. The MA appears to be a net sink for atmospheric CO2, while the WGY is in quasi-steady state. We suggest that the necessary excess P, allowing the success of nitrogen fixers and subsequent carbon production and export, is mainly brought to the upper surface by local deep winter convection at an annual timescale rather than by surface circulation. While the origin of the decoupling between phosphacline and nitracline remains uncertain, the direct link between local P upper water enrichment, N2 fixation, and organic carbon production and export, offers a possible shorter timescale than previously thought between N input by N2 fixation and carbon export. The low iron availability in the SP gyre and P availability in the MA during the stratified period may appear as the ultimate control of N input by N2 fixation. Because of the huge volume of water to consider, and because the SP Ocean is the place of intense denitrification in the east (N sink) and N2 fixation in the west (N source), precise seasonal C, N, P, and iron (Fe) budgets would be of prime interest to understand the efficiency, at the present time and in the future, of the oceanic biological carbon pump.

  17. Seasonally different carbon flux changes in the Southern Ocean in response to the southern annular mode.

    PubMed

    Hauck, J; Völker, C; Wang, T; Hoppema, M; Losch, M; Wolf-Gladrow, D A

    2013-12-01

    Stratospheric ozone depletion and emission of greenhouse gases lead to a trend of the southern annular mode (SAM) toward its high-index polarity. The positive phase of the SAM is characterized by stronger than usual westerly winds that induce changes in the physical carbon transport. Changes in the natural carbon budget of the upper 100 m of the Southern Ocean in response to a positive SAM phase are explored with a coupled ecosystem-general circulation model and regression analysis. Previously overlooked processes that are important for the upper ocean carbon budget during a positive SAM period are identified, namely, export production and downward transport of carbon north of the polar front (PF) as large as the upwelling in the south. The limiting micronutrient iron is brought into the surface layer by upwelling and stimulates phytoplankton growth and export production but only in summer. This leads to a drawdown of carbon and less summertime outgassing (or more uptake) of natural CO 2 . In winter, biological mechanisms are inactive, and the surface ocean equilibrates with the atmosphere by releasing CO 2 . In the annual mean, the upper ocean region south of the PF loses more carbon by additional export production than by the release of CO 2 into the atmosphere, highlighting the role of the biological carbon pump in response to a positive SAM event.

  18. Anticyclonic eddies are more productive than cyclonic eddies in subtropical gyres because of winter mixing.

    PubMed

    Dufois, François; Hardman-Mountford, Nick J; Greenwood, Jim; Richardson, Anthony J; Feng, Ming; Matear, Richard J

    2016-05-01

    Mesoscale eddies are ubiquitous features of ocean circulation that modulate the supply of nutrients to the upper sunlit ocean, influencing the rates of carbon fixation and export. The popular eddy-pumping paradigm implies that nutrient fluxes are enhanced in cyclonic eddies because of upwelling inside the eddy, leading to higher phytoplankton production. We show that this view does not hold for a substantial portion of eddies within oceanic subtropical gyres, the largest ecosystems in the ocean. Using space-based measurements and a global biogeochemical model, we demonstrate that during winter when subtropical eddies are most productive, there is increased chlorophyll in anticyclones compared with cyclones in all subtropical gyres (by 3.6 to 16.7% for the five basins). The model suggests that this is a consequence of the modulation of winter mixing by eddies. These results establish a new paradigm for anticyclonic eddies in subtropical gyres and could have important implications for the biological carbon pump and the global carbon cycle.

  19. Value of pH regulators in the diagnosis, prognosis and treatment of cancer.

    PubMed

    Granja, Sara; Tavares-Valente, Diana; Queirós, Odília; Baltazar, Fátima

    2017-04-01

    Altered metabolism, associated with acidification of the extracellular milieu, is one of the major features of cancer. As pH regulation is crucial for the maintenance of all biological functions, cancer cells rely on the activity of lactate exporters and proton transporters to regulate their intracellular pH. The major players in cancer pH regulation are proton pump ATPases, sodium-proton exchangers (NHEs), monocarboxylate transporters (MCTs), carbonic anhydrases (CAs) and anion exchangers (AEs), which have been shown to be upregulated in several human malignancies. Thanks to the activity of the proton pumps and transporters, tumours acidify their microenvironment, becoming more aggressive and resistant to therapy. Thus, targeting tumour pH may contribute to more effective anticancer strategies for controlling tumour progression and therapeutic resistance. In the present study, we review the role of the main pH regulators expressed in human cancer cells, including their diagnostic and prognostic value, as well as their usefulness as therapeutic targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Long-Term Patterns in Production and Export of Fecal Pellets by Krill and Salps along the Western Antarctic Peninsula

    NASA Astrophysics Data System (ADS)

    Steinberg, D. K.; Ruck, K. E.; Cope, J. S.

    2016-02-01

    The Western Antarctic Peninsula (WAP) is one of the most rapidly warming regions on Earth, and where climate-induced changes in zooplankton abundance and species composition could dramatically affect the pelagic food web and biogeochemical cycling. We examined long-term (1993 to the present) and spatial trends in summer abundance of, and fecal pellet production (FPP) by, Antarctic krill (Euphausia superba) and gelatinous salps (Salpa thompsoni) and their relationship with physical and other environmental parameters. Zooplankton were collected as part of the Palmer, Antarctica Long-Term Ecological Research Program (PAL LTER) from the epipelagic zone in a region divided into latitudinal (North, South, and Far South) and cross-shelf (coastal, shelf, slope) sub-regions. Beginning in 2009, FPP and sinking rate experiments were conducted at representative stations along these gradients. FPP peaks occurred every 4-6 years in both species in the north and south, but alternated such that some years were characterized by high krill-mediated export, and others by high salp-mediated export. In the far south (where perennial sea ice still persists), and in both coastal and shelf sub-regions, krill FFP exceeded that of salps. Conversely, off the slope, salp FPP exceeded that of krill. Variability in krill FPP was strongly and positively influenced by primary production 2-years prior, and negatively correlated with sea surface temperature (no lag). Salp FPP was most significantly correlated with sea ice parameters, with highest FPP in years of lowest sea-ice extent, duration, and area. Warmer water and ice-free conditions favored salps over krill, which also increased overall potential export of fecal pellet carbon to depth. We discuss the implications of this potential increase in biological pump efficiency as the climate warms.

  1. Mechanisms for the export of archaeal lipids down the water column in the upwelling area off Cape Blanc, North-West Africa

    NASA Astrophysics Data System (ADS)

    Ebersbach, Friederike; Goldenstein, Nadine; Iversen, Morten; Mollenhauer, Gesine; Hinrichs, Kai-Uwe

    2016-04-01

    Transport mechanisms of microbial membrane lipids from surface waters to the seafloor are poorly understood. In particular, pelagic archaeal glycerol dibiphytanyl glycerol tetraethers (GDGTs) from planktonic archaea are frequently used for reconstruction of ancient sea surface temperatures (Schouten et al. 2013). Because planktonic archaea are too small and neutrally buoyant to sink independently, transport vehicles for efficient export of fossil archaeal biomarkers to the sediment are required. The surface ocean is coupled with the deep ocean through biogenic sinking particles, a process known as the biological pump (Volk and Hoffert 1985). Two different pathways for particle formation, mainly taking place in the mesopelagic zone, are distinguished: Direct aggregation of phytoplankton blooms or grazing, resulting in phyto-detrital aggregates or reprocessed faecal material, respectively. Grazing and packaging into sinking particles is a possible export mechanism for GDGTs (Huguet et al. 2006). Moreover, it is assumed that phyto-detrital aggregates also play an important role in transporting GDGTs to the deep (Mollenhauer et al. 2015), but processes behind this pathway remain unclear. However, there are only few studies that link GDGT signals in sinking particles to the composition of the exported particulate matter (e.g. Yamamoto et al., 2012; Mollenhauer et al. 2015). Here we investigate sinking particles and suspended particulate matter (SPM) from spring blooms in 2012 and 2013 in the upwelling region in the Atlantic Ocean off Cape Blanc, Mauritania. We compare for the first time material from free-floating sediment traps (100, 200 and 400 m; purely sinking particles) with sinking particles and SPM from size fractionated in-situ pump (ISP) filters (several depths between 40 and 2350 m). This setup allows to relate the signal from archaeal lipids to (i) the flux of particulate organic carbon and the particle assemblages as revealed by the characterisation of thousands of individual particles collected in gels in addition to (ii) the sinking particles and SPM present in different particle size fractions on the filters. First results show that the large size fraction carries relatively more intact lipids indicating fresh material being attached to sinking particles rather than suspended in the water column. Furthermore, the distribution of 1G-GDGTs over depths differs from that of 2G- and HPH-GDGTs which might relate to different archaeal communities at different depths. Our findings contribute to the mechanistic understanding of the export of organic molecules through the water column and support the validation of lipid-based paleoceanographic proxies. References Huguet, C., Cartes, J.E., Sinninghe Damsté, J.S., Schouten, S., 2006. Marine crenarchaeotal membrane lipids in decapods: Implications for the TEX86 paleothermometer. Geochemistry, Geophysics, Geosystems 7 (11), Q11010. Mollenhauer, G., Basse, A., Kim, J.-H., Sinninghe Damsté, J.S., Fischer, G., 2015. A four-year record of UK'37- and TEX86-derived sea surface temperature estimates from sinking particles in the filamentous upwelling region off Cape Blanc, Mauritania. Deep Sea Research Part I: Oceanographic Research Papers 97, 67-79. doi:10.1016/j.dsr.2014.11.015 Schouten, S., Hopmans, E.C., Sinninghe Damsté, J.S., 2013. The organic geochemistry of glycerol dialkyl glycerol tetraether lipids: A review. Organic Geochemistry 54, 19-61. Volk, T., Hoffert, M.I., 1985. Ocean carbon pumps: analysis of relative strengths and efficiencies in ocean-driven atmospheric CO2 changes. Geophysical Monographs 32, 99-110. Yamamoto, M., Shimamoto, A., Fukuhara, T., Tanaka, Y., Ishizaka, J., 2012. Glycerol dialkyl glycerol tetraethers and TEX86 index in sinking particles in the western North Pacific. Organic Geochemistry 53 (0), 52-62.

  2. Gene-specific alterations of hepatic nuclear receptor regulated gene expression by ligand activation or hepatocyte-selective knockout inhibition of RXRα signaling during inflammation

    PubMed Central

    Kosters, Astrid; Tian, Feng; Wan, Yvonne Yu-Jie; Karpen, Saul J.

    2013-01-01

    Background Inflammation leads to transcriptional downregulation of many hepatic genes, particulary those activated by RXRα-heterodimers. Inflammation-mediated reduction of nuclear RXRα levels is a main factor in reduced nuclear receptor (NR)–regulated hepatic gene expression, eventually leading to cholestasis and liver damage. Aim To investigate roles for RXRα in hepatic gene expression during inflammation, using two complementary mouse models: ligand–activation of RXRα, and in mice expressing hepatocyte-specific expression of RXRα missing its DNA-binding-domain (DBD; hs-RxrαΔex4−/−) Methods To activate RXRα, mice were gavage-fed with LG268 or vehicle for 5 days. To inhibit RXRα function, hs-RxrαΔex4−/− were used. All mice were IP-injected with LPS or saline for 16 hrs prior to analysis of hepatic RNA, protein and NR-DNA binding. Results LG268-treatment attenuated the LPS-mediated reductions of several RXRα-regulated genes, coinciding with maintained RXRα occupancy in both Bsep and Ostβ promoters. Lacking full hepatocyte-RXRα function (hs-RxrαΔex4−/− mice) led to enhancement of LPS-mediated changes in gene expression, but surprisingly, maintenance of RNA levels of some RXRα-regulated genes. Investigations revealed that Hs-Rxrα−/− hepatocytes expressed an internally-truncated, ~44 kDa, RXRα-form. DNA-binding capacity of NR-heterodimers was equivalent in wt and hs-RxrαΔex4−/− livers, but reduced by LPS in both. ChIP-QPCR revealed reduced RXRα occupancy to the Bsep RXRα:FXR site was reduced, but not absent, in hs-RxrαΔex4−/− livers. Conclusions There are differential regulatory roles for hepatic RXRα, both in basal and inflammatory states, suggesting new and complex multi-domain roles for RXRα in regulating hepatic gene expression. Moreover, there is an unexpected non-obligate role for the DBD of RXRα. PMID:22098603

  3. Glacial-interglacial atmospheric CO2 change: a possible "standing volume" effect on deep-ocean carbon sequestration

    NASA Astrophysics Data System (ADS)

    Skinner, L. C.

    2009-09-01

    So far, the exploration of possible mechanisms for glacial atmospheric CO2 drawdown and marine carbon sequestration has tended to focus on dynamic or kinetic processes (i.e. variable mixing-, equilibration- or export rates). Here an attempt is made to underline instead the possible importance of changes in the standing volumes of intra-oceanic carbon reservoirs (i.e. different water-masses) in influencing the total marine carbon inventory. By way of illustration, a simple mechanism is proposed for enhancing the marine carbon inventory via an increase in the volume of relatively cold and carbon-enriched deep water, analogous to modern Lower Circumpolar Deep Water (LCDW), filling the ocean basins. A set of simple box-model experiments confirm the expectation that a deep sea dominated by an expanded LCDW-like watermass holds more CO2, without any pre-imposed changes in ocean overturning rate, biological export or ocean-atmosphere exchange. The magnitude of this "standing volume effect" (which operates by boosting the solubility- and biological pumps) might be as large as the contributions that have previously been attributed to carbonate compensation, terrestrial biosphere reduction or ocean fertilisation for example. By providing a means of not only enhancing but also driving changes in the efficiency of the biological- and solubility pumps, this standing volume mechanism may help to reduce the amount of glacial-interglacial CO2 change that remains to be explained by other mechanisms that are difficult to assess in the geological archive, such as reduced mass transport or mixing rates in particular. This in turn could help narrow the search for forcing conditions capable of pushing the global carbon cycle between glacial and interglacial modes.

  4. Conserved Allosteric Hot Spots in the Transmembrane Domains of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channels and Multidrug Resistance Protein (MRP) Pumps*

    PubMed Central

    Wei, Shipeng; Roessler, Bryan C.; Chauvet, Sylvain; Guo, Jingyu; Hartman, John L.; Kirk, Kevin L.

    2014-01-01

    ATP-binding cassette (ABC) transporters are an ancient family of transmembrane proteins that utilize ATPase activity to move substrates across cell membranes. The ABCC subfamily of the ABC transporters includes active drug exporters (the multidrug resistance proteins (MRPs)) and a unique ATP-gated ion channel (cystic fibrosis transmembrane conductance regulator (CFTR)). The CFTR channel shares gating principles with conventional ligand-gated ion channels, but the allosteric network that couples ATP binding at its nucleotide binding domains (NBDs) with conformational changes in its transmembrane helices (TMs) is poorly defined. It is also unclear whether the mechanisms that govern CFTR gating are conserved with the thermodynamically distinct MRPs. Here we report a new class of gain of function (GOF) mutation of a conserved proline at the base of the pore-lining TM6. Multiple substitutions of this proline promoted ATP-free CFTR activity and activation by the weak agonist, 5′-adenylyl-β,γ-imidodiphosphate (AMP-PNP). TM6 proline mutations exhibited additive GOF effects when combined with a previously reported GOF mutation located in an outer collar of TMs that surrounds the pore-lining TMs. Each TM substitution allosterically rescued the ATP sensitivity of CFTR gating when introduced into an NBD mutant with defective ATP binding. Both classes of GOF mutations also rescued defective drug export by a yeast MRP (Yor1p) with ATP binding defects in its NBDs. We conclude that the conserved TM6 proline helps set the energy barrier to both CFTR channel opening and MRP-mediated drug efflux and that CFTR channels and MRP pumps utilize similar allosteric mechanisms for coupling conformational changes in their translocation pathways to ATP binding at their NBDs. PMID:24876383

  5. Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis transmembrane conductance regulator (CFTR) channels and multidrug resistance protein (MRP) pumps.

    PubMed

    Wei, Shipeng; Roessler, Bryan C; Chauvet, Sylvain; Guo, Jingyu; Hartman, John L; Kirk, Kevin L

    2014-07-18

    ATP-binding cassette (ABC) transporters are an ancient family of transmembrane proteins that utilize ATPase activity to move substrates across cell membranes. The ABCC subfamily of the ABC transporters includes active drug exporters (the multidrug resistance proteins (MRPs)) and a unique ATP-gated ion channel (cystic fibrosis transmembrane conductance regulator (CFTR)). The CFTR channel shares gating principles with conventional ligand-gated ion channels, but the allosteric network that couples ATP binding at its nucleotide binding domains (NBDs) with conformational changes in its transmembrane helices (TMs) is poorly defined. It is also unclear whether the mechanisms that govern CFTR gating are conserved with the thermodynamically distinct MRPs. Here we report a new class of gain of function (GOF) mutation of a conserved proline at the base of the pore-lining TM6. Multiple substitutions of this proline promoted ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-β,γ-imidodiphosphate (AMP-PNP). TM6 proline mutations exhibited additive GOF effects when combined with a previously reported GOF mutation located in an outer collar of TMs that surrounds the pore-lining TMs. Each TM substitution allosterically rescued the ATP sensitivity of CFTR gating when introduced into an NBD mutant with defective ATP binding. Both classes of GOF mutations also rescued defective drug export by a yeast MRP (Yor1p) with ATP binding defects in its NBDs. We conclude that the conserved TM6 proline helps set the energy barrier to both CFTR channel opening and MRP-mediated drug efflux and that CFTR channels and MRP pumps utilize similar allosteric mechanisms for coupling conformational changes in their translocation pathways to ATP binding at their NBDs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Carbon export in the naturally iron-fertilized Kerguelen area of the Southern Ocean based on the 234Th approach

    NASA Astrophysics Data System (ADS)

    Planchon, F.; Ballas, D.; Cavagna, A.-J.; Bowie, A. R.; Davies, D.; Trull, T.; Laurenceau-Cornec, E. C.; Van Der Merwe, P.; Dehairs, F.

    2015-06-01

    This study examined upper-ocean particulate organic carbon (POC) export using the 234Th approach as part of the second KErguelen Ocean and Plateau compared Study expedition (KEOPS2). Our aim was to characterize the spatial and the temporal variability of POC export during austral spring (October-November 2011) in the Fe-fertilized area of the Kerguelen Plateau region. POC export fluxes were estimated at high productivity sites over and downstream of the plateau and compared to a high-nutrient low-chlorophyll (HNLC) area upstream of the plateau in order to assess the impact of iron-induced productivity on the vertical export of carbon. Deficits in 234Th activities were observed at all stations in surface waters, indicating early scavenging by particles in austral spring. 234Th export was lowest at the reference station R-2 and highest in the recirculation region (E stations) where a pseudo-Lagrangian survey was conducted. In comparison 234Th export over the central plateau and north of the polar front (PF) was relatively limited throughout the survey. However, the 234Th results support that Fe fertilization increased particle export in all iron-fertilized waters. The impact was greatest in the recirculation feature (3-4 fold at 200 m depth, relative to the reference station), but more moderate over the central Kerguelen Plateau and in the northern plume of the Kerguelen bloom (~2-fold at 200 m depth). The C : Th ratio of large (>53 μm) potentially sinking particles collected via sequential filtration using in situ pumping (ISP) systems was used to convert the 234Th flux into a POC export flux. The C : Th ratios of sinking particles were highly variable (3.1 ± 0.1 to 10.5 ± 0.2 μmol dpm-1) with no clear site-related trend, despite the variety of ecosystem responses in the fertilized regions. C : Th ratios showed a decreasing trend between 100 and 200 m depth suggesting preferential carbon loss relative to 234Th possibly due to heterotrophic degradation and/or grazing activity. C : Th ratios of sinking particles sampled with drifting sediment traps in most cases showed very good agreement with ratios for particles collected via ISP deployments (>53 μm particles). Carbon export production varied between 3.5 ± 0.9 and 11.8 ± 1.3 mmol m-2 d-1 from the upper 100 m and between 1.8 ± 0.9 and 8.2 ± 0.9 mmol m-2 d-1 from the upper 200 m. The highest export production was found inside the PF meander with a range of 5.3 ± 1.0 to 11.8 ± 1.1 mmol m-2 d-1 over the 19-day survey period. The impact of Fe fertilization is highest inside the PF meander with 2.9-4.5-fold higher carbon flux at 200 m depth in comparison to the HNLC control station. The impact of Fe fertilization was significantly less over the central plateau (stations A3 and E-4W) and in the northern branch of the bloom (station F-L) with 1.6-2.0-fold higher carbon flux compared to the reference station R. Export efficiencies (ratio of export to primary production and ratio of export to new production) were particularly variable with relatively high values in the recirculation feature (6 to 27 %, respectively) and low values (1 to 5 %, respectively) over the central plateau (station A3) and north of the PF (station F-L), indicating spring biomass accumulation. Comparison with KEOPS1 results indicated that carbon export production is much lower during the onset of the bloom in austral spring than during the peak and declining phases in late summer.

  7. Spatiotemporal Variability in Particulate Organic Carbon Export Observed Using Bio-Optical Profiling Floats

    NASA Astrophysics Data System (ADS)

    Estapa, M. L.

    2016-02-01

    Autonomous, bio-optical profiling floats are poised to broaden the number and spatiotemporal resolution of observations of the ocean's biological pump. Here, we used multiple optical sensors aboard two bio-optical profiling floats (Navis BGCi, Sea-Bird) deployed in the Sargasso Sea to derive in situ proxies for particulate carbon (PC) flux, sub-mixed layer net community production (NCP) and to drive a model of net primary production (NPP). Profiles were collected at approximately 2-day resolution, and drift-phase PC flux observations were collected at subdaily resolution at a rotating cycle of observation depths between 150 and 1000 m. The magnitudes of NPP, PC flux, and their annually-averaged ratio were generally consistent with observations at the nearby Bermuda Atlantic Timeseries Study (BATS) site. PC flux and the export ratio were enhanced in the autumn as well as in the spring, and varied over short timescales possibly due to the influence of mesoscale eddies. The relatively shallow park depths and short profile cycle lengths allow us to identify ephemeral, subsurface bio-optical features and compare them to measured fluxes and satellite-observed surface properties.

  8. Two Outer Membrane Proteins Contribute to Caulobacter crescentus Cellular Fitness by Preventing Intracellular S-Layer Protein Accumulation

    DOE PAGES

    Overton, K. Wesley; Park, Dan M.; Yung, Mimi C.; ...

    2016-09-23

    Surface layers, or S-layers, are two-dimensional protein arrays that form the outermost layer of many bacteria and archaea. They serve several functions, including physical protection of the cell from environmental threats. The high abundance of S-layer proteins necessitates a highly efficient export mechanism to transport the S-layer protein from the cytoplasm to the cell exterior.Caulobacter crescentusis unique in that it has two homologous, seemingly redundant outer membrane proteins, RsaF aand RsaF b, which together with other components form a type I protein translocation pathway for S-layer export. These proteins have homology toEscherichia coliTolC, the outer membrane channel of multidrug effluxmore » pumps. Here we provide evidence that, unlike TolC, RsaF aand RsaF bare not involved in either the maintenance of membrane stability or the active export of antimicrobial compounds. Rather, RsaF aand RsaF bare required to prevent intracellular accumulation and aggregation of the S-layer protein RsaA; deletion of RsaF aand RsaF bled to a general growth defect and lowered cellular fitness. Using Western blotting, transmission electron microscopy, and transcriptome sequencing (RNA-seq), we show that loss of both RsaF aand RsaF bled to accumulation of insoluble RsaA in the cytoplasm, which in turn caused upregulation of a number of genes involved in protein misfolding and degradation pathways. These findings provide new insight into the requirement for RsaF aand RsaF bin cellular fitness and tolerance to antimicrobial agents and further our understanding of the S-layer export mechanism on both the transcriptional and translational levels inC. crescentus. IMPORTANCEDecreased growth rate and reduced cell fitness are common side effects of protein production in overexpression systems. Inclusion bodies typically form inside the cell, largely due to a lack of sufficient export machinery to transport the overexpressed proteins to the extracellular environment. This phenomenon can conceivably also occur in natural systems. As one example of a system evolved to prevent intracellular protein accumulation, our study demonstrates thatCaulobacter crescentushas two homologous outer membrane transporter proteins that are involved in S-layer export. This is an interesting case study that demonstrates how bacteria can evolve redundancy to ensure adequate protein export functionality and maintain high cellular fitness. Moreover, we provide evidence that these two outer membrane proteins, although being the closestC. crescentushomologs to TolC inE. coli, do not process TolC functionality inC. crescentus.« less

  9. Two Outer Membrane Proteins Contribute to Caulobacter crescentus Cellular Fitness by Preventing Intracellular S-Layer Protein Accumulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Overton, K. Wesley; Park, Dan M.; Yung, Mimi C.

    ABSTRACT Surface layers, or S-layers, are two-dimensional protein arrays that form the outermost layer of many bacteria and archaea. They serve several functions, including physical protection of the cell from environmental threats. The high abundance of S-layer proteins necessitates a highly efficient export mechanism to transport the S-layer protein from the cytoplasm to the cell exterior.Caulobacter crescentusis unique in that it has two homologous, seemingly redundant outer membrane proteins, RsaF aand RsaF b, which together with other components form a type I protein translocation pathway for S-layer export. These proteins have homology toEscherichia coliTolC, the outer membrane channel of multidrugmore » efflux pumps. Here we provide evidence that, unlike TolC, RsaF aand RsaF bare not involved in either the maintenance of membrane stability or the active export of antimicrobial compounds. Rather, RsaF aand RsaF bare required to prevent intracellular accumulation and aggregation of the S-layer protein RsaA; deletion of RsaF aand RsaF bled to a general growth defect and lowered cellular fitness. Using Western blotting, transmission electron microscopy, and transcriptome sequencing (RNA-seq), we show that loss of both RsaF aand RsaF bled to accumulation of insoluble RsaA in the cytoplasm, which in turn caused upregulation of a number of genes involved in protein misfolding and degradation pathways. These findings provide new insight into the requirement for RsaF aand RsaF bin cellular fitness and tolerance to antimicrobial agents and further our understanding of the S-layer export mechanism on both the transcriptional and translational levels inC. crescentus. IMPORTANCEDecreased growth rate and reduced cell fitness are common side effects of protein production in overexpression systems. Inclusion bodies typically form inside the cell, largely due to a lack of sufficient export machinery to transport the overexpressed proteins to the extracellular environment. This phenomenon can conceivably also occur in natural systems. As one example of a system evolved to prevent intracellular protein accumulation, our study demonstrates thatCaulobacter crescentushas two homologous outer membrane transporter proteins that are involved in S-layer export. This is an interesting case study that demonstrates how bacteria can evolve redundancy to ensure adequate protein export functionality and maintain high cellular fitness. Moreover, we provide evidence that these two outer membrane proteins, although being the closestC. crescentushomologs to TolC inE. coli, do not process TolC functionality inC. crescentus.« less

  10. Two Outer Membrane Proteins Contribute to Caulobacter crescentus Cellular Fitness by Preventing Intracellular S-Layer Protein Accumulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Overton, K. Wesley; Park, Dan M.; Yung, Mimi C.

    Surface layers, or S-layers, are two-dimensional protein arrays that form the outermost layer of many bacteria and archaea. They serve several functions, including physical protection of the cell from environmental threats. The high abundance of S-layer proteins necessitates a highly efficient export mechanism to transport the S-layer protein from the cytoplasm to the cell exterior.Caulobacter crescentusis unique in that it has two homologous, seemingly redundant outer membrane proteins, RsaF aand RsaF b, which together with other components form a type I protein translocation pathway for S-layer export. These proteins have homology toEscherichia coliTolC, the outer membrane channel of multidrug effluxmore » pumps. Here we provide evidence that, unlike TolC, RsaF aand RsaF bare not involved in either the maintenance of membrane stability or the active export of antimicrobial compounds. Rather, RsaF aand RsaF bare required to prevent intracellular accumulation and aggregation of the S-layer protein RsaA; deletion of RsaF aand RsaF bled to a general growth defect and lowered cellular fitness. Using Western blotting, transmission electron microscopy, and transcriptome sequencing (RNA-seq), we show that loss of both RsaF aand RsaF bled to accumulation of insoluble RsaA in the cytoplasm, which in turn caused upregulation of a number of genes involved in protein misfolding and degradation pathways. These findings provide new insight into the requirement for RsaF aand RsaF bin cellular fitness and tolerance to antimicrobial agents and further our understanding of the S-layer export mechanism on both the transcriptional and translational levels inC. crescentus. IMPORTANCEDecreased growth rate and reduced cell fitness are common side effects of protein production in overexpression systems. Inclusion bodies typically form inside the cell, largely due to a lack of sufficient export machinery to transport the overexpressed proteins to the extracellular environment. This phenomenon can conceivably also occur in natural systems. As one example of a system evolved to prevent intracellular protein accumulation, our study demonstrates thatCaulobacter crescentushas two homologous outer membrane transporter proteins that are involved in S-layer export. This is an interesting case study that demonstrates how bacteria can evolve redundancy to ensure adequate protein export functionality and maintain high cellular fitness. Moreover, we provide evidence that these two outer membrane proteins, although being the closestC. crescentushomologs to TolC inE. coli, do not process TolC functionality inC. crescentus.« less

  11. Contribution of urban runoff in Taipei metropolitan area to dissolved inorganic nitrogen export in the Danshui River, Taiwan.

    PubMed

    Kuo, Nae-Wen; Jien, Shih-Hao; Hong, Nien-Ming; Chen, Yao-Te; Lee, Tsung-Yu

    2017-01-01

    A previous study has demonstrated that Danshui River has almost the highest dissolved inorganic nitrogen (DIN) yield in the world and exports most of the DIN in the form of ammonium unlike the world's large rivers. However, the DIN sources are poorly constrained. In this study, the contributions of major sources in the Taipei metropolitan area to the DIN export in the Danshui River were investigated. It is observed that ammonium is the major DIN species in the downstream reaches, resulting from the ammonium-dominated inputs of the effluents of wastewater treatment plants (WWTP) and rain water pumping stations (RWPS). DIN concentrations in the downstream (urban) reaches are substantially elevated. The upstream tributaries annually discharge ∼2709 t DIN to the downstream reaches. However, the DIN discharge off the downstream reaches rises to ∼17,918 t, resulting from the contribution of RWPS-collected water, i.e., ∼14,632 t, and the effluents of two WWTP, i.e., ∼577 t. RWPS-collected water inherently contains the contribution of atmospheric deposition, ∼2937 t DIN. This finding implies that ∼11,695 t (∼66 % of the downstream output) DIN flux off the Danshui River is from urban runoff and can be attributed to human activities in the Taipei metropolitan area. To improve the water quality in the Danshui River, water quality controls in urban runoff are important.

  12. Structure of a prokaryotic virtual proton pump at 3.2 Å resolution

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fang, Yiling; Jayaram, Hariharan; Shane, Tania

    2009-09-15

    To reach the mammalian gut, enteric bacteria must pass through the stomach. Many such organisms survive exposure to the harsh gastric environment (pH 1.5-4) by mounting extreme acid-resistance responses, one of which, the arginine-dependent system of Escherichia coli, has been studied at levels of cellular physiology, molecular genetics and protein biochemistry. This multiprotein system keeps the cytoplasm above pH 5 during acid challenge by continually pumping protons out of the cell using the free energy of arginine decarboxylation. At the heart of the process is a 'virtual proton pump' in the inner membrane, called AdiC, that imports L-arginine from themore » gastric juice and exports its decarboxylation product agmatine. AdiC belongs to the APC superfamily of membrane proteins, which transports amino acids, polyamines and organic cations in a multitude of biological roles, including delivery of arginine for nitric oxide synthesis, facilitation of insulin release from pancreatic {beta}-cells, and, when inappropriately overexpressed, provisioning of certain fast-growing neoplastic cells with amino acids. High-resolution structures and detailed transport mechanisms of APC transporters are currently unknown. Here we describe a crystal structure of AdiC at 3.2 {angstrom} resolution. The protein is captured in an outward-open, substrate-free conformation with transmembrane architecture remarkably similar to that seen in four other families of apparently unrelated transport proteins.« less

  13. Climate change impacts on net primary production (NPP) and export production (EP) regulated by increasing stratification and phytoplankton community structure in the CMIP5 models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fu, Weiwei; Randerson, James T.; Moore, J. Keith

    We examine climate change impacts on net primary production (NPP) and export production (sinking particulate flux; EP) with simulations from nine Earth system models (ESMs) performed in the framework of the fifth phase of the Coupled Model Intercomparison Project (CMIP5). Global NPP and EP are reduced by the end of the century for the intense warming scenario of Representative Concentration Pathway (RCP) 8.5. Relative to the 1990s, NPP in the 2090s is reduced by 2–16% and EP by 7–18%. The models with the largest increases in stratification (and largest relative declines in NPP and EP) also show the largest positivemore » biases in stratification for the contemporary period, suggesting overestimation of climate change impacts on NPP and EP. All of the CMIP5 models show an increase in stratification in response to surface–ocean warming and freshening, which is accompanied by decreases in surface nutrients, NPP and EP. There is considerable variability across the models in the magnitudes of NPP, EP, surface nutrient concentrations and their perturbations by climate change. The negative response of NPP and EP to increasing stratification reflects primarily a bottom-up control, as upward nutrient flux declines at the global scale. Models with dynamic phytoplankton community structure show larger declines in EP than in NPP. This pattern is driven by phytoplankton community composition shifts, with reductions in productivity by large phytoplankton as smaller phytoplankton (which export less efficiently) are favored under the increasing nutrient stress. Thus, the projections of the NPP response to climate change are critically dependent on the simulated phytoplankton community structure, the efficiency of the biological pump and the resulting levels of regenerated production, which vary widely across the models. In conclusion, community structure is represented simply in the CMIP5 models, and should be expanded to better capture the spatial patterns and climate-driven changes in export efficiency.« less

  14. Climate change impacts on net primary production (NPP) and export production (EP) regulated by increasing stratification and phytoplankton community structure in the CMIP5 models

    DOE PAGES

    Fu, Weiwei; Randerson, James T.; Moore, J. Keith

    2016-09-16

    We examine climate change impacts on net primary production (NPP) and export production (sinking particulate flux; EP) with simulations from nine Earth system models (ESMs) performed in the framework of the fifth phase of the Coupled Model Intercomparison Project (CMIP5). Global NPP and EP are reduced by the end of the century for the intense warming scenario of Representative Concentration Pathway (RCP) 8.5. Relative to the 1990s, NPP in the 2090s is reduced by 2–16% and EP by 7–18%. The models with the largest increases in stratification (and largest relative declines in NPP and EP) also show the largest positivemore » biases in stratification for the contemporary period, suggesting overestimation of climate change impacts on NPP and EP. All of the CMIP5 models show an increase in stratification in response to surface–ocean warming and freshening, which is accompanied by decreases in surface nutrients, NPP and EP. There is considerable variability across the models in the magnitudes of NPP, EP, surface nutrient concentrations and their perturbations by climate change. The negative response of NPP and EP to increasing stratification reflects primarily a bottom-up control, as upward nutrient flux declines at the global scale. Models with dynamic phytoplankton community structure show larger declines in EP than in NPP. This pattern is driven by phytoplankton community composition shifts, with reductions in productivity by large phytoplankton as smaller phytoplankton (which export less efficiently) are favored under the increasing nutrient stress. Thus, the projections of the NPP response to climate change are critically dependent on the simulated phytoplankton community structure, the efficiency of the biological pump and the resulting levels of regenerated production, which vary widely across the models. In conclusion, community structure is represented simply in the CMIP5 models, and should be expanded to better capture the spatial patterns and climate-driven changes in export efficiency.« less

  15. A linkage between Asian dust, dissolved iron and marine export production in the deep ocean

    NASA Astrophysics Data System (ADS)

    Han, Yongxiang; Zhao, Tianliang; Song, Lianchun; Fang, Xiaomin; Yin, Yan; Deng, Zuqin; Wang, Suping; Fan, Shuxian

    2011-08-01

    Iron-addition experiments have revealed that iron supply exerts controls on biogeochemical cycles in the ocean and ultimately influences the Earth's climate system. The iron hypothesis in its broad outlines has been proved to be correct. However, the hypothesis needs to be verified with an observable biological response to specific dust deposition events. Plankton growth following the Asian dust storm over Ocean Station PAPA (50°N, 145°W) in the North Pacific Ocean in April 2001 was the first supportive evidence of natural aeolian iron inputs to ocean; The data were obtained through the SeaWiFS satellite and robot carbon explorers by Bishop et al. Using the NARCM modeling results in this study, the calculated total dust deposition flux was 35 mg m -2 per day in PAPA region from the dust storm of 11-13 April, 2001 into 0.0615 mg m -2 d -1 (about 1100 nM) soluble iron in the surface layer at Station PAPA. It was enough for about 1100 nM to enhance the efficiency of the marine biological pump and trigger the rapid increase of POC and chlorophyll. The iron fertilization hypothesis therefore is plausible. However, even if this specific dust event can support the iron fertilization hypothesis, long-term observation data are lacking in marine export production and continental dust. In this paper, we also conducted a simple correlation analysis between the diatoms and foraminifera at about 3000 m and 4000 m at two subarctic Pacific stations and the dust aerosol production from China's mainland. The correlation coefficient between marine export production and dust storm frequency in the core area of the dust storms was significantly high, suggesting that aerosols generated by Asian dust storm are the source of iron for organic matter fixation in the North Pacific Ocean. These results suggest that there could be an interlocking chain for the change of atmospheric dust aerosol-soluble iron-marine export production.

  16. The glacial iron cycle from source to export

    NASA Astrophysics Data System (ADS)

    Hawkings, J.; Wadham, J. L.; Tranter, M.; Raiswell, R.; Benning, L. G.; Statham, P. J.; Tedstone, A. J.; Nienow, P. W.; Telling, J.; Bagshaw, E.; Simmons, S. L.

    2014-12-01

    Nutrient availability limits primary production in large sectors of the world's oceans. Iron is the major limiting nutrient in around one third of the oceanic euphotic zone, most significantly in the Southern Ocean proximal to Antarctica. In these areas the availability of bioavailable iron can influence the amount of primary production, and thus the strength of the biological pump and associated carbon drawdown from the atmosphere. Despite experiencing widespread iron limitation, the Polar oceans are among the most productive on Earth. Due to the extreme cold, remoteness and their perceived "stasis", ice sheets have previously been though of as insignificant in global biogeochemical cycles. However, large marine algal blooms have been observed in iron-limited areas where glacial influence is large, and it is possible that these areas are stimulated by glacial bioavailable iron input. Here we discuss the importance of the Greenland and Antarctic ice sheets in the global iron cycle. Using field collected trace element data, bulk meltwater chemistry and mineralogical analysis, including photomicrographs, EELS and XANES, we present, for the first time, a conceptual model of the glacial iron cycle from source to export. Using this data we discuss the sources of iron in glacial meltwater, transportation and alteration through the glacial system, and subsequent export to downstream environments. Data collected in 2012 and 2013 from two different Greenlandic glacial catchments are shown, with the most detailed breakdown of iron speciation and concentrations in glacial areas yet reported. Furthermore, the first data from Greenlandic icebergs is presented, allowing meltwater-derived and iceberg-derived iron export to be compared, and the influence of both in marine productivity to be estimated. Using our conceptual model and flux estimates from our dataset, glacial iron delivery in both the northern and southern hemisphere is discussed. Finally, we compare our flux estimates to other major iron sources to the polar regions such as aeolian dust, and discuss potential implications of increased melting of the ice sheets on the global iron cycle in the future.

  17. Predictable and efficient carbon sequestration in the North Pacific Ocean supported by symbiotic nitrogen fixation

    PubMed Central

    Karl, David M.; Church, Matthew J.; Dore, John E.; Letelier, Ricardo M.; Mahaffey, Claire

    2012-01-01

    The atmospheric and deep sea reservoirs of carbon dioxide are linked via physical, chemical, and biological processes. The last of these include photosynthesis, particle settling, and organic matter remineralization, and are collectively termed the “biological carbon pump.” Herein, we present results from a 13-y (1992–2004) sediment trap experiment conducted in the permanently oligotrophic North Pacific Subtropical Gyre that document a large, rapid, and predictable summertime (July 15–August 15) pulse in particulate matter export to the deep sea (4,000 m). Peak daily fluxes of particulate matter during the summer export pulse (SEP) average 408, 283, 24.1, 1.1, and 67.5 μmol·m−2·d−1 for total carbon, organic carbon, nitrogen, phosphorus (PP), and biogenic silica, respectively. The SEP is approximately threefold greater than mean wintertime particle fluxes and fuels more efficient carbon sequestration because of low remineralization during downward transit that leads to elevated total carbon/PP and organic carbon/PP particle stoichiometry (371:1 and 250:1, respectively). Our long-term observations suggest that seasonal changes in the microbial assemblage, namely, summertime increases in the biomass and productivity of symbiotic nitrogen-fixing cyanobacteria in association with diatoms, are the main cause of the prominent SEP. The recurrent SEP is enigmatic because it is focused in time despite the absence of any obvious predictable stimulus or habitat condition. We hypothesize that changes in day length (photoperiodism) may be an important environmental cue to initiate aggregation and subsequent export of organic matter to the deep sea. PMID:22308450

  18. Predictable and efficient carbon sequestration in the North Pacific Ocean supported by symbiotic nitrogen fixation.

    PubMed

    Karl, David M; Church, Matthew J; Dore, John E; Letelier, Ricardo M; Mahaffey, Claire

    2012-02-07

    The atmospheric and deep sea reservoirs of carbon dioxide are linked via physical, chemical, and biological processes. The last of these include photosynthesis, particle settling, and organic matter remineralization, and are collectively termed the "biological carbon pump." Herein, we present results from a 13-y (1992-2004) sediment trap experiment conducted in the permanently oligotrophic North Pacific Subtropical Gyre that document a large, rapid, and predictable summertime (July 15-August 15) pulse in particulate matter export to the deep sea (4,000 m). Peak daily fluxes of particulate matter during the summer export pulse (SEP) average 408, 283, 24.1, 1.1, and 67.5 μmol·m(-2)·d(-1) for total carbon, organic carbon, nitrogen, phosphorus (PP), and biogenic silica, respectively. The SEP is approximately threefold greater than mean wintertime particle fluxes and fuels more efficient carbon sequestration because of low remineralization during downward transit that leads to elevated total carbon/PP and organic carbon/PP particle stoichiometry (371:1 and 250:1, respectively). Our long-term observations suggest that seasonal changes in the microbial assemblage, namely, summertime increases in the biomass and productivity of symbiotic nitrogen-fixing cyanobacteria in association with diatoms, are the main cause of the prominent SEP. The recurrent SEP is enigmatic because it is focused in time despite the absence of any obvious predictable stimulus or habitat condition. We hypothesize that changes in day length (photoperiodism) may be an important environmental cue to initiate aggregation and subsequent export of organic matter to the deep sea.

  19. Restoration of enterohepatic bile acid pathways in pregnant mice following short term activation of Fxr by GW4064

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moscovitz, Jamie E.; Kong, Bo; Buckley, Kyle

    The farnesoid X receptor (Fxr) controls bile acid homeostasis by coordinately regulating the expression of synthesizing enzymes (Cyp7a1, Cyp8b1), conjugating enzymes (Bal, Baat) and transporters in the ileum (Asbt, Ostα/β) and liver (Ntcp, Bsep, Ostβ). Transcriptional regulation by Fxr can be direct, or through the ileal Fgf15/FGF19 and hepatic Shp pathways. Circulating bile acids are increased during pregnancy due to hormone-mediated disruption of Fxr signaling. While this adaptation enhances lipid absorption, elevated bile acids may predispose women to develop maternal cholestasis. The objective of this study was to determine whether short-term treatment of pregnant mice with GW4064 (a potent FXRmore » agonist) restores Fxr signaling to the level observed in virgin mice. Plasma, liver and ilea were collected from virgin and pregnant mice administered vehicle or GW4064 by oral gavage. Treatment of pregnant mice with GW4064 induced ileal Fgf15, Shp and Ostα/β mRNAs, and restored hepatic Shp, Bal, Ntcp, and Bsep back to vehicle-treated virgin levels. Pregnant mice exhibited 2.5-fold increase in Cyp7a1 mRNA compared to virgin controls, which was reduced by GW4064. Similarly treatment of mouse primary hepatocytes with plasma isolated from pregnant mice induced Cyp7a1 mRNA by nearly 3-fold as compared to virgin plasma, which could be attenuated by co-treatment with either GW4064 or recombinant FGF19 protein. Collectively, these data reveal that repressed activity of intestinal and hepatic Fxr in pregnancy, as previously demonstrated, may be restored by pharmacological activation. This study provides the basis for a novel approach to restore bile acid homeostasis in patients with maternal cholestasis. - Highlights: • Ileal bile acid pathways are altered in pregnancy in an Fxr-dependent manner. • Ileal Fxr/Fgf contributes to changes in hepatic bile acid synthesis and transport. • Treatment of pregnant mice with an Fxr agonist restores bile acid homeostasis.« less

  20. Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meng, Qiang; Chen, Xin-li; Wang, Chang-yuan

    2015-03-15

    Intrahepatic cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Appropriate regulation of bile acids in hepatocytes is critically important for protection against liver injury. In the present study, we characterized the protective effect of alisol B 23-acetate (AB23A), a natural triterpenoid, on alpha-naphthylisothiocyanate (ANIT)-induced liver injury and intrahepatic cholestasis in mice and further elucidated the mechanisms in vivo and in vitro. AB23A treatment dose-dependently protected against liver injury induced by ANIT through reducing hepatic uptake and increasing efflux of bile acid via down-regulation of hepatic uptake transporters (Ntcp)more » and up-regulation of efflux transporter (Bsep, Mrp2 and Mdr2) expression. Furthermore, AB23A reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, increased bile acid conjugation through inducing Bal, Baat and bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrate the involvement of farnesoid X receptor (FXR) in the hepatoprotective effect of AB23A. The changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo. In vitro evidences also directly demonstrated the effect of AB23A on FXR activation in a dose-dependent manner using luciferase reporter assay in HepG2 cells. In conclusion, AB23A produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes. - Highlights: • AB23A has at least three roles in protection against ANIT-induced liver injury. • AB23A decreases Ntcp, and increases Bsep, Mrp2 and Mdr2 expression. • AB23A represses Cyp7a1 and Cyp8b1 through inducing Shp and Fgf15 expression. • AB23A increases bile acid metabolism through inducing Sult2a1 expression. • FXR activation is involved in the hepatoprotective effect of AB23A.« less

  1. Understanding the recent changes in the Southern Ocean carbon cycle: A multidisciplinary approach

    NASA Astrophysics Data System (ADS)

    Manizza, M.; Kahru, M.; Menemenlis, D.; Nevison, C. D.; Mitchell, B. G.; Keeling, R. F.

    2016-12-01

    The Southern Ocean represents a key area of the global ocean for the uptake of the CO2 originating from fossil fuels emissions. In these waters, cold temperatures combined with high rates of biological production drive the carbon uptake that accounts for about one-third of the global ocean uptake.Recent studies showed that changes in the Southern Annular Mode (SAM) index, mainly a proxy of the intensity of westerly winds, had a significant impact on the temporal variability of the CO2 uptake in the Southern Ocean. In order to shed light on this problem we propose to use both satellite-derived estimates of ocean productivity and carbon export in combinations of ocean physical and biogeochemical state estimates focusing on the 2006-2013 period. While the estimates of carbon fixation and export based on remote sensing will provide key information on the spatial and temporal variations of the biological carbon pump, the ocean state estimates will provide additional information on physical and carbon cycle processes, including the air-sea CO2 fluxes of the Southern Ocean in the 2006-2013 period where model solutions have been optimized.These physical estimates will be used to force an ocean biogeochemical model (ECCO2-Darwin) that will compute the CO2 uptake for each year. The physical model, forced with optimized atmospheric forcing, aims to realistically simulate interannual ocean climate variability that drives changes in both physical and biogeochemical processes ultimately impacting the carbon uptake of the Southern Ocean, and potentially responding to the SAM index variations.Although in this study great emphasis is given to the role of physical climate variations at driving the CO2 uptake of these polar waters, we will integrate model results with estimates from remote sensing techniques to better understand role of the biological carbon pump and its variability potentially responding to the SAM index changes.

  2. Energy landscape of the reactions governing the Na+ deeply occluded state of the Na+/K+-ATPase in the giant axon of the Humboldt squid

    PubMed Central

    Castillo, Juan P.; De Giorgis, Daniela; Basilio, Daniel; Gadsby, David C.; Rosenthal, Joshua J. C.; Latorre, Ramon; Holmgren, Miguel; Bezanilla, Francisco

    2011-01-01

    The Na+/K+ pump is a nearly ubiquitous membrane protein in animal cells that uses the free energy of ATP hydrolysis to alternatively export 3Na+ from the cell and import 2K+ per cycle. This exchange of ions produces a steady-state outwardly directed current, which is proportional in magnitude to the turnover rate. Under certain ionic conditions, a sudden voltage jump generates temporally distinct transient currents mediated by the Na+/K+ pump that represent the kinetics of extracellular Na+ binding/release and Na+ occlusion/deocclusion transitions. For many years, these events have escaped a proper thermodynamic treatment due to the relatively small electrical signal. Here, taking the advantages offered by the large diameter of the axons from the squid Dosidicus gigas, we have been able to separate the kinetic components of the transient currents in an extended temperature range and thus characterize the energetic landscape of the pump cycle and those transitions associated with the extracellular release of the first Na+ from the deeply occluded state. Occlusion/deocclusion transition involves large changes in enthalpy and entropy as the ion is exposed to the external milieu for release. Binding/unbinding is substantially less costly, yet larger than predicted for the energetic cost of an ion diffusing through a permeation pathway, which suggests that ion binding/unbinding must involve amino acid side-chain rearrangements at the site. PMID:22143771

  3. Energy landscape of the reactions governing the Na+ deeply occluded state of the Na+/K+-ATPase in the giant axon of the Humboldt squid.

    PubMed

    Castillo, Juan P; De Giorgis, Daniela; Basilio, Daniel; Gadsby, David C; Rosenthal, Joshua J C; Latorre, Ramon; Holmgren, Miguel; Bezanilla, Francisco

    2011-12-20

    The Na(+)/K(+) pump is a nearly ubiquitous membrane protein in animal cells that uses the free energy of ATP hydrolysis to alternatively export 3Na(+) from the cell and import 2K(+) per cycle. This exchange of ions produces a steady-state outwardly directed current, which is proportional in magnitude to the turnover rate. Under certain ionic conditions, a sudden voltage jump generates temporally distinct transient currents mediated by the Na(+)/K(+) pump that represent the kinetics of extracellular Na(+) binding/release and Na(+) occlusion/deocclusion transitions. For many years, these events have escaped a proper thermodynamic treatment due to the relatively small electrical signal. Here, taking the advantages offered by the large diameter of the axons from the squid Dosidicus gigas, we have been able to separate the kinetic components of the transient currents in an extended temperature range and thus characterize the energetic landscape of the pump cycle and those transitions associated with the extracellular release of the first Na(+) from the deeply occluded state. Occlusion/deocclusion transition involves large changes in enthalpy and entropy as the ion is exposed to the external milieu for release. Binding/unbinding is substantially less costly, yet larger than predicted for the energetic cost of an ion diffusing through a permeation pathway, which suggests that ion binding/unbinding must involve amino acid side-chain rearrangements at the site.

  4. Wild Horse 69-kV transmission line environmental assessment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1996-12-01

    Hill County Electric Cooperative Inc. (Hill County) proposes to construct and operate a 69-kV transmission line from its North Gildford Substation in Montana north to the Canadian border. A vicinity project area map is enclosed as a figure. TransCanada Power Corporation (TCP), a Canadian power-marketing company, will own and construct the connecting 69-kV line from the international border to Express Pipeline`s pump station at Wild Horse, Alberta. This Environmental Assessment is prepared for the Department of Energy (DOE) as lead federal agency to comply with the requirements of the National Environmental Policy Act (NEPA), as part of DOE`s review andmore » approval process of the applications filed by Hill County for a DOE Presidential Permit and License to Export Electricity to a foreign country. The purpose of the proposed line is to supply electric energy to a crude oil pump station in Canada, owned by Express Pipeline Ltd. (Express). The pipeline would transport Canadian-produced oil from Hardisty, Alberta, Canada, to Caster, Wyoming. The Express Pipeline is scheduled to be constructed in 1996--97 and will supply crude oil to refineries in Wyoming and the midwest.« less

  5. Accounting System for Water Use by Vegetation in the Lower Colorado River Valley

    USGS Publications Warehouse

    Owen-Joyce, Sandra J.

    1992-01-01

    The Colorado River is the principal source of water in the valley of the Colorado River between Hoover Dam and the international boundary with Mexico (fig. 1). Agricultural, domestic, municipal, industrial, hydroelectric-power genera-tion, and recreation are the primary uses of river water in the valley. Most of the consumptive use of water from the river occurs downstream from Davis Dam, where water is diverted to irrigate crops along the river or is exported to interior regions of California and Arizona. Most of the agricultural areas are on the alluvium of the flood plain; in a few areas, land on the alluvial terraces has been cultivated. River water is consumed mainly by vegetation (crops and phreatophytes) on the flood plain. Crops were grown on 70.3 percent of the vegetated area classified by using 1984 digital image satellite data. Phreatophytes, natural vege-tation that obtain water from the alluvial aquifer, covered the remaining vegetated areas on the uncultivated flood plain. Most of the water used for irrigation is diverted or pumped from the river. In some areas, water is pumped from wells completed in the alluvial aquifer, which is hydraulically connected to the river.

  6. CD147 regulates the expression of MCT1 and lactate export in multiple myeloma cells

    PubMed Central

    Walters, Denise K; Arendt, Bonnie K; Jelinek, Diane F

    2013-01-01

    Increased use of the glycolytic pathway, even in the presence of oxygen, has recently been recognized as a key characteristic of malignant cells. However, the glycolytic phenotype results in increased lactic acid production and, in order to prevent cellular acidosis, tumor cells must increase proton efflux via upregulation of pH regulators such as proton-pumps, sodium-proton exchangers, and/or monocarboxylate transporters (MCT) (e.g., MCT1, MCT4). Interestingly, expression of MCT1 and MCT4 has been previously shown to be dependent upon expression of the transmembrane glycoprotein CD147. Recently, we demonstrated that primary patient multiple myeloma (MM) cells and human MM cell lines (HMCLs) overexpress CD147. Therefore, the goal of the current study was to specifically determine if MCT1 and MCT4 were also overexpressed in MM cells. RT-PCR analysis demonstrated both primary patient MM cells and HMCLs overexpress MCT1 and MCT4 mRNA. Notably, primary MM cells or HMCLs were found to express variable levels of MCT1 and/or MCT4 at the protein level despite CD147 expression. In those HMCLs positive for MCT1 and/or MCT4 protein expression, MCT1 and/or MCT4 were found to be associated with CD147. Specific siRNA-mediated downregulation of MCT1 but not MCT4 resulted in decreased HMCL proliferation, decreased lactate export, and increased cellular media pH. However, western blot analysis revealed that downregulation of MCT1 also downregulated CD147 and vice versa despite no effect on mRNA levels. Taken together, these data demonstrate the association between MCT1 and CD147 proteins in MM cells and importance of their association for lactate export and proliferation in MM cells. PMID:24013424

  7. CD147 regulates the expression of MCT1 and lactate export in multiple myeloma cells.

    PubMed

    Walters, Denise K; Arendt, Bonnie K; Jelinek, Diane F

    2013-10-01

    Increased use of the glycolytic pathway, even in the presence of oxygen, has recently been recognized as a key characteristic of malignant cells. However, the glycolytic phenotype results in increased lactic acid production and, in order to prevent cellular acidosis, tumor cells must increase proton efflux via upregulation of pH regulators such as proton-pumps, sodium-proton exchangers, and/or monocarboxylate transporters (MCT) (e.g., MCT1, MCT4). Interestingly, expression of MCT1 and MCT4 has been previously shown to be dependent upon expression of the transmembrane glycoprotein CD147. Recently, we demonstrated that primary patient multiple myeloma (MM) cells and human MM cell lines (HMCLs) overexpress CD147. Therefore, the goal of the current study was to specifically determine if MCT1 and MCT4 were also overexpressed in MM cells. RT-PCR analysis demonstrated both primary patient MM cells and HMCLs overexpress MCT1 and MCT4 mRNA. Notably, primary MM cells or HMCLs were found to express variable levels of MCT1 and/or MCT4 at the protein level despite CD147 expression. In those HMCLs positive for MCT1 and/or MCT4 protein expression, MCT1 and/or MCT4 were found to be associated with CD147. Specific siRNA-mediated downregulation of MCT1 but not MCT4 resulted in decreased HMCL proliferation, decreased lactate export, and increased cellular media pH. However, western blot analysis revealed that downregulation of MCT1 also downregulated CD147 and vice versa despite no effect on mRNA levels. Taken together, these data demonstrate the association between MCT1 and CD147 proteins in MM cells and importance of their association for lactate export and proliferation in MM cells.

  8. Migrant biomass and respiratory carbon flux by zooplankton and micronekton in the subtropical northeast Atlantic Ocean (Canary Islands)

    NASA Astrophysics Data System (ADS)

    Ariza, A.; Garijo, J. C.; Landeira, J. M.; Bordes, F.; Hernández-León, S.

    2015-05-01

    Diel Vertical Migration (DVM) in marine ecosystems is performed by zooplankton and micronekton, promoting a poorly accounted export of carbon to the deep ocean. Major efforts have been made to estimate carbon export due to gravitational flux and to a lesser extent, to migrant zooplankton. However, migratory flux by micronekton has been largely neglected in this context, due to its time-consuming and difficult sampling. In this paper, we evaluated gravitational and migratory flux due to the respiration of zooplankton and micronekton in the northeast subtropical Atlantic Ocean (Canary Islands). Migratory flux was addressed by calculating the biomass of migrating components and measuring the electron transfer system (ETS) activity in zooplankton and dominant species representing micronekton (Euphausia gibboides, Sergia splendens and Lobianchia dofleini). Our results showed similar biomass in both components. The main taxa contributing to DVM within zooplankton were juvenile euphausiids, whereas micronekton were mainly dominated by fish, followed by adult euphausiids and decapods. The contribution to respiratory flux of zooplankton (3.4 ± 1.9 mg C m-2 d-1) was similar to that of micronekton (2.9 ± 1.0 mg C m-2 d-1). In summary, respiratory flux accounted for 53% (range 23-71) of the gravitational flux measured at 150 m depth (11.9 ± 5.8 mg C m-2 d-1). However, based on larger migratory ranges and gut clearance rates, micronekton are expected to be the dominant component that contributes to carbon export in deeper waters. Micronekton estimates in this paper as well as those in existing literature, although variable due to regional differences and difficulties in calculating their biomass, suggest that carbon fluxes driven by this community are important for future models of the biological carbon pump.

  9. Characterization and regulation of the resistance-nodulation-cell division-type multidrug efflux pumps MdtABC and MdtUVW from the fire blight pathogen Erwinia amylovora.

    PubMed

    Pletzer, Daniel; Weingart, Helge

    2014-07-11

    The Gram-negative bacterium Erwinia amylovora is the causal agent of the devastating disease fire blight in rosaceous plants such as apple, pear, quince, raspberry, and cotoneaster. In order to survive and multiply in a host, microbes must be able to circumvent the toxic effects of antimicrobial plant compounds, such as flavonoids and tannins. E. amylovora uses multidrug efflux transporters that recognize and actively export toxic compounds out of the cells. Here, two heterotrimeric resistance-nodulation-cell division (RND)-type multidrug efflux pumps, MdtABC and MdtUVW, from E. amylovora were identified. These RND systems are unusual in that they contain two different RND proteins forming a functional pump. To find the substrate specificities of the two efflux systems, we overexpressed the transporters in a hypersensitive mutant lacking the major RND pump AcrB. Both transporters mediated resistance to several flavonoids, fusidic acid and novobiocin. Additionally, MdtABC mediated resistance towards josamycin, bile salts and silver nitrate, and MdtUVW towards clotrimazole. The ability of the mdtABC- and mdtUVW-deficient mutants to multiply in apple rootstock was reduced. Quantitative RT-PCR analyses revealed that the expression of the transporter genes was induced during infection of apple rootstock. The polyphenolic plant compound tannin, as well as the heavy metal salt tungstate was found to induce the expression of mdtABC. Finally, the expression of the mdtABC genes was shown to be regulated by BaeR, the response regulator of the two-component system BaeSR, a cell envelope stress response system that controls the adaptive responses to changes in the environment. The expression of MdtABC and MdtUVW is induced during growth of E. amylovora in planta. We identified the plant polyphenol tannin as inducer of mdtABC expression. The reduced ability of the mdtABC- and mdtUVW-deficient mutants to multiply in apple rootstock suggests that the efflux pumps are involved in resistance to plant antimicrobials, maybe including flavonoids, which were identified as substrates of both pumps. Furthermore, we found that the mdtABC operon belongs to the regulon of the two-component regulator BaeR suggesting a role of this RND transporter in the cell envelope stress response of E. amylovora.

  10. Characterization and regulation of the Resistance-Nodulation-Cell Division-type multidrug efflux pumps MdtABC and MdtUVW from the fire blight pathogen Erwinia amylovora

    PubMed Central

    2014-01-01

    Background The Gram-negative bacterium Erwinia amylovora is the causal agent of the devastating disease fire blight in rosaceous plants such as apple, pear, quince, raspberry, and cotoneaster. In order to survive and multiply in a host, microbes must be able to circumvent the toxic effects of antimicrobial plant compounds, such as flavonoids and tannins. E. amylovora uses multidrug efflux transporters that recognize and actively export toxic compounds out of the cells. Here, two heterotrimeric resistance-nodulation-cell division (RND)-type multidrug efflux pumps, MdtABC and MdtUVW, from E. amylovora were identified. These RND systems are unusual in that they contain two different RND proteins forming a functional pump. Results To find the substrate specificities of the two efflux systems, we overexpressed the transporters in a hypersensitive mutant lacking the major RND pump AcrB. Both transporters mediated resistance to several flavonoids, fusidic acid and novobiocin. Additionally, MdtABC mediated resistance towards josamycin, bile salts and silver nitrate, and MdtUVW towards clotrimazole. The ability of the mdtABC- and mdtUVW-deficient mutants to multiply in apple rootstock was reduced. Quantitative RT-PCR analyses revealed that the expression of the transporter genes was induced during infection of apple rootstock. The polyphenolic plant compound tannin, as well as the heavy metal salt tungstate was found to induce the expression of mdtABC. Finally, the expression of the mdtABC genes was shown to be regulated by BaeR, the response regulator of the two-component system BaeSR, a cell envelope stress response system that controls the adaptive responses to changes in the environment. Conclusions The expression of MdtABC and MdtUVW is induced during growth of E. amylovora in planta. We identified the plant polyphenol tannin as inducer of mdtABC expression. The reduced ability of the mdtABC- and mdtUVW-deficient mutants to multiply in apple rootstock suggests that the efflux pumps are involved in resistance to plant antimicrobials, maybe including flavonoids, which were identified as substrates of both pumps. Furthermore, we found that the mdtABC operon belongs to the regulon of the two-component regulator BaeR suggesting a role of this RND transporter in the cell envelope stress response of E. amylovora. PMID:25012600

  11. Coccolithovirus facilitation of carbon export in the North Atlantic.

    PubMed

    Laber, Christien P; Hunter, Jonathan E; Carvalho, Filipa; Collins, James R; Hunter, Elias J; Schieler, Brittany M; Boss, Emmanuel; More, Kuldeep; Frada, Miguel; Thamatrakoln, Kimberlee; Brown, Christopher M; Haramaty, Liti; Ossolinski, Justin; Fredricks, Helen; Nissimov, Jozef I; Vandzura, Rebecca; Sheyn, Uri; Lehahn, Yoav; Chant, Robert J; Martins, Ana M; Coolen, Marco J L; Vardi, Assaf; DiTullio, Giacomo R; Van Mooy, Benjamin A S; Bidle, Kay D

    2018-05-01

    Marine phytoplankton account for approximately half of global primary productivity 1 , making their fate an important driver of the marine carbon cycle. Viruses are thought to recycle more than one-quarter of oceanic photosynthetically fixed organic carbon 2 , which can stimulate nutrient regeneration, primary production and upper ocean respiration 2 via lytic infection and the 'virus shunt'. Ultimately, this limits the trophic transfer of carbon and energy to both higher food webs and the deep ocean 2 . Using imagery taken by the Moderate Resolution Imaging Spectroradiometer (MODIS) onboard the Aqua satellite, along with a suite of diagnostic lipid- and gene-based molecular biomarkers, in situ optical sensors and sediment traps, we show that Coccolithovirus infections of mesoscale (~100 km) Emiliania huxleyi blooms in the North Atlantic are coupled with particle aggregation, high zooplankton grazing and greater downward vertical fluxes of both particulate organic and particulate inorganic carbon from the upper mixed layer. Our analyses captured blooms in different phases of infection (early, late and post) and revealed the highest export flux in 'early-infected blooms' with sinking particles being disproportionately enriched with infected cells and subsequently remineralized at depth in the mesopelagic. Our findings reveal viral infection as a previously unrecognized ecosystem process enhancing biological pump efficiency.

  12. Efflux pumps as antimicrobial resistance mechanisms.

    PubMed

    Poole, Keith

    2007-01-01

    Antibiotic resistance continues to hamper antimicrobial chemotherapy of infectious disease, and while biocide resistance outside of the laboratory is as yet unrealized, in vitro and in vivo episodes of reduced biocide susceptibility are not uncommon. Efflux mechanisms, both drug-specific and multidrug, are important determinants of intrinsic and/or acquired resistance to these antimicrobials in important human pathogens. Multidrug efflux mechanisms are generally chromosome-encoded, with their expression typically resultant from mutations in regulatory genes, while drug-specific efflux mechanisms are encoded by mobile genetic elements whose acquisition is sufficient for resistance. While it has been suggested that drug-specific efflux systems originated from efflux determinants of self-protection in antibiotic-producing Actinomycetes, chromosomal multidrug efflux determinants, at least in Gram-negative bacteria, are appreciated as having an intended housekeeping function unrelated to drug export and resistance. Thus, it will be important to elucidate the intended natural function of these efflux mechanisms in order, for example, to anticipate environmental conditions or circumstances that might promote their expression and, so, compromise antimicrobial chemotherapy. Given the clinical significance of antimicrobial exporters, it is clear that efflux must be considered in formulating strategies for treatment of drug-resistant infections, both in the development of new agents, for example, less impacted by efflux or in targeting efflux directly with efflux inhibitors.

  13. Enhanced Particulate Organic Carbon Export at Eddy Edges in the Oligotrophic Western North Pacific Ocean

    PubMed Central

    Shih, Yung-Yen; Hung, Chin-Chang; Gong, Gwo-Ching; Chung, Wan-Chen; Wang, Yu-Huai; Lee, I-Huan; Chen, Kuo-Shu; Ho, Chuang-Yi

    2015-01-01

    Mesoscale eddies in the subtropical oligotrophic ocean are ubiquitous and play an important role in nutrient supply and oceanic primary production. However, it is still unclear whether these mesoscale eddies can efficiently transfer CO2 from the atmosphere to deep waters via biological pump because of the sampling difficulty due to their transient nature. In 2007, particulate organic carbon (POC) fluxes, measured below the euphotic zone at the edge of warm eddy were 136–194 mg-C m−2 d−1 which was greatly elevated over that (POC flux = 26–35 mg-C m−2 d−1) determined in the nutrient-depleted oligotrophic waters in the Western North Pacific (WNP). In 2010, higher POC fluxes (83–115 mg-C m−2 d−1) were also observed at the boundary of mesoscale eddies in the WNP. The enhanced POC flux at the edge of eddies was mainly attributed to both large denuded diatom frustules and zooplankton fecal pellets based on scanning electron microscopy (SEM) examination. The result suggests that mesoscale eddies in the oligotrophic waters in the subtropical WNP can efficiently increase the oceanic carbon export flux and the eddy edge is a crucial conduit in carbon sequestration to deep waters. PMID:26171611

  14. Increased Usage of Antiseptics Is Associated with Reduced Susceptibility in Clinical Isolates of Staphylococcus aureus.

    PubMed

    Hardy, Katherine; Sunnucks, Katie; Gil, Hannah; Shabir, Sahida; Trampari, Eleftheria; Hawkey, Peter; Webber, Mark

    2018-05-29

    Hospital-acquired infection is a major cause of morbidity and mortality, and regimes to prevent infection are crucial in infection control. These include the decolonization of vulnerable patients with methicillin-resistant Staphylococcus aureus (MRSA) carriage using antiseptics, including chlorhexidine and octenidine. Concern has been raised, however, regarding the possible development of biocide resistance. In this study, we assembled a panel of S. aureus isolates, including isolates collected before the development of chlorhexidine and octenidine and isolates, from a major hospital trust in the United Kingdom during a period when the decolonization regimes were altered. We observed significant increases in the MIC and minimum bactericidal concentration (MBC) of chlorhexidine in isolates from periods of high usage of chlorhexidine. Isolates with increased MICs and MBCs of octenidine rapidly emerged after octenidine was introduced in the trust. There was no apparent cross-resistance between the two biocidal agents. A combination of variable-number tandem repeat (VNTR) analysis, PCR for qac genes, and whole-genome sequencing was used to type isolates and examine possible mechanisms of resistance. There was no expansion of a single strain associated with decreased biocide tolerance, and biocide susceptibility did not correlate with carriage of qac efflux pump genes. Mutations within the NorA or NorB efflux pumps, previously associated with chlorhexidine export, were identified, however, suggesting that this may be an important mechanism of biocide tolerance. We present evidence that isolates are evolving in the face of biocide challenge in patients and that changes in decolonization regimes are reflected in changes in susceptibility of isolates. IMPORTANCE Infection in hospitals remains a major cause of death and disease. One way in which we combat this is by decolonizing at-risk patients from carriage of bacteria which can cause disease such as MRSA. This is done with antiseptics, including chlorhexidine and octenidine. There is concern, however, that bacteria may be able to become resistant to these antiseptics. In this study, we looked at isolates of MRSA and found that there was a correlation between the use of antiseptics and increased resistance in the isolates. We also suggest that the mechanism by which these more tolerant isolates may become resistant to antiseptics is that of changing a transport pump that exports these agents. This information suggests that we need to study the impact of antiseptics on clinically important bacteria more closely. Copyright © 2018 Hardy et al.

  15. The role of nutricline depth in regulating the ocean carbon cycle.

    PubMed

    Cermeño, Pedro; Dutkiewicz, Stephanie; Harris, Roger P; Follows, Mick; Schofield, Oscar; Falkowski, Paul G

    2008-12-23

    Carbon uptake by marine phytoplankton, and its export as organic matter to the ocean interior (i.e., the "biological pump"), lowers the partial pressure of carbon dioxide (pCO(2)) in the upper ocean and facilitates the diffusive drawdown of atmospheric CO(2). Conversely, precipitation of calcium carbonate by marine planktonic calcifiers such as coccolithophorids increases pCO(2) and promotes its outgassing (i.e., the "alkalinity pump"). Over the past approximately 100 million years, these two carbon fluxes have been modulated by the relative abundance of diatoms and coccolithophores, resulting in biological feedback on atmospheric CO(2) and Earth's climate; yet, the processes determining the relative distribution of these two phytoplankton taxa remain poorly understood. We analyzed phytoplankton community composition in the Atlantic Ocean and show that the distribution of diatoms and coccolithophorids is correlated with the nutricline depth, a proxy of nutrient supply to the upper mixed layer of the ocean. Using this analysis in conjunction with a coupled atmosphere-ocean intermediate complexity model, we predict a dramatic reduction in the nutrient supply to the euphotic layer in the coming century as a result of increased thermal stratification. Our findings indicate that, by altering phytoplankton community composition, this causal relationship may lead to a decreased efficiency of the biological pump in sequestering atmospheric CO(2), implying a positive feedback in the climate system. These results provide a mechanistic basis for understanding the connection between upper ocean dynamics, the calcium carbonate-to-organic C production ratio and atmospheric pCO(2) variations on time scales ranging from seasonal cycles to geological transitions.

  16. Evaluating Southern Ocean Carbon Eddy-Pump From Biogeochemical-Argo Floats

    NASA Astrophysics Data System (ADS)

    Llort, Joan; Langlais, C.; Matear, R.; Moreau, S.; Lenton, A.; Strutton, Peter G.

    2018-02-01

    The vertical transport of surface water and carbon into ocean's interior, known as subduction, is one of the main mechanisms through which the ocean influences Earth's climate. New instrumental approaches have shown the occurrence of localized and intermittent subduction episodes associated with small-scale ocean circulation features. These studies also revealed the importance of such events for the export of organic matter, the so-called eddy-pump. However, the transient and localized nature of episodic subduction hindered its large-scale evaluation to date. In this work, we present an approach to detect subduction events at the scale of the Southern Ocean using measurements collected by biogeochemical autonomous floats (BGCArgo). We show how subduction events can be automatically identified as anomalies of spiciness and Apparent Oxygen Utilization (AOU) below the mixed layer. Using this methodology over more than 4,000 profiles, we detected 40 subduction events unevenly distributed across the Sothern Ocean. Events were more likely found in hot spots of eddy kinetic energy (EKE), downstream major bathymetric features. Moreover, the bio-optical measurements provided by BGCArgo allowed measuring the amount of Particulate Organic Carbon (POC) being subducted and assessing the contribution of these events to the total downward carbon flux at 100 m (EP100). We estimated that the eddy-pump represents less than 19% to the EP100 in the Southern Ocean, although we observed particularly strong events able to locally duplicate the EP100. This approach provides a novel perspective on where episodic subduction occurs that will be naturally improved as BGCArgo observations continue to increase.

  17. Oceanic acidification affects marine carbon pump and triggers extended marine oxygen holes.

    PubMed

    Hofmann, Matthias; Schellnhuber, Hans-Joachim

    2009-03-03

    Rising atmospheric CO(2) levels will not only drive future global mean temperatures toward values unprecedented during the whole Quaternary but will also lead to massive acidification of sea water. This constitutes by itself an anthropogenic planetary-scale perturbation that could significantly modify oceanic biogeochemical fluxes and severely damage marine biota. As a step toward the quantification of such potential impacts, we present here a simulation-model-based assessment of the respective consequences of a business-as-usual fossil-fuel-burning scenario where a total of 4,075 Petagrams of carbon is released into the atmosphere during the current millennium. In our scenario, the atmospheric pCO(2) level peaks at approximately 1,750 microatm in the year 2200 while the sea-surface pH value drops by >0.7 units on global average, inhibiting the growth of marine calcifying organisms. The study focuses on quantifying 3 major concomitant effects. The first one is a significant (climate-stabilizing) negative feedback on rising pCO(2) levels as caused by the attenuation of biogenic calcification. The second one is related to the biological carbon pump. Because mineral ballast, notably CaCO(3), is found to play a dominant role in carrying organic matter through the water column, a reduction of its export fluxes weakens the strength of the biological carbon pump. There is, however, a third effect with severe consequences: Because organic matter is oxidized in shallow waters when mineral-ballast fluxes weaken, oxygen holes (hypoxic zones) start to expand considerably in the oceans in our model world--with potentially harmful impacts on a variety of marine ecosystems.

  18. Discovery of a Siderophore Export System Essential for Virulence of Mycobacterium tuberculosis

    PubMed Central

    Wells, Ryan M.; Jones, Christopher M.; Xi, Zhaoyong; Speer, Alexander; Danilchanka, Olga; Doornbos, Kathryn S.; Sun, Peibei; Wu, Fangming; Tian, Changlin; Niederweis, Michael

    2013-01-01

    Iron is an essential nutrient for most bacterial pathogens, but is restricted by the host immune system. Mycobacterium tuberculosis (Mtb) utilizes two classes of small molecules, mycobactins and carboxymycobactins, to capture iron from the human host. Here, we show that an Mtb mutant lacking the mmpS4 and mmpS5 genes did not grow under low iron conditions. A cytoplasmic iron reporter indicated that the double mutant experienced iron starvation even under high-iron conditions. Loss of mmpS4 and mmpS5 did not change uptake of carboxymycobactin by Mtb. Thin layer chromatography showed that the ΔmmpS4/S5 mutant was strongly impaired in biosynthesis and secretion of siderophores. Pull-down experiments with purified proteins demonstrated that MmpS4 binds to a periplasmic loop of the associated transporter protein MmpL4. This interaction was corroborated by genetic experiments. While MmpS5 interacted only with MmpL5, MmpS4 interacted with both MmpL4 and MmpL5. These results identified MmpS4/MmpL4 and MmpS5/MmpL5 as siderophore export systems in Mtb and revealed that the MmpL proteins transport small molecules other than lipids. MmpS4 and MmpS5 resemble periplasmic adapter proteins of tripartite efflux pumps of Gram-negative bacteria, however, they are not only required for export but also for efficient siderophore synthesis. Membrane association of MbtG suggests a link between siderophore synthesis and transport. The structure of the soluble domain of MmpS4 (residues 52–140) was solved by NMR and indicates that mycobacterial MmpS proteins constitute a novel class of transport accessory proteins. The bacterial burden of the mmpS4/S5 deletion mutant in mouse lungs was lower by 10,000-fold and none of the infected mice died within 180 days compared to wild-type Mtb. This is the strongest attenuation observed so far for Mtb mutants lacking genes involved in iron utilization. In conclusion, this study identified the first components of novel siderophore export systems which are essential for virulence of Mtb. PMID:23431276

  19. Multiple Calcium Export Exchangers and Pumps Are a Prominent Feature of Enamel Organ Cells

    PubMed Central

    Robertson, Sarah Y. T.; Wen, Xin; Yin, Kaifeng; Chen, Junjun; Smith, Charles E.; Paine, Michael L.

    2017-01-01

    Calcium export is a key function for the enamel organ during all stages of amelogenesis. Expression of a number of ATPase calcium transporting, plasma membrane genes (ATP2B1-4/PMCA1-4), solute carrier SLC8A genes (sodium/calcium exchanger or NCX1-3), and SLC24A gene family members (sodium/potassium/calcium exchanger or NCKX1-6) have been investigated in the developing enamel organ in earlier studies. This paper reviews the calcium export pathways that have been described and adds novel insights to the spatiotemporal expression patterns of PMCA1, PMCA4, and NCKX3 during amelogenesis. New data are presented to show the mRNA expression profiles for the four Atp2b1-4 gene family members (PMCA1-4) in secretory-stage and maturation-stage rat enamel organs. These data are compared to expression profiles for all Slc8a and Slc24a gene family members. PMCA1, PMCA4, and NCKX3 immunolocalization data is also presented. Gene expression profiles quantitated by real time PCR show that: (1) PMCA1, 3, and 4, and NCKX3 are most highly expressed during secretory-stage amelogenesis; (2) NCX1 and 3, and NCKX6 are expressed during secretory and maturation stages; (3) NCKX4 is most highly expressed during maturation-stage amelogenesis; and (4) expression levels of PMCA2, NCX2, NCKX1, NCKX2, and NCKX5 are negligible throughout amelogenesis. In the enamel organ PMCA1 localizes to the basolateral membrane of both secretory and maturation ameloblasts; PMCA4 expression is seen in the basolateral membrane of secretory and maturation ameloblasts, and also cells of the stratum intermedium and papillary layer; while NCKX3 expression is limited to Tomes' processes, and the apical membrane of maturation-stage ameloblasts. These new findings are discussed in the perspective of data already present in the literature, and highlight the multiplicity of calcium export systems in the enamel organ needed to regulate biomineralization. PMID:28588505

  20. Climate Change Response of Ocean Net Primary Production (NPP) and Export Production (EP) Regulated by Stratification Increases in The CMIP5 models

    NASA Astrophysics Data System (ADS)

    Fu, W.; Randerson, J. T.; Moore, J. K.

    2014-12-01

    Ocean warming due to rising atmospheric CO2 has increasing impacts on ocean ecosystems by modifying the ecophysiology and distribution of marine organisms, and by altering ocean circulation and stratification. We explore ocean NPP and EP changes at the global scale with simulations performed in the framework of the fifth Coupled Model Inter-comparison Project (CMIP5). Global NPP and EP are reduced considerably by the end of the century for the representative concentration pathway (RCP) 8.5 scenario, although models differ in their significantly in their direct temperature impacts on production and remineralization. The Earth system models used here project similar NPP trends albeit the magnitudes vary substantially. In general, projected changes in the 2090s for NPP range between -2.3 to -16.2% while export production reach -7 to -18% relative to 1990s. This is accompanied by increased stratification by 17-30%. Results indicate that globally reduced NPP is closely related to increased ocean stratification (R2=0.78). This is especially the case for global export production, that seems to be mostly controlled by the increased stratification (R2=0.95). We also identify phytoplankton community impacts on these patterns, that vary across the models. The negative response of NPP to climate change may be through bottom-up control, leading to a reduced capacity of oceans to regulate climate through the biological carbon pump. There are large disagreements among the CMIP5 models in terms of simulated nutrient and oxygen concentrations for the 1990s, and their trends over time with climate change. In addition, potentially important marine biogeochemical feedbacks on the climate system were not well represented in the CMIP5 models, including important feedbacks with aerosol deposition and the marine iron cycle, and feedbacks involving the oxygen minimum zones and the marine nitrogen cycle. Thus, these substantial reductions in primary productivity and export production over the 21st century simulated under the RCP 8.5 scenario were likely conservative estimates, and may need to be revised as marine biogeochemistry in Earth System Models (ESMs) continues to be developed.

  1. Late summer particulate organic carbon export and twilight zone remineralisation in the Atlantic sector of the Southern Ocean

    NASA Astrophysics Data System (ADS)

    Planchon, F.; Cavagna, A.-J.; Cardinal, D.; André, L.; Dehairs, F.

    2012-03-01

    During the Bonus-GoodHope (BGH) expedition (Jan-Mar 2008) we studied the water column distribution of total 234Th and biogenic particulate Ba (Baxs) in the Atlantic sector of the Southern Ocean. The objective was to assess the export flux of particulate organic carbon (POC) from the surface to the mesopelagic twilight zone along a section between the Cape Basin and Weddell Gyre. Export production of POC was estimated from steady state and non steady state export fluxes of 234Th which were converted into POC fluxes, using the POC/234Th ratio of large (>53 μm) suspended particles, collected via in-situ pumps. Deficits in 234Th activities were observed at all stations from the surface to the bottom of the mixed-layer. 234Th export fluxes from the upper 100 m ranged from 496 ± 57 dpm m-2 d-1 to 1195 ± 120 dpm m-2 d-1 for the steady state model and from 149 ± 18 dpm m-2 d-1 to 1217 ± 146 dpm m-2 d-1 for the non steady state model calculated for a time window of 15 to 22 days preceding the timing of the present cruise. The POC/234Thp ratio of large, potentially sinking particles (>53 μm), was observed to increase with latitude, from 1.9 ± 0.2 μmol dpm-1 and 1.7 ± 0.3 μmol dpm-1 in the Subtropical Zone (STZ) and Subantarctic Zone (SAZ), respectively, to 3.0 ± 0.2 μmol dpm-1 in the Polar Front Zone (PFZ), 4.8 ± 1.9 μmol dpm-1 at the Southern Antarctic Circumpolar Current Front (SACCF) to 4.1 ± 1.7 μmol dpm-1 in the northern Weddell Gyre, in line with an increasing contribution of larger cell diatoms. Steady state and non steady state POC export from the upper 100 m ranged from 0.9 ± 0.2 mmolC m-2 d-1 to 5.1 ± 2.1 mmolC m-2 d-1 and from 0.3 ± 0.0 mmolC m-2 d-1 to 4.9 ± 3.2 mmolC m-2 d-1, respectively. From the SAZ to the SACCF, non steady state POC export production represented only 15 to 54 % of the steady state POC flux, suggesting that the intensity of export had decreased over time partly due to the fact that regenerated-production based communities of small-sized phytoplankton became predominant. In contrast, for the HNLC area south of the SACCF, we found an excellent agreement between the two modeling approaches indicating that surface POC export remained rather constant there. Estimated POC export represented between 6 to 54 % of the potential export as represented by new production, indicating that export efficiency was particularly low throughout the studied area, except close to the SACCF. Below the export layer, in the mesopelagic zone, 234Th activities generally reached equilibrium with 238U, but sometimes were in large excess relative to 238U (234Th/238U ratio>1.1), reflecting intense remineralisation/disaggregation of 234Th-bearing particles. The accumulation of excess 234Th in the 100-600 m depth interval ranged from 458 ± 55 dpm m-2 d-1 to 3068 ± 368 dpm m-2 d-1. Using POC to 234Th ratio of sinking particles, we converted this 234Th flux into a POC remineralisation flux, which ranged between 0.9 to 9.2 mmolC m-2 d-1. Mesopelagic remineralisation was also evidenced by Baxs inventories which are related to bacterial degradation of sinking material and offer a means to quantify the flux of respired C. Highest biogenic particulate Ba (Baxs) contents were generally observed in the 200-400 m depth interval with values reaching up to >1000 pM in the northern PFZ. Depth weighted average mesopelagic Baxs (meso-Baxs) was high in the PFZ and low in the northernmost (STZ-SAZ) and the southernmost (SACCF-AZ-WG) parts of the BGH section; conversion into respired C flux yielded a range of -0.23 to 6.4 mmolC m-2 d-1. Excluding two outliers, we found a significant positive correlation for mesopelagic waters between POC remineralisation estimated from meso-Baxs and from 234Th excess (R2 = 0.73). Our results indicate that POC export production in this area of the Southern Ocean was strongly attenuated in the mesopelagic waters due to remineralisation, a process which thus appears to strongly impact on longer term bathypelagic zone sequestration of POC.

  2. 2,2'-Dihydroxychalcone, a glutathione transferase inhibitor, sensitises human colon adenocarcinoma cells to chlorambucil and melphalan, but not to actinomycin D.

    PubMed

    Goh, Kenneth; Chen, Yufan; Zheng, Lin; Ong, Laichun; Jin, Yi; Chow, Pierce; Zhang, Kai

    2008-01-01

    2,2'-Dihydroxychalcone (2,2'DHC) is a potent inhibitor of glutathione S-transferases (GSTs). Pre-treatment of human colon cancer cells by a non-toxic concentration of this GST inhibitor significantly sensitised cancer cells to chlorambucil and melphalan, which are substrates of glutathione (GSH) conjugation. However, sensitisation to actinomycin D, which has not been shown to be detoxified by GSH-related mechanisms, was not observed. These results further confirm the contribution of GSH-related mechanisms to drug resistance by increased detoxification of drugs. 2,2'DHC inhibited GST activity and the transport of GSH conjugates by cancer cells. Its combined effects on GST and glutathione conjugate export (GS-X) pump may provide more potent sensitisation of cancer cells to chemotherapeutic drugs.

  3. Carbon export in the naturally iron-fertilized Kerguelen area of the Southern Ocean based on the 234Th approach

    NASA Astrophysics Data System (ADS)

    Planchon, F.; Ballas, D.; Cavagna, A.-J.; Bowie, A. R.; Davies, D.; Trull, T.; Laurenceau, E.; Van Der Merwe, P.; Dehairs, F.

    2014-11-01

    The Kerguelen Plateau region in the Indian sector of the Southern Ocean supports annually a large-scale phytoplankton bloom which is naturally fertilized with iron. As part of the second KErguelen Ocean and Plateau compared Study expedition (KEOPS2) in austral spring (October-November 2011), we examined upper-ocean Particulate Organic Carbon (POC) export using the 234Th approach. We aimed at characterizing the spatial and the temporal variability of POC export production at high productivity sites over and downstream the Kerguelen plateau. Export production is compared to a High Nutrient Low Chlorophyll area upstream of the plateau in order to assess the impact of iron-induced productivity on the vertical export of carbon. Deficits in 234Th activities relative to its parent nuclide 238U were observed at all stations in surface waters, indicating that scavenging by particles occurred during the early stages of the phytoplankton bloom. 234Th export was lowest at reference station R-2 (412 ± 134 dpm m-2 d-1) and highest inside a~permanent meander of the Polar Front (PF) at stations E (1995 ± 176 dpm m-2 d-1, second visit E-3) where a detailed time series was obtained as part of a~pseudo-lagrangian study. 234Th export over the central plateau was relatively limited at station A3 early (776 ± 171 dpm m-2 d-1, first visit A3-1) and late in the survey (993 ± 223 dpm m-2 d-1, second visit A3-2), but it was higher at high biomass stations TNS-8 (1372 ± 255 dpm m-2 d-1) and E-4W (1068 ± 208 dpm m-2 d-1) in waters which could be considered as derived from plateau. Limited 234Th export of 973 ± 207 dpm m-2 d-1 was also found in the northern branch of the Kerguelen bloom located downstream of the island, north of the PF (station F-L). The 234Th results support that Fe fertilization increased particle export in all iron fertilized waters. The impact was greatest in the recirculation feature (3-4 fold at 200 m depth), but more moderate over the central Kerguelen plateau and in the northern plume of the Kerguelen bloom (∼2-fold at 200 m depth). The C : Th ratio of large (> 53 μm) potentially sinking particles collected via sequential filtration using in situ pumping (ISP) systems were used to convert the 234Th flux into a POC export flux. The C : Th ratios of sinking particles were highly variable (range: 3.1 ± 0.1-10.5 ± 0.2 μmol dpm-1) with no clear site related trend, despite the variety of ecosystem responses in the fertilized regions. C : Th ratios showed a decreasing trend between 100 and 200 m depth suggesting preferential loss of carbon relative to 234Th possibly due to heterotrophic degradation and/or grazing activity. Comparison of the C : Th ratios within sinking particles obtained with the drifting sediment traps showed in most cases very good agreement to those collected via ISP deployments (> 53 μm particles). Carbon export production varied between 3.5 ± 0.9 mmol m-2 d-1 and 11.8 ± 1.3 mmol m-2 d-1 from the upper 100 m and between 1.8 ± 0.9 mmol m-2 d-1 and 8.2 ± 0.9 mmol m-2 d-1 from the upper 200 m. Highest export production was found inside the PF meander with a range of 5.4 ± 0.7 mmol m-2 d-1 to 11.8 ± 1.1 mmol m-2 d-1 at 100 m depth decreasing to 5.3 ± 1.0 mmol m-2 d-1 to 8.2 ± 0.8 mmol m-2 d-1 at 200 m depth over the 19 day survey period. The impact of Fe fertilization is highest inside the PF meander with 2.9- up to 4.5-fold higher carbon flux at 200 m depth in comparison to the HNLC control station. The impact of Fe fertilization was significantly less over the central plateau (stations A3 and E-4W) and in the northern branch of the bloom (station F-L) with 1.6- up to 2.0-fold higher carbon flux compared to the reference station R. Export efficiencies (ratio of export to primary production) were particularly variable with relatively high values in the recirculation feature (6-27%) and low values (1-5%) over the central plateau (station A3) and north of the PF (station F-L) indicating spring biomass accumulation. Comparison with KEOPS1 results indicated that carbon export production is much lower during the onset of the bloom in austral spring in comparison to the peak and declining phase in late summer.

  4. Late summer particulate organic carbon export and twilight zone remineralisation in the Atlantic sector of the Southern Ocean

    NASA Astrophysics Data System (ADS)

    Planchon, F.; Cavagna, A.-J.; Cardinal, D.; André, L.; Dehairs, F.

    2013-02-01

    As part of the GEOTRACES Bonus-GoodHope (BGH) expedition (January-March 2008) in the Atlantic sector of the Southern Ocean, particulate organic carbon (POC) export was examined from the surface to the mesopelagic twilight zone using water column distributions of total 234Th and biogenic particulate Ba (Baxs). Surface POC export production was estimated from steady state and non steady state modelling of 234Th fluxes, which were converted into POC fluxes, using the POC/234Th ratio of large, potentially sinking particles (> 53 μm) collected via in situ pumps. Deficits in 234Th activities were observed at all stations from the surface to the bottom of the mixed layer, yielding 234Th export fluxes from the upper 100 m of 496 ± 214 dpm m-2 d-1 to 1195 ± 158 dpm m-2 d-1 for the steady state model and of 149 ±517 dpm m-2 d-1 to 1217 ± 231 dpm m-2 d-1 for the non steady state model. Using the POC/234Thp ratio of sinking particles (ratios varied from 1.7 ± 0.2 μmol dpm-1 to 4.8 ± 1.9 μmol dpm-1) POC export production at 100 m was calculated to range between 0.9 ± 0.4 and 5.1 ± 2.1 mmol C m-2 d-1,assuming steady state and between 0.3 ± 0.9 m-2 d-1 and 4.9 ± 3.3 mmol C m-2 d-1, assuming non steady state. From the comparison of both approaches, it appears that during late summer export decreased by 56 to 16% for the area between the sub-Antarctic zone and the southern Antarctic Circumpolar Current Front (SACCF), whereas it remained rather constant over time in the HNLC area south of the SACCF. POC export represented only 6 to 54% of new production, indicating that export efficiency was, in general, low, except in the vicinity of the SACCF, where export represented 56% of new production. Attenuation of the POC sinking flux in the upper mesopelagic waters (100-600 m depth interval) was evidenced both, from excess 234Th activities and from particulate biogenic Ba (Baxs) accumulation. Excess 234Th activities, reflected by 234Th/238U ratios as large as 1.21 ± 0.05, are attributed to remineralisation/disaggregation of 234Th-bearing particles. The accumulation of excess 234Th in the 100-600 m depth interval ranged from 458 ± 633 dpm m-2 d-1 to 3068 ± 897 dpm m-2 d-1, assuming steady state. Using the POC/234Thp ratio of sinking particles (> 53 μm), this 234Th accumulation flux was converted into a POC remineralisation flux which ranged between 0.9 ± 1.2 mmol C m-2 d-1 and 9.2 ± 2.9 mmol C m-2 d-1. Mesopelagic particulate biogenic Ba has been reported to reflect bacterial degradation of organic matter and to be related to oxygen consumption and bacterial carbon respiration. We observed that the highest Baxs contents (reaching up to > 1000 pM), in general, occurred between 200 and 400 m. Depth-weighted average mesopelagic Baxs (meso-Baxs) values were converted into respired C fluxes, which ranged between 0.23 and 6.4 mmol C m-2 d-1, in good agreement with 234Th-based remineralisation fluxes. A major outcome from this study is the observed significant positive correlation between POC remineralisation as estimated from meso-Baxs contents and from 234Th excess (R2 = 0.73; excluding 2 outliers). Remineralisation of POC in the twilight zone was particularly efficient relative to POC export resulting in negligible bathypelagic (> 600 m) POC export fluxes in the sub-Antarctic zone, the Polar Front zone and the northern Weddell Gyre, while the subtropical zone as well as the vicinity of the SACCF had significant deep POC fluxes.

  5. Ecological response to collapse of the biological pump following the mass extinction at the Cretaceous-Paleogene boundary

    NASA Astrophysics Data System (ADS)

    Vellekoop, Johan; Woelders, Lineke; Açikalin, Sanem; Smit, Jan; van de Schootbrugge, Bas; Yilmaz, Ismail Ö.; Brinkhuis, Henk; Speijer, Robert P.

    2017-02-01

    It is commonly accepted that the mass extinction associated with the Cretaceous-Paleogene (K-Pg) boundary (˜ 66 Ma) is related to the environmental effects of a large extraterrestrial impact. The biological and oceanographic consequences of the mass extinction are, however, still poorly understood. According to the Living Ocean model, the biological crisis at the K-Pg boundary resulted in a long-term reduction of export productivity in the early Paleocene. Here, we combine organic-walled dinoflagellate cyst (dinocyst) and benthic foraminiferal analyses to provide new insights into changes in the coupling of pelagic and benthic ecosystems. To this end, we perform dinocyst and benthic foraminiferal analyses on the recently discovered Tethyan K-Pg boundary section at Okçular, Turkey, and compare the results with other K-Pg boundary sites in the Tethys. The post-impact dominance of epibenthic morphotypes and an increase of inferred heterotrophic dinocysts in the early Paleocene at Okçular are consistent with published records from other western Tethyan sites. Together, these records indicate that during the early Paleocene more nutrients remained available for the Tethyan planktonic community, whereas benthic communities were deprived of food. Hence, in the post-impact phase the reduction of export productivity likely resulted in enhanced recycling of nutrients in the upper part of the water column, all along the western Tethyan margins.

  6. Tdp studies and tests for C. A. Energia Electrica de Venezuela (enelven) at planta ramon laguna, units RL-17 and RL-10. Volume 2. Unit RL-10 boiler condition assessment report. Export trade information

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1991-03-28

    The study, conducted by Babcock and Wilcox, was funded by the U.S. Trade and Development agency on behalf of Enelven. In order to maximize generated power output and minimize operating costs at Planta Ramon Laguna, tests were done to evaluate the condition of equipment at the plant. In order to identify any damage and determine the operating output of each unit, assessments were done of the furnaces, boilers, generators and boiler feed pumps being used in the plant. The report presents the results of these tests. This is the second of three volumes and it includes the following section: (1)more » Condition Assessment of Unit RL-10 Boiler.« less

  7. Earth observations taken from shuttle orbiter Columbia during STS-87 mission

    NASA Image and Video Library

    1997-11-23

    STS087-703-089 (19 November – 5 December 1997) --- Featured in this view is center pivot irrigation in central Saudi Arabia. Abundant petroleum has provided the energy source for deep-well pumps that tap groundwater stored in bedrock many thousands of years ago when the climate was much wetter. The fields are carved out of ancient alluvial fan deposits, also formed when rainfall was much greater; the fields are pushed right to the edge of the Nafud al Mazhur (sand sea), representative of the present climate. The mining of petroleum and groundwater has enabled Saudi Arabia to become an exporter of wheat and other commodities, in addition to the oil for which it is famous. This picture is one of the 70mm Earth observation visuals used by the crew at its post flight presentation events.

  8. A seasonal carbon budget for a naturally iron-fertilized bloom over the Kerguelen Plateau in the Southern Ocean

    NASA Astrophysics Data System (ADS)

    Jouandet, Marie Paule; Blain, Stephane; Metzl, Nicolas; Brunet, Christian; Trull, Thomas W.; Obernosterer, Ingrid

    2008-03-01

    During the Kerguelen Ocean and Plateau compared Study (KEOPS, January-February 2005), a high-resolution distribution of surface fugacity of carbon dioxide ( fCO 2) was obtained from underway measurements. The stations in the core of the naturally iron-fertilized bloom were characterized by low fCO 2 (311±8 μatm) compared to the atmosphere, thus representing a large CO 2 sink. This contrasted with stations typical of high-nutrient low-chlorophyll (HNLC) conditions where the surface water was roughly in equilibrium with the atmosphere ( fCO 2=372±5 μatm). The vertical distribution of dissolved inorganic carbon (DIC) also was obtained at stations within and outside the bloom. Based on this data set, we constructed a carbon budget for the mixed layer that allowed us to determine the seasonal net community production (NCP season) and the seasonal carbon export in two contrasting environments. The robustness of the approach and the errors also were estimated. The NCP season in the core of the bloom was 6.6±2.2 mol m -2, typical of productive areas of the Southern Ocean. At the HNLC station the NCP season was 3 times lower than in the bloom. Our estimate of the daily net community production (NCP daily) within the bloom compares well with shipboard measurements of NCP. The NCP daily obtained above the Kerguelen Plateau was of the same order as the estimates from Southern Ocean artificial iron-fertilization experiments (SOIREE and EisenEx). The seasonal carbon export was derived from NCP season after subtraction of the seasonal accumulation of particulate and dissolved organic carbon. In the bloom, the carbon export (5.4±1.9 mol m -2) was 3-fold higher than at the HNLC station (1.7±0.4 mol m -2). Comparison of our results to artificial iron-fertilization experiments shows that the biological pump is enhanced by natural iron fertilization.

  9. Surface ocean carbon isotope anomalies on glacial terminations: An alternative view

    NASA Astrophysics Data System (ADS)

    Lund, D. C.; Cote, M.; Schmittner, A.

    2016-12-01

    Late Pleistocene glacial terminations are characterized by surface ocean carbon isotope minima on a global scale. During the last deglaciation (i.e. Termination 1), planktonic foraminiferal δ13C anomalies occurred in the Atlantic, Indian, Pacific, and Southern Oceans. Despite the apparently ubiquitous nature of δ13C anomalies on glacial terminations, their cause remains a matter of ongoing debate. The prevailing view is that isotopically light carbon from the abyss was upwelled in the Southern Ocean, resulting in outgassing of 13C-depleted carbon to the atmosphere and its advection to lower latitudes via mode and intermediate waters (Spero and Lea, 2002). Alternatively, carbon isotope minima may be driven by weakening of the biological pump related to circulation-driven changes in the oceanic preformed nutrient budget (Schmittner and Lund, 2015). Here we assess the deep upwelling and biological pump hypotheses using a new compilation of 70 globally-distributed planktonic δ13C records from the published literature. We find that 1) the mean deglacial δ13C anomaly is similar in all ocean basins, 2) the eastern tropical Pacific yields smaller mean δ13C anomalies than the western tropical Pacific, and 3) δ13C anomalies in the Southern Ocean decrease with increasing latitude. Our results are generally inconsistent with the deep upwelling hypothesis, which predicts that the δ13C signal should be largest in the Southern Ocean and upwelling regions. Instead, the spatial pattern in δ13C anomalies supports the biological pump hypothesis, which predicts that reduced export of light carbon from the euphotic zone triggers negative carbon isotope anomalies in the surface ocean and positive anomalies at intermediate depths. Upwelling of relatively 13C-enriched intermediate waters tends to moderate carbon isotope minima in upwelling regions. Our results suggest that the initial rise in atmospheric CO2 during Termination 1 was likely due to weakening of the biological pump associated with a reduction in the Atlantic Meridional Overturning Circulation, consistent with model results (Schmittner and Lund, 2015). Spero, H., and D. Lea (2002) Science 296, 522-525. Schmittner, A., and D. Lund (2015) Climate of the Past 11, 135-152.

  10. PEP3 overexpression shortens lag phase but does not alter growth rate in Saccharomyces cerevisiae exposed to acetic acid stress

    PubMed Central

    Ding, Jun; Holzwarth, Garrett; Bradford, C. Samuel; Cooley, Ben; Yoshinaga, Allen S.; Patton-Vogt, Jana; Abeliovich, Hagai; Penner, Michael H.; Bakalinsky, Alan T.

    2017-01-01

    In fungi, two recognized mechanisms contribute to pH homeostasis: the plasma membrane proton-pumping ATPase that exports excess protons and the vacuolar proton-pumping ATPase (V-ATPase) that mediates vacuolar proton uptake. Here, we report that overexpression of PEP3 which encodes a component of the HOPS and CORVET complexes involved in vacuolar biogenesis, shortened lag phase in Saccharomyces cerevisiae exposed to acetic acid stress. By confocal microscopy, PEP3-overexpressing cells stained with the vacuolar membrane-specific dye, FM4-64 had more fragmented vacuoles than the wild-type control. The stained overexpression mutant was also found to exhibit about 3.6-fold more FM4-64 fluorescence than the wild-type control as determined by flow cytometry. While the vacuolar pH of the wild-type strain grown in the presence of 80 mM acetic acid was significantly higher than in the absence of added acid, no significant difference was observed in vacuolar pH of the overexpression strain grown either in the presence or absence of 80 mM acetic acid. Based on an indirect growth assay, the PEP3-overexpression strain exhibited higher V-ATPase activity. We hypothesize that PEP3 overexpression provides protection from acid stress by increasing vacuolar surface area and V-ATPase activity and, hence, proton-sequestering capacity. PMID:26051671

  11. Functioning of the Ocean Biological Pump in the Oxygen Minimum Zones

    NASA Astrophysics Data System (ADS)

    Moore, J. K.

    2015-12-01

    Oxygen minimum zones occur at mid-depths in the water column in regions with weak ventilation and relatively high export of organic matter from surface waters. They are important ocean for ocean biogeochemistry, and potentially for climate, as sites of water column denitrification and nitrous oxide production. Denitrification is the dominant loss process for fixed nitrogen in the oceans, and can thus affect the ocean inventory of this key nutrient. Denitrification is less energetically efficient than oxic remineralization. Larger zooplankton, which feed on sinking particles, are not present in the lowest oxygen waters. Both of these factors suggest that the remineralization of sinking particles may be slower within the OMZs than in more oxygenated waters. There is limited field evidence and from some modeling studies that remineralization is slower (remineralization length scales are longer) within OMZ waters. In this talk, I will present results from the Community Earth System Model (CESM) ocean component attempting to test this hypothesis. Comparing model results with observed ocean biogeochemical tracer distributions (i.e., phosphate, oxygen), I will examine whether slower remineralization within low oxygen waters provides a better match between simulated and observed tracer distributions. Longer remineralization length scales under low oxygen conditions would provide a negative feedback under global warming scenarios. The biological pump would transfer organic materials to depth more efficiently as ocean oxygen concentrations decline and the OMZs expand.

  12. 7 CFR 1493.80 - Evidence of export.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.80 Evidence of export. (a) Report of export. The exporter is required to provide CCC an evidence of export...

  13. 7 CFR 1493.80 - Evidence of export.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.80 Evidence of export. (a) Report of export. The exporter is required to provide CCC an evidence of export...

  14. 7 CFR 1493.80 - Evidence of export.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.80 Evidence of export. (a) Report of export. The exporter is required to provide CCC an evidence of export...

  15. 75 FR 29514 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-26

    ... Operation described below in the following Export Trade and Export Markets: Export Trade Export Product ALCC... being headed and gutted. Export Markets The Export Markets include all parts of the world except the... engage in Export Trade in the Export Markets, ALCC and its Members may undertake the following activities...

  16. Evaluation of the hydrologic system and selected water-management alternatives in the Owens Valley, California

    USGS Publications Warehouse

    Danskin, Wesley R.

    1998-01-01

    The Owens Valley, a long, narrow valley along the east side of the Sierra Nevada in eastcentral California, is the main source of water for the city of Los Angeles. The city diverts most of the surface water in the valley into the Owens River?Los Angeles Aqueduct system, which transports the water more than 200 miles south to areas of distribution and use. Additionally, ground water is pumped or flows from wells to supplement the surface-water diversions to the river? aqueduct system. Pumpage from wells needed to supplement water export has increased since 1970, when a second aqueduct was put into service, and local residents have expressed concerns that the increased pumping may have a detrimental effect on the environment and the native vegetation (indigenous alkaline scrub and meadow plant communities) in the valley. Native vegetation on the valley floor depends on soil moisture derived from precipitation and from the unconfined part of a multilayered ground-water system. This report, which describes the evaluation of the hydrologic system and selected water-management alternatives, is one in a series designed to identify the effects that ground-water pumping has on native vegetation and evaluate alternative strategies to mitigate any adverse effects caused by pumping. The hydrologic system of the Owens Valley can be conceptualized as having three parts: (1) an unsaturated zone affected by precipitation and evapotranspiration; (2) a surface-water system composed of the Owens River, the Los Angeles Aqueduct, tributary streams, canals, ditches, and ponds; and (3) a saturated ground-water system contained in the valley fill. Analysis of the hydrologic system was aided by development of a ground-water flow model of the ?aquifer system,? which is defined as the most active part of the ground-water system and which includes nearly all of the Owens Valley except for the area surrounding the Owens Lake. The model was calibrated and verified for water years 1963?88 and used to evaluate general concepts of the hydrologic system and the effects of past water-management practices. The model also was used to evaluate the likely effects of selected water-management alternatives designed to lessen the adverse effects of ground-water pumping on native vegetation. Results of the model simulations confirm that a major change in the hydrologic system was caused by the additional export of water from the valley beginning in 1970. Average ground-water pumpage increased by a factor of five, discharge from springs decreased almost to zero, reaches of the Owens River that previously had gained water from the aquifer system began losing water, and total evapotranspiration by native plants decreased by about 35 percent. Water-management practices as of 1988 were defined and evaluted using the model. Simulation results indicate that increased ground-water pumpage since 1985 for enhancement and mitigation projects within the Owens Valley has further stressed the aquifer system and resulted in declines of the water table and reduced evapotranspiration. Most of the water-table declines are beneath the western alluvial fans and in the immediate vicinity of production wells. The water-table altitude beneath the valley floor has remained relatively constant over time because of hydrologic buffers, such as evapotranspiration, springs, and permanent surface-water features. These buffers adjust the quantity of water exchanged with the aquifer system and effectively minimize variations in water-table altitude. The widespread presence of hydrologic buffers is the primary reason the water-table altitude beneath the valley floor has remained relatively constant since 1970 despite major changes in the type and location of ground-water discharge. Evaluation of selected water-management alternatives indicates that long-term variations in average runoff to the Owens Valley of as much as

  17. Tdp studies and tests for C. A. Energia Electrica de Venezuela (enelven) at planta ramon laguna, units RL-17 and RL-10. Volume 1. Executive summary, RL-17 test report, and gas conversion proposals. Export trade information

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1991-03-28

    The study, conducted by Babcock and Wilcox, was funded by the U.S. Trade and Development agency on behalf of Enelven. In order to maximize generated power output and minimize operating costs at Planta Ramon Laguna, tests were done to evaluate the condition of equipment at the plant. In order to identify any damage and determine the operating output of each unit, assessments were done of the furnaces, boilers, generators and boiler feed pumps being used in the plant. The report presents the results of these tests. This is the first of three volumes and it is divided into the followingmore » sections: (1) Executive Summary; (2) Hydrogen Damage Assessment; (3) RL-17 Gas Conversion Proposal; (4) RL-10 and RL-11 Gas Conversion Proposals.« less

  18. Molecular mechanisms of gravity-dependent signaling in human melanocytic cells involve cyclic GMP

    NASA Astrophysics Data System (ADS)

    Ivanova, Krassimira; Lambers, Britta; Block, Ingrid; Bromeis, Birgit; Das, Pranab K.; Gerzer, Rupert

    2005-08-01

    Gravity alteration (micro- and hypergravity) is known to influence cell functions. As guanosine 3',5'-cyclic monophosphate (cGMP) is an important messenger in melanocyte signaling we have compared the regulation of cGMP levels in human melanocytes and melanoma cells with different metastatic potential under hypergravity conditions. We were able to demonstrate that long-term exposure to hypergravity stimulates cGMP efflux in cultured human melanocytes and non- metastatic melanoma cells, whereas highly metastatic melanoma cells appear to be insensitive to hypergravity, most probably, due to an up-regulated cGMP efflux at 1g. Here we report that these effects are associated with the expression of the multidrug resistance proteins 4 and 5 known to act as selective export pumps for amphiphilic anions like cGMP. Thus, an altered gravity vector may induce cGMP-dependent signaling events in melanocytic cells that could be important for malignant transformation.

  19. Millennial-scale plankton regime shifts in the subtropical North Pacific Ocean.

    PubMed

    McMahon, Kelton W; McCarthy, Matthew D; Sherwood, Owen A; Larsen, Thomas; Guilderson, Thomas P

    2015-12-18

    Climate change is predicted to alter marine phytoplankton communities and affect productivity, biogeochemistry, and the efficacy of the biological pump. We reconstructed high-resolution records of changing plankton community composition in the North Pacific Ocean over the past millennium. Amino acid-specific δ(13)C records preserved in long-lived deep-sea corals revealed three major plankton regimes corresponding to Northern Hemisphere climate periods. Non-dinitrogen-fixing cyanobacteria dominated during the Medieval Climate Anomaly (950-1250 Common Era) before giving way to a new regime in which eukaryotic microalgae contributed nearly half of all export production during the Little Ice Age (~1400-1850 Common Era). The third regime, unprecedented in the past millennium, began in the industrial era and is characterized by increasing production by dinitrogen-fixing cyanobacteria. This picoplankton community shift may provide a negative feedback to rising atmospheric carbon dioxide concentrations. Copyright © 2015, American Association for the Advancement of Science.

  20. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smirnova, Anna S.; Morgun, Andrey; Shulzhenko, Natalia

    Two transcript variants (TV) of the T cell immune regulator gene 1 (TCIRG1) have already been characterized. TV1 encodes a subunit of the osteoclast vacuolar proton pump and TV2 encodes a T cell inhibitory receptor. Based on the search in dbEST, we validated by RT-PCR six new alternative splice events in TCIRG1 in most of the 28 human tissues studied. In addition, we observed that transcripts using the TV1 transcription start site and two splice forms previously described in a patient with infantile malignant osteopetrosis are also expressed in various tissues of healthy individuals. Studies of these nine splice formsmore » in cytoplasmic RNA of peripheral blood mononuclear cells showed that at least six of them could be efficiently exported from the nucleus. Since various products with nearly ubiquitous tissue distribution are generated from TCIRG1, this gene may be involved in other processes besides immune response and bone resorption.« less

  1. Druzhba feasibility study: Barsukov and Tarasov fields, 1995. Barsukov and Tarasov production histories western equipment. Export trade information

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1996-01-03

    The study, conducted by NEFT, was funded by the U.S. Trade and Development Agency. The report shows the results of a feasibility study conducted for the rehabilitation of oil wells in Baruskov and Tarasov fields. The objectives of the study include a plan for improving well and waterflood performance, and to determine materials and equipment needed. The report also covers capital and operating costs, as well as an evaluation of project economics based on Russian law. This is Volume 2 of the study containing Production Histories-Western Equipment. It is divided into the following sections: (1) Job Descriptions; (2) Barsukov Histories/Logs;more » (3) Tarasov Histories/Logs; (4) Taxes Paid by PNG; (5) Vendors Literature; (6) Rigs; (7) Liners; (8) Directional Drilling; (9) Mechanical Perforating; (10) Camps; (11) Pumps; (12) Fishing; (13) Downhole Oil/Water Separator; (14) Plastic.« less

  2. Direct comparison of 210Po, 234Th and POC particle-size distributions and export fluxes at the Bermuda Atlantic Time-series Study (BATS) site.

    PubMed

    Stewart, Gillian; Moran, S Bradley; Lomas, Michael W; Kelly, Roger P

    2011-05-01

    Particle-reactive, naturally occurring radionuclides are useful tracers of the sinking flux of organic matter from the surface to the deep ocean. Since the Joint Global Ocean Flux Study (JGOFS) began in 1987, the disequilibrium between (234)Th and its parent (238)U has become widely used as a technique to measure particle export fluxes from surface ocean waters. Another radionuclide pair, (210)Po and (210)Pb, can be used for the same purpose but has not been as widely adopted due to difficulty with accurately constraining the (210)Po/(210)Pb radiochemical balance in the ocean and because of the more time-consuming radiochemical procedures. Direct comparison of particle flux estimated in different ocean regions using these short-lived radionuclides is important in evaluating their utility and accuracy as tracers of particle flux. In this paper, we present paired (234)Th/(238)U and (210)Po/(210)Pb data from oligotrophic surface waters of the subtropical Northwest Atlantic and discuss their advantages and limitations. Vertical profiles of total and particle size-fractionated (210)Po and (234)Th activities, together with particulate organic carbon (POC) concentrations, were measured during three seasons at the Bermuda Atlantic Time-series Study (BATS) site. Both (210)Po and (234)Th reasonably predict sinking POC flux caught in sediment traps, and each tracer provides unique information about the magnitude and efficiency of the ocean's biological pump. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. 7 CFR 1493.470 - Evidence of export.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... provide CCC an evidence of export report for each shipment made under the payment guarantee. This report... participation in any of the following CCC or USDA export program: Export Enhancement Program, Dairy Export...

  4. 7 CFR 1493.470 - Evidence of export.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... provide CCC an evidence of export report for each shipment made under the payment guarantee. This report... participation in any of the following CCC or USDA export program: Export Enhancement Program, Dairy Export...

  5. 7 CFR 1493.470 - Evidence of export.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee... provide CCC an evidence of export report for each shipment made under the payment guarantee. This report... participation in any of the following CCC or USDA export program: Export Enhancement Program, Dairy Export...

  6. 7 CFR 1493.470 - Evidence of export.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC... exporter is required to provide CCC an evidence of export report for each shipment made under the payment... participation in any of the following CCC or USDA export program: Export Enhancement Program, Dairy Export...

  7. 7 CFR 1493.80 - Evidence of export.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.80 Evidence of export. (a) Report of export. The exporter is required to provide CCC an...

  8. CO2 exchange in a temperate marginal sea of the Mediterranean Sea: processes and carbon budget

    NASA Astrophysics Data System (ADS)

    Cossarini, G.; Querin, S.; Solidoro, C.

    2012-08-01

    Marginal seas play a potentially important role in the global carbon cycle; however, due to differences in the scales of variability and dynamics, marginal seas are seldom fully accounted for in global models or estimates. Specific high-resolution studies may elucidate the role of marginal seas and assist in the compilation of a complete global budget. In this study, we investigated the air-sea exchange and the carbon cycle dynamics in a marginal sub-basin of the Mediterranean Sea (the Adriatic Sea) by adopting a coupled transport-biogeochemical model of intermediate complexity including carbonate dynamics. The Adriatic Sea is a highly productive area owed to riverine fertilisation and is a site of intense dense water formation both on the northern continental shelf and in the southern sub-basin. Therefore, the study area may be an important site of CO2 sequestration in the Mediterranean Sea. The results of the model simulation show that the Adriatic Sea, as a whole, is a CO2 sink with a mean annual flux of 36 mg m-2 day-1. The northern part absorbs more carbon (68 mg m-2 day-1) due to an efficient continental shelf pump process, whereas the southern part behaves similar to an open ocean. Nonetheless, the Southern Adriatic Sea accumulates dense, southward-flowing, carbon-rich water produced on the northern shelf. During a warm year and despite an increase in aquatic primary productivity, the sequestration of atmospheric CO2 is reduced by approximately 15% due to alterations of the solubility pump and reduced dense water formation. The seasonal cycle of temperature and biological productivity modulates the efficiency of the carbon pump at the surface, whereas the intensity of winter cooling in the northern sub-basin leads to the export of C-rich dense water to the deep layer of the southern sub-basin and, subsequently, to the interior of the Mediterranean Sea.

  9. Synergetic use of Sentinel-1 and 2 to improve agro-hydrological modeling. Results of groundwater pumping estimates in south-India and nitrogen excess in south-west of France

    NASA Astrophysics Data System (ADS)

    Ferrant, S.; Le Page, M.; Kerr, Y. H.; Selles, A.; Mermoz, S.; Al-Bitar, A.; Muddu, S.; Gascoin, S.; Marechal, J. C.; Durand, P.; Salmon-Monviola, J.; Ceschia, E.; Bustillo, V.

    2016-12-01

    Nitrogen transfers at agricultural catchment level are intricately linked to water transfers. Agro-hydrological modeling approaches aim at integrating spatial heterogeneity of catchment physical properties together with agricultural practices to spatially estimate the water and nitrogen cycles. As in hydrology, the calibration schemes are designed to optimize the performance of the temporal dynamics and biases in model simulations, while ignoring the simulated spatial pattern. Yet, crop uses, i.e. transpiration and nitrogen exported by harvest, are the main fluxes at the catchment scale, highly variable in space and time. Geo-information time-series of vegetation and water index with multi-spectral optical detection S2 together with surface roughness time series with C-band radar detection S1 are used to reset soil water holding capacity parameters (depth, porosity) and agricultural practices (sowing date, irrigated area extent) of a crop model coupled with a hydrological model. This study takes two agro-hydrological contexts as demonstrators: 1-spatial nitrogen excess estimation in south-west of France, and 2-groundwater extraction for rice irrigation in south-India. Spatio-temporal patterns are involved in respectively surface water contamination due to over-fertilization and local groundwater shortages due to over-pumping for above rice inundation. Optimized Leaf Area Index profiles are simulated at the satellite images pixel level using an agro-hydrological model to reproduce spatial and temporal crop growth dynamics in south-west of France, improving the in-stream nitrogen fluxes by 12%. Accurate detection of irrigated area extents are obtained with the thresholding method based on optical indices, with a kappa of 0.81 for the dry season 2016. The actual monsoon season is monitored and will be presented. These extents drive the groundwater pumping and are highly variable in time (from 2 to 8% of the total area).

  10. 22 CFR 123.22 - Filing, retention, and return of export licenses and filing of export information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Filing, retention, and return of export licenses and filing of export information. 123.22 Section 123.22 Foreign Relations DEPARTMENT OF STATE....22 Filing, retention, and return of export licenses and filing of export information. (a) Any export...

  11. U.S. hardwood product exports, hardwood exports to Korea, hardwood resource situation, and the future of U.S. exports to Korea

    Treesearch

    Philip A. Araman

    1991-01-01

    The exerpts from this seminar are intended to give an overview of U.S. hardwood exports, hardwood exports to Korea, the hardwood resource situation, and the future of U.S. hardwood exports to Korea. It includes 1) some basic information about total U.S. hardwood exports and products, 2) information on hardwood exports to Korea from the U.S., 3) U.S. hardwood resources...

  12. Quantification of the relative contribution of the different right ventricular wall motion components to right ventricular ejection fraction: the ReVISION method.

    PubMed

    Lakatos, Bálint; Tősér, Zoltán; Tokodi, Márton; Doronina, Alexandra; Kosztin, Annamária; Muraru, Denisa; Badano, Luigi P; Kovács, Attila; Merkely, Béla

    2017-03-27

    Three major mechanisms contribute to right ventricular (RV) pump function: (i) shortening of the longitudinal axis with traction of the tricuspid annulus towards the apex; (ii) inward movement of the RV free wall; (iii) bulging of the interventricular septum into the RV and stretching the free wall over the septum. The relative contribution of the aforementioned mechanisms to RV pump function may change in different pathological conditions.Our aim was to develop a custom method to separately assess the extent of longitudinal, radial and anteroposterior displacement of the RV walls and to quantify their relative contribution to global RV ejection fraction using 3D data sets obtained by echocardiography.Accordingly, we decomposed the movement of the exported RV beutel wall in a vertex based manner. The volumes of the beutels accounting for the RV wall motion in only one direction (either longitudinal, radial, or anteroposterior) were calculated at each time frame using the signed tetrahedron method. Then, the relative contribution of the RV wall motion along the three different directions to global RV ejection fraction was calculated either as the ratio of the given direction's ejection fraction to global ejection fraction and as the frame-by-frame RV volume change (∆V/∆t) along the three motion directions.The ReVISION (Right VentrIcular Separate wall motIon quantificatiON) method may contribute to a better understanding of the pathophysiology of RV mechanical adaptations to different loading conditions and diseases.

  13. Effects of L-arabinose efflux on λ Red recombination-mediated gene knockout in multiple-antimicrobial-resistant Salmonella enterica serovar Choleraesuis.

    PubMed

    Liao, Shi-Wei; Lee, Jen-Jie; Ptak, Christopher P; Wu, Ying-Chen; Hsuan, Shih-Ling; Kuo, Chih-Jung; Chen, Ter-Hsin

    2018-03-01

    In this study, six swine-derived multiple-antimicrobial-resistant (MAR) strains of Salmonella Choleraesuis (S. Choleraesuis) were demonstrated to possess higher efflux pump activity than the wild-type (WT). L-Arabinose, a common inducer for gene expression, modulated S. Choleraesuis efflux pump activity in a dose-dependent manner. At low L-arabinose concentrations, increasing L-arabinose led to a corresponding increase in fluorophore efflux, while at higher L-arabinose concentrations, increasing L-arabinose decreased fluorophore efflux activity. The WT S. Choleraesuis that lacks TolC (ΔtolC), an efflux protein associated with bacterial antibiotic resistance and virulence, was demonstrated to possess a significantly reduced ability to extrude L-arabinose. Further, due to the rapid export of L-arabinose, an efficient method for recombination-mediated gene knockout, the L-arabinose-inducible bacteriophage λ Red recombinase system, has a reduced recombination frequency (~ 12.5%) in clinically isolated MAR Salmonella strains. An increased recombination frequency (up to 60%) can be achieved using a higher concentration of L-arabinose (fivefold) for genetic manipulation and functional analysis for MAR Salmonella using the λ Red system. The study suggests that L-arabinose serves not only as an inducer of the TolC-dependent efflux system but also acts as a competitive substrate of the efflux system. In addition, understanding the TolC-dependent efflux of L-arabinose should facilitate the optimization of L-arabinose induction in strains with high efflux activity.

  14. The role of North Atlantic Ocean circulation and biological sequestration on atmospheric CO2 uptake during the last deglaciation (CL Division Outstanding ECS Award Lecture)

    NASA Astrophysics Data System (ADS)

    Muschitiello, Francesco; D'Andrea, William J.; Dokken, Trond M.; Schmittner, Andreas

    2017-04-01

    Understanding the impact of ocean circulation on the global atmospheric CO2 budget is of paramount importance for anticipating the consequences of projected future changes in Atlantic Meridional Overturning Circulation (AMOC). In particular, the efficiency of the oceanic biological pump can impact atmospheric CO2 through changes in vertical carbon export mediated by variations in the nutrient inventory of the North Atlantic basin. However, the causal relationship between North Atlantic Ocean circulation, biological carbon sequestration, and atmospheric CO2 is poorly understood. Here we present new high-resolution planktic-benthic 14C data and biomarker records from an exceptionally well-dated marine core from the Nordic Seas spanning the last deglaciation ( 15,000-10,000 years BP). The records document for the first time large and rapid atmospheric CO2 drawdowns and increase in plankton stocks during major North Atlantic cooling events. Using transient climate simulations from a fully coupled climate-biosphere model, we show that minor perturbations of the North Atlantic biological pump resulting from surface freshening and AMOC weakening can have a major impact on the global atmospheric CO2 budget. Furthermore, our data help clarifying the timing and magnitude of the deglacial CO2 signal recorded in Antarctic ice cores. We conclude that the global CO2 budget is more sensitive to perturbations in North Atlantic circulation than previously thought, which has significance in the future debate of the AMOC response to anthropogenic warming.

  15. Expression of multidrug resistance efflux pump gene norA is iron responsive in Staphylococcus aureus.

    PubMed

    Deng, Xin; Sun, Fei; Ji, Quanjiang; Liang, Haihua; Missiakas, Dominique; Lan, Lefu; He, Chuan

    2012-04-01

    Staphylococcus aureus utilizes efflux transporter NorA to pump out a wide range of structurally dissimilar drugs, conferring low-level multidrug resistance. The regulation of norA expression has yet to be fully understood although past studies have revealed that this gene is under the control of the global transcriptional regulator MgrA and the two-component system ArlRS. To identify additional regulators of norA, we screened a transposon library in strain Newman expressing the transcriptional fusion norA-lacZ for altered β-galactosidase activity. We identify a transposon insertion in fhuB, a gene that encodes a ferric hydroxamate uptake system permease, and propose that the norA transcription is iron responsive. In agreement with this observation, addition of FeCl(3) repressed the induction of norA-lacZ, suggesting that bacterial iron uptake plays an important role in regulating norA transcription. In addition, a fur (ferric uptake regulator) deletion exhibited compromised norA transcription and reduced resistance to quinolone compared to the wild-type strain, indicating that fur functions as a positive regulator of norA. A putative Fur box identified in the promoter region of norA was confirmed by electrophoretic mobility shift and DNase I footprint assays. Finally, by employing a siderophore secretion assay, we reveal that NorA may contribute to the export of siderophores. Collectively, our experiments uncover some novel interactions between cellular iron level and norA regulation in S. aureus.

  16. Expression of Multidrug Resistance Efflux Pump Gene norA Is Iron Responsive in Staphylococcus aureus

    PubMed Central

    Deng, Xin; Sun, Fei; Ji, Quanjiang; Liang, Haihua; Missiakas, Dominique; Lan, Lefu

    2012-01-01

    Staphylococcus aureus utilizes efflux transporter NorA to pump out a wide range of structurally dissimilar drugs, conferring low-level multidrug resistance. The regulation of norA expression has yet to be fully understood although past studies have revealed that this gene is under the control of the global transcriptional regulator MgrA and the two-component system ArlRS. To identify additional regulators of norA, we screened a transposon library in strain Newman expressing the transcriptional fusion norA-lacZ for altered β-galactosidase activity. We identify a transposon insertion in fhuB, a gene that encodes a ferric hydroxamate uptake system permease, and propose that the norA transcription is iron responsive. In agreement with this observation, addition of FeCl3 repressed the induction of norA-lacZ, suggesting that bacterial iron uptake plays an important role in regulating norA transcription. In addition, a fur (ferric uptake regulator) deletion exhibited compromised norA transcription and reduced resistance to quinolone compared to the wild-type strain, indicating that fur functions as a positive regulator of norA. A putative Fur box identified in the promoter region of norA was confirmed by electrophoretic mobility shift and DNase I footprint assays. Finally, by employing a siderophore secretion assay, we reveal that NorA may contribute to the export of siderophores. Collectively, our experiments uncover some novel interactions between cellular iron level and norA regulation in S. aureus. PMID:22267518

  17. Effects of Phytoplankton Growth Phase on Delayed Settling Behavior of Marine Snow Aggregates at Sharp Density Transitions

    NASA Astrophysics Data System (ADS)

    Proctor, K. W.; Montgomery, Q. W.; Prairie, J. C.

    2016-02-01

    Marine snow aggregates play a fundamental role in the marine carbon cycle. Since marine snow aggregates are larger and thus sink faster than individual phytoplankton, aggregates often dominate carbon flux. Previous studies have shown that marine snow aggregates will significantly decrease their settling velocity when passing through sharp density transitions within the ocean, a phenomenon defined as delayed settling. Given the importance of aggregate settling to carbon export, these small-scale changes in aggregate settling dynamics may have significant impacts on the efficiency of the biological pump. However, there is still a lack of knowledge about how different physical properties of aggregates can affect this delayed settling. In this study, we investigated the effect of phytoplankton growth phase on delayed settling behavior. Using phytoplankton cultures stopped at four different growth phases, we formed marine snow aggregates in the laboratory in rotating cylindrical tanks. We then observed individual aggregates as they settled through a stratified tank. We will present data which illustrates that aggregates experience greatly reduced settling rates when passing through sharp density gradients and that the growth phase of the phytoplankton used to form these aggregates has a significant effect on this delayed settling behavior. A thorough understanding of the impact of phytoplankton growth phase on the delayed settling behavior of marine snow will offer insight into the way phytoplankton growth phase may influence the efficiency of the biological pump, carbon flux, and the carbon cycle as a whole.

  18. Ancient Systems of Sodium/Potassium Homeostasis as Predecessors of Membrane Bioenergetics.

    PubMed

    Dibrova, D V; Galperin, M Y; Koonin, E V; Mulkidjanian, A Y

    2015-05-01

    Cell cytoplasm of archaea, bacteria, and eukaryotes contains substantially more potassium than sodium, and potassium cations are specifically required for many key cellular processes, including protein synthesis. This distinct ionic composition and requirements have been attributed to the emergence of the first cells in potassium-rich habitats. Different, albeit complementary, scenarios have been proposed for the primordial potassium-rich environments based on experimental data and theoretical considerations. Specifically, building on the observation that potassium prevails over sodium in the vapor of inland geothermal systems, we have argued that the first cells could emerge in the pools and puddles at the periphery of primordial anoxic geothermal fields, where the elementary composition of the condensed vapor would resemble the internal milieu of modern cells. Marine and freshwater environments generally contain more sodium than potassium. Therefore, to invade such environments, while maintaining excess of potassium over sodium in the cytoplasm, primordial cells needed means to extrude sodium ions. The foray into new, sodium-rich habitats was the likely driving force behind the evolution of diverse redox-, light-, chemically-, or osmotically-dependent sodium export pumps and the increase of membrane tightness. Here we present a scenario that details how the interplay between several, initially independent sodium pumps might have triggered the evolution of sodium-dependent membrane bioenergetics, followed by the separate emergence of the proton-dependent bioenergetics in archaea and bacteria. We also discuss the development of systems that utilize the sodium/potassium gradient across the cell membranes.

  19. 15 CFR 752.15 - Export clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Export clearance. 752.15 Section 752... OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS SPECIAL COMPREHENSIVE LICENSE § 752.15 Export clearance. (a) Shipper's Export Declaration (SED) or Automated Export...

  20. 78 FR 37518 - Order Denying Export Privileges

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-21

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security Order Denying Export Privileges In the... Texas, Lee Roy Perez (``Perez'') was convicted of violating Section 38 of the Arms Export Control Act... of knowingly and willfully exporting and causing to be exported and attempting to export and...

  1. 7 CFR 1493.130 - Recovery of losses.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.130 Recovery of losses. (a) Notification. Upon payment of loss to the exporter or the exporter's assignee, CCC...

  2. 7 CFR 1493.130 - Recovery of losses.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.130 Recovery of losses. (a) Notification. Upon payment of loss to the exporter or the exporter's assignee, CCC...

  3. 7 CFR 1493.130 - Recovery of losses.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.130 Recovery of losses. (a) Notification. Upon payment of loss to the exporter or the exporter's assignee, CCC...

  4. Impact of iron on silicon utilization by diatoms in the Southern Ocean: A case study of Si/N cycle decoupling in a naturally iron-enriched area

    NASA Astrophysics Data System (ADS)

    Mosseri, Julie; Quéguiner, Bernard; Armand, Leanne; Cornet-Barthaux, Véronique

    2008-03-01

    Biogenic silica stocks and fluxes were investigated in austral summer over the naturally iron-fertilized Kerguelen Plateau and in nearby high-nutrient, low-chlorophyll (HNLC) off-plateau surface waters. The Kerguelen Plateau hosted a large-diatom bloom, with high levels of biogenic silica (BSi) but relatively low silicic acid (Si(OH) 4) uptake rates (1100±600 mmol m -2 and 8±4 mmol m -2 d -1, respectively). Diatoms of the naturally iron-enriched area presented high affinities for silicic acid, allowing them in combination with a beneficial nutrient vertical supply to grow in low silicic acid waters (<2 μM). Si(OH) 4 acid uptake rates were also compared with carbon and nitrogen uptake rates. As expected for diatoms growing in favourable nutrient conditions, and from previous artificial iron-enrichment experiments, Si:C and Si:NO 3 elemental uptake ratios of the natural diatom community of the plateau were close to 0.13 and 1, respectively. In contrast, diatom communities in the HNLC waters were composed of strongly silicified (high Si:C, Si:NO 3 uptake ratios) diatoms with low affinities for Si(OH) 4. Although the Si:NO 3 uptake ratio in the surface waters of the plateau was close to 1, the apparent consumption of nitrate on a seasonal basis was much lower (˜5 μM) than the apparent consumption of silicic acid (˜15 μM). This was mainly due to diatoms growing actively on ammonium (i.e. 39-77% of the total nitrogen uptake) produced by an intense heterotrophic activity. Thus we find that while Fe fertilization does increase N uptake with respect to Si uptake, rapid recycling of N decouples nitrogen and carbon export from silica export so that the "silicate pump" remains more efficient than that of N (or P). For this reason an iron-fertilized Southern Ocean is unlikely to experience nitrate exhaustion or export silicic acid to the global ocean.

  5. Ventilation of the deep Southern Ocean and changes in atmospheric CO2 during the last deglacial and glacial periods

    NASA Astrophysics Data System (ADS)

    Gottschalk, J.; Skinner, L. C.; Lippold, J. A.; Jaccard, S.; Vogel, H.; Frank, N.; Waelbroeck, C.

    2014-12-01

    The Southern Ocean is thought to have played a key role in atmospheric CO2 (CO2,atm) variations, both via its role in bringing carbon-rich deep-waters into contact with the atmosphere, and via its capacity for enhanced biologically mediated carbon export into the deep sea. The governing mechanisms of millennial scale rises in CO2,atm during the last deglacial and glacial periods have been linked controversially either with variations in biological export productivity, possibly driven by fluctuations in airborne dust supply, or to variations in southern high-latitude vertical mixing, possibly driven by changes in westerly wind stress or density stratification across the Southern Ocean water column. However, the impact of these processes on deep, southern high-latitude carbon sequestration and ocean-atmosphere CO2 exchange remain ambiguous. We present proxy evidence for the link between deep carbon storage in the sub-Antarctic Atlantic with changes in CO2,atm during the last 70 ka from sub-millennially resolved changes in bottom water oxygenation based on the uranium accumulation in authigenic coatings on foraminiferal shells and the δ13C offset between epibenthic and infaunal foraminifera (Δδ13C). We compare our results with reconstructed opal fluxes and sediment model output data to assess the impact of physical and biological processes on Southern Ocean carbon storage. While variations in sub-Antarctic Atlantic export production are intrinsically linked with changes in airborne dust supply supporting the major impact of dust on the biological soft-tissue pump, they cannot account for observed changes in pore water organic carbon respiration indicated by increasing Δδ13C and therefore, bottom water oxygen changes in the deep sub-Antarctic Atlantic. This is in strong support of millennial-scale fluctuations in deep Southern Ocean carbon storage primarily controlled by the ventilation of the deep ocean by southern-sourced water masses, which emphasize the strong control of vertical mixing and upwelling of CO2-rich water masses in the Southern Ocean on the ocean-atmosphere exchange of CO2 and variation in CO2,atm over both glacial-interglacial and millennial time scales.

  6. Hydrologically mediated iron reduction/oxidation fluctuations and dissolved organic carbon exports in tidal wetlands

    NASA Astrophysics Data System (ADS)

    Guimond, J. A.; Seyfferth, A.; Michael, H. A.

    2017-12-01

    Salt marshes are biogeochemical hotspots where large quantities of carbon are processed and stored. High primary productivity and deposition of carbon-laden sediment enable salt marsh soils to accumulate and store organic carbon. Conversely, salt marshes can laterally export carbon from the marsh platform to the tidal channel and eventually the ocean via tidal pumping. However, carbon export studies largely focus on tidal channels, missing key physical and biogeochemical mechanisms driving the mobilization of dissolved organic carbon (DOC) within the marsh platform and limiting our understanding of and ability to predict coastal carbon dynamics. We hypothesize that iron redox dynamics mediate the mobilization/immobilization of DOC in the top 30 cm of salt marsh sediment near tidal channels. The mobilized DOC can then diffuse into the flooded surface water or be advected to tidal channels. To elucidate DOC dynamics driven by iron redox cycles, we measured porewater DOC, Fe(II), total iron, total sulfate, pH, redox potential, and electrical conductivity (EC) beside the creek, at the marsh levee, and in the marsh interior in a mid-latitude tidal salt marsh in Dover, Delaware. Samples were collected at multiple tide stages during a spring and neap tide at depths of 5-75cm. Samples were also collected from the tidal channel. Continuous Eh measurements were made using in-situ electrodes. A prior study shows that DOC and Fe(II) concentrations vary spatially across the marsh. Redox conditions near the creek are affected by tidal oscillations. High tides saturate the soil and decrease redox potential, whereas at low tide, oxygen enters the sediment and increases the Eh. This pattern is always seen in the top 7-10cm of sediment, with more constant low Eh at depth. However, during neap tides, this signal penetrates deeper. Thus, between the creek and marsh levee, hydrology mediates redox conditions. Based on porewater chemistry, if DOC mobilization can be linked to redox cycles, then hydrologic oscillations can be tied to DOC dynamics and predicted with hydrologic models. By elucidating the mechanisms driving the mobilization of DOC, we can begin to better understand, quantify, and forecast coastal carbon dynamics.

  7. 76 FR 9550 - President's Export Council: Meeting of the President's Export Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-18

    ... DEPARTMENT OF COMMERCE International Trade Administration President's Export Council: Meeting of the President's Export Council AGENCY: International Trade Administration, U.S. Department of Commerce.... exports, jobs, and growth. DATES: March 11, 2011 at 9:30 a.m. (ET). ADDRESSES: The President's Export...

  8. 78 FR 37787 - Order Denying Export Privileges

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-24

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security Order Denying Export Privileges In the... District of Texas, Manuel Mario Pavon (``Pavon'') was convicted of violating Section 38 of the Arms Export... knowingly and willfully exporting and causing to be exported and attempting to export and attempting to...

  9. 75 FR 54540 - Effects of Foreign Policy-Based Export Controls

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-08

    .... 100719301-0303-02] Effects of Foreign Policy-Based Export Controls AGENCY: Bureau of Industry and Security... foreign policy-based export controls in the Export Administration Regulations to determine whether they... comments on how existing foreign policy-based export controls have affected exporters and the general...

  10. Iron availability limits the ocean nitrogen inventory stabilizing feedbacks between marine denitrification and nitrogen fixation

    NASA Astrophysics Data System (ADS)

    Moore, J. Keith; Doney, Scott C.

    2007-06-01

    Recent upward revisions in key sink/source terms for fixed nitrogen (N) in the oceans imply a short residence time and strong negative feedbacks involving denitrification and N fixation to prevent large swings in the ocean N inventory over timescales of a few centuries. We tested the strength of these feedbacks in a global biogeochemical elemental cycling (BEC) ocean model that includes water column denitrification and an explicit N fixing phytoplankton group. In the northern Indian Ocean and over longer timescales in the tropical Atlantic, we find strong stabilizing feedbacks that minimize changes in marine N inventory over timescales of ˜30-200 years. In these regions high atmospheric dust/iron inputs lead to phosphorus limitation of diazotrophs, and thus a tight link between N fixation and surface water N/P ratios. Maintenance of the oxygen minimum zones in these basins depends on N fixation driven export. The stabilizing feedbacks in other regions are significant but weaker owing to iron limitation of the diazotrophs. Thus Fe limitation appears to restrict the ability of N fixation to compensate for changes in denitrification in the current climate, perhaps leading the oceans to lose fixed N. We suggest that iron is the ultimate limiting nutrient leading to nitrogen being the proximate limiting nutrient over wide regions today. Iron stress was at least partially alleviated during more dusty, glacial times, leading to a higher marine N inventory, increased export production, and perhaps widespread phosphorus limitation of the phytoplankton community. The increased efficiency of the biological pump would have contributed to the glacial drawdown in atmospheric CO2.

  11. Marine Synechococcus Aggregation

    NASA Astrophysics Data System (ADS)

    Neuer, S.; Deng, W.; Cruz, B. N.; Monks, L.

    2016-02-01

    Cyanobacteria are considered to play an important role in the oceanic biological carbon pump, especially in oligotrophic regions. But as single cells are too small to sink, their carbon export has to be mediated by aggregate formation and possible consumption by zooplankton producing sinking fecal pellets. Here we report results on the aggregation of the ubiquitous marine pico-cyanobacterium Synechococcus as a model organism. We first investigated the mechanism behind such aggregation by studying the potential role of transparent exopolymeric particles (TEP) and the effects of nutrient (nitrogen or phosphorus) limitation on the TEP production and aggregate formation of these pico-cyanobacteria. We further studied the aggregation and subsequent settling in roller tanks and investigated the effects of the clays kaolinite and bentonite in a series of concentrations. Our results show that despite of the lowered growth rates, Synechococcus in nutrient limited cultures had larger cell-normalized TEP production, formed a greater volume of aggregates, and resulted in higher settling velocities compared to results from replete cultures. In addition, we found that despite their small size and lack of natural ballasting minerals, Synechococcus cells could still form aggregates and sink at measureable velocities in seawater. Clay minerals increased the number and reduced the size of aggregates, and their ballasting effects increased the sinking velocity and carbon export potential of aggregates. In comparison with the Synechococcus, we will also present results of the aggregation of the pico-cyanobacterium Prochlorococcus in roller tanks. These results contribute to our understanding in the physiology of marine Synechococcus as well as their role in the ecology and biogeochemistry in oligotrophic oceans.

  12. Paleoproductivity in the northwestern Pacific Ocean during the Pliocene-Pleistocene climate transition (3.0-1.8 Ma)

    NASA Astrophysics Data System (ADS)

    Venti, Nicholas L.; Billups, Katharina; Herbert, Timothy D.

    2017-02-01

    Alkenone mass accumulation rates (MARs) provide a proxy for export productivity in the northwestern Pacific (Ocean Drilling Program Site 1208) spanning the late Pliocene through early Pleistocene (3.0-1.8 Ma). We investigate changes in productivity associated with global cooling during the onset and expansion of Northern Hemisphere glaciation (NHG). Alkenone MARs vary on obliquity timescales throughout, but the amplitude increases at 2.75 Ma concurrent with the intensification of NHG and cooling of the sea surface by 3°C. The obliquity-scale variations in alkenone MARs parallel shipboard measurements of sediment color reflectance (%) with higher MARs significantly correlated (>95%) with darker (opal-rich) intervals. Variations in both lead benthic foraminiferal δ18O values by 1.5-2 kyr suggesting that export productivity may be a contributing factor, rather than a response, to the extent of continental glaciation. The biological pump is therefore a plausible mechanism for transferring atmospheric CO2 into the deep ocean during the onset of NHG and the ensuing obliquity-dominated climate regime. Obliquity-scale correlation between productivity and magnetic susceptibility is consistent with a link via westerly winds delivering terrigenous sediments and mixing the upper water column. Alkenone MARs also contain a 400 kyr modulation. Because this periodicity is a multiple of the residence time of carbon in the ocean, it may reflect inputs of new nutrients associated with eccentricity-forced changes in the terrestrial biosphere and weathering. We ascribe these findings to interactions between the East Asian winter monsoon and productivity in the North Pacific Ocean, perhaps contributing to Plio-Pleistocene climate change.

  13. 21 CFR 1312.22 - Application for export permit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Application for export permit. 1312.22 Section... EXPORTATION OF CONTROLLED SUBSTANCES Exportation of Controlled Substances § 1312.22 Application for export permit. (a) An application for a permit to export controlled substances shall be made on DEA Form 161...

  14. 19 CFR 191.73 - Export summary procedure.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Export summary procedure. 191.73 Section 191.73... TREASURY (CONTINUED) DRAWBACK Exportation and Destruction § 191.73 Export summary procedure. (a) General. The export summary procedure consists of a Chronological Summary of Exports used to support a drawback...

  15. 19 CFR 10.430 - Export requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Export requirements. 10.430 Section 10.430 Customs... Export Requirements § 10.430 Export requirements. (a) Submission of certification to CBP. An exporter or producer in the United States that signs a certification of origin for a good exported from the United...

  16. 7 CFR 1488.9a - Evidence of export for commodities delivered before export.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... COMMODITIES Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit... financial period is 12 months or less, the exporter shall furnish a certification to the Treasurer, CCC... Assistant Treasurer, CCC, certifying that the commodities have been exported. The certification must include...

  17. 7 CFR 1493.110 - Notice of default and claims for loss.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493... related obligation, the exporter or the exporter's assignee must submit a notice of default to CCC as soon...

  18. 7 CFR 1493.110 - Notice of default and claims for loss.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493... related obligation, the exporter or the exporter's assignee must submit a notice of default to CCC as soon...

  19. 7 CFR 1488.9a - Evidence of export for commodities delivered before export.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... COMMODITIES Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit... financial period is 12 months or less, the exporter shall furnish a certification to the Treasurer, CCC... Assistant Treasurer, CCC, certifying that the commodities have been exported. The certification must include...

  20. 7 CFR 1488.9a - Evidence of export for commodities delivered before export.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... COMMODITIES Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit... financial period is 12 months or less, the exporter shall furnish a certification to the Treasurer, CCC... Assistant Treasurer, CCC, certifying that the commodities have been exported. The certification must include...

  1. 7 CFR 1493.110 - Notice of default and claims for loss.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493... related obligation, the exporter or the exporter's assignee must submit a notice of default to CCC as soon...

  2. RNA Export through the NPC in Eukaryotes.

    PubMed

    Okamura, Masumi; Inose, Haruko; Masuda, Seiji

    2015-03-20

    In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC.

  3. RNA Export through the NPC in Eukaryotes

    PubMed Central

    Okamura, Masumi; Inose, Haruko; Masuda, Seiji

    2015-01-01

    In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC. PMID:25802992

  4. Retinoic acid regulates several genes in bile acid and lipid metabolism via upregulation of small heterodimer partner in hepatocytes.

    PubMed

    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. Copyright © 2014. Published by Elsevier B.V.

  5. Estimating the contribution of strong daily export events to total pollutant export from the United States in summer

    NASA Astrophysics Data System (ADS)

    Fang, Yuanyuan; Fiore, Arlene M.; Horowitz, Larry W.; Gnanadesikan, Anand; Levy, Hiram; Hu, Yongtao; Russell, Armistead G.

    2009-12-01

    While the export of pollutants from the United States exhibits notable variability from day to day and is often considered to be "episodic," the contribution of strong daily export events to total export has not been quantified. We use carbon monoxide (CO) as a tracer of anthropogenic pollutants in the Model of OZone And Related Tracers (MOZART) to estimate this contribution. We first identify the major export pathway from the United States to be through the northeast boundary (24-48°N along 67.5°W and 80-67.5°W along 48°N), and then analyze 15 summers of daily CO export fluxes through this boundary. These daily CO export fluxes have a nearly Gaussian distribution with a mean of 1100 Gg CO day-1 and a standard deviation of 490 Gg CO day-1. To focus on the synoptic variability, we define a "synoptic background" export flux equal to the 15 day moving average export flux and classify strong export days according to their fluxes relative to this background. As expected from Gaussian statistics, 16% of summer days are "strong export days," classified as those days when the CO export flux exceeds the synoptic background by one standard deviation or more. Strong export days contributes 25% to the total export, a value determined by the relative standard deviation of the CO flux distribution. Regressing the anomalies of the CO export flux through the northeast U.S. boundary relative to the synoptic background on the daily anomalies in the surface pressure field (also relative to a 15 day running mean) suggests that strong daily export fluxes are correlated with passages of midlatitude cyclones over the Gulf of Saint Lawrence. The associated cyclonic circulation and Warm Conveyor Belts (WCBs) that lift surface pollutants over the northeastern United States have been shown previously to be associated with long-range transport events. Comparison with observations from the 2004 INTEX-NA field campaign confirms that our model captures the observed enhancements in CO outflow and resolves the processes associated with cyclone passages on strong export days. "Moderate export days," defined as days when the CO flux through the northeast boundary exceeds the 15 day running mean by less than one standard deviation, represent an additional 34% of summer days and 40% of total export. These days are also associated with migratory midlatitude cyclones. The remaining 35% of total export occurs on "weak export days" (50% of summer days) when high pressure anomalies occur over the Gulf of Saint Lawrence. Our findings for summer also apply to spring, when the U.S. pollutant export is typically strongest, with similar contributions to total export and associated meteorology on strong, moderate and weak export days. Although cyclone passages are the primary driver for strong daily export events, export during days without cyclone passages also makes a considerable contribution to the total export and thereby to the global pollutant budget.

  6. 21 CFR 1313.23 - Distribution of export declaration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Distribution of export declaration. 1313.23... EXPORTATION OF LIST I AND LIST II CHEMICALS Exportation of Listed Chemicals § 1313.23 Distribution of export declaration. The required three copies of the listed chemical export declaration (DEA Form 486) will be...

  7. 7 CFR 1488.9 - Evidence of export.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Evidence of export. 1488.9 Section 1488.9 Agriculture... Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Documents Required for Financing § 1488.9 Evidence of export. (a) If the commodity is exported by rail or...

  8. 22 CFR 125.1 - Exports subject to this part.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... EXPORT OF TECHNICAL DATA AND CLASSIFIED DEFENSE ARTICLES § 125.1 Exports subject to this part. (a) The controls of this part apply to the export of technical data and the export of classified defense articles... to the controls of this subchapter. (b) A license for the export of technical data and the exemptions...

  9. ExportAid: database of RNA elements regulating nuclear RNA export in mammals.

    PubMed

    Giulietti, Matteo; Milantoni, Sara Armida; Armeni, Tatiana; Principato, Giovanni; Piva, Francesco

    2015-01-15

    Regulation of nuclear mRNA export or retention is carried out by RNA elements but the mechanism is not yet well understood. To understand the mRNA export process, it is important to collect all the involved RNA elements and their trans-acting factors. By hand-curated literature screening we collected, in ExportAid database, experimentally assessed data about RNA elements regulating nuclear export or retention of endogenous, heterologous or artificial RNAs in mammalian cells. This database could help to understand the RNA export language and to study the possible export efficiency alterations owing to mutations or polymorphisms. Currently, ExportAid stores 235 and 96 RNA elements, respectively, increasing and decreasing export efficiency, and 98 neutral assessed sequences. Freely accessible without registration at http://www.introni.it/ExportAid/ExportAid.html. Database and web interface are implemented in Perl, MySQL, Apache and JavaScript with all major browsers supported. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Fuel of the Bacterial Flagellar Type III Protein Export Apparatus.

    PubMed

    Minamino, Tohru; Kinoshita, Miki; Namba, Keiichi

    2017-01-01

    The flagellar type III export apparatus utilizes ATP and proton motive force (PMF) across the cytoplasmic membrane as the energy sources and transports flagellar component proteins from the cytoplasm to the distal growing end of the growing structure to construct the bacterial flagellum beyond the cellular membranes. The flagellar type III export apparatus coordinates flagellar protein export with assembly by ordered export of substrates to parallel with their order of the assembly. The export apparatus is composed of a PMF-driven transmembrane export gate complex and a cytoplasmic ATPase complex. Since the ATPase complex is dispensable for flagellar protein export, PMF is the primary fuel for protein unfolding and translocation. Interestingly, the export gate complex can also use sodium motive force across the cytoplasmic membrane in addition to PMF when the ATPase complex does not work properly. Here, we describe experimental protocols, which have allowed us to identify the export substrate class and the primary fuel of the flagellar type III protein export apparatus in Salmonella enterica serovar Typhimurium.

  11. 76 FR 66693 - President's Export Council: Meeting of the President's Export Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-27

    .... ACTION: Notice of an open meeting. SUMMARY: The President's Export Council will hold a meeting to discuss.... exports, jobs, and growth. DATES: November 16, 2011 at 9:30 a.m. (ET) ADDRESSES: The President's Export... on December 20, 1973 to advise the President on matters relating to U.S. export trade and report to...

  12. 50 CFR 23.53 - What are the requirements for obtaining a retrospective CITES document?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... certain specimens for personal use as specified in paragraph (d)(7) of this section. (2) The exporter or re-exporter must notify the Management Authority in the exporting or re-exporting country of the...) In general, except when the exporter or re-exporter and importer have demonstrated they were not...

  13. 21 CFR 1313.22 - Contents of export declaration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Contents of export declaration. 1313.22 Section... EXPORTATION OF LIST I AND LIST II CHEMICALS Exportation of Listed Chemicals § 1313.22 Contents of export... quantitative threshold criteria established in § 1310.04(f) of this chapter may be exported if that chemical is...

  14. The export premium: why some logs are worth more abroad.

    Treesearch

    Donald F. Flora; Wendy J. McGinnis; Christine L. Lane

    1993-01-01

    For as long as logs have been exported from the Pacific Northwest, they seem to have been worth more offshore than in the domestic market. Five reasons for the export premium are the inconvenience of trade, quality, extra "haul and hassle," continuity in export arrangements, and export embargoes. A large and increasing differential remains between export and...

  15. 21 CFR 1312.23 - Issuance of export permit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Issuance of export permit. 1312.23 Section 1312.23... CONTROLLED SUBSTANCES Exportation of Controlled Substances § 1312.23 Issuance of export permit. (a) The... regulation in § 1312.30 of this part be exported only pursuant to the issuance of an export permit. The...

  16. 76 FR 31584 - President's Export Council Subcommittee on Export Administration, Notice of Open Meeting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-01

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security President's Export Council Subcommittee on Export Administration, Notice of Open Meeting; Correction: Meeting Time and Agenda The President's Export Council Subcommittee on Export Administration (PECSEA) will meet on June 9, 2011, 10 a.m., at the U.S. Department of Commerce, Herbert C. Hoove...

  17. Reengineering ribosome export.

    PubMed

    Lo, Kai-Yin; Johnson, Arlen W

    2009-03-01

    Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages.

  18. Reengineering Ribosome Export

    PubMed Central

    Lo, Kai-Yin

    2009-01-01

    Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appears to be conserved for 60S export in higher eukaryotes. We asked if export of the large subunit requires specific receptors. We made protein fusions between mutant Nmd3 and various export receptors. Surprisingly, fusions of Mex67, the tRNA exportin Los1, Mtr2, Cse1, or Msn5 to Nmd3, lacking its Crm1-dependent nuclear export signal (NES), all functioned in export. Furthermore, these chimeric proteins supported 60S export even in the presence of the Crm1 inhibitor leptomycin B, indicating that export was now independent of Crm1. These results suggest that there is not a requirement for a specific export receptor for the large subunit, as recruitment of any receptor will suffice. Finally we show that the addition of an NES directly to the 60S ribosomal subunit protein Rpl3 promotes export. These results imply remarkable flexibility in the export pathway for the 60S subunit and help explain how different export receptors could have evolved in different eukaryotic lineages. PMID:19144820

  19. [Structure and function of the bacterial flagellar type III protein export system in Salmonella
].

    PubMed

    Minamino, Tohru

    2015-01-01

    The bacterial flagellum is a filamentous organelle that propels the bacterial cell body in liquid media. For construction of the bacterial flagellum beyond the cytoplasmic membrane, flagellar component proteins are transported by its specific protein export apparatus from the cytoplasm to the distal end of the growing flagellar structure. The flagellar export apparatus consists of a transmembrane export gate complex and a cytoplasmic ATPase ring complex. Flagellar substrate-specific chaperones bind to their cognate substrates in the cytoplasm and escort the substrates to the docking platform of the export gate. The export apparatus utilizes ATP and proton motive force across the cytoplasmic membrane as the energy sources to drive protein export and coordinates protein export with assembly by ordered export of substrates to parallel with their order of assembly. In this review, we summarize our current understanding of the structure and function of the flagellar protein export system in Salmonella enterica serovar Typhimurium.

  20. Insights into public export promotion programs in an emerging economy: the case of Malaysian SMEs.

    PubMed

    Ayob, Abu H; Freixanet, Joan

    2014-10-01

    This study evaluates the impact of public export promotion programs (EPPs) among small and medium-sized enterprises (SMEs) in Malaysia. Three indicators, level of awareness, frequency of use, and perception of usefulness, were examined according to a firm's export status. The global evaluation suggests that exporters are more frequent users of EPPs and perceive them to be more useful than non-exporters. Nonetheless, both groups demonstrate higher levels of awareness, are frequent users, and perceive the programs relating to export info/knowledge are more usefulness than programs relating to financial assistance. Further analysis also reveals that the frequency of use and the perception of usefulness for most programs are positively related to export experience, but not to export turnover. This study offers insights into the effectiveness of export programs for encouraging export initiation and expansion in an emerging economy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. 27 CFR 28.220a - Responsibility for return of wine withdrawn for export with benefit of drawback.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... of wine withdrawn for export with benefit of drawback. 28.220a Section 28.220a Alcohol, Tobacco... EXPORTATION OF ALCOHOL Exportation of Wine With Benefit of Drawback § 28.220a Responsibility for return of wine withdrawn for export with benefit of drawback. The exporter shall be responsible for arranging the...

  2. 75 FR 52453 - Entry Requirements for Certain Softwood Lumber Products Exported From Any Country Into the United...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-26

    ...)(3)(iii)(B)(3), which states that ``the exporter has paid, or committed to pay, all export charges..., to his best knowledge and belief, that the exporter has paid or committed to pay ``all export charges... discrepancies between the export permit date and the entry summary data. The commenter suggests using the...

  3. Aiding and Abetting Cancer: mRNA export and the nuclear pore

    PubMed Central

    Culjkovic-Kraljacic, Biljana; Borden, Katherine L.B

    2013-01-01

    mRNA export is a critical step in gene expression. Export of transcripts can be modulated in response to cellular signaling or stress. Consistently, mRNA export is dysregulated in primary human specimens derived from many different forms of cancer. Aberrant expression of export factors can alter export of specific transcripts encoding proteins involved in proliferation, survival and oncogenesis. These specific factors, which are not used for bulk mRNA export, are obvious therapeutic targets. Indeed, given the emerging role of mRNA export in cancer, it is not surprising that efforts to target different aspects of this pathway have reached the clinical trial stage. Thus, like transcription and translation, mRNA export may also play a critical role in cancer genesis and maintenance. PMID:23582887

  4. 77 FR 37871 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-25

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application 12-00005] Export Trade Certificate of Review ACTION: Notice of Application for an Export Trade Certificate of Review from Colombia Rice Export Quota, Inc. SUMMARY: The Export Trading Company Affairs (``ETCA'') unit, Office of...

  5. 78 FR 85 - In the Matter of: Emenike Charles Nwankwoala Currently Incarcerated at: Inmate Number 50756-037...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-02

    ... willfully exporting, causing to be exported, and attempting to export from the United States to Nigeria..., causing to exported, and attempting to export from the United States to Nigeria shotguns without having...

  6. Rules and persuasion to save energy: a description of the French connection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1977-02-07

    Mr. Syrota discusses the results of France's energy program to save 45 million tons of oil equivalent in 1985 without slowing economic growth or causing undue discomfort. A combination of persuasion and tax incentives will be used to encourage lower consumption. Industry requires stronger regulations, tax incentives (such as taxes on heavy oils), and advertising restrictions. France's per capita energy consumption in 1973 was already the lowest of the industrialized nations. Success of the program's first two years is credited to the efforts of individuals, but now new policy initiatives must be made to encourage investment in energy conservation asmore » opposed to energy production. Reduced imports because of conservation will achieve the same balance of payments advantage as increased exports. Demonstration projects will promote waste heat recovery as a significant area for energy savings. Residential efforts include lowering thermostats, improving insulation and temperature control, and encouraging heat pumps and the use of waste heat. (DCK)« less

  7. Effects of raised CO2 concentration on the egg production rate and early development of two marine copepods (Acartia steueri and Acartia erythraea).

    PubMed

    Kurihara, Haruko; Shimode, Shinji; Shirayama, Yoshihisa

    2004-11-01

    Direct injection of CO(2) into the deep ocean is receiving increasing attention as a way to mitigate increasing atmospheric CO(2) concentration. To assess the potential impact of the environmental change associated with CO(2) sequestration in the ocean, we studied the lethal and sub-lethal effects of raised CO(2) concentration in seawater on adult and early stage embryos of marine planktonic copepods. We found that the reproduction rate and larval development of copepods are very sensitive to increased CO(2) concentration. The hatching rate tended to decrease, and nauplius mortality rate to increase, with increased CO(2) concentration. These results suggest that the marine copepod community will be negatively affected by the disposal of CO(2). This could decrease on the carbon export flux to the deep ocean and change the biological pump. Clearly, further studies are needed to determine whether ocean CO(2) injection is an acceptable strategy to reduce anthropogenic CO(2).

  8. Carbon Cycling and Storage in Mangrove Forests

    NASA Astrophysics Data System (ADS)

    Alongi, Daniel M.

    2014-01-01

    Mangroves are ecologically and economically important forests of the tropics. They are highly productive ecosystems with rates of primary production equal to those of tropical humid evergreen forests and coral reefs. Although mangroves occupy only 0.5% of the global coastal area, they contribute 10-15% (24 Tg C y-1) to coastal sediment carbon storage and export 10-11% of the particulate terrestrial carbon to the ocean. Their disproportionate contribution to carbon sequestration is now perceived as a means for conservation and restoration and a way to help ameliorate greenhouse gas emissions. Of immediate concern are potential carbon losses to deforestation (90-970 Tg C y-1) that are greater than these ecosystems' rates of carbon storage. Large reservoirs of dissolved inorganic carbon in deep soils, pumped via subsurface pathways to adjacent waterways, are a large loss of carbon, at a potential rate up to 40% of annual primary production. Patterns of carbon allocation and rates of carbon flux in mangrove forests are nearly identical to those of other tropical forests.

  9. Carbon cycling and storage in mangrove forests.

    PubMed

    Alongi, Daniel M

    2014-01-01

    Mangroves are ecologically and economically important forests of the tropics. They are highly productive ecosystems with rates of primary production equal to those of tropical humid evergreen forests and coral reefs. Although mangroves occupy only 0.5% of the global coastal area, they contribute 10-15% (24 Tg C y(-1)) to coastal sediment carbon storage and export 10-11% of the particulate terrestrial carbon to the ocean. Their disproportionate contribution to carbon sequestration is now perceived as a means for conservation and restoration and a way to help ameliorate greenhouse gas emissions. Of immediate concern are potential carbon losses to deforestation (90-970 Tg C y(-1)) that are greater than these ecosystems' rates of carbon storage. Large reservoirs of dissolved inorganic carbon in deep soils, pumped via subsurface pathways to adjacent waterways, are a large loss of carbon, at a potential rate up to 40% of annual primary production. Patterns of carbon allocation and rates of carbon flux in mangrove forests are nearly identical to those of other tropical forests.

  10. Low hypoxia inducible factor-1α (HIF-1α) expression in testicular germ cell tumors - a major reason for enhanced chemosensitivity?

    PubMed

    Shenoy, Niraj; Dronca, Roxana; Quevedo, Fernando; Boorjian, Stephen A; Cheville, John; Costello, Brian; Kohli, Manish; Witzig, Thomas; Pagliaro, Lance

    2017-08-01

    The molecular basis for enhanced chemosensitivity of testicular germ cell tumors (GCT) has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far, however, the increased sensitivity of GCT has been variously attributed to multiple factors - an inability to detoxify cisplatin, a lack of export pumps, an inability to repair the DNA damage, an intact apoptotic cascade and lack of p53 mutation; but a unifying underlying etiology leading to the aforementioned processes and having a translational implication has so far been elusive. Herein, we offer evidence to support a potential significant role for the previously demonstrated low hypoxia inducible factor-1α (HIF-1α) expression in mediating the general exquisite chemosensitivity of testicular GCT, through the aforementioned processes. This molecular mechanism based hypothesis could have a significant translational implication in platinum refractory GCT as well as other platinum resistant malignancies.

  11. The potential contribution of geothermal energy to electricity supply in Saudi Arabia

    NASA Astrophysics Data System (ADS)

    Chandrasekharam, D.; Lashin, Aref; Al Arifi, Nassir

    2016-10-01

    With increase in demand for electricity at 7.5% per year, the major concern of Saudi Arabia is the amount of CO2 being emitted. The country has the potential of generating 200×106 kWh from hydrothermal sources and 120×106 terawatt hour from Enhanced Geothermal System (EGS) sources. In addition to electricity generation and desalination, the country has substantial source for direct application such as space cooling and heating, a sector that consumes 80% of the electricity generated from fossil fuels. Geothermal energy can offset easily 17 million kWh of electricity that is being used for desalination. At least a part of 181,000 Gg of CO2 emitted by conventional space cooling units can also be mitigated through ground-source heat pump technology immediately. Future development of EGS sources together with the wet geothermal systems will make the country stronger in terms of oil reserves saved and increase in exports.

  12. Carboxylic Acids Plasma Membrane Transporters in Saccharomyces cerevisiae.

    PubMed

    Casal, Margarida; Queirós, Odília; Talaia, Gabriel; Ribas, David; Paiva, Sandra

    2016-01-01

    This chapter covers the functionally characterized plasma membrane carboxylic acids transporters Jen1, Ady2, Fps1 and Pdr12 in the yeast Saccharomyces cerevisiae, addressing also their homologues in other microorganisms, as filamentous fungi and bacteria. Carboxylic acids can either be transported into the cells, to be used as nutrients, or extruded in response to acid stress conditions. The secondary active transporters Jen1 and Ady2 can mediate the uptake of the anionic form of these substrates by a H(+)-symport mechanism. The undissociated form of carboxylic acids is lipid-soluble, crossing the plasma membrane by simple diffusion. Furthermore, acetic acid can also be transported by facilitated diffusion via Fps1 channel. At the cytoplasmic physiological pH, the anionic form of the acid prevails and it can be exported by the Pdr12 pump. This review will highlight the mechanisms involving carboxylic acids transporters, and the way they operate according to the yeast cell response to environmental changes, as carbon source availability, extracellular pH and acid stress conditions.

  13. SR proteins SRp20 and 9G8 contribute to efficient export of herpes simplex virus 1 mRNAs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Escudero-Paunetto, Laurimar; Li Ling; Hernandez, Felicia P.

    2010-06-05

    Herpes simplex virus 1 (HSV-1) mRNAs are exported to the cytoplasm through the export receptor TAP/NFX1. HSV-1 multifunctional protein ICP27 interacts with TAP/NXF1, binds viral RNAs, and is required for efficient viral RNA export. In ICP27 mutant infections, viral RNA export is reduced but not ablated, indicating that other export adaptors can aid in viral RNA export. Export adaptor protein Aly/REF is recruited to viral replication compartments, however, Aly/REF knockdown has little effect on viral RNA export. SR proteins SRp20 and 9G8 interact with TAP/NXF1 and mediate export of some cellular RNAs. We report that siRNA knockdown of SRp20 ormore » 9G8 resulted in about a 10 fold decrease in virus yields and in nuclear accumulation of poly(A+) RNA. In infected cells depleted of SRp20, newly transcribed Bromouridine-labeled RNA also accumulated in the nucleus. We conclude that SRp20 and 9G8 contribute to HSV-1 RNA export.« less

  14. Adjusting export tax rebates to reduce the environmental impacts of trade: Lessons from China.

    PubMed

    Song, Peng; Mao, Xianqiang; Corsetti, Gabriel

    2015-09-15

    Export tax rebates are an important policy instrument for stimulating exports, which many developing countries make use of. However, excessive export tax rebates and inappropriate structural arrangements can lead to over-production in highly polluting industries and cause the environment to deteriorate. This paper, taking China as the study case, tests and verifies the statistical significance of the causal relationship between export tax rebates and pollution emissions. With a computable general equilibrium modeling, the current study further analyzes the effectiveness of export tax rebate adjustments aimed at alleviating environmental pressure for different time periods. It is found that before 2003, export tax rebates primarily promoted exports and boosted foreign exchange reserves, and highly polluting sectors enjoyed above-average export tax rebates, which led to increased pollution emissions. Between 2003 and 2010, the export tax rebate system was reformed to reduce support for the highly polluting export sectors, which led to decreases in emissions. Canceling export tax rebates for highly polluting sectors is shown to be the most favorable policy choice for improving the environmental performance of China's international trade. This study can serve as reference for other developing countries which similarly rely on export tax rebates, so that they can adjust their policies so as to combine economic growth with pollution control. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. 40 CFR 168.85 - Other export requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Other export requirements. 168.85... STATEMENTS OF ENFORCEMENT POLICIES AND INTERPRETATIONS Export Policy and Procedures for Exporting Unregistered Pesticides § 168.85 Other export requirements. This section describes other requirements found in...

  16. 7 CFR 51.2840 - Export packing requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Export packing requirements. 51.2840 Section 51.2840 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards...) Export Packing Requirements § 51.2840 Export packing requirements. Onions specified as meeting Export...

  17. Inspection of the Department`s export licensing process for dual-use and munitions commodities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1993-08-10

    The purpose of our inspection was to review the Department of Energy`s (Energy) export licensing process for dual-use and military (munitions) commodities subject to nuclear nonproliferation controls. Specifically, we reviewed Energy`s authorities, procedures, and policies pertaining to the export licensing process and examined procedures for safeguarding data transmitted between Energy and other agencies involved in the export licensing process. We also reviewed Energy`s role as a member of the Subgroup on Nuclear Export Coordination. Our review of the sample of 60 export cases did not find evidence to lead us to believe that Energy`s recommendations for these cases were inappropriatemore » or incorrect. We identified, however, problems regarding management systems associated with the export license review process. We found that without documentation supporting export licensing decisions by the Export Control Operations Division (ECOD), we could not determine whether ECOD analysts considered all required criteria in their review of export cases referred to Energy. For example, we found that the ECOD did not retain records documenting the bases for its advice, recommendations, or decisions regarding its reviews of export license cases or revisions to lists of controlled commodities and, therefore, was not in compliance with certain provisions of the Export Administration Act, as amended, and Energy records management directives. Additionally, we found that the degree of compliance by Energy with the export licensing review criteria contained in the Export Administration Regulations and the Nuclear Non-Proliferation Act of 1978 could not be determined because ECOD did not retain records documenting the bases for its advice and recommendations on export cases.« less

  18. Regulation of the Expression of Bacterial Multidrug Exporters by Two-Component Signal Transduction Systems.

    PubMed

    Nishino, Kunihiko

    2018-01-01

    Bacterial multidrug exporters confer resistance to a wide range of antibiotics, dyes, and biocides. Recent studies have shown that there are many multidrug exporters encoded in bacterial genome. For example, it was experimentally identified that E. coli has at least 20 multidrug exporters. Because many of these multidrug exporters have overlapping substrate spectra, it is intriguing that bacteria, with their economically organized genomes, harbor such large sets of multidrug exporter genes. The key to understanding how bacteria utilize these multiple exporters lies in the regulation of exporter expression. Bacteria have developed signaling systems for eliciting a variety of adaptive responses to their environments. These adaptive responses are often mediated by two-component regulatory systems. In this chapter, the method to identify response regulators that affect expression of multidrug exporters is described.

  19. 75 FR 52929 - President's Export Council: Meeting of the President's Export Council

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-30

    ... DEPARTMENT OF COMMERCE International Trade Administration President's Export Council: Meeting of the President's Export Council AGENCY: International Trade Administration, U.S. Department of Commerce...: The President's Export Council will convene its next meeting via live webcast on the Internet at http...

  20. 50 CFR 300.189 - Prohibitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... under § 300.182. (b) Import as an entry for consumption, purchase, receive for export, export, or re... are imported, entered for consumption, exported, or re-exported. (g) Fail to comply with the documentation requirements as specified in § 300.186, for the importation, entry for consumption, exportation...

  1. 50 CFR 300.189 - Prohibitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... under § 300.182. (b) Import as an entry for consumption, purchase, receive for export, export, or re... are imported, entered for consumption, exported, or re-exported. (g) Fail to comply with the documentation requirements as specified in § 300.186, for the importation, entry for consumption, exportation...

  2. 50 CFR 300.189 - Prohibitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... under § 300.182. (b) Import as an entry for consumption, purchase, receive for export, export, or re... are imported, entered for consumption, exported, or re-exported. (g) Fail to comply with the documentation requirements as specified in § 300.186, for the importation, entry for consumption, exportation...

  3. 78 FR 58995 - Order Denying Export Privileges

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-25

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security Order Denying Export Privileges In the...''). Specifically, Kazerani was convicted of knowingly and willfully exporting and causing the exportation of laptop..., a $10,000 criminal fine and an assessment of $100. Section 766.25 of the Export Administration...

  4. 7 CFR 1493.80 - Evidence of export.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Evidence of export. 1493.80 Section 1493.80... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103...

  5. 19 CFR 19.38 - Supervision of exportation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Supervision of exportation. 19.38 Section 19.38... Supervision of exportation. (a) Sales ticket withdrawals. Conditionally duty-free merchandise withdrawn under the sales ticket procedure for exportation shall be exported only under Customs supervision as...

  6. 19 CFR 19.38 - Supervision of exportation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Supervision of exportation. 19.38 Section 19.38... Supervision of exportation. (a) Sales ticket withdrawals. Conditionally duty-free merchandise withdrawn under the sales ticket procedure for exportation shall be exported only under Customs supervision as...

  7. 19 CFR 19.38 - Supervision of exportation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Supervision of exportation. 19.38 Section 19.38... Supervision of exportation. (a) Sales ticket withdrawals. Conditionally duty-free merchandise withdrawn under the sales ticket procedure for exportation shall be exported only under Customs supervision as...

  8. 19 CFR 19.38 - Supervision of exportation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Supervision of exportation. 19.38 Section 19.38... Supervision of exportation. (a) Sales ticket withdrawals. Conditionally duty-free merchandise withdrawn under the sales ticket procedure for exportation shall be exported only under Customs supervision as...

  9. 19 CFR 19.38 - Supervision of exportation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Supervision of exportation. 19.38 Section 19.38... Supervision of exportation. (a) Sales ticket withdrawals. Conditionally duty-free merchandise withdrawn under the sales ticket procedure for exportation shall be exported only under Customs supervision as...

  10. 77 FR 73627 - 2012 LNG Export Study

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-11

    ... DEPARTMENT OF ENERGY 2012 LNG Export Study AGENCY: Office of Fossil Energy, Department of Energy. ACTION: Notice of availability of 2012 LNG Export Study and request for comments. Freeport LNG Expansion... liquefied natural gas (LNG) export cumulative impact study (LNG Export Study) in the above- referenced...

  11. 40 CFR 799.19 - Chemical imports and exports.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Chemical imports and exports. 799.19... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS General Provisions § 799.19 Chemical imports and exports. Persons who export or who intend to export...

  12. 75 FR 11118 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-10

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application No. 99-4A005] Export Trade Certificate of Review ACTION: Notice of Application ( 99-4A005) to Amend the Export Trade Certificate of Review Issued to California Almond Export Association, LLC, Application no. 99-00005. SUMMARY: The Export...

  13. 14 CFR 21.325 - Export airworthiness approvals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Export airworthiness approvals. 21.325... AIRCRAFT CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS Export Airworthiness Approvals § 21.325 Export airworthiness approvals. (a) Kinds of approvals. (1) Export airworthiness approval of Class I products is issued...

  14. 7 CFR 1493.470 - Evidence of export.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Evidence of export. 1493.470 Section 1493.470... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Supplier Credit Guarantee Program Operations § 1493.470 Evidence of export. (a) Report of export. The...

  15. 75 FR 51980 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-24

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application No. 84-21A12] Export Trade Certificate of Review ACTION: Notice of Issuance of an amended Export Trade Certificate of Review to Northwest... amended Export Trade Certificate of Review to Northwest Fruit Exporters on August 18, 2010. The...

  16. 27 CFR 28.30 - Export status.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export status. 28.30... Export status. (a) Distilled spirits and wines manufactured, produced, bottled in bottles packed in... such purposes are considered to be exported. Export status is not acquired until application on Form...

  17. 40 CFR 799.19 - Chemical imports and exports.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Chemical imports and exports. 799.19 Section 799.19 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES... General Provisions § 799.19 Chemical imports and exports. Persons who export or who intend to export...

  18. 40 CFR 799.19 - Chemical imports and exports.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 33 2012-07-01 2012-07-01 false Chemical imports and exports. 799.19... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS General Provisions § 799.19 Chemical imports and exports. Persons who export or who intend to export...

  19. 40 CFR 799.19 - Chemical imports and exports.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 33 2013-07-01 2013-07-01 false Chemical imports and exports. 799.19... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS General Provisions § 799.19 Chemical imports and exports. Persons who export or who intend to export...

  20. 40 CFR 799.19 - Chemical imports and exports.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Chemical imports and exports. 799.19... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS General Provisions § 799.19 Chemical imports and exports. Persons who export or who intend to export...

  1. 75 FR 52505 - Fiscal Year 2011 Veterinary Import/Export Services, Veterinary Diagnostic Services, and Export...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-26

    ...] Fiscal Year 2011 Veterinary Import/Export Services, Veterinary Diagnostic Services, and Export... certain veterinary diagnostic services; and for export certification of plants and plant products. The..., through September 30, 2011). FOR FURTHER INFORMATION CONTACT: For information on Veterinary Diagnostic...

  2. 31 CFR 592.201 - Prohibited importation and exportation of any rough diamond; permitted importation or exportation...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of any rough diamond; permitted importation or exportation of any rough diamond. 592.201 Section 592... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ROUGH DIAMONDS CONTROL REGULATIONS Prohibitions § 592.201 Prohibited importation and exportation of any rough diamond; permitted importation or exportation...

  3. 31 CFR 592.201 - Prohibited importation and exportation of any rough diamond; permitted importation or exportation...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... of any rough diamond; permitted importation or exportation of any rough diamond. 592.201 Section 592... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ROUGH DIAMONDS CONTROL REGULATIONS Prohibitions § 592.201 Prohibited importation and exportation of any rough diamond; permitted importation or exportation...

  4. 31 CFR 592.201 - Prohibited importation and exportation of any rough diamond; permitted importation or exportation...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of any rough diamond; permitted importation or exportation of any rough diamond. 592.201 Section 592... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ROUGH DIAMONDS CONTROL REGULATIONS Prohibitions § 592.201 Prohibited importation and exportation of any rough diamond; permitted importation or exportation...

  5. 31 CFR 592.201 - Prohibited importation and exportation of any rough diamond; permitted importation or exportation...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... of any rough diamond; permitted importation or exportation of any rough diamond. 592.201 Section 592... FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY ROUGH DIAMONDS CONTROL REGULATIONS Prohibitions § 592.201 Prohibited importation and exportation of any rough diamond; permitted importation or exportation...

  6. 48 CFR 552.211-88 - Vehicle export preparation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Vehicle export preparation... Vehicle export preparation. As prescribed in 511.204(b)(8), insert the following clause: Vehicle Export Preparation (JAN 2010) Vehicles shall be prepared for export on wheels, unboxed, unless otherwise specified in...

  7. 48 CFR 552.211-88 - Vehicle export preparation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Vehicle export preparation... Vehicle export preparation. As prescribed in 511.204(b)(8), insert the following clause: Vehicle Export Preparation (JAN 2010) Vehicles shall be prepared for export on wheels, unboxed, unless otherwise specified in...

  8. 19 CFR 192.3 - Penalties.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) EXPORT CONTROL Exportation of Used Self-Propelled Vehicles, Vessels, and Aircraft § 192.3 Penalties. (a... importer or exporter who knowingly imports, exports or attempts to import or export: (1) Any stolen self-propelled vehicle, vessel, aircraft or part of a self-propelled vehicle, vessel or aircraft; or (2) Any self...

  9. 19 CFR 192.3 - Penalties.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) EXPORT CONTROL Exportation of Used Self-Propelled Vehicles, Vessels, and Aircraft § 192.3 Penalties. (a... importer or exporter who knowingly imports, exports or attempts to import or export: (1) Any stolen self-propelled vehicle, vessel, aircraft or part of a self-propelled vehicle, vessel or aircraft; or (2) Any self...

  10. 50 CFR 300.183 - Permit holder reporting and recordkeeping requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... biweekly report of entries for consumption, exports and re-exports of fish and fish products regulated... products regulated under this subpart except shark fins were entered for consumption, exported, or re..., that is entered for consumption, exported, or re-exported. (3) A biweekly report is not required for...

  11. 50 CFR 300.183 - Permit holder reporting and recordkeeping requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... biweekly report of entries for consumption, exports and re-exports of fish and fish products regulated... products regulated under this subpart except shark fins were entered for consumption, exported, or re..., that is entered for consumption, exported, or re-exported. (3) A biweekly report is not required for...

  12. 50 CFR 300.183 - Permit holder reporting and recordkeeping requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... biweekly report of entries for consumption, exports and re-exports of fish and fish products regulated... products regulated under this subpart except shark fins were entered for consumption, exported, or re..., that is entered for consumption, exported, or re-exported. (3) A biweekly report is not required for...

  13. 76 FR 11756 - Action Affecting Export Privileges; Ali Amirnazmi; Order Denying Export Privileges

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-03

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security Action Affecting Export Privileges; Ali Amirnazmi; Order Denying Export Privileges In the Matter of: Ali Amirnazmi, Register 63302-066, FCI... release and forfeit $81,277.37. Section 766.25 of the Export Administration Regulations (``EAR'' or...

  14. 15 CFR 2012.3 - Export certificates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Export certificates. 2012.3 Section... STATES TRADE REPRESENTATIVE IMPLEMENTATION OF TARIFF-RATE QUOTAS FOR BEEF § 2012.3 Export certificates... export certificate is in effect with respect to the beef. (b) To be valid, an export certificate shall...

  15. 31 CFR 592.304 - Exporting authority.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Exporting authority. 592.304 Section... § 592.304 Exporting authority. (a) The term exporting authority means one or more entities designated by a Participant from whose territory a shipment of rough diamonds is being exported as having the...

  16. 78 FR 1837 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application No. 84-23A12] Export Trade Certificate of Review ACTION: Notice of issuance of an Export Trade Certificate of Review to Northwest Fruit Exporters, Application No. 84-23A12. SUMMARY: The U.S. Department of Commerce issued an amended Export Trade...

  17. 76 FR 55010 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-06

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application No. 84-22A12] Export Trade Certificate of Review ACTION: Notice of issuance of an Export Trade Certificate of Review to Northwest Fruit Exporters, Application no. 84-22A12. SUMMARY: The U.S. Department of Commerce issued an amended Export Trade...

  18. 50 CFR 222.205 - Import and export requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Import and export requirements. 222.205... Certificates of Exemption for Pre-Act Endangered Species Parts § 222.205 Import and export requirements. (a... intended for importation into or exportation from the United States, shall not be imported or exported...

  19. 40 CFR 89.909 - Export exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Export exemptions. 89.909 Section 89....909 Export exemptions. (a) A new nonroad engine intended solely for export, and so labeled or tagged..., 1200 Pennsylvania Ave., NW., Washington, DC 20460. New nonroad engines exported to such countries must...

  20. 78 FR 53727 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-30

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application No. 84-24A12] Export Trade Certificate of Review ACTION: Notice of Issuance of an Export Trade Certificate of Review to Northwest Fruit Exporters, Application No. 84-24A12. SUMMARY: The U.S. Department of Commerce issued an amended Export Trade...

  1. 40 CFR 92.909 - Export exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Export exemptions. 92.909 Section 92....909 Export exemptions. (a) A new locomotive or locomotive engine intended solely for export, and so... from EPA standards. (c) It is a condition of any exemption for the purpose of export under paragraph (a...

  2. 9 CFR 91.3 - General export requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false General export requirements. 91.3... HANDLING OF LIVESTOCK FOR EXPORTATION General Provisions § 91.3 General export requirements. (a) All... accompanied from the State of origin of the export movement to the port of embarkation by an origin health...

  3. 40 CFR 91.1009 - Export exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Export exemptions. 91.1009 Section 91....1009 Export exemptions. (a) A new marine SI engine intended solely for export, and so labeled or tagged...., Washington, DC 20460. New marine SI engines exported to such countries must comply with EPA certification...

  4. 37 CFR 5.19 - Export of technical data.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Export of technical data. 5..., DEPARTMENT OF COMMERCE GENERAL SECRECY OF CERTAIN INVENTIONS AND LICENSES TO EXPORT AND FILE APPLICATIONS IN FOREIGN COUNTRIES Licenses for Foreign Exporting and Filing § 5.19 Export of technical data. (a) Under...

  5. 7 CFR 1493.280 - Evidence of export report.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Evidence of export report. 1493.280 Section 1493.280... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Facility Guarantee Program (FGP) Operations § 1493.280 Evidence of export report. (a) Report of export. The...

  6. 7 CFR 35.8 - Date of export.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Date of export. 35.8 Section 35.8 Agriculture... Practices), DEPARTMENT OF AGRICULTURE COMMODITY STANDARDS AND STANDARD CONTAINER REGULATIONS EXPORT GRAPES AND PLUMS Definitions § 35.8 Date of export. Date of export means the date of loading on board the...

  7. 48 CFR 552.211-88 - Vehicle export preparation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Vehicle export preparation... Vehicle export preparation. As prescribed in 511.204(b)(8), insert the following clause: Vehicle Export Preparation (JAN 2010) Vehicles shall be prepared for export on wheels, unboxed, unless otherwise specified in...

  8. 9 CFR 322.3 - Transferring products for export.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Transferring products for export. 322... INSPECTION AND CERTIFICATION EXPORTS 1 § 322.3 Transferring products for export. When inspected and passed products for export are transferred from tank cars to other containers on vessels, such transfer shall be...

  9. 78 FR 37520 - Order Denying Export Privileges

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-21

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security Order Denying Export Privileges In the... Molina, Jr. (``Molina'') was convicted of violating Section 38 of the Arms Export Control Act (22 U.S.C... attempting to export and causing to be exported from the United States to Mexico two AK47 semi-automatic...

  10. 77 FR 60377 - Order Denying Export Privileges

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-03

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security Order Denying Export Privileges In the... causing to be violated the United States trade restriction with Iran by exporting and attempting to export... Foreign Assets Control for such an export. Avanessian was also convicted of one count of conspiracy (18 U...

  11. 10 CFR 431.405 - Exported equipment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Exported equipment. 431.405 Section 431.405 Energy... EQUIPMENT General Provisions § 431.405 Exported equipment. Under Sections 330 and 345 of the Act, this Part... for export from the United States (or such equipment was imported for export), unless such equipment...

  12. 77 FR 16768 - Export Sales Reporting Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-22

    ... DEPARTMENT OF AGRICULTURE Office of the Secretary 7 CFR Part 20 RIN 0551-AA70 Export Sales... for pork (fresh, chilled, and frozen box/primal cuts) and distillers dried grain (DDG) to the Export...: Contact Peter W. Burr, Branch Chief, Export Sales Reporting Branch, Import Policies and Export Reporting...

  13. 40 CFR 725.920 - Exports and imports.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Exports and imports. 725.920 Section... on Significant New Uses of Microorganisms § 725.920 Exports and imports. (a) Exports. Persons who intend to export a microorganism identified in subpart M of this part, or in any proposed rule which...

  14. 76 FR 54193 - Fiscal Year 2012 Veterinary Import/Export, Diagnostic Services, and Export Certification for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-31

    ...] Fiscal Year 2012 Veterinary Import/Export, Diagnostic Services, and Export Certification for Plants and.... SUMMARY: This notice pertains to user fees charged for Veterinary Services animal quarantine and other..., organisms, and vectors; for certain veterinary diagnostic services; and for export certification of plants...

  15. 7 CFR 1493.70 - Guarantee rates and fees.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.70... length of the payment terms provided for in the export sale contract, the degree of risk that CCC assumes...

  16. 7 CFR 1493.90 - Certification requirements for the evidence of export.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... certifications with respect to a GSM-102 or GSM-103 payment guarantee, CCC will have the right, notwithstanding...

  17. 7 CFR 1488.9 - Evidence of export.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5... truck, the exporter shall furnish to the Treasurer, CCC, one copy of the bill of lading covering the... carrier, the exporter shall furnish to the Treasurer, CCC, one non-negotiable copy or photo copy or other...

  18. 7 CFR 1493.70 - Guarantee rates and fees.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.70... length of the payment terms provided for in the export sale contract, the degree of risk that CCC assumes...

  19. 7 CFR 1493.90 - Certification requirements for the evidence of export.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... certifications with respect to a GSM-102 or GSM-103 payment guarantee, CCC will have the right, notwithstanding...

  20. 7 CFR 1493.50 - Certification requirements for obtaining payment guarantee.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program... requirements of § 1493.30, and the exporter will immediately notify CCC if there is a change of circumstances...

  1. 7 CFR 1493.50 - Certification requirements for obtaining payment guarantee.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program... requirements of § 1493.30, and the exporter will immediately notify CCC if there is a change of circumstances...

  2. 7 CFR 1493.70 - Guarantee rates and fees.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103) Operations § 1493.70... length of the payment terms provided for in the export sale contract, the degree of risk that CCC assumes...

  3. 7 CFR 1493.50 - Certification requirements for obtaining payment guarantee.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program... requirements of § 1493.30, and the exporter will immediately notify CCC if there is a change of circumstances...

  4. 7 CFR 1493.90 - Certification requirements for the evidence of export.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS CCC Export Credit Guarantee Program (GSM-102) and CCC Intermediate Export Credit Guarantee Program (GSM-103... certifications with respect to a GSM-102 or GSM-103 payment guarantee, CCC will have the right, notwithstanding...

  5. A new regulatory pathway of mRNA export by an F-box protein, Mdm30.

    PubMed

    Durairaj, Geetha; Lahudkar, Shweta; Bhaumik, Sukesh R

    2014-02-01

    Mdm30, an F-box protein in yeast, has been recently shown to promote mRNA export. However, it remains unknown how Mdm30 facilitates mRNA export. Here, we show that Mdm30 targets the Sub2 component of the TREX (Transcription/Export) complex for ubiquitylation and subsequent proteasomal degradation. Such a targeted degradation of Sub2 enhances the recruitment of the mRNA export adaptor, Yra1, to the active genes to promote mRNA export. Together, these results elucidate that Mdm30 promotes mRNA export by lowering Sub2's stability and consequently enhancing Yra1 recruitment, thus illuminating new regulatory mechanisms of mRNA export by Mdm30.

  6. HIV-1 Rev protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment

    PubMed Central

    Taniguchi, Ichiro; Mabuchi, Naoto; Ohno, Mutsuhito

    2014-01-01

    Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be well-controlled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoprotein remodeling activity of Rev may favor viral gene expression. PMID:24753416

  7. Feasibility of ground-water features of the alternate plan for the Mountain Home project, Idaho

    USGS Publications Warehouse

    Nace, Raymond L.; West, S.W.; Mowder, R.W.

    1957-01-01

    An early plan of the U. S. Bureau of Reclamation proposed to irrigate 183,000 acres on the arid Snake River Plain south of Boise, Idaho (Mountain Home project) with Boise River water. That water would have been replaced to the Boise Valley with water imported from the Payette River. An alternate plan, proposed in 1953, would divert water from the Boise River to the plain; part of the water would be replaced by pumping ground water in the Boise valley and by importing water from the Snake River. Pumping of ground water in the Boise Valley also would help to drain waterlogged land. The present report evaluates the feasibility of the alternate plan in relation to geology and the occurrence and quality of ground water. The mean annual temperature at Boise is 50.8 ? F and there is an average of 172 days between killing frosts. The annual evaporation rate from open-water surfaces in the area is about 33 inches. Runoff in the Boise River is chiefly from precipitation on mountain slopes at altitudes above 3,000 feet, east of Boise Diversion Dam. The surface-water supply of the Boise Valley is more Than ample for the valley, owing to large upstream storage and regulatory dams and reservoirs. The valley also contains a large volume of ground water in storage, and the perennial rate of recharge is large. The computed consumptive depletion of surface water in the valley is nearly 600,000 acre-feet a year. Apparent depletion, computed from adjusted runoff at Notus, is 1,070,000 acre-feet. The difference of 470,000 acre-feet represents ground-water underflow and ungaged surface outflow from the area east of Notus. After the beginning of irrigation, around the turn of the century, the water table in the Boise Valley rose steadily; the amount of rise at some places was as much as 140 feet. Shallow perched zones of saturation were created locally. More than 100,000 acres of Boise Valley land now is waterlogged or threatened with waterlogging, despite the presence of more than 325 miles of surface drains. Successful operation of the alternate plan would depend, not only on providing adequate water to replace that exported from the Boise Valley, but also on satisfactory drainage of waterlogged land. That is, water management in the valley would have to couple economical pumping of irrigation water with effective drainage by pumping. The average of recorded yearly diversions from the Boise River is 1,280,000 acre-feet of live water (natural flow in a stream) and 201,000 acre-feet cf recycled water. Gross diversions of record in some recent single years of ample water supply reportedly exceeded 1,800,000 acre-feet. Ground water, on the other hand is used on a relatively small scale, yearly pumpage being only about 150,000 acre-feet. The feasibility of exporting 600,000 acre-feet of Boise River water would depend on the availability of replacement water in the Boise Valley and on the availability of the required surface water in the South Fork of the Boise River at the proposed point of diversion to the Mountain Home project. In 6 of the 20 years, 1931-50, recorded diversions of live and return water from th2 Boise River exceeded the live flow at the Boise Diversion Dam by 3,865 to 107,640 acre-feet. Moreover, although the average residual discharge in the river post Notus was 701,000 acre-feet, in most years some river reaches above Notus were dry at times, owing to diversion of all water from the river. Much of the flow past Notus is surface waste and effluent ground water, which averages about 422,000 acre-feet a year. The total of potential yearly ground water recharge in the Boise Valley, derived from precipitation, incoming underflow, and infiltration of irrigation water, is about 554,000 acre-feet in the feasible exchange-pumping area and areas tributary thereto. Identified and estimated consumptive depletion of ground water in the valley is about 230,000 acre-feet a year, but not all that depletion is within the exchange are

  8. Polyamines control of cation transport across plant membranes: implications for ion homeostasis and abiotic stress signaling.

    PubMed

    Pottosin, Igor; Shabala, Sergey

    2014-01-01

    Polyamines are unique polycationic metabolites, controlling a variety of vital functions in plants, including growth and stress responses. Over the last two decades a bulk of data was accumulated providing explicit evidence that polyamines play an essential role in regulating plant membrane transport. The most straightforward example is a blockage of the two major vacuolar cation channels, namely slow (SV) and fast (FV) activating ones, by the micromolar concentrations of polyamines. This effect is direct and fully reversible, with a potency descending in a sequence Spm(4+) > Spd(3+) > Put(2+). On the contrary, effects of polyamines on the plasma membrane (PM) cation and K(+)-selective channels are hardly dependent on polyamine species, display a relatively low affinity, and are likely to be indirect. Polyamines also affect vacuolar and PM H(+) pumps and Ca(2+) pump of the PM. On the other hand, catabolization of polyamines generates H2O2 and other reactive oxygen species (ROS), including hydroxyl radicals. Export of polyamines to the apoplast and their oxidation there by available amine oxidases results in the induction of a novel ion conductance and confers Ca(2+) influx across the PM. This mechanism, initially established for plant responses to pathogen attack (including a hypersensitive response), has been recently shown to mediate plant responses to a variety of abiotic stresses. In this review we summarize the effects of polyamines and their catabolites on cation transport in plants and discuss the implications of these effects for ion homeostasis, signaling, and plant adaptive responses to environment.

  9. Phase 0 and phase III transport in various organs: combined concept of phases in xenobiotic transport and metabolism.

    PubMed

    Döring, Barbara; Petzinger, Ernst

    2014-08-01

    The historical phasing concept of drug metabolism and elimination was introduced to comprise the two phases of metabolism: phase I metabolism for oxidations, reductions and hydrolyses, and phase II metabolism for synthesis. With this concept, biological membrane barriers obstructing the accessibility of metabolism sites in the cells for drugs were not considered. The concept of two phases was extended to a concept of four phases when drug transporters were detected that guided drugs and drug metabolites in and out of the cells. In particular, water soluble or charged drugs are virtually not able to overcome the phospholipid membrane barrier. Drug transporters belong to two main clusters of transporter families: the solute carrier (SLC) families and the ATP binding cassette (ABC) carriers. The ABC transporters comprise seven families with about 20 carriers involved in drug transport. All of them operate as pumps at the expense of ATP splitting. Embedded in the former phase concept, the term "phase III" was introduced by Ishikawa in 1992 for drug export by ABC efflux pumps. SLC comprise 52 families, from which many carriers are drug uptake transporters. Later on, this uptake process was referred to as the "phase 0 transport" of drugs. Transporters for xenobiotics in man and animal are most expressed in liver, but they are also present in extra-hepatic tissues such as in the kidney, the adrenal gland and lung. This review deals with the function of drug carriers in various organs and their impact on drug metabolism and elimination.

  10. Closing the irrigation deficit in Cambodia: Implications for transboundary impacts on groundwater and Mekong River flow

    NASA Astrophysics Data System (ADS)

    Erban, Laura E.; Gorelick, Steven M.

    2016-04-01

    Rice production in Cambodia, essential to food security and exports, is largely limited to the wet season. The vast majority (96%) of land planted with rice during the wet season remains fallow during the dry season. This is in large part due to lack of irrigation capacity, increases in which would entail significant consequences for Cambodia and Vietnam, located downstream on the Mekong River. Here we quantify the extent of the dry season ;deficit; area in the Cambodian Mekong River catchment, using a recent agricultural survey and our analysis of MODIS satellite data. Irrigation of this land for rice production would require a volume of water up to 31% of dry season Mekong River flow to Vietnam. However, the two countries share an aquifer system in the Mekong Delta, where irrigation demand is increasingly met by groundwater. We estimate expansion rates of groundwater-irrigated land to be >10% per year in the Cambodian Delta using LANDSAT satellite data and simulate the effects of future expansion on groundwater levels over a 25-year period. If groundwater irrigation continues to expand at current rates, the water table will drop below the lift limit of suction pump wells, used for domestic supply by >1.5 million people, throughout much of the area within 15 years. Extensive groundwater irrigation jeopardizes access for shallow domestic water supply wells, raises the costs of pumping for all groundwater users, and may exacerbate arsenic contamination and land subsidence that are already widespread hazards in the region.

  11. Polyamines control of cation transport across plant membranes: implications for ion homeostasis and abiotic stress signaling

    PubMed Central

    Pottosin, Igor; Shabala, Sergey

    2014-01-01

    Polyamines are unique polycationic metabolites, controlling a variety of vital functions in plants, including growth and stress responses. Over the last two decades a bulk of data was accumulated providing explicit evidence that polyamines play an essential role in regulating plant membrane transport. The most straightforward example is a blockage of the two major vacuolar cation channels, namely slow (SV) and fast (FV) activating ones, by the micromolar concentrations of polyamines. This effect is direct and fully reversible, with a potency descending in a sequence Spm4+ > Spd3+ > Put2+. On the contrary, effects of polyamines on the plasma membrane (PM) cation and K+-selective channels are hardly dependent on polyamine species, display a relatively low affinity, and are likely to be indirect. Polyamines also affect vacuolar and PM H+ pumps and Ca2+ pump of the PM. On the other hand, catabolization of polyamines generates H2O2 and other reactive oxygen species (ROS), including hydroxyl radicals. Export of polyamines to the apoplast and their oxidation there by available amine oxidases results in the induction of a novel ion conductance and confers Ca2+ influx across the PM. This mechanism, initially established for plant responses to pathogen attack (including a hypersensitive response), has been recently shown to mediate plant responses to a variety of abiotic stresses. In this review we summarize the effects of polyamines and their catabolites on cation transport in plants and discuss the implications of these effects for ion homeostasis, signaling, and plant adaptive responses to environment. PMID:24795739

  12. Increased Usage of Antiseptics Is Associated with Reduced Susceptibility in Clinical Isolates of Staphylococcus aureus

    PubMed Central

    Hardy, Katherine; Sunnucks, Katie; Gil, Hannah; Shabir, Sahida; Trampari, Eleftheria; Hawkey, Peter

    2018-01-01

    ABSTRACT Hospital-acquired infection is a major cause of morbidity and mortality, and regimes to prevent infection are crucial in infection control. These include the decolonization of vulnerable patients with methicillin-resistant Staphylococcus aureus (MRSA) carriage using antiseptics, including chlorhexidine and octenidine. Concern has been raised, however, regarding the possible development of biocide resistance. In this study, we assembled a panel of S. aureus isolates, including isolates collected before the development of chlorhexidine and octenidine and isolates, from a major hospital trust in the United Kingdom during a period when the decolonization regimes were altered. We observed significant increases in the MIC and minimum bactericidal concentration (MBC) of chlorhexidine in isolates from periods of high usage of chlorhexidine. Isolates with increased MICs and MBCs of octenidine rapidly emerged after octenidine was introduced in the trust. There was no apparent cross-resistance between the two biocidal agents. A combination of variable-number tandem repeat (VNTR) analysis, PCR for qac genes, and whole-genome sequencing was used to type isolates and examine possible mechanisms of resistance. There was no expansion of a single strain associated with decreased biocide tolerance, and biocide susceptibility did not correlate with carriage of qac efflux pump genes. Mutations within the NorA or NorB efflux pumps, previously associated with chlorhexidine export, were identified, however, suggesting that this may be an important mechanism of biocide tolerance. We present evidence that isolates are evolving in the face of biocide challenge in patients and that changes in decolonization regimes are reflected in changes in susceptibility of isolates. PMID:29844113

  13. Effects of Phytoplankton Growth Phase on the Formation and Properties of Marine Snow

    NASA Astrophysics Data System (ADS)

    Montgomery, Q. W.; Proctor, K. W.; Prairie, J. C.

    2016-02-01

    Marine snow aggregates often dominate carbon export from the upper mixed layer to the deep ocean. Thus, understanding the formation and the properties of these aggregates is essential to the study of the biological pump. Aggregate formation is determined by both the encounter rate and the stickiness of the particles that they are composed of. Stickiness of phytoplankton has been linked to production of transparent exopolymer particles (TEP), which has been previously shown to vary in concentration throughout different parts of the phytoplankton growth cycle. The objective of this study is to determine the effects of the growth phase of the diatom Thalassiosira weissflogii to both TEP production and the properties of the resulting aggregates produced. Cultures of T. weissflogii were stopped at separate phases of the phytoplankton growth curve and incubated in rotating cylindrical tanks to form aggregates. Aggregate properties such as size, density, and porosity were measured at the end of each period of roller incubation. Preliminary results describe little variation in the size of the aggregates formed from different parts of the growth phase, but show a significant effect of growth phase on aggregate density. Density is an important factor in the settling of marine aggregates. Therefore, variations in aggregate density during different growth phases may have large implications for the efficiency of the biological pump during different stages of a phytoplankton bloom. Further examination will be performed on the potential effects of TEP abundance on the properties of the aggregates formed at separate growth phases and the resulting implications for carbon flux.

  14. Introduction to the project DUNE, a DUst experiment in a low Nutrient, low chlorophyll Ecosystem

    NASA Astrophysics Data System (ADS)

    Guieu, C.; Dulac, F.; Ridame, C.; Pondaven, P.

    2013-07-01

    The main goal of the project DUNE was to estimate the impact of atmospheric deposition on an oligotrophic ecosystem based on mesocosm experiments simulating strong atmospheric inputs of Aeolian dust. Atmospheric deposition is now recognized as a significant source of macro- and micro-nutrients for the surface ocean, but the quantification of its role on the biological carbon pump is still poorly determined. We proposed in DUNE to investigate the role of atmospheric inputs on the functioning of an oligotrophic system particularly well adapted to this kind of study: the Mediterranean Sea. The Mediterranean Sea - etymologically, sea surrounded by land - is submitted to atmospheric inputs that are very variable both in frequency and intensity. During the thermal stratification period, only atmospheric deposition is prone to fertilize Mediterranean surface waters which has become very oligotrophic due to the nutrient depletion (after the spring bloom). This paper describes the objectives of DUNE and the implementation plan of a series of mesocosms experiments during which either wet or dry and a succession of two wet deposition fluxes of 10 g m-2 of Saharan dust have been simulated. After the presentation of the main biogeochemical initial conditions of the site at the time of each experiment, a general overview of the papers published in this special issue is presented, including laboratory results on the solubility of trace elements in erodible soils in addition to results from the mesocosm experiments. Our mesocosm experiments aimed at being representative of real atmospheric deposition events onto the surface of oligotrophic marine waters and were an original attempt to consider the vertical dimension in the study of the fate of atmospheric deposition within surface waters. Results obtained can be more easily extrapolated to quantify budgets and parameterize processes such as particle migration through a "captured water column". The strong simulated dust deposition events were found to impact the dissolved concentrations of inorganic dissolved phosphorus, nitrogen, iron and other trace elements. In the case of Fe, adsorption on sinking particles yields a decrease in dissolved concentration unless binding ligands were produced following a former deposition input and associated fertilization. For the first time, a quantification of the C export induced by the aerosol addition was possible. Description and parameterization of biotic (heterotrophs and autotrophs, including diazotrophs) and abiotic processes (ballast effect due to lithogenic particles) after dust addition in sea surface water, result in a net particulate organic carbon export in part controlled by the "lithogenic carbon pump".

  15. Biosynthetic Approaches to Isotope Enrichment for Applications in Neutron Scattering and High Field NMR Spectroscopy: Methylotrophic

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mary E. lidstrom

    Limitations in current isotopic labeling methods present a substantial bottleneck for the application of advanced structural techniques to many important biochemical problems. New tools are required to efficiently produce the necessary labeling patterns in biochemical precursors and incorporate them into protein molecules for structural studies. This project proposed involved one aspect of this problem, the development of expression vectors for a methylotrophic bacterium, Methylobacterium extorquens AM1. If high-level, efficient expression could be obtained in such a bacterium, it would be possible to use low-cost {sup 2}H- and/or {sup 13}C-labeled substrates such as methanol to label proteins. The Lidstrom laboratory atmore » the University of Washington worked closely with the collaborators at Los Alamos National Laboratories in the development and use of these vectors. (1) Overexpression of a target gene, bacterial dehalogenase--This enzyme was expressed in Methylobacterium extorquens AM1 using a high level methanol-inducible promoter, the mxaF promoter. High expression was achieved, but most was in an insoluble form. They expressed this protein in a mutant lacking polybetahydroxybutyrate granules, and high expression was achieved, up to 10% of the total soluble protein. The recombinant protein was purified and shown to be active, with characteristics similar to the enzyme produced in E. coli. (2) Development of regulated expression systems--A number of regulated promoters were tested in M. extorquens AM1, the most promising of which appeared to be the E. coli lac promoter coupled to the Laciq regulator. The repressor was shown to be active and a chromosomal insertion construct was generated that repressed the low-level lac promoter activity in M. extorquens AM1. However, IPTG induced this system only poorly. A number of studies were carried out leading to the conclusion that IPTG entered the cell but was exported by one or more export pumps. Target genes for such pumps were mutated but none of these showed increased induction. A number of methods were used to permeabilize the cell, and a 2-fold increase in induction was obtained with one of these. The activity of the lac promoter was increased by inserting a recently-identified M. extorquens AM1 enhancer element upstream. The promoter increased in activity 5-6 fold with this addition. In summary, they have developed a suite of expression tools and host mutant strains for expressing a variety of heterologous proteins in this methylotroph. These are now available for testing by the LANL collaborators in labeling reactors to obtain labeled proteins of interest.« less

  16. Microinjection and Fluorescence In Situ Hybridization Assay for Studying mRNA Export in Mammalian Cells.

    PubMed

    Wang, Ke; Shi, Min; Cheng, Hong

    2017-01-01

    Microinjection and Fluorescence in situ Hybridization (FISH) assay is a useful method for mRNA export studies, which can overcome the problems of traditional transfection in cells. Here, we describe the method of microinjection and FISH assay applied in investigation of mRNA export. By this method we can estimate the mRNA export kinetics, examining mRNA export in cells with low transfection efficiencies, and observing nuclear export of aberrant RNAs.

  17. A Los1p-independent pathway for nuclear export of intronless tRNAs in Saccharomycescerevisiae.

    PubMed

    Feng, Wenqin; Hopper, Anita K

    2002-04-16

    Los1p, the Saccharomyces cerevisiae exportin-t homologue, binds tRNA and functions in pre-tRNA splicing and export of mature tRNA from the nucleus to the cytosol. Because LOS1 is unessential in yeast, other pathways for tRNA nuclear export must exist. We report that Cca1p, which adds nucleotides C, C, and A to the 3' end of tRNAs, is a multicopy suppressor of the defect in tRNA nuclear export caused by los1 null mutations. Mes1p, methionyl-tRNA synthetase, also suppresses the defect in nuclear export of tRNA(Met) in los1 cells. Thus, Cca1p and Mes1p seem to function in a Los1p-independent tRNA nuclear export pathway. Heterokaryon analysis indicates that Cca1p is a nucleus/cytosol-shuttling protein, providing the potential for Cca1p to function as an exporter or an adapter in this tRNA nuclear export pathway. In yeast, most mutations that affect tRNA nuclear export also cause defects in pre-tRNA splicing leading to tight coupling of the splicing and export processes. In contrast, we show that overexpressed Cca1p corrects the nuclear export, but not the pre-tRNA-splicing defects of los1Kan(r) cells, thereby uncoupling pre-tRNA splicing and tRNA nuclear export.

  18. An Interaction between KSHV ORF57 and UIF Provides mRNA-Adaptor Redundancy in Herpesvirus Intronless mRNA Export

    PubMed Central

    Jackson, Brian R.; Boyne, James R.; Noerenberg, Marko; Taylor, Adam; Hautbergue, Guillaume M.; Walsh, Matthew J.; Wheat, Rachel; Blackbourn, David J.; Wilson, Stuart A.; Whitehouse, Adrian

    2011-01-01

    The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs. PMID:21814512

  19. 22 CFR 125.1 - Exports subject to this part.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... EXPORT OF TECHNICAL DATA AND CLASSIFIED DEFENSE ARTICLES § 125.1 Exports subject to this part. (a) The controls of this part apply to the export of technical data and the export of classified defense articles... defense articles if the technical data is determined by the Directorate of Defense Trade Controls to be...

  20. 26 CFR 1.970-1 - Export trade corporations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 10 2014-04-01 2013-04-01 true Export trade corporations. 1.970-1 Section 1.970... (CONTINUED) INCOME TAXES (CONTINUED) Export Trade Corporations § 1.970-1 Export trade corporations. (a) In general. Sections 970 through 972 provide in general that if a controlled foreign corporation is an export...

  1. 26 CFR 1.970-1 - Export trade corporations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 10 2011-04-01 2011-04-01 false Export trade corporations. 1.970-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Export Trade Corporations § 1.970-1 Export trade corporations. (a) In general. Sections 970 through 972 provide in general that if a controlled foreign corporation is an export...

  2. 26 CFR 1.970-1 - Export trade corporations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 10 2012-04-01 2012-04-01 false Export trade corporations. 1.970-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Export Trade Corporations § 1.970-1 Export trade corporations. (a) In general. Sections 970 through 972 provide in general that if a controlled foreign corporation is an export...

  3. 26 CFR 1.970-1 - Export trade corporations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 10 2013-04-01 2013-04-01 false Export trade corporations. 1.970-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Export Trade Corporations § 1.970-1 Export trade corporations. (a) In general. Sections 970 through 972 provide in general that if a controlled foreign corporation is an export...

  4. 22 CFR 123.17 - Exports of firearms, ammunition, and personal protective gear.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Exports of firearms, ammunition, and personal... REGULATIONS LICENSES FOR THE EXPORT OF DEFENSE ARTICLES § 123.17 Exports of firearms, ammunition, and personal...; (2) The firearms and accompanying ammunition to be exported is with the individual's baggage or...

  5. 26 CFR 1.970-1 - Export trade corporations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 10 2010-04-01 2010-04-01 false Export trade corporations. 1.970-1 Section 1... (CONTINUED) INCOME TAXES Export Trade Corporations § 1.970-1 Export trade corporations. (a) In general. Sections 970 through 972 provide in general that if a controlled foreign corporation is an export trade...

  6. 40 CFR 273.40 - Exports.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Exports. 273.40 Section 273.40... UNIVERSAL WASTE MANAGEMENT Standards for Large Quantity Handlers of Universal Waste § 273.40 Exports. A... exporter in 40 CFR 262.53, 262.56(a)(1) through (4), (6), and (b) and 262.57; (b) Export such universal...

  7. 77 FR 13990 - Export Sales Reporting Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-08

    ... DEPARTMENT OF AGRICULTURE Office of the Secretary 7 CFR Part 20 RIN 0551-AA70 Export Sales... grain (DDG) to the Export Sales Reporting Requirements. Under this proposed rule, all exporters of U.S. pork and DDG would be required to report on a weekly basis, information on the export sales of pork and...

  8. 19 CFR 10.9 - Articles exported for processing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Articles exported for processing. 10.9 Section 10... Exported and Returned § 10.9 Articles exported for processing. (a) Except as otherwise provided for in this... returned after having been exported for further processing and which are claimed to be subject to duty only...

  9. 40 CFR 94.909 - Export exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Export exemptions. 94.909 Section 94... Export exemptions. (a) A new engine intended solely for export, and so labeled or tagged on the outside... of export under paragraph (a) of this section, that such exemption is void ab initio with respect to...

  10. 21 CFR 312.110 - Import and export requirements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Import and export requirements. 312.110 Section... export requirements. (a) Imports. An investigational new drug offered for import into the United States.... (b) Exports. An investigational new drug may be exported from the United States for use in a clinical...

  11. 40 CFR 273.20 - Exports.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Exports. 273.20 Section 273.20... UNIVERSAL WASTE MANAGEMENT Standards for Small Quantity Handlers of Universal Waste § 273.20 Exports. A... exporter in 40 CFR 262.53, 262.56(a) (1) through (4), (6), and (b) and 262.57; (b) Export such universal...

  12. 19 CFR 10.66 - Articles exported for temporary exhibition and returned; horses exported for horse racing and...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... exportation of such articles, an application on Customs Form 4455 (accompanied by an appropriate inventory... 19 Customs Duties 1 2010-04-01 2010-04-01 false Articles exported for temporary exhibition and... ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Articles Exported for...

  13. 40 CFR 80.1430 - Requirements for exporters of renewable fuels.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... calendar year i, in gallons. k = A discrete volume of exported renewable fuel. VOLk = The standardized volume of discrete volume k of exported renewable fuel that the exporter knows or has reason to know is... associated with discrete volume k. Σ = Sum involving all volumes of cellulosic biofuel exported. DCB,i-1...

  14. 19 CFR 146.67 - Transfer of merchandise for exportation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...; DEPARTMENT OF THE TREASURY (CONTINUED) FOREIGN TRADE ZONES Transfer of Merchandise From a Zone § 146.67 Transfer of merchandise for exportation. (a) Direct exportation. Any merchandise in a zone may be exported... territory for exportation at the port where the zone is located, will be made under an entry for immediate...

  15. 19 CFR 146.67 - Transfer of merchandise for exportation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...; DEPARTMENT OF THE TREASURY (CONTINUED) FOREIGN TRADE ZONES Transfer of Merchandise From a Zone § 146.67 Transfer of merchandise for exportation. (a) Direct exportation. Any merchandise in a zone may be exported... territory for exportation at the port where the zone is located, will be made under an entry for immediate...

  16. 19 CFR 146.67 - Transfer of merchandise for exportation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...; DEPARTMENT OF THE TREASURY (CONTINUED) FOREIGN TRADE ZONES Transfer of Merchandise From a Zone § 146.67 Transfer of merchandise for exportation. (a) Direct exportation. Any merchandise in a zone may be exported... territory for exportation at the port where the zone is located, will be made under an entry for immediate...

  17. 19 CFR 146.67 - Transfer of merchandise for exportation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...; DEPARTMENT OF THE TREASURY (CONTINUED) FOREIGN TRADE ZONES Transfer of Merchandise From a Zone § 146.67 Transfer of merchandise for exportation. (a) Direct exportation. Any merchandise in a zone may be exported... territory for exportation at the port where the zone is located, will be made under an entry for immediate...

  18. 19 CFR 146.67 - Transfer of merchandise for exportation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...; DEPARTMENT OF THE TREASURY (CONTINUED) FOREIGN TRADE ZONES Transfer of Merchandise From a Zone § 146.67 Transfer of merchandise for exportation. (a) Direct exportation. Any merchandise in a zone may be exported... territory for exportation at the port where the zone is located, will be made under an entry for immediate...

  19. 14 CFR 21.339 - Special export airworthiness approval for aircraft.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... export airworthiness approval for an aircraft engine, propeller, or article is issued. (c) If the FAA... difference between the aircraft to be exported and its type design. § 21.331 Issuance of export airworthiness approvals for aircraft engines, propellers, and articles. (a) A person may obtain from the FAA an export...

  20. Fluorescent recovery after photobleaching (FRAP) analysis of nuclear export rates identifies intrinsic features of nucleocytoplasmic transport.

    PubMed

    Cardarelli, Francesco; Tosti, Luca; Serresi, Michela; Beltram, Fabio; Bizzarri, Ranieri

    2012-02-17

    A quantitative description of carrier-mediated nuclear export in live cells is presented. To this end, we fused a prototypical leucine-rich nuclear export signal (NES) to GFP as a cargo model and expressed the fluorescent chimera in live CHO-K1 cells. By modeling FRAP data, we calculate the NES affinity for the export machinery and the maximum rate of nuclear export achievable at saturation of endogenous carriers. The measured active-export time through the Nuclear Pore Complex (NPC) is 18 ms, remarkably similar to the previously determined active-import rate. Also, our results reveal that active export/import and active export/passive diffusion fluxes are uncoupled, thus complementing previous reports on active import/passive diffusion uncoupling. These findings suggest differential gating at the NPC level.

  1. 7 CFR 1493.2 - Purposes of programs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS Restrictions and Criteria for Export Credit Guarantee Programs § 1493.2 Purposes of programs. CCC may use export credit guarantees: (a...

  2. 7 CFR 1493.2 - Purposes of programs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS Restrictions and Criteria for Export Credit Guarantee Programs § 1493.2 Purposes of programs. CCC may use export credit guarantees: (a...

  3. 7 CFR 1493.2 - Purposes of programs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OF AGRICULTURE EXPORT PROGRAMS CCC EXPORT CREDIT GUARANTEE PROGRAMS Restrictions and Criteria for Export Credit Guarantee Programs § 1493.2 Purposes of programs. CCC may use export credit guarantees: (a...

  4. Protein export through the bacterial flagellar type III export pathway.

    PubMed

    Minamino, Tohru

    2014-08-01

    For construction of the bacterial flagellum, which is responsible for bacterial motility, the flagellar type III export apparatus utilizes both ATP and proton motive force across the cytoplasmic membrane and exports flagellar proteins from the cytoplasm to the distal end of the nascent structure. The export apparatus consists of a membrane-embedded export gate made of FlhA, FlhB, FliO, FliP, FliQ, and FliR and a water-soluble ATPase ring complex consisting of FliH, FliI, and FliJ. FlgN, FliS, and FliT act as substrate-specific chaperones that do not only protect their cognate substrates from degradation and aggregation in the cytoplasm but also efficiently transfer the substrates to the export apparatus. The ATPase ring complex facilitates the initial entry of the substrates into the narrow pore of the export gate. The export gate by itself is a proton-protein antiporter that uses the two components of proton motive force, the electric potential difference and the proton concentration difference, for different steps of the export process. A specific interaction of FlhA with FliJ located in the center of the ATPase ring complex allows the export gate to efficiently use proton motive force to drive protein export. The ATPase ring complex couples ATP binding and hydrolysis to its assembly-disassembly cycle for rapid and efficient protein export cycle. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. © 2013 Elsevier B.V. All rights reserved.

  5. Climate change and dissolved organic carbon export to the Gulf of Maine

    USGS Publications Warehouse

    Huntington, Thomas G.; Balch, William M.; Aiken, George R.; Sheffield, Justin; Luo, Lifeng; Roesler, Collin S.; Camill, Philip

    2016-01-01

    Ongoing climate change is affecting the concentration, export (flux), and timing of dissolved organic carbon (DOC) exported to the Gulf of Maine (GoM) through changes in hydrologic regime. DOC export was calculated for water years 1950 through 2013 for 20 rivers and for water years 1930 through 2013 for 14 rivers draining to the GoM. DOC export was also estimated for the 21st century based on climate and hydrologic modeling in a previously published study. DOC export was calculated by using the regression model LOADEST to fit seasonally adjusted concentration discharge (C-Q) relations. Our results are an analysis of the sensitivity of DOC export to changes in hydrologic conditions over time since land cover and vegetation were held constant over time. Despite large interannual variability, all rivers had increasing DOC export during winter and these trends were significant (p < 0.05) in 10 out of 20 rivers for 1950 to 2013 and in 13 out of 14 rivers for 1930 to 2013. All rivers also had increasing annual export of DOC although fewer trends were statistically significant than for winter export. Projections for DOC export during the 21st century were variable depending on the climate model and greenhouse gas emission scenario that affected future river discharge through effects on precipitation and evapotranspiration. The most consistent result was a significant increase in DOC export in winter in all model-by-emission scenarios. DOC export was projected to decrease during the summer in all model-by-emission scenarios, with statistically significant decreases in half of the scenarios.

  6. Modeling the dynamical sinking of biogenic particles in eastern-boundary upwelling systems

    NASA Astrophysics Data System (ADS)

    Rossi, Vincent; Monroy, Pedro; López, Cristobal; Hernández-García, Emilio; Dewitte, Boris; Paulmier, Aurélien; Garçon, Véronique

    2017-04-01

    Although most of the organic material produced by photosynthesis in the upper ocean is recycled in surface waters, a significant portion sinks into the deep ocean where it is stored for long time-scales. Knowledge of the export flux of organic carbon from the sea surface to depths is needed to estimate the efficiency of the biological carbon pump, a key process of global carbon cycling. We study how the sinking of biogenic particles produced in the euphotic layer is affected by subsurface ocean currents as derived from a regional dynamical model. In the range of sizes and densities appropriate for marine biogenic particles, the sinking trajectories are given by the equation of motion of small particles in a fluid flow (Maxey-Riley equation). We use a modelled 3-dimensional velocity field with major energetic structures in the mesoscale and we assess the influence of physical processes such as the Coriolis force and the inertia of the particles. We find that the latter forces are negligible as compared to the most important terms, which are passive motion with the velocity of the flow and a constant added vertical velocity due to gravity. Horizontal two-dimensional clustering is observed at depth, similar to the inhomogeneities observed in sinking ocean particles. Based on ensemble experiments, we explore the influence of the mean flow and the mesoscale eddy field on particles lateral advection and size fractionation. This modeling framework allows us to extend the concept of particle source funnels and helps interpreting particles fluxes estimated from sediment traps deployed in upwelling systems, informing the spatial mismatch between surface production and particle export.

  7. Cenozoic planktonic marine diatom diversity and correlation to climate change

    USGS Publications Warehouse

    Lazarus, David; Barron, John; Renaudie, Johan; Diver, Patrick; Türke, Andreas

    2014-01-01

    Marine planktonic diatoms export carbon to the deep ocean, playing a key role in the global carbon cycle. Although commonly thought to have diversified over the Cenozoic as global oceans cooled, only two conflicting quantitative reconstructions exist, both from the Neptune deep-sea microfossil occurrences database. Total diversity shows Cenozoic increase but is sample size biased; conventional subsampling shows little net change. We calculate diversity from a separately compiled new diatom species range catalog, and recalculate Neptune subsampled-in-bin diversity using new methods to correct for increasing Cenozoic geographic endemism and decreasing Cenozoic evenness. We find coherent, substantial Cenozoic diversification in both datasets. Many living cold water species, including species important for export productivity, originate only in the latest Miocene or younger. We make a first quantitative comparison of diatom diversity to the global Cenozoic benthic ∂18O (climate) and carbon cycle records (∂13C, and 20-0 Ma pCO2). Warmer climates are strongly correlated with lower diatom diversity (raw: rho = .92, p2 were only moderately higher than today. Diversity is strongly correlated to both ∂13C and pCO2 over the last 15 my (for both: r>.9, detrended r>.6, all p<.001), but only weakly over the earlier Cenozoic, suggesting increasingly strong linkage of diatom and climate evolution in the Neogene. Our results suggest that many living marine planktonic diatom species may be at risk of extinction in future warm oceans, with an unknown but potentially substantial negative impact on the ocean biologic pump and oceanic carbon sequestration. We cannot however extrapolate our my-scale correlations with generic climate proxies to anthropogenic time-scales of warming without additional species-specific information on proximate ecologic controls.

  8. Limited impact of ocean acidification on phytoplankton community structure and carbon export in an oligotrophic environment: Results from two short-term mesocosm studies in the Mediterranean Sea

    NASA Astrophysics Data System (ADS)

    Gazeau, F.; Sallon, A.; Pitta, P.; Tsiola, A.; Maugendre, L.; Giani, M.; Celussi, M.; Pedrotti, M. L.; Marro, S.; Guieu, C.

    2017-02-01

    Modifications in the strength of the biological pump as a consequence of ocean acidification, whether positive or negative, have the potential to impact atmospheric CO2 and therefore climate. So far, most plankton community perturbation studies have been performed in nutrient-rich areas although there are some indications that CO2-dependent growth could differ in nutrient-replete vs. -limited regions and with different community compositions. Two in situ mesocosm experiments were performed in the NW Mediterranean Sea during two seasons with contrasted environmental conditions: summer oligotrophic stratified waters in the Bay of Calvi vs. winter mesotrophic well-mixed waters in the Bay of Villefranche. Nine mesocosms were deployed for 20 and 12 d, respectively, and subjected to seven CO2 levels (3 controls, 6 elevated levels). Both phytoplankton assemblages were dominated by pico- and nano-phytoplankton cells. Although haptophyceae and dinoflagellates benefited from short-term CO2 enrichment in summer, their response remained small with no consequences on organic matter export due to strong environmental constraints (nutrient availability). In winter, most of the plankton growth and associated nutrient consumption occurred during the 4-day acidification period (before the experimental phase). During the remaining experimental period, characterized by low nutrient availability, plankton growth was minimal and no clear CO2-dependency was found for any of the tested parameters. While there is a strong confidence on the absence of significant effect of short-term CO2 addition under oligotrophic conditions, more investigations are needed to assess the response of plankton communities in winter when vertical mixing and weather conditions are major factors controlling plankton dynamics.

  9. MEDUSA-2.0: an intermediate complexity biogeochemical model of the marine carbon cycle for climate change and ocean acidification studies

    NASA Astrophysics Data System (ADS)

    Yool, A.; Popova, E. E.; Anderson, T. R.

    2013-10-01

    MEDUSA-1.0 (Model of Ecosystem Dynamics, nutrient Utilisation, Sequestration and Acidification) was developed as an "intermediate complexity" plankton ecosystem model to study the biogeochemical response, and especially that of the so-called "biological pump", to anthropogenically driven change in the World Ocean (Yool et al., 2011). The base currency in this model was nitrogen from which fluxes of organic carbon, including export to the deep ocean, were calculated by invoking fixed C:N ratios in phytoplankton, zooplankton and detritus. However, due to anthropogenic activity, the atmospheric concentration of carbon dioxide (CO2) has significantly increased above its natural, inter-glacial background. As such, simulating and predicting the carbon cycle in the ocean in its entirety, including ventilation of CO2 with the atmosphere and the resulting impact of ocean acidification on marine ecosystems, requires that both organic and inorganic carbon be afforded a more complete representation in the model specification. Here, we introduce MEDUSA-2.0, an expanded successor model which includes additional state variables for dissolved inorganic carbon, alkalinity, dissolved oxygen and detritus carbon (permitting variable C:N in exported organic matter), as well as a simple benthic formulation and extended parameterizations of phytoplankton growth, calcification and detritus remineralisation. A full description of MEDUSA-2.0, including its additional functionality, is provided and a multi-decadal spin-up simulation (1860-2005) is performed. The biogeochemical performance of the model is evaluated using a diverse range of observational data, and MEDUSA-2.0 is assessed relative to comparable models using output from the Coupled Model Intercomparison Project (CMIP5).

  10. Carbon fluxes within the epipelagic zone of the Humboldt Current System off Chile: The significance of euphausiids and diatoms as key functional groups for the biological pump

    NASA Astrophysics Data System (ADS)

    González, Humberto E.; Daneri, Giovanni; Iriarte, José L.; Yannicelli, Beatriz; Menschel, Eduardo; Barría, Claudio; Pantoja, Silvio; Lizárraga, Lorena

    2009-12-01

    The information from 54 drifting sediment traps deployed between 1997 and 2006 along the Humboldt Current System off Chile (from 19.9°S to 42.2°S) was analyzed to contribute to unveiling the recurrent global-ocean issue of the lack of relationship between gross primary production (GPP) and particulate organic carbon (POC) export below 50 m depth. When the proportion of carbon that effectively sinks is relatively low compared to the carbon being fixed through GPP, a significant amount (average of 32%) of the sinking organic matter is composed of diatoms, regardless of GPP rates. Such a fraction seems to be affected by the physiological state of phytoplankton. In contrast, when the fraction of carbon sinking is high relative to GPP, most of sinking organic matter is composed of euphausid faecal strings. Such a situation occurs at relatively low values of GPP and chlorophyll-a. Most of these high sinking rates of pellets and low phytoplankton biomass occur during summer, when physical conditions favour the presence of phytoplankton blooms, and when the GPP/Biomass ratio indicates healthy phytoplankton physiological conditions. All this evidence supports the assessment of the relevance of euphausiids as key species in the Humboldt Current System pointing to (i) the top-down control that euphausiids are capable of exerting over primary producer biomass, and (ii) euphausiids‘ paramount role on total organic carbon flux over the Concepción continental shelf, regarding both POC export to the sediments and possibly the channelling of GPP directly to higher trophic levels.

  11. Annual Net Community Production in the Western Subtropical North Pacific Determined from Argo-O2 Measurements

    NASA Astrophysics Data System (ADS)

    Yang, B.; Emerson, S. R.; Bushinsky, S. M.

    2016-02-01

    Export of organic carbon from the surface ocean to depth (the biological pump) helps maintain the pCO2 of the atmosphere and the O2 content of the oxygen minimum zones of the ocean. In the upper ocean, at steady state over a seasonal cycle the net organic carbon export is equal to the Annual Net Community Production (ANCP). The geographic distribution of this quantity determined by satellite-predicted Net Primary Production (NPP) and the recycling efficiency in the euphotic zone is more heterogeneous than the limited experimental estimates of ANCP. We evaluate the relationship between these two estimates of ANCP in the subtropical Western North Pacific Ocean ( 165o E and 20o N) using oxygen measurements on Argo Floats. In January of 2015 we deployed four floats with Anderaa oxygen sensors attached to a 60 cm stick on top of the float end cap, which can be readily calibrated against atmospheric pO2. We present data from these floats and air-sea oxygen flux calculations. The degree of oxygen supersaturation in summer is 1-2 percent, and in winter it fluctuates between being over and undersaturated. Evaluating the role of bubbles in winter is critical to an accurate determination of the annual flux. While there is not a full year of data at the time of writing this abstract, there will be when the Ocean Science meeting is held. So far, after nine months of measurements, there is a net flux of oxygen to the atmosphere, indicating that photosynthesis exceeds respiration. In February we will present a full annual cycle of air-sea oxygen flux and an estimate of ANCP in this very rarely studied region of the ocean.

  12. Revealing the hidden health costs embodied in Chinese exports.

    PubMed

    Jiang, Xujia; Zhang, Qiang; Zhao, Hongyan; Geng, Guannan; Peng, Liqun; Guan, Dabo; Kan, Haidong; Huo, Hong; Lin, Jintai; Brauer, Michael; Martin, Randall V; He, Kebin

    2015-04-07

    China emits a considerable amount of air pollutants when producing goods for export. Previous efforts have emphasized the magnitude of export-related emissions; however, their health consequences on the Chinese population have not been quantified. Here, we present an interdisciplinary study to estimate the health impact of export-related air pollution. The results show that export-related emissions elevated the annual mean population weighted PM2.5 by 8.3 μg/m(3) (15% of the total) in 2007, causing 157,000 deaths and accounting for 12% of the total mortality attributable to PM2.5-related air pollution. Compared to the eastern coastal provinces, the inner regions experience much larger export-related health losses relative to their economic production gains, owing to huge inter-regional disparities in export structures and technology levels. A shift away from emission-intensive production structure and export patterns, especially in inner regions, could significantly help improve national exports while alleviating the inter-regional cost-benefit inequality. Our results provide the first quantification of health consequences from air pollution related to Chinese exports. The proposed policy recommendations, based on health burden, economic production gains, and emission analysis, would be helpful to develop more sustainable and effective national and regional export strategies.

  13. Variation in watershed nitrogen input and export across the Willamette River Basin

    NASA Astrophysics Data System (ADS)

    Goodwin, K. E.; Compton, J. E.; Sobota, D. J.

    2011-12-01

    Nitrogen (N) export from watersheds is influenced by hydrology, land use/cover, and the timing and spatial arrangement of N inputs and removal within basins. We examined the relationship between N input and watershed N export for 25 monitoring stations between 1996 and 2006 within the Willamette River Basin, western Oregon USA. We hypothesized that N export would be strongly correlated with N inputs, and that much of the N inputs comes from agricultural activities located in lowland portions of the basin. We also expected that N export would be strongly seasonal, reflecting the Mediterranean climate of the region. We found a wide range of export from the monitored WRB sub-basins, ranging from 1 to nearly 70 kg N ha-1 yr-1. Lower per unit area N export reflected a high proportion of watershed area in the predominantly forested Cascade Mountains, while the higher N export basins had a greater proportion of agricultural areas, particularly areas dominated by cultivated crops with high N requirements. Export of N varied greatly from year to year (up to nearly 200%), responding to interannual changes in precipitation and runoff. Export was strongly seasonal, with at least 50%, and often 75%, of the N export occurring during the fall and winter months. Snowmelt dominated Cascade Mountain streams tended to maintain flow and N export during the summer, compared with the basins draining Coast-Range and valley areas, which have less snow and spring rain inputs to maintain summer flow. Agricultural N inputs of synthetic and manure fertilizer were strongly correlated with N export from the sub-basins. Across the WRB, N export appears to be more strongly related to fertilizer application rates, as opposed to agricultural areas, indicating the importance of specific crops and crop practices as opposed to considering all agricultural lands the same in analyses of watershed N dynamics. This reinforces the need for careful tracking of N inputs to inform water quality monitoring and management. Annual N export was strongly driven by precipitation and runoff, suggesting that changes in hydrology will have important effects on N export downstream and to coastal areas in the future.

  14. 27 CFR 28.40 - Evidence of exportation: distilled spirits and wine.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...: distilled spirits and wine. 28.40 Section 28.40 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO... Provisions Evidence of Exportation and Use § 28.40 Evidence of exportation: distilled spirits and wine. The exportation of any shipment of distilled spirits or wine may be evidenced by: (a) A copy of the export bill of...

  15. 75 FR 5804 - Small and Medium-Sized Enterprises: U.S. and EU Export Activities, and Barriers and Opportunities...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-04

    ... significant constraints that U.S. SMEs face in their efforts to export. The strategies that SMEs have adopted to address or overcome those constraints. The benefits to SMEs of increased export opportunities from... arrangements that have been most beneficial to SMEs that export. The characteristics of SMEs that export...

  16. The effect of exchange rates on southern pine exports

    Treesearch

    H.W. Wisdom; James E. Granskog

    2003-01-01

    Changes in exchange rates affect southern pine exports by changing the cost of southern wood in foreign markets. A strong dollar discourages exports; a weak dollar encourages exports. A simple economic export market model is developed to determine whether changes in the exchange rates in foreign markets of southern pine products have, in fact, let to significant...

  17. Are there regional differences in US hardwood product exports?

    Treesearch

    Matt Bumgardner; Scott Bowe; William Luppold

    2016-01-01

    Exporting is a critical component of the product mix for many domestic hardwood firms. Previous research has identified factors associated with hardwood lumber exporting behavior, but less is known about the advantages and disadvantages to exporting associated with the region within which a firm is located, or about exporting of secondary hardwood products. A procedure...

  18. U.S. hardwood exports, hardwood exports to Japan, hardwood resource situation, and the future of U.S. exports to Japan

    Treesearch

    Philip A. Araman

    1989-01-01

    This paper looks at some basic information about total U.S. hardwood exports and products as well as hardwood exports to Japan. It also discusses the U.S. hardwood resource situation and how we can best use the resource base to suppy Japanâs needs.

  19. 19 CFR 113.55 - Cancellation of export bonds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Cancellation of export bonds. 113.55 Section 113... export bonds. (a) Manner of cancellation. A bond to assure exportation as defined in § 101.1 of this... shall be signed by a revenue officer of the foreign country to which the merchandise is exported, unless...

  20. 22 CFR 123.22 - Filing, retention, and return of export licenses and filing of export information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Filing, retention, and return of export licenses and filing of export information. 123.22 Section 123.22 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS LICENSES FOR THE EXPORT OF DEFENSE ARTICLES § 123.22 Filing, retention...

  1. 22 CFR 123.22 - Filing, retention, and return of export licenses and filing of export information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Filing, retention, and return of export licenses and filing of export information. 123.22 Section 123.22 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS LICENSES FOR THE EXPORT OF DEFENSE ARTICLES § 123.22 Filing, retention...

  2. 22 CFR 123.22 - Filing, retention, and return of export licenses and filing of export information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Filing, retention, and return of export licenses and filing of export information. 123.22 Section 123.22 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS LICENSES FOR THE EXPORT OF DEFENSE ARTICLES § 123.22 Filing, retention...

  3. 22 CFR 123.22 - Filing, retention, and return of export licenses and filing of export information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Filing, retention, and return of export licenses and filing of export information. 123.22 Section 123.22 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS LICENSES FOR THE EXPORT OF DEFENSE ARTICLES § 123.22 Filing, retention...

  4. 22 CFR 123.9 - Country of ultimate destination and approval of reexports or retransfers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... destination on an application for an export license, or on a Shipper's Export Declaration where an exemption... the export license, or on the Shipper's Export Declaration in cases where an exemption is claimed... the invoice whenever defense articles on the U.S. Munitions List are to be exported: These commodities...

  5. 15 CFR 732.5 - Steps regarding Shipper's Export Declaration or Automated Export System record, Destination...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... than anti-terrorism (AT). The only exception to this requirement would be the return of unwanted... be entered on the invoice and on the bill of lading, air waybill, or other export control document... THE EAR § 732.5 Steps regarding Shipper's Export Declaration or Automated Export System record...

  6. 15 CFR 732.5 - Steps regarding Shipper's Export Declaration or Automated Export System record, Destination...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... than anti-terrorism (AT). The only exception to this requirement would be the return of unwanted... be entered on the invoice and on the bill of lading, air waybill, or other export control document... THE EAR § 732.5 Steps regarding Shipper's Export Declaration or Automated Export System record...

  7. 15 CFR 732.5 - Steps regarding Shipper's Export Declaration or Automated Export System record, Destination...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... than anti-terrorism (AT). The only exception to this requirement would be the return of unwanted... be entered on the invoice and on the bill of lading, air waybill, or other export control document... THE EAR § 732.5 Steps regarding Shipper's Export Declaration or Automated Export System record...

  8. 15 CFR 732.5 - Steps regarding Shipper's Export Declaration or Automated Export System record, Destination...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... than anti-terrorism (AT). The only exception to this requirement would be the return of unwanted... be entered on the invoice and on the bill of lading, air waybill, or other export control document... THE EAR § 732.5 Steps regarding Shipper's Export Declaration or Automated Export System record...

  9. 7 CFR 1488.21 - Exporter's records and accounts.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... COMMODITIES Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Miscellaneous Provisions § 1488.21 Exporter's records and accounts. CCC shall have...

  10. 7 CFR 1488.21 - Exporter's records and accounts.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... COMMODITIES Financing of Export Sales of Agricultural Commodities From Private Stocks Under CCC Export Credit Sales Program (GSM-5) Miscellaneous Provisions § 1488.21 Exporter's records and accounts. CCC shall have...

  11. A Herpesvirus Protein Selectively Inhibits Cellular mRNA Nuclear Export.

    PubMed

    Gong, Danyang; Kim, Yong Hoon; Xiao, Yuchen; Du, Yushen; Xie, Yafang; Lee, Kevin K; Feng, Jun; Farhat, Nisar; Zhao, Dawei; Shu, Sara; Dai, Xinghong; Chanda, Sumit K; Rana, Tariq M; Krogan, Nevan J; Sun, Ren; Wu, Ting-Ting

    2016-11-09

    Nuclear mRNA export is highly regulated to ensure accurate cellular gene expression. Viral inhibition of cellular mRNA export can enhance viral access to the cellular translation machinery and prevent anti-viral protein production but is generally thought to be nonselective. We report that ORF10 of Kaposi's sarcoma-associated herpesvirus (KSHV), a nuclear DNA virus, inhibits mRNA export in a transcript-selective manner to control cellular gene expression. Nuclear export inhibition by ORF10 requires an interaction with an RNA export factor, Rae1. Genome-wide analysis reveals a subset of cellular mRNAs whose nuclear export is blocked by ORF10 with the 3' UTRs of ORF10-targeted transcripts conferring sensitivity to export inhibition. The ORF10-Rae1 interaction is important for the virus to express viral genes and produce infectious virions. These results suggest that a nuclear DNA virus can selectively interfere with RNA export to restrict host gene expression for optimal replication. Published by Elsevier Inc.

  12. Fluorescent Recovery after Photobleaching (FRAP) Analysis of Nuclear Export Rates Identifies Intrinsic Features of Nucleocytoplasmic Transport*

    PubMed Central

    Cardarelli, Francesco; Tosti, Luca; Serresi, Michela; Beltram, Fabio; Bizzarri, Ranieri

    2012-01-01

    A quantitative description of carrier-mediated nuclear export in live cells is presented. To this end, we fused a prototypical leucine-rich nuclear export signal (NES) to GFP as a cargo model and expressed the fluorescent chimera in live CHO-K1 cells. By modeling FRAP data, we calculate the NES affinity for the export machinery and the maximum rate of nuclear export achievable at saturation of endogenous carriers. The measured active-export time through the Nuclear Pore Complex (NPC) is 18 ms, remarkably similar to the previously determined active-import rate. Also, our results reveal that active export/import and active export/passive diffusion fluxes are uncoupled, thus complementing previous reports on active import/passive diffusion uncoupling. These findings suggest differential gating at the NPC level. PMID:22190681

  13. A Los1p-independent pathway for nuclear export of intronless tRNAs in Saccharomyces cerevisiae

    PubMed Central

    Feng, Wenqin; Hopper, Anita K.

    2002-01-01

    Los1p, the Saccharomyces cerevisiae exportin-t homologue, binds tRNA and functions in pre-tRNA splicing and export of mature tRNA from the nucleus to the cytosol. Because LOS1 is unessential in yeast, other pathways for tRNA nuclear export must exist. We report that Cca1p, which adds nucleotides C, C, and A to the 3′ end of tRNAs, is a multicopy suppressor of the defect in tRNA nuclear export caused by los1 null mutations. Mes1p, methionyl-tRNA synthetase, also suppresses the defect in nuclear export of tRNAMet in los1 cells. Thus, Cca1p and Mes1p seem to function in a Los1p-independent tRNA nuclear export pathway. Heterokaryon analysis indicates that Cca1p is a nucleus/cytosol-shuttling protein, providing the potential for Cca1p to function as an exporter or an adapter in this tRNA nuclear export pathway. In yeast, most mutations that affect tRNA nuclear export also cause defects in pre-tRNA splicing leading to tight coupling of the splicing and export processes. In contrast, we show that overexpressed Cca1p corrects the nuclear export, but not the pre-tRNA-splicing defects of los1∷Kanr cells, thereby uncoupling pre-tRNA splicing and tRNA nuclear export. PMID:11959996

  14. The Bacterial Flagellar Type III Export Gate Complex Is a Dual Fuel Engine That Can Use Both H+ and Na+ for Flagellar Protein Export

    PubMed Central

    Minamino, Tohru; Morimoto, Yusuke V.; Hara, Noritaka; Aldridge, Phillip D.; Namba, Keiichi

    2016-01-01

    The bacterial flagellar type III export apparatus utilizes ATP and proton motive force (PMF) to transport flagellar proteins to the distal end of the growing flagellar structure for self-assembly. The transmembrane export gate complex is a H+–protein antiporter, of which activity is greatly augmented by an associated cytoplasmic ATPase complex. Here, we report that the export gate complex can use sodium motive force (SMF) in addition to PMF across the cytoplasmic membrane to drive protein export. Protein export was considerably reduced in the absence of the ATPase complex and a pH gradient across the membrane, but Na+ increased it dramatically. Phenamil, a blocker of Na+ translocation, inhibited protein export. Overexpression of FlhA increased the intracellular Na+ concentration in the presence of 100 mM NaCl but not in its absence, suggesting that FlhA acts as a Na+ channel. In wild-type cells, however, neither Na+ nor phenamil affected protein export, indicating that the Na+ channel activity of FlhA is suppressed by the ATPase complex. We propose that the export gate by itself is a dual fuel engine that uses both PMF and SMF for protein export and that the ATPase complex switches this dual fuel engine into a PMF-driven export machinery to become much more robust against environmental changes in external pH and Na+ concentration. PMID:26943926

  15. The Bacterial Flagellar Type III Export Gate Complex Is a Dual Fuel Engine That Can Use Both H+ and Na+ for Flagellar Protein Export.

    PubMed

    Minamino, Tohru; Morimoto, Yusuke V; Hara, Noritaka; Aldridge, Phillip D; Namba, Keiichi

    2016-03-01

    The bacterial flagellar type III export apparatus utilizes ATP and proton motive force (PMF) to transport flagellar proteins to the distal end of the growing flagellar structure for self-assembly. The transmembrane export gate complex is a H+-protein antiporter, of which activity is greatly augmented by an associated cytoplasmic ATPase complex. Here, we report that the export gate complex can use sodium motive force (SMF) in addition to PMF across the cytoplasmic membrane to drive protein export. Protein export was considerably reduced in the absence of the ATPase complex and a pH gradient across the membrane, but Na+ increased it dramatically. Phenamil, a blocker of Na+ translocation, inhibited protein export. Overexpression of FlhA increased the intracellular Na+ concentration in the presence of 100 mM NaCl but not in its absence, suggesting that FlhA acts as a Na+ channel. In wild-type cells, however, neither Na+ nor phenamil affected protein export, indicating that the Na+ channel activity of FlhA is suppressed by the ATPase complex. We propose that the export gate by itself is a dual fuel engine that uses both PMF and SMF for protein export and that the ATPase complex switches this dual fuel engine into a PMF-driven export machinery to become much more robust against environmental changes in external pH and Na+ concentration.

  16. The aspartyl protease TgASP5 mediates the export of the Toxoplasma GRA16 and GRA24 effectors into host cells.

    PubMed

    Curt-Varesano, Aurélie; Braun, Laurence; Ranquet, Caroline; Hakimi, Mohamed-Ali; Bougdour, Alexandre

    2016-02-01

    Toxoplasma gondii and Plasmodium species are obligatory intracellular parasites that export proteins into the infected cells in order to interfere with host-signalling pathways, acquire nutrients or evade host defense mechanisms. With regard to export mechanism, a wealth of information in Plasmodium spp. is available, while the mechanisms operating in T. gondii remain uncertain. The recent discovery of exported proteins in T. gondii, mainly represented by dense granule resident proteins, might explain this discrepancy and offers a unique opportunity to study the export mechanism in T. gondii. Here, we report that GRA16 export is mediated by two protein elements present in its N-terminal region. Because the first element contains a putative Plasmodium export element linear motif (RRLAE), we hypothesized that GRA16 export depended on a maturation process involving protein cleavage. Using both N- and C-terminal epitope tags, we provide evidence for protein proteolysis occurring in the N-terminus of GRA16. We show that TgASP5, the T. gondii homolog of Plasmodium plasmepsin V, is essential for GRA16 export and is directly responsible for its maturation in a Plasmodium export element-dependent manner. Interestingly, TgASP5 is also involved in GRA24 export, although the GRA24 maturation mechanism is TgASP5-independent. Our data reveal different modus operandi for protein export, in which TgASP5 should play multiple functions. © 2015 John Wiley & Sons Ltd.

  17. 77 FR 41885 - Privacy Act of 1974: Implementation of Exemptions; Export-Import Bank of the United States Office...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-17

    ... EXPORT-IMPORT BANK OF THE UNITED STATES 12 CFR Part 404 [EXIM-OIG-2012-0010] RIN 3048-AA02 Privacy Act of 1974: Implementation of Exemptions; Export-Import Bank of the United States Office of Inspector..., Export-Import Bank of the United States. ACTION: Final rule. SUMMARY: The Export-Import Bank of the...

  18. Comparison between Canadian Canola Harvest and Export Surveys.

    PubMed

    Barthet, Véronique J

    2016-07-20

    Parameters, such as oil, protein, glucosinolates, chlorophyll content and fatty acid composition, were determined using reference methods for both harvest survey samples and Canadian Canola exports. Canola harvest survey and export data were assessed to evaluate if canola harvest survey data can be extrapolated to predict the quality of the Canadian canola exports. There were some differences in some measured parameters between harvest and export data, while other parameters showed little difference. Protein content and fatty acid composition showed very similar data for harvest and export averages. Canadian export data showed lower oil content when compared to the oil content of harvest survey was mainly due to a diluting effect of dockage in the export cargoes which remained constant over the years (1.7% to 1.9%). Chlorophyll was the least predictable parameter; dockage quality as well as commingling of the other grades in Canola No. 1 Canada affected the chlorophyll content of the exports. Free fatty acids (FFA) were also different for the export and harvest survey. FFA levels are affected by storage conditions; they increase during the shipping season and, therefore, are difficult to predict from their harvest survey averages.

  19. In Vitro Comparison of Adipokine Export Signals.

    PubMed

    Sharafi, Parisa; Kocaefe, Y Çetin

    2016-01-01

    Mammalian cells are widely used for recombinant protein production in research and biotechnology. Utilization of export signals significantly facilitates production and purification processes. 35 years after the discovery of the mammalian export machinery, there still are obscurities regarding the efficiency of the export signals. The aim of this study was the comparative evaluation of the efficiency of selected export signals using adipocytes as a cell model. Adipocytes have a large capacity for protein secretion including several enzymes, adipokines, and other signaling molecules, providing a valid system for a quantitative evaluation. Constructs that expressed N-terminal fusion export signals were generated to express Enhanced Green Fluorescence Protein (EGFP) as a reporter for quantitative and qualitative evaluation. Furthermore, fluorescent microscopy was used to trace the intracellular traffic of the reporter. The export efficiency of six selected proteins secreted from adipocytes was evaluated. Quantitative comparison of intracellular and exported fractions of the recombinant constructs demonstrated a similar efficiency among the studied sequences with minor variations. The export signal of Retinol Binding Protein (RBP4) exhibited the highest efficiency. This study presents the first quantitative data showing variations among export signals, in adipocytes which will help optimization of recombinant protein distribution.

  20. A short conserved motif in ALYREF directs cap- and EJC-dependent assembly of export complexes on spliced mRNAs

    PubMed Central

    Gromadzka, Agnieszka M.; Steckelberg, Anna-Lena; Singh, Kusum K.; Hofmann, Kay; Gehring, Niels H.

    2016-01-01

    The export of messenger RNAs (mRNAs) is the final of several nuclear posttranscriptional steps of gene expression. The formation of export-competent mRNPs involves the recruitment of export factors that are assumed to facilitate transport of the mature mRNAs. Using in vitro splicing assays, we show that a core set of export factors, including ALYREF, UAP56 and DDX39, readily associate with the spliced RNAs in an EJC (exon junction complex)- and cap-dependent manner. In order to elucidate how ALYREF and other export adaptors mediate mRNA export, we conducted a computational analysis and discovered four short, conserved, linear motifs present in RNA-binding proteins. We show that mutation in one of the new motifs (WxHD) in an unstructured region of ALYREF reduced RNA binding and abolished the interaction with eIF4A3 and CBP80. Additionally, the mutation impaired proper localization to nuclear speckles and export of a spliced reporter mRNA. Our results reveal important details of the orchestrated recruitment of export factors during the formation of export competent mRNPs. PMID:26773052

  1. Comparison between Canadian Canola Harvest and Export Surveys

    PubMed Central

    Barthet, Véronique J.

    2016-01-01

    Parameters, such as oil, protein, glucosinolates, chlorophyll content and fatty acid composition, were determined using reference methods for both harvest survey samples and Canadian Canola exports. Canola harvest survey and export data were assessed to evaluate if canola harvest survey data can be extrapolated to predict the quality of the Canadian canola exports. There were some differences in some measured parameters between harvest and export data, while other parameters showed little difference. Protein content and fatty acid composition showed very similar data for harvest and export averages. Canadian export data showed lower oil content when compared to the oil content of harvest survey was mainly due to a diluting effect of dockage in the export cargoes which remained constant over the years (1.7% to 1.9%). Chlorophyll was the least predictable parameter; dockage quality as well as commingling of the other grades in Canola No. 1 Canada affected the chlorophyll content of the exports. Free fatty acids (FFA) were also different for the export and harvest survey. FFA levels are affected by storage conditions; they increase during the shipping season and, therefore, are difficult to predict from their harvest survey averages. PMID:27447675

  2. Twelve year interannual and seasonal variability of stream carbon export from a boreal peatland catchment

    NASA Astrophysics Data System (ADS)

    Leach, J. A.; Larsson, A.; Wallin, M. B.; Nilsson, M. B.; Laudon, H.

    2016-07-01

    Understanding stream carbon export dynamics is needed to accurately predict how the carbon balance of peatland catchments will respond to climatic and environmental change. We used a 12 year record (2003-2014) of continuous streamflow and manual spot measurements of total organic carbon (TOC), dissolved inorganic carbon (DIC), methane (CH4), and organic carbon quality (carbon-specific ultraviolet absorbance at 254 nm per dissolved organic carbon) to assess interannual and seasonal variability in stream carbon export for a peatland catchment (70% mire and 30% forest cover) in northern Sweden. Mean annual total carbon export for the 12 year period was 12.2 gCm-2 yr-1, but individual years ranged between 6 and 18 gCm-2 yr-1. TOC, which was primarily composed of dissolved organic carbon (>99%), was the dominant form of carbon being exported, comprising 63% to 79% of total annual exports, and DIC contributed between 19% and 33%. CH4 made up less than 5% of total export. When compared to previously published annual net ecosystem exchange (NEE) for the studied peatland system, stream carbon export typically accounted for 12 to 50% of NEE for most years. However, in 2006 stream carbon export accounted for 63 to 90% (estimated uncertainty range) of NEE due to a dry summer which suppressed NEE, followed by a wet autumn that resulted in considerable stream export. Runoff exerted a primary control on stream carbon export from this catchment; however, our findings suggest that seasonal variations in biologic and hydrologic processes responsible for production and transport of carbon within the peatland were secondary influences on stream carbon export. Consideration of these seasonal dynamics is needed when predicting stream carbon export response to environmental change.

  3. Monitoring and Predicting the Export and Fate of Global Ocean Net Primary Production: The EXPORTS Field Program

    NASA Astrophysics Data System (ADS)

    Exports Science Definition Team

    2016-04-01

    Ocean ecosystems play a critical role in the Earth's carbon cycle and its quantification on global scales remains one of the greatest challenges in global ocean biogeochemistry. The goal of the EXport Processes in the Ocean from Remote Sensing (EXPORTS) science plan is to develop a predictive understanding of the export and fate of global ocean primary production and its implications for the Earth's carbon cycle in present and future climates. NASA's satellite ocean-color data record has revolutionized our understanding of global marine systems. EXPORTS is designed to advance the utility of NASA ocean color assets to predict how changes in ocean primary production will impact the global carbon cycle. EXPORTS will create a predictive understanding of both the export of organic carbon from the euphotic zone and its fate in the underlying "twilight zone" (depths of 500 m or more) where variable fractions of exported organic carbon are respired back to CO2. Ultimately, it is the sequestration of deep organic carbon transport that defines the impact of ocean biota on atmospheric CO2 levels and hence climate. EXPORTS will generate a new, detailed understanding of ocean carbon transport processes and pathways linking upper ocean phytoplankton processes to the export and fate of organic matter in the underlying twilight zone using a combination of field campaigns, remote sensing and numerical modeling. The overarching objective for EXPORTS is to ensure the success of future satellite missions by establishing mechanistic relationships between remotely sensed signals and carbon cycle processes. Through a process-oriented approach, EXPORTS will foster new insights on ocean carbon cycling that will maximize its societal relevance and be a key component in the U.S. investment to understand Earth as an integrated system.

  4. 7 CFR 1280.106 - Exporter.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE LAMB PROMOTION, RESEARCH, AND INFORMATION ORDER Lamb Promotion, Research, and Information Order Definitions § 1280.106 Exporter. Exporter means any person who exports domestic live lambs from the United States. ...

  5. Rapid reconnaissance hydrogeologic modeling on public lands using analytic element solutions coupled with MODFLOW - application to the Eagle Creek watershed, New Mexico

    NASA Astrophysics Data System (ADS)

    Congdon, R. D.

    2012-12-01

    There is frequently a need in land management agencies for a quick and easy method for estimating hydrogeologic conditions in a watershed for which there is very little subsurface information. Setting up a finite difference or finite element model takes valuable time that often is not available when decisions need to be made quickly. An analytic element model (AEM), GFLOW in this case, may enable the investigator to produce a preliminary steady-state model for a watershed, and to easily evaluate variants of the conceptual model. Use of preexisting data, such as stream gage data or USGS reports makes the job much easier. Solutions to analytic element models are obtained within seconds. The Eagle Creek watershed in central New Mexico is a site of local water supply issues in an area of volcanic and plutonic rocks. Parameters estimated by groundwater consultants and the USGS, and discharge data from three USGS stream gages were used to set up the steady-state analytical model (GFLOW). Matching gage records with line-sink fluxes facilitated conceptualization of local groundwater flow and quick analysis of the effects of steady water supply pumping on Eagle Creek. Because of steep topgraphy and limited access, a water supply well is located within the stream channel within 20 meters of the creek, and it would be useful to evaluate the effects of the well on stream flow. A USGS report (SIR 2010-5205) revealed a section of Eagle Creek with a high vertical conductivity which results in flow loss of up to 34 l/s (including flow to the water table and flow into alluvium) when the well was pumped and the water table was lowered below the channel bottom. The water supply well was simulated with a steady-state well pumping at the average and maximum rates of 12 l/s and 31 l/s. The initial simulation shows that pumping at these rates results in stream flow loss of 19% and 51%, respectively. The simulation was conducted with average flow conditions, and this information will be important in planning for management during periods of drought, as well as times of more normal precipitation; as water uses must be balanced with the needs of the existing ecosystem. Alternatives, such as low conductivity blocks between stream channels and different volumetric and geographic pumping scenarios may also be readily explored in an AEM. Exporting these scenarios into MODFLOW simulations will enable us to evaluate transient and cyclical pumping effects on the surface waters for each AEM conceptualization, as well as being able to simulate seasonal recharge. However, in many cases the use of MODFLOW may not be necessary, if the AEM proves sufficient to answer the relevant questions. Symbiotic use of GFLOW and MODFLOW will be an invaluable aid in evaluating groundwater and its uses in National Forest watersheds, especially in cases when time is a critical factor in informed decision-making.

  6. The production and exportation of artemisinin-derived drugs in China: current status and existing challenges.

    PubMed

    Huang, Yangmu; Li, Hui; Peng, Danlu; Wang, Yu; Ren, Qiaomeng; Guo, Yan

    2016-07-15

    As the discoverer and a major manufacturer of artemisinin, China has made valuable contributions to malaria control and the global market of artemisinin-derived drugs. This study aims to explore the production and export status of artemisinin-derived drugs in China during 2011 and 2014 to provide a clear understanding of China's participation in this field and also to provide guidance for its future role on global malaria control. Production and exportation data were obtained from the Ministry of Industry and Information Technology (MIIT) database of the People's Republic China and monthly reports of the General Administration of Customs of China, respectively. The production volume, export volume, export value, and export area of artemisinin and its derivatives (artemether, artesunate, dihydroartemisinin), including both active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs), were descripted and analysed by Microsoft Excel. Between 2011 and 2013, the total production volume of artemisinin-derived APIs and FPPs reached 543.41 metric tons (MT) and 14.79 MT, respectively. The total export value and volume of artemisinin-derived APIs during 2012 and 2014 was US$ 211.39 million and 338.53 MT; the total export value and volume of FPPs was US$ 227.17 million and 4401.44 MT. Compared with the sharply decreasing trend of API exports each year, the export value of FPPs kept at a more stable level, with 14.66 % increase in 2013 and 5.31 % decrease in 2014. As for exportation areas, India was the largest purchaser of APIs, accounting for nearly a half of the total amount, while FPPs mainly exported to African countries. Exports of artemisinin derivatives for China have been transforming from API-dominated to FPP-dominated. However, the exportation of artemisinin-derived drugs in China still face the challenges of small market share in the global FPP market and indirect sale of FPPs through a third country due to the deficiency in obtaining relevant certification into global market.

  7. Structural basis of RND-type multidrug exporters

    PubMed Central

    Yamaguchi, Akihito; Nakashima, Ryosuke; Sakurai, Keisuke

    2015-01-01

    Bacterial multidrug exporters are intrinsic membrane transporters that act as cellular self-defense mechanism. The most notable characteristics of multidrug exporters is that they export a wide range of drugs and toxic compounds. The overexpression of these exporters causes multidrug resistance. Multidrug-resistant pathogens have become a serious problem in modern chemotherapy. Over the past decade, investigations into the structure of bacterial multidrug exporters have revealed the multidrug recognition and export mechanisms. In this review, we primarily discuss RND-type multidrug exporters particularly AcrAB-TolC, major drug exporter in Gram-negative bacteria. RND-type drug exporters are tripartite complexes comprising a cell membrane transporter, an outer membrane channel and an adaptor protein. Cell membrane transporters and outer membrane channels are homo-trimers; however, there is no consensus on the number of adaptor proteins in these tripartite complexes. The three monomers of a cell membrane transporter have varying conformations (access, binding, and extrusion) during transport. Drugs are exported following an ordered conformational change in these three monomers, through a functional rotation mechanism coupled with the proton relay cycle in ion pairs, which is driven by proton translocation. Multidrug recognition is based on a multisite drug-binding mechanism, in which two voluminous multidrug-binding pockets in cell membrane exporters recognize a wide range of substrates as a result of permutations at numerous binding sites that are specific for the partial structures of substrate molecules. The voluminous multidrug-binding pocket may have numerous binding sites even for a single substrate, suggesting that substrates may move between binding sites during transport, an idea named as multisite-drug-oscillation hypothesis. This hypothesis is consistent with the apparently broad substrate specificity of cell membrane exporters and their highly efficient ejection of drugs from the cell. Substrates are transported through dual multidrug-binding pockets via the peristaltic motion of the substrate translocation channel. Although there are no clinically available inhibitors of bacterial multidrug exporters, efforts to develop inhibitors based on structural information are underway. PMID:25941524

  8. Structural basis of RND-type multidrug exporters.

    PubMed

    Yamaguchi, Akihito; Nakashima, Ryosuke; Sakurai, Keisuke

    2015-01-01

    Bacterial multidrug exporters are intrinsic membrane transporters that act as cellular self-defense mechanism. The most notable characteristics of multidrug exporters is that they export a wide range of drugs and toxic compounds. The overexpression of these exporters causes multidrug resistance. Multidrug-resistant pathogens have become a serious problem in modern chemotherapy. Over the past decade, investigations into the structure of bacterial multidrug exporters have revealed the multidrug recognition and export mechanisms. In this review, we primarily discuss RND-type multidrug exporters particularly AcrAB-TolC, major drug exporter in Gram-negative bacteria. RND-type drug exporters are tripartite complexes comprising a cell membrane transporter, an outer membrane channel and an adaptor protein. Cell membrane transporters and outer membrane channels are homo-trimers; however, there is no consensus on the number of adaptor proteins in these tripartite complexes. The three monomers of a cell membrane transporter have varying conformations (access, binding, and extrusion) during transport. Drugs are exported following an ordered conformational change in these three monomers, through a functional rotation mechanism coupled with the proton relay cycle in ion pairs, which is driven by proton translocation. Multidrug recognition is based on a multisite drug-binding mechanism, in which two voluminous multidrug-binding pockets in cell membrane exporters recognize a wide range of substrates as a result of permutations at numerous binding sites that are specific for the partial structures of substrate molecules. The voluminous multidrug-binding pocket may have numerous binding sites even for a single substrate, suggesting that substrates may move between binding sites during transport, an idea named as multisite-drug-oscillation hypothesis. This hypothesis is consistent with the apparently broad substrate specificity of cell membrane exporters and their highly efficient ejection of drugs from the cell. Substrates are transported through dual multidrug-binding pockets via the peristaltic motion of the substrate translocation channel. Although there are no clinically available inhibitors of bacterial multidrug exporters, efforts to develop inhibitors based on structural information are underway.

  9. 7 CFR 1218.6 - Exporter.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.6 Exporter. Exporter means a person involved in exporting blueberries from another country to the United States. ...

  10. 7 CFR 1218.6 - Exporter.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.6 Exporter. Exporter means a person involved in exporting blueberries from another country to the United States. ...

  11. 7 CFR 1218.6 - Exporter.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.6 Exporter. Exporter means a person involved in exporting blueberries from another country to the United States. ...

  12. 7 CFR 1218.6 - Exporter.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.6 Exporter. Exporter means a person involved in exporting blueberries from another country to the United States. ...

  13. 7 CFR 1218.6 - Exporter.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE BLUEBERRY PROMOTION, RESEARCH, AND INFORMATION ORDER Blueberry Promotion, Research, and Information Order Definitions § 1218.6 Exporter. Exporter means a person involved in exporting blueberries from another country to the United States. ...

  14. 77 FR 72324 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application No. 85-17A18] Export Trade Certificate of Review ACTION: Notice of Application to Amend the Export Trade Certificate of Review Issued to... to amend an Export [[Page 72325

  15. 50 CFR 14.92 - What are the exemptions to the import/export license requirement?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS IMPORTATION, EXPORTATION, AND TRANSPORTATION OF WILDLIFE... subchapter and that are for export only; and (3) Live aquatic invertebrates of the Class Pelecypoda, commonly...

  16. 26 CFR 1.993-1 - Definition of qualified export receipts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Gross receipts. The term “gross receipts” is defined by section 993(f) and § 1.993-6. (4) Qualified export assets. The term “qualified export assests” is defined by section 993(b) and § 1.993-2. (5) Export property. The term “export property” is defined by section 993(c) and § 1.993-3. (6) Related person. The...

  17. 15 CFR 754.5 - Horses for export by sea.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Horses for export by sea. 754.5... CONTROLS § 754.5 Horses for export by sea. (a) License requirement. As indicated by the letters “SS” in the... No. 1 to part 774 of the EAR) a license is required for the export of horses exported by sea to all...

  18. 15 CFR 754.5 - Horses for export by sea.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Horses for export by sea. 754.5... CONTROLS § 754.5 Horses for export by sea. (a) License requirement. As indicated by the letters “SS” in the... No. 1 to part 774 of the EAR) a license is required for the export of horses exported by sea to all...

  19. 15 CFR 754.5 - Horses for export by sea.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Horses for export by sea. 754.5... CONTROLS § 754.5 Horses for export by sea. (a) License requirement. As indicated by the letters “SS” in the... No. 1 to part 774 of the EAR) a license is required for the export of horses exported by sea to all...

  20. 15 CFR 754.5 - Horses for export by sea.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Horses for export by sea. 754.5... CONTROLS § 754.5 Horses for export by sea. (a) License requirement. As indicated by the letters “SS” in the... No. 1 to part 774 of the EAR) a license is required for the export of horses exported by sea to all...

  1. 15 CFR 754.5 - Horses for export by sea.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Horses for export by sea. 754.5... CONTROLS § 754.5 Horses for export by sea. (a) License requirement. As indicated by the letters “SS” in the... No. 1 to part 774 of the EAR) a license is required for the export of horses exported by sea to all...

  2. Agencies Should Assess Vulnerabilities and Improve Guidance for Protecting Export-Controlled Information at Companies

    DTIC Science & Technology

    2006-12-01

    Supplement DOD Department of Defense DOL Department of Labor DTSA Defense Technology Security Administration EAR Export Administration Regulations...and outreach to companies on the export regulations. DOD: The Defense Technology Security Administration ( DTSA ) represents DOD on export control...and technologies, which DOD oversees. DTSA serves an advisory role in State’s and Commerce’s export license review processes and offers technical

  3. Sharing the load: Mex67–Mtr2 cofunctions with Los1 in primary tRNA nuclear export

    PubMed Central

    Chatterjee, Kunal; Majumder, Shubhra; Wan, Yao; Shah, Vijay; Wu, Jingyan; Huang, Hsiao-Yun

    2017-01-01

    Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcribed intron-containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms. As tRNA nuclear export is essential, we previously interrogated the budding yeast proteome to identify candidates that function in tRNA nuclear export. Here, we provide molecular, genetic, cytological, and biochemical evidence that the Mex67–Mtr2 (TAP–p15) heterodimer, best characterized for its essential role in mRNA nuclear export, cofunctions with Los1 in tRNA nuclear export. Inactivation of Mex67 or Mtr2 leads to rapid accumulation of end-matured unspliced tRNAs in the nucleus. Remarkably, merely fivefold overexpression of Mex67–Mtr2 can substitute for Los1 in los1Δ cells. Moreover, in vivo coimmunoprecipitation assays with tagged Mex67 document that the Mex67 binds tRNAs. Our data also show that tRNA exporters surprisingly exhibit differential tRNA substrate preferences. The existence of multiple tRNA exporters, each with different tRNA preferences, may indicate that the proteome can be regulated by tRNA nuclear export. Thus, our data show that Mex67–Mtr2 functions in primary nuclear export for a subset of yeast tRNAs. PMID:29212662

  4. Sharing the load: Mex67-Mtr2 cofunctions with Los1 in primary tRNA nuclear export.

    PubMed

    Chatterjee, Kunal; Majumder, Shubhra; Wan, Yao; Shah, Vijay; Wu, Jingyan; Huang, Hsiao-Yun; Hopper, Anita K

    2017-11-01

    Eukaryotic transfer RNAs (tRNAs) are exported from the nucleus, their site of synthesis, to the cytoplasm, their site of function for protein synthesis. The evolutionarily conserved β-importin family member Los1 (Exportin-t) has been the only exporter known to execute nuclear export of newly transcribed intron-containing pre-tRNAs. Interestingly, LOS1 is unessential in all tested organisms. As tRNA nuclear export is essential, we previously interrogated the budding yeast proteome to identify candidates that function in tRNA nuclear export. Here, we provide molecular, genetic, cytological, and biochemical evidence that the Mex67-Mtr2 (TAP-p15) heterodimer, best characterized for its essential role in mRNA nuclear export, cofunctions with Los1 in tRNA nuclear export. Inactivation of Mex67 or Mtr2 leads to rapid accumulation of end-matured unspliced tRNAs in the nucleus. Remarkably, merely fivefold overexpression of Mex67-Mtr2 can substitute for Los1 in los1 Δ cells. Moreover, in vivo coimmunoprecipitation assays with tagged Mex67 document that the Mex67 binds tRNAs. Our data also show that tRNA exporters surprisingly exhibit differential tRNA substrate preferences. The existence of multiple tRNA exporters, each with different tRNA preferences, may indicate that the proteome can be regulated by tRNA nuclear export. Thus, our data show that Mex67-Mtr2 functions in primary nuclear export for a subset of yeast tRNAs. © 2017 Chatterjee et al.; Published by Cold Spring Harbor Laboratory Press.

  5. A plasma membrane-type Ca[sup 2+]-ATPase of 120 kilodaltons on the endoplasmic reticulum from carrot (Daucus carota) cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, F.H.; Ratterman, D.M.; Sze, H.

    1993-06-01

    Cytosolic Ca[sup 2+] levels are regulated in part by Ca[sup 2+]-pumping ATPases that export Ca[sup 2+] from the cytoplasm; The types and properties of Ca[sup 2+] pumps in plants are not well understood. The kinetic properties of a 120-kD phosphoenzyme (PE) intermediate formed during the reaction cycle of a Ca[sup 2+]-ATPase from suspension-cultured carrot (Daucus carota) cells are characterized. Only one Ca[sup 2+]-dependent phosphoprotein was formed when carrot membrane vesicles were incubated with [[gamma]-[sup 32]P]ATP. Formation of this 120-kD phosphoprotein was inhibited by vanadate, enhanced by La[sup 3+], and decreased by hydroxylamine, confirming its identification as an intermediate of amore » phosphorylated-type Ca[sup 2+]-translocating ATPase. The 120-kD Ca[sup 2+]-ATPase was most abundant in endoplasmic reticulum-enriched fractions, in which the Ca[sup 2+]-ATPase was estimated to be 0.1% of membrane protein. Direct quantitation of Ca[sup 2+]-dependent phosphoprotein was used to examine the kinetics of PE formation. PE formation exhibited a K[sub m] for Ca[sup 2+] of 1 to 2 [mu]m and a K[sub m] for ATP of 67 nm. Relative affinities of substrates, determined by competition experiments, were 0.075 [mu]m for ATP, 1 [mu]m for ADP, 100 [mu]m for ITP, and 250 [mu]m for GTP. Thapsigargin and cyclopiazonic acid, specific inhibitors of animal sarcoplasmic/endoplasmic reticulum Ca[sup 2+]-ATPase, had no effect on PE formation; erythrosin B inhibited with 50% inhibition at <0.1 [mu]m. Calmodulin (1 [mu]m) stimulated PE formation by 25%. The results indicate that the carrot 120-kD Ca[sup 2+]-ATPase is similar but not identical to animal plasma membrane-type Ca[sup 2+]-ATPase and yet is located on endomembranes, such as the endoplasmic reticulum. This type of Ca[sup 2+] pump may reside on the cortical endoplasmic reticulum, thought to play a major role in anchoring the cytoskeleton and in facilitating secretion. 34 refs., 9 figs., 3 tabs.« less

  6. Carbon Sinks in a Changing Climate: Relative Buoyancy and Sinking Potentials of Various Antarctic Phytoplankton and Ice Algae

    NASA Astrophysics Data System (ADS)

    Nirmel, S.; Selz, V.

    2016-12-01

    Polar phytoplankton play instrumental roles in global biogeochemical cycles, sometimes serving as massive carbon sinks via the biological pump. In addition to phytoplankton, sea ice supports a significant amount of ice algae, the essential primary producers for the ecosystem in winter and early spring. While sea ice habitat declines on regional scales, the fate of sea ice algae post-ice melt remains relatively unknown, despite its importance in understanding how the biological pump might be affected by sea ice loss. Through a series of settling column experiments on the icebreaker Nathaniel B. Palmer, we aimed to address the question: What controls the fate of the carbon-rich ice algae across the Western Antarctic Peninsula (WAP) during ice melt? We focused on whether species composition affects the sinking potential of ice algal communities. Using FlowCAM imagery, we classified samples collected from the buoyant, neutral, and negatively buoyant portions of the settling columns into genus-level taxonomic classes. We used image parameters and geometric shape equations to calculate the biovolume of each taxonomic group. We further explored relationships between taxa-specific sinking potentials, environmental parameters (temperature and nutrients), and physiological properties of associated algal communities (as described by Fast Rate Repetition fluorometry). Results indicate that colonial Phaeocystis antarctica tends to dominate lower regions of the settling column. Moreover, we observe strong correlations between geographic location and both nutrients and phytoplankton physiology. We found that these three factors are indeed related to taxa-specific buoyancy and sinking indices. An understanding of these relationships sheds more light on the role P. antarctica (a carbon-rich bloom-forming genus) plays in the biological pump; higher sinking rates suggest greater carbon export to depth, while lower sinking rates increase the likelihood of carbon being respired back into the environment by heterotrophs at the surface. This study advances our knowledge on the roles sea ice algae and phytoplankton play in biogeochemical cycles and offers a glimpse into how such cycles may function in a changing climate.

  7. 14 CFR 21.269 - Export airworthiness approvals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Export airworthiness approvals. 21.269 Section 21.269 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION....269 Export airworthiness approvals. The manufacturer may issue export airworthiness approvals. ...

  8. 77 FR 61740 - Call for Applications for the International Buyer Program-Calendar Years 2014 and 2015

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-11

    ..., providing export counseling to exhibitors, and providing export counseling and matchmaking services at the...-on assistance such as export counseling and market analysis to U.S. companies interested in exporting...

  9. 78 FR 54238 - President's Export Council; Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-03

    ... DEPARTMENT OF COMMERCE International Trade Administration President's Export Council; Meeting... meeting. SUMMARY: The President's Export Council will hold a meeting to deliberate on recommendations related to promoting the expansion of U.S. exports. Topics may include trade promotion authority...

  10. 14 CFR 21.269 - Export airworthiness approvals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Export airworthiness approvals. 21.269 Section 21.269 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION....269 Export airworthiness approvals. The manufacturer may issue export airworthiness approvals. ...

  11. IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs

    PubMed Central

    Yu, Minjia; Qian, Wen; Wang, Han; Zhou, Gao; Chen, Xing; Yang, Hui; Hong, Lingzi; Zhao, Junjie; Qin, Luke; Fukuda, Koichi; Flotho, Annette; Gao, Ji; Dongre, Ashok; Carman, Julie A; Kang, Zizhen; Su, Bing; Kern, Timothy S; Smith, Jonathan D; Hamilton, Thomas A; Melchior, Frauke; Fox, Paul L

    2017-01-01

    Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation. PMID:28990926

  12. A non-canonical mechanism for Crm1-export cargo complex assembly.

    PubMed

    Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Faza, Marius Boulos; Panse, Vikram Govind

    2015-04-21

    The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export.

  13. IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs.

    PubMed

    Zhou, Hao; Bulek, Katarzyna; Li, Xiao; Herjan, Tomasz; Yu, Minjia; Qian, Wen; Wang, Han; Zhou, Gao; Chen, Xing; Yang, Hui; Hong, Lingzi; Zhao, Junjie; Qin, Luke; Fukuda, Koichi; Flotho, Annette; Gao, Ji; Dongre, Ashok; Carman, Julie A; Kang, Zizhen; Su, Bing; Kern, Timothy S; Smith, Jonathan D; Hamilton, Thomas A; Melchior, Frauke; Fox, Paul L; Li, Xiaoxia

    2017-10-09

    Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation.

  14. Influence of export control policy on the competitiveness of machine tool producing organizations

    NASA Astrophysics Data System (ADS)

    Ahrstrom, Jeffrey D.

    The possible influence of export control policies on producers of export controlled machine tools is examined in this quantitative study. International market competitiveness theories hold that market controlling policies such as export control regulations may influence an organization's ability to compete (Burris, 2010). Differences in domestic application of export control policy on machine tool exports may impose throttling effects on the competitiveness of participating firms (Freedenberg, 2010). Commodity shipments from Japan, Germany, and the United States to the Russian market will be examined using descriptive statistics; gravity modeling of these specific markets provides a foundation for comparison to actual shipment data; and industry participant responses to a user developed survey will provide additional data for analysis using a Kruskal-Wallis one-way analysis of variance. There is scarce academic research data on the topic of export control effects within the machine tool industry. Research results may be of interest to industry leadership in market participation decisions, advocacy arguments, and strategic planning. Industry advocates and export policy decision makers could find data of interest in supporting positions for or against modifications of export control policies.

  15. 40 CFR 168.71 - Export pesticide devices.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Export pesticide devices. 168.71 Section 168.71 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS STATEMENTS OF ENFORCEMENT POLICIES AND INTERPRETATIONS Export Policy and Procedures for Exporting Pesticides...

  16. 40 CFR 168.71 - Export pesticide devices.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Export pesticide devices. 168.71 Section 168.71 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS STATEMENTS OF ENFORCEMENT POLICIES AND INTERPRETATIONS Export Policy and Procedures for Exporting Pesticides...

  17. 75 FR 44761 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-29

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application 10-00004] Export Trade Certificate of Review ACTION: Notice of Application for an Export Trade Certificate of Review From Canned Wild Salmon Export Council, LLC (``CWSEC''). SUMMARY: The Office of Competition and Economic Analysis...

  18. 78 FR 60250 - Order Denying Export Privileges

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... DEPARTMENT OF COMMERCE Bureau of Industry and Security Order Denying Export Privileges In the... knowingly and willfully causing and attempting to cause the export of digital microwave radios to Iran.... Section 766.25 of the Export Administration Regulations (``EAR'' or [[Page 60251

  19. 77 FR 37385 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-21

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application 12-00004] Export Trade Certificate of Review ACTION: Notice of Application for an Export Trade Certificate of Review Colombia Poultry Export Quota, Inc. (COLOM-PEQ). SUMMARY: The Office of Competition and Economic Analysis, International...

  20. 75 FR 8040 - Export Trade Certificate of Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-23

    ... DEPARTMENT OF COMMERCE International Trade Administration [Application 10-00001] Export Trade Certificate of Review ACTION: Notice of Application for an Export Trade Certificate of Review from Alaska Longline Cod Commission (``ALCC'') SUMMARY: The Export Trading Company Affairs (``ETCA'') unit, Office of...

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