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Sample records for pyochelin-iron uptake pathway

  1. Pathways of arsenic uptake and efflux.

    Science.gov (United States)

    Yang, Hung-Chi; Fu, Hsueh-Liang; Lin, Yung-Feng; Rosen, Barry P

    2012-01-01

    Arsenic is the most prevalent environmental toxic substance and ranks first on the U.S. Environmental Protection Agency's Superfund List. Arsenic is a carcinogen and a causative agent of numerous human diseases. Paradoxically arsenic is used as a chemotherapeutic agent for treatment of acute promyelocytic leukemia. Inorganic arsenic has two biological important oxidation states: As(V) (arsenate) and As(III) (arsenite). Arsenic uptake is adventitious because the arsenate and arsenite are chemically similar to required nutrients. Arsenate resembles phosphate and is a competitive inhibitor of many phosphate-utilizing enzymes. Arsenate is taken up by phosphate transport systems. In contrast, at physiological pH, the form of arsenite is As(OH)(3), which resembles organic molecules such as glycerol. Consequently, arsenite is taken into cells by aquaglyceroporin channels. Arsenic efflux systems are found in nearly every organism and evolved to rid cells of this toxic metalloid. These efflux systems include members of the multidrug resistance protein family and the bacterial exchangers Acr3 and ArsB. ArsB can also be a subunit of the ArsAB As(III)-translocating ATPase, an ATP-driven efflux pump. The ArsD metallochaperone binds cytosolic As(III) and transfers it to the ArsA subunit of the efflux pump. Knowledge of the pathways and transporters for arsenic uptake and efflux is essential for understanding its toxicity and carcinogenicity and for rational design of cancer chemotherapeutic drugs. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Radiolabeling as a tool to study uptake pathways in plants

    Energy Technology Data Exchange (ETDEWEB)

    Schymura, Stefan; Hildebrand, Heike; Franke, Karsten [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Reactive Transport; Fricke, T. [Vita34 BioPlanta, Leipzig (Germany)

    2017-06-01

    The identification of major uptake pathways in plants is an important factor when evaluation the fate of manufactured nanoparticles in the environment and the associated risks. Using different radiolabeling techniques we were able to show a predominantly particulate uptake for CeO{sub 2} nanoparticles (NPs) in contrast to a possible uptake in the form of ionic cerium.

  3. Comparative Studies on Uptake Pathway of Cadmium by Perna viridis

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Experiments were designed to expose the filter-feeding bivalve Perna viridis to different Cd-contaminated water environments in order to compare the different pathways through which Cd is accumulated. Results show that mussels can accumulate Cd through seawater, food, sediment and suspended particle pathways in a short period of time. Mussels uptake of Cd through the seawater pathway reaches the highest concentration approximately 3 and 9 times larger than through the algae and sediment pathways respectively after 7 d. This indicates that the Cd-accumulation through seawater is most efficient. Results also indicate that the uptake directly through contaminated algae, particles or sediments ingested by mussels is less important when compared with the uptake of Cd by mussels through the seawater pathway. Metal uptake pathways and mechanisms of bioaccumulation by marine bivalve are also discussed in this paper.

  4. Comparative studies on uptake pathway of cadmium by Perna viridis

    Science.gov (United States)

    Zhanqiang, Fang

    2006-01-01

    Experiments were designed to expose the filter-feeding bivalve Perna viridis to different Cd-contaminated water environments in order to compare the different pathways through which Cd is accumulated. Results show that mussels can accumulate Cd through seawater, food, sediment and suspended particle pathways in a short period of time. Mussels' uptake of Cd through the seawater pathway reaches the highest concentration approximately 3 and 9 times larger than through the algae and sediment pathways respectively after 7 d. This indicates that the Cd-accumulation through seawater is most efficient. Results also indicate that the uptake directly through contaminated algae, particles or sediments ingested by mussels is less important when compared with the uptake of Cd by mussels through the seawater pathway. Metal uptake pathways and mechanisms of bioaccumulation by marine bivalve are also discussed in this paper.

  5. [Pathways of arsenic uptake in prokaryotic and eukaryotic cells].

    Science.gov (United States)

    Lis, Paweł; Litwin, Ireneusz; Maciaszczyk-Dziubińska, Ewa

    2010-01-01

    Mechanisms of arsenic uptake and detoxification are present in all studied organisms. These mechanisms are considerably well described in unicellular organisms such as bacterium Escherichia coli and baker's yeast Saccharomyces cerevisiae, still leaving much to be revealed in multicellular organisms. Full identification of arsenic uptake and detoxification is of great importance. This knowledge can be very helpful in improving effectiveness of arsenic-containing drugs used in chemotherapy of parasitoses as well as in treatment of acute promielyocytic leukemia. Increased proficiency of bioremediation of arsenic-contaminated soils can be obtained by using plants hyperaccumulating arsenic. This kind of plants can be engineered by modulating expression levels of genes encoding arsenic transporters. The same technique may be used to decrease levels of accumulated arsenic in crops. The aim of this paper is to review current knowledge about systems of arsenic uptake in every studied organism--from bacteria to human.

  6. Uptake of chemicals from indoor air: Pathways and health effects

    DEFF Research Database (Denmark)

    Bekö, Gabriel

    2016-01-01

    Building occupants are exposed to manufactured chemicals. Exposure in the indoor environment can occur via non-dietary ingestion (e.g. indoor dust), inhalation and dermal absorption including dermal uptake directly from air. The extent of dermal uptake from air has been previously studied...... intake from inhalation. Further experiments have been conducted with nicotine and the results are similar. Some of the SVOCs present indoors may have adverse health effects or are categorized as potential endocrine-disrupting compounds. It has been suggested that the health effects of a chemical may...

  7. Cellular uptake and intracellular pathways of PLL-g-PEG-DNA nanoparticles.

    Science.gov (United States)

    Lühmann, Tessa; Rimann, Markus; Bittermann, Anne Greet; Hall, Heike

    2008-09-01

    Polycationic molecules form condensates with DNA and are used for gene therapy as an alternative to viral vectors. As clinical efficacy corresponds to cellular uptake, intracellular stability of the condensates, and bioavailability of the DNA, it is crucial to analyze uptake mechanisms and trafficking pathways. Here, a detailed study of uptake, stability, and localization of PLL-g-PEG-DNA nanoparticles within COS-7 cells is presented, using FACS analysis to assess the involvement of different uptake mechanisms, colocalization studies with markers indicative for different endocytotic pathways, and immunofluorescence staining to analyze colocalization with intracellular compartments. PLL-g-PEG-DNA nanoparticles were internalized in an energy-dependent manner after 2 h and accumulated in the perinuclear region after >6 h. The nanoparticles were found to be stable within the cytoplasm for at least 24 h and did not colocalize with the endosomal pathway. Nanoparticle uptake was approximately 50% inhibited by genistein, an inhibitor of the caveolae-mediated pathway. However, genistein did not inhibit gene expression, and PLL-g-PEG-DNA nanoparticles were not colocalized with caveolin-1 indicating that caveolae-mediated endocytosis is not decisive for DNA delivery. Clathrin-mediated endocytosis and macropinocytosis pathways were reduced by 17 and 24%, respectively, in the presence of the respective inhibitors. When cells were transfected in the presence of double and triple inhibitors, transfection efficiencies were increasingly reduced by 40 and 70%, respectively; however, no differences were found between the different uptake mechanisms. These findings suggest that PLL-g-PEG-DNA nanoparticles enter by several pathways and might therefore be an efficient and versatile tool to deliver therapeutic DNA.

  8. Pathways of trace metal uptake in the lugworm Arenicola marina

    Energy Technology Data Exchange (ETDEWEB)

    Casado-Martinez, M.C. [Department of Zoology, Natural History Museum, Cromwell Road, London SW7 5BD (United Kingdom)], E-mail: c.casado-martinez@nhm.ac.uk; Smith, B.D. [Department of Zoology, Natural History Museum, Cromwell Road, London SW7 5BD (United Kingdom); Valls, T.A. del [Unesco UNITWIN Wicop Chair, Department of Physical-Chemistry, University of Cadiz, Poligono Industrial Rio San Pedro s/n, C.P. 11510 Puerto Real, Cadiz (Spain); Rainbow, P.S. [Department of Zoology, Natural History Museum, Cromwell Road, London SW7 5BD (United Kingdom)

    2009-04-02

    Radiotracer techniques were used to determine the rates of trace metal (Ag, Cd and Zn) uptake and elimination (33 psu, 10 deg. C) from water and sediment by the deposit-feeding polychaete Arenicola marina, proposed as a test species for estuarine-marine sediments in whole-sediment toxicity tests. Metal uptake rates from solution increase with increasing dissolved metal concentrations, with uptake rate constants ({+-} SE) (l g{sup -1} d{sup -1}) of 1.21 {+-} 0.11 (Ag), 0.026 {+-} 0.002 (Zn) and 0.012 {+-} 0.001 (Cd). Assimilation efficiencies from ingested sediments were measured using a pulse-chase radiotracer feeding technique in two different lugworm populations, one from a commercial supplier (Blyth, Northumberland, UK) and the other a field-collected population from the outer Thames estuary (UK). Assimilation efficiencies ranged from 2 to 20% for Zn, 1 to 6% for Cd and 1 to 9% for Ag for the Northumberland worms, and from 3 to 22% for Zn, 6 to 70% for Cd and 2 to 15% for Ag in the case of the Thames population. Elimination of accumulated metals followed a two-compartment model, with similar efflux rate constants for Zn and Ag and lower rates of elimination of Cd from the slow pool. Efflux rate constants ({+-} SE) of Zn and Ag accumulated from the dissolved phase were 0.037 {+-} 0.002 and 0.033 {+-} 0.006 d{sup -1} whereas Cd was eliminated with an efflux rate constant one order of magnitude lower (0.003 {+-} 0.002 d{sup -1}). When metals were accumulated from ingested sediments, the efflux rate constants for the slow-exchanging compartment were of the same order of magnitude for the three metals, and of the same order of magnitude as those derived after the dissolved exposure for Zn and Ag (0.042 {+-} 0.004 and 0.056 {+-} 0.012 d{sup -1} for Zn and 0.044 {+-} 0.012 and 0.069 {+-} 0.016 d{sup -1} for Ag for the Northumberland and Thames populations, respectively). Cd accumulated from ingested sediments was eliminated with a rate constant not different from the

  9. Dynamin like protein 1 participated in the hemoglobin uptake pathway of Plasmodium falciparum

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hong-chang; GAO Yu-hui; ZHONG Xiang; WANG Heng

    2009-01-01

    Background During the blood stage of malaria infection, parasites internalize in the host red blood cells and degrade massive amounts of hemoglobin for their development. Although the morphology of the parasite's hemoglobin uptake pathway has been clearly observed, little has been known about its molecular mechanisms. Methods The recombinant proteins from Plasmodium falciparum, dynamin like protein 1 (PfDYN1) and 2 (PfDYN2) GTPase domain, were expressed in E .coli and showed GTPase activity. By using a dynamin inhibitor, dynasore, we demonstrated the involvement of PfDYN1 in the hemoglobin uptake pathway. Results The GTPase activity of the two recombinant proteins was inhibited by dynasore in vitro. Treatment of parasite cultures with 80 μmol/L dynasore at the ring and early trophozoite stage resulted in substantial inhibition of parasite growth and in an obvious decline of hemoglobin quantum. Furthermore, reduced intraceliular hemozoin accumulation and decreased uptake of the FITC-dextran were also observed, together with distinctive changes in the ultrastructure of parasites after the dynasore treatment. Conclusions Our results show that PfDYN1 plays an important role in the hemoglobin uptake pathway of P. Falciparum and suggest its possibility of being a novel target for malaria chemotherapy.

  10. The minute virus of mice exploits different endocytic pathways for cellular uptake

    Energy Technology Data Exchange (ETDEWEB)

    Garcin, Pierre O.; Panté, Nelly, E-mail: pante@zoology.ubc.ca

    2015-08-15

    The minute virus of mice, prototype strain (MVMp), is a non-enveloped, single-stranded DNA virus of the family Parvoviridae. Unlike other parvoviruses, the mechanism of cellular uptake of MVMp has not been studied in detail. We analyzed MVMp endocytosis in mouse LA9 fibroblasts and a tumor cell line derived from epithelial–mesenchymal transition through polyomavirus middle T antigen transformation in transgenic mice. By a combination of immunofluorescence and electron microscopy, we found that MVMp endocytosis occurs at the leading edge of migrating cells in proximity to focal adhesion sites. By using drug inhibitors of various endocytic pathways together with immunofluorescence microscopy and flow cytometry analysis, we discovered that MVMp can use a number of endocytic pathways, depending on the host cell type. At least three different mechanisms were identified: clathrin-, caveolin-, and clathrin-independent carrier-mediated endocytosis, with the latter occurring in transformed cells but not in LA9 fibroblasts. - Highlights: • MVMp uptake takes place at the leading edge of migrating cells. • MVMp exploits a variety of endocytic pathways. • MVMp could use clathrin- and caveolin-mediated endocytosis. • MVMp could also use clathrin-independent carriers for cellular uptake.

  11. Biocompatibility, uptake and endocytosis pathways of polystyrene nanoparticles in primary human renal epithelial cells.

    Science.gov (United States)

    Monti, Daria Maria; Guarnieri, Daniela; Napolitano, Giuliana; Piccoli, Renata; Netti, Paolo; Fusco, Sabato; Arciello, Angela

    2015-01-10

    Recent years have witnessed an unprecedented growth in the number of applications—such as drug delivery, nutraceuticals and production of improved biocompatible materials—in the areas of nanoscience and nanotechnology. Engineered nanoparticles (NPs) are an important tool for the development of quite a few of these applications. Despite intense research activity, mechanisms regulating the uptake of NPs into cells are not completely defined, being the phenomenon dramatically influenced by physico-chemical properties of NPs and cell-specific differences. Since the cellular uptake of NPs is a prerequisite for their use in nanomedicine, the definition of their internalization pathway is crucial. For this reason, we used 44 nm polystyrene NPs as a model to analyze the uptake and endocytosis pathways in primary human renal cortical epithelial (HRCE) cells, which play a key role in the clearance of drugs. NPs were found not to affect the viability and cell cycle progression of HRCE cells. Distinct internalization pathways were analyzed by the use of drugs known to inhibit specific endocytosis routes. Analyses, performed by confocal microscopy in combination with quantitative spectrofluorimetric assays, indicated that NPs enter HRCE cells through multiple mechanisms, either energy-dependent (endocytosis) or energy-independent.

  12. Nitrogen uptake and regeneration pathways in the equatorial Pacific: a basin scale modeling study

    Directory of Open Access Journals (Sweden)

    X. Wang

    2009-08-01

    Full Text Available It is well known that most primary production is fueled by regenerated nitrogen in the open ocean. Therefore, studying the nitrogen cycle by focusing on uptake and regeneration pathways would advance our understanding of nitrogen dynamics in the marine ecosystem. Here, we carry out a basin-scale modeling study, by assessing model simulations of nitrate and ammonium, and rates of nitrate uptake, ammonium uptake and regeneration in the equatorial Pacific. Model-data comparisons show that the model is able to reproduce many observed features of nitrate, ammonium, such as the deep ammonium maximum (DAM. The model also reproduces the observed de-coupling of ammonium uptake and regeneration, i.e. regeneration rate greater than uptake rate in the lower euphotic zone. The de-coupling largely explains the observed DAM in the equatorial Pacific Ocean. Our study indicates that zooplankton excretion and remineralization of organic nitrogen play a different role in nitrogen regeneration. Rates of zooplankton excretion vary from <0.01 mmol m−3 d−1 to 0.1 mmol m−3 d−1 in the upper euphotic zone while rates of remineralization fall within a narrow range (0.015–0.025 mmol m−3 d−1. Zooplankton excretion contributes up to 70% of total ammonium regeneration in the euphotic zone, and is largely responsible for the spatial variability of nitrogen regeneration. However, remineralization provides a steady supply of ammonium in the upper ocean, and is a major source of inorganic nitrogen for the oligotrophic regions. Overall, ammonium generation and removal are approximately balanced over the top 150 m in the equatorial Pacific.

  13. Nitrogen uptake and regeneration pathways in the equatorial Pacific: a basin scale modeling study

    Directory of Open Access Journals (Sweden)

    R. Le Borgne

    2009-11-01

    Full Text Available It is well known that most primary production is fueled by regenerated nitrogen in the open ocean. Therefore, studying the nitrogen cycle by focusing on uptake and regeneration pathways would advance our understanding of nitrogen dynamics in the marine ecosystem. Here, we carry out a basin-scale modeling study, by assessing model simulations of nitrate and ammonium, and rates of nitrate uptake, ammonium uptake and regeneration in the equatorial Pacific. Model-data comparisons show that the model is able to reproduce many observed features of nitrate, ammonium, such as the deep ammonium maximum (DAM. The model also reproduces the observed de-coupling of ammonium uptake and regeneration, i.e., regeneration rate greater than uptake rate in the lower euphotic zone. The de-coupling largely explains the observed DAM in the equatorial Pacific Ocean. Our study indicates that zooplankton excretion and remineralization of organic nitrogen play a different role in nitrogen regeneration. Rates of zooplankton excretion vary from <0.01 mmol m−3 d−1 to 0.1 mmol m−3 d−1 in the upper euphotic zone while rates of remineralization fall within a narrow range (0.015–0.025 mmol m−3 d−1 . Zooplankton excretion contributes up to 70% of total ammonium regeneration in the euphotic zone, and is largely responsible for the spatial variability of nitrogen regeneration. However, remineralization provides a steady supply of ammonium in the upper ocean, and is a major source of inorganic nitrogen for the oligotrophic regions. Overall, ammonium generation and removal are approximately balanced over the top 150 m in the equatorial Pacific.

  14. Ursolic acid increases glucose uptake through the PI3K signaling pathway in adipocytes.

    Directory of Open Access Journals (Sweden)

    Yonghan He

    Full Text Available BACKGROUND: Ursolic acid (UA, a triterpenoid compound, is reported to have a glucose-lowering effect. However, the mechanisms are not fully understood. Adipose tissue is one of peripheral tissues that collectively control the circulating glucose levels. OBJECTIVE: The objective of the present study was to determine the effect and further the mechanism of action of UA in adipocytes. METHODS AND RESULTS: The 3T3-L1 preadipocytes were induced to differentiate and treated with different concentrations of UA. NBD-fluorescent glucose was used as the tracer to measure glucose uptake and Western blotting used to determine the expression and activity of proteins involved in glucose transport. It was found that 2.5, 5 and 10 µM of UA promoted glucose uptake in a dose-dependent manner (17%, 29% and 35%, respectively. 10 µM UA-induced glucose uptake with insulin stimulation was completely blocked by the phosphatidylinositol (PI 3-kinase (PI3K inhibitor wortmannin (1 µM, but not by SB203580 (10 µM, the inhibitor of mitogen-activated protein kinase (MAPK, or compound C (2.5 µM, the inhibitor of AMP-activated kinase (AMPK inhibitor. Furthermore, the downstream protein activities of the PI3K pathway, phosphoinositide-dependent kinase (PDK and phosphoinositide-dependent serine/threoninekinase (AKT were increased by 10 µM of UA in the presence of insulin. Interestingly, the activity of AS160 and protein kinase C (PKC and the expression of glucose transporter 4 (GLUT4 were stimulated by 10 µM of UA under either the basal or insulin-stimulated status. Moreover, the translocation of GLUT4 from cytoplasm to cell membrane was increased by UA but decreased when the PI3K inhibitor was applied. CONCLUSIONS: Our results suggest that UA stimulates glucose uptake in 3T3-L1 adipocytes through the PI3K pathway, providing important information regarding the mechanism of action of UA for its anti-diabetic effect.

  15. Foliar uptake of radiocaesium from irrigation water by paddy rice (Oryza sativa): an overlooked pathway in contaminated environments.

    Science.gov (United States)

    Uematsu, Shinichiro; Vandenhove, Hildegarde; Sweeck, Lieve; Hees, May Van; Wannijn, Jean; Smolders, Erik

    2017-04-01

    Flooded (paddy) rice (Oryza sativa) can take up ions from the irrigation water by foliar uptake via the exposed stem base. We hypothesised that the stem base uptake of radiocaesium (RCs) is a pathway for rice grown in RCs-contaminated environments. We developed a bi-compartmental device which discriminates the stem base from root RCs uptake from solutions, thereby using RCs isotopes ((137) Cs and (134) Cs) with < 2% solution leak between the compartments. Radiocaesium uptake was linear over time (0-24 h). Radiocaesium uptake to the entire plant, expressed per dry weight of the exposed parts, was sixfold higher for the roots than for the exposed stem base. At equal RCs concentrations in both compartments, the exposed stem base and root uptake contributed almost equally to the total shoot RCs concentrations. Reducing potassium supply to the roots not only increased the root RCs uptake but also increased RCs uptake by the stem base. This study was the first to experimentally demonstrate active and internally regulated RCs uptake by the stem base of rice. Scenario calculations for the Fukushima-affected area predict that RCs in irrigation water could be an important source of RCs in rice as indirectly suggested from field data. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  16. The interplay between P uptake pathways in mycorrhizal peas: a combined physiological and gene‐silencing approach

    DEFF Research Database (Denmark)

    Grønlund, Mette; Albrechtsen, Merete Tryde; Johansen, Ida Elisabeth

    2013-01-01

    Arbuscular mycorrhizal fungi (AMF) have a key role in plant phosphate (Pi) uptake by their efficient capture of soil phosphorus (P) that is transferred to the plant via Pi transporters in the root cortical cells. The activity of this mycorrhizal Pi uptake pathway is often associated with downregu......Arbuscular mycorrhizal fungi (AMF) have a key role in plant phosphate (Pi) uptake by their efficient capture of soil phosphorus (P) that is transferred to the plant via Pi transporters in the root cortical cells. The activity of this mycorrhizal Pi uptake pathway is often associated...... this interplay we modulated the delivery of Pi via the mycorrhizal pathway in Pisum sativum by two means: (1) Partial downregulation by virus-induced gene silencing of PsPT4, a putative Pi transporter gene in the mycorrhizal pathway. This resulted in decreased fungal development in roots and soil and led...... to reduced plant Pi uptake. (2) Changing the percentage of AMF-colonized root length by using non-, half-mycorrhizal or full-mycorrhizal split-root systems. The combination of split roots, use of 32P and 33P isotopes and partial silencing of PsPT4 enabled us to show that the expression of PsPT1, a putative...

  17. Carnitine uptake by AGP2 in yeast Saccharomyces cerevisiae is dependent on Hog1 MAP kinase pathway.

    Science.gov (United States)

    Lee, Jiyoung; Lee, Boyoung; Shin, Dongjin; Kwak, Sang-Soo; Bahk, Jeong Dong; Lim, Chae Oh; Yun, Dae-Jin

    2002-06-30

    The AGP2 gene encodes a plasma membrane carnitine transporter in S. cerevisiae. Here, we report the identification of AGP2 as an osmotic stress response gene. AGP2 was isolated from mTn3 tagged mutants that contained in-frame fusions with lacZ. The expression of AGP2 was down-regulated by osmotic stresses, including NaCl, sorbitol, and KCI. We also found that carnitine uptake was inhibited by NaCl. In the ssk1delta stelldelta double-mutant strain, the expression of AGP2 and the uptake of carnitine were greatly reduced compared to the wild-type strain. Furthermore, carnitine uptake was inhibited by the constitutive expression of PBS2, which encodes a MAPKK that activates Hog1. We concluded, therefore, that the HOG pathway plays an important role in the regulation of carnitine uptake in S. cerevisiae.

  18. Pentavalent antimony uptake pathway through erythrocyte membranes: molecular and atomic fluorescence approaches.

    Science.gov (United States)

    Barrera, Camila; López, Silvana; Aguilar, Luis; Mercado, Luis; Bravo, Manuel; Quiroz, Waldo

    2016-04-01

    Previous studies by our group have shown that Sb(V) is able to enter red blood cells in a dynamic process and is reduced to Sb(III) by glutathione. The present study aims to investigate a possible entry pathway for Sb(V) through the erythrocyte membrane. Applying fluorescence spectroscopy studies with Laurdan and diphenylhexatriene (DPH) probes, it was found that there was no interaction between Sb(V) and membrane lipids. By comparing the Sb(V) entry percentages through lipid vesicles and sealed erythrocyte membranes, it was found that Sb(V) required protein channels to pass through the membrane. The competitive inhibition results using HCO3 (-) and Cl(-) showed that the Sb(V) uptake rate through the membrane fell approximately 50-70 % until full inhibition was reached, which was possibly due to the inhibition of the anion exchanger 1 (AE1) channel. Finally, the fluorescence measurements with the 5-iodoacetamidofluorescein (5-IAF) probe showed that Sb(V) interacted with membrane protein SH groups during this process.

  19. An iron-dependent and transferrin-mediated cellular uptake pathway for plutonium.

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, M. P.; Gorman-Lewis, D.; Aryal, B. P.; Paunesku, T.; Vogt, S.; Rickert, P. G.; Seifert, S.; Lai, B.; Woloschak, G. E.; Soderholm, L. (Chemical Sciences and Engineering Division); ( XSD); (Univ. of Chicago); (Northwestern Univ.)

    2011-08-01

    Plutonium is a toxic synthetic element with no natural biological function, but it is strongly retained by humans when ingested. Using small-angle X-ray scattering, receptor binding assays and synchrotron X-ray fluorescence microscopy, we find that rat adrenal gland (PC12) cells can acquire plutonium in vitro through the major iron acquisition pathway -- receptor-mediated endocytosis of the iron transport protein serum transferrin; however, only one form of the plutonium-transferrin complex is active. Low-resolution solution models of plutonium-loaded transferrins derived from small-angle scattering show that only transferrin with plutonium bound in the protein's C-terminal lobe (C-lobe) and iron bound in the N-terminal lobe (N-lobe) (Pu{sub c}Fe{sub N}Tf) adopts the proper conformation for recognition by the transferrin receptor protein. Although the metal-binding site in each lobe contains the same donors in the same configuration and both lobes are similar, the differences between transferrin's two lobes act to restrict, but not eliminate, cellular Pu uptake.

  20. An iron-dependent and transferrin-mediated cellular uptake pathway for plutonium.

    Science.gov (United States)

    Jensen, Mark P; Gorman-Lewis, Drew; Aryal, Baikuntha; Paunesku, Tatjana; Vogt, Stefan; Rickert, Paul G; Seifert, Soenke; Lai, Barry; Woloschak, Gayle E; Soderholm, L

    2011-06-26

    Plutonium is a toxic synthetic element with no natural biological function, but it is strongly retained by humans when ingested. Using small-angle X-ray scattering, receptor binding assays and synchrotron X-ray fluorescence microscopy, we find that rat adrenal gland (PC12) cells can acquire plutonium in vitro through the major iron acquisition pathway--receptor-mediated endocytosis of the iron transport protein serum transferrin; however, only one form of the plutonium-transferrin complex is active. Low-resolution solution models of plutonium-loaded transferrins derived from small-angle scattering show that only transferrin with plutonium bound in the protein's C-terminal lobe (C-lobe) and iron bound in the N-terminal lobe (N-lobe) (Pu(C)Fe(N)Tf) adopts the proper conformation for recognition by the transferrin receptor protein. Although the metal-binding site in each lobe contains the same donors in the same configuration and both lobes are similar, the differences between transferrin's two lobes act to restrict, but not eliminate, cellular Pu uptake.

  1. Mycorrhiza and PGPB modulate maize biomass, nutrient uptake and metabolic pathways in maize grown in mining-impacted soil.

    Science.gov (United States)

    Dhawi, Faten; Datta, Rupali; Ramakrishna, Wusirika

    2015-12-01

    Abiotic stress factors including poor nutrient content and heavy metal contamination in soil, can limit plant growth and productivity. The main goal of our study was to evaluate element uptake, biomass and metabolic responses in maize roots growing in mining-impacted soil with the combination of arbuscular mycorrhiza (My) and plant growth promoting bacteria (PGPB/B). Maize plants subjected to PGPB, My and combined treatments showed a significant increase in biomass and uptake of some elements in shoot and root. Metabolite analysis identified 110 compounds that were affected ≥2-fold compared to control, with 69 metabolites upregulated in the My group, 53 metabolites in the My+B group and 47 metabolites in B group. Pathway analysis showed that impact on glyoxylate and dicarboxylate metabolism was common between My and My+B groups, whereas PGPB group showed a unique effect on fatty acid biosynthesis with significant increase in palmitic acid and stearic acid. Differential regulation of some metabolites by mycorrhizal treatment correlated with root biomass while PGPB regulated metabolites correlated with biomass increase in shoot. Overall, the combination of rhizospheric microorganisms used in our study significantly increased maize nutrient uptake and growth relative to control. The changes in metabolic pathways identified during the symbiotic interaction will improve our understanding of mechanisms involved in rhizospheric interactions that are responsible for increased growth and nutrient uptake in crop plants. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. Mycorrhizal phosphate uptake pathway in maize: vital for growth and cob development on nutrient poor agricultural and greenhouse soils

    Science.gov (United States)

    Willmann, Martin; Gerlach, Nina; Buer, Benjamin; Polatajko, Aleksandra; Nagy, Réka; Koebke, Eva; Jansa, Jan; Flisch, René; Bucher, Marcel

    2013-01-01

    Arbuscular mycorrhizal fungi (AMF) form a mutually beneficial symbiosis with plant roots providing predominantly phosphorus in the form of orthophosphate (Pi) in exchange for plant carbohydrates on low P soils. The goal of this work was to generate molecular-genetic evidence in support of a major impact of the mycorrhizal Pi uptake (MPU) pathway on the productivity of the major crop plant maize under field and controlled conditions. Here we show, that a loss-of-function mutation in the mycorrhiza-specific Pi transporter gene Pht1;6 correlates with a dramatic reduction of above-ground biomass and cob production in agro-ecosystems with low P soils. In parallel mutant pht1;6 plants exhibited an altered fingerprint of chemical elements in shoots dependent on soil P availability. In controlled environments mycorrhiza development was impaired in mutant plants when grown alone. The presence of neighboring mycorrhizal nurse plants enhanced the reduced mycorrhiza formation in pht1;6 roots. Uptake of 33P-labeled orthophosphate via the MPU pathway was strongly impaired in colonized mutant plants. Moreover, repression of the MPU pathway resulted in a redirection of Pi to neighboring plants. In line with previous results, our data highlight the relevance of the MPU pathway in Pi allocation within plant communities and in particular the role of Pht1;6 for the establishment of symbiotic Pi uptake and for maize productivity and nutritional value in low-input agricultural systems. In a first attempt to identify cellular pathways which are affected by Pht1;6 activity, gene expression profiling via RNA-Seq was performed and revealed a set of maize genes involved in cellular signaling which exhibited differential regulation in mycorrhizal pht1;6 and control plants. The RNA data provided support for the hypothesis that fungal supply of Pi and/or Pi transport across Pht1;6 affects cell wall biosynthesis and hormone metabolism in colonized root cells. PMID:24409191

  3. IL-15 Activates the Jak3/STAT3 Signaling Pathway to Mediate Glucose Uptake in Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    James E Krolopp

    2016-12-01

    Full Text Available Myokines are specialized cytokines that are secreted from skeletal muscle (SKM in response to metabolic stimuli, such as exercise. Interleukin-15 (IL-15 is a myokine with potential to reduce obesity and increase lean mass through induction of metabolic processes. It has been previously shown that IL-15 acts to increase glucose uptake in SKM cells. However, the downstream signals orchestrating the link between IL-15 signaling and glucose uptake have not been fully explored. Here we employed the mouse SKM C2C12 cell line to examine potential downstream targets of IL-15-induced alterations in glucose uptake. Following differentiation, C2C12 cells were treated overnight with 100 ng/ml of IL-15. Activation of factors associated with glucose metabolism (Akt and AMPK and known downstream targets of IL-15 (Jak1, Jak3, STAT3, and STAT5 were assessed with IL-15 stimulation. IL-15 stimulated glucose uptake and GLUT4 translocation to the plasma membrane. IL-15 treatment had no effect on phospho-Akt, phospho-Akt substrates, phospho-AMPK, phospho-Jak1, or phospho-STAT5. However, with IL-15, phospho-Jak3 and phospho-STAT3 levels were increased along with increased interaction of Jak3 and STAT3. Additionally, IL-15 induced a translocation of phospho-STAT3 from the cytoplasm to the nucleus. We have evidence that a mediator of glucose uptake, HIF1α, expression was dependent on IL-15 induced STAT3 activation. Finally, upon inhibition of STAT3 the positive effects of IL-15 on glucose uptake and GLUT4 translocation were abolished. Taken together, we provide evidence for a novel signaling pathway for IL-15 acting through Jak3/STAT3 to regulate glucose metabolism.

  4. Quercetin, a Lead Compound against Type 2 Diabetes Ameliorates Glucose Uptake via AMPK Pathway in Skeletal Muscle Cell Line

    Directory of Open Access Journals (Sweden)

    R. Dhanya

    2017-06-01

    Full Text Available Herein we investigated the molecular mechanism of action of the citrus flavonoid, quercetin in skeletal muscle cells (L6 myotubes. Taking advantage of protein kinase inhibitors, we proved that the effect of quercetin on 2-NBDG uptake in L6 myotubes was not through insulin signaling pathway, but through adenosine monophosphate kinase (AMPK pathway and its downstream target p38 MAPK. An increase in the cellular AMP to ATP ratio on pretreatment may account for AMPK activation which was coupled with a transient change in mitochondrial membrane potential. In addition, quercetin triggered a rise in intracellular calcium suggesting that calcium-calmodulin mediated protein kinase (CaMKK may also be involved. Quercetin shared a similar mechanism with the well-known drug metformin, highlighting it as a promising compound for the management of type 2 diabetes. The AMPK signaling pathway could contribute to correction of insulin resistance through bypassing the insulin-regulated system for GLUT4 translocation.

  5. Mycorrhizal phosphate uptake pathway in maize: Vital for growth and cob development on nutrient poor agricultural and greenhouse soils

    Directory of Open Access Journals (Sweden)

    Martin eWillmann

    2013-12-01

    Full Text Available Arbuscular mycorrhizal fungi (AMF form a mutually beneficial symbiosis with plant roots providing predominantly phosphorus in the form of orthophosphate (Pi in exchange for plant carbohydrates on low P soils. The goal of this work was to generate molecular-genetic evidence in support of a major impact of the mycorrhizal Pi uptake (MPU pathway on the productivity of the major crop plant maize under field and controlled conditions. Here we show, that a loss-of-function mutation in the mycorrhiza-specific Pi transporter gene Pht1;6 correlates with a dramatic reduction of above-ground biomass and cob production in agro-ecosystems with low P soils. In parallel mutant pht1;6 plants exhibited an altered fingerprint of chemical elements in shoots dependent on soil P availability. In controlled environments mycorrhiza development was impaired in mutant plants when grown alone. The presence of neighbouring mycorrhizal nurse plants enhanced the reduced mycorrhiza formation in pht1;6 roots. Uptake of 33P-labelled orthophosphate via the MPU pathway was strongly impaired in colonized mutant plants. Moreover, repression of the MPU pathway resulted in a redirection of Pi to neighbouring plants. In line with previous results, our data highlight the relevance of the MPU pathway in Pi allocation within plant communities and in particular the role of Pht1;6 for the establishment of symbiotic Pi uptake and for maize productivity and nutritional value in low-input agricultural systems. In a first attempt to identify cellular pathways which are affected by Pht1;6 activity, gene expression profiling via RNA-Seq was performed and revealed a set of maize genes involved in cellular signalling which exhibited differential regulation in mycorrhizal pht1;6 and control plants. The RNA data provided support for the hypothesis that fungal supply of Pi and/or Pi transport across Pht1;6 affects cell wall biosynthesis and hormone metabolism in colonized root cells.

  6. Intracellular trafficking pathways in silver nanoparticle uptake and toxicity in Caenorhabditis elegans.

    Science.gov (United States)

    Maurer, Laura L; Yang, Xinyu; Schindler, Adam J; Taggart, Ross K; Jiang, Chuanjia; Hsu-Kim, Heileen; Sherwood, David R; Meyer, Joel N

    2016-09-01

    We used the nematode Caenorhabditis elegans to study the roles of endocytosis and lysosomal function in uptake and subsequent toxicity of silver nanoparticles (AgNP) in vivo. To focus on AgNP uptake and effects rather than silver ion (AgNO3) effects, we used a minimally dissolvable AgNP, citrate-coated AgNPs (CIT-AgNPs). We found that the clathrin-mediated endocytosis inhibitor chlorpromazine reduced the toxicity of CIT-AgNPs but not AgNO3. We also tested the sensitivity of three endocytosis-deficient mutants (rme-1, rme-6 and rme-8) and two lysosomal function deficient mutants (cup-5 and glo-1) as compared to wild-type (N2 strain). One of the endocytosis-deficient mutants (rme-6) took up less silver and was resistant to the acute toxicity of CIT-AgNPs compared to N2s. None of those mutants showed altered sensitivity to AgNO3. Lysosome and lysosome-related organelle mutants were more sensitive to the growth-inhibiting effects of both CIT-AgNPs and AgNO3. Our study provides mechanistic evidence suggesting that early endosome formation is necessary for AgNP-induced toxicity in vivo, as rme-6 mutants were less sensitive to the toxic effects of AgNPs than C. elegans with mutations involved in later steps in the endocytic process.

  7. PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway

    Science.gov (United States)

    Xu, Jialin; Shimpi, Prajakta; Armstrong, Laura; Salter, Deanna; Slitt, Angela L.

    2016-01-01

    PFOS is a chemical of nearly ubiquitous exposure in humans. Recent studies have associated PFOS exposure to adipose tissue-related effects. The present study was to determine whether PFOS alters the process of adipogenesis and regulates insulin-stimulated glucose uptake in mouse and human preadipocytes. In murine-derived 3T3-L1 preadipocytes, PFOS enhanced hormone-induced differentiation to adipocytes and adipogenic gene expression, increased insulin-stimulated glucose uptake at concentrations ranging from 10 to 100 µM, and enhanced Glucose transporter type 4 and Insulin receptor substrate-1 expression. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), NAD(P)H dehydrogenase, quinone 1 and Glutamate-cysteine ligase, catalytic subunit were significantly induced in 3T3-L1 cells treated with PFOS, along with a robust induction of Antioxidant Response Element (ARE) reporter in mouse embryonic fibroblasts isolated from ARE-hPAP transgenic mice by PFOS treatment. Chromatin immunoprecipitation assays further illustrated that PFOS increased Nrf2 binding to ARE sites in mouse Nqo1 promoter, suggesting that PFOS activated Nrf2 signaling in murine-derived preadipocytes. Additionally, PFOS administration in mice (100 µg/kg/day) induced adipogenic gene expression and activated Nrf2 signaling in epididymal white adipose tissue. Moreover, the treatment on human visceral preadipocytes illustrated that PFOS (5 and 50 µM) promoted adipogenesis and increased cellular lipid accumulation. It was observed that PFOS increased Nrf2 binding to ARE sites in association with Nrf2 signaling activation, induction of Peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α expression, and increased adipogenesis. This study points to a potential role PFOS in dysregulation of adipose tissue expandability, and warrants further investigations on the adverse effects of persistent pollutants on human health. PMID:26548598

  8. Estradiol-17beta-BSA stimulates Ca(2+) uptake through nongenomic pathways in primary rabbit kidney proximal tubule cells: involvement of cAMP and PKC.

    Science.gov (United States)

    Han, H J; Lee, Y H; Park, S H

    2000-04-01

    The effect of estradiol-17beta-BSA (E(2)-BSA) on Ca(2+) uptake and its related signal pathways were examined in the primary cultured rabbit kidney proximal tubule cells. E(2)-BSA (10(-9) M) significantly stimulated Ca(2+) uptake from 2 h by 13% and at 8 h by 35% as compared to control, respectively. This stimulatory effect of E(2)-BSA was not inhibited by tamoxifen (10(-8) M, an intracellular estrogen receptor antagonist), actinomycin D (10(-7) M, a transcription inhibitor), and cycloheximide (4 x 10(-5) M, a protein synthesis inhibitor). However, E(2)-BSA-induced stimulation of Ca(2+) uptake was blocked by methoxyverapamil (10(-6) M, an L-type calcium channel blocker) and 5-(N-ethyl-N-isopropyl)-amiloride (10(-5) M, a Na(+)/H(+) antiporter blocker). These results suggest that E(2)-BSA stimulates Ca(2+) uptake through nongenomic pathways. Thus, we investigated which signal pathways were related to E(2)-BSA-induced stimulation of Ca(2+) uptake. 8-Br-cAMP (10(-6) M) alone increased Ca(2+) uptake by 22% compared to control. When E(2)-BSA combined with 8-Br-cAMP, Ca(2+) uptake was not significantly stimulated compared to E(2)-BSA. SQ 22536 (10(-6) M, an adenylate cyclase inhibitor) and myristoylated protein kinase A inhibitor amide 14-22 (10(-6) M, a protein kinase A inhibitor) blocked E(2)-BSA-induced stimulation of Ca(2+) uptake and E(2)-BSA also increased cAMP generation by 26% of that of control. In addition, TPA (0.02 ng/ml, an artificial PKC promoter) stimulated the Ca(2+) uptake by 14%, and the cotreatment of TPA and E(2)-BSA did not significantly stimulate Ca(2+) uptake compared to E(2)-BSA. E(2)-BSA-induced stimulation of Ca(2+) uptake was blocked by U 73122 (10(-6) M, a phospholipase C inhibitor) or bisindolylmaleimide I (10(-6) M, a protein kinase C inhibitor). Indeed, E(2)-BSA stimulated PKC activity by 26%. In conclusion, E(2)-BSA (10(-9) M) stimulated Ca(2+) uptake by nongenomic action, which is mediated by cAMP and PKC pathways.

  9. Identification of a novel pathway involving a GATA transcription factor in yeast and possibly in plant Zn uptake and homeostasis

    Institute of Scientific and Technical Information of China (English)

    Matthew J. Milner; Nicole S. Pence; Jiping Liu; Leon V. Kochian

    2014-01-01

    To gain a better understanding of the regulation of Zn homeostasis in plants and the degree of conservation of Zn homeostasis between plants and yeast, a cDNA library from the Zn/Cd hyperaccumulating plant species, Noccaea caerules-cens, was screened for its ability to restore growth under Zn limiting conditions in the yeast mutant zap1D. ZAP1 is a transcription factor that activates the Zn dependent transcrip-tion of yeast genes involved in Zn uptake, including ZRT1, the yeast high affinity Zn transporter. From this screen two members of the E2F family of transcription factors were found to activate ZRT1 expression in a Zn independent manner. The activation of ZRT1 by the plant E2F proteins involves E2F-mediated activation of a yeast GATA transcription factor which in turn activates ZRT1 expression. A ZRT1 promoter region necessary for activation by E2F and GATA proteins is upstream of two zinc responsive elements previously shown to bind ZAP1 in ZRT1. This activation may not involve direct binding of E2F to the ZRT1 promoter. The expression of E2F genes in yeast does not replace function of ZAP1; instead it appears to activate a novel GATA regulatory pathway involved in Zn uptake and homeostasis that is not Zn responsive.

  10. Using Perls Staining to Trace the Iron Uptake Pathway in Leaves of a Prunus Rootstock Treated with Iron Foliar Fertilizers.

    Science.gov (United States)

    Rios, Juan J; Carrasco-Gil, Sandra; Abadía, Anunciación; Abadía, Javier

    2016-01-01

    The aim of this study was to trace the Fe uptake pathway in leaves of Prunus rootstock (GF 677; Prunus dulcis × Prunus persica) plants treated with foliar Fe compounds using the Perls blue method, which detects labile Fe pools. Young expanded leaves of Fe-deficient plants grown in nutrient solution were treated with Fe-compounds using a brush. Iron compounds used were the ferrous salt FeSO4, the ferric salts Fe2(SO4)3 and FeCl3, and the chelate Fe(III)-EDTA, all of them at concentrations of 9 mM Fe. Leaf Fe concentration increases were measured at 30, 60, 90 min, and 24 h, and 70 μm-thick leaf transversal sections were obtained with a vibrating microtome and stained with Perls blue. In vitro results show that the Perls blue method is a good tool to trace the Fe uptake pathway in leaves when using Fe salts, but is not sensitive enough when using synthetic Fe(III)-chelates such as Fe(III)-EDTA and Fe(III)-IDHA. Foliar Fe fertilization increased leaf Fe concentrations with all Fe compounds used, with inorganic Fe salts causing larger leaf Fe concentration increases than Fe(III)-EDTA. Results show that Perls blue stain appeared within 30 min in the stomatal areas, indicating that Fe applied as inorganic salts was taken up rapidly via stomata. In the case of using FeSO4 a progression of the stain was seen with time toward vascular areas in the leaf blade and the central vein, whereas in the case of Fe(III) salts the stain mainly remained in the stomatal areas. Perls stain was never observed in the mesophyll areas, possibly due to the low concentration of labile Fe pools.

  11. Green tea epigallocatechin gallate inhibits insulin stimulation of adipocyte glucose uptake via the 67-kilodalton laminin receptor and AMP-activated protein kinase pathways.

    Science.gov (United States)

    Hsieh, Chi-Fen; Tsuei, Yi-Wei; Liu, Chi-Wei; Kao, Chung-Cheng; Shih, Li-Jane; Ho, Low-Tone; Wu, Liang-Yi; Wu, Chi-Peng; Tsai, Pei-Hua; Chang, Hsin-Huei; Ku, Hui-Chen; Kao, Yung-Hsi

    2010-10-01

    Insulin and (-)-epigallocatechin gallate (EGCG) are reported to regulate obesity and fat accumulation, respectively. This study investigated the pathways involved in EGCG modulation of insulin-stimulated glucose uptake in 3T3-L1 and C3H10T1/2 adipocytes. EGCG inhibited insulin stimulation of adipocyte glucose uptake in a dose- and time-dependent manner. The concentration of EGCG that decreased insulin-stimulated glucose uptake by 50-60% was approximately 5-10 µM for a period of 2 h. At 10 µM, EGCG and gallic acid were more effective than (-)-epicatechin, (-)-epigallocatechin, and (-)-epicatechin 3-gallate. We identified the EGCG receptor [also known as the 67-kDa laminin receptor (67LR)] in fat cells and extended the findings for this study to clarify whether EGCG-induced changes in insulin-stimulated glucose uptake in adipocytes could be mediated through the 67LR. Pretreatment of adipocytes with a 67LR antibody, but not normal rabbit immunoglobulin, prevented the effects of EGCG on insulin-increased glucose uptake. This suggests that the 67LR mediates the effect of EGCG on insulin-stimulated glucose uptake in adipocytes. Moreover, pretreatment with an AMP-activated protein kinase (AMPK) inhibitor, such as compound C, but not with a glutathione (GSH) activator, such as N-acetyl-L-cysteine (NAC), blocked the antiinsulin effect of EGCG on adipocyte glucose uptake. These data suggest that EGCG exerts its anti-insulin action on adipocyte glucose uptake via the AMPK, but not the GSH, pathway. The results of this study possibly support that EGCG mediates fat content. © Georg Thieme Verlag KG Stuttgart · New York.

  12. Adrenoceptors promote glucose uptake into adipocytes and muscle by an insulin-independent signaling pathway involving mechanistic target of rapamycin complex 2.

    Science.gov (United States)

    Mukaida, Saori; Evans, Bronwyn A; Bengtsson, Tore; Hutchinson, Dana S; Sato, Masaaki

    2017-02-01

    Uptake of glucose into skeletal muscle and adipose tissue plays a vital role in metabolism and energy balance. Insulin released from β-islet cells of the pancreas promotes glucose uptake in these target tissues by stimulating translocation of GLUT4 transporters to the cell surface. This process is complex, involving signaling proteins including the mechanistic (or mammalian) target of rapamycin (mTOR) and Akt that intersect with multiple pathways controlling cell survival, growth and proliferation. mTOR exists in two forms, mTOR complex 1 (mTORC1), and mTOR complex 2 (mTORC2). mTORC1 has been intensively studied, acting as a key regulator of protein and lipid synthesis that integrates cellular nutrient availability and energy balance. Studies on mTORC2 have focused largely on its capacity to activate Akt by phosphorylation at Ser473, however recent findings demonstrate a novel role for mTORC2 in cellular glucose uptake. For example, agonists acting at β2-adrenoceptors (ARs) in skeletal muscle or β3-ARs in brown adipose tissue increase glucose uptake in vitro and in vivo via mechanisms dependent on mTORC2 but not Akt. In this review, we will focus on the signaling pathways downstream of β-ARs that promote glucose uptake in skeletal muscle and brown adipocytes, and will highlight how the insulin and adrenergic pathways converge and interact in these cells. The identification of insulin-independent mechanisms that promote glucose uptake should facilitate novel treatment strategies for metabolic disease.

  13. Co-Administration of an Excipient Oligonucleotide Helps Delineate Pathways of Productive and Nonproductive Uptake of Phosphorothioate Antisense Oligonucleotides in the Liver.

    Science.gov (United States)

    Donner, Aaron J; Wancewicz, Edward V; Murray, Heather M; Greenlee, Sarah; Post, Noah; Bell, Melanie; Lima, Walt F; Swayze, Eric E; Seth, Punit P

    2017-08-01

    Phosphorothioate (PS) modified antisense oligonucleotides (ASOs) have progressed rapidly in the clinic for treating a variety of disease indications. We previously demonstrated that the activity of PS ASOs in the liver can be enhanced by co-infusion of an excipient oligonucleotide (EON). It was posited that the EON saturates a nonproductive uptake pathway(s) thereby permitting accumulation of the PS ASO in a productive tissue compartment. In this report, we measured PS ASO activity following administration by bolus, infusion or co-fusion with EON within hepatocytes and nonparenchymal cells (NPCs), of the liver. This revealed that while ASOs accumulate preferentially in NPCs, they are intrinsically more active in hepatocytes. Furthermore, we show that the EON enhances ASO potency when infused up to 72 h before or after administration of the active ASO suggesting that the EON can saturate and displace the ASO from nonproductive to productive compartments. Physical presence of the EON in tissues was required for optimal potentiation suggesting that there is a dynamic distribution of the ASO and EON between the compartments. Lastly, using a candidate approach, we confirmed Stabilin-2 as a molecular pathway for ASO uptake in sinusoidal endothelial cells and the ASGR as a pathway for ASO uptake into hepatocytes in the liver.

  14. The inability of phosphatidylinositol 3-kinase activation to stimulate GLUT4 translocation indicates additional signaling pathways are required for insulin-stimulated glucose uptake.

    Science.gov (United States)

    Isakoff, S J; Taha, C; Rose, E; Marcusohn, J; Klip, A; Skolnik, E Y

    1995-10-24

    Recent experimental evidence has focused attention to the role of two molecules, insulin receptor substrate 1 (IRS-1) and phosphatidylinositol 3-kinase (PI3-kinase), in linking the insulin receptor to glucose uptake; IRS-1 knockout mice are insulin resistant, and pharmacological inhibitors of PI3-kinase block insulin-stimulated glucose uptake. To investigate the role of PI3-kinase and IRS-1 in insulin-stimulated glucose uptake we examined whether stimulation of insulin-sensitive cells with platelet-derived growth factor (PDGF) or with interleukin 4 (IL-4) stimulates glucose uptake; the activated PDGF receptor (PDGFR) directly binds and activates PI3-kinase, whereas the IL-4 receptor (IL-4R) activates PI3-kinase via IRS-1 or the IRS-1-related molecule 4PS. We found that stimulation of 3T3-L1 adipocytes with PDGF resulted in tyrosine phosphorylation of the PDGFR and activation of PI3-kinase in these cells. To examine whether IL-4 stimulates glucose uptake, L6 myoblasts were engineered to overexpress GLUT4 as well as both chains of the IL-4R (L6/IL-4R/GLUT4); when these L6/IL-4R/GLUT4 myoblasts were stimulated with IL-4, IRS-1 became tyrosine phosphorylated and associated with PI3-kinase. Although PDGF and IL-4 can activate PI3-kinase in the respective cell lines, they do not possess insulin's ability to stimulate glucose uptake and GLUT4 translocation to the plasma membrane. These findings indicate that activation of PI3-kinase is not sufficient to stimulate GLUT4 translocation to the plasma membrane. We postulate that activation of a second signaling pathway by insulin, distinct from PI3-kinase, is necessary for the stimulation of glucose uptake in insulin-sensitive cells.

  15. Mechanism of riboflavin uptake by cultured human retinal pigment epithelial ARPE-19 cells: possible regulation by an intracellular Ca2+-calmodulin-mediated pathway.

    Science.gov (United States)

    Said, Hamid M; Wang, Shuling; Ma, Thomas Y

    2005-07-15

    In mammalian cells (including those of the ocular system), the water-soluble vitamin B2 (riboflavin, RF) assumes an essential role in a variety of metabolic reactions and is critical for normal cellular functions, growth and development. Cells of the human retinal pigment epithelium (hRPE) play an important role in providing a sufficient supply of RF to the retina, but nothing is known about the mechanism of the vitamin uptake by these cells and its regulation. Our aim in the present study was to address this issue using the hRPE ARPE-19 cells as the retinal epithelial model. Our results show RF uptake in the hRPE to be: (1) energy and temperature dependent and occurring without metabolic alteration in the transported substrate, (2) pH but not Na+ dependent, (3) saturable as a function of concentration with an apparent Km of 80 +/- 14 nM, (4) trans-stimulated by unlabelled RF and its structural analogue lumiflavine, (5) cis-inhibited by the RF structural analogues lumiflavine and lumichrome but not by unrelated compounds, and (6) inhibited by the anion transport inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS) as well as by the Na+ -H+ exchange inhibitor amiloride and the sulfhydryl group inhibitor p-chloromercuriphenylsulphonate (p-CMPS). Maintaining the hRPE cells in a RF-deficient medium led to a specific and significant up-regulation in RF uptake which was mediated via changes in the number and affinity of the RF uptake carriers. While modulating the activities of intracellular protein kinase A (PKA)-, protein kinase C (PKC)-, protein tyrosine kinase (PTK)-, and nitric oxide (NO)-mediated pathways were found to have no role in regulating RF uptake, a role for the Ca2+ -calmodulin-mediated pathway was observed. These studies demonstrate for the first time the involvement of a specialized carrier-mediated mechanism for RF uptake by hRPE cells and show that the process is

  16. Global Hepatic Uptake of {sup 99m}Tc-MAA During VQ Scintigraphy Secondary to Synchronous Superior and Inferior Vena Caval Obstruction: a Demonstraion of Trans-Portal Venous Collateral Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Conway, Oliver; Lloyd, Simon; Gruening, Thomas [Derriford Hospital, Plymouth (United States)

    2013-12-15

    A 38-year-old woman underwent lung scintigraphy. Injection of technetium-99m macroaggregated albumin ({sup 99m}Tc-MAA) via the left antecubital fossa revealed global hepatic uptake. Review of contemporary computed tomography (CT) imaging demonstrated synchronous superior and inferior vena cava (SVC and IVC) obstruction, with formation of systemic-portal venous collateral pathways. Systemic-portal venous collateralisation can in rare circumstances lead to focal hepatic uptake of {sup 99m}Tc-MAA during lung scintigraphy. This case of global hepatic uptake, secondary to synchronous SVC and IVC obstruction, demonstrates the trans-portal venous collateral pathways leading to this unusual imaging outcome.

  17. Dibenzoylmethane exerts metabolic activity through regulation of AMP-activated protein kinase (AMPK-mediated glucose uptake and adipogenesis pathways.

    Directory of Open Access Journals (Sweden)

    Nami Kim

    Full Text Available Dibenzoylmethane (DBM has been shown to exert a variety of beneficial effects on human health. However, the mechanism of action is poorly understood. In this study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK and stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake. DBM increased the concentration of intracellular calcium and glucose uptake due to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase inhibitor. DBM stimulated phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK, which was blocked by pretreatment with compound C, an AMPK inhibitor. The expression of glucose transporter type 4 (GLUT4 was increased by DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat accumulation in the liver and abdomen in mice fed a high-fat diet. In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC, the rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene, fatty acid synthase (FAS, was suppressed by DBM in an AMPK-dependent manner. These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.

  18. On the pathway of cellular uptake: new insight into the interaction between the cell membrane and very small nanoparticles

    Directory of Open Access Journals (Sweden)

    Claudia Messerschmidt

    2016-09-01

    Full Text Available For any living cell the exchange with its environment is vital. Therefore, many different kinds of cargo are able to enter cells via energy-dependent or -independent routes. Nanoparticles are no exemption. It is known that small silica nanoparticles with a diameter below 50 nm are taken up by cells and that their uptake exerts pronounced toxic effects beyond a certain concentration threshold. However, neither the exact uptake mechanism of these particles nor the actual reason for their toxicity has yet been elucidated. In this study we examined the uptake of silica nanoparticles with a diameter of 7, 12 and 22 nm by means of transmission electron microscopy, accompanied by toxicological assays. We show that for every particle diameter tested a different membrane morphology during uptake can be observed and that the amount of particles entering in one event is different for the three sizes. Silica particles with a diameter of 22 nm show single-particle internalization with a membrane wrapped around the particles in the cytosol, whereas 12 nm particles display row-like multi-particle uptake into elongated membrane structures and those with a diameter of 7 nm or less end up in tubular endocytic structures containing many particles. These membrane morphologies proved to be highly reproducible as we found them in five different cell lines. Additionally, we performed ATP and LDH assays to determine particle toxicity. Exceeding a certain concentration threshold the nanoparticles showed a high toxic potential both in the biochemical assay measurements and from morphological findings. We could not find any hint at the induction of apoptosis, neither morphologically nor biochemically. In this regard we discuss membrane damage and consumption as one possible mechanism of toxicity, linking morphological observations to toxicological findings to bridge the gap in understanding the mechanism of toxicity of small nanoparticles.

  19. The phosphoinositide 3-kinase signaling pathway is involved in the control of modified low-density lipoprotein uptake by human macrophages.

    Science.gov (United States)

    Michael, Daryn R; Davies, Thomas S; Laubertová, Lucia; Gallagher, Hayley; Ramji, Dipak P

    2015-03-01

    The transformation of macrophages into lipid-loaded foam cells is a critical early event in the pathogenesis of atherosclerosis. Both receptor-mediated uptake of modified LDL, mediated primarily by scavenger receptors-A (SR-A) and CD36 along with other proteins such as lipoprotein lipase (LPL), and macropinocytosis contribute to macrophage foam cell formation. The signaling pathways that are involved in the control of foam cell formation are not fully understood. In this study, we have investigated the role of phosphoinositide 3-kinase (PI3K) in relation to foam cell formation in human macrophages. The pan PI3K inhibitor LY294002 attenuated the uptake of modified LDL and macropinocytosis, as measured by Lucifer Yellow uptake, by human macrophages. In addition, the expression of SR-A, CD36 and LPL was attenuated by LY294002. The use of isoform-selective PI3K inhibitors showed that PI3K-β, -γ and -δ were all required for the expression of SR-A and CD36 whereas only PI3K-γ was necessary in the case of LPL. These studies reveal a pivotal role of PI3K in the control of macrophage foam cell formation and provide further evidence for their potential as therapeutic target against atherosclerosis.

  20. 1α,25-Dihydroxyvitamin D(3) signaling pathways on calcium uptake in 30-day-old rat Sertoli cells.

    Science.gov (United States)

    Zanatta, Leila; Zamoner, Ariane; Gonçalves, Renata; Zanatta, Ana Paula; Bouraïma-Lelong, Hélène; Carreau, Serge; Silva, Fátima Regina Mena Barreto

    2011-11-29

    1α,25-Dihydroxyvitamin D(3) (1,25D(3)) is the active metabolite of vitamin D(3) and the major calcium regulatory hormone in tissues. The aim of this work was to investigate the mechanism of action of 1,25D(3) on (45)Ca(2+) uptake in Sertoli cells from 30-day-old rats. Results showed that 10(-9) and 10(-12) M 1,25D(3) increased the rate of (45)Ca(2+) uptake 5 and 15 min after hormone exposure and that 1α,25(OH)(2) lumisterol(3) (JN) produced a similar effect suggesting that 1,25D(3) action occurs via a putative membrane receptor. The involvement of voltage-dependent calcium channels (VDCC) in 1,25D(3) action was evidenced by using nifedipine, while the use of Bapta-AM demonstrated that intracellular calcium was not implicated. Moreover, the incubation with ouabain and digoxin increased the rate of (45)Ca(2+) uptake, indicating that the effect of 1,25D(3) may also result from Na(+)/K(+)-ATPase inhibition. In addition, we demonstrated that the mechanism underlying the hormone action involved extracellular signal-regulated kinase (ERK) and protein kinase C (PKC) activation in a phospholipase C-independent way. Furthermore, a local elevation of the level of cAMP, as demonstrated by incubating cells with dibutyryl cAMP or a phosphodiesterase inhibitor, produced an effect similar to that of 1,25D(3), and the inhibition of protein kinase A (PKA) nullified the hormone action. In conclusion, the stimulatory effect of 1,25D(3) on (45)Ca(2+) uptake in Sertoli cells occurs via VDCC, as well as PKA, PKC, and ERK activation. These protein kinases seem to act by inhibiting Na(+)/K(+)-ATPase or directly phosphorylating calcium channels. The Na(+)/K(+)-ATPase inhibition may result in Na(+)/Ca(2+) exchanger activation in reverse mode and consequently induce the uptake of calcium into the cells.

  1. Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia.

    Science.gov (United States)

    Kozyraki, R; Fyfe, J; Verroust, P J; Jacobsen, C; Dautry-Varsat, A; Gburek, J; Willnow, T E; Christensen, E I; Moestrup, S K

    2001-10-23

    Cubilin is a 460-kDa protein functioning as an endocytic receptor for intrinsic factor vitamin B(12) complex in the intestine and as a receptor for apolipoprotein A1 and albumin reabsorption in the kidney proximal tubules and the yolk sac. In the present study, we report the identification of cubilin as a novel transferrin (Tf) receptor involved in catabolism of Tf. Consistent with a cubilin-mediated endocytosis of Tf in the kidney, lysosomes of human, dog, and mouse renal proximal tubules strongly accumulate Tf, whereas no Tf is detectable in the endocytic apparatus of the renal tubule epithelium of dogs with deficient surface expression of cubilin. As a consequence, these dogs excrete increased amounts of Tf in the urine. Mice with deficient synthesis of megalin, the putative coreceptor colocalizing with cubilin, also excrete high amounts of Tf and fail to internalize Tf in their proximal tubules. However, in contrast to the dogs with the defective cubilin expression, the megalin-deficient mice accumulate Tf on the luminal cubilin-expressing surface of the proximal tubule epithelium. This observation indicates that megalin deficiency causes failure in internalization of the cubilin-ligand complex. The megalin-dependent, cubilin-mediated endocytosis of Tf and the potential of the receptors thereby to facilitate iron uptake were further confirmed by analyzing the uptake of (125)I- and (59)Fe-labeled Tf in cultured yolk sac cells.

  2. Liposomal drug deposits in poly(dopamine) coatings: effect of their composition, cell type, uptake pathway considerations, and shear stress.

    Science.gov (United States)

    Lynge, Martin E; Fernandez-Medina, Marina; Postma, Almar; Städler, Brigitte

    2014-12-01

    Implantable devices equipped with coatings which have the ability to carry and deliver active compounds are of great interest. We report the assembly of liposome-containing poly(dopamine) films, and their interaction with adhering cells. The liposome composition is varied by adding lipophilic dopamine-conjugates and charged lipids. The cell mean fluorescence (CMF) of adhering cells due to the internalization of fluorescent cargo is found to be similar for coatings with the lipophilic-dopamine conjugates, while the charge affects the amount and location of the internalized cargo. The uptake mechanism for cargo by myoblasts using chemical inhibitors is found to be dependent on the used type of liposome. The CMF is significantly reduced for endothelial cells adhering to coatings with applied shear stress.

  3. An update on iron acquisition by Legionella pneumophila: new pathways for siderophore uptake and ferric iron reduction.

    Science.gov (United States)

    Cianciotto, Nicholas P

    2015-01-01

    Iron acquisition is critical for the growth and pathogenesis of Legionella pneumophila, the causative agent of Legionnaires' disease. L. pneumophila utilizes two main modes of iron assimilation, namely ferrous iron uptake via the FeoB system and ferric iron acquisition through the action of the siderophore legiobactin. This review highlights recent studies concerning the mechanism of legiobactin assimilation, the impact of c-type cytochromes on siderophore production, the importance of legiobactin in lung infection and a newfound role for a bacterial pyomelanin in iron acquisition. These data demonstrate that key aspects of L. pneumophila iron acquisition are significantly distinct from those of long-studied, 'model' organisms. Indeed, L. pneumophila may represent a new paradigm for a variety of other intracellular parasites, pathogens and under-studied bacteria.

  4. Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway.

    Science.gov (United States)

    Leem, Kang-Hyun; Kim, Myung-Gyou; Hahm, Young-Tae; Kim, Hye Kyung

    2016-12-09

    Opuntia ficus-indica var. saboten (OFS) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na⁺-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK) is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C) and p38 MAPK (SB203580) abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4) translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight) in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway.

  5. Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway

    Directory of Open Access Journals (Sweden)

    Kang-Hyun Leem

    2016-12-01

    Full Text Available Opuntia ficus-indica var. saboten (OFS has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na+-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C and p38 MAPK (SB203580 abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4 translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway.

  6. Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway

    Science.gov (United States)

    Leem, Kang-Hyun; Kim, Myung-Gyou; Hahm, Young-Tae; Kim, Hye Kyung

    2016-01-01

    Opuntia ficus-indica var. saboten (OFS) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na+-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK) is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C) and p38 MAPK (SB203580) abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4) translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight) in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway. PMID:27941667

  7. EGF Uptake and Degradation Assay to Determine the Effect of HTLV Regulatory Proteins on the ESCRT-Dependent MVB Pathway.

    Science.gov (United States)

    Murphy, Colin; Sheehy, Noreen

    2017-01-01

    The endosomal sorting complex required for transport (ESCRT) pathway plays key roles in multivesicular bodies (MVBs) formation and lysosomal degradation of membrane receptors, viral budding, and midbody abscission during cytokinesis. The epidermal growth factor receptor (EGFR) is regarded as a prototypical cargo of the MVB/ESCRT pathway and following stimulation by epidermal growth factor (EGF) EGFR/EGF complexes are internalized, sorted into MVBs, and degraded by lysosomes or recycled back to the cell membrane. Here, we describe an assay to analyze the effect of human T-cell leukemia (HTLV) regulatory proteins on the functionality of ESCRT-dependent MVB/lysosomal trafficking of EGFR/EGF complexes. This is performed by direct visualization and quantification of the rate of EGF-Alexa595/EGFR internalization and degradation in HeLa cells expressing HTLV regulatory proteins by immunofluorescence and western blot.

  8. A novel insulin receptor-binding protein from Momordica charantia enhances glucose uptake and glucose clearance in vitro and in vivo through triggering insulin receptor signaling pathway.

    Science.gov (United States)

    Lo, Hsin-Yi; Ho, Tin-Yun; Li, Chia-Cheng; Chen, Jaw-Chyun; Liu, Jau-Jin; Hsiang, Chien-Yun

    2014-09-10

    Diabetes, a common metabolic disorder, is characterized by hyperglycemia. Insulin is the principal mediator of glucose homeostasis. In a previous study, we identified a trypsin inhibitor, named Momordica charantia insulin receptor (IR)-binding protein (mcIRBP) in this study, that might interact with IR. The physical and functional interactions between mcIRBP and IR were clearly analyzed in the present study. Photo-cross-linking coupled with mass spectrometry showed that three regions (17-21, 34-40, and 59-66 residues) located on mcIRBP physically interacted with leucine-rich repeat domain and cysteine-rich region of IR. IR-binding assay showed that the binding behavior of mcIRBP and insulin displayed a cooperative manner. After binding to IR, mcIRBP activated the kinase activity of IR by (5.87 ± 0.45)-fold, increased the amount of phospho-IR protein by (1.31 ± 0.03)-fold, affected phosphoinositide-3-kinase/Akt pathways, and consequently stimulated the uptake of glucose in 3T3-L1 cells by (1.36 ± 0.12)-fold. Intraperitoneal injection of 2.5 nmol/kg mcIRBP significantly decreased the blood glucose levels by 20.9 ± 3.2% and 10.8 ± 3.6% in normal and diabetic mice, respectively. Microarray analysis showed that mcIRBP affected genes involved in insulin signaling transduction pathway in mice. In conclusion, our findings suggest that mcIRBP is a novel IRBP that binds to sites different from the insulin-binding sites on IR and stimulates both the glucose uptake in cells and the glucose clearance in mice.

  9. A putative transport protein is involved in citrulline excretion and re-uptake during arginine deiminase pathway activity by Lactobacillus sakei.

    Science.gov (United States)

    Rimaux, Tom; Rivière, Audrey; Hebert, Elvira María; Mozzi, Fernanda; Weckx, Stefan; De Vuyst, Luc; Leroy, Frédéric

    2013-04-01

    Arginine conversion through the arginine deiminase (ADI) pathway is a common metabolic trait of Lactobacillus sakei which is ascribed to an arc operon and which inquisitively involves citrulline excretion and re-uptake. The aim of this study was to verify whether a putative transport protein (encoded by the PTP gene) plays a role in citrulline-into-ornithine conversion by L. sakei strains. This was achieved through a combination of fermentation experiments, gene expression analysis via quantitative real-time reverse transcription PCR (RT-qPCR) and construction of a PTP knock-out mutant. Expression of the PTP gene was modulated by environmental pH and was highest in the end-exponential or mid-exponential growth phase for L. sakei strains CTC 494 and 23K, respectively. In contrast to known genes of the arc operon, the PTP gene showed low expression at pH 7.0, in agreement with the finding that citrulline-into-ornithine conversion is inhibited at this pH. The presence of additional energy sources also influenced ADI pathway activity, in particular by decreasing citrulline-into-ornithine conversion. Further insight into the functionality of the PTP gene was obtained with a knock-out mutant of L. sakei CTC 494 impaired in the PTP gene, which displayed inhibition in its ability to convert extracellular citrulline into ornithine. In conclusion, results indicated that the PTP gene may putatively encode a citrulline/ornithine antiporter.

  10. Two chalcones, 4-hydroxyderricin and xanthoangelol, stimulate GLUT4-dependent glucose uptake through the LKB1/AMP-activated protein kinase signaling pathway in 3T3-L1 adipocytes.

    Science.gov (United States)

    Ohta, Mitsuhiro; Fujinami, Aya; Kobayashi, Norihiro; Amano, Akiko; Ishigami, Akihito; Tokuda, Harukuni; Suzuki, Nobutaka; Ito, Fumitake; Mori, Taisuke; Sawada, Morio; Iwasa, Koichi; Kitawaki, Jo; Ohnishi, Katsunori; Tsujikawa, Muneo; Obayashi, Hiroshi

    2015-07-01

    4-Hydroxyderricin (4HD) and xanthoangelol (XAG) are major components of n-hexane/ethyl acetate (5:1) extract of the yellow-colored stem juice of Angelica keiskei. 4-Hydroxyderricin and XAG have been reported to increase glucose transporter 4 (GLUT4)-dependent glucose uptake in 3T3-L1 adipocytes, but the detailed mechanism of this phenomenon remains unknown. This present study was aimed at clarifying the detailed mechanism by which 4HD and XAG increase GLUT4-dependent glucose uptake in 3T3-L1 adipocytes. Both 4HD and XAG increased glucose uptake and GLUT4 translocation to the plasma membrane. 4-Hydroxyderricin and XAG also stimulated the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) and its downstream target acetyl-CoA carboxylase. In addition, phosphorylation of liver kinase B1 (LKB1), which acts upstream of AMPK, was also increased by 4HD and XAG treatment. Small interfering RNA knockdown of LKB1 attenuated 4HD- and XAG-stimulated AMPK phosphorylation and suppressed glucose uptake. These findings demonstrate that 4HD and XAG can increase GLUT4-dependent glucose uptake through the LKB1/AMPK signaling pathway in 3T3-L1 adipocytes.

  11. Enhancement of glucose uptake in muscular cell by soybean charged peptides isolated by electrodialysis with ultrafiltration membranes (EDUF): activation of the AMPK pathway.

    Science.gov (United States)

    Roblet, Cyril; Doyen, Alain; Amiot, Jean; Pilon, Geneviève; Marette, André; Bazinet, Laurent

    2014-03-15

    Soy peptides consumption has been associated with beneficial effects in type 2 diabetes patients. However, the peptide fractions responsible for these effects, and their mechanisms of action, have not been identified yet. In this study, we have isolated soybean peptides by electrodialysis with an ultrafiltration membrane (EDUF) at 50 V/100 kDa, and tested them for their capacity to improve glucose uptake in L6 muscle cells. We observed that these fractions were able to significantly enhance glucose uptake in the presence of insulin. The reported bioactivity would be due to the low molecular weight peptides (300-500 Da) recovered. Moreover, we observed that an enhancement of glucose uptake was correlated to the activation of the AMPK enzyme, well known for its capacity to increase glucose uptake in muscle cells. To our knowledge, this is the first time that bioactive peptides with glucose uptake activity have been isolated from a complex soy matrix, and that the implication of AMPK in it is demonstrated. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Targeting the cubilin receptor through the vitamin B(12) uptake pathway: cytotoxicity and mechanistic insight through fluorescent Re(I) delivery.

    Science.gov (United States)

    Viola-Villegas, Nerissa; Rabideau, Amy E; Bartholomä, Mark; Zubieta, Jon; Doyle, Robert P

    2009-08-27

    The intrinsic factor (IF) vitamin B(12) ileum anchored receptor, cubilin, mediates endocytotic uptake of the IF complex of vitamin B(12) to the blood serum. This receptor was targeted for the selective delivery and accumulation of a new bioprobe, a B(12) conjugate of rhenium 2, in the cubilin expressing placental choriocarcinoma BeWo cell line. Competitive uptake and cytotoxicity assays of 2 were investigated and interactions with nuclear DNA explored. In addition, the mechanism of internalization of 2 was confirmed to proceed in an IF-cubilin mediated fashion via siRNA transfection experiments. These studies show the great potential of cubilin as a new target for the delivery of B(12) based conjugates for cancer diagnostics and/or treatment.

  13. Mechanism of riboflavin uptake by cultured human retinal pigment epithelial ARPE-19 cells: possible regulation by an intracellular Ca2+-calmodulin-mediated pathway

    OpenAIRE

    Said, Hamid M.; Wang, S.L.; Ma, T Y

    2005-01-01

    In mammalian cells (including those of the ocular system), the water-soluble vitamin B-2 (riboflavin, RF) assumes an essential role in a variety of metabolic reactions and is critical for normal cellular functions, growth and development. Cells of the human retinal pigment epithelium (hRPE) play an important role in providing a sufficient supply of RF to the retina, but nothing is known about the mechanism of the vitamin uptake by these cells and its regulation. Our aim in the present study w...

  14. Mitochondrial calcium uptake.

    Science.gov (United States)

    Williams, George S B; Boyman, Liron; Chikando, Aristide C; Khairallah, Ramzi J; Lederer, W J

    2013-06-25

    Calcium (Ca(2+)) uptake into the mitochondrial matrix is critically important to cellular function. As a regulator of matrix Ca(2+) levels, this flux influences energy production and can initiate cell death. If large, this flux could potentially alter intracellular Ca(2+) ([Ca(2+)]i) signals. Despite years of study, fundamental disagreements on the extent and speed of mitochondrial Ca(2+) uptake still exist. Here, we review and quantitatively analyze mitochondrial Ca(2+) uptake fluxes from different tissues and interpret the results with respect to the recently proposed mitochondrial Ca(2+) uniporter (MCU) candidate. This quantitative analysis yields four clear results: (i) under physiological conditions, Ca(2+) influx into the mitochondria via the MCU is small relative to other cytosolic Ca(2+) extrusion pathways; (ii) single MCU conductance is ∼6-7 pS (105 mM [Ca(2+)]), and MCU flux appears to be modulated by [Ca(2+)]i, suggesting Ca(2+) regulation of MCU open probability (P(O)); (iii) in the heart, two features are clear: the number of MCU channels per mitochondrion can be calculated, and MCU probability is low under normal conditions; and (iv) in skeletal muscle and liver cells, uptake per mitochondrion varies in magnitude but total uptake per cell still appears to be modest. Based on our analysis of available quantitative data, we conclude that although Ca(2+) critically regulates mitochondrial function, the mitochondria do not act as a significant dynamic buffer of cytosolic Ca(2+) under physiological conditions. Nevertheless, with prolonged (superphysiological) elevations of [Ca(2+)]i, mitochondrial Ca(2+) uptake can increase 10- to 1,000-fold and begin to shape [Ca(2+)]i dynamics.

  15. Macroalgae mitigation potential for fish aquaculture effluents: an approach coupling nitrogen uptake and metabolic pathways using Ulva rigida and Enteromorpha clathrata.

    Science.gov (United States)

    Aníbal, Jaime; Madeira, Hélder T; Carvalho, Liliana F; Esteves, Eduardo; Veiga-Pires, Cristina; Rocha, Carlos

    2014-12-01

    Aquaculture effluents are rich in nitrogen compounds that may enhance local primary productivity, leading to the development of algae blooms. The goal of this study was to assess the potential use of naturally occurring green macroalgae (Ulva and Enteromorpha) as bioremediators for nitrogen-rich effluents from a fish aquaculture plant, by evaluating their respective uptake dynamics under controlled conditions. Ulva and Enteromorpha were incubated separately in aquaculture effluent from a local pilot station. Algae tissue and water samples were collected periodically along 4 h. For each sample, nitrate, nitrite, and ammonia concentrations were quantified in the effluent, while internal algae reserve pools and nitrate reductase activity (NRA) were determined within the algae tissues. Both macroalgae absorbed all dissolved inorganic nitrogen compounds in less than 1 h, favoring ammonia over nitrate. Ulva stored nitrate temporarily as an internal reserve and only used it after ammonia availability decreased, whereas Enteromorpha stored and metabolized ammonia and nitrate simultaneously. These distinct dynamics of ammonia and nitrate uptake supported an increase in NRA during the experiment. This study supports the hypothesis that Ulva or Enteromorpha can be used as bioremediators in aquaculture effluents to mitigate excess of dissolved inorganic nitrogen.

  16. Analysis of Sensitive CO2 Pathways and Genes Related to Carbon Uptake and Accumulation in Chlamydomonas reinhardtii through Genomic Scale Modeling and Experimental Validation

    Science.gov (United States)

    Winck, Flavia V.; Melo, David O. Páez; Riaño-Pachón, Diego M.; Martins, Marina C. M.; Caldana, Camila; Barrios, Andrés F. González

    2016-01-01

    The development of microalgae sustainable applications needs better understanding of microalgae biology. Moreover, how cells coordinate their metabolism toward biomass accumulation is not fully understood. In this present study, flux balance analysis (FBA) was performed to identify sensitive metabolic pathways of Chlamydomonas reinhardtii under varied CO2 inputs. The metabolic network model of Chlamydomonas was updated based on the genome annotation data and sensitivity analysis revealed CO2 sensitive reactions. Biological experiments were performed with cells cultivated at 0.04% (air), 2.5, 5, 8, and 10% CO2 concentration under controlled conditions and cell growth profiles and biomass content were measured. Pigments, lipids, proteins, and starch were further quantified for the reference low (0.04%) and high (10%) CO2 conditions. The expression level of candidate genes of sensitive reactions was measured and validated by quantitative real time PCR. The sensitive analysis revealed mitochondrial compartment as the major affected by changes on the CO2 concentrations and glycolysis/gluconeogenesis, glyoxylate, and dicarboxylate metabolism among the affected metabolic pathways. Genes coding for glycerate kinase (GLYK), glycine cleavage system, H-protein (GCSH), NAD-dependent malate dehydrogenase (MDH3), low-CO2 inducible protein A (LCIA), carbonic anhydrase 5 (CAH5), E1 component, alpha subunit (PDC3), dual function alcohol dehydrogenase/acetaldehyde dehydrogenase (ADH1), and phosphoglucomutase (GPM2), were defined, among other genes, as sensitive nodes in the metabolic network simulations. These genes were experimentally responsive to the changes in the carbon fluxes in the system. We performed metabolomics analysis using mass spectrometry validating the modulation of carbon dioxide responsive pathways and metabolites. The changes on CO2 levels mostly affected the metabolism of amino acids found in the photorespiration pathway. Our updated metabolic network was

  17. Mapping cellular Fe-S cluster uptake and exchange reactions - divergent pathways for iron-sulfur cluster delivery to human ferredoxins.

    Science.gov (United States)

    Fidai, Insiya; Wachnowsky, Christine; Cowan, J A

    2016-12-07

    Ferredoxins are protein mediators of biological electron-transfer reactions and typically contain either [2Fe-2S] or [4Fe-4S] clusters. Two ferredoxin homologues have been identified in the human genome, Fdx1 and Fdx2, that share 43% identity and 69% similarity in protein sequence and both bind [2Fe-2S] clusters. Despite the high similarity, the two ferredoxins play very specific roles in distinct physiological pathways and cannot replace each other in function. Both eukaryotic and prokaryotic ferredoxins and homologues have been reported to receive their Fe-S cluster from scaffold/delivery proteins such as IscU, Isa, glutaredoxins, and Nfu. However, the preferred and physiologically relevant pathway for receiving the [2Fe-2S] cluster by ferredoxins is subject to speculation and is not clearly identified. In this work, we report on in vitro UV-visible (UV-vis) circular dichroism studies of [2Fe-2S] cluster transfer to the ferredoxins from a variety of partners. The results reveal rapid and quantitative transfer to both ferredoxins from several donor proteins (IscU, Isa1, Grx2, and Grx3). Transfer from Isa1 to Fdx2 was also observed to be faster than that of IscU to Fdx2, suggesting that Fdx2 could receive its cluster from Isa1 instead of IscU. Several other transfer combinations were also investigated and the results suggest a complex, but kinetically detailed map for cellular cluster trafficking. This is the first step toward building a network map for all of the possible iron-sulfur cluster transfer pathways in the mitochondria and cytosol, providing insights on the most likely cellular pathways and possible redundancies in these pathways.

  18. Analysis of sensitive CO2 pathways and genes related to carbon uptake and accumulation in Chlamydomonas reinhardtii through genomic scale modeling and experimental validation

    Directory of Open Access Journals (Sweden)

    Flavia Vischi Winck

    2016-02-01

    Full Text Available The development of microalgae sustainable applications needs better understanding of microalgae biology. Moreover, how cells coordinate their metabolism towards biomass accumulation is not fully understood. In this present study, flux balance analysis (FBA was performed to identify sensitive metabolic pathways of Chlamydomonas reinhardtii under varied CO2 inputs. The metabolic network model of Chlamydomonas was updated based on the genome annotation data and sensitivity analysis revealed CO2 sensitive reactions. Biological experiments were performed with cells cultivated at 0.04% (air, 2.5%, 5%, 8% and 10% CO2 concentration under controlled conditions and cell growth profiles and biomass content were measured. Pigments, lipids, proteins and starch were further quantified for the reference low (0.04% and high (10% CO2 conditions. The expression level of candidate genes of sensitive reactions was measured and validated by quantitative real time qPCR. The sensitive analysis revealed mitochondrial compartment as the major affected by high CO2 levels and glycolysis/gluconeogenesis, glyoxylate and dicarboxylate metabolism among the affected metabolic pathways. Genes coding for glycerate kinase (GLYK, glycine cleavage system, H-protein (GCSH, NAD-dependent malate dehydrogenase (MDH3, low-CO2 inducible protein A (LCIA, carbonic anhydrase 5 (CAH5, E1 component, alpha subunit (PDC3, dual function alcohol dehydrogenase/acetaldehyde dehydrogenase (ADH1 and phosphoglucomutase (GPM2, were defined, among other genes, as sensitive nodes in the metabolic network simulations. These genes were experimentally responsive to the changes in the carbon fluxes in the system. We performed metabolomics analysis using mass spectrometry validating the modulation of carbon dioxide responsive pathways and metabolites. The changes on CO2 levels mostly affected the metabolism of amino acids found in the photorespiration pathway. Our updated metabolic network was compared to

  19. Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: the effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids.

    Science.gov (United States)

    Lam, Y Y; Hatzinikolas, G; Weir, J M; Janovská, A; McAinch, A J; Game, P; Meikle, P J; Wittert, G A

    2011-01-01

    The study aims to determine the effect of long-chain saturated and polyunsaturated (PUFA) fatty acids, specifically palmitic acid (PA; 16:0), docosahexaenoic acid (DHA; 22:6n-3) and linoleic acid (LA; 18:2n-6), and their interactions with factors from adipose tissue, on insulin sensitivity and lipid metabolism in skeletal muscle. L6 myotubes were cultured with PA, DHA or LA (0.4mmol/l), with or without conditioned media from human subcutaneous (SC) and visceral (IAB) fat. Insulin-stimulated glucose uptake, lipid content, mRNA expression of key genes involved in nutrient utilization and protein expression of inhibitor protein inhibitor kappa B (IκB)-α and mammalian target of rapamycin (mTOR) were measured. PA and IAB fat reduced insulin-stimulated glucose uptake and their combined effect was similar to that of PA alone. PA-induced insulin resistance was ameliorated by inhibiting the de novo synthesis of ceramide, IκBα degradation or mTOR activation. The PA effect was also partially reversed by DHA and completely by LA in the presence of SC fat. PA increased diacylglycerol content, which was reduced by LA and to a greater extent when either IAB or SC fat was also present. PA increased SCD1 whereas DHA and LA increased AMPKα2 mRNA. In the presence of SC or IAB fat, the combination of PA with either DHA or LA decreased SCD1 and increased AMPKα2 mRNA. PA-induced insulin resistance in skeletal muscle involves inflammatory (nuclear factor kappa B/mTOR) and nutrient (ceramide) pathways. PUFAs promote pathways, at a transcriptional level, that increase fat oxidation and synergize with factors from SC fat to abrogate PA-induced insulin resistance. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Thyroid Scan and Uptake

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ... the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a ...

  1. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses ... the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a ...

  2. Thyroid Scan and Uptake

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z Thyroid Scan and Uptake Thyroid scan and uptake uses small ... Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is a type ...

  3. Exosomes: Mechanisms of Uptake

    Directory of Open Access Journals (Sweden)

    Kelly J. McKelvey

    2015-07-01

    Full Text Available Exosomes are 30–100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non- immune cell types (e.g., cancer cells and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of para‐ mount importance.

  4. Exosomes: Mechanisms of Uptake

    Directory of Open Access Journals (Sweden)

    Kelly J. McKelvey

    2015-07-01

    Full Text Available Exosomes are 30–100 nm microvesicles which contain complex cellular signals of RNA, protein and lipids. Because of this, exosomes are implicated as having limitless therapeutic potential for the treatment of cancer, pregnancy complications, infections, and autoimmune diseases. To date we know a considerable amount about exosome biogenesis and secretion, but there is a paucity of data regarding the uptake of exosomes by immune and non-immune cell types (e.g., cancer cells and the internal signalling pathways by which these exosomes elicit a cellular response. Answering these questions is of paramount importance.

  5. Orexin-A promotes Glu uptake by OX1R/PKCα/ERK1/2/GLT-1 pathway in astrocytes and protects co-cultured astrocytes and neurons against apoptosis in anoxia/hypoglycemic injury in vitro.

    Science.gov (United States)

    Shu, Qing; Zhang, Jianhuai; Ma, Wei; Lei, Youying; Zhou, Dan

    2017-01-01

    Orexin-A, which is an endogenous neuropeptide, is reported to have a protective role in ischemic stroke. High-concentration glutamic acid (Glu) induced by hypoxia injury in ischemic stroke can be inhibited by glial glutamate transporter GLT-1 which is only expressed in astroglia cells. A previous study reported that Orexin-A may regulate GLT-1 expression. However, the role of orexin-A in the regulation of GLT-1 in ischemic stroke still remains unclear. In this study, we aimed to investigate the effect and the underlying mechanism of orexin-A on Glu uptake in astrocytes in vitro and this effect on protecting the neurons from anoxia/hypoglycemic injury. The expression of GLT-1 significantly increased in the astrocytes with orexin-A treatment under anoxia/hypoglycemic conditions, promoting the uptake of Glu and inhibiting the apoptosis of co-cultured cells of astrocytes and neurons. However, these effects were significantly weakened by treatment with orexin-A receptor 1 (OX1R) antagonist. Orexin-A significantly up-regulated the expressions of PKCα and ERK1/2 under anoxia/hypoglycemic conditions in astrocytes, whereas the OX1R antagonist markedly reversed the effect. Furthermore, PKCα or ERK1/2 inhibitor significantly constrained the GLT-1 expression in astrocytes and facilitated the apoptosis of co-cultured cells, and GLT-1 overexpression could reverse those effects of PKCα or ERK1/2 inhibitor. Taken together, orexin-A promoted the GLT-1 expression via OX1R/PKCα/ERK1/2 pathway in astrocytes and protected co-cultured cells against anoxia/hypoglycemic injury.

  6. Thyroid Scan and Uptake

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    Full Text Available ... Uptake? A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) ... of thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that ...

  7. Thyroid Scan and Uptake

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    Full Text Available ... limitations of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan ... tissues in your body. top of page How is the procedure performed? Nuclear medicine imaging is usually ...

  8. Thyroid Scan and Uptake

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    Full Text Available ... Uptake? A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) ... of thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that ...

  9. Thyroid Scan and Uptake

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    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... code: Phone no: Thank you! Do you have a personal story about radiology? Share your patient story ...

  10. Thyroid Scan and Uptake

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    Full Text Available ... known as a thyroid uptake. It is a measurement of thyroid function, but does not involve imaging. ... eating can affect the accuracy of the uptake measurement. Jewelry and other metallic accessories should be left ...

  11. Thyroid Scan and Uptake

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    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... encourage linking to this site. × Recommend RadiologyInfo to a friend Send to (friend's e-mail address): From ( ...

  12. Thyroid Scan and Uptake

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    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician ... of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is also known as a thyroid uptake. ...

  13. Thyroid Scan and Uptake

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    Full Text Available ... of the Thyroid Scan and Uptake? What is a Thyroid Scan and Uptake? A thyroid scan is ... encourage linking to this site. × Recommend RadiologyInfo to a friend Send to (friend's e-mail address): From ( ...

  14. Thyroid Scan and Uptake

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    Full Text Available Toggle navigation Test/Treatment Patient Type Screening/Wellness Disease/Condition Safety En Español More Info Images/Videos About Us News Physician ... of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is also known as a thyroid uptake. ...

  15. Thyroid Scan and Uptake

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    Full Text Available ... uptake are not performed on patients who are pregnant because of the risk of exposing the fetus to radiation. These tests are also not recommended for breastfeeding women. Nuclear medicine procedures can be time consuming. It ...

  16. Thyroid Scan and Uptake

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    Full Text Available ... is taken by mouth, in either liquid or capsule form, it is typically swallowed up to 24 ... I-123 or I-131) in liquid or capsule form to swallow. The thyroid uptake will begin ...

  17. Thyroid Scan and Uptake

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    Full Text Available ... which are encased in metal and plastic and most often shaped like a box, attached to a ... will I experience during and after the procedure? Most thyroid scan and thyroid uptake procedures are painless. ...

  18. Thyroid Scan and Uptake

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    Full Text Available ... scan and uptake uses small amounts of radioactive materials called radiotracers, a special camera and a computer ... last two months that used iodine-based contrast material. Your doctor will instruct you on how to ...

  19. Thyroid Scan and Uptake

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    Full Text Available ... eat for several hours before your exam because eating can affect the accuracy of the uptake measurement. ... often unattainable using other imaging procedures. For many diseases, nuclear medicine scans yield the most useful information ...

  20. Thyroid Scan and Uptake

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    Full Text Available ... RAIU) is also known as a thyroid uptake. It is a measurement of thyroid function, but does ... they offer the potential to identify disease in its earliest stages as well as a patient’s immediate ...

  1. Thyroid Scan and Uptake

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    Full Text Available ... time for the imaging to begin, you will sit in a chair facing a stationary probe positioned ... counter used for thyroid uptake exams. The patient sits with the camera directed at the neck for ...

  2. Thyroid Scan and Uptake

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    Full Text Available ... for several hours before your exam because eating can affect the accuracy of the uptake measurement. Jewelry ... small hand-held device resembling a microphone that can detect and measure the amount of the radiotracer ...

  3. Thyroid Scan and Uptake

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    Full Text Available ... information about your thyroid’s size, shape, position and function that is often unattainable using other imaging procedures. ... thyroid uptake. It is a measurement of thyroid function, but does not involve imaging. Nuclear medicine is ...

  4. Thyroid Scan and Uptake

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    Full Text Available ... A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is ... thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that uses ...

  5. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... RAIU) is also known as a thyroid uptake. It is a measurement of thyroid function, but does ... they offer the potential to identify disease in its earliest stages as well as a patient’s immediate ...

  6. Routes and mechanisms of extracellular vesicle uptake

    Directory of Open Access Journals (Sweden)

    Laura Ann Mulcahy

    2014-08-01

    Full Text Available Extracellular vesicles (EVs are small vesicles released by donor cells that can be taken up by recipient cells. Despite their discovery decades ago, it has only recently become apparent that EVs play an important role in cell-to-cell communication. EVs can carry a range of nucleic acids and proteins which can have a significant impact on the phenotype of the recipient. For this phenotypic effect to occur, EVs need to fuse with target cell membranes, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest because they are deregulated in diseases such as cancer and they could be harnessed to deliver drugs to target cells. It is therefore important to understand the molecular mechanisms by which EVs are taken up into cells. This comprehensive review summarizes current knowledge of EV uptake mechanisms. Cells appear to take up EVs by a variety of endocytic pathways, including clathrin-dependent endocytosis, and clathrin-independent pathways such as caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft–mediated internalization. Indeed, it seems likely that a heterogeneous population of EVs may gain entry into a cell via more than one route. The uptake mechanism used by a given EV may depend on proteins and glycoproteins found on the surface of both the vesicle and the target cell. Further research is needed to understand the precise rules that underpin EV entry into cells.

  7. The Uptake of GABA in Trypanosoma cruzi.

    Science.gov (United States)

    Galvez Rojas, Robert L; Ahn, Il-Young; Suárez Mantilla, Brian; Sant'Anna, Celso; Pral, Elizabeth Mieko Furusho; Silber, Ariel Mariano

    2015-01-01

    Gamma aminobutyric acid (GABA) is widely known as a neurotransmitter and signal transduction molecule found in vertebrates, plants, and some protozoan organisms. However, the presence of GABA and its role in trypanosomatids is unknown. Here, we report the presence of intracellular GABA and the biochemical characterization of its uptake in Trypanosoma cruzi, the etiological agent of Chagas' disease. Kinetic parameters indicated that GABA is taken up by a single transport system in pathogenic and nonpathogenic forms. Temperature dependence assays showed a profile similar to glutamate transport, but the effect of extracellular cations Na(+) , K(+) , and H(+) on GABA uptake differed, suggesting a different uptake mechanism. In contrast to reports for other amino acid transporters in T. cruzi, GABA uptake was Na(+) dependent and increased with pH, with a maximum activity at pH 8.5. The sensitivity to oligomycin showed that GABA uptake is dependent on ATP synthesis. These data point to a secondary active Na(+) /GABA symporter energized by Na(+) -exporting ATPase. Finally, we show that GABA occurs in the parasite's cytoplasm under normal culture conditions, indicating that it is regularly taken up from the culture medium or synthesized through an still undescribed metabolic pathway.

  8. Osmotic stress response in Acinetobacter baylyi: identification of a glycine-betaine biosynthesis pathway and regulation of osmoadaptive choline uptake and glycine-betaine synthesis through a choline-responsive BetI repressor.

    Science.gov (United States)

    Scholz, Anica; Stahl, Julia; de Berardinis, Veronique; Müller, Volker; Averhoff, Beate

    2016-04-01

    Acinetobacter baylyi, a ubiquitous soil bacterium, can cope with high salinity by uptake of choline as precursor of the compatible solute glycine betaine. Here, we report on the identification of a choline dehydrogenase (BetA) and a glycine betaine aldehyde dehydrogenase (BetB) mediating the oxidation of choline to glycine betaine. The betAB genes were found to form an operon together with the potential transcriptional regulator betI. The transcription of the betIBA operon and the two recently identified choline transporters was upregulated in response to choline and choline plus salt. The finding that the osmo-independent transporter BetT1 undergoes a higher upregulation in response to choline alone than betT2 suggests that BetT1 does not primarily function in osmoadaptation. Electrophoretic mobility shift assays led to the conclusion that BetI mediates transcriptional regulation of both, the betIBA gene operon and the choline transporters. BetI was released from the DNA in response to choline which together with the transcriptional upregulation of the bet genes in the presence of choline suggests that BetI is a choline sensing transcriptional repressor.

  9. Thyroid Scan and Uptake

    Medline Plus

    Full Text Available ... type your comment or suggestion into the following text box: Comment: E-mail: Area code: Phone no: Thank you! Images × Image Gallery Photograph of a typical probe counter used for thyroid uptake exams. The patient sits with the camera directed at the neck for five minutes, and then the leg for ...

  10. α-Melanocyte stimulating hormone promotes muscle glucose uptake via melanocortin 5 receptors

    Directory of Open Access Journals (Sweden)

    Pablo J. Enriori

    2016-10-01

    Conclusion: These data describe a novel endocrine circuit that modulates glucose homeostasis by pituitary α-MSH, which increases muscle glucose uptake and thermogenesis through the activation of a MC5R-PKA-pathway, which is disrupted in obesity.

  11. Arsenic uptake and metabolism in plants.

    Science.gov (United States)

    Zhao, F J; Ma, J F; Meharg, A A; McGrath, S P

    2009-03-01

    Arsenic (As) is an element that is nonessential for and toxic to plants. Arsenic contamination in the environment occurs in many regions, and, depending on environmental factors, its accumulation in food crops may pose a health risk to humans.Recent progress in understanding the mechanisms of As uptake and metabolism in plants is reviewed here. Arsenate is taken up by phosphate transporters. A number of the aquaporin nodulin26-like intrinsic proteins (NIPs) are able to transport arsenite,the predominant form of As in reducing environments. In rice (Oryza sativa), arsenite uptake shares the highly efficient silicon (Si) pathway of entry to root cells and efflux towards the xylem. In root cells arsenate is rapidly reduced to arsenite, which is effluxed to the external medium, complexed by thiol peptides or translocated to shoots. One type of arsenate reductase has been identified, but its in planta functions remain to be investigated. Some fern species in the Pteridaceae family are able to hyperaccumulate As in above-ground tissues. Hyperaccumulation appears to involve enhanced arsenate uptake, decreased arsenite-thiol complexation and arsenite efflux to the external medium, greatly enhanced xylem translocation of arsenite, and vacuolar sequestration of arsenite in fronds. Current knowledge gaps and future research directions are also identified.

  12. Uptake of nuclides by plants

    Energy Technology Data Exchange (ETDEWEB)

    Greger, Maria [Stockholm Univ. (Sweden). Dept. of Botany

    2004-04-01

    This review on plant uptake of elements has been prepared to demonstrate how plants take up different elements. The work discusses the nutrient elements, as well as the general uptake and translocation in plants, both via roots and by foliar absorption. Knowledge of the uptake by the various elements within the periodic system is then reviewed. The work also discusses transfer factors (TF) as well as difficulties using TF to understand the uptake by plants. The review also focuses on species differences. Knowledge necessary to understand and calculate plant influence on radionuclide recirculation in the environment is discussed, in which the plant uptake of a specific nuclide and the fate of that nuclide in the plant must be understood. Plants themselves determine the uptake, the soil/sediment determines the availability of the nuclides and the nuclides themselves can interact with each other, which also influences the uptake. Consequently, it is not possible to predict the nuclide uptake in plants by only analysing the nuclide concentration of the soil/substrate.

  13. Uptake of trifluoroacetate by Pinus ponderosa via atmospheric pathway

    Science.gov (United States)

    Benesch, J. A.; Gustin, M. S.

    Trifluoroacetate (TFA, CF 3COO -), a break down product of hydro(chloro)-fluorocarbons (HFC/HCFCs), has been suggested to contribute to forest decline syndrome. To investigate the possible effects, Pinus ponderosa was exposed to TFA applied as mist (150 and 10,000 ng l -1) to foliar surfaces. Needles accumulated TFA as a function of concentration and time. However, no adverse physiological responses, as plant morphology, photosynthetic and conductance rates, were observed at the TFA concentrations used in this study.

  14. BPA uptake in rat tissues after partial hepatectomy

    Energy Technology Data Exchange (ETDEWEB)

    Slatkin, D.N.; Nawrocky, M.M.; Coderre, J.A.; Fisher, C.D.; Joel, D.D.; Lombardo, D.T.; Micca, P.L.

    1996-12-31

    In boron neutron capture therapy (BNCT), boron given as boronophenylalanine (BPA) accumulates transiently not only in tumors but also in normal tissues. Average boron concentrations in transplanted 9L gliosarcoma tumors of 20 rats were 2.5 to 3.7 times concentrations found in blood. Although boron levels in a variety of tissues were also higher than blood the concentrations were less than the lowest found in the tumor. Further note than although BPA is a structural analogue of phenylalanine (Phe), the pathway of BPA uptake into regenerating liver may not be linked to Phe uptake mechanisms.

  15. Uptake of /sup 131/I by some hydroponically grown crops

    Energy Technology Data Exchange (ETDEWEB)

    Asprer, G.A.; Lansangan, L.M.; de la Paz, L.R. (Philippine Atomic Energy Commission, Diliman, Quezon City)

    Biologically labelled vegetables which include kangkong and sweet potato tops were grown hydroponically in a modified Hoagland-Arnon nutrient solution containing radioiodine with 0.5% non-radioactive Nal solution as the medium. The crops considered in this study are commonly eaten by Filipinos. The concentration of the solution as well as the uptake in the plant system were determined at various time intervals. The extent of radioiodine uptake through air-water-plant pathway is one of the parameters needed for calculating the dose that the general populace could be exposed to, due to radioactivity in the environment.

  16. Regulatory mechanisms for glycogenolysis and K+ uptake in brain astrocytes.

    Science.gov (United States)

    DiNuzzo, Mauro; Mangia, Silvia; Maraviglia, Bruno; Giove, Federico

    2013-11-01

    Recent advances in brain energy metabolism support the notion that glycogen in astrocytes is necessary for the clearance of neuronally-released K(+) from the extracellular space. However, how the multiple metabolic pathways involved in K(+)-induced increase in glycogen turnover are regulated is only partly understood. Here we summarize the current knowledge about the mechanisms that control glycogen metabolism during enhanced K(+) uptake. We also describe the action of the ubiquitous Na(+)/K(+) ATPase for both ion transport and intracellular signaling cascades, and emphasize its importance in understanding the complex relation between glycogenolysis and K(+) uptake.

  17. Nanodiamond internalization in cells and the cell uptake mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Perevedentseva, E. [National Dong Hwa University, Department of Physics (China); Hong, S.-F.; Huang, K.-J. [National Dong Hwa University, Department of Life Sciences (China); Chiang, I.-T.; Lee, C.-Y. [National Dong Hwa University, Department of Physics (China); Tseng, Y.-T. [National Dong Hwa University, Department of Life Sciences (China); Cheng, C.-L., E-mail: clcheng@mail.ndhu.edu.tw [National Dong Hwa University, Department of Physics (China)

    2013-08-15

    Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed.

  18. Nanodiamond internalization in cells and the cell uptake mechanism

    Science.gov (United States)

    Perevedentseva, E.; Hong, S.-F.; Huang, K.-J.; Chiang, I.-T.; Lee, C.-Y.; Tseng, Y.-T.; Cheng, C.-L.

    2013-08-01

    Cell type-dependent penetration of nanodiamond in living cells is one of the important factors for using nanodiamond as cellular markers/labels, for drug delivery as well as for other biomedical applications. In this work, internalization of 100 nm nanodiamonds by A549 lung human adenocarcinoma cell, Beas-2b non-tumorigenic human bronchial epithelial cell, and HFL-1 fibroblast-like human fetal lung cell is studied and compared. The penetration of nanodiamond into the cells was observed using confocal fluorescence imaging and Raman imaging methods. Visualization of the nanodiamond in cells allows comparison of the internalization for diamond nanoparticles in cancer A549 cell, non-cancer HFL-1, and Beas-2b cells. The dose-dependent and time-dependent behavior of nanodiamond uptake is observed in both cancer as well as non-cancer cells. The mechanism of nanodiamond uptake by cancer and non-cancer cells is analyzed by blocking different pathways. The uptake of nanodiamond in both cancer and non-cancer cells was found predominantly via clathrin-dependent endocytosis. In spite of observed similarity in the uptake mechanism for cancer and non-cancer cells, the nanodiamond uptake for cancer cell quantitatively exceeds the uptake for non-cancer cells, for the studied cell lines. The observed difference in internalization of nanodiamond by cancer and non-cancer cells is discussed.

  19. Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway.

    Science.gov (United States)

    Gandhi, Gopalsamy Rajiv; Jothi, Gnanasekaran; Antony, Poovathumkal James; Balakrishna, Kedike; Paulraj, Michael Gabriel; Ignacimuthu, Savarimuthu; Stalin, Antony; Al-Dhabi, Naif Abdullah

    2014-12-15

    In this study, the therapeutic efficacy of gallic acid from Cyamopsis tetragonoloba (L.) Taub. (Fabaceae) beans was examined against high-fat diet fed-streptozotocin-induced experimental type 2 diabetic rats. Molecular-dockings were done to determine the putative binding modes of gallic acid into the active sites of key insulin-signaling markers. Gallic acid (20 mg/kg) given to high-fat diet fed-streptozotocin-induced rats lowered body weight gain, fasting blood glucose and plasma insulin in diabetic rats. It further restored the alterations of biochemical parameters to near normal levels in diabetic treated rats along with cytoprotective action on pancreatic β-cell. Histology of liver and adipose tissues supported the biochemical findings. Gallic acid significantly enhanced the level of peroxisome proliferator-activated receptor γ (PPARγ) expression in the adipose tissue of treated rat compared to untreated diabetic rat; it also slightly activated PPARγ expressions in the liver and skeletal muscle. Consequently, it improved insulin-dependent glucose transport in adipose tissue through translocation and activation of glucose transporter protein 4 (GLUT4) in phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (p-Akt) dependent pathway. Gallic acid docked with PPARγ; it exhibited promising interactions with the GLUT4, glucose transporter protein 1 (GLUT1), PI3K and p-Akt. These findings provided evidence to show that gallic acid could improve adipose tissue insulin sensitivity, modulate adipogenesis, increase adipose glucose uptake and protect β-cells from impairment. Hence it can be used in the management of obesity-associated type 2 diabetes mellitus.

  20. The specific uptake size index for quantifying radiopharmaceutical uptake

    Energy Technology Data Exchange (ETDEWEB)

    Fleming, John S [Department of Medical Physics and Bioengineering, Southampton University Hospitals NHS Trust, Southampton (United Kingdom); Bolt, Livia [Department of Medical Physics and Bioengineering, Southampton University Hospitals NHS Trust, Southampton (United Kingdom); Stratford, Jennifer S [Department of Medical Physics and Bioengineering, Southampton University Hospitals NHS Trust, Southampton (United Kingdom); Kemp, Paul M [Department of Nuclear Medicine, Southampton University Hospitals NHS Trust, Southampton (United Kingdom)

    2004-07-21

    Quantitative indices of radionuclide uptake in an object of interest provide a useful adjunct to qualitative interpretation in the diagnostic application of radionuclide imaging. This note describes a new measure of total uptake of an organ, the specific uptake size index (SUSI). It can either be related in absolute terms to the total activity injected or to the specific activity in a reference region. As it depends on the total activity in the object, the value obtained will not depend on the resolution of the imaging process, as is the case with some other similar quantitative indices. This has been demonstrated in an experiment using simulated images. The application of the index to quantification of dopamine receptor SPECT imaging and parathyroid-thyroid subtraction planar scintigraphy is described. The index is considered to be of potential value in reducing variation in quantitative assessment of uptake in objects with applications in all areas of radionuclide imaging. (note)

  1. Influence of Acute and Chronic Exercise on Glucose Uptake

    Directory of Open Access Journals (Sweden)

    Martin Röhling

    2016-01-01

    Full Text Available Insulin resistance plays a key role in the development of type 2 diabetes. It arises from a combination of genetic predisposition and environmental and lifestyle factors including lack of physical exercise and poor nutrition habits. The increased risk of type 2 diabetes is molecularly based on defects in insulin signaling, insulin secretion, and inflammation. The present review aims to give an overview on the molecular mechanisms underlying the uptake of glucose and related signaling pathways after acute and chronic exercise. Physical exercise, as crucial part in the prevention and treatment of diabetes, has marked acute and chronic effects on glucose disposal and related inflammatory signaling pathways. Exercise can stimulate molecular signaling pathways leading to glucose transport into the cell. Furthermore, physical exercise has the potential to modulate inflammatory processes by affecting specific inflammatory signaling pathways which can interfere with signaling pathways of the glucose uptake. The intensity of physical training appears to be the primary determinant of the degree of metabolic improvement modulating the molecular signaling pathways in a dose-response pattern, whereas training modality seems to have a secondary role.

  2. Influence of Acute and Chronic Exercise on Glucose Uptake.

    Science.gov (United States)

    Röhling, Martin; Herder, Christian; Stemper, Theodor; Müssig, Karsten

    2016-01-01

    Insulin resistance plays a key role in the development of type 2 diabetes. It arises from a combination of genetic predisposition and environmental and lifestyle factors including lack of physical exercise and poor nutrition habits. The increased risk of type 2 diabetes is molecularly based on defects in insulin signaling, insulin secretion, and inflammation. The present review aims to give an overview on the molecular mechanisms underlying the uptake of glucose and related signaling pathways after acute and chronic exercise. Physical exercise, as crucial part in the prevention and treatment of diabetes, has marked acute and chronic effects on glucose disposal and related inflammatory signaling pathways. Exercise can stimulate molecular signaling pathways leading to glucose transport into the cell. Furthermore, physical exercise has the potential to modulate inflammatory processes by affecting specific inflammatory signaling pathways which can interfere with signaling pathways of the glucose uptake. The intensity of physical training appears to be the primary determinant of the degree of metabolic improvement modulating the molecular signaling pathways in a dose-response pattern, whereas training modality seems to have a secondary role.

  3. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN......(-) and H2O, respectively), were included as control samples. The results indicated that B12 derivatives delivered cisplatin to both cellular cytosol and nuclei with an efficiency of one third compared to the uptake of free cisplatin cis-[Pt(II)Cl2(NH3)2]. In addition, uptake of charged B12 derivatives...

  4. In vivo methods to study uptake of nanoparticles into the brain.

    Science.gov (United States)

    van Rooy, Inge; Cakir-Tascioglu, Serpil; Hennink, Wim E; Storm, Gert; Schiffelers, Raymond M; Mastrobattista, Enrico

    2011-03-01

    Several in vivo techniques have been developed to study and measure the uptake of CNS compounds into the brain. With these techniques, various parameters can be determined after drug administration, including the blood-to-brain influx constant (K(in)), the permeability-surface area (PS) product, and the brain uptake index (BUI). These techniques have been mostly used for drugs that are expected to enter the brain via transmembrane diffusion or by carrier-mediated transcytosis. Drugs that have limitations in entering the brain via such pathways have been encapsulated in nanoparticles (based on lipids or synthetic polymers) to enhance brain uptake. Nanoparticles are different from CNS compounds in size, composition and uptake mechanisms. This has led to different methods and approaches to study brain uptake in vivo. Here we discuss the techniques generally used to measure nanoparticle uptake in addition to the techniques used for CNS compounds. Techniques include visualization methods, behavioral tests, and quantitative methods.

  5. Bundle Sheath Leakiness and Light Limitation during C-4 Leaf and Canopy CO2 Uptake

    NARCIS (Netherlands)

    Kromdijk, J.; Schepers, H.E.; Albanito, F.; Fitton, N.; Carroll, F.; Jones, M.B.; Finnan, J.; Lanigan, G.J.; Griffiths, H.

    2008-01-01

    Perennial species with the C-4 pathway hold promise for biomass-based energy sources. We have explored the extent that CO2 uptake of such species may be limited by light in a temperate climate. One energetic cost of the C-4 pathway is the leakiness (phi) of bundle sheath tissues, whereby a variable

  6. Water uptake and water supply

    NARCIS (Netherlands)

    Sonneveld, C.; Voogt, W.

    2009-01-01

    The water uptake and the water supply do not directly affect the mineral absorption of plants. However, many connections exist between the management of minerals and water. The most evident of those connections are following

  7. Octreotide Uptake in Parathyroid Adenoma

    Science.gov (United States)

    Karaçavuş, Seyhan; Kula, Mustafa; Cihan Karaca, Züleyha; Ünlühızarcı, Kürşad; Tutuş, Ahmet; Bayram, Fahri; Çoban, Ganime

    2012-01-01

    The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB) and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive Conflict of interest:None declared. PMID:23487397

  8. Caveolae-dependent and -independent uptake of albumin in cultured rodent pulmonary endothelial cells.

    Directory of Open Access Journals (Sweden)

    Hui-Hua Li

    Full Text Available Although a critical role for caveolae-mediated albumin transcytosis in pulmonary endothelium is well established, considerably less is known about caveolae-independent pathways. In this current study, we confirmed that cultured rat pulmonary microvascular (RPMEC and pulmonary artery (RPAEC endothelium endocytosed Alexa488-labeled albumin in a saturable, temperature-sensitive mode and internalization resulted in co-localization by fluorescence microscopy with cholera B toxin and caveolin-1. Although siRNA to caveolin-1 (cav-1 in RPAEC significantly inhibited albumin uptake, a remnant portion of albumin uptake was cav-1-independent, suggesting alternative pathways for albumin uptake. Thus, we isolated and cultured mouse lung endothelial cells (MLEC from wild type and cav-1(-/- mice and noted that ~ 65% of albumin uptake, as determined by confocal imaging or live cell total internal reflectance fluorescence microscopy (TIRF, persisted in total absence of cav-1. Uptake of colloidal gold labeled albumin was evaluated by electron microscopy and demonstrated that albumin uptake in MLEC from cav-1(-/- mice was through caveolae-independent pathway(s including clathrin-coated pits that resulted in endosomal accumulation of albumin. Finally, we noted that albumin uptake in RPMEC was in part sensitive to pharmacological agents (amiloride [sodium transport inhibitor], Gö6976 [protein kinase C inhibitor], and cytochalasin D [inhibitor of actin polymerization] consistent with a macropinocytosis-like process. The amiloride sensitivity accounting for macropinocytosis also exists in albumin uptake by both wild type and cav-1(-/- MLEC. We conclude from these studies that in addition to the well described caveolar-dependent pulmonary endothelial cell endocytosis of albumin, a portion of overall uptake in pulmonary endothelial cells is cav-1 insensitive and appears to involve clathrin-mediated endocytosis and macropinocytosis-like process.

  9. Mechanisms of Ocean Heat Uptake

    Science.gov (United States)

    Garuba, Oluwayemi

    An important parameter for the climate response to increased greenhouse gases or other radiative forcing is the speed at which heat anomalies propagate downward in the ocean. Ocean heat uptake occurs through passive advection/diffusion of surface heat anomalies and through the redistribution of existing temperature gradients due to circulation changes. Atlantic meridional overturning circulation (AMOC) weakens in a warming climate and this should slow the downward heat advection (compared to a case in which the circulation is unchanged). However, weakening AMOC also causes a deep warming through the redistributive effect, thus increasing the downward rate of heat propagation compared to unchanging circulation. Total heat uptake depends on the combined effect of these two mechanisms. Passive tracers in a perturbed CO2 quadrupling experiments are used to investigate the effect of passive advection and redistribution of temperature anomalies. A new passive tracer formulation is used to separate ocean heat uptake into contributions due to redistribution and passive advection-diffusion of surface heating during an ocean model experiment with abrupt increase in surface temperature. The spatial pattern and mechanisms of each component are examined. With further experiments, the effects of surface wind, salinity and temperature changes in changing circulation and the resulting effect on redistribution in the individual basins are isolated. Analysis of the passive advection and propagation path of the tracer show that the Southern ocean dominates heat uptake, largely through vertical and horizontal diffusion. Vertical diffusion transports the tracer across isopycnals down to about 1000m in 100 years in the Southern ocean. Advection is more important in the subtropical cells and in the Atlantic high latitudes, both with a short time scale of about 20 years. The shallow subtropical cells transport the tracer down to about 500m along isopycnal surfaces, below this vertical

  10. Different endocytotic uptake mechanisms for nanoparticles in epithelial cells and macrophages

    Directory of Open Access Journals (Sweden)

    Dagmar A. Kuhn

    2014-09-01

    Full Text Available Precise knowledge regarding cellular uptake of nanoparticles is of great importance for future biomedical applications. Four different endocytotic uptake mechanisms, that is, phagocytosis, macropinocytosis, clathrin- and caveolin-mediated endocytosis, were investigated using a mouse macrophage (J774A.1 and a human alveolar epithelial type II cell line (A549. In order to deduce the involved pathway in nanoparticle uptake, selected inhibitors specific for one of the endocytotic pathways were optimized regarding concentration and incubation time in combination with fluorescently tagged marker proteins. Qualitative immunolocalization showed that J774A.1 cells highly expressed the lipid raft-related protein flotillin-1 and clathrin heavy chain, however, no caveolin-1. A549 cells expressed clathrin heavy chain and caveolin-1, but no flotillin-1 uptake-related proteins. Our data revealed an impeded uptake of 40 nm polystyrene nanoparticles by J774A.1 macrophages when actin polymerization and clathrin-coated pit formation was blocked. From this result, it is suggested that macropinocytosis and phagocytosis, as well as clathrin-mediated endocytosis, play a crucial role. The uptake of 40 nm nanoparticles in alveolar epithelial A549 cells was inhibited after depletion of cholesterol in the plasma membrane (preventing caveolin-mediated endocytosis and inhibition of clathrin-coated vesicles (preventing clathrin-mediated endocytosis. Our data showed that a combination of several distinguishable endocytotic uptake mechanisms are involved in the uptake of 40 nm polystyrene nanoparticles in both the macrophage and epithelial cell line.

  11. Surface-modified gold nanoshells for enhanced cellular uptake.

    Science.gov (United States)

    Liang, Zhongshi; Liu, Yun; Li, Xiangyang; Wu, Qinge; Yu, Jiahui; Luo, Shufang; Lai, Lihui; Liu, Shunying

    2011-09-15

    Gold nanoshells have shown a great potential for use as agents in a wide variety of biomedical applications, and some of which require the delivery of large numbers of gold nanoshells onto or into the cells. Here, we develop a ready method to enhance the cellular uptake of gold nanoshells by modifying with meso-2,3-dimercaptosuccinic acid (DMSA). The quantifiable technique of inductively coupled plasma atomic emissions spectroscopy (ICP-AES) and transmission electron microscopy (TEM) were used to investigate the cellular uptake of unmodified and DMSA-modified gold nanoshells. Three cell lines (RAW 264.7, A549, and BEL-7402) were involved and the results indicated that the cellular uptake of the DMSA-modified gold nanoshells was obviously enhanced versus the unmodified gold nanoshells. The reason possibly lies in the nonspecific adsorption of serum protein on the DMSA-modified gold nanoshells (DMSA-GNs), which consequently enhanced the cellular uptake. As a continued effort, in vitro experiments with endocytic inhibitors suggested the DMSA-GNs internalized into cells via receptor-mediated endocytosis (RME) pathway. This study has provided a valuable insight into the effects of surface modification on cellular uptake of nanoparticles.

  12. New views on cellular uptake and trafficking of manufactured nanoparticles

    Science.gov (United States)

    Treuel, Lennart; Jiang, Xiue; Nienhaus, Gerd Ulrich

    2013-01-01

    Nanoparticles (NPs) are of similar size to typical cellular components and proteins, and can efficiently intrude living cells. A detailed understanding of the involved processes at the molecular level is important for developing NPs designed for selective uptake by specific cells, for example, for targeted drug delivery. In addition, this knowledge can greatly assist in the engineering of NPs that should not penetrate cells so as to avoid adverse health effects. In recent years, a wide variety of experiments have been performed to elucidate the mechanisms underlying cellular NP uptake. Here, we review some select recent studies, which are often based on fluorescence microscopy and sophisticated strategies for specific labelling of key cellular components. We address the role of the protein corona forming around NPs in biological environments, and describe recent work revealing active endocytosis mechanisms and pathways involved in their cellular uptake. Passive uptake is also discussed. The current state of knowledge is summarized, and we point to issues that still need to be addressed to further advance our understanding of cellular NP uptake. PMID:23427093

  13. Elucidating the role of dissolution in CeO{sub 2} nanoparticle plant uptake by smart radiolabeling

    Energy Technology Data Exchange (ETDEWEB)

    Schymura, Stefan; Hildebrand, Heike; Franke, Karsten [Institute of Resource Ecology, Helmholtz-Zentrum Dresden-Rossendorf, Leipzig (Germany); Fricke, Thomas [Vita34 AG, Business Unit BioPlanta, Leipzig (Germany); University of Bonn, Institute of Crop Science and Resource Conservation, Division Plant Nutrition (Germany)

    2017-06-19

    The identification of major uptake pathways in plants is an important factor when evaluating the fate of manufactured nanoparticles in the environment and the associated risks. Using different radiolabeling techniques we were able to show a predominantly particulate uptake for CeO{sub 2} nanoparticles in contrast to a possible uptake in the form of ionic cerium. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  14. The interrelation between aPKC and glucose uptake in the skeletal muscle during contraction and insulin stimulation.

    Science.gov (United States)

    Santos, J M; Benite-Ribeiro, S A; Queiroz, G; Duarte, J A

    2014-12-01

    Contraction and insulin increase glucose uptake in skeletal muscle. While the insulin pathway, better characterized, requires activation of phosphoinositide 3-kinase (PI3K) and atypical protein kinase (aPKC), muscle contraction seems to share insulin-activated components to increase glucose uptake. This study aimed to investigate the interrelation between the pathway involved in glucose uptake evoked by insulin and muscle contraction. Isolated muscle of rats was treated with solvent (control), insulin, wortmannin (PI3K inhibitor) and the combination of insulin plus wortmannin. After treatment, muscles were electrically stimulated (contracted) or remained at rest. Glucose transporter 4 (GLUT4) localization, glucose uptake and phospho-aPKC (aPKC activated form) were assessed. Muscle contraction and insulin increased glucose uptake in all conditions when compared with controls not stimulating an effect that was accompanied by an increase in GLUT4 and of phospho-aPKC at the muscle membrane. Contracted muscles treated with insulin did not show additive effects on glucose uptake or aPKC activity compared with the response when these stimuli were applied alone. Inhibition of PI3K blocked insulin effect on glucose uptake and aPKC but not in the contractile response. Thus, muscle contraction seems to stimulate aPKC and glucose uptake independently of PI3K. Therefore, aPKC may be a convergence point and a rate limit step in the pathway by which, insulin and contraction, increase glucose uptake in skeletal muscle.

  15. Presenilin promotes dietary copper uptake.

    Directory of Open Access Journals (Sweden)

    Adam Southon

    Full Text Available Dietary copper is essential for multicellular organisms. Copper is redox active and required as a cofactor for enzymes such as the antioxidant Superoxide Dismutase 1 (SOD1. Copper dyshomeostasis has been implicated in Alzheimer's disease. Mutations in the presenilin genes encoding PS1 and PS2 are major causes of early-onset familial Alzheimer's disease. PS1 and PS2 are required for efficient copper uptake in mammalian systems. Here we demonstrate a conserved role for presenilin in dietary copper uptake in the fly Drosophila melanogaster. Ubiquitous RNA interference-mediated knockdown of the single Drosophila presenilin (PSN gene is lethal. However, PSN knockdown in the midgut produces viable flies. These flies have reduced copper levels and are more tolerant to excess dietary copper. Expression of a copper-responsive EYFP construct was also lower in the midgut of these larvae, indicative of reduced dietary copper uptake. SOD activity was reduced by midgut PSN knockdown, and these flies were sensitive to the superoxide-inducing chemical paraquat. These data support presenilin being needed for dietary copper uptake in the gut and so impacting on SOD activity and tolerance to oxidative stress. These results are consistent with previous studies of mammalian presenilins, supporting a conserved role for these proteins in mediating copper uptake.

  16. Adjusting ammonium uptake via phosphorylation.

    Science.gov (United States)

    Lanquar, Viviane; Frommer, Wolf B

    2010-06-01

    In plants, AMT/MEP/Rh superfamily mediates high affinity ammonium uptake. AMT/MEP transporters form a trimeric complex, which requires a productive interaction between subunits in order to be functional. The AMT/MEP C-terminal domain is highly conserved in more than 700 AMT homologs from cyanobacteria to higher plants with no cases found to be lacking this domain. AMT1;1 exists in active and inactive states, probably controlled by the spatial positioning of the C-terminus. Ammonium triggers the phosphorylation of a conserved threonine residue (T460) in the C-terminus of AMT1;1 in a time- and concentration-dependent manner. The T460 phosphorylation level correlates with a decrease of root ammonium uptake. We propose that ammonium-induced phosphorylation modulates ammonium uptake as a general mechanism to protect against ammonium toxicity.

  17. Lactate, Glucose and Oxygen Uptake in Human Brain During Recovery from Maximal Exercise

    DEFF Research Database (Denmark)

    Kojiro, I.; Schmalbruch, I.K.; Quistorff, B.

    1999-01-01

    Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake......Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake...

  18. Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes.

    Science.gov (United States)

    Mullins, Garrett R; Wang, Lifu; Raje, Vidisha; Sherwood, Samantha G; Grande, Rebecca C; Boroda, Salome; Eaton, James M; Blancquaert, Sara; Roger, Pierre P; Leitinger, Norbert; Harris, Thurl E

    2014-12-09

    Anabolic and catabolic signaling oppose one another in adipose tissue to maintain cellular and organismal homeostasis, but these pathways are often dysregulated in metabolic disorders. Although it has long been established that stimulation of the β-adrenergic receptor inhibits insulin-stimulated glucose uptake in adipocytes, the mechanism has remained unclear. Here we report that β-adrenergic-mediated inhibition of glucose uptake requires lipolysis. We also show that lipolysis suppresses glucose uptake by inhibiting the mammalian target of rapamycin (mTOR) complexes 1 and 2 through complex dissociation. In addition, we show that products of lipolysis inhibit mTOR through complex dissociation in vitro. These findings reveal a previously unrecognized intracellular signaling mechanism whereby lipolysis blocks the phosphoinositide 3-kinase-Akt-mTOR pathway, resulting in decreased glucose uptake. This previously unidentified mechanism of mTOR regulation likely contributes to the development of insulin resistance.

  19. Tumor uptake of radioruthenium compounds

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S C; Richards, P; Meinken, G E; Larson, S M; Grunbaum, Z

    1980-01-01

    The use of ruthenium-97 as a scintigraphic agent, particularly for tumor localization, is investigated. The tumor uptake of ruthenium chloride and ruthenium-labelled transferrin is evaluated and their application as tumor-imagine agents is compared to gallium-67 citrate. (ACR)

  20. Prostatic uptake of Ga-67

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, W.T.; Rosen, P.R.; Weiland, F.L.; Ritchey, M.L.

    1984-08-01

    Midline activity low in the pelvis seen on Ga-67 scans is frequently attributed to colonic excretion of radionuclide. Two cases of infectious prostatitis with focal uptake of Ga-67 within the prostate gland are described. A technique of using limited quantities of barium administered by enema and appropriate positional imaging, which localized pelvic activity to the prostate, is described.

  1. Octreotide Uptake in Parathyroid Adenoma

    Directory of Open Access Journals (Sweden)

    Seyhan Karaçavuş

    2012-08-01

    Full Text Available The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive parathyroid tumors. (MIRT 2012;21:77-79

  2. Cellular uptake of metallated cobalamins

    DEFF Research Database (Denmark)

    Tran, MQT; Stürup, Stefan; Lambert, Ian H.;

    2016-01-01

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-...

  3. Physiological and transcriptomic aspects of urea uptake and assimilation in Arabidopsis plants.

    Science.gov (United States)

    Mérigout, Patricia; Lelandais, Maud; Bitton, Frédérique; Renou, Jean-Pierre; Briand, Xavier; Meyer, Christian; Daniel-Vedele, Françoise

    2008-07-01

    Urea is the major nitrogen (N) form supplied as fertilizer in agriculture, but it is also an important N metabolite in plants. Urea transport and assimilation were investigated in Arabidopsis (Arabidopsis thaliana). Uptake studies using (15)N-labeled urea demonstrated the capacity of Arabidopsis to absorb urea and that the urea uptake was regulated by the initial N status of the plants. Urea uptake was stimulated by urea but was reduced by the presence of ammonium nitrate in the growth medium. N deficiency in plants did not affect urea uptake. Urea exerted a repressive effect on nitrate influx, whereas urea enhanced ammonium uptake. The use of [(15)N]urea and [(15)N]ammonium tracers allowed us to show that urea and ammonium assimilation pathways were similar. Finally, urea uptake was less efficient than nitrate uptake, and urea grown-plants presented signs of N starvation. We also report the first analysis, to our knowledge, of Arabidopsis gene expression profiling in response to urea. Our transcriptomic approach revealed that nitrate and ammonium transporters were transcriptionally regulated by urea as well as key enzymes of the glutamine synthetase-glutamate synthase pathway. AtDUR3, a high-affinity urea transporter in Arabidopsis, was strongly up-regulated by urea. Moreover, our transcriptomic data suggest that other genes are also involved in urea influx.

  4. Pulmonary uptake of morphine (M)

    Energy Technology Data Exchange (ETDEWEB)

    Roerig, D.L.; Bunke, S.S.; Kotrly, K.J.; Dawson, C.A.; Kampine, J.P.

    1986-03-01

    Previously the authors reported less than 5% of M was taken up during the first pass through the human lung. The low uptake of this basic lipophilic amine was further investigated in a single pass isolated perfused rat lung (IPL) in comparison to uptake of radiolabelled H/sub 2/O, antipyrine (A), aminopyrine (AM), nicotine (N) and phenylethylamine (P). The IPL was perfused for 5 min with each drug (5nmol/ml) and effluent collected in 10 sec fractions. Pulmonary extraction was calculated using indocyanine green dye as a non-extractable reference indicator. Accumulation of all compounds in the IPL reached an apparent equilibrium within 4 min. At equilibrium lung/perfusate conc. ratios for H/sub 2/O, A, AM, N, P and M were 1.04, 0.84, 0.85, 1.44, 2.57 and 1.13 respectively. The time course of M uptake differed from the other compounds since initial extraction of M was low (23%) compared to 75%, 53%, 35%, 82% and 86% for H/sub 2/O, A, AM, N and P respectively. Also, the half time to equilibrium for M was longer (50 sec) compared to 18, 21, 26, 19 and 22 sec for H/sub 2/O, A, AM, N and P respectively. The low initial pulmonary extraction of M compared to these compounds followed by greater M extraction during the remainder of drug infusion suggests uptake mechanisms for M different than the flow limited uptake for water and other basic amine drugs.

  5. Lactate promotes glutamine uptake and metabolism in oxidative cancer cells.

    Science.gov (United States)

    Pérez-Escuredo, Jhudit; Dadhich, Rajesh K; Dhup, Suveera; Cacace, Andrea; Van Hée, Vincent F; De Saedeleer, Christophe J; Sboarina, Martina; Rodriguez, Fabien; Fontenille, Marie-Joséphine; Brisson, Lucie; Porporato, Paolo E; Sonveaux, Pierre

    2016-01-01

    Oxygenated cancer cells have a high metabolic plasticity as they can use glucose, glutamine and lactate as main substrates to support their bioenergetic and biosynthetic activities. Metabolic optimization requires integration. While glycolysis and glutaminolysis can cooperate to support cellular proliferation, oxidative lactate metabolism opposes glycolysis in oxidative cancer cells engaged in a symbiotic relation with their hypoxic/glycolytic neighbors. However, little is known concerning the relationship between oxidative lactate metabolism and glutamine metabolism. Using SiHa and HeLa human cancer cells, this study reports that intracellular lactate signaling promotes glutamine uptake and metabolism in oxidative cancer cells. It depends on the uptake of extracellular lactate by monocarboxylate transporter 1 (MCT1). Lactate first stabilizes hypoxia-inducible factor-2α (HIF-2α), and HIF-2α then transactivates c-Myc in a pathway that mimics a response to hypoxia. Consequently, lactate-induced c-Myc activation triggers the expression of glutamine transporter ASCT2 and of glutaminase 1 (GLS1), resulting in improved glutamine uptake and catabolism. Elucidation of this metabolic dependence could be of therapeutic interest. First, inhibitors of lactate uptake targeting MCT1 are currently entering clinical trials. They have the potential to indirectly repress glutaminolysis. Second, in oxidative cancer cells, resistance to glutaminolysis inhibition could arise from compensation by oxidative lactate metabolism and increased lactate signaling.

  6. Phosphate uptake studies of cross-linked chitosan bead materials.

    Science.gov (United States)

    Mahaninia, Mohammad H; Wilson, Lee D

    2017-01-01

    A systematic experimental study is reported that provides a molecular based understanding of cross-linked chitosan beads and their adsorption properties in aqueous solution containing phosphate dianion (HPO4(2-)) species. Synthetically modified chitosan using epichlorohydrin and glutaraldehyde cross-linkers result in surface modified beads with variable hydrophile-lipophile character and tunable HPO4(2-) uptake properties. The kinetic and thermodynamic adsorption properties of cross-linked chitosan beads with HPO4(2-) species were studied in aqueous solution. Complementary structure and physicochemical characterization of chitosan beads via potentiometry, Raman spectroscopy, DSC, and dye adsorption measurements was carried out to establish structure-property relationships. The maximum uptake (Qm) of bead systems with HPO4(2-) at equilibrium was 52.1mgg(-1); whereas, kinetic uptake results for chitosan bead/phosphate systems are relatively rapid (0.111-0.113min(-1)) with an intraparticle diffusion rate-limiting step. The adsorption process follows a multi-step pathway involving inner- and outer-sphere complexes with significant changes in hydration. Phosphate uptake strongly depends on the composition and type of cross-linker used for preparation of chitosan beads. The adsorption isotherms and structural characterization of bead systems illustrate the role of surface charge, hydrophile-lipophile balance, adsorption site accessibility, and hydration properties of the chitosan bead surface. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Nitrogen uptake kinetics of freshly isolated zooxanthellae

    Digital Repository Service at National Institute of Oceanography (India)

    Wafar, M.V.M.; Wafar, S.; Rajkumar, R.

    Zooxanthellae freshly isolated from the coral host Pocillopora damicornis exhibited substrate-saturable uptake kinetics for ammonium, nitrate and urea. Maximum uptake velocity for ammonium [10.1 nmol. ( mu chl-a)./1h/1] was greater than...

  8. Short term uptake and transport process for metformin in roots of Phragmites australis and Typha latifolia.

    Science.gov (United States)

    Cui, H; Hense, B A; Müller, J; Schröder, P

    2015-09-01

    Metformin (MET) as an emerging contaminant has been detected in surface water and wastewater in numerous countries, due to insufficient retention in classical waste water treatment plants. In order to characterize the uptake of the compound during phytotreatment of waste water, a short term Pitman chamber experiment was carried out to assess the characteristics of MET uptake and transport by roots. Three different concentrations (0.5, 1.0 and 2.0 mmol L(-)(1)) were applied to cattail (Typha latifolia) and reed (Phragmites australis) roots which were used to investigate the uptake mechanism because they are frequently utilized in phytoremediation. In addition, quinidine was used as an inhibitor to assess the role of organic cation transporters (OCTs) in the uptake of MET by T. latifolia. The transport process of MET is different from carbamazepine (CBZ) and caffeine (CFN). In both T. latifolia and P. australis, the uptake processes were independent of initial concentrations. Quinidine, a known inhibitor of organic cation transporters, can significantly affect MET uptake by T. latifolia roots with inhibition ratios of 70-74%. Uptake into the root could be characterized by a linear model with R(2) values in the range of 0.881-0.999. Overall, the present study provides evidence that MET is taken up by plant roots and has the potential for subsequent translocation. OCTs could be one of the important pathways for MET uptake into the plant. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Water uptake by growing cells: an assessment of the controlling roles of wall relaxation, solute uptake, and hydraulic conductance

    Science.gov (United States)

    Cosgrove, D. J.

    1993-01-01

    Growing plant cells increase in volume principally by water uptake into the vacuole. There are only three general mechanisms by which a cell can modulate the process of water uptake: (a) by relaxing wall stress to reduce cell turgor pressure (thereby reducing cell water potential), (b) by modifying the solute content of the cell or its surroundings (likewise affecting water potential), and (c) by changing the hydraulic conductance of the water uptake pathway (this works only for cells remote from water potential equilibrium). Recent studies supporting each of these potential mechanisms are reviewed and critically assessed. The importance of solute uptake and hydraulic conductance is advocated by some recent studies, but the evidence is indirect and conclusions remain controversial. For most growing plant cells with substantial turgor pressure, it appears that reduction in cell turgor pressure, as a consequence of wall relaxation, serves as the major initiator and control point for plant cell enlargement. Two views of wall relaxation as a viscoelastic or a chemorheological process are compared and distinguished.

  10. Molecular pathways

    DEFF Research Database (Denmark)

    Cox, Thomas R; Erler, Janine Terra

    2014-01-01

    that 45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection...... of fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases. Clin Cancer Res; 20(14); 3637-43. ©2014 AACR....

  11. Ceruloplasmin ferroxidase activity stimulates cellular iron uptake by a trivalent cation-specific transport mechanism

    Science.gov (United States)

    Attieh, Z. K.; Mukhopadhyay, C. K.; Seshadri, V.; Tripoulas, N. A.; Fox, P. L.

    1999-01-01

    The balance required to maintain appropriate cellular and tissue iron levels has led to the evolution of multiple mechanisms to precisely regulate iron uptake from transferrin and low molecular weight iron chelates. A role for ceruloplasmin (Cp) in vertebrate iron metabolism is suggested by its potent ferroxidase activity catalyzing conversion of Fe2+ to Fe3+, by identification of yeast copper oxidases homologous to Cp that facilitate high affinity iron uptake, and by studies of "aceruloplasminemic" patients who have extensive iron deposits in multiple tissues. We have recently shown that Cp increases iron uptake by cultured HepG2 cells. In this report, we investigated the mechanism by which Cp stimulates cellular iron uptake. Cp stimulated the rate of non-transferrin 55Fe uptake by iron-deficient K562 cells by 2-3-fold, using a transferrin receptor-independent pathway. Induction of Cp-stimulated iron uptake by iron deficiency was blocked by actinomycin D and cycloheximide, consistent with a transcriptionally induced or regulated transporter. Cp-stimulated iron uptake was completely blocked by unlabeled Fe3+ and by other trivalent cations including Al3+, Ga3+, and Cr3+, but not by divalent cations. These results indicate that Cp utilizes a trivalent cation-specific transporter. Cp ferroxidase activity was required for iron uptake as shown by the ineffectiveness of two ferroxidase-deficient Cp preparations, copper-deficient Cp and thiomolybdate-treated Cp. We propose a model in which iron reduction and subsequent re-oxidation by Cp are essential for an iron uptake pathway with high ion specificity.

  12. The signalling imprints of nanoparticle uptake by bone marrow derived dendritic cells.

    Science.gov (United States)

    Karlson, Tanya De L; Kong, Ying Ying; Hardy, Charles L; Xiang, Sue Dong; Plebanski, Magdalena

    2013-05-01

    Nanoparticles (NP) possess remarkable adjuvant and carrier capacity, therefore are used in the development of various vaccine formulations. Our previous studies demonstrated that inert non-toxic 40-50 nm polystyrene NP (PS-NP) can promote strong CD8 T cell and antibody responses to the antigen, in the absence of observable inflammatory responses. Furthermore, instillation of PS-NP inhibited the development of allergic airway inflammation by induction of an immunological imprint via modulation of dendritic cell (DC) function without inducing oxidative stress in the lungs in mice. This is in contrast to many studies which show that a variety of ambient and man-made NP promote lung immunopathology, raising concerns generally about the safe use of NPs in biomedicine. Most NPs are capable of inducing inflammatory pathways in DC largely mediated by signalling via the extracellular signal-regulated kinase 1/2 (ERK). Herein, we investigate whether PS-NPs also activate ERK in DC in vitro. Our data show that PS-NP do not induce ERK activation in two different types of bone marrow derived (BM) DC cultures (expanded with GM-CSF or with GM-CSF together with IL-4). The absence of such signalling was not due to lack of PS-NP uptake by BM-DC as confirmed by confocal microscopy and flow cytometry. The process of NP uptake by DC usually initiates ERK signalling, suggesting an unusual uptake pathway may be engaged by PS-NPs. Indeed, data herein showns that uptake of PS-NP by BM-DC was substantially inhibited by phorbol myristate acetate (PMA) but not cytochalasin D (CCD), suggesting an uptake pathway utilising caveole for PS-NP. Together these data show that BM-DC take up PS-NP via a caveole-dependent pathway which does not trigger ERK signalling which may explain their efficient uptake by DC, without the concomitant activation of conventional inflammatory pathways.

  13. Amino acid uptake in rust fungi.

    Science.gov (United States)

    Struck, Christine

    2015-01-01

    The plant pathogenic rust fungi colonize leaf tissue and feed off their host plants without killing them. Certain economically important species of different genera such as Melampsora, Phakopsora, Puccinia, or Uromyces are extensively studied for resolving the mechanisms of the obligate biotrophy. As obligate parasites rust fungi only can complete their life cycle on living hosts where they grow through the leaf tissue by developing an extended network of intercellular hyphae from which intracellular haustoria are differentiated. Haustoria are involved in key functions of the obligate biotrophic lifestyle: suppressing host defense responses and acquiring nutrients. This review provides a survey of rust fungi nitrogen nutrition with special emphasis on amino acid uptake. A variety of sequences of amino acid transporter genes of rust fungi have been published; however, transport activity of only three in planta highly up-regulated amino acid permeases have been characterized. Functional and immunohistochemical investigations have shown the specificity and localization of these transporters. Sequence data of various genome projects allowed identification of numerous rust amino acid transporter genes. An in silico analysis reveals that these genes can be classified into different transporter families. In addition, genetic and molecular data of amino acid transporters have provided new insights in the corresponding metabolic pathways.

  14. Hormonal control of sulfate uptake and assimilation.

    Science.gov (United States)

    Koprivova, Anna; Kopriva, Stanislav

    2016-08-01

    Plant hormones have a plethora of functions in control of plant development, stress response, and primary metabolism, including nutrient homeostasis. In the plant nutrition, the interplay of hormones with responses to nitrate and phosphate deficiency is well described, but relatively little is known about the interaction between phytohormones and regulation of sulfur metabolism. As for other nutrients, sulfate deficiency results in modulation of root architecture, where hormones are expected to play an important role. Accordingly, sulfate deficiency induces genes involved in metabolism of tryptophane and auxin. Also jasmonate biosynthesis is induced, pointing to the need of increase the defense capabilities of the plants when sulfur is limiting. However, hormones affect also sulfate uptake and assimilation. The pathway is coordinately induced by jasmonate and the key enzyme, adenosine 5'-phosphosulfate reductase, is additionally regulated by ethylene, abscisic acid, nitric oxid, and other phytohormones. Perhaps the most intriguing link between hormones and sulfate assimilation is the fact that the main regulator of the response to sulfate starvation, SULFATE LIMITATION1 (SLIM1) belongs to the family of ethylene related transcription factors. We will review the current knowledge of interplay between phytohormones and control of sulfur metabolism and discuss the main open questions.

  15. Fluorescence-based measurement of cystine uptake through xCT shows requirement for ROS detoxification in activated lymphocytes.

    Science.gov (United States)

    Siska, Peter J; Kim, Bumki; Ji, Xiangming; Hoeksema, Megan D; Massion, Pierre P; Beckermann, Kathryn E; Wu, Jianli; Chi, Jen-Tsan; Hong, Jiyong; Rathmell, Jeffrey C

    2016-11-01

    T and B lymphocytes undergo metabolic re-programming upon activation that is essential to allow bioenergetics, cell survival, and intermediates for cell proliferation and function. To support changes in the activity of signaling pathways and to provide sufficient and necessary intracellular metabolites, uptake of extracellular nutrients increases sharply with metabolic re-programming. One result of increased metabolic activity can be reactive oxygen species (ROS), which can be toxic when accumulated in excess. Uptake of cystine allows accumulation of cysteine that is necessary for glutathione synthesis and ROS detoxification. Cystine uptake is required for T cell activation and function but measurements based on radioactive labeling do not allow analysis on single cell level. Here we show the critical role for cystine uptake in T cells using a method for measurement of cystine uptake using a novel CystineFITC probe. T cell receptor stimulation lead to upregulation of the cystine transporter xCT (SLC7a11) and increased cystine uptake in CD4+ and CD8+ human T cells. Similarly, lipopolysaccharide stimulation increased cystine uptake in human B cells. The CystineFITC probe was not toxic and could be metabolized to prevent cystine starvation induced cell death. Furthermore, blockade of xCT or competition with natural cystine decreased uptake of CystineFITC. CystineFITC is thus a versatile tool that allows measurement of cystine uptake on single cell level and shows the critical role for cystine uptake for T cell ROS regulation and activation.

  16. An evolutionary perspective on zinc uptake by human fungal pathogens†

    Science.gov (United States)

    Wilson, Duncan

    2015-01-01

    The mammalian immune system has evolved sophisticated mechanisms to withhold essential micronutrients from invading pathogens. These processes, collectively known as nutritional immunity serve to limit microbial proliferation and bolster killing of the invader. Successful pathogens, therefore, have developed strategies to counteract nutritional immunity and acquire essential micronutrients in the restrictive environment of the infected host. Here I take advantage of the now large number of sequenced fungal genomes to explore the zinc acquisition strategies of human fungal pathogens and reflect on the evolutionary context of these uptake pathways. PMID:25652414

  17. Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Hazawa, Masaharu; Tomiyama, Kenichi; Saotome-Nakamura, Ai; Obara, Chizuka; Yasuda, Takeshi; Gotoh, Takaya; Tanaka, Izumi; Yakumaru, Haruko; Ishihara, Hiroshi; Tajima, Katsushi, E-mail: tajima@nirs.go.jp

    2014-04-18

    Highlights: • Radiation increases cellular uptake of exosomes. • Radiation induces colocalization of CD29 and CD81. • Exosomes selectively bind the CD29/CD81 complex. • Radiation increases the cellular uptake of exosomes through CD29/CD81 complex formation. - Abstract: Exosomes mediate intercellular communication, and mesenchymal stem cells (MSC) or their secreted exosomes affect a number of pathophysiologic states. Clinical applications of MSC and exosomes are increasingly anticipated. Radiation therapy is the main therapeutic tool for a number of various conditions. The cellular uptake mechanisms of exosomes and the effects of radiation on exosome–cell interactions are crucial, but they are not well understood. Here we examined the basic mechanisms and effects of radiation on exosome uptake processes in MSC. Radiation increased the cellular uptake of exosomes. Radiation markedly enhanced the initial cellular attachment to exosomes and induced the colocalization of integrin CD29 and tetraspanin CD81 on the cell surface without affecting their expression levels. Exosomes dominantly bound to the CD29/CD81 complex. Knockdown of CD29 completely inhibited the radiation-induced uptake, and additional or single knockdown of CD81 inhibited basal uptake as well as the increase in radiation-induced uptake. We also examined possible exosome uptake processes affected by radiation. Radiation-induced changes did not involve dynamin2, reactive oxygen species, or their evoked p38 mitogen-activated protein kinase-dependent endocytic or pinocytic pathways. Radiation increased the cellular uptake of exosomes through CD29/CD81 complex formation. These findings provide essential basic insights for potential therapeutic applications of exosomes or MSC in combination with radiation.

  18. DNA UPTAKE BY TRANSFORMABLE BACTERIA

    Energy Technology Data Exchange (ETDEWEB)

    LACKS,S.A.

    1999-09-07

    The various processes of DNA uptake by cells can be categorized as: viral DNA entry, conjugation, or transformation. Within each category, a variety of mechanisms have been found. However, considerable similarities occur among the different mechanisms of conjugation and, especially, transformation. All of these natural mechanisms of DNA transfer are quite elaborate and involve multiple protein components, as the case may be, of the virus, the donor cell, and the recipient cell. The mechanisms of viral infection and conjugation will be discussed mainly with respect to their relevance to transformation.

  19. DNA Uptake by Transformable Bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Lacks, Sanford A.

    1999-03-31

    The various processes of DNA uptake by cells can be categorized as: viral DNA entry, conjugation, or transformation. Within each category, a variety of mechanisms have been found. However, considerable similarities occur among the different mechanisms of conjugation and, especially, transformation. All of these natural mechanisms of DNA transfer are quite elaborate and involve multiple protein components, as the case may be, of the virus, the donor cell, and the recipient cell. The mechanisms of viral infection and conjugation will be discussed mainly with respect to their relevance to transformation.

  20. Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: Experimental verification

    DEFF Research Database (Denmark)

    Weschler, Charles J.; Bekö, Gabriel; Koch, Holger M.;

    2015-01-01

    Background: Fundamental considerations indicate that, for certain phthalate esters, dermal absorption from air is an uptake pathway that is comparable to or greater than inhalation. Yet this pathway has not been experimentally evaluated and has been largely overlooked when assessing uptake...... of phthalate esters. Objectives: This study investigated transdermal uptake, directly from air, of diethyl phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans. Methods: In a series of experiments, six human participants were exposed for 6 hr in a chamber containing deliberately elevated air...... concentrations of DEP and DnBP. The participants either wore a hood and breathed air with phthalate concentrations substantially below those in the chamber or did not wear a hood and breathed chamber air. All urinations were collected from initiation of exposure until 54 hr later. Metabolites of DEP and Dn...

  1. Leaf and Stem CO2 Uptake in the Three Subfamilies of the Cactaceae 1

    Science.gov (United States)

    Nobel, Park S.; Hartsock, Terry L.

    1986-01-01

    Net CO2 uptake over 24-hour periods was examined for the leaves and for the stems of 11 species of cacti representing all three subfamilies. For Pereskia aculeata, Pereskia grandifolia, and Maihuenia poeppigii (subfamily Pereskioideae), all the net shoot CO2 uptake was by the leaves and during the daytime. In contrast, for the leafless species Carnegiea gigantea, Ferocactus acanthodes, Coryphantha vivipara, and Mammillaria dioica (subfamily Cactoideae), all the shoot net CO2 uptake was by the stems and at night. Similarly, for leafless Opuntia ficus-indica (subfamily Opuntioideae), all net CO2 uptake occurred at night. For leafy members of the Opuntioideae (Pereskiopsis porteri, Quiabentia chacoensis, Austrocylindropuntia subulata), at least 88% of the shoot CO2 uptake over 24 hours was by the leaves and some CO2 uptake occurred at night. Leaves responded to the instantaneous level of photosynthetically active radiation (PAR) during the daytime, as occurs for C3 plants, whereas nocturnal CO2 uptake by stems of O. ficus-indica and F. acanthodes responded to the total daily PAR, as occurs for Crassulacean acid metabolism (CAM) plants. Thus, under the well-watered conditions employed, the Pereskioideae behaved as C3 plants, the Cactoideae behaved as CAM plants, and the Opuntioideae exhibited characteristics of both pathways. PMID:16664741

  2. Leaf and Stem CO(2) Uptake in the Three Subfamilies of the Cactaceae.

    Science.gov (United States)

    Nobel, P S; Hartsock, T L

    1986-04-01

    Net CO(2) uptake over 24-hour periods was examined for the leaves and for the stems of 11 species of cacti representing all three subfamilies. For Pereskia aculeata, Pereskia grandifolia, and Maihuenia poeppigii (subfamily Pereskioideae), all the net shoot CO(2) uptake was by the leaves and during the daytime. In contrast, for the leafless species Carnegiea gigantea, Ferocactus acanthodes, Coryphantha vivipara, and Mammillaria dioica (subfamily Cactoideae), all the shoot net CO(2) uptake was by the stems and at night. Similarly, for leafless Opuntia ficus-indica (subfamily Opuntioideae), all net CO(2) uptake occurred at night. For leafy members of the Opuntioideae (Pereskiopsis porteri, Quiabentia chacoensis, Austrocylindropuntia subulata), at least 88% of the shoot CO(2) uptake over 24 hours was by the leaves and some CO(2) uptake occurred at night. Leaves responded to the instantaneous level of photosynthetically active radiation (PAR) during the daytime, as occurs for C(3) plants, whereas nocturnal CO(2) uptake by stems of O. ficus-indica and F. acanthodes responded to the total daily PAR, as occurs for Crassulacean acid metabolism (CAM) plants. Thus, under the well-watered conditions employed, the Pereskioideae behaved as C(3) plants, the Cactoideae behaved as CAM plants, and the Opuntioideae exhibited characteristics of both pathways.

  3. [Axolemmal transporters for neurotransmitter uptake].

    Science.gov (United States)

    García-López, M

    Neurotransmission is a fundamental process in interneuronal communication. It starts with the release of the neurotransmitter following a nerve impulse and ends either by uptake by specific specific transporters or by metabolization to an inactive compound. In this review we will consider the molecular, ion dependence and electrogenic properties of the axolemal transporters for neurotransmitters and also the pathological consequences of their impairment as well as the drugs that can interact with them. Most axolemmal transporters have been cloned and grouped into two large families according to their molecular characteristics and electrogenic properties: 1. Those dependent on Na+/Cl- include transporters of GABA, noradrenaline, dopamine, serotonin, choline, proline, betaine, glycine and taurine, and 2. Those dependent on Na+/K+, which include the transporters of glutamate, alanine, serine and cysteine. The clonation of transporters has permitted (and will continue to permit) the correlation of molecular alterations of transporters with different neuro-degenerative disorders (e.g. multiple sclerosis, Parkinson's disease, Alzheimer's disease), with brain lesions (e.g. cerebral ischemia, status epilepticus) and with psychiatric alterations (e.g. schizophrenia, depression). In this respect, chemical synthesis of new selective drugs which interact with the different systems for uptake of neurotransmitters will offer new approaches to the treatment of many disorders of the central nervous system which still have no satisfactory drug treatment.

  4. Metal uptake and acute toxicity in zebrafish: Common mechanisms across multiple metals

    Energy Technology Data Exchange (ETDEWEB)

    Alsop, Derek, E-mail: alsopde@mcmaster.ca [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada); Wood, Chris M. [Department of Biology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4K1 (Canada)

    2011-10-15

    All metals tested reduced calcium uptake in zebrafish larvae. However, it was whole body sodium loss that was functionally related to toxicity. The zebrafish larvae acute toxicity assay save time, space and resources. - Abstract: Zebrafish larvae (Danio rerio) were used to examine the mechanisms of action and acute toxicities of metals. Larvae had similar physiological responses and sensitivities to waterborne metals as adults. While cadmium and zinc have previously been shown to reduce Ca{sup 2+} uptake, copper and nickel also decreased Ca{sup 2+} uptake, suggesting that the epithelial transport of all these metals is through Ca{sup 2+} pathways. However, exposure to cadmium, copper or nickel for up to 48 h had little or no effect on total whole body Ca{sup 2+} levels, indicating that the reduction of Ca{sup 2+} uptake is not the acute toxic mechanism of these metals. Instead, mortalities were effectively related to whole body Na{sup +}, which decreased up to 39% after 48 h exposures to different metals around their respective 96 h LC50s. Decreases in whole body K{sup +} were also observed, although they were not as pronounced or frequent as Na{sup +} losses. None of the metals tested inhibited Na{sup +} uptake in zebrafish (Na{sup +} uptake was in fact increased with exposure) and the observed losses of Na{sup +}, K{sup +}, Ca{sup 2+} and Mg{sup 2+} were proportional to the ionic gradients between the plasma and water, indicating diffusive ion loss with metal exposure. This study has shown that there is a common pathway for metal uptake and a common mechanism of acute toxicity across groups of metals in zebrafish. The disruption of ion uptake accompanying metal exposure does not appear to be responsible for the acute toxicity of metals, as has been previously suggested, but rather the toxicity is instead due to total ion loss (predominantly Na{sup +}).

  5. Designing pathways

    DEFF Research Database (Denmark)

    Scheuer, John Damm

    2010-01-01

    The theoretical background in this chapter is organizational studies and especially theories about design and design processes in organizations. The concept of design is defined as a particular kind of work aimed at making arrangements in order to change existing situations into desired ones....... The illustrative case example is the introduction of clinical pathways in a psychiatric department. The contribution to a general core of design research is the development of the concept of design work and a critical discussion of the role of technological rules in design work....

  6. Designing pathways

    DEFF Research Database (Denmark)

    2010-01-01

    The theoretical background in this chapter is organizational studies and especially theories about design and design processes in organizations. The concept of design is defined as a particular kind of work aimed at making arrangements in order to change existing situations into desired ones....... The illustrative case example is the introduction of clinical pathways in a psychiatric department. The contribution to a general core of design research is the development of the concept of design work and a critical discussion of the role of technological rules in design work....

  7. Cell uptake survey of pegylated nanographene oxide

    Science.gov (United States)

    Vila, M.; Portolés, M. T.; Marques, P. A. A. P.; Feito, M. J.; Matesanz, M. C.; Ramírez-Santillán, C.; Gonçalves, G.; Cruz, S. M. A.; Nieto, A.; Vallet-Regi, M.

    2012-11-01

    Graphene and more specifically, nanographene oxide (GO) has been proposed as a highly efficient antitumoral therapy agent. Nevertheless, its cell uptake kinetics, its influence in different types of cells and the possibility of controlling cellular internalization timing, is still a field that remains unexplored. Herein, different cell types have been cultured in vitro for several incubation periods in the presence of 0.075 mg ml-1 pegylated GO solutions. GO uptake kinetics revealed differences in the agent’s uptake amount and speed as a function of the type of cell involved. Osteoblast-like cells GO uptake is higher and faster without resulting in greater cell membrane damage. Moreover, the dependence on the commonly used PEG nature (number of branches) also influences the viability and cell uptake speed. These facts play an important role in the future definition of timing parameters and selective cell uptake control in order to achieve an effective therapy.

  8. Increased muscle glucose uptake during contractions

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, H; Richter, E A

    1984-01-01

    We reinvestigated the prevailing concept that muscle contractions only elicit increased muscle glucose uptake in the presence of a so-called "permissive" concentration of insulin (Berger et al., Biochem. J. 146: 231-238, 1975; Vranic and Berger, Diabetes 28: 147-163, 1979). Hindquarters from rats......-methylglucose uptake increased during contractions and glucose uptake was negative at rest and zero during contractions. An increase in muscle transport and uptake of glucose during contractions does not require the presence of insulin. Furthermore, glucose transport in contracting muscle may only increase if glycogen...

  9. Radioiodine uptake in inactive pulmonary tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Bakheet, S.M.; Powe, J.; Al Suhaibani, H. [Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Hammami, M.M.; Bazarbashi, M. [Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)

    1999-06-01

    Radioiodine may accumulate at sites of inflammation or infection. We have seen such accumulation in six thyroid cancer patients with a history of previously treated pulmonary tuberculosis. We also review the causes of false-positive radioiodine uptake in lung infection/inflammation. Eight foci of radioiodine uptake were seen on six iodine-123 diagnostic scans. In three foci, the uptake was focal and indistinguishable from thyroid cancer pulmonary metastases from thyroid cancer. In the remaining foci, the uptake appeared nonsegmental, linear or lobar, suggesting a false-positive finding. The uptake was unchanged, variable in appearance or non-persistent on follow-up scans and less extensive than the fibrocystic changes seen on chest radiographs. In the two patients studied, thyroid hormone level did not affect the radioiodine lung uptake and there was congruent gallium-67 uptake. None of the patients had any evidence of thyroid cancer recurrence or of reactivation of tuberculosis and only two patients had chronic intermittent chest symptoms. Severe bronchiectasis, active tuberculosis, acute bronchitis, respiratory bronchiolitis, rheumatoid arthritis-associated lung disease and fungal infection such as Allescheria boydii and aspergillosis can lead to different patterns of radioiodine chest uptake mimicking pulmonary metastases. Pulmonary scarring secondary to tuberculosis may predispose to localized radioiodine accumulation even in the absence of clinically evident active infection. False-positive radioiodine uptake due to pulmonary infection/inflammation should be considered in thyroid cancer patients prior to the diagnosis of pulmonary metastases. (orig.) With 4 figs., 1 tab., 9 refs.

  10. Pathway collages: personalized multi-pathway diagrams.

    Science.gov (United States)

    Paley, Suzanne; O'Maille, Paul E; Weaver, Daniel; Karp, Peter D

    2016-12-13

    Metabolic pathway diagrams are a classical way of visualizing a linked cascade of biochemical reactions. However, to understand some biochemical situations, viewing a single pathway is insufficient, whereas viewing the entire metabolic network results in information overload. How do we enable scientists to rapidly construct personalized multi-pathway diagrams that depict a desired collection of interacting pathways that emphasize particular pathway interactions? We define software for constructing personalized multi-pathway diagrams called pathway-collages using a combination of manual and automatic layouts. The user specifies a set of pathways of interest for the collage from a Pathway/Genome Database. Layouts for the individual pathways are generated by the Pathway Tools software, and are sent to a Javascript Pathway Collage application implemented using Cytoscape.js. That application allows the user to re-position pathways; define connections between pathways; change visual style parameters; and paint metabolomics, gene expression, and reaction flux data onto the collage to obtain a desired multi-pathway diagram. We demonstrate the use of pathway collages in two application areas: a metabolomics study of pathogen drug response, and an Escherichia coli metabolic model. Pathway collages enable facile construction of personalized multi-pathway diagrams.

  11. Role of water states on water uptake and proton transport in Nafion using molecular simulations and bimodal network

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Gi Suk [Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Mechanical Engineering; Kaviany, Massoud [Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Mechanical Engineering; Gostick, Jeffrey T. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division; Kientiz, Brian [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division; Weber, Adam Z. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Environmental Energy Technologies Division; Kim, Moo Hwan [Pohang Univ. of Science and Technology (POSTECH) (Korea, Republic of). Dept. of Mechanical Engineering

    2011-04-07

    In this paper, using molecular simulations and a bimodal-domain network, the role of water state on Nafion water uptake and water and proton transport is investigated. Although the smaller domains provide moderate transport pathways, their effectiveness remains low due to strong, resistive water molecules/domain surface interactions. Finally, the water occupancy of the larger domains yields bulk-like water, and causes the observed transition in the water uptake and significant increases in transport properties.

  12. Uptake, translocation, and toxicity of gold nanorods in maize

    Science.gov (United States)

    Moradi Shahmansouri, Nastaran

    root and leaf cells. However, the translocation factor of gold nanorods from root to leaf was very low in this experiment. In the second experiment, maize seedlings were exposed to different (lower) concentrations of gold nanorods measured at 4.5x10-3 mg/l, 0.45 mg/l, and 2.25 mg/l for 10 days. Transpiration and biomass measurements demonstrated that the higher concentration of gold nanorods caused lower water uptake and growth, but lower concentrations did not show a significant toxic effect. According to ICP-MS results, root systems of the exposed plants were surrounded by high concentrations of sorbed nanorods, which physically interfered with uptake pathways and, thus, inhibited plant growth and nutritional uptake.

  13. Dynamics and mechanisms of quantum dot nanoparticle cellular uptake

    Directory of Open Access Journals (Sweden)

    Telford William G

    2010-06-01

    Full Text Available Abstract Background The rapid growth of the nanotechnology industry and the wide application of various nanomaterials have raised concerns over their impact on the environment and human health. Yet little is known about the mechanism of cellular uptake and cytotoxicity of nanoparticles. An array of nanomaterials has recently been introduced into cancer research promising for remarkable improvements in diagnosis and treatment of the disease. Among them, quantum dots (QDs distinguish themselves in offering many intrinsic photophysical properties that are desirable for targeted imaging and drug delivery. Results We explored the kinetics and mechanism of cellular uptake of QDs with different surface coatings in two human mammary cells. Using fluorescence microscopy and laser scanning cytometry (LSC, we found that both MCF-7 and MCF-10A cells internalized large amount of QD655-COOH, but the percentage of endocytosing cells is slightly higher in MCF-7 cell line than in MCF-10A cell line. Live cell fluorescent imaging showed that QD cellular uptake increases with time over 40 h of incubation. Staining cells with dyes specific to various intracellular organelles indicated that QDs were localized in lysosomes. Transmission electron microscopy (TEM images suggested a potential pathway for QD cellular uptake mechanism involving three major stages: endocytosis, sequestration in early endosomes, and translocation to later endosomes or lysosomes. No cytotoxicity was observed in cells incubated with 0.8 nM of QDs for a period of 72 h. Conclusions The findings presented here provide information on the mechanism of QD endocytosis that could be exploited to reduce non-specific targeting, thereby improving specific targeting of QDs in cancer diagnosis and treatment applications. These findings are also important in understanding the cytotoxicity of nanomaterials and in emphasizing the importance of strict environmental control of nanoparticles.

  14. Normal cerebral FDG uptake during childhood

    Energy Technology Data Exchange (ETDEWEB)

    London, Kevin [The Children' s Hospital at Westmead, Department of Nuclear Medicine, Sydney, NSW (Australia); University of Sydney, Discipline of Paediatrics and Child Health, Sydney Medical School, Sydney, NSW (Australia); Howman-Giles, Robert [The Children' s Hospital at Westmead, Department of Nuclear Medicine, Sydney, NSW (Australia); University of Sydney, Disciplines of Imaging and Paediatrics and Child Health, Sydney Medical School, Sydney, NSW (Australia)

    2014-04-15

    Current understanding of cerebral FDG uptake during childhood originates from a small number of studies in patients with neurological abnormalities. Our aim was to describe cerebral FDG uptake in a dataset of FDG PET scans in children more likely to represent a normal population. We reviewed cerebral FDG PET scans in children up to 16 years of age with suspected/proven extracranial malignancies and the following exclusions: central nervous system metastases, previous malignancies, previous chemotherapy or radiotherapy, development of cerebral metastases during therapy, neurological conditions, taking antiepileptic medication or medications likely to interfere with cerebral metabolism, and general anaesthesia within 24 h. White matter, basal ganglia, thalamus and the cerebellar cortex were analysed using regional SUV{sub max}, and the cerebral cortex, basal ganglia, thalamus and cerebellum were analysed using a regional relative uptake analysis in comparison to maximal cortical uptake. Scans from 30 patients (age range 11 months to 16 years, mean age 10 years 5 months) were included. All regions showed increasing SUV{sub max} with age. The parietal, occipital, lateral temporal and medial temporal lobes showed lower rates of increasing FDG uptake causing changing patterns of regional FDG uptake during childhood. The cortical regions showing the most intense uptake in early childhood were the parietal and occipital lobes. At approximately 7 years of age these regions had relatively less uptake than the frontal lobes and at approximately 10 years of age these regions had relatively less uptake than the thalamus. Relative FDG uptake in the brain has not reached an adult pattern by 1 year of age, but continues to change up to 16 years of age. The changing pattern is due to different regional rates of increasing cortical FDG uptake, which is less rapid in the parietal, occipital and temporal lobes than in the frontal lobes. (orig.)

  15. Effect of Uptake-one inhibitors on the uptake of norepinephrine and metaiodobenzylguanidine

    Energy Technology Data Exchange (ETDEWEB)

    Tobes, M.C.; Jaques, S. Jr.; Wieland, D.M.; Sisson, J.C.

    1985-08-01

    The mechanisms underlying the uptake of the radiopharmaceutical metaiodobenzylguanidine (MIBG) and the catecholamine norepinephrine (NE) were studied using cultured bovine adrenomedullary cells as an in vitro model system. Sodium-dependent and sodium-independent uptake systems have been identified and characterized for both MIBG and NE. The sodium-dependent uptake of Ne and MIBG was inhibited by the selective Uptake-one inhibitors, desmethylimipramine (DMI) and cocaine, whereas the sodium-independent uptake for NE and MIBG was much less sensitive to inhibition by these agents. The sodium-dependent uptake system fulfills the criteria for the neuronal Uptake-one system, and the sodium-independent uptake system fulfills the criteria for a passive diffusion mechanism. Arterial concentrations proximal to the dog adrenal were very small suggesting that the sodium-dependent (Uptake-one) system is predominant in vivo. Consistent with the in vitro observations, the in vivo uptake of MIBG and NE into dog adrenal medullae was effectively blocked by pretreatment with DMI or cocaine. Therefore, iodine-131 MIBG scintigraphy of the adrenal appears to reflect uptake by way of the Uptake-one system.

  16. Membrane receptor-initiated signaling in 1,25(OH)2D3-stimulated calcium uptake in intestinal epithelial cells.

    Science.gov (United States)

    Khanal, Ramesh C; Peters, Tremaine M Sterling; Smith, Nathan M; Nemere, Ilka

    2008-11-01

    Demonstrating 1,25(OH)2D3-stimulated calcium uptake in isolated chick intestinal epithelial cells has been complicated by simultaneous enhancement of both uptake and efflux. We now report that in intestinal cells of adult birds, or those of young birds cultured for 72 h, 1,25(OH)2D3-stimulates 45Ca uptake to greater than 140% of corresponding controls within 3 min of addition. Such cells have lost hormone-stimulated protein kinase C (PKC) activity, believed to mediate calcium efflux. To further test this hypothesis, freshly isolated cells were preincubated with calphostin C, and calcium uptake monitored in the presence or absence of steroid. Only cells treated with the PKC inhibitor demonstrated a significant increase in 45Ca uptake in response to 1,25(OH)2D3, relative to corresponding controls. In addition, phorbol ester was shown to stimulate efflux, while forskolin stimulated uptake. To further investigate the mechanisms involved in calcium uptake, we assessed the role of TRPV6 and its activation by beta-glucuronidase. beta-Glucuronidase secretion from isolated intestinal epithelial cells was significantly increased by treatment with 1,25(OH)2D3, PTH, or forskolin, but not by phorbol ester. Treatment of cells with beta-glucuronidase, in turn, stimulated 45Ca uptake. Finally, transfection of cells with siRNA to either beta-glucuronidase or TRPV6 abolished 1,25(OH)2D3-enhanced calcium uptake relative to controls transfected with scrambled siRNA. Confocal microscopy further indicated rapid redistribution of enzyme and calcium channel after steroid. 1,25(OH)2D3 and PTH increase calcium uptake by stimulating the PKA pathway to release beta-glucuronidase, which in turn activates TRPV6. 1,25(OH)2D3-enhanced calcium efflux is mediated by the PKC pathway.

  17. Uptake of organic nitrogen by plants

    Science.gov (United States)

    Torgny Nasholm; Knut Kielland; Ulrika. Ganeteg

    2009-01-01

    Languishing for many years in the shadow of plant inorganic nitrogen (N) nutrition research, studies of organic N uptake have attracted increased attention during the last decade. The capacity of plants to acquire organic N, demonstrated in laboratory and field settings, has thereby been well established. Even so, the ecological significance of organic N uptake for...

  18. Incidental fleurodeoxyglucose uptake in the prostate.

    Science.gov (United States)

    Wong, W L; Moule, R N; Nunan, T

    2010-11-01

    This commentary confirms the rarity of prostatic cancer associated with incidental prostatic fleurodeoxyglucose (FDG) uptake. The study adds to the literature by showing that even if a prostate lesion is FDG avid it is unlikely to be due to cancer. The commentary considers the management of incidental prostate FDG uptake on the basis of the available evidence.

  19. Radio-active iodine uptake in vitiligo

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, V.; Shankar, V.; Chaudhary, S.; Bhatia, K.K.; Mehta, L.K.; Arora, D.R. (Medical College and Hospital, Rohtak-124001 (India))

    1990-01-01

    Vitiligo and thyroid disease are commonly associated disorders. Twenty-two clinically euthyroid vitiligo patients were studied for functional assessment of thyroid by radioactive iodine uptake assay. Half of them showed abnormal uptake values at 24 hours. Of these patients, 90% had lower values indicating a tendency towards developing hypothyroid state. Subclinical thyroid dysfunction in vitiligo appears to be an adaptive change. (author).

  20. Uptake of ricinB-quantum dot nanoparticles by a macropinocytosis-like mechanism

    Directory of Open Access Journals (Sweden)

    Iversen Tore

    2012-07-01

    Full Text Available Abstract Background There is a huge effort in developing ligand-mediated targeting of nanoparticles to diseased cells and tissue. The plant toxin ricin has been shown to enter cells by utilizing both dynamin-dependent and -independent endocytic pathways. Thus, it is a representative ligand for addressing the important issue of whether even a relatively small ligand-nanoparticle conjugate can gain access to the same endocytic pathways as the free ligand. Results Here we present a systematic study concerning the internalization mechanism of ricinB:Quantum dot (QD nanoparticle conjugates in HeLa cells. Contrary to uptake of ricin itself, we found that internalization of ricinB:QDs was inhibited in HeLa cells expressing dominant-negative dynamin. Both clathrin-, Rho-dependent uptake as well as a specific form of macropinocytosis involve dynamin. However, the ricinB:QD uptake was not affected by siRNA-mediated knockdown of clathrin or inhibition of Rho-dependent uptake caused by treating cells with the Clostridium C3 transferase. RicinB:QD uptake was significantly reduced by cholesterol depletion with methyl-β-cyclodextrin and by inhibitors of actin polymerization such as cytochalasin D. Finally, we found that uptake of ricinB:QDs was blocked by the amiloride analog EIPA, an inhibitor of macropinocytosis. Upon entry, the ricinB:QDs co-localized with dextran, a marker for fluid-phase uptake. Thus, internalization of ricinB:QDs in HeLa cells critically relies on a dynamin-dependent macropinocytosis-like mechanism. Conclusions Our results demonstrate that internalization of a ligand-nanoparticle conjugate can be dependent on other endocytic mechanisms than those used by the free ligand, highlighting the challenges of using ligand-mediated targeting of nanoparticles-based drug delivery vehicles to cells of diseased tissues.

  1. Electrogenicity of hepatocellular fatty acid uptake.

    Science.gov (United States)

    Elsing, C; Kassner, A; Gajdzik, L; Graf, J; Stremmel, W

    1998-08-18

    Sensitivity of cellular fatty acids uptake to the membrane potential difference is still a matter of controversy. For direct evaluation of potential sensitivity the effect of changing membrane potential on uptake of a fluorescent long chain fatty acid derivative, 12-NBD-stearate, in isolated rat hepatocytes, was examined. Changes in membrane potential were achieved by patch clamp procedures. Fatty acid influx was simultaneously determined by recording of cell fluorescence. Hyperpolarization from -30 to -70 mV accelerated fatty acid influx whereas depolarization to +50 mV reduced uptake. After obtaining equilibrium hyperpolarization increased cell fluorescence, whereas depolarization pushed NBD-stearate out of cells. Potential sensitivity of uptake was dependent on the fatty acid concentrations in the medium with most prominent effects at low unbound concentrations. These data show that, at low fatty acid concentrations, uptake is, in part, driven by an intracellular negative electric membrane potential.

  2. Root uptake of lead by Norway spruce grown on Pb-210 spiked soils

    DEFF Research Database (Denmark)

    Hovmand, M.F.; Nielsen, Sven Poul; Johnsen, I.

    2009-01-01

    . Calculations of the specific activity in plant material and in the supporting pot soil showed that less than 2% of the Pb content of needles and twigs originates from root uptake and approximately 98% are deposited from the atmosphere. Atmospheric Pb has declined by a factor of 7 from 1980 to 2007 but is still...... a major pathway of Pb to vegetation and topsoils. The conclusion from the experiment is that the internal circulation of Pb through root uptake, translocation and litterfall, gives an insignificant input of Pb to the forest floor compared to atmospheric deposition....

  3. Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle.

    Science.gov (United States)

    Sylow, Lykke; Jensen, Thomas E; Kleinert, Maximilian; Mouatt, Joshua R; Maarbjerg, Stine J; Jeppesen, Jacob; Prats, Clara; Chiu, Tim T; Boguslavsky, Shlomit; Klip, Amira; Schjerling, Peter; Richter, Erik A

    2013-04-01

    In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucose uptake is unknown. Therefore, we studied the effects of in vivo exercise and ex vivo muscle contractions on Rac1 signaling and its regulatory role in glucose uptake in mice and humans. Muscle Rac1-GTP binding was increased after exercise in mice (~60-100%) and humans (~40%), and this activation was AMP-activated protein kinase independent. Rac1 inhibition reduced contraction-stimulated glucose uptake in mouse muscle by 55% in soleus and by 20-58% in extensor digitorum longus (EDL; P contraction-stimulated increment in glucose uptake was decreased by 27% (P = 0.1) and 40% (P muscles, respectively, of muscle-specific inducible Rac1 knockout mice. Furthermore, depolymerization of the actin cytoskeleton decreased contraction-stimulated glucose uptake by 100% and 62% (P muscles, respectively. These are the first data to show that Rac1 is activated during muscle contraction in murine and human skeletal muscle and suggest that Rac1 and possibly the actin cytoskeleton are novel regulators of contraction-stimulated glucose uptake.

  4. Effects of physicochemical properties of zinc oxide nanoparticles on cellular uptake

    Science.gov (United States)

    Yu, J.; Baek, M.; Chung, H. E.; Choi, S. J.

    2011-07-01

    Zinc oxide (ZnO) nanoparticles have been used as a source of zinc, an essential trace element in food industry and also widely applied to various cosmetic products. However, there are few researches demonstrating that the cellular uptake behaviours of ZnO with respect to the physicochemical characteristics such as particle size and surface charge in human cells. In this study, we evaluated the cellular uptake of ZnO with two different sizes (20 and 70 nm) and different charges (positive and negative). Human lung epithelial cells were exposed to ZnO for a given time, and then the uptake amount of ZnO was measured with inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The results showed that the smaller sized ZnO could more easily enter the cells than the larger sized ZnO. In terms of surface charge, positively charged ZnO showed high cellular uptake compared to ZnO with negative charge. The internalization pathway of positively charged ZnO nanoparticles was determined to be primarily related to the energy-dependent endocytosis. It is, therefore, concluded that the particle size and surface charge of ZnO nanoparticles are critical factors influencing on their cellular uptake. Understanding the cellular uptake behaviours of nanoparticles with respect to physicochemical properties may be important to predict their toxicity potential on human.

  5. IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival.

    Science.gov (United States)

    Wofford, Jessica A; Wieman, Heather L; Jacobs, Sarah R; Zhao, Yuxing; Rathmell, Jeffrey C

    2008-02-15

    Lymphocyte homeostasis requires coordination of metabolic processes with cellular energetic and biosynthetic demands but mechanisms that regulate T-cell metabolism are uncertain. We show that interleukin-7 (IL-7) is a key regulator of glucose uptake in T lymphocytes. To determine how IL-7 affects glucose uptake, we analyzed IL-7 signaling mechanisms and regulation of the glucose transporter, Glut1. The IL-7 receptor (IL-7R) stimulated glucose uptake and cell-surface localization of Glut1 in a manner that required IL-7R Y449, which promoted rapid signal transducer and activator of transcription 5 (STAT5) activation and a delayed yet sustained activation of Akt. Each pathway was necessary for IL-7 to promote glucose uptake, as Akt1(-/-) T cells or PI3-kinase inhibition and RNAi of STAT5 led to defective glucose uptake in response to IL-7. STAT5 and Akt acted in a linear pathway, with STAT5-mediated transcription leading to Akt activation, which was necessary for STAT5 and IL-7 to promote glucose uptake and prevent cell death. Importantly, IL-7 required glucose uptake to promote cell survival. These data demonstrate that IL-7 promotes glucose uptake via a novel signaling mechanism in which STAT5 transcriptional activity promotes Akt activation to regulate Glut1 trafficking and glucose uptake that is critical for IL-7 to prevent T-cell death and maintain homeostasis.

  6. Transferrin iron uptake is stimulated by ascorbate via an intracellular reductive mechanism.

    Science.gov (United States)

    Lane, Darius J R; Chikhani, Sherin; Richardson, Vera; Richardson, Des R

    2013-06-01

    Although ascorbate has long been known to stimulate dietary iron (Fe) absorption and non-transferrin Fe uptake, the role of ascorbate in transferrin Fe uptake is unknown. Transferrin is a serum Fe transport protein supplying almost all cellular Fe under physiological conditions. We sought to examine ascorbate's role in this process, particularly as cultured cells are typically ascorbate-deficient. At typical plasma concentrations, ascorbate significantly increased (59)Fe uptake from transferrin by 1.5-2-fold in a range of cells. Moreover, ascorbate enhanced ferritin expression and increased (59)Fe accumulation in ferritin. The lack of effect of cycloheximide or the cytosolic aconitase inhibitor, oxalomalate, on ascorbate-mediated (59)Fe uptake from transferrin indicate increased ferritin synthesis or cytosolic aconitase activity was not responsible for ascorbate's activity. Experiments with membrane-permeant and -impermeant ascorbate-oxidizing reagents indicate that while extracellular ascorbate is required for stimulation of (59)Fe uptake from (59)Fe-citrate, only intracellular ascorbate is needed for transferrin (59)Fe uptake. Additionally, experiments with l-ascorbate analogs indicate ascorbate's reducing ene-diol moiety is necessary for its stimulatory activity. Importantly, neither N-acetylcysteine nor buthionine sulfoximine, which increase or decrease intracellular glutathione, respectively, affected transferrin-dependent (59)Fe uptake. Thus, ascorbate's stimulatory effect is not due to a general increase in cellular reducing capacity. Ascorbate also did not affect expression of transferrin receptor 1 or (125)I-transferrin cellular flux. However, transferrin receptors, endocytosis, vacuolar-type ATPase activity and endosomal acidification were required for ascorbate's stimulatory activity. Therefore, ascorbate is a novel modulator of the classical transferrin Fe uptake pathway, acting via an intracellular reductive mechanism.

  7. Effects of Tryptophan Content and Backbone Spacing on the Uptake Efficiency of Cell-Penetrating Peptides

    KAUST Repository

    Rydberg, Hanna A.

    2012-07-10

    Cell-penetrating peptides (CPPs) are able to traverse cellular membranes and deliver macromolecular cargo. Uptake occurs through both endocytotic and nonendocytotic pathways, but the molecular requirements for efficient internalization are not fully understood. Here we investigate how the presence of tryptophans and their position within an oligoarginine influence uptake mechanism and efficiency. Flow cytometry and confocal fluorescence imaging are used to estimate uptake efficiency, intracellular distribution and toxicity in Chinese hamster ovarian cells. Further, membrane leakage and lipid membrane affinity are investigated. The peptides contain eight arginine residues and one to four tryptophans, the tryptophans positioned either at the N-terminus, in the middle, or evenly distributed along the amino acid sequence. Our data show that the intracellular distribution varies among peptides with different tryptophan content and backbone spacing. Uptake efficiency is higher for the peptides with four tryptophans in the middle, or evenly distributed along the peptide sequence, than for the peptide with four tryptophans at the N-terminus. All peptides display low cytotoxicity except for the one with four tryptophans at the N-terminus, which was moderately toxic. This finding is consistent with their inability to induce efficient leakage of dye from lipid vesicles. All peptides have comparable affinities for lipid vesicles, showing that lipid binding is not a decisive parameter for uptake. Our results indicate that tryptophan content and backbone spacing can affect both the CPP uptake efficiency and the CPP uptake mechanism. The low cytotoxicity of these peptides and the possibilities of tuning their uptake mechanism are interesting from a therapeutic point of view. © 2012 American Chemical Society.

  8. DEVELOPMENT OF AN IN VITRO RADIOACTIVE IODIDE UPTAKE ASSAY (RAIU) WITH HUMAN NIS-EXPRESSING HEK293T-EPA CELL LINE

    Science.gov (United States)

    Many high-throughput screening (HTPS) assays are available in the US EPA ToxCast program for estrogen and androgen pathways; only a limited number of assays exist for thyroid pathways. One potential target of thyroid-disrupting chemicals is the active uptake of iodide into the t...

  9. DEVELOPMENT OF AN IN VITRO RADIOACTIVE IODIDE UPTAKE ASSAY (RAIU) WITH HUMAN NIS-EXPRESSING HEK293T-EPA CELL LINE

    Science.gov (United States)

    Many high-throughput screening (HTPS) assays are available in the US EPA ToxCast program for estrogen and androgen pathways; only a limited number of assays exist for thyroid pathways. One potential target of thyroid-disrupting chemicals is the active uptake of iodide into the t...

  10. Non-specific cellular uptake of surface-functionalized quantum dots

    CERN Document Server

    Kelf, T A; Sun, J; Kim, E J; Goldys, E M; Zvyagin, A V; 10.1088/0957-4484/21/28/285105

    2010-01-01

    We report a systematic empirical study of nanoparticle internalization into cells via non-specific pathways. The nanoparticles were comprised of commercial quantum dots (QDs) that were highly visible under a fluorescence confocal microscope. Surface-modified QDs with basic biologically-significant moieties, e.g. carboxyl, amino, streptavidin were used, in combination with the surface derivatization with polyethylene glycol (PEG) in a range of immortalized cell lines. Internalization rates were derived from image analysis and a detailed discussion about the effect of nanoparticle size, charge and surface groups is presented. We find that PEG-derivatization dramatically suppresses the non-specific uptake while PEG-free carboxyl and amine functional groups promote QD internalization. These uptake variations displayed a remarkable consistency across different cell types. The reported results are important for experiments concerned with cellular uptake of surface-functionalized nanomaterials, both when non-specifi...

  11. Magnetic field enhanced cell uptake efficiency of magnetic silica mesoporous nanoparticles.

    Science.gov (United States)

    Liu, Qian; Zhang, Jixi; Xia, Weiliang; Gu, Hongchen

    2012-06-01

    The advantages of using magnetic mesoporous silica nanoparticles (M-MSNs) in biomedical applications have been widely recognized. However, poor uptake efficiency may hinder the potential of M-MSNs in many applications, such as cell tracking, drug delivery, fluorescence and magnetic resonance imaging. An external magnetic field may improve the cellular uptake efficiency. In this paper, we evaluated the effect of a magnetic field on the uptake of M-MSNs. We found that the internalization of M-MSNs by A549 cancer cells could be accelerated and enhanced by a magnetic field. An endocytosis study indicated that M-MSNs were internalized by A549 cells mainly through an energy-dependent pathway, namely clathrin-induced endocytosis. Transmission electron microscopy showed that M-MSNs were trafficked into lysosomes. With the help of a magnetic field, anticancer drug-loaded M-MSNs induced elevated cancer cell growth inhibition.

  12. PARTITIONING THE RELATIVE INFLUENCE OF SOIL N, MYCORRHIZAE, AND FOLIAR N UPTAKE ON FOLIAR δ15N PATTERNS: CAN WE DETECT FOLIAR UPTAKE OF REACTIVE N?

    Science.gov (United States)

    Vallano, D.; Sparks, J. P.

    2009-12-01

    Vegetation is an important sink for atmospheric reactive N in N-limited systems and may be capable of incorporating reactive N compounds directly into leaves through the foliar uptake pathway. A proxy for atmospheric reactive N entering vegetation would be useful to estimate the impact of direct foliar N uptake on plant metabolism. Natural abundance foliar N isotopic composition (δ15N) is a practical tool for this purpose because plant-available N sources often have different isotopic compositions. Current understanding of foliar δ15N suggests these values primarily represent the integration of soil δ15N, direct foliar N uptake, mycorrhizal fractionation, and within-plant fractionations. Using a potted plant mesocosm system, we estimated the influence of mycorrhizae on foliar δ15N patterns in red maple (Acer rubrum) seedlings along an N deposition gradient in New York State. We found that mycorrhizal associations altered foliar δ15N in red maple seedlings from 0.03 - 1.01‰ across sites. Along the same temporal and spatial scales, we examined the influence of soil δ15N, foliar N uptake, and mycorrhizae on foliar δ15N in adult stands of American beech (Fagus grandifolia), black birch (Betula lenta), red maple (A. rubrum), and red oak (Quercus rubra). Using multiple regression models, atmospheric NO2 concentration explained 0%, 69%, 23%, and 45% of the residual variation in foliar δ15N remaining in American beech, red maple, red oak, and black birch, respectively, after accounting for soil δ15N. Our results suggest that foliar δ15N may be used to estimate pollution-derived atmospheric reactive N entering vegetation via the foliar N uptake pathway.

  13. Skeletal muscle glucose uptake during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik A.

    2005-01-01

    The increase in skeletal muscle glucose uptake during exercise results from a coordinated increase in rates of glucose delivery (higher capillary perfusion), surface membrane glucose transport, and intracellular substrate flux through glycolysis. The mechanism behind the movement of GLUT4...

  14. RIMSULFURON UPTAKE, TRANSLOCATION, METABOLISM AND

    Directory of Open Access Journals (Sweden)

    Fuentes Cilia L.

    2003-08-01

    Full Text Available

    Research was conducted to determine the role in selectivity

    of uptake, translocation, metabolism and ALS (acetolactate

    synthase activity of rimsulfuron in two maize (

    Zea mays

    L. hybrids (‘Cargill 2127’, tolerant, and ‘Pioneer 3897’,

    sensitive grown at temperatures of 14°C and 21°C. Forty

    eight hours after treatment (HAT, uptake of rimsulfuron

    was 40% and 67% in ‘Pioneer 3897’, and 26% and 43%

    in ‘Cargill 2127’ at 14°C and 21°C, respectively. Neither

    total translocation nor allocation of rimsulfuron in various

    organs differed greatly between the hybrids. Translocation

    of

     

    14C-rimsulfuron was greater at 21°C (53% than at 14°C

    (23%, 48 HAT. In ‘Pioneer 3897’ over 65% and 30% of

  15. Uptake of AV-1451 in meningiomas.

    Science.gov (United States)

    Bruinsma, Tyler J; Johnson, Derek R; Fang, Ping; Senjem, Matthew; Josephs, Keith A; Whitwell, Jennifer L; Boeve, Bradley F; Pandey, Mukesh K; Kantarci, Kejal; Jones, David T; Vemuri, Prashanthi; Murray, Melissa; Graff-Radford, Jonathan; Schwarz, Christopher G; Knopman, David S; Petersen, Ronald C; Jack, Clifford R; Lowe, Val J

    2017-09-08

    AV-1451 is an imaging agent labeled with the positron-emitting radiolabel Fluorine-18. 18F-AV-1451 binds paired helical filament tau (PHF-tau), a pathology related to Alzheimer's disease. In our study of AV-1451 uptake in the brains of cognitively normal subjects, we noted a case of a meningioma with visually significant uptake of AV-1451. We initiated the present retrospective study to further examine cases of meningioma that underwent AV-1451 imaging. We searched the patient records of 650 patients who had undergone AV-1451 at our institution for the keyword "meningioma" to identify potential cases. PET/CT and MRI results were visually reviewed and semi-quantitative analysis of PET was performed. A paired student's t test was run between background and tumor standard uptake values. Fisher's exact test was used to examine the association between AV-1451 uptake and presence of calcifications on CT. We identified 12 cases of meningioma, 58% (7/12) of which demonstrated uptake greater than background using both visual analysis and tumor-to-normal cortex ratios (T/N + 1.90 ± 0.83). The paired student's t test revealed no statistically significant difference between background and tumor standard uptake values (p = 0.09); however, cases with a T/N ratio greater than one showed statistically higher uptake in tumor tissue (p = 0.01). A significant association was noted between AV-1451 uptake and presence of calcifications (p = 0.01). AV-1451 PET imaging should be reviewed concurrently with anatomic imaging to prevent misleading interpretations of PHF-tau distribution due to meningiomas.

  16. A study of uranium uptake in plants

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, A.; Singh, Surinder; Virk, H.S. (Guru Nanak Dev Univ., Amritsar (India). Dept. of Physics)

    1988-01-01

    A fission track technique has been used to study the uptake of uranium in Tomato Plant. Lexan plastic has been employed as the external detector for recording induced fission tracks due to uranium. The uranium uptake rate is found to increase as the growth proceeds. The uranium concentration is also determined in Phlox, Calendula and Dog Flower, grown under normal conditions. The uranium content is found to vary in different parts of the plants. (author).

  17. Policy Pathways: Energy Management Programmes for Industry

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-09-06

    The IEA Policy Pathway publications provide details on how to implement specific recommendations drawn from the IEA 25 Energy Efficiency Policy Recommendations. This Policy Pathway, jointly produced by the International Energy Agency and the Institute for Industrial Productivity, develops the critical steps for policy makers implementing energy management programmes for industry. Optimising energy use in industry is essential to improve industrial competitiveness and achieve wider societal goals such as energy security, economic recovery and development, climate change mitigation and environmental protection.While there is significant potential to decrease energy consumption in this sector, opportunities to improve energy efficiency are still under-exploited. Energy management programmes have shown to be instrumental in addressing many of the barriers that inhibit wide-scale uptake of energy management in industry. The Policy Pathway builds on lessons learned from country experiences and provides actionable guidance on how to plan and design, implement, evaluate and monitor energy management programmes for industry.

  18. Platinum uptake from chloride solutions using biosorbents

    Directory of Open Access Journals (Sweden)

    Mehmet Hakan Morcali

    2013-04-01

    Full Text Available Present work investigates platinum uptake from synthetically prepared, dilute platinum-bearing solutions using biomass residues, i.e. pistachio nut shell and rice husk, which are abundant in Turkey, and provides a comparison between these two biosorbents. Effects of the different uptake parameters, sorbent dosage, contact time, temperature and pH of solution on platinum uptake (% were studied in detail on a batch sorption. Before the pistachio nut shell was activated, platinum uptake (% was poor compared to the rice husk. However, after the pistachio nut shell was activated at 1000 °C under an argon atmosphere, the platinum uptake (% increased two-fold. The pistachio nut shell (original and activated and rice husk were shown to be better than commercially available activated carbon in terms of adsorption capacity. These two sorbents have also been characterized by FTIR and SEM. Adsorption equilibrium data best complied with the Langmuir isotherm model. Maximum adsorption capacities, Qmax, at 25 °C were found to be 38.31 and 42.02 mg.g- 1for the activated pistachio nut shell and rice husk, respectively. Thermodynamic calculations using the measured ∆H°, ∆S° and ∆G° values indicate that the uptake process was spontaneous and endothermic. The experimental data were shown to be fit the pseudo-second-order kinetic model.

  19. Uptake and metabolism of iron oxide nanoparticles in brain cells.

    Science.gov (United States)

    Petters, Charlotte; Irrsack, Ellen; Koch, Michael; Dringen, Ralf

    2014-09-01

    Magnetic iron oxide nanoparticles (IONPs) are used for various applications in biomedicine, for example as contrast agents in magnetic resonance imaging, for cell tracking and for anti-tumor treatment. However, IONPs are also known for their toxic effects on cells and tissues which are at least in part caused by iron-mediated radical formation and oxidative stress. The potential toxicity of IONPs is especially important concerning the use of IONPs for neurobiological applications as alterations in brain iron homeostasis are strongly connected with human neurodegenerative diseases. Since IONPs are able to enter the brain, potential adverse consequences of an exposure of brain cells to IONPs have to be considered. This article describes the pathways that allow IONPs to enter the brain and summarizes the current knowledge on the uptake, the metabolism and the toxicity of IONPs for the different types of brain cells in vitro and in vivo.

  20. Structure and uptake mechanism of bacteriocins targeting peptidoglycan renewal.

    Science.gov (United States)

    Zeth, Kornelius

    2012-12-01

    Bacteriocins are narrow-spectrum protein antibiotics released to kill related bacteria of the same niche. Uptake of bacteriocins depends critically on the presence of an uptake receptor in the outer membrane, a translocation pore and an energy-dependent activating system of the inner membrane. Most bacteriocins act on the inner membrane as pore-forming toxins or they target cytoplasmic DNA/RNA and ribosomal synthesis respectively. Only two bacteriocins are known to become activated in the periplasmic space and to inhibit the renewal process of the peptidoglycan structure. In Escherichia coli, the Cma (colicin M) phosphatase is activated in the periplasmic space by the FkpA chaperone and subsequently degrades the C55-PP precursor unit of the peptidoglycan. Pst (pesticin) from Yersinia pestis carries a lysozyme homology domain to degrade peptidoglycan. Import of Pst is only achieved if the N-terminal translocation domain can span the outer membrane and if extensive unfolding of the protein during membrane passage is permitted. There is considerable plasticity in the import pathway since a chimaera comprising the activity domain replaced by T4 lysozyme is also translocated and active in killing those bacteria carrying the FyuA receptor.

  1. Root Uptake of Lipophilic Zinc−Rhamnolipid Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Stacey, Samuel P.; McLaughlin, Michael J.; Cakmak, Ismail; Hettiarachchi, Ganga M.; Scheckel, Kirk G.; Karkkainen, Michael (Sabanci); (EPA); (CSIRO/LW); (Adelaide)

    2009-06-16

    This study investigated the formation and plant uptake of lipophilic metal-rhamnolipid complexes. Monorhamnosyl and dirhamnosyl rhamnolipids formed lipophilic complexes with copper (Cu), manganese (Mn), and zinc (Zn). Rhamnolipids significantly increased Zn absorption by Brassica napus var. Pinnacle roots in {sup 65}Zn-spiked ice-cold solutions, compared with ZnSO{sub 4} alone. Therefore, rhamnolipid appeared to facilitate Zn absorption via a nonmetabolically mediated pathway. Synchrotron XRF and XAS showed that Zn was present in roots as Zn-phytate-like compounds when roots were treated with Zn-free solutions, ZnSO{sub 4}, or Zn-EDTA. With rhamnolipid application, Zn was predominantly found in roots as the Zn-rhamnolipid complex. When applied to a calcareous soil, rhamnolipids increased dry matter production and Zn concentrations in durum (Triticum durum L. cv. Balcali-2000) and bread wheat (Triticum aestivum L. cv. BDME-10) shoots. Rhamnolipids either increased total plant uptake of Zn from the soil or increased Zn translocation by reducing the prevalence of insoluble Zn-phytate-like compounds in roots.

  2. Cellular uptake and dynamics of unlabeled freestanding silicon nanowires.

    Science.gov (United States)

    Zimmerman, John F; Parameswaran, Ramya; Murray, Graeme; Wang, Yucai; Burke, Michael; Tian, Bozhi

    2016-12-01

    The ability to seamlessly merge electronic devices with biological systems at the cellular length scale is an exciting prospect for exploring new fundamental cell biology and in designing next-generation therapeutic devices. Semiconductor nanowires are well suited for achieving this goal because of their intrinsic size and wide range of possible configurations. However, current studies have focused primarily on delivering substrate-bound nanowire devices through mechanical abrasion or electroporation, with these bulkier substrates negating many of the inherent benefits of using nanoscale materials. To improve on this, an important next step is learning how to distribute these devices in a drug-like fashion, where cells can naturally uptake and incorporate these electronic components, allowing for truly noninvasive device integration. We show that silicon nanowires (SiNWs) can potentially be used as such a system, demonstrating that label-free SiNWs can be internalized in multiple cell lines (96% uptake rate), undergoing an active "burst-like" transport process. Our results show that, rather than through exogenous manipulation, SiNWs are internalized primarily through an endogenous phagocytosis pathway, allowing cellular integration of these materials. To study this behavior, we have developed a robust set of methodologies for quantitatively examining high-aspect ratio nanowire-cell interactions in a time-dependent manner on both single-cell and ensemble levels. This approach represents one of the first dynamic studies of semiconductor nanowire internalization and offers valuable insight into designing devices for biomolecule delivery, intracellular sensing, and photoresponsive therapies.

  3. Direct translocation as major cellular uptake for CADY self-assembling peptide-based nanoparticles.

    Directory of Open Access Journals (Sweden)

    Anna Rydström

    Full Text Available Cell penetrating peptides constitute a potent approach to overcome the limitations of in vivo siRNA delivery. We recently proposed a peptide-based nanoparticle system, CADY, for efficient delivery of siRNA into numerous cell lines. CADY is a secondary amphipathic peptide that forms stable complexes with siRNA thereby improving both their cellular uptake and biological response. With the aim of understanding the cellular uptake mechanism of CADY:siRNA complexes, we have combined biochemical, confocal and electron microscopy approaches. In the present work, we provide evidence that the major route for CADY:siRNA cellular uptake involves direct translocation through the membrane but not the endosomal pathway. We have demonstrated that CADY:siRNA complexes do not colocalize with most endosomal markers and remain fully active in the presence of inhibitors of the endosomal pathway. Moreover, neither electrostatic interactions with cell surface heparan sulphates nor membrane potential are essential for CADY:siRNA cell entry. In contrast, we have shown that CADY:siRNA complexes clearly induce a transient cell membrane permeabilization, which is rapidly restored by cell membrane fluidity. Therefore, we propose that direct translocation is the major gate for cell entry of CADY:siRNA complexes. Membrane perturbation and uptake are driven mainly by the ability of CADY to interact with phospholipids within the cell membrane, followed by rapid localization of the complex in the cytoplasm, without affecting cell integrity or viability.

  4. Lack of CD2AP disrupts Glut4 trafficking and attenuates glucose uptake in podocytes.

    Science.gov (United States)

    Tolvanen, Tuomas A; Dash, Surjya Narayan; Polianskyte-Prause, Zydrune; Dumont, Vincent; Lehtonen, Sanna

    2015-12-15

    The adapter protein CD2-associated protein (CD2AP) functions in various signaling and vesicle trafficking pathways, including endosomal sorting and/or trafficking and degradation pathways. Here, we investigated the role of CD2AP in insulin-dependent glucose transporter 4 (Glut4, also known as SLC2A4) trafficking and glucose uptake. Glucose uptake was attenuated in CD2AP(-/-) podocytes compared with wild-type podocytes in the basal state, and CD2AP(-/-) podocytes failed to increase glucose uptake in response to insulin. Live-cell imaging revealed dynamic trafficking of HA-Glut4-GFP in wild-type podocytes, whereas in CD2AP(-/-) podocytes, HA-Glut4-GFP clustered perinuclearly. In subcellular membrane fractionations, CD2AP co-fractionated with Glut4, IRAP (also known as LNPEP) and sortilin, constituents of Glut4 storage vesicles (GSVs). We further found that CD2AP forms a complex with GGA2, a clathrin adaptor, which sorts Glut4 to GSVs, suggesting a role for CD2AP in this process. We also found that CD2AP forms a complex with clathrin and connects clathrin to actin in the perinuclear region. Furthermore, clathrin recycling back to trans-Golgi membranes from the vesicular fraction containing GSVs was defective in the absence of CD2AP. This leads to reduced insulin-stimulated trafficking of GSVs and attenuated glucose uptake into CD2AP(-/-) podocytes.

  5. Plant uptake of dual-labeled organic N biased by inorganic C uptake

    DEFF Research Database (Denmark)

    Rasmussen, Jim; Sauheitl, Leopold; Eriksen, Jørgen;

    2010-01-01

    Direct plant uptake of organic nitrogen (N) is often studied using the dual-labeling approach (15N + 13C or 15N + 14C). However, the method might be hampered by uptake of labeled inorganic carbon (C) produced by mineralization of labeled organic compounds. Here we report the results from a triple...... glycine or CO2-3 , but found no differences in uptake rates between these C-sources. The uptake of inorganic C to the shoot tissue was higher for maize grown in full light compared to shading, which indicates a passive uptake of inorganic C with water. We conclude that uptake of inorganic C produced...... labeling experiment (15N + 13C + 14C) investigating whether root uptake of labeled inorganic C can bias the results obtained in studies of organic N uptake using dual-labeled amino acids (15N, 13C). In a rhizosphere tube experiment we investigated 13C and 14C uptake by maize either supplied with labeled...

  6. Modulatory Role of Surface Coating of Superparamagnetic Iron Oxide Nanoworms in Complement Opsonization and Leukocyte Uptake

    DEFF Research Database (Denmark)

    Inturi, Swetha; Wang, Guankui; Chen, Fangfang

    2015-01-01

    Notwithstanding rapid advances of nanotechnology in diagnostic imaging and drug delivery, the engineered nanocarriers still exhibit substantial lack of hemocompatibility. Thus, when injected systemically, nanoparticles are avidly recognized by blood leukocytes and platelets, but the mechanisms of...... alternative pathway and by nanoparticle surface coating. These results provide important insights into the mechanisms of hemocompatibility of nanomedicines....... demonstrated that neutrophils, monocytes, lymphocytes and eosinophils took up SPIO NWs, and the uptake was prevented by EDTA (a general complement inhibitor) and by antiproperdin antibody (an inhibitor of the alternative pathway of the complement system). Cross-linking and hydrogelation of SPIO NWs surface...

  7. Cellular uptake of fluorophore-labeled glyco-DNA-gold nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Witten, Katrin G.; Ruff, Julie [RWTH Aachen University, Institute of Inorganic Chemistry and JARA - Fundamentals of Future Information Technology (Germany); Mohr, Anne; Goertz, Dieter; Recker, Tobias; Rinis, Natalie [RWTH Aachen University, Institute of Biochemistry and Molecular Biology, University Hospital Aachen (Germany); Rech, Claudia; Elling, Lothar [RWTH Aachen University, Laboratory for Biomaterials, Institute of Biotechnology and Helmholtz-Institute for Biomedical Engineering (Germany); Mueller-Newen, Gerhard [RWTH Aachen University, Institute of Biochemistry and Molecular Biology, University Hospital Aachen (Germany); Simon, Ulrich, E-mail: ulrich.simon@ac.rwth-aachen.de [RWTH Aachen University, Institute of Inorganic Chemistry and JARA - Fundamentals of Future Information Technology (Germany)

    2013-10-15

    DNA-functionalized gold nanoparticles (AuNP-DNA) were hybridized with complementary di-N-acetyllactosamine-(di-LacNAc, [3Gal({beta}1-4)GlcNAc({beta}1-]2)-modified oligonucleotides to form glycol-functionalized particles, AuNP-DNA-di-LacNAc. While AuNP-DNA are known to be taken up by cells via scavenger receptors, glycol-functionalized particles have shown to be taken up via asialoglycoprotein receptors (ASGP-R). In this work, the interaction of these new particles with HepG2 cells was analyzed, which express scavenger receptors class B type I (SR-BI) and ASGP-R. To study the contribution of these receptors as potential mediators for cellular uptake, receptor-blocking experiments were performed with d-lactose, a ligand for ASGP-R, Fucoidan, a putative ligand for SR-BI, and a SR-BI blocking antibody. Labeling with Cy5-modified DNA ligands enabled us to monitor the particle uptake by confocal fluorescence microscopy and flow cytometry, in order to discriminate the two putative pathways by competitive binding studies. While SR-BI-antibody and d-lactose had no inhibiting effects on particle uptake Fucoidan led to a complete inhibition. Thus, a receptor-mediated uptake by the two receptors studied could not be proven and therefore other uptake mechanisms have to be considered.

  8. Cellular uptake of fluorophore-labeled glyco-DNA-gold nanoparticles

    Science.gov (United States)

    Witten, Katrin G.; Ruff, Julie; Mohr, Anne; Görtz, Dieter; Recker, Tobias; Rinis, Natalie; Rech, Claudia; Elling, Lothar; Müller-Newen, Gerhard; Simon, Ulrich

    2013-10-01

    DNA-functionalized gold nanoparticles (AuNP-DNA) were hybridized with complementary di- N-acetyllactosamine-( di-LacNAc, [3Gal(β1-4)GlcNAc(β1-]2)-modified oligonucleotides to form glycol-functionalized particles, AuNP-DNA- di-LacNAc. While AuNP-DNA are known to be taken up by cells via scavenger receptors, glycol-functionalized particles have shown to be taken up via asialoglycoprotein receptors (ASGP-R). In this work, the interaction of these new particles with HepG2 cells was analyzed, which express scavenger receptors class B type I (SR-BI) and ASGP-R. To study the contribution of these receptors as potential mediators for cellular uptake, receptor-blocking experiments were performed with d-lactose, a ligand for ASGP-R, Fucoidan, a putative ligand for SR-BI, and a SR-BI blocking antibody. Labeling with Cy5-modified DNA ligands enabled us to monitor the particle uptake by confocal fluorescence microscopy and flow cytometry, in order to discriminate the two putative pathways by competitive binding studies. While SR-BI-antibody and d-lactose had no inhibiting effects on particle uptake Fucoidan led to a complete inhibition. Thus, a receptor-mediated uptake by the two receptors studied could not be proven and therefore other uptake mechanisms have to be considered.

  9. Effect of serum proteins on polystyrene nanoparticle uptake and intracellular trafficking in endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Guarnieri, Daniela; Guaccio, Angela; Fusco, Sabato; Netti, Paolo A., E-mail: nettipa@unina.it [Istituto Italiano di Tecnologia, Center for Advanced Biomaterials for Health Care atCRIB (Italy)

    2011-09-15

    The physico-chemical properties of nanoparticles (NPs), such as small dimensions, surface charge and surface functionalization, control their capability to interact with cells and, in particular, with sub-cellular components. This interaction can be also influenced by the adsorption of molecules present in biological fluids, like blood, on NP surface. Here, we analysed the effect of serum proteins on 49 and 100 nm red fluorescent polystyrene NP uptake in porcine aortic endothelial (PAE) cells, as a model for vascular transport. To this aim, NP uptake kinetic, endocytic pathway and intracellular trafficking were studied by monitoring NPs inside cells through confocal microscopy and multiple particle tracking (MPT). We demonstrated that NPs are rapidly internalized by cells in serum-free (SF) medium, according to a saturation kinetic. Conversely, in 10% foetal bovine serum-enriched (SE) medium, NP uptake rate results drastically reduced. Moreover, NP internalization depends on an active endocytic mechanism that does not involve clathrin- and caveolae-mediated vesicular transport, in both SE and SF media. Furthermore, MPT data indicate that NP intracellular trafficking is unaffected by protein presence. Indeed, approximately 50-60% of internalized NPs is characterized by a sub-diffusive behaviour, whereas the remaining fraction shows an active motion. These findings demonstrate that the unspecific protein adsorption on NP surface can affect cellular uptake in terms of internalization kinetics, but it is not effective in controlling active and cellular-mediated uptake mechanisms of NPs and their intracellular routes.

  10. Cellular uptake of a dexamethasone palmitate-low density lipoprotein complex by macrophages and foam cells.

    Science.gov (United States)

    Tauchi, Yoshihiko; Chono, Sumio; Morimoto, Kazuhiro

    2003-04-01

    To evaluate the utility of a dexamethasone palmitate (DP)-low density lipoprotein (LDL) complex to transport drug into foam cells, the cellular uptake of DP-LDL complex by macrophages and foam cells was examined. The DP-LDL complex was prepared by incubation with DP and LDL, and the DP-LDL complex and murine macrophages were incubated. No cellular uptake of the DP-LDL complex by macrophages was found until 6 h after the start of incubation, but this gradually increased from 12 to 48 h. On the other hand, the cellular uptake of the oxidized DP-LDL complex was already apparent at 3 h after the start incubation, and then markedly increased until 48 h incubation along with that of the lipid emulsion (LE) containing DP (DP-LE). The cellular uptake of DP-LE by foam cells was significantly lower than that by macrophages. However, the cellular uptake of DP-LDL complex by foam cells was similar to that by macrophages. These findings suggest that the DP-LDL complex is oxidatively modified, and then incorporated into macrophages and foam cells through the scavenger receptor pathway. Since selective delivery of drugs into foam cells in the early stage of atherosclerosis is a useful protocol for antiatherosclerosis treatment, the DP-LDL complex appears to be a potentially useful drug-carrier complex for future antiatherosclerotic therapy.

  11. Differential functions of the Apoer2 intracellular domain in selenium uptake and cell signaling.

    Science.gov (United States)

    Masiulis, Irene; Quill, Timothy A; Burk, Raymond F; Herz, Joachim

    2009-01-01

    Apolipoprotein E receptor 2 (Apoer2) is a multifunctional transport and signaling receptor that regulates the uptake of selenium into the mouse brain and testis through endocytosis of selenoprotein P (Sepp1). Mice deficient in Apoer2 or Sepp1 are infertile, with kinked and hypomotile spermatozoa. They also develop severe neurological defects on a low selenium diet, due to a profound impairment of selenium uptake. Little is known about the function of Apoer2 in the testis beyond its role as a Sepp1 receptor. By contrast, in the brain, Apoer2 is an essential component of the Reelin signaling pathway, which is required for proper neuronal organization and synapse function. Using knock-in mice, we have functionally dissociated the signaling motifs in the Apoer2 cytoplasmic domain from Sepp1 uptake. Selenium concentration of brain and testis was normal in the knock-in mutants, in contrast to Apoer2 knock-outs. Thus, the neurological defects in the signaling impaired knock-in mice are not caused by a selenium uptake defect, but instead are a direct consequence of a disruption of the Reelin signal. Reduced sperm motility was observed in some of the knock-in mice, indicating a novel signaling role for Apoer2 in sperm development and function that is independent of selenium uptake.

  12. Uptake of polychlorinated biphenyls and organochlorine pesticides from soil and air into radishes (Raphanus sativus)

    Energy Technology Data Exchange (ETDEWEB)

    Mikes, Ondrej; Cupr, Pavel [RECETOX, Research Centre for Environmental Chemistry and Ecotoxicology, Masaryk University, Kamenice 126/3, 625 00 Brno (Czech Republic); Trapp, Stefan [Department of Environmental Engineering, Technical University of Denmark, Miljoevej 113, DK-2800 Kgs. Lyngby (Denmark); Klanova, Jana [RECETOX, Research Centre for Environmental Chemistry and Ecotoxicology, Masaryk University, Kamenice 126/3, 625 00 Brno (Czech Republic)], E-mail: klanova@recetox.muni.cz

    2009-02-15

    Uptake of organochlorine pesticides and polychlorinated biphenyls from soil and air into radishes was measured at a heavily contaminated field site. The highest contaminant concentrations were found for DDT and its metabolites, and for {beta}-hexachlorocyclohexane. Bioconcentration factor (BCF, defined as a ratio between the contaminant concentration in the plant tissue and concentration in soil) was determined for roots, edible bulbs and shoots. Root BCF values were constant and not correlated to log K{sub OW}. A negative correlation between BCF and log K{sub OW} was found for edible bulbs. Shoot BCF values were rather constant and varied between 0.01 and 0.22. Resuspended soil particles may facilitate the transport of chemicals from soil to shoots. Elevated POP concentrations found in shoots of radishes grown in the control plot support the hypothesis that the uptake from air was more significant for shoots than the one from soil. The uptake of POPs from air was within the range of theoretical values predicted from log K{sub OA}. - Uptake from air represented for majority of persistent organochlorines a dominant pathway into shoots while uptake from soil was dominant for roots.

  13. Nitrate uptake across biomes and the influence of elemental stoichiometry: A new look at LINX II

    Science.gov (United States)

    Wymore, Adam S.; Coble, Ashley A.; Rodríguez-Cardona, Bianca; McDowell, William H.

    2016-08-01

    Considering recent increases in anthropogenic N loading, it is essential to identify the controls on N removal and retention in aquatic ecosystems because the fate of N has consequences for water quality in streams and downstream ecosystems. Biological uptake of nitrate (NO3-) is a major pathway by which N is removed from these ecosystems. Here we used data from the second Lotic Intersite Nitrogen eXperiment (LINX II) in a multivariate analysis to identify the primary drivers of variation in NO3- uptake velocity among biomes. Across 69 study watersheds in North America, dissolved organic carbon:NO3- ratios and photosynthetically active radiation were identified as the two most important predictor variables in explaining NO3- uptake velocity. However, within a specific biome the predictor variables of NO3- uptake velocity varied and included various physical, chemical, and biological attributes. Our analysis demonstrates the broad control of elemental stoichiometry on NO3- uptake velocity as well as the importance of biome-specific predictors. Understanding this spatial variation has important implications for biome-specific watershed management and the downstream export of NO3-, as well as for development of spatially explicit global models that describe N dynamics in streams and rivers.

  14. K+ uptake in plant roots. The systems involved, their regulation and parallels in other organisms.

    Science.gov (United States)

    Nieves-Cordones, Manuel; Alemán, Fernando; Martínez, Vicente; Rubio, Francisco

    2014-05-15

    Potassium (K(+)) is an essential macronutrient for plants. It is taken into the plant by the transport systems present in the plasma membranes of root epidermal and cortical cells. The identity of these systems and their regulation is beginning to be understood and the systems of K(+) transport in the model species Arabidopsis thaliana remain far better characterized than in any other plant species. Roots can activate different K(+) uptake systems to adapt to their environment, important to a sessile organism that needs to cope with a highly variable environment. The mechanisms of K(+) acquisition in the model species A. thaliana are the best characterized at the molecular level so far. According to the current model, non-selective channels are probably the main pathways for K(+) uptake at high concentrations (>10mM), while at intermediate concentrations (1mM), the inward rectifying channel AKT1 dominates K(+) uptake. Under lower concentrations of external K(+) (100μM), AKT1 channels, together with the high-affinity K(+) uptake system HAK5 contribute to K(+) acquisition, and at extremely low concentrations (root K(+) uptake are shared by other organisms, whilst others are specific to plants. This indicates that some crucial properties of the ancestral of K(+) transport systems have been conserved through evolution while others have diverged among different kingdoms.

  15. The role of biological rates in the simulated warming effect on oceanic CO2 uptake

    Science.gov (United States)

    Cao, Long; Zhang, Han

    2017-05-01

    Marine biology plays an important role in the ocean carbon cycle. However, the effect of warming-induced changes in biological rates on oceanic CO2 uptake has been largely overlooked. We use an Earth system model of intermediate complexity to investigate the effect of temperature-induced changes in biological rates on oceanic uptake of atmospheric CO2 and compare it with the effects from warming-induced changes in CO2 solubility and ocean mixing and circulation. Under the representative CO2 concentration pathway RCP 8.5 and its extension, by year 2500, relative to the simulation without warming effect on the ocean carbon cycle, CO2-induced warming reduces cumulative oceanic CO2 uptake by 469 Pg C, of which about 20% is associated with the warming-induced change in marine biological rates. In our simulations, the bulk effect of biological-mediated changes on CO2 uptake is smaller than that mediated by changes in CO2 solubility and ocean mixing and circulation. However, warming-induced changes in individual biological rates, including phytoplankton growth, phytoplankton mortality, and detritus remineralization, are found to affect oceanic CO2 uptake by an amount greater than or comparable to that caused by changes in CO2 solubility and ocean physics. Our simulations, which include only a few temperature-dependent biological processes, demonstrate the important role of biological rates in the oceanic CO2 uptake. In reality, many more complicated biological processes are sensitive to temperature change, and their responses to warming could substantially affect oceanic uptake of atmospheric CO2.

  16. Role of sucrose in the heterogeneous uptake of dimethylamine by ammonium sulfate aerosol particles

    Science.gov (United States)

    Chu, Y.; Chan, C. K.

    2016-12-01

    Alkyl amines are important alkaline gases besides ammonia in the atmosphere and widely detected in both gas and particle phases. Heterogeneous uptake by pre-existing particles containing acids as well as ammonium salts is one of the major pathways of alkyl amines partitioning into aerosols. Recently, phase state of ammonium salt particles has been revealed to largely affect the degree of alkyl amines uptake. Using an electrodynamic balance coupled with Raman spectroscopy, we extend the study by investigating the alkyl amine uptake by ammonium sulfate (AS) - sucrose mixed particles, since ambient aerosols usually consist of a mixed phase of organics and inorganics. Sucrose is a surrogate of hydrophilic viscous organics that can alter the phase of AS at low relative humidity (RH) and dimethylamine (DMA) is selected for its abundance amongst alkyl amine compounds. DMA uptake occurred effectively at not only 70% RH but also RH as low as 10%, significantly below the AS crystallization point. The net uptake coefficient decreased as RH decreased for fixed initial AS - sucrose particle compositions. Interestingly, it followed a first increasing then decreasing trend as sucrose molar fraction increased from 0 to 0.5, at RH below 30%. Sucrose, albeit inert to DMA vapor, indirectly affected the interaction between DMA and AS - sucrose particles. On one hand, it absorbed water at low RH and delayed the efflorescence of AS to promote DMA uptake. On the other hand, the particle became more viscous with higher sucrose concentration and exhibited an effective mass transport barrier. Hence, the uptake of alkyl amines may occur slowly once ammonium salts are mixed with viscous organics, such as those secondary organic materials formed via the oxidation of biogenic volatile organic compounds, in the particle phase. Acknowledgment This work is supported by Research Grants Council (RGC) of Hong Kong Special Administrative Region, China (GRF 16300214). The grant from Hong Kong RGC Ph

  17. Toxic Compounds in Our Food: Arsenic Uptake By Rice and Potential Mitigation By Silicon

    Science.gov (United States)

    Seyfferth, A.; Gill, R.; Penido, E.

    2014-12-01

    Arsenic is a ubiquitous element in soils worldwide and has the potential to negatively impact human and ecosystem health under certain biogeochemical conditions. While arsenic is relatively immobile in most oxidized soils due to a high affinity for soil solids, arsenic becomes mobilized under reduced soil conditions due to the reductive dissolution of iron(III) oxides thereby releasing soil-bound arsenic. Since arsenic is a well-known carcinogen, this plant-soil process has the potential to negatively impact the lives of billions of rice consumers worldwide upon plant uptake and grain storage of released arsenic. Moreover, arsenic uptake by rice is excacerbated by the use of As-laden groundwater for rice irrigation. One proposed strategy to decrease arsenic uptake by rice plants is via an increase in dissolved silicon in paddy soil solution (pore-water), since silicic acid and arsenous acid share an uptake pathway. However, several soil processes that influence arsenic cycling may be affected by silicon including desorption from bulk soil, formation and mineralogy of iron(III) oxide plaque, and adsorption/desorption onto/from iron plaque; the effect of silicon on these soil processes will ultimately dictate the effectiveness of altered dissolved silicon in decreasing arsenic uptake at the root, which in turn dictates the concentration of arsenic found in grains. Furthermore, the source of silicon may impact carbon cycling and, in particular, methane emissions. Here, impacts of altered dissolved silicon on processes that affect rhizospheric biogeochemical cycling of arsenic and subsequent plant-uptake, and how it influences other biogeochemical cycles such as carbon and iron are investigated. We show that silicon can decrease arsenic uptake and grain storage under certain conditions, and that altered silicon affects the type of iron (III) oxide that comprises iron plaque.

  18. Uptake of Helicobacter pylori outer membrane vesicles by gastric epithelial cells.

    Science.gov (United States)

    Parker, Heather; Chitcholtan, Kenny; Hampton, Mark B; Keenan, Jacqueline I

    2010-12-01

    Helicobacter pylori bacteria colonize the human stomach where they stimulate a persistent inflammatory response. H. pylori is considered noninvasive; however, lipopolysaccharide (LPS)-enriched outer membrane vesicles (OMV), continuously shed from the surface of this bacterium, are observed within gastric epithelial cells. The mechanism of vesicle uptake is poorly understood, and this study was undertaken to examine the roles of bacterial VacA cytotoxin and LPS in OMV binding and cholesterol and clathrin-mediated endocytosis in vesicle uptake by gastric epithelial cells. OMV association was examined using a fluorescent membrane dye to label OMV, and a comparison was made between the associations of vesicles from a VacA(+) strain and OMV from a VacA(-) isogenic mutant strain. Within 20 min, essentially all associated OMV were intracellular, and vesicle binding appeared to be facilitated by the presence of VacA cytotoxin. Uptake of vesicles from the VacA(+) strain was inhibited by H. pylori LPS (58% inhibition with 50 μg/ml LPS), while uptake of OMV from the VacA(-) mutant strain was less affected (25% inhibition with 50 μg/ml LPS). Vesicle uptake did not require cholesterol. However, uptake of OMV from the VacA(-) mutant strain was inhibited by a reduction in clathrin-mediated endocytosis (42% with 15 μg/ml chlorpromazine), while uptake of OMV from the VacA(+) strain was less affected (25% inhibition with 15 μg/ml chlorpromazine). We conclude that VacA toxin enhances the association of H. pylori OMV with cells and that the presence of the toxin may allow vesicles to exploit more than one pathway of internalization.

  19. Uptake of Helicobacter pylori Outer Membrane Vesicles by Gastric Epithelial Cells▿

    Science.gov (United States)

    Parker, Heather; Chitcholtan, Kenny; Hampton, Mark B.; Keenan, Jacqueline I.

    2010-01-01

    Helicobacter pylori bacteria colonize the human stomach where they stimulate a persistent inflammatory response. H. pylori is considered noninvasive; however, lipopolysaccharide (LPS)-enriched outer membrane vesicles (OMV), continuously shed from the surface of this bacterium, are observed within gastric epithelial cells. The mechanism of vesicle uptake is poorly understood, and this study was undertaken to examine the roles of bacterial VacA cytotoxin and LPS in OMV binding and cholesterol and clathrin-mediated endocytosis in vesicle uptake by gastric epithelial cells. OMV association was examined using a fluorescent membrane dye to label OMV, and a comparison was made between the associations of vesicles from a VacA+ strain and OMV from a VacA− isogenic mutant strain. Within 20 min, essentially all associated OMV were intracellular, and vesicle binding appeared to be facilitated by the presence of VacA cytotoxin. Uptake of vesicles from the VacA+ strain was inhibited by H. pylori LPS (58% inhibition with 50 μg/ml LPS), while uptake of OMV from the VacA− mutant strain was less affected (25% inhibition with 50 μg/ml LPS). Vesicle uptake did not require cholesterol. However, uptake of OMV from the VacA− mutant strain was inhibited by a reduction in clathrin-mediated endocytosis (42% with 15 μg/ml chlorpromazine), while uptake of OMV from the VacA+ strain was less affected (25% inhibition with 15 μg/ml chlorpromazine). We conclude that VacA toxin enhances the association of H. pylori OMV with cells and that the presence of the toxin may allow vesicles to exploit more than one pathway of internalization. PMID:20876296

  20. Mercury emission and plant uptake of trace elements during early stage of soil amendment using flue gas desulfurization materials.

    Science.gov (United States)

    A pilot-scale field study was carried out to investigate the distribution of Hg and other selected elements in the three potential mitigation pathways, i.e., emission to ambient air, uptake by surface vegetation (i.e., grass), and rainfall infiltration, after flue gas desulfurization (FGD) material ...

  1. Fast intracellular dissolution and persistent cellular uptake of silver nanoparticles in CHO-K1 cells: implication for cytotoxicity

    DEFF Research Database (Denmark)

    Jiang, Xiumei; Miclaus, Teodora; Wang, Liming

    2015-01-01

    Toxicity of silver nanoparticles (Ag NPs) has been reported both in vitro and in vivo. However, the intracellular stability and chemical state of Ag NPs are still not very well studied. In this work, we systematically investigated the cellular uptake pathways, intracellular dissolution and chemic...

  2. Selenium Uptake and Volatilization by Marine Algae

    Science.gov (United States)

    Luxem, Katja E.; Vriens, Bas; Wagner, Bettina; Behra, Renata; Winkel, Lenny H. E.

    2015-04-01

    Selenium (Se) is an essential trace nutrient for humans. An estimated one half to one billion people worldwide suffer from Se deficiency, which is due to low concentrations and bioavailability of Se in soils where crops are grown. It has been hypothesized that more than half of the atmospheric Se deposition to soils is derived from the marine system, where microorganisms methylate and volatilize Se. Based on model results from the late 1980s, the atmospheric flux of these biogenic volatile Se compounds is around 9 Gt/year, with two thirds coming from the marine biosphere. Algae, fungi, and bacteria are known to methylate Se. Although algal Se uptake, metabolism, and methylation influence the speciation and bioavailability of Se in the oceans, these processes have not been quantified under environmentally relevant conditions and are likely to differ among organisms. Therefore, we are investigating the uptake and methylation of the two main inorganic Se species (selenate and selenite) by three globally relevant microalgae: Phaeocystis globosa, the coccolithophorid Emiliania huxleyi, and the diatom Thalassiosira oceanica. Selenium uptake and methylation were quantified in a batch experiment, where parallel gas-tight microcosms in a climate chamber were coupled to a gas-trapping system. For E. huxleyi, selenite uptake was strongly dependent on aqueous phosphate concentrations, which agrees with prior evidence that selenite uptake by phosphate transporters is a significant Se source for marine algae. Selenate uptake was much lower than selenite uptake. The most important volatile Se compounds produced were dimethyl selenide, dimethyl diselenide, and dimethyl selenyl sulfide. Production rates of volatile Se species were larger with increasing intracellular Se concentration and in the decline phase of the alga. Similar experiments are being carried out with P. globosa and T. oceanica. Our results indicate that marine algae are important for the global cycling of Se

  3. Physiologically based pharmacokinetic modeling for 1-bromopropane in F344 rats using gas uptake inhalation experiments.

    Science.gov (United States)

    Garner, C Edwin; Liang, Shenxuan; Yin, Lei; Yu, Xiaozhong

    2015-05-01

    1-Bromopropane (1-BP) was introduced into the workplace as an alternative to ozone-depleting solvents and increasingly used in manufacturing industry. The potential exposure to 1-BP and the current reports of adverse effects associated with occupational exposure to high levels of 1-BP have increased the need to understand the mechanism of 1-BP toxicity in animal models as a mean of understanding risk in workers. Physiologically based pharmacokinetic (PBPK) model for 1-BP has been developed to examine 2 metabolic pathway assumptions for gas-uptake inhalation study. Based on previous gas-uptake experiments in the Fischer 344 rat, the PBPK model was developed by simulating the 1-BP concentration in a closed chamber. In the model, we tested the hypothesis that metabolism responsibilities were shared by the p450 CYP2E1 and glutathione (GSH) conjugation. The results showed that 2 metabolic pathways adequately simulated 1-BP closed chamber concentration. Furthermore, the above model was tested by simulating the gas-uptake data of the female rats pretreated with 1-aminobenzotrizole, a general P450 suicide inhibitor, or d,l-buthionine (S,R)-sulfoximine, an inhibitor of GSH synthesis, prior to exposure to 800 ppm 1-BP. The comparative investigation on the metabolic pathway of 1-BP through the PBPK modeling in both sexes provides critical information for understanding the role of p450 and GSH in the metabolism of 1-BP and eventually helps to quantitatively extrapolate current animal studies to human.

  4. Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes.

    Science.gov (United States)

    Mitsuhashi, Kazuteru; Senmaru, Takafumi; Fukuda, Takuya; Yamazaki, Masahiro; Shinomiya, Katsuhiko; Ueno, Morio; Kinoshita, Shigeru; Kitawaki, Jo; Katsuyama, Masato; Tsujikawa, Muneo; Obayashi, Hiroshi; Nakamura, Naoto; Fukui, Michiaki

    2016-01-01

    Decreases in serum testosterone concentrations in aging men are associated with metabolic disorders. Testosterone has been reported to increase GLUT4-dependent glucose uptake in skeletal muscle cells and cardiomyocytes. However, studies on glucose uptake occurring in response to testosterone stimulation in adipocytes are currently not available. This study was designed to determine the effects of testosterone on glucose uptake in adipocytes. Glucose uptake was assessed with 2-[(3)H] deoxyglucose in 3T3-L1 adipocytes. GLUT4 translocation was evaluated in plasma membrane (PM) sheets and PM fractions by immunofluorescence and immunoblotting, respectively. Activation of GLUT4 translocation-related protein kinases, including Akt, AMPK, LKB1, CaMKI, CaMKII, and Cbl was followed by immunoblotting. Expression levels of androgen receptor (AR) mRNA and AR translocation to the PM were assessed by real-time RT-PCR and immunoblotting, respectively. The results showed that both high-dose (100 nM) testosterone and testosterone-BSA increased glucose uptake and GLUT4 translocation to the PM, independently of the intracellular AR. Testosterone and testosterone-BSA stimulated the phosphorylation of AMPK, LKB1, and CaMKII. The knockdown of LKB1 by siRNA attenuated testosterone- and testosterone-BSA-stimulated AMPK phosphorylation and glucose uptake. These results indicate that high-dose testosterone and testosterone-BSA increase GLUT4-dependent glucose uptake in 3T3-L1 adipocytes by inducing the LKB1/AMPK signaling pathway.

  5. Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.

    Directory of Open Access Journals (Sweden)

    Jong Hyun Kim

    suggest that AMPK-mediated PLD1 activation is required for (14C-glucose uptake through ERK stimulation. We propose that the AMPK-mediated PLD1 pathway may provide crucial clues to understanding the mechanisms involved in glucose uptake.

  6. Cyclic Strain Enhances Cellular Uptake of Nanoparticles

    Directory of Open Access Journals (Sweden)

    Jia Hu

    2015-01-01

    Full Text Available Nanoparticles (NPs have gained increasing interest in recent years due to their potential use as drug carrier, imaging, and diagnostic agents in pharmaceutical and biomedical applications. While many cells in vivo experience mechanical forces, little is known about the correlation of the mechanical stimulation and the internalization of NPs into cells. This paper investigates the effects of applied cyclic strain on NP uptake by cells. Bovine aortic endothelial cells (BAECs were cultured on collagen-coated culture plates and placed under cyclic equal-axial strains. NPs of sizes ranging from 50 to 200 nm were loaded at a concentration of 0.02 mg/mL and cyclic strains from 5 to 15% were applied to the cells for one hour. The cyclic strain results in a significant enhancement in NP uptake, which increases almost linearly with strain level. The enhanced uptake also depends on size of the NPs with the highest uptake observed on 100 nm NP. The effect of enhanced NP uptake lasts around 13 hours after cyclic stretch. Such in vitro cell stretch systems mimic physiological conditions of the endothelial cells in vivo and could potentially serve as a biomimetic platform for drug therapeutic evaluation.

  7. Scaling laws in phytoplankton nutrient uptake affinity

    Directory of Open Access Journals (Sweden)

    Christian eLindemann

    2016-03-01

    Full Text Available Nutrient uptake affinity affects the competitive ability of microbial organisms at low nutrient concentrations. From the theory of diffusion limitation it follows that uptake affinity scales linearly with the cell radius. This is in conflict with some observations suggesting that uptake affinity scales to a quantity that is closer to the square of the radius, i.e. to cell surface area. We show that this apparent conflict can be resolved by nutrient uptake theory. Pure diffusion limitation assumes that the cell is a perfect sink which means that it is able to absorb all encountered nutrients instantaneously. Here we provide empirical evidence that the perfect sink strategy is not common in phytoplankton. Although small cells are indeed favored by a large surface to volume ratio, we show that they are punished by higher relative investment cost in order to fully benefit from the larger surface to volume ratio. We show that there are two reasons for this. First, because the small cells need a higher transporter density in order to maximize their affinity, and second because the relative cost of a transporter is higher for a small than for a large cell. We suggest that this might explain why observed uptake affinities do not scale linearly with the cell radius.

  8. Scaling laws in phytoplankton nutrient uptake affinity

    DEFF Research Database (Denmark)

    Lindemann, Christian; Fiksen, Øyvind; Andersen, Ken Haste

    2016-01-01

    instantaneously. Here we provide empirical evidence that the perfect sink strategy is not common in phytoplankton. Although small cells are indeed favored by a large surface to volume ratio, we show that they are punished by higher relative investment cost in order to fully benefit from the larger surface......Nutrient uptake affinity affects the competitive ability of microbial organisms at low nutrient concentrations. From the theory of diffusion limitation it follows that uptake affinity scales linearly with the cell radius. This is in conflict with some observations suggesting that uptake affinity...... to volume ratio. We show that there are two reasons for this. First, because the small cells need a higher transporter density in order to maximize their affinity, and second because the relative cost of a transporter is higher for a small than for a large cell. We suggest that this might explain why...

  9. Explaining variation in Down's syndrome screening uptake

    DEFF Research Database (Denmark)

    Crombag, Neeltje M T H; Vellinga, Ynke E; Kluijfhout, Sandra A

    2014-01-01

    BACKGROUND: The offer of prenatal Down's syndrome screening is part of routine antenatal care in most of Europe; however screening uptake varies significantly across countries. Although a decision to accept or reject screening is a personal choice, it is unlikely that the widely differing uptake...... rates across countries can be explained by variation in individual values alone.The aim of this study was to compare Down's syndrome screening policies and programmes in the Netherlands, where uptake is relatively low ( 90% respectively....... RESULTS: There were many similarities in the demographics, healthcare systems, government abortion legislation and Down's syndrome screening policy across the studied countries. However, the additional cost for Down's syndrome screening over and above standard antenatal care in the Netherlands...

  10. Uranium uptake by hydroponically cultivated crop plants

    Energy Technology Data Exchange (ETDEWEB)

    Soudek, Petr; Petrova, Sarka [Laboratory of Plant Biotechnologies, Joint Laboratory of Institute of Experimental Botany AS CR, v.v.i. and Crop Research Institute, v.v.i., Rozvojova 263, 162 05 Prague 6 (Czech Republic); Benesova, Dagmar [Laboratory of Plant Biotechnologies, Joint Laboratory of Institute of Experimental Botany AS CR, v.v.i. and Crop Research Institute, v.v.i., Rozvojova 263, 162 05 Prague 6 (Czech Republic); Faculty of Environment Technology, Institute of Chemical Technology, Technicka 5, 166 28 Prague 6 (Czech Republic); Dvorakova, Marcela [Laboratory of Plant Biotechnologies, Joint Laboratory of Institute of Experimental Botany AS CR, v.v.i. and Crop Research Institute, v.v.i., Rozvojova 263, 162 05 Prague 6 (Czech Republic); Vanek, Tomas, E-mail: vanek@ueb.cas.cz [Laboratory of Plant Biotechnologies, Joint Laboratory of Institute of Experimental Botany AS CR, v.v.i. and Crop Research Institute, v.v.i., Rozvojova 263, 162 05 Prague 6 (Czech Republic)

    2011-06-15

    Hydroponicaly cultivated plants were grown on medium containing uranium. The appropriate concentrations of uranium for the experiments were selected on the basis of a standard ecotoxicity test. The most sensitive plant species was determined to be Lactuca sativa with an EC{sub 50} value about 0.1 mM. Cucumis sativa represented the most resistant plant to uranium (EC{sub 50} = 0.71 mM). Therefore, we used the uranium in a concentration range from 0.1 to 1 mM. Twenty different plant species were tested in hydroponic solution supplemented by 0.1 mM or 0.5 mM uranium concentration. The uranium accumulation of these plants varied from 0.16 mg/g DW to 0.011 mg/g DW. The highest uranium uptake was determined for Zea mays and the lowest for Arabidopsis thaliana. The amount of accumulated uranium was strongly influenced by uranium concentration in the cultivation medium. Autoradiography showed that uranium is mainly localized in the root system of the plants tested. Additional experiments demonstrated the possibility of influencing the uranium uptake from the cultivation medium by amendments. Tartaric acid was able to increase uranium uptake by Brassica oleracea and Sinapis alba up to 2.8 times or 1.9 times, respectively. Phosphate deficiency increased uranium uptake up to 4.5 times or 3.9 times, respectively, by Brassica oleracea and S. alba. In the case of deficiency of iron or presence of cadmium ions we did not find any increase in uranium accumulation. - Highlights: > The uranium accumulation in twenty different plant species varied from 0.160 to 0.011 mg/g DW. > Uranium is mainly localized in the root system. > Tartaric acid was able to increase uranium uptake by Brassica oleracea and Sinapis alba. > The phosphates deficiency increase the uranium uptake.

  11. Enantioselective cellular uptake of chiral semiconductor nanocrystals

    Science.gov (United States)

    Martynenko, I. V.; Kuznetsova, V. A.; Litvinov, I. K.; Orlova, A. O.; Maslov, V. G.; Fedorov, A. V.; Dubavik, A.; Purcell-Milton, F.; Gun'ko, Yu K.; Baranov, A. V.

    2016-02-01

    The influence of the chirality of semiconductor nanocrystals, CdSe/ZnS quantum dots (QDs) capped with L- and D-cysteine, on the efficiency of their uptake by living Ehrlich Ascite carcinoma cells is studied by spectral- and time-resolved fluorescence microspectroscopy. We report an evident enantioselective process where cellular uptake of the L-Cys QDs is almost twice as effective as that of the D-Cys QDs. This finding paves the way for the creation of novel approaches to control the biological properties and behavior of nanomaterials in living cells.

  12. Diffuse FDG renal uptake in lymphoma.

    Science.gov (United States)

    Navalkissoor, Shaunak; Szyszko, Teresa; Gnanasegaran, Gopinath; Nunan, Thomas

    2010-10-01

    In patients presenting with acute renal failure and known/suspected lymphoma, the diagnosis of diffuse renal involvement is important, as there is potential for rapid resolution with chemotherapy. Although FDG is excreted through the kidneys and focal renal disease may be difficult to identify, diffuse renal FDG is more easily recognized and is always abnormal. We report a patient presenting with acute renal failure and suspected lymphoma. F-18 FDG PET/CT study demonstrated diffuse increased FDG uptake in bilaterally enlarged kidneys. Following 1 cycle of chemotherapy, the renal function normalized. An interim F-18 FDG PET/CT demonstrated normal size and FDG uptake within both kidneys.

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

    Directory of Open Access Journals (Sweden)

    Daphna D.J. Habets

    2012-09-01

    Full Text Available Aim: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/ long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-λ knockout mice the roles of atypical PKCs (PKC-ζ and PKC-λ in regulating cardiac glucose and fatty acid uptake. Results: Neither insulin-stimulated nor AMPK-mediated glucose and fatty acid uptake were inhibited upon genetic PKC-λ ablation in cardiomyocytes. In contrast, myristoylated PKC-ζ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty acid uptake by >80% in both wild-type and PKC-λ-knockout cardiomyocytes. In PKC-λ knockout cardiomyocytes, PKC-ζ is the sole remaining atypical PKC isoform, and its expression level is not different from wild-type cardiomyocytes, in which it contributes to 29% and 17% of total atypical PKC expression and phosphorylation, respectively. Conclusion: Taken together, atypical PKCs are necessary for insulin-stimulated and AMPK-mediated glucose uptake into the heart, as well as for insulin-stimulated and AMPK-mediated fatty acid uptake. However, the residual PKC-ζ activity in PKC-λ-knockout cardiomyocytes is sufficient to allow optimal stimulation of glucose and fatty acid uptake, indicating that atypical PKCs are necessary but not rate-limiting in the regulation of cardiac substrate uptake and that PKC-λ and PKC-ζ have interchangeable functions in these processes.

  14. Uptake of duck hepatitis B virus into hepatocytes occurs by endocytosis but does not require passage of the virus through an acidic intracellular compartment.

    OpenAIRE

    Köck, J; Borst, E M; Schlicht, H J

    1996-01-01

    The infectious entry pathway of duck hepatitis B virus (DHBV) was investigated with primary duck hepatocytes. Virus uptake was measured by a selective PCR technique which allows for the detection of a successful infection without the need for viral replication or gene expression. To test whether DHBV uptake occurs by endocytosis, the effects of energy depletion were analyzed. The requirement for an acidic intracellular pH was tested with the lysosomotropic agent ammonium chloride. The data sh...

  15. f-Ratios calculated with and without urea uptake in nitrogen uptake by phytoplankton

    Digital Repository Service at National Institute of Oceanography (India)

    Wafar, M.V.M.; Corre, P.L.; L'Helguen, S.

    nitrate. Qualitatively this is recognized: “the f ratio derived from nitrate and ammonium uptake alone would overestimate the true ratio of new/total production” (Harrison et al., 1987); “non-inclusion of urea uptake overesti- mates thef-ratio” (Probyn... of Plankton Research. 5,657-676. Hansel1 C. A. and J. J. Gocring (19X9) A method for estimating uptake and production rates for urea in scawatcr using “N urea and lJC urea. Cunadian Journal of Fisheries und Aquatic Science, 46, 198-202. Harrison W. G., E. J...

  16. Endocytotic uptake of nutrients in carnivorous plants.

    Science.gov (United States)

    Adlassnig, Wolfram; Koller-Peroutka, Marianne; Bauer, Sonja; Koshkin, Edith; Lendl, Thomas; Lichtscheidl, Irene K

    2012-07-01

    Carnivorous plants trap, digest and absorb animals in order to supplement their mineral nutrition. Nutrients absorbed by the plant include different nitrogen species, phosphate, potassium, trace elements and small organic compounds. Uptake is usually thought to be performed via specific channels, but this study provides evidence that endocytosis is involved as well. Traps of the carnivorous plants Nepenthes coccinea, Nepenthes ventrata, Cephalotus follicularis, Drosophyllum lusitanicum, Drosera capensis, Dionaea muscipula, Aldrovanda vesiculosa, Genlisea violacea × lobata, Sarracenia psittacina and Sarracenia purpurea were stained with methylene blue in order to identify possible sites of uptake. The permeable parts of the traps were incubated with fluorescein isothiocyanate labelled bovine serum albumin (FITC-BSA) and other fluorescent endocytosis markers, combined with the soluble protein BSA or respiratory inhibitors. Uptake was studied by confocal microscopy. In Nepenthes, small fluorescent vesicles became visible 1 h after incubation with FITC-BSA. These vesicles fused to larger compartments within 30 h. A similar behaviour was found in the related genera Drosera, Dionaea, Aldrovanda and Drosophyllum but also in Cephalotus with glands of different evolutionary origin. In Genlisea and Sarracenia, no evidence for endocytosis was found. We propose that in many carnivorous plants, nutrient uptake by carriers is supplemented by endocytosis, which enables absorption and intracellular digestion of whole proteins. The advantage for the plant of reducing secretion of enzymes for extracellular digestion is evident. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

  17. Thiamin function, metabolism, uptake, and transport.

    Science.gov (United States)

    Manzetti, Sergio; Zhang, Jin; van der Spoel, David

    2014-02-11

    Vitamins are crucial components in the diet of animals and many other living organisms. One of these essential nutrients, thiamin, is known to be involved in several cell functions, including energy metabolism and the degradation of sugars and carbon skeletons. Other roles that are connected to this vitamin are neuronal communication, immune system activation, signaling and maintenance processes in cells and tissues, and cell-membrane dynamics. Because of the key functions of thiamin, uptake and transport through the body are crucial. Its uptake route is relatively complex, encompassing a variety of protein families, including the solute carrier anion transporters, the alkaline phosphatase transport system, and the human extraneuronal monoamine transporter family, some of which are multispecific proteins. There are two known structures of protein (subunits) involved in thiamin uptake in prokaryotes. Binding of thiamin to these proteins is strongly guided by electrostatic interactions. The lack of structural information about thiamin binding proteins for higher organisms remains a bottleneck for understanding the uptake process of thiamin in atomic detail. This review includes recent data on thiamin metabolism, related deficiencies and pathologies, and the latest findings on thiamin binding transporters.

  18. Plant uptake of radionuclides and rhizosphere factors

    Energy Technology Data Exchange (ETDEWEB)

    Arie, Tsutomu; Gouthu, S.; Ambe, Shizuko; Yamaguchi, Isamu [Institute of Physical and Chemical Research, Wako, Saitama (Japan); Hirata, Hiroaki

    1999-03-01

    Influence of soil factors such as nuclide availability, pH, organic carbon, cation exchange capacity (CEC), exchangeable cations (Ca{sup 2+}, Mg{sup 2+}, and K{sup +}), phosphate absorption coefficient (PAC), physical composition of soil (coarse sand, fine sand, silt, and clay), soil texture, and rhizosphere microbes on uptake of radionuclides by plants are studied. (author)

  19. Lysozyme uptake by oxidized starch polymer microgels

    NARCIS (Netherlands)

    Li, Y.; Vries, R.D.; Kleijn, M.; Slaghek, T.; Timmermans, J.; Stuart, M.C.; Norde, W.

    2010-01-01

    With the aim of determining suitable conditions for uptake and release of globular proteins on microgels, we studied the interaction between phosphated, highly cross-linked, negatively charged oxidized potato starch polymer (OPSP) microgel particles and lysozyme from hen eggs. Our microgel shows a

  20. Nicotinamide ribosyl uptake mutants in Haemophilus influenzae.

    Science.gov (United States)

    Herbert, Mark; Sauer, Elizabeta; Smethurst, Graeme; Kraiss, Anita; Hilpert, Anna-Karina; Reidl, Joachim

    2003-09-01

    The gene for the nicotinamide riboside (NR) transporter (pnuC) was identified in Haemophilus influenzae. A pnuC mutant had only residual NR uptake and could survive in vitro with high concentrations of NR, but could not survive in vivo. PnuC may represent a target for the development of inhibitors for preventing H. influenzae disease.

  1. FDG uptake, a surrogate of tumour hypoxia?

    NARCIS (Netherlands)

    Dierckx, Rudi Andre; de Wiele, Christophe Van

    2008-01-01

    Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-D-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceutic

  2. Water Uptake Mechanism in Crispy Bread Crust

    NARCIS (Netherlands)

    Nieuwenhuijzen, van N.H.; Meinders, M.B.J.; Tromp, R.H.; Hamer, R.J.; Vliet, van T.

    2008-01-01

    Crispness is an important quality characteristic of dry solid food products such as crispy rolls. Its retention is directly related to the kinetics of water uptake by the crust. In this study, a method for the evaluation of the water sorption kinetics in bread crust is proposed. Two different sorpti

  3. Reduction of radioiodine uptake in hyperthyroid patients

    Energy Technology Data Exchange (ETDEWEB)

    Goebel, R.; Leb, G.; Passath, A.

    1984-04-01

    We compared the /sup 131/I-uptake values in hyperthyroid patients for the two years 1973 and 1982. A pronounced fall (70,8% and 61,1% resp.) was found. This fall was greater in Graves' disease than in autonomous adenoma.

  4. New concepts for dynamic plant uptake models

    DEFF Research Database (Denmark)

    Rein, Arno; Legind, Charlotte Nielsen; Trapp, Stefan

    2011-01-01

    Models for the prediction of chemical uptake into plants are widely applied tools for human and wildlife exposure assessment, pesticide design and for environmental biotechnology such as phytoremediation. Steady-state considerations are often applied, because they are simple and have a small data...

  5. Effects of transport inhibitors on the cellular uptake of carboxylated polystyrene nanoparticles in different cell lines.

    Directory of Open Access Journals (Sweden)

    Tiago dos Santos

    Full Text Available Nanotechnology is expected to play a vital role in the rapidly developing field of nanomedicine, creating innovative solutions and therapies for currently untreatable diseases, and providing new tools for various biomedical applications, such as drug delivery and gene therapy. In order to optimize the efficacy of nanoparticle (NP delivery to cells, it is necessary to understand the mechanisms by which NPs are internalized by cells, as this will likely determine their ultimate sub-cellular fate and localisation. Here we have used pharmacological inhibitors of some of the major endocytic pathways to investigate nanoparticle uptake mechanisms in a range of representative human cell lines, including HeLa (cervical cancer, A549 (lung carcinoma and 1321N1 (brain astrocytoma. Chlorpromazine and genistein were used to inhibit clathrin and caveolin mediated endocytosis, respectively. Cytochalasin A and nocodazole were used to inhibit, respectively, the polymerisation of actin and microtubule cytoskeleton. Uptake experiments were performed systematically across the different cell lines, using carboxylated polystyrene NPs of 40 nm and 200 nm diameters, as model NPs of sizes comparable to typical endocytic cargoes. The results clearly indicated that, in all cases and cell types, NPs entered cells via active energy dependent processes. NP uptake in HeLa and 1321N1 cells was strongly affected by actin depolymerisation, while A549 cells showed a stronger inhibition of NP uptake (in comparison to the other cell types after microtubule disruption and treatment with genistein. A strong reduction of NP uptake was observed after chlorpromazine treatment only in the case of 1321N1 cells. These outcomes suggested that the same NP might exploit different uptake mechanisms to enter different cell types.

  6. Carbon uptake, microbial community structure, and mineralization of layered mats from Imperial Geyser, Yellowstone National Park

    Science.gov (United States)

    Woycheese, K. M.; Grabenstatter, J.; Haddad, A.; Ricci, J. N.; Johnson, H.; Berelson, W.; Spear, J. R.; Caporaso, J. G.; International Geobiology Course 2011

    2011-12-01

    Layered microbial mats provide an analog for early microbial communities, and remain one of the few microbiological structures consistently preserved in the geologic record. Despite this, growth rates, metabolic capabilities, and methods of mineralization in modern communities are poorly understood. Imperial Geyser, an alkaline siliceous hot spring in Yellowstone National Park, provides a useful setting to study these parameters. Mat and water samples (T = 64-40 °C) were collected for 13C analysis and 13C-spiked bicarbonate and acetate incubation experiments. Carbon isotopes were measured for the stream water, pore water and biomass. We experimentally determined rates of bicarbonate uptake, acetate uptake and mineral content. Bicarbonate uptake rates ranged from 0 - 0.4% per day, while acetate uptake rates ranged from 0 - 2.0% per day. These results indicate that the mat biomass is capable of turnover in about 300 days resulting in potential growth rates of 1-2 cm/year. Organic carbon content (% dry weight) ranged from 2 to 16%, and decreased with depth in the mat. The mineral content of these mats is predominantly amorphous SiO2. An inverse correlation between mineral percent and bicarbonate uptake rate was observed, suggesting that there may be a link between metabolism and the prevention of mineralization. Comparing the 13C and carbon uptake rates with 16S rDNA pyrosequencing data we were able to hypothesize the carbon fixation pathways and heterotrophic interactions occurring in this environment. In general, two patterns of 13C values were observed. The first pattern was characterized by increased heterotrophy with depth. In the other, preliminary evidence supporting a photoheterotrophic lifestyle for Roseiflexus spp. was found.

  7. Dermal versus total uptake of benzene from mineral spirits solvent during parts washing.

    Science.gov (United States)

    Bogen, Kenneth T; Sheehan, Patrick J

    2014-07-01

    Quantitative approaches to assessing exposure to, and associated risk from, benzene in mineral spirits solvent (MSS), used widely in parts washing and degreasing operations, have focused primarily on the respiratory pathway. The dermal contribution to total benzene uptake from such operations remains uncertain because measuring in vivo experimental dermal uptake of this volatile human carcinogen is difficult. Unprotected dermal uptake involves simultaneous sustained immersion events and transient splash/wipe events, each yielding residues subject to evaporation as well as dermal uptake. A two-process dermal exposure framework to assess dermal uptake to normal and damaged skin was applied to estimate potential daily dermal benzene dose (Dskin ) to workers who used historical or current formulations of recycled MSS in manual parts washers. Measures of evaporation and absorption of MSS dermally applied to human subjects were modeled to estimate in vivo dermal uptake of benzene in MSS. Uncertainty and interindividual variability in Dskin was characterized by Monte Carlo simulation, conditioned on uncertainty and/or variability estimated for each model input. Dermal exposures are estimated to average 33% of total (inhalation + dermal) benzene parts washing dose, with approximately equal predicted portions of dermal dose due to splash/wipe and to continuous contact with MSS. The estimated median (95th percentile) dermal and total daily benzene doses from parts washing are: 0.0069 (0.024) and 0.025 (0.18) mg/day using current, and 0.027 (0.085) and 0.098 (0.69) mg/day using historical, MSS solvents, respectively. © 2014 Society for Risk Analysis.

  8. Dynamics of mitochondrial Ca2+ uptake in MICU1-knockdown cells.

    Science.gov (United States)

    de la Fuente, Sergio; Matesanz-Isabel, Jessica; Fonteriz, Rosalba I; Montero, Mayte; Alvarez, Javier

    2014-02-15

    MICU1 (Ca2+ uptake protein 1, mitochondrial) is an important regulator of the MCU (Ca2+ uniporter protein, mitochondrial) that has been shown recently to act as a gatekeeper of the MCU at low [Ca2+]c (cytosolic [Ca2+]). In the present study we have investigated in detail the dynamics of MCU activity after shRNA-knockdown of MICU1 and we have found several new interesting properties. In MICU1-knockdown cells, the rate of mitochondrial Ca2+ uptake was largely increased at a low [Ca2+]c (4 μM). In the 2-4 μM range a mixed behaviour was observed, where mitochondrial Ca2+ uptake started earlier in the MICU1-silenced cells, but at a lower rate than in the controls. The sensitivity of Ca2+ uptake to Ruthenium Red and Ru360 was similar at both high and low [Ca2+]c, indicating that the same Ca2+ pathway was operating in both cases. The increased Ca2+-uptake rate observed at a [Ca2+]c below 2 μM was transient and became inhibited during Ca2+ entry. Development of this inhibition was slow, requiring 5 min for completion, and was hardly reversible. Therefore MICU1 acts both as a MCU gatekeeper at low [Ca2+]c and as a cofactor necessary to reach the maximum Ca2+-uptake rate at high [Ca2+]c. Moreover, in the absence of MICU1, the MCU becomes sensitive to a slow-developing inhibition that requires prolonged increases in [Ca2+]c in the low micromolar range.

  9. High density lipoprotein (HDL promotes glucose uptake in adipocytes and glycogen synthesis in muscle cells.

    Directory of Open Access Journals (Sweden)

    Qichun Zhang

    Full Text Available BACKGROUND: High density lipoprotein (HDL was reported to decrease plasma glucose and promote insulin secretion in type 2 diabetes patients. This investigation was designed to determine the effects and mechanisms of HDL on glucose uptake in adipocytes and glycogen synthesis in muscle cells. METHODS AND RESULTS: Actions of HDL on glucose uptake and GLUT4 translocation were assessed with 1-[(3H]-2-deoxyglucose and plasma membrane lawn, respectively, in 3T3-L1 adipocytes. Glycogen analysis was performed with amyloglucosidase and glucose oxidase-peroxidase methods in normal and palmitate-treated L6 cells. Small interfering RNA was used to observe role of scavenger receptor type I (SR-BI in glucose uptake of HDL. Corresponding signaling molecules were detected by immunoblotting. HDL stimulated glucose uptake in a time- and concentration-dependent manner in 3T3-L1 adipocytes. GLUT4 translocation was significantly increased by HDL. Glycogen deposition got enhanced in L6 muscle cells paralleling with elevated glycogen synthase kinase3 (GSK3 phosphorylation. Meanwhile, increased phosphorylations of Akt-Ser473 and AMP activated protein kinase (AMPK α were detected in 3T3-L1 adipocytes. Glucose uptake and Akt-Ser473 activation but not AMPK-α were diminished in SR-BI knock-down 3T3-L1 cells. CONCLUSIONS: HDL stimulates glucose uptake in 3T3-L1 adipocytes through enhancing GLUT4 translocation by mechanisms involving PI3K/Akt via SR-BI and AMPK signaling pathways, and increases glycogen deposition in L6 muscle cells through promoting GSK3 phosphorylation.

  10. Application of Pb isotopes to track the sources and routes of metal uptake in the earthworm Eisenia fetida

    Directory of Open Access Journals (Sweden)

    Bader Albogami

    2014-12-01

    Full Text Available The aim of this work is to determine the important routes of metal uptake in earthworms to enable a better understanding of the primary source of metal uptake in the environment. Earthworms can take up chemicals from pore water and soil both by ingestion and through contact with their skin. However, it is unclear which pathway is the most important for metal uptake. An experiment was designed in which both soil chemistry and foods were artificially manipulated, producing different pools of soil lead (Pb with different isotope compositions at a range of Pb concentrations. Earthworms (Eiseniafetida were exposed to different lead concentrations through the addition of 500 mg/kg lead oxide (Pb3O4 to soil and 500 mg/kg lead nitrate to food (manure, with distinctly different isotopic compositions. Earthworms were also exposed to combinations of soil only and soil plus food in order to quantify the proportions of Pb taken up from each component. After acid digestion of the earthworm tissues, the Pb isotope composition of the accumulated lead in the earthworms was measured using a Thermo-fisher, iCAPQ, ICP-MS for 208Pb/206Pb and 207Pb/206Pb ratios measured relative to NIST SRM 981, allowing us to determine the pathway of lead uptake. Mixing calculations have been used to deconvolute the lead isotope signatures and identify the amount of lead taken up by the earthworms from the different soil pools. Differences in bioaccumulation factors and the relative amounts of lead accumulated from different pools changes as a function of concentration in the different pools. Earthworms were shown to uptake lead from bothsoil and food sources through ingestion route. Our findings suggest that a major pathway of lead uptake in earthworm species is heavily influenced by their ecology.

  11. Metabolism pathways in chronic lymphocytic leukemia.

    Science.gov (United States)

    Rozovski, Uri; Hazan-Halevy, Inbal; Barzilai, Merav; Keating, Michael J; Estrov, Zeev

    2016-01-01

    Alterations in chronic lymphocytic leukemia (CLL) cell metabolism have been studied by several investigators. Unlike normal B lymphocytes or other leukemia cells, CLL cells, like adipocytes, store lipids and utilize free fatty acids (FFA) to produce chemical energy. None of the recently identified mutations in CLL directly affects metabolic pathways, suggesting that genetic alterations do not directly contribute to CLL cells' metabolic reprogramming. Conversely, recent data suggest that activation of STAT3 or downregulation of microRNA-125 levels plays a crucial role in the utilization of FFA to meet the CLL cells' metabolic needs. STAT3, known to be constitutively activated in CLL, increases the levels of lipoprotein lipase (LPL) that mediates lipoprotein uptake and shifts the CLL cells' metabolism towards utilization of FFA. Herein, we review the evidence for altered lipid metabolism, increased mitochondrial activity and formation of reactive oxygen species (ROS) in CLL cells, and discuss the possible therapeutic strategies to inhibit lipid metabolism pathways in patient with CLL.

  12. Hydrogen sulfide promotes calcium uptake in larval zebrafish.

    Science.gov (United States)

    Kwong, Raymond W M; Perry, Steve F

    2015-07-01

    Hydrogen sulfide (H2S) can act as a signaling molecule for various ion channels and/or transporters; however, little is known about its potential involvement in Ca(2+) balance. Using developing zebrafish (Danio rerio) as an in vivo model system, the present study demonstrated that acute exposure to H2S donors increased Ca(2+) influx at 4 days postfertilization, while chronic (3-day) exposure caused a rise in whole body Ca(2+) levels. The mRNA expression of Ca(2+)-transport-related genes was unaffected by H2S exposure, suggesting that posttranscriptional modifications were responsible for the altered rates of Ca(2+) uptake. Indeed, treatment of fish with the protein kinase A inhibitor H-89 abolished the H2S-mediated stimulation of Ca(2+) influx, suggesting that H2S increased Ca(2+) influx by activating cAMP-protein kinase A pathways. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are two key enzymes in the endogenous synthesis of H2S. Using an antisense morpholino knockdown approach, we demonstrated that Ca(2+) influx was reduced in CBS isoform b (CBSb)- but not in CSE-deficient fish. Interestingly, the reduction in Ca(2+) influx in CBSb-deficient fish was observed only in fish that were acclimated to low-Ca(2+) water (i.e., 25 μM Ca(2+); control: 250 μM Ca(2+)). Similarly, mRNA expression of cbsb but not cse was increased in fish acclimated to low-Ca(2+) water. Results from whole-mount immunohistochemistry further revealed that CBSb was expressed in Na(+)-K(+)-ATPase-rich cells, which are implicated in Ca(2+) uptake in zebrafish larvae. Collectively, the present study suggests a novel role for H2S in promoting Ca(2+) influx, particularly in a low-Ca(2+) environment.

  13. Small organic molecules modulating iodine uptake in thyroid

    Energy Technology Data Exchange (ETDEWEB)

    Ambroise, Y. [CEA Saclay, DSV/DBJC/SMMCB, 91 - Gif-sur-Yvette (France)

    2006-07-01

    The thyroid gland accumulates large quantities of iodine. This uptake is needed for the production of iodinated hormones (T3 and T4). The first step in the iodine accumulation is a basolateral transport of iodide ions by the cloned 'Natrium Iodide Sym-porter' also called NIS. Using high-throughput screening techniques, we have identified a series of inhibitors of the iodide uptake in thyrocytes. These compounds are of medical significance in case of thyroid deregulation and can also offer solutions for radio-iodine detoxification in case of emergency situations (nuclear industry...). In addition, these small organic molecules can be important tools for the understanding of NIS structure and functions In parallel, we have identified and characterized a single compound capable to strongly enhance the amount of intra-cellular iodide in rat thyrocytes (FRTL5) as well as in HEK293 cells transfected with hNIS (Natrium/Iodide Sym-porter). Preliminary studies show that this effect is NIS dependant, and is induced by alternative and unknown mechanisms. Future work will consist in unraveling the mode of action of this molecule. These informations will help us not only to better understand the iodide pathways in the thyroid, but also to design more active analogues. We will use photo-labelling techniques to identify new proteins involved in the iodide transfer and retention. In addition, preliminary experiments are underway to validate our compound as an anti-cancer agent. Targeted NIS gene delivery into tumors plus radio-iodide injection leads to tumor size regression. Unfortunately, doses of radioactivity are to high for safe treatment. Our compound may lead to enhanced radio-iodide entrapment, thus necessitating lower doses of radioactivity for tumor regression. (author)

  14. Design of a bistable switch to control cellular uptake.

    Science.gov (United States)

    Oyarzún, Diego A; Chaves, Madalena

    2015-12-06

    Bistable switches are widely used in synthetic biology to trigger cellular functions in response to environmental signals. All bistable switches developed so far, however, control the expression of target genes without access to other layers of the cellular machinery. Here, we propose a bistable switch to control the rate at which cells take up a metabolite from the environment. An uptake switch provides a new interface to command metabolic activity from the extracellular space and has great potential as a building block in more complex circuits that coordinate pathway activity across cell cultures, allocate metabolic tasks among different strains or require cell-to-cell communication with metabolic signals. Inspired by uptake systems found in nature, we propose to couple metabolite import and utilization with a genetic circuit under feedback regulation. Using mathematical models and analysis, we determined the circuit architectures that produce bistability and obtained their design space for bistability in terms of experimentally tuneable parameters. We found an activation-repression architecture to be the most robust switch because it displays bistability for the largest range of design parameters and requires little fine-tuning of the promoters' response curves. Our analytic results are based on on-off approximations of promoter activity and are in excellent qualitative agreement with simulations of more realistic models. With further analysis and simulation, we established conditions to maximize the parameter design space and to produce bimodal phenotypes via hysteresis and cell-to-cell variability. Our results highlight how mathematical analysis can drive the discovery of new circuits for synthetic biology, as the proposed circuit has all the hallmarks of a toggle switch and stands as a promising design to control metabolic phenotypes across cell cultures. © 2015 The Author(s).

  15. Genetic impairment of AMPK{alpha}2 signaling does not reduce muscle glucose uptake during treadmill exercise in mice

    DEFF Research Database (Denmark)

    Maarbjerg, Stine Just; Jørgensen, Sebastian Beck; Rose, Adam John

    2009-01-01

    Some studies suggest that the 5'-AMP-activated protein kinase (AMPK) is important in regulating muscle glucose uptake in response to intense electrically stimulated contractions. However, it is unknown if AMPK regulates muscle glucose uptake during in vivo exercise. We studied this in male...... measured signaling of alternative exercise sensitive pathways which might be compensatorily increased in AMPK-KD muscles. However, increases in phosphorylation of CaMKII, Trisk95, p38 MAPK and ERK1/2 were not higher in AMPK-KD than in WT muscle. Collectively, these findings suggest that alpha2-AMPK...

  16. Transcobalamin derived from bovine milk stimulates apical uptake of vitamin B12 into human intestinal epithelial cells.

    Science.gov (United States)

    Hine, Brad; Boggs, Irina; Green, Ralph; Miller, Joshua W; Hovey, Russell C; Humphrey, Rex; Wheeler, Thomas T

    2014-11-01

    Intestinal uptake of vitamin B12 (hereafter B12) is impaired in a significant proportion of the human population. This impairment is due to inherited or acquired defects in the expression or function of proteins involved in the binding of diet-derived B12 and its uptake into intestinal cells. Bovine milk is an abundant source of bioavailable B12 wherein it is complexed with transcobalamin. In humans, transcobalamin functions primarily as a circulatory protein, which binds B12 following its absorption and delivers it to peripheral tissues via its cognate receptor, CD320. In the current study, the transcobalamin-B12 complex was purified from cows' milk and its ability to stimulate uptake of B12 into cultured bovine, mouse and human cell lines was assessed. Bovine milk-derived transcobalamin-B12 complex was absorbed by all cell types tested, suggesting that the uptake mechanism is conserved across species. Furthermore, the complex stimulated the uptake of B12 via the apical surface of differentiated Caco-2 human intestinal epithelial cells. These findings suggest the presence of an alternative transcobalamin-mediated uptake pathway for B12 in the human intestine other than that mediated by the gastric glycoprotein, intrinsic factor. Our findings highlight the potential for transcobalamin-B12 complex derived from bovine milk to be used as a natural bioavailable alternative to orally administered free B12 to overcome B12 malabsorption.

  17. Investigation of biomimetic shear stress on cellular uptake and mechanism of polystyrene nanoparticles in various cancer cell lines.

    Science.gov (United States)

    Kang, Taehee; Park, Chulhun; Lee, Beom-Jin

    2016-12-01

    Cancer cells in the tumor microenvironment are affected by fluid shear stress generated by blood flow in the vascular microenvironment and interstitial flows in the tumor microenvironment. Thus, we investigated how fluidic shear stress affects cellular uptake as well as the endocytosis mechanism of nanoparticles using a biomimetic microfluidic system that mimics the human dynamic environment. Positively charged amino-modified polystyrene nanoparticles (PSNs) at 100 μg/mL were delivered to cancer cells under static and biomimetic dynamic conditions (0.5 dyne/cm(2)). Additionally, the experiment was done in the presence of endocytosis inhibitors specific for one of the endocytosis pathways. To evaluate cellular uptake of cationic PSNs, the fluorescence intensity of cationic PSNs in cancer cells was measured by flow cytometer and fluorescence images were taken using confocal laser scanning microscopy. Cancer cells in dynamic conditions exhibited higher cellular uptake of PSNs and showed different cellular uptake mechanisms compared with those in static conditions. From these results, it suggested that biomimetic dynamic conditions stimulated specific endocytosis and prompted cellular uptake. It was also important to consider fluidic shear stress as one of the critical factors because cellular uptake and drug delivery could play a key role in cancer cells and metastasis.

  18. Uptake and depuration of 131I from labelled diatoms (Skeletonema costatum) to the edible periwinkle (Littorina littorea).

    Science.gov (United States)

    Wilson, R C; Vives I Batlle, J; Watts, S J; McDonald, P; Parker, T G

    2007-01-01

    Uptake and depuration of (131)I into winkles through consumption of the diatom Skeletonema costatum is described. The work follows on from previous studies that investigated the uptake of iodine into winkles from seawater and seaweed. Incorporation of (131)I in S. costatum from labelled seawater followed linear first-order kinetics with an uptake half-time of 0.40 days. Iodine uptake in winkles from labelled S. costatum also followed linear first-order kinetics, with a calculated equilibrium concentration (C(infinity)) of 42Bqkg(-1) and a transfer factor (TF) of 1.1x10(-4) with respect to labelled diatom food. This TF is lower than that observed for uptake of (131)I in winkles from labelled seaweed. For the depuration stage, a biphasic sequence with biological half-lives of 1.3 and 255 days was determined. The first phase is biokinetically important, given that winkles can lose two-thirds of their activity during that period. This study shows that, whilst winkles can obtain radioactive iodine from phytoplankton consumption, they do not retain the majority of that activity for very long. Hence, compared with other exposure pathways, such as uptake from seawater and macroalgae, incorporation from phytoplankton is a relatively minor exposure route.

  19. Uptake and depuration of {sup 131}I from labelled diatoms (Skeletonema costatum) to the edible periwinkle (Littorina littorea)

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, R.C. [Westlakes Scientific Consulting Ltd., The Princess Royal Building, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3LN (United Kingdom)]. E-mail: richard.c.wilson@westlakes.ac.uk; Vives i Batlle, J. [Westlakes Scientific Consulting Ltd., The Princess Royal Building, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3LN (United Kingdom); Watts, S.J. [Westlakes Scientific Consulting Ltd., The Princess Royal Building, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3LN (United Kingdom); McDonald, P. [Westlakes Scientific Consulting Ltd., The Princess Royal Building, Westlakes Science and Technology Park, Moor Row, Cumbria CA24 3LN (United Kingdom); Parker, T.G. [British Nuclear Group, Sellafield, Cumbria CA20 1PG (United Kingdom)

    2007-07-15

    Uptake and depuration of {sup 131}I into winkles through consumption of the diatom Skeletonema costatum is described. The work follows on from previous studies that investigated the uptake of iodine into winkles from seawater and seaweed. Incorporation of {sup 131}I in S. costatum from labelled seawater followed linear first-order kinetics with an uptake half-time of 0.40 days. Iodine uptake in winkles from labelled S. costatum also followed linear first-order kinetics, with a calculated equilibrium concentration (C {sub {infinity}}) of 42 Bq kg{sup -1} and a transfer factor (TF) of 1.1 x 10{sup -4} with respect to labelled diatom food. This TF is lower than that observed for uptake of {sup 131}I in winkles from labelled seaweed. For the depuration stage, a biphasic sequence with biological half-lives of 1.3 and 255 days was determined. The first phase is biokinetically important, given that winkles can lose two-thirds of their activity during that period. This study shows that, whilst winkles can obtain radioactive iodine from phytoplankton consumption, they do not retain the majority of that activity for very long. Hence, compared with other exposure pathways, such as uptake from seawater and macroalgae, incorporation from phytoplankton is a relatively minor exposure route.

  20. A Novel Two-Component System, GluR-GluK, Involved in Glutamate Sensing and Uptake in Streptomyces coelicolor.

    Science.gov (United States)

    Li, Lei; Jiang, Weihong; Lu, Yinhua

    2017-09-15

    Two-component systems (TCSs), the predominant signal transduction pathways employed by bacteria, play important roles in physiological metabolism in Streptomyces Here, a novel TCS, GluR-GluK (encoded by SCO5778-SCO5779), which is located divergently from the gluABCD operon encoding a glutamate uptake system, was identified as being involved in glutamate sensing and uptake as well as antibiotic biosynthesis in Streptomyces coelicolor Under the condition of minimal medium (MM) supplemented with different concentrations of glutamate, deletion of the gluR-gluK operon (gluR-K) resulted in enhanced actinorhodin (ACT) but reduced undecylprodigiosin (RED) and yellow type I polyketide (yCPK) production, suggesting that GluR-GluK plays a differential role in antibiotic biosynthesis. Furthermore, we found that the response regulator GluR directly promotes the expression of gluABCD under the culture condition of MM with a high concentration of glutamate (75 mM). Using the biolayer interferometry assay, we demonstrated that glutamate acts as the direct signal of the histidine kinase GluK. It was therefore suggested that upon sensing high concentrations of glutamate, GluR-GluK would be activated and thereby facilitate glutamate uptake by increasing gluABCD expression. Finally, we demonstrated that the role of GluR-GluK in antibiotic biosynthesis is independent of its function in glutamate uptake. Considering the wide distribution of the glutamate-sensing (GluR-GluK) and uptake (GluABCD) module in actinobacteria, it could be concluded that the GluR-GluK signal transduction pathway involved in secondary metabolism and glutamate uptake should be highly conserved in this bacterial phylum.IMPORTANCE In this study, a novel two-component system (TCS), GluR-GluK, was identified to be involved in glutamate sensing and uptake as well as antibiotic biosynthesis in Streptomyces coelicolor A possible GluR-GluK working model was proposed. Upon sensing high glutamate concentrations (such as 75

  1. Measuring the serotonin uptake site using (/sup 3/H)paroxetine--a new serotonin uptake inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Gleiter, C.H.; Nutt, D.J.

    1988-01-01

    Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand.

  2. GABA and glutamate uptake and metabolism in retinal glial (Müller cells

    Directory of Open Access Journals (Sweden)

    Andreas eBringmann

    2013-04-01

    Full Text Available Müller cells, the principal glial cells of the retina, support the synaptic activity by the uptake and metabolization of extracellular neurotransmitters. Müller cells express uptake and exchange systems for various neurotransmitters including glutamate and -aminobutyric acid (GABA. Müller cells remove the bulk of extracellular glutamate in the inner retina and contribute to the glutamate clearance around photoreceptor terminals. By the uptake of glutamate, Müller cells are involved in the shaping and termination of the synaptic activity, particularly in the inner retina. Reactive Müller cells are neuroprotective, e.g., by the clearance of excess extracellular glutamate, but may also contribute to neuronal degeneration by a malfunctioning or even reversal of glial glutamate transporters, or by a downregulation of the key enzyme, glutamine synthetase. This review summarizes the present knowledge about the role of Müller cells in the clearance and metabolization of extracellular glutamate and GABA. Some major pathways of GABA and glutamate metabolism in Müller cells are described; these pathways are involved in the glutamate-glutamine cycle of the retina, in the defense against oxidative stress via the production of glutathione, and in the production of substrates for the neuronal energy metabolism.

  3. Uranium perturbs signaling and iron uptake response in Arabidopsis thaliana roots.

    Science.gov (United States)

    Doustaly, Fany; Combes, Florence; Fiévet, Julie B; Berthet, Serge; Hugouvieux, Véronique; Bastien, Olivier; Aranjuelo, Iker; Leonhardt, Nathalie; Rivasseau, Corinne; Carrière, Marie; Vavasseur, Alain; Renou, Jean-Pierre; Vandenbrouck, Yves; Bourguignon, Jacques

    2014-04-01

    Uranium is a natural element which is mainly redistributed in the environment due to human activity, including accidents and spillages. Plants may be useful in cleaning up after incidents, although little is yet known about the relationship between metal speciation and plant response. Here, J-Chess modeling was used to predict U speciation and exposure conditions affecting U bioavailability for plants. The model was confirmed by exposing Arabidopsis thaliana plants to U under hydroponic conditions. The early root response was characterized using complete Arabidopsis transcriptome microarrays (CATMA). Expression of 111 genes was modified at the three timepoints studied. The associated biological processes were further examined by real-time quantitative RT-PCR. Annotation revealed that oxidative stress, cell wall and hormone biosynthesis, and signaling pathways (including phosphate signaling) were affected by U exposure. The main actors in iron uptake and signaling (IRT1, FRO2, AHA2, AHA7 and FIT1) were strongly down-regulated upon exposure to uranyl. A network calculated using IRT1, FRO2 and FIT1 as bait revealed a set of genes whose expression levels change under U stress. Hypotheses are presented to explain how U perturbs the iron uptake and signaling response. These results give preliminary insights into the pathways affected by uranyl uptake, which will be of interest for engineering plants to help clean areas contaminated with U.

  4. Nocturnal versus diurnal CO2 uptake: how flexible is Agave angustifolia?

    Science.gov (United States)

    Winter, Klaus; Garcia, Milton; Holtum, Joseph A M

    2014-07-01

    Agaves exhibit the water-conserving crassulacean acid metabolism (CAM) photosynthetic pathway. Some species are potential biofuel feedstocks because they are highly productive in seasonally dry landscapes. In plants with CAM, high growth rates are often believed to be associated with a significant contribution of C3 photosynthesis to total carbon gain when conditions are favourable. There has even been a report of a shift from CAM to C3 in response to overwatering a species of Agave. We investigated whether C3 photosynthesis can contribute substantially to carbon uptake and growth in young and mature Agave angustifolia collected from its natural habitat in Panama. In well-watered plants, CO2 uptake in the dark contributed about 75% of daily carbon gain. This day/night pattern of CO2 exchange was highly conserved under a range of environmental conditions and was insensitive to intensive watering. Elevated CO2 (800 ppm) stimulated CO2 fixation predominantly in the light. Exposure to CO2-free air at night markedly enhanced CO2 uptake during the following light period, but CO2 exchange rapidly reverted to its standard pattern when CO2 was supplied during the subsequent 24h. Although A. angustifolia consistently engages in CAM as its principal photosynthetic pathway, its relatively limited photosynthetic plasticity does not preclude it from occupying a range of habitats, from relatively mesic tropical environments in Panama to drier habitats in Mexico.

  5. Quantitative kinetics analysis of BMP2 uptake into cells and its modulation by BMP antagonists.

    Science.gov (United States)

    Alborzinia, Hamed; Schmidt-Glenewinkel, Hannah; Ilkavets, Iryna; Breitkopf-Heinlein, Katja; Cheng, Xinlai; Hortschansky, Peter; Dooley, Steven; Wölfl, Stefan

    2013-01-01

    Bone morphogenetic proteins (BMPs) are members of the TGFβ family of signaling proteins and play an important role during development and in tissue formation. BMP signaling is a well-studied process, which is initiated through binding of cognate receptors and processed through activation of Smad downstream mediators. A hallmark of BMP signaling is its modulation at the extracellular level through specific antagonists. Although it had been shown that BMP and TGFβ receptors are internalized following activation, little is known about the fate of BMP ligands. We prepared biologically active fluorescently labeled BMP2 and quantitatively analyzed its binding and uptake in cells using flow cytometry and confocal microscopy. Exogenous BMP2 was rapidly bound to the cell surface and subsequently internalized in a time-dependent manner and accumulated in the cell center. Although binding to the cell surface was limited by binding sites at the beginning, internalization continously increased with time, after a short delay. Using different inhibitors we found that internalization of BMP2 through endosomal particles occurred in a clathrin-dependent pathway. Furthermore, uptake of BMP2 was modulated in strikingly different ways by BMP2 antagonists. Although Noggin and Gremlin increased BMP2 uptake, Chordin blocked BMP2 uptake, which was concentration dependent in both cases. In conclusion, our findings present interesting mechanisms for the modulation of BMP signaling by concentration gradients of BMP ligands and antagonists in a dose- and time-dependent manner, which can provide an explanation of some properties of the BMP regulatory network.

  6. Enhanced thymidine uptake causes the lowered thymidine requirement of D. discoideum auxotroph HPS 401

    Energy Technology Data Exchange (ETDEWEB)

    Hurley, D.L.; Deering, R.A. (Pennsylvania State Univ., University Park (USA))

    1988-11-01

    Dictyostelium discoideum strain HPS 401 contains a spontaneous mutation that lowers the amount of thymidine required for cell growth relative to that of the auxotrophic parental strain HPS 400. Assays for enzymes related to thymidine metabolism reveal that none of the strains tested (HPS 401, HPS 400, and prototrophic HPS 83 cells) contain detectable thymidine phosphorylase activity and that the specific activity of thymidine kinase is the same in these three strains. Thin-layer chromatography of extracts from cells grown on radiolabeled thymidine shows that there is no detectable conversion of thymidine to thymine in any of these strains. These analyses show that HPS 401 has rapid intracellular accumulation of thymidine, while only slight uptake is observed with HPS 400 or wild-type strains. HPS 401 also shows greater uptake of uridine in comparison to HPS 400 and wild-type cells. Thymidylate uptake was the same for all three strains. Thus, the mutation giving rise to the HPS 401 phenotype selectively increases the uptake of thymidine into the cell, where it can be efficiently utilized for DNA synthesis by the salvage pathways of nucleotide metabolism.

  7. Growth, Nitrogen Uptake and Flow in Maize Plants Affected by Root Growth Restriction

    Institute of Scientific and Technical Information of China (English)

    Liang-zheng Xu; Jun-fang Niu; Chun-jian Li; Fu-suo Zhang

    2009-01-01

    The objective of the present study was to investigate the influence of a reduced maize root-system size on root growth and nitrogen (N) uptake and flow within plants. Restriction of shoot-borne root growth caused a strong decrease in the absorption of root: shoot dry weight ratio and a reduction in shoot growth. On the other hand, compensatory growth and an increased N uptake rate in the remaining roots were observed. Despite the limited long-distance transport pathway in the mesocotyl with restriction of shoot-borne root growth, N cycling within these plants was higher than those in control plants, implying that xylem and phloem flow velocities via the mesocotyl were considerably higher than in plants with an intact root system. The removal of the seminal roots in addition to restricting shoot-borne root development did not affect whole plant growth and N uptake, except for the stronger compensatory growth of the primary roots. Our results suggest that an adequate N supply to maize plant is maintained by compensatory growth of the remaining roots, increased N uptake rate and flow velocities within the xylem and phloem via the mesocotyl, and reduction in the shoot growth rate.

  8. Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain.

    Science.gov (United States)

    Momosaki, Sotaro; Ito, Miwa; Tonomura, Misato; Abe, Kohji

    2015-01-01

    Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [(13) N]Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate-glutamine pathway. The present study investigated the effect of an inhibitor of GS on [(13) N]ammonia uptake in order to clarify the feasibility of measuring GS activity in the living brain. l-Methionine sulfoximine (MSO), a selective GS inhibitor was microinjected into the ipsilateral striatum in rats. [(13) N]Ammonia uptake was quantified by autoradiography method as well as small animal positron emission tomography (PET) scans. The GS activity of the brain homogenate was assayed from the γ-glutamyl transferase reaction. Autoradiograms showed a decrease of [(13) N]ammonia radioactivity on the MSO-injected side compared with the saline-injected side of the striatum. This reduction could be detected with a small animal PET scanner. MSO had no effect on cerebral blood flow measured by uptake of [(15) O]H2 O. The reduction of [(13) N]ammonia uptake was closely related to the results of GS activity assay. These results indicated that [(13) N]ammonia may enable measurement of GS activity in the living brain.

  9. Nanoparticle synthesis and delivery by an aerosol route for watermelon plant foliar uptake

    Energy Technology Data Exchange (ETDEWEB)

    Wang Weining [Washington University in St. Louis, Aerosol and Air Quality Research Laboratory, Department of Energy, Environmental and Chemical Engineering (United States); Tarafdar, Jagadish C. [Central Arid Zone Research Institute (India); Biswas, Pratim, E-mail: pbiswas@wustl.edu [Washington University in St. Louis, Aerosol and Air Quality Research Laboratory, Department of Energy, Environmental and Chemical Engineering (United States)

    2013-01-15

    An aerosol process was developed for synthesis and delivery of nanoparticles for living watermelon plant foliar uptake. This is an efficient technique capable of generating nanoparticles with controllable particle sizes and number concentrations. Aerosolized nanoparticles were easily applied to leaf surfaces and enter the stomata via gas uptake, avoiding direct interaction with soil systems, eliminating potential ecological risks. The uptake and transport of nanoparticles inside the watermelon plants were investigated systematically by various techniques, such as elemental analysis by inductively coupled plasma mass spectrometry and plant anatomy by transmission electron microscopy. The results revealed that certain fractions of nanoparticles (d{sub p} < 100 nm) generated by the aerosol process could enter the leaf following the stomatal pathway, then pass through the stem, and reach the root of the watermelon plants. The particle size and number concentration played an important role in nanoparticle translocation inside the plants. In addition, the nanoparticle application method, working environment, and leaf structure are also important factors to be considered for successful plant foliar uptake.

  10. Determinants of the uptake of very low density lipoprotein remnants by the perfused rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Arbeeny, C.M.; Rifici, V.A.; Handley, D.A.; Eder, H.A.

    1987-11-01

    The receptor-mediated uptake of very low density lipoprotein (VLDL) remnants by the rat liver was studied. Livers were perfused with native /sup 125/I-VLDL remnants, radiolabeled apo E-deficient remnants, and radiolabeled remnants that contained reductively methylated apo B and unmodified apo E. The specific uptake of the apo E-deficient remnants was 20% of that for the native remnants, whereas the specific uptake of the remnants containing unreactive apo B was 78% of the control value. This suggests that the apo E of VLDL remnants is the principal ligand for binding to the receptor, and in the absence of apo E, apo B may participate in binding. This conclusion is supported by the finding that dimyristoyl phosphatidylcholine (DMPC)- apo E complexes were effective in competing for the hepatic uptake of /sup 125/I-VLDL remnants. The intracellular distribution of radioactivity was analyzed by Percoll density gradient centrifugation. At five minutes after perfusion, radioactivity was associated with the plasma membrane and lysosomal fractions, and at 30 minutes most of the radioactivity was associated with the lysosomal fraction. Binding and internalization of VLDL remnants was also directly visualized by electron microscopy. Internalization proceeded by coated pit-coated vesicle formation with subsequent delivery to lysosomes. Our findings demonstrate that the apo E of VLDL remnants mediates binding to the hepatic receptor and that the internalization and degradation of VLDL remnants is by a similar pathway to that previously described for LDL.

  11. Effect of Three Statins on Glucose Uptake of Cardiomyocytes and its Mechanism.

    Science.gov (United States)

    Jiang, Zhenhuan; Yu, Bo; Li, Yang

    2016-08-11

    BACKGROUND The aim of this study was to investigate the effects of different statins on glucose uptake and to confirm its mechanism in primary cultured rat cardiomyocytes after administration of atorvastatin, pravastatin, and rosuvastatin. MATERIAL AND METHODS Primary cultured rat cardiomyocytes were randomly assigned to 5 groups: normal control group (OB), insulin group (S1), statin 1-μM (S2), 5-μM (S3), and 10-μM (S4) groups for 3 different statins. The 2-[3H]-DG uptake of each group was determined and the mRNA and protein expression levels of glucose transporter type 4 (GLUT4), insulin receptor substrate (IRs), and RhoA were assessed. RESULTS After treatment with different concentrations of statins and insulin, the 2-[3H]-DG uptake showed a significant negative correlation with the concentration of atorvastatin (Pstatins. CONCLUSIONS These results confirm that atorvastatin can inhibit insulin-induced glucose uptake in primary cultured rat cardiomyocytes by regulating the PI3K/Akt insulin signal transduction pathway.

  12. Endothelial glycocalyx conditions influence nanoparticle uptake for passive targeting

    Directory of Open Access Journals (Sweden)

    Cheng MJ

    2016-07-01

    intracellular spaces, whereas the degraded glycocalyx trapped the PEG-AuNP within the glycocalyx. The repaired glycocalyx model partially restored HS thickness to 1.2 µm and 44% coverage of the ECs, but it was able to reverse the NP uptake back to baseline levels. In summary, this study showed that the glycocalyx structure is critical for NP uptake by ECs and may serve as a passive pathway for delivering NPs to dysfunctional ECs. Keywords: glycocalyx, heparan sulfate, endothelial cells, NP, gold

  13. Heme iron uptake by Caco-2 cells is a saturable, temperature sensitive and modulated by extracellular pH and potassium.

    Science.gov (United States)

    Arredondo, Miguel; Kloosterman, Janneke; Núñez, Sergio; Segovia, Fabián; Candia, Valeria; Flores, Sebastián; Le Blanc, Solange; Olivares, Manuel; Pizarro, Fernando

    2008-11-01

    It is known that heme iron and inorganic iron are absorbed differently. Heme iron is found in the diet mainly in the form of hemoglobin and myoglobin. The mechanism of iron absorption remains uncertain. This study focused on the heme iron uptake by Caco-2 cells from a hemoglobin digest and its response to different iron concentrations. We studied the intracellular Fe concentration and the effect of time, K+ depletion, and cytosol acidification on apical uptake and transepithelial transport in cells incubated with different heme Fe concentrations. Cells incubated with hemoglobin-digest showed a lower intracellular Fe concentration than cells grown with inorganic Fe. However, uptake and transepithelial transport of Fe was higher in cells incubated with heme Fe. Heme Fe uptake had a low Vmax and Km as compared to inorganic Fe uptake and did not compete with non-heme Fe uptake. Heme Fe uptake was inhibited in cells exposed to K+ depletion or cytosol acidification. Heme oxygenase 1 expression increased and DMT1 expression decreased with higher heme Fe concentrations in the media. The uptake of heme iron is a saturable and temperature-dependent process and, therefore, could occur through a mechanism involving both a receptor and the endocytic pathway.

  14. Requirement of glycogenolysis for uptake of increased extracellular K+ in astrocytes: potential implications for K+ homeostasis and glycogen usage in brain.

    Science.gov (United States)

    Xu, Junnan; Song, Dan; Xue, Zhanxia; Gu, Li; Hertz, Leif; Peng, Liang

    2013-03-01

    The importance of astrocytic K(+) uptake for extracellular K(+) ([K(+)](e)) clearance during neuronal stimulation or pathophysiological conditions is increasingly acknowledged. It occurs by preferential stimulation of the astrocytic Na(+),K(+)-ATPase, which has higher K(m) and V(max) values than its neuronal counterpart, at more highly increased [K(+)](e) with additional support of the cotransporter NKCC1. Triggered by a recent DiNuzzo et al. paper, we used administration of the glycogenolysis inhibitor DAB to primary cultures of mouse astrocytes to determine whether K(+) uptake required K(+)-stimulated glycogenolysis. KCl was increased by either 5 mM (stimulating only the Na(+),K(+)-ATPase) or 10 mM (stimulating both transporters) in glucose-containing saline media prepared to become iso-osmotic after the addition. DAB completely inhibited both uptakes, the Na(+),K(+)-ATPase-mediated by preventing Na(+) uptake for stimulation of its intracellular Na(+)-activated site, and the NKCC1-mediated uptake by inhibition of depolarization- and L-channel-mediated Ca(2+) uptake. Drugs inhibiting the signaling pathways involved in either of these processes also abolished K(+) uptake. Assuming similar in vivo characteristics, partly supported by literature data, K(+)-stimulated astrocytic K(+) uptake must discontinue after normalization of extracellular K(+). This will allow Kir1.4-mediated release and reuptake by the less powerful neuronal Na(+),K(+)-ATPase.

  15. {sup 18}F-FDG uptake at the surgical margin after hepatic resection: Patterns of uptake and differential diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Peungjesada, Silanath [University New Mexico, Department of Radiology, Albuquerque, NM (United States); Aloia, Thomas A. [University of Texas MD Anderson Cancer Center, Department of Surgical Oncology, Unit 444, Houston, TX (United States); Fox, Patricia [University of Texas MD Anderson Cancer Center, Department of Biostatistics, Unit 1411, Houston, TX (United States); Chasen, Beth [University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Unit 1483, Houston, TX (United States); Shin, Sooyoung; Loyer, Evelyne M. [University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Unit 1473, Houston, TX (United States); Baiomy, Ali [Cairo University, National Cancer Center, Cairo (Egypt)

    2015-08-15

    To evaluate the patterns of {sup 18}F-FDG uptake at the surgical margin after hepatectomy to identify features that may differentiate benign and malignant uptake. Patients who had undergone a PET/CT after hepatectomy were identified. Delay between resection and PET/CT, presence of uptake at the surgical margin, pattern of uptake, and maximal standardized value were recorded. The PET/CT findings were correlated with contrast-enhanced CT or MRI. There were 26 patients with increased 18F-FDG uptake; uptake was diffuse in seven and focal in 19. Diffuse uptake was due to inflammation in all cases. Focal uptake was due to recurrence in 12 and inflammation in seven cases. Defining a focal pattern only as a positive for malignancy yielded 100 % sensitivity, 87 % specificity, 37 % false positive rate. As expected, SUV{sub max} was significantly higher for recurrence than inflammation, but did overlap. Contrast-enhanced CT allowed differentiation between malignant and benign uptake in all cases. F-FDG uptake after hepatectomy does not equate to recurrence and yields a high false positive rate. Diffuse uptake did not require additional evaluation in our sample. Focal uptake, however, may be due to recurrence; differentiating benign and malignant nodular uptake relies on optimal contrast-enhanced CT or MRI. (orig.)

  16. Effect of wortmannin and phorbol ester on Paramecium fluid-phase uptake in the presence of transferrin.

    Science.gov (United States)

    Wiejak, J; Surmacz, L; Wyroba, E

    2001-01-01

    The kinetics of the uptake of the fluid phase marker Lucifer Yellow (LY), and its alteration by wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI-3K), and the PKC modulators: GF 109203 X, an inhibitor, and phorbol ester, an activator was studied in eukaryotic model Paramecium aurelia. Spectrophotometric quantification of LY accumulation was performed in the presence or absence of transferrin, a marker of receptor-mediated endocytosis. Internalization of LY showed a curvilinear kinetics: the high initial rate of LY uptake (575 ng LY/mg protein/hr) decreased almost 5-fold within 15 min, reaching plateau at 126 ng/mg protein/hr. Transferrin induced a small increase (7.5%) in the fluid phase uptake rate (after 5 min) followed by a small decrease at longer incubation times. Lucifer Yellow and transferrin (visualized by streptavidin-FITC) were localized in Paramecium by 3-D reconstruction by confocal microscopy. LY showed a scattered, diffuse fluorescence typical of fluid phase uptake whereas transferrin accumulated in membrane-surrounded endosomes. Wortmannin did not affect LY accumulation but decreased it when transferrin was present in the incubation medium. This suggests an effect on the transferrin uptake pathway, presumably on the stage of internalization in "mixing" endosomes to which transferrin and LY were targeted. Phorbol ester diminished LY accumulation by 22% and this effect persisted up to 25 min of incubation. PKC inhibitor did not affect LY uptake. However, in the presence of transferrin, the LY uptake increased within the first 15 minutes followed by a rapid 20% decrease in comparison to the control. Such an effect of PKC modulators suggests that PMA action on fluid phase uptake is not directly mediated by PKC.

  17. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes.

    Science.gov (United States)

    Storey, Stephen M; McIntosh, Avery L; Huang, Huan; Landrock, Kerstin K; Martin, Gregory G; Landrock, Danilo; Payne, H Ross; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

    2012-04-15

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null mice and hepatocytes. Taken together

  18. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes

    Science.gov (United States)

    Storey, Stephen M.; McIntosh, Avery L.; Huang, Huan; Landrock, Kerstin K.; Martin, Gregory G.; Landrock, Danilo; Payne, H. Ross; Atshaves, Barbara P.; Kier, Ann B.

    2012-01-01

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null mice and hepatocytes. Taken together

  19. Hydrogen Uptake of DPB Getter Pellets

    Energy Technology Data Exchange (ETDEWEB)

    Dinh, L N; Schildbach, M A; Herberg, J L; Saab, A P; Weigle, J; Chinn, S C; Maxwell, R S; McLean II, W

    2008-05-30

    The physical and chemical properties of 1,4-diphenylbutadiyne (DPB) blended with carbon-supported Pd (DPB-Pd/C) in the form of pellets during hydrogenation were investigated. A thermogravimetric analyzer (TGA) was employed to measure the kinetics of the hydrogen uptake by the DPB getter pellets. The kinetics obtained were then used to develop a semi-empirical model, based on gas diffusion into solids, to predict the performance of the getter pellets under various conditions. The accuracy of the prediction model was established by comparing the prediction models with independent experimental data on hydrogen pressure buildup in sealed systems containing DPB getter pellets and subjected to known rates of hydrogen input. The volatility of the hydrogenated DPB products and its effects on the hydrogen uptake kinetics were also analyzed.

  20. Quantifying uncertainty in future ocean carbon uptake

    Science.gov (United States)

    Dunne, John P.

    2016-10-01

    Attributing uncertainty in ocean carbon uptake between societal trajectory (scenarios), Earth System Model construction (structure), and inherent natural variation in climate (internal) is critical to make progress in identifying, understanding, and reducing those uncertainties. In the present issue of Global Biogeochemical Cycles, Lovenduski et al. (2016) disentangle these drivers of uncertainty in ocean carbon uptake over time and space and assess the resulting implications for the emergence timescales of structural and scenario uncertainty over internal variability. Such efforts are critical for establishing realizable and efficient monitoring goals and prioritizing areas of continued model development. Under recently proposed climate stabilization targets, such efforts to partition uncertainty also become increasingly critical to societal decision-making in the context of carbon stabilization.

  1. Calcium Uptake in Crude Tissue Preparation

    Science.gov (United States)

    Bidwell, Philip A.; Kranias, Evangelia G.

    2016-01-01

    SUMMARY The various isoforms of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) are responsible for the Ca2+ uptake from the cytosol into the endoplasmic or sarcoplasmic reticulum (ER/SR). In some tissues, the activity of SERCA can be modulated by binding partners, such as phospholamban and sarcolipin. The activity of SERCA can be characterized by its apparent affinity for Ca2+ as well as maximal enzymatic velocity. Both parameters can be effectively determined by the protocol described here. Specifically, we describe the measurement of the rate of oxalate-facilitated 45Ca uptake into the SR of crude mouse ventricular homogenates. This protocol can easily be adapted for different tissues and animal models as well as cultured cells. PMID:26695031

  2. Astaxanthin uptake in domestic dogs and cats

    Directory of Open Access Journals (Sweden)

    Massimino Stefan

    2010-06-01

    Full Text Available Abstract Background Research on the uptake and transport of astaxanthin is lacking in most species. We studied the uptake of astaxanthin by plasma, lipoproteins and leukocytes in domestic dogs and cats. Methods Mature female Beagle dogs (18 to 19 mo old; 11 to 14 kg BW were dosed orally with 0, 0.1, 0.5, 2.5, 10 or 40 mg astaxanthin and blood taken at 0, 3, 6, 9, 12, 18 and 24 h post-administration (n = 8/treatment. Similarly, mature domestic short hair cats (12 mo old; 3 to 3.5 kg body weight were fed a single dose of 0, 0.02, 0.08, 0.4, 2, 5, or 10 mg astaxanthin and blood taken (n = 8/treatment at the same interval. Results Both dogs and cats showed similar biokinetic profiles. Maximal astaxanthin concentration in plasma was approximately 0.14 μmol/L in both species, and was observed at 6 h post-dosing. The plasma astaxanthin elimination half-life was 9 to 18 h. Astaxanthin was still detectable by 24 h in both species. In a subsequent study, dogs and cats were fed similar doses of astaxanthin daily for 15 to 16 d and astaxanthin uptake by plasma, lipoproteins, and leukocytes studied. In both species, plasma astaxanthin concentrations generally continued to increase through d 15 or 16 of supplementation. The astaxanthin was mainly associated with high density lipoprotein (HDL. In blood leukocytes, approximately half of the total astaxanthin was found in the mitochondria, with significant amounts also associated with the microsomes and nuclei. Conclusion Dogs and cats absorb astaxanthin from the diet. In the blood, the astaxanthin is mainly associated with HDL, and is taken up by blood leukocytes, where it is distributed to all subcellular organelles. Certain aspects of the biokinetic uptake of astaxanthin in dogs and cats are similar to that in humans.

  3. Cyclic Strain Enhances Cellular Uptake of Nanoparticles

    OpenAIRE

    Jia Hu; Yaling Liu

    2015-01-01

    Nanoparticles (NPs) have gained increasing interest in recent years due to their potential use as drug carrier, imaging, and diagnostic agents in pharmaceutical and biomedical applications. While many cells in vivo experience mechanical forces, little is known about the correlation of the mechanical stimulation and the internalization of NPs into cells. This paper investigates the effects of applied cyclic strain on NP uptake by cells. Bovine aortic endothelial cells (BAECs) were cultured on ...

  4. 21 CFR 868.1730 - Oxygen uptake computer.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Oxygen uptake computer. 868.1730 Section 868.1730...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1730 Oxygen uptake computer. (a) Identification. An oxygen uptake computer is a device intended to compute the amount of oxygen consumed by a...

  5. Carboxylates and the uptake of ammonium by excised maize roots

    NARCIS (Netherlands)

    Breteler, H.

    1975-01-01

    The effect of carboxylates (organic acid anions) on NH 4 uptake was studied by changing the carboxylate level of roots prior to uptake experi ments. Succinate was the most effective stimulator of ammonium uptake. The oxocarboxylates (α-oxoglutarate, oxaloacetate and

  6. Determinants in the uptake of the human papillomavirus vaccine

    DEFF Research Database (Denmark)

    de Casadevante, Victoria Fernández; Cuesta, Julita Gil; Cantarero Arevalo, Lourdes

    2015-01-01

    of HPVV uptake in Europe. Methods: We performed a systematic Pubmed, Scopus, and Science Direct search to find articles published from HPVV availability in European countries until April 2014. No age restriction was applied. We included all studies assessing factors associated with HPVV uptake. Uptake...

  7. CONSEXPO 3.0, consumer exposure and uptake models

    NARCIS (Netherlands)

    Veen MP van; LBM

    2001-01-01

    The report provides a modelling approach to consumer exposure to chemicals, based on mathematical contact, exposure and uptake models. For each route of exposure, a number of exposure and uptake models are included. A general framework joins the exposure and uptake models selected by the user. By c

  8. Capturing Individual Uptake: Toward a Disruptive Research Methodology

    Science.gov (United States)

    Bastian, Heather

    2015-01-01

    This article presents and illustrates a qualitative research methodology for studies of uptake. It does so by articulating a theoretical framework for qualitative investigations of uptake and detailing a research study designed to invoke and capture students' uptakes in a first-year writing classroom. The research design sought to make uptake…

  9. Uptake and retention of amitriptyline by kaolinite.

    Science.gov (United States)

    Lv, Guocheng; Stockwell, Christie; Niles, Jacqueline; Minegar, Skylar; Li, Zhaohui; Jiang, Wei-Teh

    2013-12-01

    As the most commonly prescribed tricyclic antidepressant, amitriptyline (AT) is frequently detected in wastewater, surface runoff, and effluents from sewage treatment plants, and could potentially reach agriculture land through the application of municipal biosolids or reclaimed water. Kaolinite is one of the most important soil components under warm and humid climate conditions. In this study, the uptake and retention of AT by kaolinite from aqueous solution were investigated by batch tests, XRD, and FTIR analyses. The uptake of AT on kaolinite was instantaneous, attributed to surface adsorption as confirmed by XRD analyses. Quantitative correlation between desorption of exchangeable cations and AT adsorption confirmed experimentally that cation exchange was the dominant mechanism of AT uptake on kaolinite. The values for free energy of adsorption also suggested physi-sorption such as cation exchange. Solution pH had minimal influence at pH 5-11 even though the pKa value of AT was 9.4 and the surface charge of kaolinite was pH-dependent. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. A thermodynamic formulation of root water uptake

    Science.gov (United States)

    Hildebrandt, Anke; Kleidon, Axel; Bechmann, Marcel

    2016-08-01

    By extracting bound water from the soil and lifting it to the canopy, root systems of vegetation perform work. Here we describe how root water uptake can be evaluated thermodynamically and demonstrate that this evaluation provides additional insights into the factors that impede root water uptake. We derive an expression that relates the energy export at the base of the root system to a sum of terms that reflect all fluxes and storage changes along the flow path in thermodynamic terms. We illustrate this thermodynamic formulation using an idealized setup of scenarios with a simple model. In these scenarios, we demonstrate why heterogeneity in soil water distribution and rooting properties affect the impediment of water flow even though the mean soil water content and rooting properties are the same across the scenarios. The effects of heterogeneity can clearly be identified in the thermodynamics of the system in terms of differences in dissipative losses and hydraulic energy, resulting in an earlier start of water limitation in the drying cycle. We conclude that this thermodynamic evaluation of root water uptake conveniently provides insights into the impediments of different processes along the entire flow path, which goes beyond resistances and also accounts for the role of heterogeneity in soil water distribution.

  11. Arsenic as a food chain contaminant: mechanisms of plant uptake and metabolism and mitigation strategies.

    Science.gov (United States)

    Zhao, Fang-Jie; McGrath, Steve P; Meharg, Andrew A

    2010-01-01

    Arsenic (As) is an environmental and food chain contaminant. Excessive accumulation of As, particularly inorganic arsenic (As(i)), in rice (Oryza sativa) poses a potential health risk to populations with high rice consumption. Rice is efficient at As accumulation owing to flooded paddy cultivation that leads to arsenite mobilization, and the inadvertent yet efficient uptake of arsenite through the silicon transport pathway. Iron, phosphorus, sulfur, and silicon interact strongly with As during its route from soil to plants. Plants take up arsenate through the phosphate transporters, and arsenite and undissociated methylated As species through the nodulin 26-like intrinsic (NIP) aquaporin channels. Arsenate is readily reduced to arsenite in planta, which is detoxified by complexation with thiol-rich peptides such as phytochelatins and/or vacuolar sequestration. A range of mitigation methods, from agronomic measures and plant breeding to genetic modification, may be employed to reduce As uptake by food crops.

  12. Cellular uptake and cytotoxicity of positively charged chitosan gold nanoparticles in human lung adenocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seon Young; Jang, Soo Hwa [Seoul National University, Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Institute for Veterinary Science (Korea, Republic of); Park, Jin; Jeong, Saeromi; Park, Jin Ho; Ock, Kwang Su [Soongsil University, Department of Chemistry (Korea, Republic of); Lee, Kangtaek [Yonsei University, Department of Chemical and Biomolecular Engineering (Korea, Republic of); Yang, Sung Ik [Kyung Hee University, College of Environment and Applied Chemistry (Korea, Republic of); Joo, Sang-Woo, E-mail: sjoo@ssu.ac.kr [Soongsil University, Department of Chemistry (Korea, Republic of); Ryu, Pan Dong; Lee, So Yeong, E-mail: leeso@snu.ac.kr [Seoul National University, Laboratory of Veterinary Pharmacology, College of Veterinary Medicine and Institute for Veterinary Science (Korea, Republic of)

    2012-12-15

    Cellular uptake, cytotoxicity, and mechanisms of cytotoxicity of the positively charged Au nanoparticles (NPs) were examined in A549 cells, which are one of the most characterized pulmonary cellular systems. Positively charged Au NPs were prepared by chemical reduction using chitosan. The dimension and surface charge of Au NPs were examined by transmission electron microscopy (TEM), dynamic light scattering, and zeta potential measurements. The uptake of Au NPs into A549 cells was also monitored using TEM and dark-field microscopy (DFM) and z-stack confocal microRaman spectroscopy. DFM live cell imaging was also performed to monitor the entry of chitosan Au NPs in real time. The cytotoxic assay, using both methylthiazol tetrazolium and lactate dehydrogenase assays revealed that positively charged Au NPs decreased cell viability. Flow cytometry, DNA fragmentation, real-time PCR, and western blot analysis suggest that positively charged chitosan Au NPs provoke cell damage through both apoptotic and necrotic pathways.

  13. Desalted duck egg white peptides promote calcium uptake by counteracting the adverse effects of phytic acid.

    Science.gov (United States)

    Hou, Tao; Liu, Weiwei; Shi, Wen; Ma, Zhili; He, Hui

    2017-03-15

    The structure of the desalted duck egg white peptides-calcium chelate was characterized by fluorescence spectroscopy, fourier transform infrared spectroscopy, and dynamic light scattering. Characterization results showed structural folding and aggregation of amino acids or oligopeptides during the chelation process. Desalted duck egg white peptides enhanced the calcium uptake in the presence of oxalate, phosphate and zinc ions in Caco-2 monolayers. Animal model indicated that desalted duck egg white peptides effectively enhanced the mineral absorption and counteracted the deleterious effects of phytic acid. These findings suggested that desalted duck egg white peptides might promote calcium uptake in three pathways: 1) desalted duck egg white peptides bind with calcium to form soluble chelate and avoid precipitate; 2) the chelate is absorbed as small peptides by enterocyte; and 3) desalted duck egg white peptides regulate the proliferation and differentiation of enterocytes through the interaction with transient receptor potential vanilloid 6 calcium channel.

  14. Effect of the counter anion of cesium on foliar uptake and translocation

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Hidenao [Department of Radioecology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho, Kamikita-gun, Aomori 039-3212 (Japan)], E-mail: hhidenao@ies.or.jp; Tsukada, Hirofumi; Kawabata, Hitoshi [Department of Radioecology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho, Kamikita-gun, Aomori 039-3212 (Japan); Chikuchi, Yuki [JGC Plantech Aomori Co. Ltd., Rokkasho, Aomori 039-3212 (Japan); Takaku, Yuichi; Hisamatsu, Shun' ichi [Department of Radioecology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho, Kamikita-gun, Aomori 039-3212 (Japan)

    2009-01-15

    Direct deposition of radioactive material onto crops is one important pathway for safety assessment of radionuclides released from nuclear facilities. Foliar uptake of Cs by radish (Raphanus sativus L. cv. Redchim) was studied by applying droplets of Cs solution (CsCl or CsNO{sub 3}) on an upper leaf surface. The uptake of Cs was strongly affected by counter anions of Cs in the applied solution. Approximately 80% of Cs was absorbed for CsCl solution, while only 20% was absorbed for CsNO{sub 3}. The partition of absorbed Cs between leaf and root tuber was quite similar for both Cs compounds, which indicated that behavior of the absorbed Cs in radish was the same for both.

  15. Sorption, Uptake, and Translocation of Pharmaceuticals across Multiple Interfaces in Soil Environment

    Science.gov (United States)

    Zhang, W.; Liu, C. H.; Bhalsod, G.; Zhang, Y.; Chuang, Y. H.; Boyd, S. A.; Teppen, B. J.; Tiedje, J. M.; Li, H.

    2015-12-01

    Pharmaceuticals are contaminants of emerging concern frequently detected in soil and water environments, raising serious questions on their potential impact on human and ecosystem health. Overuse and environmental release of antibiotics (i.e., a group of pharmaceuticals extensively used in human medicine and animal agriculture) pose enormous threats to the health of human, animal, and the environment, due to proliferation of antibiotic resistant bacteria. Recently, we have examined interactions of pharmaceuticals with soil geosorbents, bacteria, and vegetable crops in order to elucidate pathways of sorption, uptake, and translocation of pharmaceuticals across the multiple interfaces in soils. Sorption of pharmaceuticals by biochars was studied to assess the potential of biochar soil amendment for reducing the transport and bioavailability of antibiotics. Our preliminary results show that carbonaceous materials such as biochars and activated carbon had strong sorption capacities for antibiotics, and consequently decreased the uptake and antibiotic resistance gene expression by an Escherichia coli bioreporter. Thus, biochar soil amendment showed the potential for reducing selection pressure on antibiotic resistant bacteria. Additionally, since consumption of pharmaceutical-tainted food is a direct exposure pathway for humans, it is important to assess the uptake and accumulation of pharmaceuticals in food crops grown in contaminated soils or irrigated with reclaimed water. Therefore, we have investigated the uptake and accumulations of pharmaceuticals in greenhouse-grown lettuce under contrasting irrigation practices (i.e., overhead or surface irrigations). Preliminary results indicate that greater pharmaceutical concentrations were measured in overhead irrigated lettuce than in surface irrigated lettuce. This could have important implications when selecting irrigation scheme to use the reclaimed water for crop irrigation. In summary, proper soil and water management

  16. Modelling water uptake efficiency of root systems

    Science.gov (United States)

    Leitner, Daniel; Tron, Stefania; Schröder, Natalie; Bodner, Gernot; Javaux, Mathieu; Vanderborght, Jan; Vereecken, Harry; Schnepf, Andrea

    2016-04-01

    Water uptake is crucial for plant productivity. Trait based breeding for more water efficient crops will enable a sustainable agricultural management under specific pedoclimatic conditions, and can increase drought resistance of plants. Mathematical modelling can be used to find suitable root system traits for better water uptake efficiency defined as amount of water taken up per unit of root biomass. This approach requires large simulation times and large number of simulation runs, since we test different root systems under different pedoclimatic conditions. In this work, we model water movement by the 1-dimensional Richards equation with the soil hydraulic properties described according to the van Genuchten model. Climatic conditions serve as the upper boundary condition. The root system grows during the simulation period and water uptake is calculated via a sink term (after Tron et al. 2015). The goal of this work is to compare different free software tools based on different numerical schemes to solve the model. We compare implementations using DUMUX (based on finite volumes), Hydrus 1D (based on finite elements), and a Matlab implementation of Van Dam, J. C., & Feddes 2000 (based on finite differences). We analyse the methods for accuracy, speed and flexibility. Using this model case study, we can clearly show the impact of various root system traits on water uptake efficiency. Furthermore, we can quantify frequent simplifications that are introduced in the modelling step like considering a static root system instead of a growing one, or considering a sink term based on root density instead of considering the full root hydraulic model (Javaux et al. 2008). References Tron, S., Bodner, G., Laio, F., Ridolfi, L., & Leitner, D. (2015). Can diversity in root architecture explain plant water use efficiency? A modeling study. Ecological modelling, 312, 200-210. Van Dam, J. C., & Feddes, R. A. (2000). Numerical simulation of infiltration, evaporation and shallow

  17. Metabolic pathways promoting cancer cell survival and growth.

    Science.gov (United States)

    Boroughs, Lindsey K; DeBerardinis, Ralph J

    2015-04-01

    Activation of oncogenes and loss of tumour suppressors promote metabolic reprogramming in cancer, resulting in enhanced nutrient uptake to supply energetic and biosynthetic pathways. However, nutrient limitations within solid tumours may require that malignant cells exhibit metabolic flexibility to sustain growth and survival. Here, we highlight these adaptive mechanisms and also discuss emerging approaches to probe tumour metabolism in vivo and their potential to expand the metabolic repertoire of malignant cells even further.

  18. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms.

    Science.gov (United States)

    Kang, Changkeun; Lee, Hyunkyoung; Jung, Eun-Sun; Seyedian, Ramin; Jo, MiNa; Kim, Jehein; Kim, Jong-Shu; Kim, Euikyung

    2012-12-15

    Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C(2)C(12) skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients.

  19. Mechanism of cellular uptake and impact of ferucarbotran on macrophage physiology.

    Directory of Open Access Journals (Sweden)

    Chung-Yi Yang

    Full Text Available Superparamagnetic iron oxide (SPIO nanoparticles are contrast agents used for magnetic resonance imaging. Ferucarbotran is a clinically approved SPIO-coated carboxydextran with a diameter of about 45-60 nm. We investigated the mechanism of cellular uptake of Ferucarbotran with a cell model using the murine macrophage cell line Raw 264.7. We observed a dose-dependent uptake of these SPIO particles by spectrophotometer analysis and also a dose-dependent increase in the granularity of the macrophages as determined by flow cytometry. There was a linear correlation between the side scattering mean value and iron content (P<0.001, R(2 = 0. 8048. For evaluation of the endocytotic pathway of these ingested SPIO particles, different inhibitors of the endocytotic pathways were employed. There was a significant decrease of side scattering counts in the cells and a less significant change in signal intensity based on magnetic resonance in the phenylarsine oxide-treated macrophages. After labeling with SPIO particles, the macrophages showed an increase in the production of reactive oxygen species at 2, 24, and 48 h; a decrease in mitochondrial membrane potential at 24 h; and an increase in cell proliferation at 24 h. We concluded that Ferucarbotran was internalized into macrophages via the clathrin-mediated pathway and can change the cellular behavior of these cells after labeling.

  20. Cellular uptake and transcytosis of lipid-based nanoparticles across the intestinal barrier: Relevance for oral drug delivery.

    Science.gov (United States)

    Neves, Ana Rute; Queiroz, Joana Fontes; Costa Lima, Sofia A; Figueiredo, Francisco; Fernandes, Rui; Reis, Salette

    2016-02-01

    Oral administration is the preferred route for drug delivery and nanosystems represent a promising tool for protection and transport of hardly soluble, chemically unstable and poorly permeable drugs through the intestinal barrier. In the present work, we have studied lipid nanoparticles cellular uptake, internalization pathways and transcytosis routes through Caco-2 cell monolayers. Both lipid nanosystems presented similar size (∼180nm) and surface charge (-30mV). Nanostructured lipid carriers showed a higher cellular uptake and permeability across the barrier, but solid lipid nanoparticles could enter cells faster than the former. The internalization of lipid nanoparticles occurs mainly through a clathrin-mediated endocytosis mechanism, although caveolae-mediated endocytosis is also involved in the uptake. Both lipid nanoparticles were able to cross the intestinal barrier by a preferential transcellular route. This work contributed to a better knowledge of the developed nanosystems for the oral delivery of a wide spectrum of drugs. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. A review of plant-pharmaceutical interactions: from uptake and effects in crop plants to phytoremediation in constructed wetlands

    DEFF Research Database (Denmark)

    Carvalho, Pedro N; Basto, M Clara P; Almeida, C Marisa R;

    2014-01-01

    the potential impact of veterinary and human pharmaceuticals on arable land. However, plant uptake as well as phytotoxicity data are scarcely studied. Simultaneously, phytoremediation as a tool for pharmaceutical removal from soils, sediments and water is starting to be researched, with promising results...... and biosolids, accelerates the introduction of these compounds into arable lands and crops. Despite the low concentrations of pharmaceuticals usually found, the continuous introduction into the environment from different pathways makes them 'pseudo-persistent'. Several reviews have been published regarding....... This review gives an in-depth overview of the phytotoxicity of pharmaceuticals, their uptake and their removal by plants. The aim of the current work was to map the present knowledge concerning pharmaceutical interactions with plants in terms of uptake and the use of plant-based systems for phytoremediation...

  2. Leukemia inhibitory factor increases glucose uptake in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Brandt, Nina; O'Neill, Hayley M; Kleinert, Maximilian;

    2015-01-01

    abolished LIF-induced glucose uptake and STAT3 Tyr705-P, whereas, incubation with LY-294002 and Wortmannin suppressed both basal and LIF-induced glucose uptake and Akt Ser473-P, indicating that JAK- and PI3-kinase signaling is required for LIF-stimulated glucose uptake. Incubation with Rapamycin and AZD8055...... indicated that Mammalian Target of Rapamycin complex (mTORC) 2, but not mTORC1, also is required for LIF-stimulated glucose uptake. In contrast to CNTF, LIF-stimulation did not alter palmitate oxidation. LIF-stimulated glucose uptake was maintained in EDL from obese insulin resistant mice, whereas soleus...

  3. Berberine activates GLUT1-mediated glucose uptake in 3T3-L1 adipocytes.

    Science.gov (United States)

    Kim, So Hui; Shin, Eun-Jung; Kim, Eun-Do; Bayaraa, Tsenguun; Frost, Susan Cooke; Hyun, Chang-Kee

    2007-11-01

    It has recently been known that berberine, an alkaloid of medicinal plants, has anti-hyperglycemic effects. To explore the mechanism underlying this effect, we used 3T3-L1 adipocytes for analyzing the signaling pathways that contribute to glucose transport. Treatment of berberine to 3T3-L1 adipocytes for 6 h enhanced basal glucose uptake both in normal and in insulin-resistant state, but the insulin-stimulated glucose uptake was not augmented significantly. Inhibition of phosphatidylinositol 3-kinase (PI 3-K) by wortmannin did not affect the berberine effect on basal glucose uptake. Berberine did not augment tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate (IRS)-1. Further, berberine had no effect on the activity of the insulin-sensitive downstream kinase, atypical protein kinase C (PKCzeta/lambda). However, interestingly, extracellular signal-regulated kinases (ERKs), which have been known to be responsible for the expression of glucose transporter (GLUT)1, were significantly activated in berberine-treated 3T3-L1 cells. As expected, the level of GLUT1 protein was increased both in normal and insulin-resistant cells in response to berberine. But berberine affected the expression of GLUT4 neither in normal nor in insulin-resistant cells. In addition, berberine treatment increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 cells, which has been reported to be associated with GLUT1-mediated glucose uptake. Together, we concluded that berberine increases glucose transport activity of 3T3-L1 adipocytes by enhancing GLUT1 expression and also stimulates the GLUT1-mediated glucose uptake by activating GLUT1, a result of AMPK stimulation.

  4. ars1, an Arabidopsis mutant exhibiting increased tolerance to arsenate and increased phosphate uptake.

    Science.gov (United States)

    Lee, David A; Chen, Alice; Schroeder, Julian I

    2003-09-01

    Arsenic is one of the most toxic pollutants at contaminated sites, yet little is known about the mechanisms by which certain plants survive exposure to high arsenic levels. To gain insight into the mechanisms of arsenic tolerance in plants, we developed a genetic screen to isolate Arabidopsis thaliana mutants with altered tolerance to arsenic. We report here on the isolation of a mutant arsenic resisant 1 (ars1) with increased tolerance to arsenate. ars1 germinates and develops under conditions that completely inhibit growth of wild-type plants and shows a semi-dominant arsenic resistance phenotype. ars1 accumulates levels of arsenic similar to that accumulated by wild-type plants, suggesting that ars1 plants have an increased ability to detoxify arsenate. However, ars1 plants produce phytochelatin levels similar to levels produced by the wild type, and the enhanced resistance of ars1 is not abolished by the gamma-glutamylcysteine synthetase inhibitor l-buthionine sulfoxime (BSO). Furthermore, ars1 plants do not show resistance to arsenite or other toxic metals such as cadmium and chromium. However, ars1 plants do show a higher rate of phosphate uptake than that shown by wild-type plants, and wild-type plants grown with an excess of phosphate show increased tolerance to arsenate. Traditional models of arsenate tolerance in plants are based on the suppression of phosphate uptake pathways and consequently on the reduced uptake of arsenate. Our data suggest that arsenate tolerance in ars1 could be due to a new mechanism mediated by increased phosphate uptake in ars1. Models discussing how increased phosphate uptake could contribute to arsenate tolerance are discussed.

  5. Beryllium uptake and related biological effects studied in THP-1 differentiated macrophages.

    Science.gov (United States)

    Ding, Jian; Lin, Lin; Hang, Wei; Yan, Xiaomei

    2009-11-01

    Investigation of cellular uptake of metal compounds is important in understanding metal-related toxicity and diseases. Inhalation of beryllium aerosols can cause chronic beryllium disease, a progressive, granulomatous fibrosis of the lung. Studies in laboratory animals and cultured animal cells indicate that alveolar macrophages take up beryllium compounds and participate in a hypersensitivity immune response to a beryllium-containing antigen. In the present work, human monocyte cell line THP-1 was induced with phorbol myristate acetate to differentiate into a macrophage. This cell with characteristics of human alveolar macrophages was employed to study cellular beryllium uptake and related biological effects. Morphological changes, phagocytosis of fluorescent latex beads, and cell surface CD14 expression were used to verify the successful differentiation of THP-1 monocytes into macrophages. An improved mass spectrometry method for quantitative analysis of intracellular beryllium as opposed to the traditional radioisotopic approach was developed using ICP-MS. The influence of the solubility of beryllium compounds, exposure duration, and beryllium concentration on the incorporation of beryllium was studied. Our data indicated that the uptake of particulate BeO was much more significant than that of soluble BeSO(4), suggesting the major cellular uptake pathway is phagocytosis. Nevertheless, subsequent DAPI nuclear staining and PARP cleavage study indicated that beryllium uptake had a negligible effect on the apoptosis of THP-1 macrophages compared to the unstimulated macrophage control. Meanwhile, no substantial variation of tumour necrosis factor-alpha production was observed for THP-1 macrophages upon beryllium exposure. These data imply alveolar macrophages could have some level of tolerance to beryllium and this may explain why most Be-exposed individuals remain healthy throughout life.

  6. Signaling cascade of insulin-induced stimulation of L-dopa uptake in renal proximal tubule cells.

    Science.gov (United States)

    Carranza, Andrea; Musolino, Patricia L; Villar, Marcelo; Nowicki, Susana

    2008-12-01

    The inward l-dihydroxyphenylalanine (L-dopa) transport supplies renal proximal tubule cells (PTCs) with the precursor for dopamine synthesis. We have previously described insulin-induced stimulation of L-dopa uptake into PTCs. In the present paper we examined insulin-related signaling pathways involved in the increase of l-dopa transport into isolated rat PTCs. Insulin (50-500 microU/ml) increased L-dopa uptake by PTCs, reaching the maximal increment (60% over the control) at 200 microU/ml. At this concentration, insulin also increased insulin receptor tyrosine phosphorylation. Both effects were abrogated by the tyrosine kinase inhibitor genistein (5 microM). In line, inhibition of the protein tyrosine phosphatase by pervanadate (0.2-100 microM) caused a concentration-dependent increase in both the uptake of L-dopa (up to 400%) and protein tyrosine phosphorylation. A synergistic effect between pervanadate and insulin on L-dopa uptake was observed only when threshold (0.2 microM), but not maximal (5 microM), concentrations of pervanadate were assayed. Insulin-induced stimulation of L-dopa uptake was also abolished by inhibition of phosphatidylinositol 3-kinase (PI3K; 100 nM wortmannin, and 25 microM LY-294002) and protein kinase C (PKC; 1 microM RO-318220). Insulin-induced activation of PKC-zeta was confirmed in vitro by its translocation from the cytosol to the membrane fraction, and in vivo by immunohistochemistry studies. Insulin caused a wortmannin-sensitive increase in Akt/protein kinase B (Akt/PKB) phosphorylation and a dose-dependent translocation of Akt/PKB to the membrane fraction. Our findings suggest that insulin activates PKC-zeta, and Akt/PKB downstream of PI3K, and that these pathways contribute to the insulin-induced increase of L-dopa uptake into PTCs.

  7. Pediatric Exercise Testing: Value and Implications of Peak Oxygen Uptake

    Directory of Open Access Journals (Sweden)

    Paolo T. Pianosi

    2017-01-01

    Full Text Available Peak oxygen uptake (peak V ˙ O 2 measured by clinical exercise testing is the benchmark for aerobic fitness. Aerobic fitness, estimated from maximal treadmill exercise, is a predictor of mortality in adults. Peak V ˙ O 2 was shown to predict longevity in patients aged 7–35 years with cystic fibrosis over 25 years ago. A surge of exercise studies in young adults with congenital heart disease over the past decade has revealed significant prognostic information. Three years ago, the first clinical trial in children with pulmonary arterial hypertension used peak V ˙ O 2 as an endpoint that likewise delivered clinically relevant data. Cardiopulmonary exercise testing provides clinicians with biomarkers and clinical outcomes, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response hidden at rest. Momentum from these pioneering observations in multiple disease states should impel clinicians to employ similar methods in other patient populations; e.g., sickle cell disease. Advances in pediatric exercise science will elucidate new pathways that may identify novel biomarkers. Our initial aim of this essay is to highlight the clinical relevance of exercise testing to determine peak V ˙ O 2 , and thereby convince clinicians of its merit, stimulating future clinical investigators to broaden the application of exercise testing in pediatrics.

  8. Arsenic uptake and speciation in vegetables grown under greenhouse conditions.

    Science.gov (United States)

    Smith, E; Juhasz, A L; Weber, J

    2009-04-01

    The accumulation of arsenic (As) by vegetables is a potential human exposure pathway. The speciation of As in vegetables is an important consideration due to the varying toxicity of different As species. In this study, common Australian garden vegetables were hydroponically grown with As-contaminated irrigation water to determine the uptake and species of As present in vegetable tissue. The highest concentrations of total As were observed in the roots of all vegetables and declined in the aerial portions of the plants. Total As accumulation in the edible portions of the vegetables decreased in the order radish > mung bean > lettuce = chard. Arsenic was present in the roots of radish, chard, and lettuce as arsenate (As(V)) and comprised between 77 and 92% of the total As present, whereas in mung beans, arsenite (As(III)) comprised 90% of the total As present. In aerial portions of the vegetables, As was distributed equally between both As(V) and As(III) in radish and chard but was present mainly as As(V) in lettuce. The presence of elevated As in vegetable roots suggests that As species may be complexed by phytochelatins, which limits As translocation to aerial portions of the plant.

  9. The diatom molecular toolkit to handle nitrogen uptake.

    Science.gov (United States)

    Rogato, Alessandra; Amato, Alberto; Iudicone, Daniele; Chiurazzi, Maurizio; Ferrante, Maria Immacolata; d'Alcalà, Maurizio Ribera

    2015-12-01

    Nutrient concentrations in the oceans display significant temporal and spatial variability, which strongly affects growth, distribution and survival of phytoplankton. Nitrogen (N) in particular is often considered a limiting resource for prominent marine microalgae, such as diatoms. Diatoms possess a suite of N-related transporters and enzymes and utilize a variety of inorganic (e.g., nitrate, NO3(-); ammonium, NH4(+)) and organic (e.g., urea; amino acids) N sources for growth. However, the molecular mechanisms allowing diatoms to cope efficiently with N oscillations by controlling uptake capacities and signaling pathways involved in the perception of external and internal clues remain largely unknown. Data reported in the literature suggest that the regulation and the characteristic of the genes, and their products, involved in N metabolism are often diatom-specific, which correlates with the peculiar physiology of these organisms for what N utilization concerns. Our study reveals that diatoms host a larger suite of N transporters than one would expected for a unicellular organism, which may warrant flexible responses to variable conditions, possibly also correlated to the phases of life cycle of the cells. All this makes N transporters a crucial key to reveal the balance between proximate and ultimate factors in diatom life.

  10. Pediatric Exercise Testing: Value and Implications of Peak Oxygen Uptake.

    Science.gov (United States)

    Pianosi, Paolo T; Liem, Robert I; McMurray, Robert G; Cerny, Frank J; Falk, Bareket; Kemper, Han C G

    2017-01-24

    Peak oxygen uptake (peak V ˙ O 2 ) measured by clinical exercise testing is the benchmark for aerobic fitness. Aerobic fitness, estimated from maximal treadmill exercise, is a predictor of mortality in adults. Peak V ˙ O 2 was shown to predict longevity in patients aged 7-35 years with cystic fibrosis over 25 years ago. A surge of exercise studies in young adults with congenital heart disease over the past decade has revealed significant prognostic information. Three years ago, the first clinical trial in children with pulmonary arterial hypertension used peak V ˙ O 2 as an endpoint that likewise delivered clinically relevant data. Cardiopulmonary exercise testing provides clinicians with biomarkers and clinical outcomes, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response hidden at rest. Momentum from these pioneering observations in multiple disease states should impel clinicians to employ similar methods in other patient populations; e.g., sickle cell disease. Advances in pediatric exercise science will elucidate new pathways that may identify novel biomarkers. Our initial aim of this essay is to highlight the clinical relevance of exercise testing to determine peak V ˙ O 2 , and thereby convince clinicians of its merit, stimulating future clinical investigators to broaden the application of exercise testing in pediatrics.

  11. Conservation of PHO pathway in ascomycetes and the role of Pho84

    Indian Academy of Sciences (India)

    Parul Tomar; Sinha Sinha

    2014-06-01

    In budding yeast, Saccharomyces cerevisiae, the phosphate signalling and response pathway, known as PHO pathway, monitors phosphate cytoplasmic levels by controlling genes involved in scavenging, uptake and utilization of phosphate. Recent attempts to understand the phosphate starvation response in other ascomycetes have suggested the existence of both common and novel components of the budding yeast PHO pathway in these ascomycetes. In this review, we discuss the components of PHO pathway, their roles in maintaining phosphate homeostasis in yeast and their conservation across ascomycetes. The role of high-affinity transporter, Pho84, in sensing and signalling of phosphate has also been discussed.

  12. Isoorientin reverts TNF-α-induced insulin resistance in adipocytes activating the insulin signaling pathway.

    Science.gov (United States)

    Alonso-Castro, Angel Josabad; Zapata-Bustos, Rocio; Gómez-Espinoza, Guadalupe; Salazar-Olivo, Luis A

    2012-11-01

    Isoorientin (ISO) is a plant C-glycosylflavonoid with purported antidiabetic effects but unexplored mechanisms of action. To gain insight into its antidiabetic mechanisms, we assayed nontoxic ISO concentrations on the 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxy-d-glucose (2-NBDG) uptake by murine 3T3-F442A and human sc adipocytes. In insulin-sensitive adipocytes, ISO stimulated the 2-NBDG uptake by 210% (murine) and 67% (human), compared with insulin treatment. Notably, ISO also induced 2-NBDG uptake in murine (139%) and human (60%) adipocytes made resistant to insulin by treatment with TNF-α, compared with the incorporation induced in these cells by rosiglitazone. ISO induction of glucose uptake in adipocytes was abolished by inhibitors of the insulin signaling pathway. These inhibitors also blocked the proper phosphorylation of insulin signaling pathway components induced by ISO in both insulin-sensitive and insulin-resistant adipocytes. Additionally, ISO stimulated the transcription of genes encoding components of insulin signaling pathway in murine insulin-sensitive and insulin-resistant adipocytes. In summary, we show here that ISO exerts its antidiabetic effects by activating the insulin signaling pathway in adipocytes, reverts the insulin resistance caused in these cells by TNF-α by stimulating the proper phosphorylation of proteins in this signaling pathway, and induces the expression of genes encoding these proteins.

  13. Protein Corona Influences Cellular Uptake of Gold Nanoparticles by Phagocytic and Nonphagocytic Cells in a Size-Dependent Manner.

    Science.gov (United States)

    Cheng, Xiaju; Tian, Xin; Wu, Anqing; Li, Jianxiang; Tian, Jian; Chong, Yu; Chai, Zhifang; Zhao, Yuliang; Chen, Chunying; Ge, Cuicui

    2015-09-23

    The interaction at nanobio is a critical issue in designing safe nanomaterials for biomedical applications. Recent studies have reported that it is nanoparticle-protein corona rather than bare nanoparticle that determines the nanoparticle-cell interactions, including endocytic pathway and biological responses. Here, we demonstrate the effects of protein corona on cellular uptake of different sized gold nanoparticles in different cell lines. The experimental results show that protein corona significantly decreases the internalization of Au NPs in a particle size- and cell type-dependent manner. Protein corona exhibits much more significant inhibition on the uptake of large-sized Au NPs by phagocytic cell than that of small-sized Au NPs by nonphagocytic cell. The endocytosis experiment indicates that different endocytic pathways might be responsible for the differential roles of protein corona in the interaction of different sized Au NPs with different cell lines. Our findings can provide useful information for rational design of nanomaterials in biomedical application.

  14. Mycorrhiza and heavy metal resistant bacteria enhance growth, nutrient uptake and alter metabolic profile of sorghum grown in marginal soil.

    Science.gov (United States)

    Dhawi, Faten; Datta, Rupali; Ramakrishna, Wusirika

    2016-08-01

    The main challenge for plants growing in nutrient poor, contaminated soil is biomass reduction, nutrient deficiency and presence of heavy metals. Our aim is to overcome these challenges using different microbial combinations in mining-impacted soil and focus on their physiological and biochemical impacts on a model plant system, which has multiple applications. In the current study, sorghum BTx623 seedlings grown in mining-impacted soil in greenhouse were subjected to plant growth promoting bacteria (PGPB or B) alone, PGPB with arbuscular mycorrhizal fungi (My), My alone and control group with no treatment. Root biomass and uptake of most of the elements showed significant increase in all treatment groups in comparison with control. Mycorrhiza group showed the best effect followed by My + B and B groups for uptake of majority of the elements by roots. On the contrary, biomass of both shoot and root was more influenced by B treatment than My + B and My treatments. Metabolomics identified compounds whose levels changed in roots of treatment groups significantly in comparison to control. Upregulation of stearic acid, sorbitol, sebacic acid and ferulic acid correlated positively with biomass and uptake of almost all elements. Two biochemical pathways, fatty acid biosynthesis and galactose metabolism, were regulated in all treatment groups. Three common pathways were upregulated only in My and My + B groups. Our results suggest that PGPB enhanced metabolic activities which resulted in increase in element uptake and sorghum root biomass whether accompanied with mycorrhiza or used solely.

  15. Serial changes in BMIPP uptake in relation to thallium uptake in the rat myocardium after ischaemia

    Energy Technology Data Exchange (ETDEWEB)

    Noriyasu, Kazuyuki; Tsukamoto, Takahiro; Kohya, Tetsuro; Kitabatake, Akira [Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo (Japan); Mabuchi, Megumi; Morita, Koichi; Tamaki, Nagara [Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, N-15, W-7, Kita-Ku, 060-8638 Sapporo (Japan); Kuge, Yuji [Department of Tracer Kinetics, Hokkaido University Graduate School of Medicine, Sapporo (Japan)

    2003-12-01

    Several clinical studies have shown that iodine-123 labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) uptake is often lower than the uptake of perfusion tracers in patients with ischaemic heart disease. However, BMIPP accumulation may not decrease during the acute phase of a stunned myocardium in patients with acute coronary syndrome. We evaluated serial changes in BMIPP and perfusion tracer uptake in the myocardium after ischaemia. We performed a 20-min left coronary artery occlusion followed by reperfusion in male Wister rats. One hour after the reperfusion, echocardiography was performed. Intravenous injection of iodine-125 labelled BMIPP and thallium-201 was performed 1 day (acute group) and 5 days (subacute group) after the operation. To determine the myocardial distribution of {sup 125}I-BMIPP and {sup 201}Tl, dual-tracer autoradiography was conducted. We identified regions of interest in the anterolateral wall as an area at risk and in the inferoseptum as a remote control area. The anterolateral wall/inferoseptum ratio (A/I ratio) was calculated to compare the distributions of {sup 125}I-BMIPP and {sup 201}Tl. Coronary occlusion induced hypokinesia in the anterolateral region 1 h after the reperfusion. The A/I ratio of {sup 125}I-BMIPP was significantly higher than that of {sup 201}Tl in the acute group (1.01{+-}0.15 vs 0.80{+-}0.23, P<0.001). On the other hand, there was no significant difference between the A/I ratios of {sup 125}I-BMIPP and {sup 201}Tl in the subacute group (0.88{+-}0.18 vs 0.85{+-}0.18). Two rats showed a significantly lower A/I ratio of {sup 125}I-BMIPP than {sup 201}Tl in the subacute phase. These data suggest that BMIPP uptake is preserved despite a decrease in perfusion in the acute phase after ischaemia. In the subacute phase, on the other hand, BMIPP uptake is similar to or even lower than thallium uptake. Since BMIPP uptake may change with time after ischaemia, careful interpretation of BMIPP uptake after

  16. Characterization of cadmium uptake in Lactobacillus plantarum and isolation of cadmium and manganese uptake mutants

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Z.; Reiske, H.R.; Wilson, D.B.

    1999-11-01

    Two different Cd{sup 2+} uptake systems were identified in Lactobacillus plantarum. One is a high-affinity, high-velocity Mn{sup 2+} uptake system which also takes up Cd{sup 2+} and is induced by Mn{sup 2+} starvation. The calculated K{sub m} and V{sub max} are 0.26 {mu}M and 3.6 {mu}mol g of dry cell{sup {minus}1} min{sup {minus}1}, respectively. Unlike Mn{sup 2+} uptake, which is facilitated by citrate and related tricarboxylic acids, Cd{sup 2+} uptake is weakly inhibited by citrate. Cd{sup 2+} and Mn{sup 2+} are competitive inhibitors of each other, and the affinity of the system for Cd{sup 2+} is higher than that for Mn{sup 2+}. The other Cd{sup 2+} uptake system is expressed in Mn{sup 2+}-sufficient cells, and no K{sub m} can be calculated for it because uptake is nonsaturable. Mn{sup 2+} does not compete for transport through this system, nor does any other tested cation, i.e., Zn{sup 2+}, Cu{sup 2+}, Co{sup 2+}, Mg{sup 2+}, Ca{sup 2+}, Fe{sup 2+}, or Ni{sup 2+}. Both systems require energy, since uncouplers completely inhibit their activities. Two Mn{sup 2+}-dependent L. plantarum mutants were isolated by chemical mutagenesis and ampicillin enrichment. They required more than 5,000 times as much Mn{sup 2+} for growth as the parental strain. Mn{sup 2+} starvation-induced Cd{sup 2+} uptake in both mutants was less than 5% the wild-type rate. The low level of long-term Mn{sup 2+} or Cd{sup 2+} accumulation by the mutant strains also shows that the mutations eliminate the high-affinity Mn{sup 2+} and Cd{sup 2+} uptake system.

  17. Fermentation process using specific oxygen uptake rates as a process control

    Science.gov (United States)

    Van Hoek; Pim , Aristidou; Aristos , Rush; Brian

    2007-06-19

    Specific oxygen uptake (OUR) is used as a process control parameter in fermentation processes. OUR is determined during at least the production phase of a fermentation process, and process parameters are adjusted to maintain the OUR within desired ranges. The invention is particularly applicable when the fermentation is conducted using a microorganism having a natural PDC pathway that has been disrupted so that it no longer functions. Microorganisms of this sort often produce poorly under strictly anaerobic conditions. Microaeration controlled by monitoring OUR allows the performance of the microorganism to be optimized.

  18. Fermentation process using specific oxygen uptake rates as a process control

    Energy Technology Data Exchange (ETDEWEB)

    Van Hoek, Pim; Aristidou, Aristos; Rush, Brian J.

    2016-08-30

    Specific oxygen uptake (OUR) is used as a process control parameter in fermentation processes. OUR is determined during at least the production phase of a fermentation process, and process parameters are adjusted to maintain the OUR within desired ranges. The invention is particularly applicable when the fermentation is conducted using a microorganism having a natural PDC pathway that has been disrupted so that it no longer functions. Microorganisms of this sort often produce poorly under strictly anaerobic conditions. Microaeration controlled by monitoring OUR allows the performance of the microorganism to be optimized.

  19. Fermentation process using specific oxygen uptake rates as a process control

    Energy Technology Data Exchange (ETDEWEB)

    Van Hoek, Pim; Aristidou, Aristos; Rush, Brian

    2014-09-09

    Specific oxygen uptake (OUR) is used as a process control parameter in fermentation processes. OUR is determined during at least the production phase of a fermentation process, and process parameters are adjusted to maintain the OUR within desired ranges. The invention is particularly applicable when the fermentation is conducted using a microorganism having a natural PDC pathway that has been disrupted so that it no longer functions. Microorganisms of this sort often produce poorly under strictly anaerobic conditions. Microaeration controlled by monitoring OUR allows the performance of the microorganism to be optimized.

  20. Notes on the history of cellular uptake and deiodination of thyroid hormone.

    Science.gov (United States)

    Hennemann, Georg

    2005-08-01

    In this mini review on the history of the research devoted to thyroid hormone metabolism two pathways are discussed, i.e. uptake and subsequent deiodination in cells and tissues. In the 1950's the investigations of these processes were greatly stimulated when 131I became available for research purposes. The true nature of both mechanisms surfaced in the 1970's when it became apparent that transport of thyroid hormones into cells was a regulated carrier mediated process, while deiodination appeared to be catalyzed by different types of enzymes. Kinetic data indicated that these processes were of great importance in the ultimate regulation of thyroid hormone bio-availability.

  1. Characterization of the sulfate uptake and assimilation pathway from Xanthomonas citri - targets for bacterial growth inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Tambascia, C.; Balan, A. [Laboratorio Nacional de Biociencias - LNBIO, Campinas, SP (Brazil)

    2012-07-01

    Full text: Microorganisms require sulfur for growth and obtain it either for inorganic sulfate or organosulfur compounds. ATP-Binding Cassete (SulT family) or major facilitator superfamily-type (SulP) transporters are responsible for the sulfate transport into the cell. In Xanthomonas citri, the phytopathogenic bacterium that causes the canker citrus disease, there are no reports related to the importance of these transporters during in vitro or in vivo infection. We identified in X. citri genome all the genes that belong to the well-characterized cys regulon from Escherichia coli and Salmonella typhimurium, which includes three ABC transporters and all the enzymes necessary for sulfate oxide reduction to sulfide and cysteine. Once these genes have been shown to be extremely important for bacteria growth and development in different environments, we chose the sbpcysWUA and cysDNCHIJG operons, which encodes the ABC inorganic sulfate ABC transporter and all the enzymes necessary for conversion of sulfate in cysteine, respectively. As a step for crystallization trials and resolution of their tridimensional structures, the referred genes were amplified and cloned into the cloning vector pGEM T-easy. In addition, using bioinformatics tools and molecular modeling we characterized all the protein functions as well as built tridimensional models of their structure for determination of the active sites. The importance of each protein is discussed aiming the discovery of a good target for development of inhibitors that could block the bacterium growth. (author)

  2. Green tea: molecular targets in glucose uptake, inflammation, and insulin signaling pathways

    Science.gov (United States)

    Obesity is a major public health problem that leads to increased risk of developing diabetes, cardiovascular, and related diseases. The number of overweight and obese Americans has increased since the 1960s, and obesity may be responsible for as many as 300,000 deaths and medical costs in excess of...

  3. Quantification of nanowire uptake by live cells

    KAUST Repository

    Margineanu, Michael B.

    2015-05-01

    Nanostructures fabricated by different methods have become increasingly important for various applications at the cellular level. In order to understand how these nanostructures “behave” and for studying their internalization kinetics, several attempts have been made at tagging and investigating their interaction with living cells. In this study, magnetic iron nanowires with an iron oxide layer are coated with (3-Aminopropyl)triethoxysilane (APTES), and subsequently labeled with a fluorogenic pH-dependent dye pHrodo™ Red, covalently bound to the aminosilane surface. Time-lapse live imaging of human colon carcinoma HCT 116 cells interacting with the labeled iron nanowires is performed for 24 hours. As the pHrodo™ Red conjugated nanowires are non-fluorescent outside the cells but fluoresce brightly inside, internalized nanowires are distinguished from non-internalized ones and their behavior inside the cells can be tracked for the respective time length. A machine learning-based computational framework dedicated to automatic analysis of live cell imaging data, Cell Cognition, is adapted and used to classify cells with internalized and non-internalized nanowires and subsequently determine the uptake percentage by cells at different time points. An uptake of 85 % by HCT 116 cells is observed after 24 hours incubation at NW-to-cell ratios of 200. While the approach of using pHrodo™ Red for internalization studies is not novel in the literature, this study reports for the first time the utilization of a machine-learning based time-resolved automatic analysis pipeline for quantification of nanowire uptake by cells. This pipeline has also been used for comparison studies with nickel nanowires coated with APTES and labeled with pHrodo™ Red, and another cell line derived from the cervix carcinoma, HeLa. It has thus the potential to be used for studying the interaction of different types of nanostructures with potentially any live cell types.

  4. Interventions for increasing uptake in screening programmes

    Directory of Open Access Journals (Sweden)

    Droste, Sigrid

    2006-08-01

    Full Text Available Introduction: Opportunities for the early detection of disease are not sufficiently being taken advantage of. Specific interventions could increase the uptake of prevention programmes. A comprehensive analysis of effectiveness and cost-effectiveness of these interventions with reference to Germany is still needed. Objectives: This report aimed to describe and assess interventions to increase uptake in primary and secondary prevention and to explore the assessment of their cost-effectiveness. Methods: 29 scientific databases were systematically searched in a wide strategy. Additional references were located from bibliographies. All published systematic reviews and primary studies were assessed for inclusion without language restrictions. Teams of two reviewers identified the literature, extracted data and assessed the quality of the publications independently. Results: Four HTA reports and 22 systematic reviews were identified for the medical evaluation covering a variety of interventions. The economic evaluation was based on two HTA-reports, one meta-analysis and 15 studies. The evidence was consistent for the effectiveness of invitations and reminders aimed at users, and for prompts aimed at health care professionals. These interventions were the most commonly analysed. (Financial Incentives for users and professionals were identified in a small number of studies. Limited evidence was available for cost-effectiveness showing incremental costs for follow-up reminders and invitations by telephone. Evidence for ethical, social and legal aspects pointed to needs in vulnerable populations. Discussion: The material was heterogeneous regarding interventions used, study populations and settings. The majority of references originated from the United States and focused on secondary prevention. Approaching all target groups by invitations and reminders was recommended to increase uptake in prevention programmes in general. Conclusions: Further research

  5. Fluorescent Nanoparticle Uptake for Brain Tumor Visualization

    Directory of Open Access Journals (Sweden)

    Rachel Tréhin

    2006-04-01

    Full Text Available Accurate delineation of tumor margins is vital to the successful surgical resection of brain tumors. We have previously developed a multimodal nanoparticle CLIO-Cy5.5, which is detectable by both magnetic resonance imaging and fluorescence, to assist in intraoperatively visualizing tumor boundaries. Here we examined the accuracy of tumor margin determination of orthotopic tumors implanted in hosts with differing immune responses to the tumor. Using a nonuser-based signal intensity method applied to fluorescent micrographs of 9L gliosarcoma green fluorescent protein (GFP tumors, mean overestimations of 2 and 24 µm were obtained using Cy5.5 fluorescence, compared to the true tumor margin determined by GFP fluorescence, in nude mice and rats, respectively. To resolve which cells internalized the nanoparticle and to quantitate degree of uptake, tumors were disaggregated and cells were analyzed by flow cytometry and fluorescence microscopy. Nanoparticle uptake was seen in both CD11b+ cells (representing activated microglia and macrophages and tumor cells in both animal models by both methods. CD11b+ cells were predominantly found at the tumor margin in both hosts, but were more pronounced at the margin in the rat model. Additional metastatic (CT26 colon and primary (Gli36 glioma brain tumor models likewise demonstrated that the nanoparticle was internalized both by tumor cells and by host cells. Together, these observations suggest that fluorescent nanoparticles provide an accurate method of tumor margin estimation based on a combination of tumor cell and host cell uptake for primary and metastatic tumors in animal model systems and offer potential for clinical translation.

  6. Clinical relevance of intestinal peptide uptake

    Institute of Scientific and Technical Information of China (English)

    Hugh; James; Freeman

    2015-01-01

    AIM: To determine available information on an independent peptide transporter 1(Pep T1) and its potential relevance to treatment, this evaluation was completed.METHODS: Fully published English language literature articles sourced through Pub Med related to protein digestion and absorption, specifically human peptide and amino acid transport, were accessed and reviewed.Papers from 1970 to the present, with particular emphasis on the past decade, were examined. In addition,abstracted information translated to English in Pub Med was also included. Finally, studies and reviews relevant to nutrient or drug uptake, particularly in human intestine were included for evaluation. This work represents a summary of all of these studies with particular reference to peptide transporter mediated assimilation of nutrients and pharmacologically active medications.RESULTS: Assimilation of dietary protein in humans involves gastric and pancreatic enzyme hydrolysis to luminal oligopeptides and free amino acids. During the ensuing intestinal phase, these hydrolytic products are transported into the epithelial cell and, eventually, the portal vein. A critical component of this process is the uptake of intact di-peptides and tri-peptides by an independent Pep T1. A number of "peptide-mimetic" pharmaceutical agents may also be transported through this carrier, important for uptake of different antibiotics, antiviral agents and angiotensin-converting enzyme inhibitors. In addition, specific peptide products of intestinal bacteria may also be transported by Pep T1, with initiation and persistence of an immune response including increased cytokine production and associated intestinal inflammatory changes. Interestingly, these inflammatory changes may also be attenuated with orallyadministered anti-inflammatory tripeptides administered as site-specific nanoparticles and taken up by this Pep T1 transport protein. CONCLUSION: Further evaluation of the role of this transporter in treatment of

  7. Characteristics of sterol uptake in Saccharomyces cerevisiae.

    OpenAIRE

    Lorenz, R T; Rodriguez, R J; Lewis, T A; Parks, L W

    1986-01-01

    A Saccharomyces cerevisiae sterol auxotroph, FY3 (alpha hem1 erg7 ura), was used to probe the characteristics of sterol uptake in S. cerevisiae. The steady-state cellular concentration of free sterol at the late exponential phase of growth could be adjusted within a 10-fold range by varying the concentration of exogenously supplied sterol. When cultured on 1 microgram of sterol ml-1, the cells contained a minimal cellular free-cholesterol concentration of 0.85 nmol/mg (dry weight) and were te...

  8. High tumor uptake of (64)Cu

    DEFF Research Database (Denmark)

    Jørgensen, Jesper Tranekjær; Persson, Morten; Madsen, Jacob

    2013-01-01

    The use of copper-based positron emission tomography (PET) tracers in cancer studies is increasing. However, as copper has previously been found in high concentrations in human tumor tissue in vivo, instability of PET tracers could result in tumor accumulation of non-tracer-bound radioactive copper...... that may influence PET measurements. Here we determine the degree of (64)Cu uptake in five commonly used human cancer xenograft models in mice. Additionally, we compare copper accumulation in tumor tissue to gene expression of human copper transporter 1 (CTR1)....

  9. AKT inhibitors promote cell death in cervical cancer through disruption of mTOR signaling and glucose uptake.

    Directory of Open Access Journals (Sweden)

    Ramachandran Rashmi

    Full Text Available BACKGROUND: PI3K/AKT pathway alterations are associated with incomplete response to chemoradiation in human cervical cancer. This study was performed to test for mutations in the PI3K pathway and to evaluate the effects of AKT inhibitors on glucose uptake and cell viability. EXPERIMENTAL DESIGN: Mutational analysis of DNA from 140 pretreatment tumor biopsies and 8 human cervical cancer cell lines was performed. C33A cells (PIK3CAR88Q and PTENR233* were treated with increasing concentrations of two allosteric AKT inhibitors (SC-66 and MK-2206 with or without the glucose analogue 2-deoxyglucose (2-DG. Cell viability and activation status of the AKT/mTOR pathway were determined in response to the treatment. Glucose uptake was evaluated by incubation with 18F-fluorodeoxyglucose (FDG. Cell migration was assessed by scratch assay. RESULTS: Activating PIK3CA (E545K, E542K and inactivating PTEN (R233* mutations were identified in human cervical cancer. SC-66 effectively inhibited AKT, mTOR and mTOR substrates in C33A cells. SC-66 inhibited glucose uptake via reduced delivery of Glut1 and Glut4 to the cell membrane. SC-66 (1 µg/ml-56% and MK-2206 (30 µM-49% treatment decreased cell viability through a non-apoptotic mechanism. Decreases in cell viability were enhanced when AKT inhibitors were combined with 2-DG. The scratch assay showed a substantial reduction in cell migration upon SC-66 treatment. CONCLUSIONS: The mutational spectrum of the PI3K/AKT pathway in cervical cancer is complex. AKT inhibitors effectively block mTORC1/2, decrease glucose uptake, glycolysis, and decrease cell viability in vitro. These results suggest that AKT inhibitors may improve response to chemoradiation in cervical cancer.

  10. Improvement of galactose uptake in Saccharomyces cerevisiae through overexpression of phosphoglucomutase: Example of transcript analysis as a tool in inverse metabolic engineering

    DEFF Research Database (Denmark)

    Bro, Christoffer; Knudsen, S.; Regenberg, Birgitte

    2005-01-01

    Through genome-wide transcript analysis of a reference strain and two recombinant Saccharomyces cerevisiae strains with different rates of galactose uptake, we obtained information about the global transcriptional response to metabolic engineering of the GAL gene regulatory network. One......-regulated in the two recombinant strains with higher galactose uptake rates. This indicated that PGM2 is a target for overexpression in terms of increasing the flux through the Leloir pathway, and through overexpression of PGM2 the galactose uptake rate could be increased by 70% compared to that of the reference...... strain. Based on our findings, we concluded that phosphoglucomutase plays a key role in controlling the flux through the Leloir pathway, probably due to increased conversion of glucose-l-phosphate to glucose-6-phosphate. This conclusion was supported by measurements of sugar phosphates, which showed...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Aim: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-¿ knockout mice the roles of atypical PKCs (PKC-¿ and PKC-¿) in regulating...... acid uptake by >80% in both wild-type and PKC-¿-knockout cardiomyocytes. In PKC-¿ knockout cardiomyocytes, PKC-¿ is the sole remaining atypical PKC isoform, and its expression level is not different from wild-type cardiomyocytes, in which it contributes to 29% and 17% of total atypical PKC expression...... and phosphorylation, respectively. Conclusion: Taken together, atypical PKCs are necessary for insulin-stimulated and AMPK-mediated glucose uptake into the heart, as well as for insulin-stimulated and AMPK-mediated fatty acid uptake. However, the residual PKC-¿ activity in PKC-¿-knockout cardiomyocytes is sufficient...

  12. ApoA-IV improves insulin sensitivity and glucose uptake in mouse adipocytes via PI3K-Akt Signaling

    Science.gov (United States)

    Li, Xiaoming; Wang, Fei; Xu, Min; Howles, Philip; Tso, Patrick

    2017-01-01

    Insulin resistance is a risk factor for type 2 diabetes mellitus. We investigated the effect of ApoA-IV on glucose uptake in the adipose and muscle tissues of mice and cultured 3T3-L1 adipocytes. We found that treatment with ApoA-IV lowered fasting blood glucose in both WT and diabetic KKAy mice by increasing glucose uptake in cardiac muscle, white adipose tissue, and brown adipose tissue through a mechanism that was partially insulin independent. Cell culture experiments showed that ApoA-IV improved glucose uptake in adipocytes in the absence of insulin by upregulating GLUT4 translocation by PI3K mediated activation of Akt signaling pathways. Considering our previous finding that ApoA-IV treatment enhanced pancreatic insulin secretion, these results suggests that ApoA-IV acts directly upon adipose tissue to improve glucose uptake and indirectly via insulin signaling. Our findings warrant future studies to identify the receptor for ApoA-IV and the downstream targets of PI3K-Akt signaling that regulate glucose uptake in adipocytes as potential therapeutic targets for treating insulin resistance. PMID:28117404

  13. Mechanisms of dsRNA uptake in insects and potential of RNAi for pest control: a review.

    Science.gov (United States)

    Huvenne, Hanneke; Smagghe, Guy

    2010-03-01

    RNA interference already proved its usefulness in functional genomic research on insects, but it also has considerable potential for the control of pest insects. For this purpose, the insect should be able to autonomously take up the dsRNA, for example through feeding and digestion in its midgut. In this review we bring together current knowledge on the uptake mechanisms of dsRNA in insects and the potential of RNAi to affect pest insects. At least two pathways for dsRNA uptake in insects are described: the transmembrane channel-mediated uptake mechanism based on Caenorhabditis elegans' SID-1 protein and an 'alternative' endocytosis-mediated uptake mechanism. In the second part of the review dsRNA feeding experiments on insects are brought together for the first time, highlighting the achievement of implementing RNAi in insect control with the first successful experiments in transgenic plants and the diversity of successfully tested insect orders/species and target genes. We conclude with points of discussion and concerns regarding further research on dsRNA uptake mechanisms and the promising application possibilities for RNAi in insect control.

  14. Active macropinocytosis induction by stimulation of epidermal growth factor receptor and oncogenic Ras expression potentiates cellular uptake efficacy of exosomes.

    Science.gov (United States)

    Nakase, Ikuhiko; Kobayashi, Nahoko Bailey; Takatani-Nakase, Tomoka; Yoshida, Tetsuhiko

    2015-06-03

    Exosomes are approximately 100-nm vesicles that consist of a lipid bilayer of cellular membranes secreted in large quantities from various types of normal and disease-related cells. Endocytosis has been reported as a major pathway for the cellular uptake of exosomes; however, the detailed mechanisms of their cellular uptake are still unknown. Here, we demonstrate the active induction of macropinocytosis (accompanied by actin reorganisation, ruffling of plasma membrane, and engulfment of large volumes of extracellular fluid) by stimulation of cancer-related receptors and show that the epidermal growth factor (EGF) receptor significantly enhances the cellular uptake of exosomes. We also demonstrate that oncogenic K-Ras-expressing MIA PaCa-2 cells exhibit intensive macropinocytosis that actively transports extracellular exosomes into the cells compared with wild-type K-Ras-expressing BxPC-3 cells. Furthermore, encapsulation of the ribosome-inactivating protein saporin with EGF in exosomes using our simple electroporation method produces superior cytotoxicity via the enhanced cellular uptake of exosomes. Our findings contribute to the biological, pharmaceutical, and medical research fields in terms of understanding the macropinocytosis-mediated cellular uptake of exosomes with applications for exosomal delivery systems.

  15. Involvement of the mannose receptor in the uptake of Der p 1, a major mite allergen, by human dendritic cells.

    Science.gov (United States)

    Deslée, Gaëtan; Charbonnier, Anne-Sophie; Hammad, Hamida; Angyalosi, Gerhild; Tillie-Leblond, Isabelle; Mantovani, Alberto; Tonnel, André-Bernard; Pestel, Joël

    2002-11-01

    Immature dendritic cells (DCs) take up antigens in peripheral tissues and, after antigen processing, mature to efficiently stimulate T cells in secondary lymph nodes. In allergic airway diseases DCs have been shown to be involved in the induction and maintenance of a T(H)2-type profile. The present study was undertaken to determine pathways of Der p 1 (a house dust mite allergen) uptake by human DCs and to compare Der p 1 uptake between DCs from patients with house dust mite allergy and DCs from healthy donors. Monocyte-derived DCs (MD-DCs) were obtained from patients with house dust mite allergy (n = 13) and healthy donors (n = 11). Der p 1 was labeled with rhodamine. Der p 1 uptake by MD-DCs was analyzed by means of flow cytometry and confocal microscopy. Rhodamine- labeled Der p 1 was demonstrated to be taken up by MD-DCs in a dose-, time-, and temperature- dependent manner. The involvement of the mannose receptor (MR) in the Der p 1 uptake was demonstrated by using (1) inhibitors of the MR- mediated endocytosis (mannan and blocking anti-MR mAb), which inhibited the Der p 1 uptake from 40 % to 50 %, and (2) confocal microscopy showing the colocalization of rhodamine-labeled Der p 1 with FITC-dextran. Interestingly, compared with DCs from healthy donors, DCs from allergic patients expressed more MR and were more efficient in Der p 1 uptake. These results suggest that the MR could play a key role in the Der p 1 allergen uptake by DCs and in the pathogenesis of allergic diseases in dust mite -sensitive patients.

  16. Effect of wortmannin and phorbol ester on Paramecium fluid-phase uptake in the presence of transferrin

    Directory of Open Access Journals (Sweden)

    J Wiejak

    2009-12-01

    Full Text Available The kinetics of the uptake of the fluid phase marker Lucifer Yellow (LY, and its alteration by wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI-3K, and the PKC modulators: GF 109203 X, an inhibitor, and phorbol ester, an activator was studied in eukaryotic model Paramecium aurelia. Spectrophotometric quantification of LY accumulation was performed in the presence or absence of transferrin, a marker of receptor-mediated endocytosis. Internalization of LY showed a curvilinear kinetics: the high initial rate of LYuptake (575 ng LY/ mg protein /hr decreased almost 5-fold within 15 min, reaching plateau at 126 ng/ mg protein /hr. Transferrin induced a small increase (7.5% in the fluid phase uptake rate (after 5 min followed by a small decrease at longer incubation times. Lucifer Yellow and transferrin (visualized by streptavidin– FITC were localized in Paramecium by 3-D reconstruction by confocal microscopy. LY showed a scattered, diffuse fluorescence typical of fluid phase uptake whereas transferrin accumulated in membrane-surrounded endosomes. Wortmannin did not affect LY accumulation but decreased it when transferrin was present in the incubation medium. This suggests an effect on the transferrin uptake pathway, presumably on the stage of internalization in “mixing” endosomes to which transferrin and LY were targeted. Phorbol ester diminished LY accumulation by 22% and this effect persisted up to 25 min of incubation. PKC inhibitor did not affect LY uptake. However, in the presence of transferrin, the LY uptake increased within the first 15 minutes followed by a rapid 20% decrease in comparison to the control. Such an effect of PKC modulators suggests that PMA action on fluid phase uptake is not directly mediated by PKC.

  17. Chloroquine Increases Glucose Uptake via Enhancing GLUT4 Translocation and Fusion with the Plasma Membrane in L6 Cells

    Directory of Open Access Journals (Sweden)

    Qi Zhou

    2016-05-01

    Full Text Available Background/Aims: Chloroquine can induce an increase in the cellular uptake of glucose; however, the underlying mechanism is unclear. Methods: In this study, translocation of GLUT4 and intracellular Ca2+ changes were simultaneously observed by confocal microscope in L6 cells stably over-expressing IRAP-mOrange. The GLUT4 fusion with the plasma membrane (PM was traced using HA-GLUT4-GFP. Glucose uptake was measured using a cell-based glucose uptake assay. GLUT4 protein was detected by Western blotting and mRNA level was detected by RT-PCR. Results: We found that chloroquine induced significant increases in glucose uptake, glucose transporter GLUT4 translocation to the plasma membrane (GTPM, GLUT4 fusion with the PM, and intracellular Ca2+ in L6 muscle cells. Chloroquine-induced increases of GTPM and intracellular Ca2+ were inhibited by Gallein (Gβγ inhibitor and U73122 (PLC inhibitor. However, 2-APB (IP3R blocker only blocked the increase in intracellular Ca2+ but did not inhibit GTPM increase. These results indicate that chloroquine, via the Gβγ-PLC-IP3-IP3R pathway, induces elevation of Ca2+, and this Ca2+ increase does not play a role in chloroqui-ne-evoked GTPM increase. However, GLUT4 fusion with the PM and glucose uptake were significantly inhibited with BAPTA-AM. This suggests that Ca2+ enhances GLUT4 fusion with the PM resulting in glucose uptake increase. Conclusion: Our data indicate that chloroquine via Gβγ-PLC-IP3-IP3R induces Ca2+ elevation, which in turn promotes GLUT4 fusion with the PM. Moreover, chloroquine can enhance GLUT4 trafficking to the PM. These mechanisms eventually result in glucose uptake increase in control and insulin-resistant L6 cells. These findings suggest that chloroquine might be a potential drug for improving insulin tolerance in diabetic patients.

  18. The effect of G1c6P uptake and its subsequent oxidation within pea root plastids on nitrite reduction and glutamate synthesis

    NARCIS (Netherlands)

    Bowsher, Caroline G.; Lacey, Anne E.; Hanke, Guy T.; Clarkson, David T.; Saker, Les R.; Stulen, Ineke; Emes, Michael J.

    2007-01-01

    In roots, nitrate assimilation is dependent upon a supply of reductant that is initially generated by oxidative metabolism including the pentose phosphate pathway (OPPP). The uptake of nitrite into the plastids and its subsequent reduction by nitrite reductase (NiR) and glutamate synthase (GOGAT) ar

  19. Atmospheric deposition of trace elements around point sources and human health risk assessment. II: Uptake of arsenic and chromium by vegetables grown near a wood preservation factory

    DEFF Research Database (Denmark)

    Larsen, Erik Huusfeldt; Moseholm, Lars; Nielsen, Margot M.

    1992-01-01

    Kale, lettuce, carrots and potatoes were grown in 20 experimental plots surrounding a wood preservation factory, to investigate the amount and pathways for plant uptake of arsenic and chromium. Arsenate used in the wood preservation process is converted to the more toxic arsenite by incineration...

  20. Akt and Rac1 signalling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance

    DEFF Research Database (Denmark)

    Sylow, Lykke; Kleinert, Maximilian; Pehmøller, Christian

    2014-01-01

    Skeletal muscle plays a major role in regulating whole body glucose metabolism. Akt and Rac1 are important regulators of insulin-stimulated glucose uptake in skeletal muscle. However the relative role of each pathway and how they interact is not understood. Here we delineate how Akt and Rac1 path...

  1. Patterns of radioiodine uptake by the lactating breast

    Energy Technology Data Exchange (ETDEWEB)

    Bakheet, S.M. (Dept. of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)); Hammami, M.M. (Dept. of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia))

    1994-07-01

    Breast uptake of radioiodine, if not suspected, may be misinterpreted as thyroid cancer metastasis to the lung. To characterize the patterns of radioiodine breast uptake, we retrospectively studied 20 radioiodine scans that were performed within 1 week of cessation of breast feeding. Four patterns of uptake were identified: ''full'', ''focal'', ''crescent'' and ''irregular''. The uptake was asymmetric in 60% (left>right in 45%, right>left in 15%), symmetric in 25% and unilateral in 15% of cases. A characteristic full bilateral uptake was present in 40% of cases. In three cases with the irregular pattern, caused in part by external contamination with radioactive milk, the uptake closely mimicked lung metastases. Delayed images, obtained in one case, showed an apparent radioiodine shift from the breast to the thyroid, suggesting that the presence of breast uptake can modulate radioiodine uptake by thyroid tissue. In a case of unilateral breast uptake, a history of mastitis was obtained, which to our knowledge has not been previously reported. Breast uptake of radioiodine may take several scintigraphic patterns that are not always characteristic of the lactating breast and may affect the apparent extent of thyroid remnant/metastasis. (orig.)

  2. Impact of nitrite on aerobic phosphorus uptake by poly-phosphate accumulating organisms in enhanced biological phosphorus removal sludges.

    Science.gov (United States)

    Zeng, Wei; Li, Boxiao; Yang, Yingying; Wang, Xiangdong; Li, Lei; Peng, Yongzhen

    2014-02-01

    Impact of nitrite on aerobic phosphorus (P) uptake of poly-phosphate accumulating organisms (PAOs) in three different enhanced biological phosphorus removal (EBPR) systems was investigated, i.e., the enriched PAOs culture fed with synthetic wastewater, the two lab-scale sequencing batch reactors (SBRs) treating domestic wastewater for nutrient removal through nitrite-pathway nitritation and nitrate-pathway nitrification, respectively. Fluorescence in situ hybridization results showed that PAOs in the three sludges accounted for 72, 7.6 and 6.5% of bacteria, respectively. In the enriched PAOs culture, at free nitrous acid (FNA) concentration of 0.47 × 10(-3) mg HNO₂-N/L, aerobic P-uptake and oxidation of intercellular poly-β-hydroxyalkanoates were both inhibited. Denitrifying phosphorus removal under the aerobic conditions was observed, indicating the existence of PAOs using nitrite as electron acceptor in this culture. When the FNA concentration reached 2.25 × 10(-3) mg HNO2-N/L, denitrifying phosphorus removal was also inhibited. And the inhibition ceased once nitrite was exhausted. Corresponding to both SBRs treating domestic wastewater with nitritation and nitrification pathway, nitrite inhibition on aerobic P-uptake by PAOs did not occur even though FNA concentration reached 3 × 10(-3) and 2.13 × 10(-3) mg HNO₂-N/L, respectively. Therefore, PAOs taken from different EBPR activated sludges had different tolerance to nitrite.

  3. A Metabolic Probe-Enabled Strategy Reveals Uptake and Protein Targets of Polyunsaturated Aldehydes in the Diatom Phaeodactylum tricornutum.

    Directory of Open Access Journals (Sweden)

    Stefanie Wolfram

    Full Text Available Diatoms are unicellular algae of crucial importance as they belong to the main primary producers in aquatic ecosystems. Several diatom species produce polyunsaturated aldehydes (PUAs that have been made responsible for chemically mediated interactions in the plankton. PUA-effects include chemical defense by reducing the reproductive success of grazing copepods, allelochemical activity by interfering with the growth of competing phytoplankton and cell to cell signaling. We applied a PUA-derived molecular probe, based on the biologically highly active 2,4-decadienal, with the aim to reveal protein targets of PUAs and affected metabolic pathways. By using fluorescence microscopy, we observed a substantial uptake of the PUA probe into cells of the diatom Phaeodactylum tricornutum in comparison to the uptake of a structurally closely related control probe based on a saturated aldehyde. The specific uptake motivated a chemoproteomic approach to generate a qualitative inventory of proteins covalently targeted by the α,β,γ,δ-unsaturated aldehyde structure element. Activity-based protein profiling revealed selective covalent modification of target proteins by the PUA probe. Analysis of the labeled proteins gave insights into putative affected molecular functions and biological processes such as photosynthesis including ATP generation and catalytic activity in the Calvin cycle or the pentose phosphate pathway. The mechanism of action of PUAs involves covalent reactions with proteins that may result in protein dysfunction and interference of involved pathways.

  4. A Metabolic Probe-Enabled Strategy Reveals Uptake and Protein Targets of Polyunsaturated Aldehydes in the Diatom Phaeodactylum tricornutum.

    Science.gov (United States)

    Wolfram, Stefanie; Wielsch, Natalie; Hupfer, Yvonne; Mönch, Bettina; Lu-Walther, Hui-Wen; Heintzmann, Rainer; Werz, Oliver; Svatoš, Aleš; Pohnert, Georg

    2015-01-01

    Diatoms are unicellular algae of crucial importance as they belong to the main primary producers in aquatic ecosystems. Several diatom species produce polyunsaturated aldehydes (PUAs) that have been made responsible for chemically mediated interactions in the plankton. PUA-effects include chemical defense by reducing the reproductive success of grazing copepods, allelochemical activity by interfering with the growth of competing phytoplankton and cell to cell signaling. We applied a PUA-derived molecular probe, based on the biologically highly active 2,4-decadienal, with the aim to reveal protein targets of PUAs and affected metabolic pathways. By using fluorescence microscopy, we observed a substantial uptake of the PUA probe into cells of the diatom Phaeodactylum tricornutum in comparison to the uptake of a structurally closely related control probe based on a saturated aldehyde. The specific uptake motivated a chemoproteomic approach to generate a qualitative inventory of proteins covalently targeted by the α,β,γ,δ-unsaturated aldehyde structure element. Activity-based protein profiling revealed selective covalent modification of target proteins by the PUA probe. Analysis of the labeled proteins gave insights into putative affected molecular functions and biological processes such as photosynthesis including ATP generation and catalytic activity in the Calvin cycle or the pentose phosphate pathway. The mechanism of action of PUAs involves covalent reactions with proteins that may result in protein dysfunction and interference of involved pathways.

  5. Liver uptake of biguanides in rats.

    Science.gov (United States)

    Sogame, Yoshihisa; Kitamura, Atsushi; Yabuki, Masashi; Komuro, Setsuko

    2011-09-01

    Metformin is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus. The liver is the primary target, metformin being taken up into human and rat hepatocytes via an active transport mechanism. The present study was designed to compare hepatic uptake of two biguanides, metformin and phenformin, in vitro and in vivo. In in vitro experiments, performed using rat cryopreserved hepatocytes, phenformin exhibited a much higher affinity and transport than metformin, with marked differences in kinetics. The K(m) values for metformin and phenformin were 404 and 5.17μM, respectively, with CLint (V(max)/K(m)) values 1.58μl/min per 10(6) cells and 34.7μl/min per 10(6) cells. In in vivo experiments, when (14)C-metformin and (14)C-phenformin were given orally to male rats at a dose of 50mg/kg, the liver concentrations of radioactivity at 0.5 hour after dosing were 21.5μg eq./g with metformin but 147.1μg eq./g for phenformin, ratios of liver to plasma concentrations being 4.2 and 61.3, respectively. In conclusion, the results suggest that uptake of biguanides by rat hepatocytes is in line with the liver distribution found in vivo, phenformin being more efficiently taken up by liver than metformin after oral administration.

  6. Vaccine production, distribution, access and uptake

    Science.gov (United States)

    Smith, Jon; Lipsitch, Marc; Almond, Jeffrey W.

    2011-01-01

    Making human vaccines available on a global scale requires the use of complex production methods, meticulous quality control and reliable distribution channels that ensure the products are potent and effective at their point of use. The technologies involved in manufacturing different types of vaccines may strongly influence vaccine cost, ease of industrial scale-up, stability and ultimately world-wide availability. Manufacturing complexity is compounded by the need for different formulations for different countries and age groups. Reliable vaccine production in appropriate quantities and at affordable prices is the cornerstone of developing global vaccination policies. However, ensuring optimal access and uptake also requires strong partnerships between private manufacturers, regulatory authorities and national and international public health services. For vaccines whose supplies are limited, either due to rapidly emerging diseases or longer-term mismatch of supply and demand, prioritizing target groups can increase vaccine impact. Focusing on influenza vaccines as an example that well illustrates many of the relevant points, this article considers current production, distribution, access and other factors that ultimately impact on vaccine uptake and population-level effectiveness. PMID:21664680

  7. Mitochondrial calcium uptake capacity modulates neocortical excitability.

    Science.gov (United States)

    Sanganahalli, Basavaraju G; Herman, Peter; Hyder, Fahmeed; Kannurpatti, Sridhar S

    2013-07-01

    Local calcium (Ca(2+)) changes regulate central nervous system metabolism and communication integrated by subcellular processes including mitochondrial Ca(2+) uptake. Mitochondria take up Ca(2+) through the calcium uniporter (mCU) aided by cytoplasmic microdomains of high Ca(2+). Known only in vitro, the in vivo impact of mCU activity may reveal Ca(2+)-mediated roles of mitochondria in brain signaling and metabolism. From in vitro studies of mitochondrial Ca(2+) sequestration and cycling in various cell types of the central nervous system, we evaluated ranges of spontaneous and activity-induced Ca(2+) distributions in multiple subcellular compartments in vivo. We hypothesized that inhibiting (or enhancing) mCU activity would attenuate (or augment) cortical neuronal activity as well as activity-induced hemodynamic responses in an overall cytoplasmic and mitochondrial Ca(2+)-dependent manner. Spontaneous and sensory-evoked cortical activities were measured by extracellular electrophysiology complemented with dynamic mapping of blood oxygen level dependence and cerebral blood flow. Calcium uniporter activity was inhibited and enhanced pharmacologically, and its impact on the multimodal measures were analyzed in an integrated manner. Ru360, an mCU inhibitor, reduced all stimulus-evoked responses, whereas Kaempferol, an mCU enhancer, augmented all evoked responses. Collectively, the results confirm aforementioned hypotheses and support the Ca(2+) uptake-mediated integrative role of in vivo mitochondria on neocortical activity.

  8. Pharmacokinetics of sevoflurane uptake into the brain.

    Science.gov (United States)

    Turner, M J; McCulloch, T J; Kennedy, R R; Baker, A B

    2004-12-01

    Two recent studies have examined the pharmacokinetics of sevoflurane in adults. Lu et al.(Pharmacokinetics of sevoflurane uptake into the brain and body, Anaesthesia 2003; 58: 951-6) observed that jugular bulb sevoflurane concentration initially rose unexpectedly rapidly and then approached arterial concentrations unexpectedly slowly, suggesting that a blood-brain diffusion barrier exists. They also observed a large alveolar-arterial sevoflurane gradient, suggesting that an alveolar-arterial diffusion barrier exists. Nakamura et al. (Predicted sevoflurane partial pressure in the brain with an uptake and distribution model: Comparison with the measured value in internal jugular vein blood. Journal of Clinical Monitoring and Computing 1999; 15: 299-305) found no diffusion barriers. We used a computer model to analyse both data sets and show that the observations of Lu et al. can be explained by contamination of jugular samples with extracerebral blood. It is possible that the alveolar-arterial gradients observed by Lu et al. are due to discrepancies in conversions between blood concentrations and gas partial pressures. Our study suggests that there is no blood-brain diffusion barrier for sevoflurane and that the data of Lu et al. must be interpreted with caution.

  9. Regulation of K uptake, water uptake, and growth of tomato during K starvation and recovery

    NARCIS (Netherlands)

    Amor, del F.M.; Marcelis, L.F.M.

    2004-01-01

    In order to analyze the dynamics of growth, water and K uptake, the effects of 1, 3 and 7 days of potassium starvation and the recovery capability during 7 days afterwards were investigated in vegetative tomato plants. After 7 days of K starvation, plant dry matter was reduced by 36% compared to con

  10. Regulation of nutrient uptake, water uptake and growth under calcium starvation and recovery

    NARCIS (Netherlands)

    Amor, del F.M.; Marcelis, L.F.M.

    2003-01-01

    To analyze the dynamics of growth, water and nutrient uptake, the effects of 1, 3 and 7 d of calcium starvation and the recovery capability during 7 d afterwards were investigated in vegetative tomato plants. Results showed that after only 1 d of Ca-starvation, leaf photosynthesis, leaf expansion an

  11. Quantitative fluorescence imaging reveals point of release for lipoproteins during LDLR-dependent uptake[S

    Science.gov (United States)

    Pompey, Shanica; Zhao, Zhenze; Luby-Phelps, Kate; Michaely, Peter

    2013-01-01

    The LDL receptor (LDLR) supports efficient uptake of both LDL and VLDL remnants by binding lipoprotein at the cell surface, internalizing lipoprotein through coated pits, and releasing lipoprotein in endocytic compartments before returning to the surface for further rounds of uptake. While many aspects of lipoprotein binding and receptor entry are well understood, it is less clear where, when, and how the LDLR releases lipoprotein. To address these questions, the current study employed quantitative fluorescence imaging to visualize the uptake and endosomal processing of LDL and the VLDL remnant β-VLDL. We find that lipoprotein release is rapid, with most release occurring prior to entry of lipoprotein into early endosomes. Published biochemical studies have identified two mechanisms of lipoprotein release: one that involves the β-propeller module of the LDLR and a second that is independent of this module. Quantitative imaging comparing uptake supported by the normal LDLR or by an LDLR variant incapable of β-propeller-dependent release shows that the β-propeller-independent process is sufficient for release for both lipoproteins but that the β-propeller process accelerates both LDL and β-VLDL release. Together these findings define where, when, and how lipoprotein release occurs and provide a generalizable methodology for visualizing endocytic handling in situ. PMID:23296879

  12. Alternative pathway for atmospheric particles growth.

    Science.gov (United States)

    Monge, Maria Eugenia; Rosenørn, Thomas; Favez, Olivier; Müller, Markus; Adler, Gabriela; Abo Riziq, Ali; Rudich, Yinon; Herrmann, Hartmut; George, Christian; D'Anna, Barbara

    2012-05-01

    Credible climate change predictions require reliable fundamental scientific knowledge of the underlying processes. Despite extensive observational data accumulated to date, atmospheric aerosols still pose key uncertainties in the understanding of Earth's radiative balance due to direct interaction with radiation and because they modify clouds' properties. Specifically, major gaps exist in the understanding of the physicochemical pathways that lead to aerosol growth in the atmosphere and to changes in their properties while in the atmosphere. Traditionally, the driving forces for particle growth are attributed to condensation of low vapor pressure species following atmospheric oxidation of volatile compounds by gaseous oxidants. The current study presents experimental evidence of an unaccounted-for new photoinduced pathway for particle growth. We show that heterogeneous reactions activated by light can lead to fast uptake of noncondensable Volatile Organic Compounds (VOCs) at the surface of particles when only traces of a photosensitizer are present in the seed aerosol. Under such conditions, size and mass increase; changes in the chemical composition of the aerosol are also observed upon exposure to volatile organic compounds such as terpenes and near-UV irradiation. Experimentally determined growth rate values match field observations, suggesting that this photochemical process can provide a new, unaccounted-for pathway for atmospheric particle growth and should be considered by models.

  13. Biochemical and physiological characterisation of the purine degradation pathway in plants

    OpenAIRE

    Werner, Andrea

    2013-01-01

    Plant growth is often limited by nitrogen availability in the soil. Not only do plants depend on efficient nitrogen uptake, they also require effective means to internally redistribute nitrogen during every stage of development. The purine degradation pathway contributes to this nitrogen recycling in plants. In tropical legumes it is also of central importance to the plants’ nitrogen supply under nitrogen-fixing conditions. This is the first time that the complete ureide degradation pathway h...

  14. FDG uptake in the pathologically proven papillary thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Sung; Yun, Mi Jin; Cho, Arthur; Lee, Jong Doo [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2007-02-15

    Metastatic thyroid cancers with I-131 uptake have been known to show no increase of FDG uptake whereas those without I-131 uptake tend to demonstrate increased uptake on PET. In this study, we evaluated the degree of FDG uptake in primary thyroid cancers of papillary histology before surgery. Forty FDG PET studies were performed on the patients who had papillary cancer proven by fine needle aspiration. The degree of FDG uptake was visually categorized as positive or negative (positive if the tumor showed discernible FDG; negative if the tumor didn't) and the peak standard uptake value (peak SUV) of the papillary thyroid cancer (PTC) were compared with the size of PTC. The mean size of 26 PTC with positive FDG uptake was 1.9{+-} 1.4 cm (0.5 {approx} 5 cm). In 13 PTC with negative FDG uptake, the mean size of those was 0.5 {+-} 0.2 cm (0.2 {approx} 0.9 cm). All PTC larger than 1 cm (2.5 {+-}1.4 cm, 1 {approx} 5 cm) have positive FDG uptake (peak SUV = 6.4 {+-} 5.7, 1.7 {approx} 22.7). Among the micropapillary thyroid cancer (microPTC; PTC smaller than 1 cm), 8 microPTC show positive FDG uptake (peak SUV = 2.9 {+-} 1.3, 1.7 {approx} 5.5), while 13 microPTC show negative finding (peak SUV 1.3 {+-} 0.2, 1.1{approx} 1.7). The size of microPTC with positive FDG uptake is significantly larger than that of microPTC with negative FDG uptake (0.7 {+-} 0.1cm vs 0.4 {+-} 0.2 cm, {rho} = 0.01). All PTCs larger than 1cm show positive FDG uptake in our study. In other words, thyroid lesions larger than 1cm with negative FDG uptake are unlikely to be PTC. So far, only poorly differentiated thyroid cancers are known to show increased FDG uptake. Our results seem to be contradictory to what is known in the literature. Further study is needed to understand better the significance of increased FDG uptake in PTC in relation to expression of NIS and GLUT.

  15. A systems toxicology approach on the mechanism of uptake and toxicity of MWCNT in Caenorhabditis elegans.

    Science.gov (United States)

    Eom, Hyun-Jeong; Roca, Carlos P; Roh, Ji-Yeon; Chatterjee, Nivedita; Jeong, Jae-Seong; Shim, Ilseob; Kim, Hyun-Mi; Kim, Phil-Je; Choi, Kyunghee; Giralt, Francesc; Choi, Jinhee

    2015-09-01

    The increased volumes of carbon nanotubes (CNTs) being utilized in industrial and biomedical processes carries with it an increased risk of unintentional release into the environment, requiring a thorough hazard and risk assessment. In this study, the toxicity of pristine and hydroxylated (OH-) multiwall CNTs (MWCNTs) was investigated in the nematode Caenorhabditis elegans using an integrated systems toxicology approach. To gain an insight into the toxic mechanism of MWCNTs, microarray and proteomics were conducted for C. elegans followed by pathway analyses. The results of pathway analyses suggested endocytosis, phagocytosis, oxidative stress and endoplasmic reticulum (ER) stress, as potential mechanisms of uptake and toxicity, which were subsequently investigated using loss-of-function mutants of genes of those pathways. The expression of phagocytosis related genes (i.e. ced-10 and rab-7) were significantly increased upon exposure to OH-MWCNT, concomitantly with the rescued toxicity by loss-of-function mutants of those genes, such as ced-10(n3246) and rab-7(ok511). An increased sensitivity of the hsp-4(gk514) mutant by OH-MWCNT, along with a decreased expression of hsp-4 at both gene and protein level suggests that MWCNTs may affect ER stress response in C. elegans. Collectively, the results implied phagocytosis to be a potential mechanism of uptake of MWCNTs, and ER and oxidative stress as potential mechanisms of toxicity. The integrated systems toxicology approach applied in this study provided a comprehensive insight into the toxic mechanism of MWCNTs in C. elegans, which may eventually be used to develop an "Adverse Outcome Pathway (AOP)", a recently introduced concept as a conceptual framework to link molecular level responses to higher level effects.

  16. Uptake and incorporation of pyrimidines in Euglena gracilis.

    Science.gov (United States)

    Wasternack, C H

    1976-08-01

    In photoorganotrophically grown cells of Euglena gracilis the uptake and incorporation degree of 12 different pyrimidines were tested. The rate of uptake of pyrimidines has distinct maxima in the late log phase and in the stationary phase of cell multiplication. The kinetics of uptake are linear in the first 2 h, do not show saturation at various concentrations and increase with the concetrations. No accumulation of the pyrimidines at various concentrations could be observed in the first 2 h of incubation. Membrane inhibitors as uranyl acetate inhibit the uptake of the reference substance alpha-AIB, which is wellknown transported by an active transport mechanism, but have no effect on uptake rate of uracil and cytosine. It could not be observed an energy requirement tested in temperature dependence and with electron transport inhibitors. Uptake of uridine, uracil, barbituric acid and alpha-AIB is inhibited by cycloheximide in a different manner after 5 - 10 min.

  17. Uptake of thallium-201 in enlarged thyroid glands. Concise communication

    Energy Technology Data Exchange (ETDEWEB)

    Fukuchi, M.; Kido, A.; Hyodo, K.; Tachibana, K.; Onoue, K.; Morita, T.; Nagai, K.

    1979-08-01

    We have investigated the thyroid uptake of Tl-201 in 37 patients with various types of goiter, and in six with normal thyroids. Significant thallium uptake was found in all cases in which there was thyroid enlargement, including Graves' disease, toxic thyroid nodule, primary hypothyroidism, simple goiter, Hashimoto's disease, thyroid carcinoma, and thyroid adenoma. If goiter was absent, however, there was no demonstrable uptake - e.g., in secondary hypothyroidism, subacute thyroiditis, and the normal controls. Thallium uptake did not correlate with thyroid function tests such as BMR, T/sub 3/-RU, T/sub 3/, T/sub 4/, TSH, antithyroid antibodies, or the 24-hr I-131 uptake. In 23 patients with diffuse goiter, on the other hand, maximum Tl-201 uptake correlated well with thyroid weight: r = 0.836 (p < 0.001); y = 0.02 x + 0.06.

  18. Aquaglyceroporins are involved in uptake of arsenite into murine gastrointestinal tissues.

    Science.gov (United States)

    Wang, Chun; Chen, Gang; Jiang, Junkang; Qiu, Lianglin; Hosoi, Kazuo; Yao, Chenjuan

    2009-01-01

    Aquaglyceroporins (AQGPs) are members of aquaporin (AQP) family and belong to a subgroup of this water channel family; they are transmembrane proteins that transport water as well as glycerol and other solutes of small molecules. Recent studies have also identified that AQGPs are important transporters of trivalent metalloid in some mammalian cells. However, the uptake routes of arsenite in mammals are still less defined. In this study, to understand the routes of arsenite intake in mammals, mice were treated with Hg(II), glycerol, and As(III) and uptake of As(III) into the gastrointestinal tissues was measured. The level of inorganic arsenic (iAs) in gastrointestinal tissues after As(III) stimulation was much higher than Hg(II) +As(III) or glycerol+As(III) group. RT-PCR results showed that AQGPs were extensively expressed in gastrointestinal tissues of mice. We also treated Caco-2 cells with Hg(II) and As(III); the level of iAs in a group treated with Hg(II)+As(III) decreased compared with As(III)-treated group. Our results suggested that AQGPs could be important transporters in arsenite uptake into gastrointestinal tissues of mice, but more data are need to prove if AQGPs is the only pathway involved in As transport in mammals or just one of them.

  19. External stimulation by nanosecond pulsed electric fields to enhance cellular uptake of nanoparticles

    Science.gov (United States)

    Franklin, Samantha; Beier, Hope T.; Ibey, Bennett L.; Nash, Kelly

    2015-03-01

    As an increasing number of studies use gold nanoparticles (AuNPs) for potential medicinal, biosensing and therapeutic applications, the synthesis and use of readily functional, bio-compatible nanoparticles is receiving much interest. For these efforts, the particles are often taken up by the cells to allow for optimum sensing or therapeutic measures. This process typically requires incubation of the particles with the cells for an extended period. In an attempt to shorten and control this incubation, we investigated whether nanosecond pulsed electric field (nsPEF) exposure of cells will cause a controlled uptake of the particles. NsPEF are known to induce the formation of nanopores in the plasma membrane, so we hypothesized that by controlling the number, amplitude or duration of the nsPEF exposure, we could control the size of the nanopores, and thus control the particle uptake. Chinese hamster ovary (CHO-K1) cells were incubated sub-10 nm AuNPs with and without exposure to 600-ns electrical pulses. Contrary to our hypothesis, the nsPEF exposure was found to actually decrease the particle uptake in the exposed cells. This result suggests that the nsPEF exposure may be affecting the endocytotic pathway and processes due to membrane disruption.

  20. Substrate uptake and subcellular compartmentation of anoxic cholesterol catabolism in Sterolibacterium denitrificans.

    Science.gov (United States)

    Lin, Ching-Wen; Wang, Po-Hsiang; Ismail, Wael; Tsai, Yu-Wen; El Nayal, Ashraf; Yang, Chia-Ying; Yang, Fu-Chun; Wang, Chia-Hsiang; Chiang, Yin-Ru

    2015-01-09

    Cholesterol catabolism by actinobacteria has been extensively studied. In contrast, the uptake and catabolism of cholesterol by Gram-negative species are poorly understood. Here, we investigated microbial cholesterol catabolism at the subcellular level. (13)C metabolomic analysis revealed that anaerobically grown Sterolibacterium denitrificans, a β-proteobacterium, adopts an oxygenase-independent pathway to degrade cholesterol. S. denitrificans cells did not produce biosurfactants upon growth on cholesterol and exhibited high cell surface hydrophobicity. Moreover, S. denitrificans did not produce extracellular catabolic enzymes to transform cholesterol. Accordingly, S. denitrificans accessed cholesterol by direction adhesion. Cholesterol is imported through the outer membrane via a putative FadL-like transport system, which is induced by neutral sterols. The outer membrane steroid transporter is able to selectively import various C27 sterols into the periplasm. S. denitrificans spheroplasts exhibited a significantly higher efficiency in cholest-4-en-3-one-26-oic acid uptake than in cholesterol uptake. We separated S. denitrificans proteins into four fractions, namely the outer membrane, periplasm, inner membrane, and cytoplasm, and we observed the individual catabolic reactions within them. Our data indicated that, in the periplasm, various periplasmic and peripheral membrane enzymes transform cholesterol into cholest-4-en-3-one-26-oic acid. The C27 acidic steroid is then transported into the cytoplasm, in which side-chain degradation and the subsequent sterane cleavage occur. This study sheds light into microbial cholesterol metabolism under anoxic conditions.

  1. Non-specific cellular uptake of surface-functionalized quantum dots

    Energy Technology Data Exchange (ETDEWEB)

    Kelf, T A; Sreenivasan, V K A; Sun, J; Goldys, E M; Zvyagin, A V [MQ Photonics Centre, Faculty of Science, Macquarie University, Sydney (Australia); Kim, E J, E-mail: azvyagin@science.mq.edu.au [Department of Science Education-Chemical Education Major, Daegu University, Gyeonbuk (Korea, Republic of)

    2010-07-16

    We report a systematic empirical study of nanoparticle internalization into cells via non-specific pathways. The nanoparticles were comprised of commercial quantum dots (QDs) that were highly visible under a fluorescence confocal microscope. Surface-modified QDs with basic biologically significant moieties, e.g. carboxyl, amino, and streptavidin, were used, in combination with surface derivatization with polyethylene glycol (PEG) for a range of immortalized cell lines. Internalization rates were derived from image analysis and a detailed discussion about the effect of nanoparticle size, charge and surface groups is presented. We find that PEG derivatization dramatically suppresses the non-specific uptake while PEG-free carboxyl and amine functional groups promote QD internalization. These uptake variations displayed a remarkable consistency across different cell types. The reported results are important for experiments concerned with cellular uptake of surface-functionalized nanomaterials, both when non-specific internalization is undesirable and when it is intended for material to be internalized as efficiently as possible.

  2. Radiocesium uptake, trophic transfer, and exposure in three estuarine fish with contrasting feeding habits.

    Science.gov (United States)

    Pan, Ke; Wang, Wen-Xiong

    2016-11-01

    This study investigated the effects of different environmental factors on (137)Cs uptake in three subtropical estuarine fish, and the trophic transfer of (137)Cs in the fish from different preys. Our data showed that salinity, potassium, and temperature had appreciable effects on the dissolved uptake of (137)Cs in the fish, but no conclusive relationship was found between the effects of salinity and potassium concentration on the uptake. The dietary assimilation of (137)Cs was 51-55% in the omnivorous fish Siganus fuscescens when fed with macroalgae or bivalve tissues, and was much lower than those in carnivorous fish Sebastiscus marmoratus and Jarbua terapon (70-79%). Dietary pathway dominated the (137)Cs accumulation in the omnivorous and carnivorous fish, both of which exhibited strong potential to biomagnify (137)Cs from their preys. Using the biokinetic model, we demonstrated that salinity and temperature only had minor effects on the overall accumulation of (137)Cs in carnivorous species living in estuarine environment. Modeling calculation suggested that it would take 37-80 days for the fish to reach 95% of steady-state concentration, and lower somatic growth increased the time to reach steady-state in the fish.

  3. Uptake of inorganic mercury by human locus ceruleus and corticomotor neurons: implications for amyotrophic lateral sclerosis

    Science.gov (United States)

    2013-01-01

    Background Environmental toxins are suspected to play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS). In an attempt to determine which pathways these toxins can use to enter motor neurons we compared the distribution of mercury in the CNS of a human and of mice that had been exposed to inorganic mercury. Results In the human who had been exposed to metallic mercury, mercury was seen predominantly in the locus ceruleus and corticomotor neurons, as well as in scattered glial cells. In mice that had been exposed to mercury vapor or mercuric chloride, mercury was present in lower motor neurons in the spinal cord and brain stem. Conclusions In humans, inorganic mercury can be taken up predominantly by corticomotor neurons, possibly when the locus ceruleus is upregulated by stress. This toxin uptake into corticomotor neurons is in accord with the hypothesis that ALS originates in these upper motor neurons. In mice, inorganic mercury is taken up predominantly by lower motor neurons. The routes toxins use to enter motor neurons depends on the nature of the toxin, the duration of exposure, and possibly the amount of stress (for upper motor neuron uptake) and exercise (for lower motor neuron uptake) at the time of toxin exposure. PMID:24252585

  4. Leucaena leucocephala fruit aqueous extract stimulates adipogenesis, lipolysis, and glucose uptake in primary rat adipocytes.

    Science.gov (United States)

    Kuppusamy, Umah Rani; Arumugam, Bavani; Azaman, Nooriza; Jen Wai, Chai

    2014-01-01

    Leucaena leucocephala had been traditionally used to treat diabetes. The present study was designed to evaluate in vitro "insulin-like" activities of Leucaena leucocephala (Lam.) deWit. aqueous fruit extract on lipid and glucose metabolisms. The ability of the extract to stimulate adipogenesis, inhibit lipolysis, and activate radio-labeled glucose uptake was assessed using primary rat adipocytes. Quantitative Real-Time RT-PCR was performed to investigate effects of the extract on expression levels of genes (protein kinases B, AKT; glucose transporter 4, GLUT4; hormone sensitive lipase, HSL; phosphatidylinositol-3-kinases, PI3KA; sterol regulatory element binding factor 1, Srebp1) involved in insulin-induced signaling pathways. L. leucocephala aqueous fruit extract stimulated moderate adipogenesis and glucose uptake into adipocytes when compared to insulin. Generally, the extract exerted a considerable level of lipolytic effect at lower concentration but decreased gradually at higher concentration. The findings concurred with RT-PCR analysis. The expressions of GLUT4 and HSL genes were upregulated by twofold and onefold, respectively, whereas AKT, PI3KA, and Srebp1 genes were downregulated. The L. leucocephala aqueous fruit extract may be potentially used as an adjuvant in the treatment of Type 2 diabetes mellitus and weight management due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

  5. Uptake dynamics of inorganic mercury and methylmercury by the earthworm Pheretima guillemi.

    Science.gov (United States)

    Dang, Fei; Zhao, Jie; Zhou, Dongmei

    2016-02-01

    Mercury uptake dynamics in the earthworm Pheretima guillemi, including the dissolved uptake rate constant (ku) from pore-water and assimilation efficiencies (AEs) from mercury-contaminated soil, was quantified in this study. Dissolved uptake rate constants were 0.087 and 0.553 L g(-1) d(-1) for inorganic mercury (IHg) and methylmercury (MeHg), respectively. Assimilation efficiency of IHg in field-contaminated soil was 7.2%, lower than 15.4% of spiked soil. In contrast, MeHg exhibited comparable AEs for both field-contaminated and spiked soil (82.4-87.2%). Within the framework of biodynamic model, we further modelled the exposure pathways (dissolved exposure vs soil ingestion) to source the accumulated mercury in Pheretima guillemi. The model showed that the relative importance of soil ingestion to mercury bioaccumulation depended largely on mercury partitioning coefficients (K(d)), and was also influenced by soil ingestion rate of earthworms. In the examined field-contaminated soil, almost (>99%) accumulated IHg and MeHg was predicted to derive from soil ingestion. Therefore, soil ingestion should be carefully considered when assessing mercury exposure risk to earthworms.

  6. Leucaena leucocephala Fruit Aqueous Extract Stimulates Adipogenesis, Lipolysis, and Glucose Uptake in Primary Rat Adipocytes

    Directory of Open Access Journals (Sweden)

    Umah Rani Kuppusamy

    2014-01-01

    Full Text Available Leucaena leucocephala had been traditionally used to treat diabetes. The present study was designed to evaluate in vitro “insulin-like” activities of Leucaena leucocephala (Lam. deWit. aqueous fruit extract on lipid and glucose metabolisms. The ability of the extract to stimulate adipogenesis, inhibit lipolysis, and activate radio-labeled glucose uptake was assessed using primary rat adipocytes. Quantitative Real-Time RT-PCR was performed to investigate effects of the extract on expression levels of genes (protein kinases B, AKT; glucose transporter 4, GLUT4; hormone sensitive lipase, HSL; phosphatidylinositol-3-kinases, PI3KA; sterol regulatory element binding factor 1, Srebp1 involved in insulin-induced signaling pathways. L. leucocephala aqueous fruit extract stimulated moderate adipogenesis and glucose uptake into adipocytes when compared to insulin. Generally, the extract exerted a considerable level of lipolytic effect at lower concentration but decreased gradually at higher concentration. The findings concurred with RT-PCR analysis. The expressions of GLUT4 and HSL genes were upregulated by twofold and onefold, respectively, whereas AKT, PI3KA, and Srebp1 genes were downregulated. The L. leucocephala aqueous fruit extract may be potentially used as an adjuvant in the treatment of Type 2 diabetes mellitus and weight management due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

  7. Uptake of Sulfadiazine Sulfonamide from Water by Clinoptilolite

    OpenAIRE

    Zhaohui Li; Christie Stockwell; Jacqueline Niles; Skylar Minegar; Hanlie Hong

    2013-01-01

    The interactions between sulfadiazine (SDZ), a sulfonamide antibiotic, and clinoptilolite, a hydrophilic zeolite, were investigated under batch experimental conditions. The uptake of SDZ on the zeolite followed a linear sorption isotherm under neutral pH conditions. Higher SDZ uptake on the zeolite was observed when solution pH was below the or above the values of SDZ, while minimal SDZ uptake was observed when the solution pH was between the and values of SDZ. These observations suggeste...

  8. Coupling of Groundwater Transport and Plant Uptake Models

    DEFF Research Database (Denmark)

    Rein, Arno; Bauer-Gottwein, Peter; Trapp, Stefan

    2010-01-01

    Plants significantly influence contaminant transport and fate. Important processes are uptake of soil and groundwater contaminants, as well as biodegradation in plants and their root zones. Models for the prediction of chemical uptake into plants are required for the setup of mass balances...... to groundwater transport simulation tools. Exemplary simulations of plant uptake were carried out, in order to estimate concentrations in the soilplant- air system and the influence of plants on contaminant mass fluxes from soil to groundwater....

  9. DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl

  10. The Uptake by Plants of Diethylstilboestrol and of Its Glucuronide

    DEFF Research Database (Denmark)

    Gregers Hansen, B.

    1964-01-01

    The uptake of diethylstilboestrol and its glucuronide by plants could, under certain circumstances, present a potential health hazard. The relative uptake of the two compounds has therefore been studied in rye grass, red clover, mushrooms, and maize in pot and water culture experiments. It is con......The uptake of diethylstilboestrol and its glucuronide by plants could, under certain circumstances, present a potential health hazard. The relative uptake of the two compounds has therefore been studied in rye grass, red clover, mushrooms, and maize in pot and water culture experiments...

  11. Water uptake in the cat flea Ctenocephalides felis (Pulicidae: Siphonaptera).

    Science.gov (United States)

    Thiemann, T; Fielden, L J; Kelrick, M I

    2003-12-01

    To counteract water loss due to excretion, cuticular transpiration and respiration, various groups of arthropods have developed mechanisms for active uptake of water vapor from unsaturated air. In this study, active uptake capabilities and water loss rates were examined in the various developmental stages of the cat flea, Ctenocephalides felis. To determine critical equilibrium humidity, the lowest relative humidity at which active water uptake can occur, pre-desiccated immature and adult fleas were placed in a series of humidity regimes ranging from 44 to 93% RH. Active uptake occurred in larval stages at relative humidities above 53% and in pre-pupae at 75-93% RH. Pupae and adults did not demonstrate active uptake at any humidity. Optimal uptake for larvae occurred between 20 and 30 degrees C. When placed over Drierite (water loss than pre-pupal and pupal stages. Active water uptake is necessary to ensure proper development of the larvae of C. felis. Active uptake ceases after the larval-pupal ecdysis and it appears that adults have lost the ability to actively uptake water.

  12. Contraction stimulates muscle glucose uptake independent of atypical PKC.

    Science.gov (United States)

    Yu, Haiyan; Fujii, Nobuharu L; Toyoda, Taro; An, Ding; Farese, Robert V; Leitges, Michael; Hirshman, Michael F; Mul, Joram D; Goodyear, Laurie J

    2015-11-01

    Exercise increases skeletal muscle glucose uptake, but the underlying mechanisms are only partially understood. The atypical protein kinase C (PKC) isoforms λ and ζ (PKC-λ/ζ) have been shown to be necessary for insulin-, AICAR-, and metformin-stimulated glucose uptake in skeletal muscle, but not for treadmill exercise-stimulated muscle glucose uptake. To investigate if PKC-λ/ζ activity is required for contraction-stimulated muscle glucose uptake, we used mice with tibialis anterior muscle-specific overexpression of an empty vector (WT), wild-type PKC-ζ (PKC-ζ(WT)), or an enzymatically inactive T410A-PKC-ζ mutant (PKC-ζ(T410A)). We also studied skeletal muscle-specific PKC-λ knockout (MλKO) mice. Basal glucose uptake was similar between WT, PKC-ζ(WT), and PKC-ζ(T410A) tibialis anterior muscles. In contrast, in situ contraction-stimulated glucose uptake was increased in PKC-ζ(T410A) tibialis anterior muscles compared to WT or PKC-ζ(WT) tibialis anterior muscles. Furthermore, in vitro contraction-stimulated glucose uptake was greater in soleus muscles of MλKO mice than WT controls. Thus, loss of PKC-λ/ζ activity increases contraction-stimulated muscle glucose uptake. These data clearly demonstrate that PKC-λζ activity is not necessary for contraction-stimulated glucose uptake.

  13. Short-term uptake of heavy metals by periphyton algae

    Energy Technology Data Exchange (ETDEWEB)

    Vymazal, J.

    1984-12-31

    The utilization of periphyton for the removal of heavy metals from enriched small streams has been examined. By means of short-term batch laboratory experiments the courses of metal uptake have been studied. For uptake study naturally growing periphyton community and periphytic filamentous algae Cladophora glomerata and Oedogonium rivulare have been used. Uptakes of nine heavy metals (Pb, Cd, Cu, Co, Cr, Ni, Zn, Fe and Mn) have been determined during four hours exposure. In addition the influence of humic substances on heavy metals uptake has been determined. Uptake of all metals increased during four hours exposure but not in the same way. Some metals were removed continuously (Ni, Cr, Fe and Mn), other metals were removed more rapidly during the first hour or first two hours of exposure and then only slight removal continued (Cu, Pb, Cd, Co). Uptake of Zn was rather unambiguous. Results of these experiments suggest that the course of uptake for individual metals could be similar for most periphyton algae. It was established that humic substances significantly reduce heavy metals uptake. The highest decrease of uptake was observed in Cu, Cr, Co and Cd. The results of model experiments are being tested in a pilot scale with respect to the demands of engineering practice. (J.R.)

  14. Evaluation of diffuse lung uptake in radiogallium scans

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Tetsuya (Toyama Medical and Pharmaceutical Univ. (Japan). Faculty of Medicine); Tatsuno, Ikuo

    1982-08-01

    Diffuse lung uptake of radiogallium was observed in 12 of 239 scans (5.0%). All of 12 patients received radiation therapy (average dose: 34Gy) and 9 of 12 patients were also placed on chemotherapy (average duration: 7 weeks). The most common cause of diffuse lung uptake was infection which included interstitial pneumonitis and the second was pleuritis. Of the 12 patients, 7 patients died an average of 3.6 months later since diffuse lung uptake was observed. Therefore, when we recognize diffuse lung uptake, we must perform closer examination and appropriate therapy as early as possible.

  15. Uptake of the Influenza Vaccination in Pregnancy

    LENUS (Irish Health Repository)

    Crosby, DA

    2016-09-01

    Influenza is caused by a highly infectious RNA virus, which usually occurs in a seasonal pattern with epidemics in the winter months. The objective of this study was to determine the uptake of the influenza vaccine in a pregnant population and ascertain the reasons why some women did not receive it. A prospective cohort study was conducted over a two-week period in January 2016 in the National Maternity Hospital Dublin, a tertiary referral maternity hospital delivering over 9000 infants per year. There were 504 women studied over the 2-week period. Overall, 197(39.1%) women received the vaccine at a mean gestational age 20.9 weeks (SD 7.0). Given the increased rates of influenza in the community and the associated implications for mother and infant, it is important that pregnant women are educated regarding the risks of influenza in pregnancy and encourage this cohort to be vaccinated.

  16. Cellular uptake and trafficking of antisense oligonucleotides.

    Science.gov (United States)

    Crooke, Stanley T; Wang, Shiyu; Vickers, Timothy A; Shen, Wen; Liang, Xue-Hai

    2017-03-01

    Antisense oligonucleotides (ASOs) modified with phosphorothioate (PS) linkages and different 2' modifications can be used either as drugs (e.g., to treat homozygous familial hypercholesterolemia and spinal muscular atrophy) or as research tools to alter gene expression. PS-ASOs can enter cells without additional modification or formulation and can be designed to mediate sequence-specific cleavage of different types of RNA (including mRNA and non-coding RNA) targeted by endogenous RNase H1. Although PS-ASOs function in both the cytoplasm and nucleus, localization to different subcellular regions can affect their therapeutic potency. Cellular uptake and intracellular distribution of PS ASOs are mediated by protein interactions. The main proteins involved in these processes have been identified, and intracellular sites in which PS ASOs are active, or inactive, cataloged.

  17. Uptake of water droplets by nonwetting capillaries

    CERN Document Server

    Willmott, Geoff R; Hendy, Shaun C

    2010-01-01

    We present direct experimental evidence that water droplets can spontaneously penetrate non-wetting capillaries, driven by the action of Laplace pressure due to high droplet curvature. Using high-speed optical imaging, microcapillaries of radius 50 to 150 micron, and water microdroplets of average radius between 100 and 1900 micron, we demonstrate that there is a critical droplet radius below which water droplets can be taken up by hydrophobised glass and polytetrafluoroethylene (PTFE) capillaries. The rate of capillary uptake is shown to depend strongly on droplet size, with smaller droplets being absorbed more quickly. Droplet size is also shown to influence meniscus motion in a pre-filled non-wetting capillary, and quantitative measurements of this effect result in a derived water-PTFE static contact angle between 96 degrees and 114 degrees. Our measurements confirm recent theoretical predictions and simulations for metal nanodroplets penetrating carbon nanotubes (CNTs). The results are relevant to a wide ...

  18. Sertraline reduces glutamate uptake in human platelets.

    Science.gov (United States)

    Rodrigues, Débora Olmedo; Bristot, Ivi Juliana; Klamt, Fábio; Frizzo, Marcos Emílio

    2015-12-01

    Mitochondrial damage and declines in ATP levels have been recently attributed to sertraline. The effects of sertraline on different parameters were investigated in washed platelets from 18 healthy male volunteers, after 24h of drug exposure. Sertraline toxicity was observed only at the highest concentrations, 30 and 100 μM, which significantly reduced platelet viability to 76 ± 3% and 20 ± 2%, respectively. The same concentrations significantly decreased total ATP to 73 ± 3% and 13 ± 2%, respectively. Basal values of glycogen were not significantly affected by sertraline treatment. Glutamate uptake was significantly reduced after treatment with 3, 30 and 100 μM, by 28 ± 6%, 32 ± 5% and 54 ± 4%, respectively. Our data showed that sertraline at therapeutic concentrations does not compromise platelet viability and ATP levels, but they suggest that in a situation where extracellular glutamate levels are potentially increased, sertraline might aggravate an excitotoxic condition.

  19. ORCID Uptake in the Astronomical Community

    Science.gov (United States)

    Holmquist, Jane

    2015-08-01

    The IAU General Assembly provides librarians with a unique opportunity to interact with astronomers from all over the world. From the perspective of an ORCID Ambassador, the Focus Group Meeting on "Scholarly Publication in Astronomy" also provides an opportunity to demonstrate the cooperation and collaboration needed by individual astronomers, societies, librarians, publishers and bibliographic database providers to achieve universal adoption of ORCID, a standard unique identifier for authors, just as the DOI (digital object identifier) has been adopted for each journal article published.I propose to 1) present at the Focus Group Meeting an update on the uptake of ORCID by members of the astronomical community and 2) set up a small station (TBA) near the IAU registration area where librarians can show researchers how to register for an ORCID in 30 seconds.

  20. Heme uptake by Leishmania amazonensis is mediated by the transmembrane protein LHR1.

    Directory of Open Access Journals (Sweden)

    Chau Huynh

    Full Text Available Trypanosomatid protozoan parasites lack a functional heme biosynthetic pathway, so must acquire heme from the environment to survive. However, the molecular pathway responsible for heme acquisition by these organisms is unknown. Here we show that L. amazonensis LHR1, a homolog of the C. elegans plasma membrane heme transporter HRG-4, functions in heme transport. Tagged LHR1 localized to the plasma membrane and to endocytic compartments, in both L. amazonensis and mammalian cells. Heme deprivation in L. amazonensis increased LHR1 transcript levels, promoted uptake of the fluorescent heme analog ZnMP, and increased the total intracellular heme content of promastigotes. Conversely, deletion of one LHR1 allele reduced ZnMP uptake and the intracellular heme pool by approximately 50%, indicating that LHR1 is a major heme importer in L. amazonensis. Viable parasites with correct replacement of both LHR1 alleles could not be obtained despite extensive attempts, suggesting that this gene is essential for the survival of promastigotes. Notably, LHR1 expression allowed Saccharomyces cerevisiae to import heme from the environment, and rescued growth of a strain deficient in heme biosynthesis. Syntenic genes with high sequence identity to LHR1 are present in the genomes of several species of Leishmania and also Trypanosoma cruzi and Trypanosoma brucei, indicating that therapeutic agents targeting this transporter could be effective against a broad group of trypanosomatid parasites that cause serious human disease.

  1. Stable fluorescence conjugation of ZnO nanoparticles and their size dependent cellular uptake.

    Science.gov (United States)

    Kim, Kyoung-Min; Kim, Min-Kyu; Paek, Hee-Jeong; Choi, Soo-Jin; Oh, Jae-Min

    2016-09-01

    We evaluated size dependent cellular uptake of ZnO nanoparticles utilizing stably introduced Cy5.5, which emits long-wavelength fluorescence. Through (3-aminopropyl)triethoxysilane modification, ZnO nanoparticles of different sizes (20 and 70nm) were functionalized with amine moiety, which was further reacted with Cy5.5-N-hydroxylsuccinimide ester to make covalently conjugated Cy5.5 dye on ZnO nanoparticles. Field emission-scanning electron microscopic images revealed that average particle size as well as particle morphology of ZnO nanoparticles were not altered by Cy5.5 conjugation. Zeta potential measurement confirmed that the positive surface charge of ZnO nanoparticles was well preserved after successive conjugation reactions. Based on infrared, ultraviolet-visible light and photoluminescence spectroscopies, we verify that the Cy5.5 was stably introduced to ZnO nanoparticles without serious aggregation. Surface conjugated Cy5.5 showed high stability in deionized water, phosphate buffered saline and cell culture medium, showing less than 2% of release during 85h. Confocal microscopy and fluorescence-activated cell sorting analysis demonstrated that smaller ZnO nanoparticles were more taken up in greater quantities by HaCaT cells. Moreover, systematic study on cellular uptake pathway showed that smaller ZnO nanoparticles were internalized into cells mainly by clathrin-mediated endocytosis, while larger ZnO nanoparticles entered cells via several pathways.

  2. Physiological controls on seawater uptake and calcification in the benthic foraminifer Ammonia tepida

    Directory of Open Access Journals (Sweden)

    J. Bijma

    2009-07-01

    Full Text Available During the last decades conceptual models describing the calcification pathway of foraminifera and its physiological controls have been developed. These models are derived by combining data of tracer experiments and microscopic observations obtained from different species. Although vital for understanding their calcitic isotopic and trace elemental composition, direct observational evidence on e.g. seawater vacuolization and intracellular Ca-cycling is lacking for most species. To analyse the relation between seawater uptake and calcification, we incubated juveniles of the cosmopolitan benthic, intertidal foraminifer Ammonia tepida with various fluorescent probes. Visualizing the membranes of endocytosed vesicles was achieved by incubating specimens with the dye FM1-43, while Ca ions in the calcification vesicles were detected by the Ca2+-indicator Fluo3-AM. Uptake of fluorescent latex-beads (0.5 μm diameter and subsequent transport to the site of chamber formation provided additional evidence that endocytosis is related to the calcification pathway and not merely involved in membrane cycling. Our results show for the first time that endocytosis of seawater is part of the calcification process in Ammonia tepida. Data on the intracellular calcium ion-cycling allowed for calculating a preliminary cellular Ca-budget during foraminiferal calcification.

  3. Selective cellular uptake and induction of apoptosis of cancer-targeted selenium nanoparticles.

    Science.gov (United States)

    Huang, Yanyu; He, Lizhen; Liu, Wen; Fan, Cundong; Zheng, Wenjie; Wong, Yum-Shing; Chen, Tianfeng

    2013-09-01

    Selenium nanoparticles (SeNPs) have garnered a great deal of attention as potential cancer therapeutic payloads. However, the in vivo targeting drug delivery has been challenging. Herein, we describe the synthesis of tansferrin (Tf)-conjugated SeNPs and its use as a cancer-targeted drug delivery system to achieve enhanced cellular uptake and anticancer efficacy. Tf as targeting ligand significantly enhances the cellular uptake of doxorubicin (DOX)-loaded SeNPs through clathrin-mediated and caveolae/lipid raft-mediated endocytosis in cancer cells overexpressing transferrin receptor, and increases their selectivity between cancer and normal cells. DOX-loaded and Tf-conjugated SeNPs (Tf-SeNPs) exhibits unprecedented enhanced cytotoxicity toward cancer cells through induction of apoptosis with the involvement of intrinsic and extrinsic pathways. Internalized Tf-SeNPs triggers intracellular ROS overproduction, thus activates p53 and MAPKs pathways to promote cell apoptosis. In the nude mice xenograft experiment, Tf-SeNPs significantly inhibits the tumor growth via induction of p53-mediated apoptosis. This cancer-targeted design of SeNPs opens a new path for synergistic treating of cancer with higher efficacy and decreased side effects.

  4. Molecular identification and cellular localization of a potential transport system involved in cystine/cysteine uptake in human lenses.

    Science.gov (United States)

    Lim, Julie C; Lam, Leo; Li, Bo; Donaldson, Paul J

    2013-11-01

    In this study we have sought to identify whether cystine uptake mechanisms previously identified in the rat lens are also found in the human lens. Using a combination of reverse transcriptase PCR, Western blotting and immunohistochemistry, we show that the light chain subunit of the cystine/glutamate exchanger (XC-), xCT, and members of the glutamate transporter family (XAG) which include the Excitatory Amino Acid Transporter 4 (EAAT4) and the Alanine Serine Cysteine Transporter 2 (ASCT2) are all present at the transcript and protein level in human lenses. We demonstrate that in young lenses xCT, EAAT4 and ASCT2 are expressed in all regions indicating that a potential cystine uptake pathway similar to that found in the rat might also exist in human lenses. However, with increasing age, the immunolabeling for all transporters decreases, with no xCT labelling detected in the centre of old donor lenses. Our results show that XC- and EAAT4/ASCT2 may work together to mediate cystine uptake in the lens core of young human lenses. This suggests that the lens contains uptake mechanisms that are capable of accumulating cystine/cysteine in the lens centre where cysteine can be used as an antioxidant or cystine utilised as a source for protein-S-S-cysteine (PSSC) formation to buffer against oxidative stress. With increasing age, transporters in the lens core undergo age dependent post translational modifications. However, despite processing of these transporters with age, our results indicate that this cystine uptake pathway could account for the increased PSSC levels previously observed in the nucleus of older human lenses.

  5. Early changes in [{sup 18}F]FLT uptake after chemotherapy: an experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Dittmann, Helmut; Dohmen, Bernhard Matthias; Bartusek, Gabi; Pritzkow, Maren; Bares, Roland [Department of Nuclear Medicine, Eberhard-Karls-University, Roentgenweg 13, 72076 Tuebingen (Germany); Kehlbach, Rainer [Department of Diagnostic Radiology, Eberhard-Karls-University, Tuebingen (Germany); Sarbia, Mario [Institute of Pathology, Heinrich-Heine-University, Duesseldorf (Germany)

    2002-11-01

    -FU and MTX massively increase FLT accumulation per cell independent of dose, i.e. cytotoxicity. Early after treatment, this increase is not predictive of proliferation inhibition but reflects activated salvage pathway of DNA synthesis. By contrast, CDDP results in an early decline in FLT but not in FDG uptake. This drug-specific modulation of FLT uptake has to be taken into account in positron emission tomography studies using FLT for treatment monitoring. (orig.)

  6. A kinetic fluorescence assay reveals unusual features of Ca++ uptake in Plasmodium falciparum-infected erythrocytes

    Science.gov (United States)

    2014-01-01

    Background To facilitate development within erythrocytes, malaria parasites increase their host cell uptake of diverse solutes including Ca++. The mechanism and molecular basis of increased Ca++ permeability remains less well studied than that of other solutes. Methods Based on an appropriate Ca++ affinity and its greater brightness than related fluorophores, Fluo-8 was selected and used to develop a robust fluorescence-based assay for Ca++ uptake by human erythrocytes infected with Plasmodium falciparum. Results Both uninfected and infected cells exhibited a large Ca++-dependent fluorescence signal after loading with the Fluo-8 dye. Probenecid, an inhibitor of erythrocyte organic anion transporters, abolished the fluorescence signal in uninfected cells; in infected cells, this agent increased fluorescence via mechanisms that depend on parasite genotype. Kinetic fluorescence measurements in 384-well microplates revealed that the infected cell Ca++ uptake is not mediated by the plasmodial surface anion channel (PSAC), a parasite nutrient channel at the host membrane; it also appears to be distinct from mammalian Ca++ channels. Imaging studies confirmed a low intracellular Ca++ in uninfected cells and higher levels in both the host and parasite compartments of infected cells. Parasite growth inhibition studies revealed a conserved requirement for extracellular Ca++. Conclusions Nondestructive loading of Fluo-8 into human erythrocytes permits measurement of Ca++ uptake kinetics. The greater Ca++ permeability of cells infected with malaria parasites is apparent when probenecid is used to inhibit Fluo-8 efflux at the host membrane. This permeability is mediated by a distinct pathway and may be essential for intracellular parasite development. The miniaturized assay presented here should help clarify the precise transport mechanism and may identify inhibitors suitable for antimalarial drug development. PMID:24885754

  7. 7-O-methylaromadendrin stimulates glucose uptake and improves insulin resistance in vitro.

    Science.gov (United States)

    Zhang, Wei Yun; Lee, Jung-Jin; Kim, In-Su; Kim, Yohan; Park, Jeong-Sook; Myung, Chang-Seon

    2010-01-01

    The stimulation of glucose uptake into peripheral tissues is an important mechanism for the removal of glucose in blood and for the management of diabetes mellitus (DM). Since recent results have demonstrated the beneficial effects of flavonoids in relation to DM, this study was designed to examine the effects of 7-O-methylaromadendrin (7-O-MA), a flavonoid isolated from Inula viscosa, on glucose uptake into liver and fat tissue, and investigate the molecular mechanisms involved. 7-O-MA at 10 microM significantly stimulated insulin-induced glucose uptake measured by 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG) in both human hepatocellular liver carcinoma (HepG2) cells and differentiated 3T3-L1 adipocytes. Adipocyte-specific fatty acid binding protein (aP2) gene expression was increased by 7-O-MA in adipocytes, and both gene and protein level of peroxisome proliferator-activated receptor gamma2 (PPARgamma2) was also increased. Moreover, 7-O-MA stimulated the reactivation of insulin-mediated phosphorylation of phosphatidylinositol 3-kinase (PI3K)-linked protein kinase B (Akt/PKB) and adenosine 5'-monophosphate-activated protein kinase (AMPK) in high glucose-induced, insulin-resistant HepG2 cells, and this effect was blocked by either LY294002, a PI3K inhibitor, or compound C, an AMPK inhibitor. Therefore, these results suggest that 7-O-MA might stimulate glucose uptake via PPARgamma2 activation and improve insulin resistance via PI3K and AMPK-dependent pathways, and be a potential candidate for the management of type 2 DM.

  8. Pathway Commons, a web resource for biological pathway data.

    Science.gov (United States)

    Cerami, Ethan G; Gross, Benjamin E; Demir, Emek; Rodchenkov, Igor; Babur, Ozgün; Anwar, Nadia; Schultz, Nikolaus; Bader, Gary D; Sander, Chris

    2011-01-01

    Pathway Commons (http://www.pathwaycommons.org) is a collection of publicly available pathway data from multiple organisms. Pathway Commons provides a web-based interface that enables biologists to browse and search a comprehensive collection of pathways from multiple sources represented in a common language, a download site that provides integrated bulk sets of pathway information in standard or convenient formats and a web service that software developers can use to conveniently query and access all data. Database providers can share their pathway data via a common repository. Pathways include biochemical reactions, complex assembly, transport and catalysis events and physical interactions involving proteins, DNA, RNA, small molecules and complexes. Pathway Commons aims to collect and integrate all public pathway data available in standard formats. Pathway Commons currently contains data from nine databases with over 1400 pathways and 687,000 interactions and will be continually expanded and updated.

  9. Atmospheric nitrous oxide uptake in boreal spruce forest soil

    Science.gov (United States)

    Siljanen, Henri; Welti, Nina; Heikkinen, Juha; Biasi, Christina; Martikainen, Pertti

    2017-04-01

    Nitrous oxide (N2O) uptake from the atmosphere has been found in forest soils but environmental factors controlling the uptake and its atmospheric impact are poorly known. We measured N2O fluxes over growing season in a boreal spruce forest having control plots and plots with long nitrogen fertilization history. Also methane (CH4) fluxes were measured to compare the atmospheric impact of N2O and CH4fluxes. Soil chemical and physical characteristics and climatic conditions were measured as background data. Nitrous oxide consumption and uptake mechanisms were measured in complementary laboratory incubation experiments using stable isotope approaches. Gene transcript numbers of nitrous oxide reductase (nosZ) I and II genes were quantified along the incubation with elevated N2O atmosphere. The spruce forests without fertilization history showed highest N2O uptake rates whereas pine forest had low emissions. Nitrous oxide uptake correlated positively with soil moisture, high soil silt content, and low temperature. Nitrous oxide uptake varied seasonally, being highest in spring and autumn when temperature was low and water content was high. The spruce forest was sink for CH4.Methane fluxes were decoupled from the N2O fluxes (i.e. when the N2O uptake was high the CH4 uptake was low). By using GWP approach, the cooling effect of N2O uptake was on average 30% of the cooling effect of CH4 uptake in spruce forest without fertilization. Anoxic conditions promoted higher N2O consumption rates in all soils. Gene transcription of nosZ-I genes were activated at beginning of the incubation. However, atypical/clade-II nosZ was not detected. These results suggests, that also N2O uptake rates have to be considered when accounting for the GHG budget of spruce forests.

  10. The Haptoglobin-CD163-Heme Oxygenase-1 Pathway for Hemoglobin Scavenging

    DEFF Research Database (Denmark)

    Thomsen, Jens Haugbølle; Etzerodt, Anders; Svendsen, Pia

    2013-01-01

    The haptoglobin- (Hp-) CD163-heme oxygenase-1 (HO-1) pathway is an efficient captor-receptor-enzyme system to circumvent the hemoglobin (Hb)/heme-induced toxicity during physiological and pathological hemolyses. In this pathway, Hb tightly binds to Hp leading to CD163-mediated uptake of the complex...... and put pressure on backup protecting systems such as the hemopexin-CD91-HO pathway. The Hp-CD163-HO-1 pathway proteins are regulated by the acute phase mediator interleukin-6 (IL-6), but other regulatory factors indicate that this upregulation is a counteracting anti-inflammatory response during...... inflammation. The heme metabolites including bilirubin converted from biliverdin have overall an anti-inflammatory effect and thus reinforce the anti-inflammatory efficacy of the Hp-CD163-HO-1 pathway. Future studies of animal models of inflammation should further define the importance of the pathway...

  11. Silver Uptake, Distribution, and Effect on Calcium, Phosphorus, and Sulfur Uptake 1

    Science.gov (United States)

    Koontz, Harold V.; Berle, Karen L.

    1980-01-01

    Bean, corn, and tomato plants were grown in a nutrient solution labeled with 32P, 45Ca, or 35S and varying concentrations of AgNO3. Following a 6-hour treatment period, plants were harvested and analyzed. A low Ag+ concentration (50 nanomolar) inhibited the shoot uptake of the ions investigated. In the roots, Ca uptake increased whereas P and S uptake decreased. Autoradiograms of bean and corn plants, using 110mAg, showed that Ag+ was uniformly deposited in the bean shoot, but corn shoots had regions of high activity along the leaf margins and at the tips where guttation had occurred. Roots were heavily labeled and shoots (especially the new growth) continued to accumulate Ag+ even after the intact plant was returned to Ag-free solution. Silver was believed to be phloem-mobile since it was exported from a treated leaf. Bean plants removed one-half the Ag+ from 4 liters of nutrient solution containing 50 nanomolar AgNO3 within 1.5 hours, but took 16 hours for 20 liters of solution. Images PMID:16661185

  12. Uptake and depuration of 131I by the edible periwinkle Littorina littorea: uptake from seawater.

    Science.gov (United States)

    Vives i Batlle, J; Wilson, R C; McDonald, P; Parker, T G

    2005-01-01

    Uptake and depuration experiments for the edible periwinkle Littorina littorea have been performed using 131I-labelled seawater. Throughout the experimental phase the winkles were fed on unlabelled Chondrus crispus. 131I concentrations in winkles during uptake followed linear first-order kinetics with an uptake half-time of 11 days, whereas for depuration a triphasic sequence with biological half-lives of 4, 23 and 56 days was determined. In general, iodine turnover in winkles via labelled seawater appears to be slower than observed for other molluscs (2-3 days). Most of the activity prior to and after depuration is found to be in the shell, with indications that shell and soft parts accumulate and depurate 131I at a similar rate. The operculum displays the highest specific activity of all fractions with a concentration factor of 750 l kg(-1). Concentration factors for whole winkle, shell, soft parts and digestive gland are in the order of 40-60 l kg(-1), higher than the IAEA recommended CF value for iodine in molluscs of 10 l kg(-1). The 131I CF in winkles is closer to that of the conservative radionuclides 99Tc and 137Cs than the CF of the particle reactive radionuclides (239,240)Pu and 241Am.

  13. Uptake and depuration of {sup 131}I by the edible periwinkle Littorina littorea: uptake from seawater

    Energy Technology Data Exchange (ETDEWEB)

    Vives i Batlle, J. E-mail: Jordi.Vives@westlakes.ac.uk; Wilson, R.C.; McDonald, P.; Parker, T.G

    2004-09-01

    Uptake and depuration experiments for the edible periwinkle Littorina littorea have been performed using {sup 131}I-labelled seawater. Throughout the experimental phase the winkles were fed on unlabelled Chondrus crispus. {sup 131}I concentrations in winkles during uptake followed linear first-order kinetics with an uptake half-time of 11 days, whereas for depuration a triphasic sequence with biological half-lives of 4, 23 and 56 days was determined. In general, iodine turnover in winkles via labelled seawater appears to be slower than observed for other molluscs (2-3 days). Most of the activity prior to and after depuration is found to be in the shell, with indications that shell and soft parts accumulate and depurate {sup 131}I at a similar rate. The operculum displays the highest specific activity of all fractions with a concentration factor of 750 l kg{sup -1}. Concentration factors for whole winkle, shell, soft parts and digestive gland are in the order of 40-60 l kg{sup -1}, higher than the IAEA recommended CF value for iodine in molluscs of 10 l kg{sup -1}. The {sup 131}I CF in winkles is closer to that of the conservative radionuclides {sup 99}Tc and {sup 137}Cs than the CF of the particle reactive radionuclides {sup 239,240}Pu and {sup 241}Am.

  14. Astragalus polysaccharide stimulates glucose uptake in L6 myotubes through AMPK activation and AS160/TBC1D4 phosphorylation

    Institute of Scientific and Technical Information of China (English)

    Jian LIU; Si-tu YANG; Lang BU; Jing-ping OU-YANG; Jing-fang ZHANG; Jin-zhi LU; De-ling ZHANG; Ke LI; Ke SU; Jing WANG; Ye-min ZHANG; Nian WANG

    2013-01-01

    Aim:To establish the mechanism responsible for the stimulation of glucose uptake by Astragalus polysaccharide (APS),extracted from Astragalus membranaceus Bunge,in L6 myotubes in vitro.Methods:APS-stimulated glucose uptake in L6 myotubes was measured using the 2-deoxy-[3H]-D-glucose method.The adenine nucleotide contents in the cells were measured by HPLC.The phosphorylation of AMP-activated protein kinase (AMPK) and Akt substrate of 160 kDa (AS160) was examined using Western blot analysis.The cells transfected with 4P mutant AS160 (AS160-4P) were constructed using gene transfer approach.Results:Treatment of L6 myotubes with APS (100-1600 μg/mL) significantly increased glucose uptake in time-and concentration-dependent manners.The maximal glucose uptake was reached in the cells treated with APS (400 μg/mL) for 36 h.The APS-stimulated glucose uptake was significantly attenuated by pretreatment with Compound C,a selective AMPK inhibitor or in the cells overexpressing AS160-4P.Treatment of L6 myotubes with APS strongly promoted the activation of AMPK.We further demonstrated that either Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) or liver kinase B1 (LKB1) mediated APS-induced activation of AMPK in L6 myotubes,and the increased cellular AMP:ATP ratio was also involved.Treatment of L6 myotubes with APS robustly enhanced the phosphorylation of AS160,which was significantly attenuated by pretreatment with Compound C.Conclusion:Our results demonstrate that APS stimulates glucose uptake in L6 myotubes through the AMP-AMPK-AS160 pathway,which may contribute to its hypoglycemic effect.

  15. Exploring levels of hexosamine biosynthesis pathway intermediates and protein kinase C isoforms in muscle and fat tissue of Zucker Diabetic Fatty rats.

    NARCIS (Netherlands)

    Bosch, R.R.; Janssen, S.W.J.; Span, P.N.; Olthaar, A.J.; Emst-de Vries, S.E. van; Willems, P.H.G.M.; Martens, G.J.M.; Hermus, A.R.M.M.; Sweep, C.G.J.

    2003-01-01

    Many studies suggest that insulin resistance develops and/or is maintained by an increased flux of glucose through the hexosamine biosynthesis pathway. This pathway may attenuate insulin-stimulated glucose uptake by activating protein kinase C (PKC). Therefore, we investigated whether the concentrat

  16. Lung uptake of thallium-201: a marker of defect reversibility?

    Science.gov (United States)

    Sanderson, R.; Woldman, S.; McCurrach, G.; Martin, W.; Hutton, I.

    1998-06-01

    High lung uptake of thallium-201 at stress is reported to be associated with a large number of perfusion defects and poor prognosis. This study was performed to assess whether the reversibility of stress perfusion defects was related to lung uptake. Gated planar thallium scans at stress and at redistribution from 102 consecutive patients with essentially normal left ventricular ejection fraction (using gated blood pool ventriculography) were graded in terms of defect size. Lung and myocardial uptake of thallium were quantitated by region of interest methods relative to the given activity in a previously validated method. There was no significant correlation (non-parametric) between lung uptake and degree of redistribution (). There was a weak but positive correlation between lung uptake and defect size (). Both exercise time and double product showed a negative correlation with lung uptake (e.g. for double product, ). In conclusion, contrary to our expectation, lung uptake is not related to the degree of redistribution. High lung uptake seems to reflect poor cardiovascular reserve.

  17. Increased Brain Fatty Acid Uptake in Metabolic Syndrome

    Science.gov (United States)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti; Hirvonen, Jussi; Fielding, Barbara A.; Virtanen, Kirsi; Oikonen, Vesa; Kemppainen, Jukka; Viljanen, Tapio; Guiducci, Letizia; Haaparanta-Solin, Merja; Någren, Kjell; Solin, Olof; Nuutila, Pirjo

    2010-01-01

    OBJECTIVE To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it. RESEARCH DESIGN AND METHODS We measured brain fatty acid uptake in a group of 23 patients with MS and 7 age-matched healthy control subjects during fasting conditions using positron emission tomography (PET) with [11C]-palmitate and [18F]fluoro-6-thia-heptadecanoic acid ([18F]-FTHA). Sixteen MS subjects were restudied after 6 weeks of very low calorie diet intervention. RESULTS At baseline, brain global fatty acid uptake derived from [18F]-FTHA was 50% higher in patients with MS compared with control subjects. The mean percentage increment was 130% in the white matter, 47% in the gray matter, and uniform across brain regions. In the MS group, the nonoxidized fraction measured using [11C]-palmitate was 86% higher. Brain fatty acid uptake measured with [18F]-FTHA-PET was associated with age, fasting serum insulin, and homeostasis model assessment (HOMA) index. Both total and nonoxidized fractions of fatty acid uptake were associated with BMI. Rapid weight reduction decreased brain fatty acid uptake by 17%. CONCLUSIONS To our knowledge, this is the first study on humans to observe enhanced brain fatty acid uptake in patients with MS. Both fatty acid uptake and accumulation appear to be increased in MS patients and reversed by weight reduction. PMID:20566663

  18. Uptake of /sup 131/I by a papillary meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Preisman, R.A. (Rees-Stealy Medical Clinic, San Diego, CA); Halpern, S.E.; Shishido, R.; Waltz, T.; Callipari, F.; Reit, R.

    1977-08-01

    Significant uptake of /sup 131/I commonly occurs in thyroid malignancies, especially if the remaining normal thyroid tissue is removed prior to scanning. We report a case showing marked uptake of /sup 131/I by a papillary meningioma of the thoracic spinal cord. To our knowledge, this radionuclide has not been previously shown to accumulate in a meningioma.

  19. Matrix stiffness affects endocytic uptake of MK2-inhibitor peptides.

    Directory of Open Access Journals (Sweden)

    Jamie L Brugnano

    Full Text Available In this study, the role of substrate stiffness on the endocytic uptake of a cell-penetrating peptide was investigated. The cell-penetrating peptide, an inhibitor of mitogen-activated protein kinase activated protein kinase II (MK2, enters a primary mesothelial cell line predominantly through caveolae. Using tissue culture polystyrene and polyacrylamide gels of varying stiffness for cell culture, and flow cytometry quantification and enzyme-linked immunoassays (ELISA for uptake assays, we showed that the amount of uptake of the peptide is increased on soft substrates. Further, peptide uptake per cell increased at lower cell density. The improved uptake seen on soft substrates in vitro better correlates with in vivo functional studies where 10-100 µM concentrations of the MK2 inhibitor cell penetrating peptide demonstrated functional activity in several disease models. Additional characterization showed actin polymerization did not affect uptake, while microtubule polymerization had a profound effect on uptake. This work demonstrates that cell culture substrate stiffness can play a role in endocytic uptake, and may be an important consideration to improve correlations between in vitro and in vivo drug efficacy.

  20. Matrix stiffness affects endocytic uptake of MK2-inhibitor peptides.

    Science.gov (United States)

    Brugnano, Jamie L; Panitch, Alyssa

    2014-01-01

    In this study, the role of substrate stiffness on the endocytic uptake of a cell-penetrating peptide was investigated. The cell-penetrating peptide, an inhibitor of mitogen-activated protein kinase activated protein kinase II (MK2), enters a primary mesothelial cell line predominantly through caveolae. Using tissue culture polystyrene and polyacrylamide gels of varying stiffness for cell culture, and flow cytometry quantification and enzyme-linked immunoassays (ELISA) for uptake assays, we showed that the amount of uptake of the peptide is increased on soft substrates. Further, peptide uptake per cell increased at lower cell density. The improved uptake seen on soft substrates in vitro better correlates with in vivo functional studies where 10-100 µM concentrations of the MK2 inhibitor cell penetrating peptide demonstrated functional activity in several disease models. Additional characterization showed actin polymerization did not affect uptake, while microtubule polymerization had a profound effect on uptake. This work demonstrates that cell culture substrate stiffness can play a role in endocytic uptake, and may be an important consideration to improve correlations between in vitro and in vivo drug efficacy.

  1. Cobalt uptake and binding in human red blood cells

    DEFF Research Database (Denmark)

    Simonsen, Lars Ole; Brown, Anthony M; Harbak, Henrik

    2011-01-01

    The basal uptake and cytoplasmic binding of cobalt was studied in human red cells using (57)Co as tracer. The basal uptake is linear with time, at a rate of about 10 µmol (l cells)(-1) h(-1) at 100 µM [Co(2+)](o), and is almost irreversible, as there is hardly any efflux into excess EDTA. Ionophore...

  2. Cerebral ammonia uptake and accumulation during prolonged exercise in humans

    DEFF Research Database (Denmark)

    Nybo, Lars; Dalsgaard, Mads K.; Steensberg, Adam

    2005-01-01

    We evaluated whether peripheral ammonia production during prolonged exercise enhances the uptake and subsequent accumulation of ammonia within the brain. Two studies determined the cerebral uptake of ammonia (arterial and jugular venous blood sampling combined with Kety-Schmidt-determined cerebra...

  3. Increased brain fatty acid uptake in metabolic syndrome

    DEFF Research Database (Denmark)

    Karmi, Anna; Iozzo, Patricia; Viljanen, Antti

    2010-01-01

    To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it.......To test whether brain fatty acid uptake is enhanced in obese subjects with metabolic syndrome (MS) and whether weight reduction modifies it....

  4. High radio-isotope uptakes in patients with hypothyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Wing, J.; Kalk, W.J.; Ganda, C. (University of the Witwatersrand, Johannesburg (South Africa). Dept. of Medicine)

    1982-12-04

    Hypothyroidism is usually associated with a low radio-isotope uptake by the thyriod gland. We report 8 cases of Hashimoto's thyroiditis with clinical and biochemical hypothyroidism and with borderline high or overtly increased technetium-99m pertechnetate and/or iodine-131 uptakes.

  5. Uptake and depuration of gold nanoparticles in Daphnia magna

    DEFF Research Database (Denmark)

    Skjolding, Lars Michael; Kern, Kristina; Hjorth, Rune

    2014-01-01

    This study presents a series of short-term studies (total duration 48 h) of uptake and depuration of engineered nanoparticles (ENP) in neonate Daphnia magna. Gold nanoparticles (Au NP) were used to study the influence of size, stabilizing agent and feeding on uptake and depuration kinetics...

  6. Uptake of water from soils by plant roots

    NARCIS (Netherlands)

    Raats, P.A.C.

    2007-01-01

    Uptake of water by plant roots can be considered at two different Darcian scales, referred to as the mesoscopic and macroscopic scales. At the mesoscopic scale, uptake of water is represented by a flux at the soil¿root interface, while at the macroscopic scale it is represented by a sink term in the

  7. Predictors of hpv vaccination uptake: a longitudinal study among parents

    NARCIS (Netherlands)

    Hofman, R.; Empelen, P. van; Richardus, J.H.; Kok, I.M.C.M. de; Koning, H.J. de; Ballegooijen, M. van; Korfage, I.J.

    2014-01-01

    To assess among parents longitudinal predictors of human papillomavirus (HPV) vaccination uptake for their daughters, random samples of parents were identified via municipal services and sent baseline questionnaires in June 2009 and follow-up questionnaires in November 2011 after their uptake

  8. Uptake and depuration of gold nanoparticles in Daphnia magna

    DEFF Research Database (Denmark)

    Skjolding, Lars Michael; Kern, Kristina; Hjorth, Rune

    2014-01-01

    This study presents a series of short-term studies (total duration 48 h) of uptake and depuration of engineered nanoparticles (ENP) in neonate Daphnia magna. Gold nanoparticles (Au NP) were used to study the influence of size, stabilizing agent and feeding on uptake and depuration kinetics...

  9. Exploring the Relationship between Characteristics of Recasts and Learner Uptake

    Science.gov (United States)

    Sheen, Younghee

    2006-01-01

    This study presents a taxonomy of the recasts that arose in communicative ESL and EFL classrooms. The taxonomy is used to examine the relationship between different characteristics of recasts and learner uptake/repair. Characteristics that were significantly related to uptake were the length of recasts (short vs. long), the linguistic focus…

  10. Skeletal muscle glucose uptake during dynamic exercise in humans

    DEFF Research Database (Denmark)

    Richter, Erik; Kiens, Bente; Saltin, Bengt;

    1988-01-01

    uptake was not compensated for by increased uptake of free fatty acids but was accompanied by decreases in plasma insulin and increases in plasma epinephrine and norepinephrine. During work with large muscle masses, arterial lactate increased to approximately 6 mM, and net leg lactate release reverted...

  11. Evidence for facilitated lactate uptake in lizard skeletal muscle.

    Science.gov (United States)

    Donovan, E R; Gleeson, T T

    2001-12-01

    To understand more fully lactate metabolism in reptilian muscle, lactate uptake in lizard skeletal muscle was measured and its similarities to the monocarboxylate transport system found in mammals were examined. At 2 min, uptake rates of 15 mmol l(-1) lactate into red iliofibularis (rIF) were 2.4- and 2.2-fold greater than white iliofibularis (wIF) and mouse soleus, respectively. alpha-Cyano-4-hydroxycinnamate (15 mmol l(-1)) caused little inhibition of uptake in wIF but caused a 42-54 % reduction in the uptake rate of lactate into rIF, suggesting that much of the lactate uptake by rIF is via protein-mediated transport. N-ethymaleimide (ETH) (10 mmol l(-1)) also caused a reduction in the rate of uptake, but measurements of adenylate and phosphocreatine concentrations show that ETH had serious effects on rIF and wIF and may not be appropriate for transport inhibition studies in reptiles. The higher net uptake rate by rIF than by wIF agrees with the fact that rIF shows much higher rates of lactate utilization and incorporation into glycogen than wIF. This study also suggests that lactate uptake by reptilian muscle is similar to that by mammalian muscle and that, evolutionarily, this transport system may be relatively conserved even in animals with very different patterns of lactate metabolism.

  12. Methionine Uptake and Required Radiation Dose to Control Glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Iuchi, Toshihiko, E-mail: tiuchi@chiba-cc.jp [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hatano, Kazuo [Division of Radiation Oncology, Tokyo Bay Advanced Imaging and Radiation Oncology Clinic, Makuhari, Chiba (Japan); Uchino, Yoshio [Division of Nuclear Medicine, Chiba Ryogo Center, Chiba (Japan); Itami, Makiko [Division of Surgical Pathology, Chiba Cancer Center, Chiba (Japan); Hasegawa, Yuzo; Kawasaki, Koichiro; Sakaida, Tsukasa [Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Hara, Ryusuke [Division of Radiation Oncology, Chiba Cancer Center, Chiba (Japan)

    2015-09-01

    Purpose: The purpose of this study was to retrospectively assess the feasibility of radiation therapy planning for glioblastoma multiforme (GBM) based on the use of methionine (MET) positron emission tomography (PET), and the correlation among MET uptake, radiation dose, and tumor control. Methods and Materials: Twenty-two patients with GBM who underwent MET-PET prior to radiation therapy were enrolled. MET uptake in 30 regions of interest (ROIs) from 22 GBMs, biologically effective doses (BEDs) for the ROIs and their ratios (MET uptake:BED) were compared in terms of whether the ROIs were controlled for >12 months. Results: MET uptake was significantly correlated with tumor control (odds ratio [OR], 10.0; P=.005); however, there was a higher level of correlation between MET uptake:BED ratio and tumor control (OR, 40.0; P<.0001). These data indicated that the required BEDs for controlling the ROIs could be predicted in terms of MET uptake; BED could be calculated as [34.0 × MET uptake] Gy from the optimal threshold of the MET uptake:BED ratio for tumor control. Conclusions: Target delineation based on MET-PET was demonstrated to be feasible for radiation therapy treatment planning. MET-PET could not only provide precise visualization of infiltrating tumor cells but also predict the required radiation doses to control target regions.

  13. Diffusely increased bone scintigraphic uptake in patellofemoral pain syndrome

    OpenAIRE

    Naslund, J.; Odenbring, S; Naslund, U; Lundeberg, T

    2005-01-01

    Objectives: Painful disorders of the patellofemoral joint are one of the most frequent complaints in orthopaedic and sports medicine. The aims of this study were to determine whether bone scintigrams of patients suffering from patellofemoral pain syndrome (PFPS) show diffuse uptake and in what bony compartment of the knee uptake, if any, was localised.

  14. An approach to monitor influenza vaccination uptake across Europe.

    NARCIS (Netherlands)

    Kroneman, M.; Paget, J.; Meuwissen, L.; Joseph, C.; Kennedy, H.

    2008-01-01

    Currently, the monitoring of influenza vaccination uptake is mainly a national issue. As influenza infection easily crosses international borders, it is in the interest of all countries to have a high vaccine uptake in people who may be vulnerable when influenza spreads. A Europe-wide monitoring

  15. Photoactivation of GLUT4 translocation promotes glucose uptake via PI3-K/Akt2 signaling in 3T3-L1 adipocytes

    Directory of Open Access Journals (Sweden)

    Lei Huang

    2014-05-01

    Full Text Available Insulin resistance is a hallmark of the metabolic syndrome and type 2 diabetes. Dysfunction of PI-3K/Akt signaling was involved in insulin resistance. Glucose transporter 4 (GLUT4 is a key factor for glucose uptake in muscle and adipose tissues, which is closely regulated by PI-3K/Akt signaling in response to insulin treatment. Low-power laser irradiation (LPLI has been shown to regulate various physiological processes and induce the synthesis or release of multiple molecules such as growth factors, which (especially red and near infrared light is mainly through the activation of mitochondrial respiratory chain and the initiation of intracellular signaling pathways. Nevertheless, it is unclear whether LPLI could promote glucose uptake through activation of PI-3K/Akt/GLUT4 signaling in 3T3L-1 adipocytes. In this study, we investigated how LPLI promoted glucose uptake through activation of PI-3K/Akt/GLUT4 signaling pathway. Here, we showed that GLUT4 was localized to the Golgi apparatus and translocated from cytoplasm to cytomembrane upon LPLI treatment in 3T3L-1 adipocytes, which enhanced glucose uptake. Moreover, we found that glucose uptake was mediated by the PI3-K/Akt2 signaling, but not Akt1 upon LPLI treatment with Akt isoforms gene silence and PI3-K/Akt inhibitors. Collectively, our results indicate that PI3-K/Akt2/GLUT4 signaling act as the key regulators for improvement of glucose uptake under LPLI treatment in 3T3L-1 adipocytes. More importantly, our findings suggest that activation of PI3-K/Akt2/GLUT4 signaling by LPLI may provide guidance in practical applications for promotion of glucose uptake in insulin-resistant adipose tissue.

  16. Uptake of Sulfadiazine Sulfonamide from Water by Clinoptilolite

    Directory of Open Access Journals (Sweden)

    Zhaohui Li

    2013-01-01

    Full Text Available The interactions between sulfadiazine (SDZ, a sulfonamide antibiotic, and clinoptilolite, a hydrophilic zeolite, were investigated under batch experimental conditions. The uptake of SDZ on the zeolite followed a linear sorption isotherm under neutral pH conditions. Higher SDZ uptake on the zeolite was observed when solution pH was below the or above the values of SDZ, while minimal SDZ uptake was observed when the solution pH was between the and values of SDZ. These observations suggested that hydrophobic interaction between SDZ and the zeolite was minimal due to the hydrophilic nature of the substrate. Electrostatic interactions and ion bridging were attributed to the elevated SDZ uptake under low and high pH conditions. As SDZ had a low value, the hydrophilic nature of the substrate prevented extensive uptake of SDZ, which could contribute to its extensive detection in the environment, including surface water and wastewater.

  17. Mitochondrial Ca2+ uptake in skeletal muscle health and disease

    CERN Document Server

    Zhou, Jingsong; Yi, Jianxun

    2016-01-01

    Muscle uses Ca2+ as a messenger to control contraction and relies on ATP to maintain the intracellular Ca2+ homeostasis. Mitochondria are the major sub-cellular organelle of ATP production. With a negative inner membrane potential, mitochondria take up Ca2+ from their surroundings, a process called mitochondrial Ca2+ uptake. Under physiological conditions, Ca2+ uptake into mitochondria promotes ATP production. Excessive uptake causes mitochondrial Ca2+ overload, which activates downstream adverse responses leading to cell dysfunction. Moreover, mitochondrial Ca2+ uptake could shape spatio-temporal patterns of intracellular Ca2+ signaling. Malfunction of mitochondrial Ca2+ uptake is implicated in muscle degeneration. Unlike non-excitable cells, mitochondria in muscle cells experience dramatic changes of intracellular Ca2+ levels. Besides the sudden elevation of Ca2+ level induced by action potentials, Ca2+ transients in muscle cells can be as short as a few milliseconds during a single twitch or as long as min...

  18. Mechanisms and regulation of Na(+) uptake by freshwater fish.

    Science.gov (United States)

    Kumai, Yusuke; Perry, Steve F

    2012-12-01

    Mechanisms of ion uptake by freshwater (FW) fish have received considerable attention over the past 80 years. Through an assortment of techniques incorporating whole animal physiology, electrophysiology and molecular biological approaches, three models have been proposed to account for Na(+) uptake. (1) Direct exchange of Na(+) and H(+) via one or more types of Na(+)/H(+) exchanger (slc9), (2) uptake of Na(+) through epithelial Na(+) channels energized by an electrical gradient created by H(+)-ATPase and (3) Na(+)/Cl(-) co-transport (slc12). While each mechanism is supported at least in part by theoretical or experimental data, there are several outstanding questions that have not yet been fully resolved. Furthermore, there are few details concerning how these Na(+) uptake mechanisms are fine tuned in response to the fluctuating FW environments. In this review, we summarize the current understanding of these three Na(+) uptake mechanisms and discuss their regulation by endocrine (cortisol and prolactin) and neurohumoral (catecholamines) factors.

  19. Technique for measuring carbon monoxide uptake in mice

    Energy Technology Data Exchange (ETDEWEB)

    Depledge, M.H.; Collis, C.H.; Chir, B.; Barrett, A.

    1981-04-01

    A new method has been developed for measuring carbon monoxide (CO) uptake in mice. Each animal was placed in a syringe and allowed to rebreathe a mixture of CO and helium (He) for 60 s. CO uptake was detemined from a comparison of CO and He concentrations before and after rebreathing. Weight specific CO uptake increased with body weight in CBA mice weighing between 20 to 35 gr. In larger mice, size dependence was less marked, although a slight fall in CO uptake was observed in older animals. Anaesthesia reduced ventilatory rate and CO uptake to a variable extent. The method is reproducible, non-invasive and does not require anaesthesia; consequently, it can be used to study serial changes in lung function. It is sensitive enough to detect lung damage in CBA mice following 16 Gy total body irradiation. Values of diffusing capacity obtained for mice using this method are consistent with published values.

  20. Regulation of myosin light chain kinase during insulin-stimulated glucose uptake in 3T3-L1 adipocytes.

    Directory of Open Access Journals (Sweden)

    Shelly Woody

    Full Text Available Myosin II (MyoII is required for insulin-responsive glucose transporter 4 (GLUT4-mediated glucose uptake in 3T3-L1 adipocytes. Our previous studies have shown that insulin signaling stimulates phosphorylation of the regulatory light chain (RLC of MyoIIA via myosin light chain kinase (MLCK. The experiments described here delineate upstream regulators of MLCK during insulin-stimulated glucose uptake. Since 3T3-L1 adipocytes express two MyoII isoforms, we wanted to determine which isoform was required for insulin-stimulated glucose uptake. Using a siRNA approach, we demonstrate that a 60% decrease in MyoIIA protein expression resulted in a 40% inhibition of insulin-stimulated glucose uptake. We also show that insulin signaling stimulates the phosphorylation of MLCK. We further show that MLCK can be activated by calcium as well as signaling pathways. We demonstrate that adipocytes treated with the calcium chelating agent, 1,2-b (iso-aminophenoxy ethane-N,N,N',N'-tetra acetic acid, (BAPTA (in the presence of insulin impaired the insulin-induced phosphorylation of MLCK by 52% and the RLC of MyoIIA by 45% as well as impairing the recruitment of MyoIIA to the plasma membrane when compared to cells treated with insulin alone. We further show that the calcium ionophore, A23187 alone stimulated the phosphorylation of MLCK and the RLC associated with MyoIIA to the same extent as insulin. To identify signaling pathways that might regulate MLCK, we examined ERK and CaMKII. Inhibition of ERK2 impaired phosphorylation of MLCK and insulin-stimulated glucose uptake. In contrast, while inhibition of CaMKII did inhibit phosphorylation of the RLC associated with MyoIIA, inhibition of CAMKIIδ did not impair MLCK phosphorylation or translocation to the plasma membrane or glucose uptake. Collectively, our results are the first to delineate a role for calcium and ERK in the activation of MLCK and thus MyoIIA during insulin-stimulated glucose uptake in 3T3-L1 adipocytes.

  1. Use of glycolytic pathways for inhibiting or measuring oncogenic signaling

    Energy Technology Data Exchange (ETDEWEB)

    Onodera, Yasuhito; Bissell, Mina

    2017-06-27

    Disclosed are methods in which glucose metabolism is correlated to oncogenesis through certain specific pathways; inhibition of certain enzymes is shown to interfere with oncogenic signaling, and measurement of certain enzyme levels is correlated with patient survival. The present methods comprise measuring level of expression of at least one of the enzymes involved in glucose uptake or metabolism, wherein increased expression of the at least one of the enzymes relative to expression in a normal cell correlates with poor prognosis of disease in a patient. Preferably the genes whose expression level is measured include GLUT3, PFKP, GAPDH, ALDOC, LDHA and GFPT2. Also disclosed are embodiments directed towards downregulating the expression of some genes in glucose uptake and metabolism.

  2. Dermal uptake directly from air under transient conditions: advances in modeling and comparisons with experimental results for human subjects

    DEFF Research Database (Denmark)

    Morrison, G C; Weschler, Charles J.; Bekö, Gabriel

    2016-01-01

    To better understand the dermal exposure pathway, we enhance an existing mechanistic model of transdermal uptake by including skin surface lipids (SSL) and consider the impact of clothing. Addition of SSL increases the overall resistance to uptake of SVOCs from air but also allows for rapid...... transfer of SVOCs to sinks like clothing or clean air. We test the model by simulating di-ethyl phthalate (DEP) and di-n-butyl phthalate (DnBP) exposures of six bare-skinned (Weschler et al. 2015, Environ. Health Perspect., 123, 928) and one clothed participant (Morrison et al. 2016, J. Expo. Sci. Environ...

  3. In vitro characterization of cadmium and zinc uptake via the gastro-intestinal tract of the rainbow trout (Oncorhynchus mykiss): Interactive effects and the influence of calcium

    Energy Technology Data Exchange (ETDEWEB)

    Ojo, Adeola A. [Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 (Canada)], E-mail: adeolaojo25@yahoo.com; Wood, Chris M. [Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1 (Canada)], E-mail: woodcm@mcmaster.ca

    2008-08-11

    An in vitro gut sac technique was employed to study whether Cd and Zn uptake mechanisms in the gastro-intestinal tract of the rainbow trout are similar to those at the gills, where both metals are taken up via the Ca transport pathway. Metal accumulation in surface mucus, in the mucosal epithelium, and transport into the blood space were assayed using radiolabelled Cd or Zn concentrations of 50 {mu}mol L{sup -1} in the luminal (internal) saline. Elevated luminal Ca (10 or 100 mmol L{sup -1}versus 1 mmol L{sup -1}) reduced Cd uptake into all three phases by approximately 60% in the stomach, but had no effect in the anterior, mid, or posterior intestine. This finding is in accordance with recent in vivo evidence that Ca is taken up mainly via the stomach, and that high [Ca] diets inhibit Cd accumulation from the food specifically in this section of the tract. In contrast, 10 mmol L{sup -1} luminal Ca had no effect on Zn transport in any section, whereas 100 mmol L{sup -1} Ca stimulated Zn uptake, by approximately threefold, into all three phases in the stomach only. There was no influence of elevated luminal Zn (10 mmol L{sup -1}) on Cd uptake in the stomach or anterior intestine, or of high Cd (10 mmol L{sup -1}) on Zn uptake in these sections. However, high [Zn] stimulated Cd transport into the blood space but inhibited accumulation in the mucosal epithelium and/or mucus-binding in the mid and posterior intestine, whereas high [Cd] exerted a reciprocal effect in the mid-intestine only. We conclude that Cd uptake occurs via an important Ca-sensitive mechanism in the stomach which is different from that at the gills, while Cd transport mechanisms in the intestine are not directly Ca-sensitive. Zn uptake does not appear to involve Ca uptake pathways, in contrast to the gills. These results are discussed in the context of other possible Cd and Zn transport pathways, and the emerging role of the stomach as an organ of divalent metal uptake.

  4. Clinical Pathway for Thyroidectomy.

    Science.gov (United States)

    Villar del Moral, Jesús María; Soria Aledo, Víctor; Colina Alonso, Alberto; Flores Pastor, Benito; Gutiérrez Rodríguez, María Teresa; Ortega Serrano, Joaquín; Parra Hidalgo, Pedro; Ros López, Susana

    2015-05-01

    Clinical pathways are care plans applicable to patient care procedures that present variations in practice and a predictable clinical course. They are designed not as a substitute for clinical judgment, but rather as a means to improve the effectiveness and efficiency of the procedures. This clinical pathway is the result of a collaborative work of the Sections of Endocrine Surgery and Quality Management of the Spanish Association of Surgeons. It attempts to provide a framework for standardizing the performance of thyroidectomy, the most frequently performed operation in endocrine surgery. Along with the usual documents of clinical pathways (temporary matrix, variance tracking and information sheets, assessment indicators and a satisfaction questionnaire) it includes a review of the scientific evidence around different aspects of pre, intra and postoperative management. Among others, antibiotic and antithrombotic prophylaxis, preoperative preparation in hyperthyroidism, intraoperative neuromonitoring and systems for obtaining hemostasis are included, along with management of postoperative hypocalcemia.

  5. Use of low-calcium cultivars to reduce cadmium uptake and accumulation in edible amaranth (Amaranthus mangostanus L.).

    Science.gov (United States)

    He, Bao-Yan; Yu, Dan-Ping; Chen, Yan; Shi, Jia-Li; Xia, Yan; Li, Qu-Sheng; Wang, Li-Li; Ling, Ling; Zeng, Eddy Y

    2017-03-01

    This study aimed to investigate the mechanism of low Cd accumulation in crops using edible amaranth (Amaranthus mangostanus L.) as a model. Fifteen amaranth cultivars were grown in long-term contaminated soil, and the differences in soil Cd mobilization, root uptake, and root-shoot translocation between low- and high-Cd accumulating cultivars were examined. The transport pathways of Cd across the root were further identified in Hoagland nutrient solution using the Ca channel blocker La(3+), the ATP inhibitor 2, 4-dinitrophenol (DNP), and a nutrition-deficient culture. Cd concentrations in amaranth cultivars varied about six-fold and showed an elevated trend as the concentration of Ca and Zn increased (p low-Cd cultivars were significantly lower than those of high-Cd cultivars, and decreased with decreasing levels of soluble rhizosphere exudates. These findings indicated that low co-mobilization of Cd with essential metals mediated by root-induced exudates of low-Cd cultivars contributed to its low accumulation in amaranth. Uptake of Cd was inhibited along with Ca by La(3+) and DNP, but was promoted by Ca or Fe deficiency treatment. Therefore, the Ca pathway is likely the mode of Cd entry into amaranth roots, although Zn and Fe transporters may also be involved. Low-Ca cultivars exhibited lower Cd uptake capability than high-Ca cultivars. The low translocation efficiency of Cd from root to shoot also contributed to its low content accumulation in edible parts of amaranth.

  6. Analysis of the global ocean sampling (GOS project for trends in iron uptake by surface ocean microbes.

    Directory of Open Access Journals (Sweden)

    Eve Toulza

    Full Text Available Microbial metagenomes are DNA samples of the most abundant, and therefore most successful organisms at the sampling time and location for a given cell size range. The study of microbial communities via their DNA content has revolutionized our understanding of microbial ecology and evolution. Iron availability is a critical resource that limits microbial communities' growth in many oceanic areas. Here, we built a database of 2319 sequences, corresponding to 140 gene families of iron metabolism with a large phylogenetic spread, to explore the microbial strategies of iron acquisition in the ocean's bacterial community. We estimate iron metabolism strategies from metagenome gene content and investigate whether their prevalence varies with dissolved iron concentrations obtained from a biogeochemical model. We show significant quantitative and qualitative variations in iron metabolism pathways, with a higher proportion of iron metabolism genes in low iron environments. We found a striking difference between coastal and open ocean sites regarding Fe(2+ versus Fe(3+ uptake gene prevalence. We also show that non-specific siderophore uptake increases in low iron open ocean environments, suggesting bacteria may acquire iron from natural siderophore-like organic complexes. Despite the lack of knowledge of iron uptake mechanisms in most marine microorganisms, our approach provides insights into how the iron metabolic pathways of microbial communities may vary with seawater iron concentrations.

  7. Heterogeneous uptake and reactivity of formic acid on calcium carbonate particles: a Knudsen cell reactor, FTIR and SEM study.

    Science.gov (United States)

    Al-Hosney, Hashim A; Carlos-Cuellar, Sofia; Baltrusaitis, Jonas; Grassian, Vicki H

    2005-10-21

    The heterogeneous uptake and reactivity of formic acid (HCOOH), a common gas-phase organic acid found in the environment, on calcium carbonate (CaCO(3)) particles have been investigated using a Knudsen cell reactor, Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). FTIR measurements show that the adsorption of formic acid on the surface of calcium carbonate results in the formation of calcium formate. Besides calcium formate, carbonic acid is also a reaction product under dry conditions (dry conditions and at low pressures, the initial uptake coefficient of formic acid on CaCO(3) particles is measured to be 3 +/- 1 x 10(-3) and decreases as the surface saturates with adsorbed products. The maximum surface coverage of formic acid under dry conditions is determined to be (3 +/- 1)x 10(14) molecules cm(-2). Under humidified conditions (RH >10%), adsorbed water on the surface of the carbonate particles participates in the surface reactivity of these particles, which results in the enhanced uptake kinetics and extent of reaction of this organic acid on CaCO(3) as well as opens up several new reaction pathways. These reaction pathways include: (i) the water-assisted dissociation of carbonic acid to CO(2) and H(2)O and (ii) the formation of calcium formate islands and crystallites, as evident by SEM images. The results presented here show that adsorbed water plays a potentially important role in the surface chemistry of gas-phase organic acids on calcium carbonate particles.

  8. EXPLANATORY VARIANCE IN MAXIMAL OXYGEN UPTAKE

    Directory of Open Access Journals (Sweden)

    Jacalyn J. Robert McComb

    2006-06-01

    Full Text Available The purpose of this study was to develop a prediction equation that could be used to estimate maximal oxygen uptake (VO2max from a submaximal water running protocol. Thirty-two volunteers (n =19 males, n = 13 females, ages 18 - 24 years, underwent the following testing procedures: (a a 7-site skin fold assessment; (b a land VO2max running treadmill test; and (c a 6 min water running test. For the water running submaximal protocol, the participants were fitted with an Aqua Jogger Classic Uni-Sex Belt and a Polar Heart Rate Monitor; the participants' head, shoulders, hips and feet were vertically aligned, using a modified running/bicycle motion. A regression model was used to predict VO2max. The criterion variable, VO2max, was measured using open-circuit calorimetry utilizing the Bruce Treadmill Protocol. Predictor variables included in the model were percent body fat (% BF, height, weight, gender, and heart rate following a 6 min water running protocol. Percent body fat accounted for 76% (r = -0.87, SEE = 3.27 of the variance in VO2max. No other variables significantly contributed to the explained variance in VO2max. The equation for the estimation of VO2max is as follows: VO2max ml.kg-1·min-1 = 56.14 - 0.92 (% BF.

  9. Iron uptake and metabolism in pseudomonads.

    Science.gov (United States)

    Cornelis, Pierre

    2010-05-01

    Pseudomonads are ubiquitous Gram-negative gamma proteobacteria known for their extreme versatility and adaptability. Some are plant pathogens (Pseudomonas syringae) which have to survive on the surface of leaves while others can colonize the rhizosphere or survive in soil (Pseudomonas fluorescens, Pseudomonas putida), and one species, Pseudomonas entomophila, is an insect pathogen. The most investigated species, Pseudomonas aeruginosa, is known to be an opportunistic pathogen able to infect plants, nematodes, insects, and mammals, including humans. Like for other bacteria, iron is a key nutrient for pseudomonads. The fluorescent pseudomonads produce siderophores, the best known being the fluorescent high-affinity peptidic pyoverdines. Often diverse secondary siderophores of lower affinity are produced as well (pyochelin, pseudomonin, corrugatins and ornicorrugatins, yersiniabactin, and thioquinolobactin). Reflecting their large capacity of adaptation to changing environment and niche colonization, pseudomonads are able to obtain their iron from heme or from siderophores produced by other microorganisms (xenosiderophores) via the expression of outer membrane TonB-dependent receptors. As expected, iron uptake is exquisitely and hierarchically regulated in these bacteria. In this short review, the diversity of siderophores produced, receptors, and finally the way iron homeostasis is regulated in P. aeruginosa, P. syringae, P. putida, and P. fluorescens, will be presented and, when possible, put in relation with the lifestyle and the ecological niche.

  10. Cellular uptake: lessons from supramolecular organic chemistry.

    Science.gov (United States)

    Gasparini, Giulio; Bang, Eun-Kyoung; Montenegro, Javier; Matile, Stefan

    2015-07-04

    The objective of this Feature Article is to reflect on the importance of established and emerging principles of supramolecular organic chemistry to address one of the most persistent problems in life sciences. The main topic is dynamic covalent chemistry on cell surfaces, particularly disulfide exchange for thiol-mediated uptake. Examples of boronate and hydrazone exchange are added for contrast, comparison and completion. Of equal importance are the discussions of proximity effects in polyions and counterion hopping, and more recent highlights on ring tension and ion pair-π interactions. These lessons from supramolecular organic chemistry apply to cell-penetrating peptides, particularly the origin of "arginine magic" and the "pyrenebutyrate trick," and the currently emerging complementary "disulfide magic" with cell-penetrating poly(disulfide)s. They further extend to the voltage gating of neuronal potassium channels, gene transfection, and the delivery of siRNA. The collected examples illustrate that the input from conceptually innovative chemistry is essential to address the true challenges in biology beyond incremental progress and random screening.

  11. Pegylated silica nanoparticles: cytotoxicity and macrophage uptake

    Science.gov (United States)

    Glorani, Giulia; Marin, Riccardo; Canton, Patrizia; Pinto, Marcella; Conti, Giamaica; Fracasso, Giulio; Riello, Pietro

    2017-08-01

    Here, we present a thorough study of pegylated silica nanoparticle (SNP) interaction with different biological environments. The SNPs have a mean diameter of about 40 nm and are coated with polyethylene glycol (PEG) of different molecular weights. The physicochemical characterization of SNPs allowed the confirmation of the binding of PEG chains to the silica surface, the reproducibility of the synthesis and the narrow size-dispersion. In view of clarifying the SNP interaction with biological environments, we first assessed the SNP reactivity after the incubation with two cell lines (macrophages RAW 264.7 and primary human fibroblasts), observing a reduced toxicity of pegylated SNPs compared to the bare ones. Then, we investigated the effect of the protein adsorption on the SNP surface using the model serum protein, bovine serum albumin (BSA). We found that the protein adsorption takes place more heavily on poorly pegylated SNPs, promoting the uptake of the latter by macrophages and leading to an increased mortality of these cells. To better understand this mechanism by means of flow cytometry, the dye Ru(bpy)3Cl2 was incorporated in the SNPs. The overall results highlight the SNP potentialities as a drug delivery system, thanks to the low interactions with the macrophages.

  12. Factors Infuencing Women in Pap Smear Uptake

    Science.gov (United States)

    Wijayanti, K. E.; Alam, I. G.

    2017-03-01

    Objective: Pap smear has proven can decrease death caused by cervical cancer. However, in Indonesia, only few woman who already did pap smear. The aim of this study was to investigate women’s knowledge about pap smear cervical cancer, and to investigate factors influence women to do pap smear test. Methods: Quantitative data colected through questionairre towards 31 women who did pap smear and 55 women who did not do pap smear. Questionairre was made using Health Belief model as a guideline to examine percieved susceptibility, perceived serioussnes, perceived benefits and perceived barriers. Chi square and multiple logistic regresion were used to investigate difference in knowledge and what the most factor that influence women to take pap smear test. Results: There’s significance knowledge difference betweeen women who did and did not do pap smear. But furthermore, by using Multiple Logistic Regression test, appearantly knowledge was not a strong predictor factor for women to take pap smear test (koefisiensi β = -0,164) Conclusion: Perceived barriers were factors that affected pap smear uptake in women in Indonesia. Few respondents get the wrong informations about pap smear, cevical cancer and its symptoms

  13. Substantial global carbon uptake by cement carbonation

    Science.gov (United States)

    Xi, Fengming; Davis, Steven J.; Ciais, Philippe; Crawford-Brown, Douglas; Guan, Dabo; Pade, Claus; Shi, Tiemao; Syddall, Mark; Lv, Jie; Ji, Lanzhu; Bing, Longfei; Wang, Jiaoyue; Wei, Wei; Yang, Keun-Hyeok; Lagerblad, Björn; Galan, Isabel; Andrade, Carmen; Zhang, Ying; Liu, Zhu

    2016-12-01

    Calcination of carbonate rocks during the manufacture of cement produced 5% of global CO2 emissions from all industrial process and fossil-fuel combustion in 2013. Considerable attention has been paid to quantifying these industrial process emissions from cement production, but the natural reversal of the process--carbonation--has received little attention in carbon cycle studies. Here, we use new and existing data on cement materials during cement service life, demolition, and secondary use of concrete waste to estimate regional and global CO2 uptake between 1930 and 2013 using an analytical model describing carbonation chemistry. We find that carbonation of cement materials over their life cycle represents a large and growing net sink of CO2, increasing from 0.10 GtC yr-1 in 1998 to 0.25 GtC yr-1 in 2013. In total, we estimate that a cumulative amount of 4.5 GtC has been sequestered in carbonating cement materials from 1930 to 2013, offsetting 43% of the CO2 emissions from production of cement over the same period, not including emissions associated with fossil use during cement production. We conclude that carbonation of cement products represents a substantial carbon sink that is not currently considered in emissions inventories.

  14. Design and synthesis of lupeol analogues and their glucose uptake stimulatory effect in L6 skeletal muscle cells.

    Science.gov (United States)

    Khan, Mohammad Faheem; Maurya, Chandan Kumar; Dev, Kapil; Arha, Deepti; Rai, Amit Kumar; Tamrakar, Akhilesh Kumar; Maurya, Rakesh

    2014-06-15

    Structure modifications of lupeol at the isopropylene moiety have been described via allylic oxidation using selenium dioxide. The antidiabetic efficacy of lupeol analogues were evaluated in vitro as glucose uptake stimulatory effect in L6 skeletal muscle cells. From all tested compounds, 2, 3, 4b and 6b showed significant stimulation of glucose uptake with respective percent stimulation of 173.1 (p <0.001), 114.1 (p <0.001), 98.3 (p <0.001) and 107.3 (p <0.001) at 10μM concentration. Stimulation of glucose uptake by these compounds is associated with enhanced translocation of glucose transporter 4 (GLUT4) and activation of IRS-1/PI3-K/AKT-dependent signaling pathway in L6 cells. Structure-activity relationship analysis of these analogues demonstrated that the integrity of α,β-unsaturated carbonyl and acetyl moieties were important in the retention of glucose uptake stimulatory effect. It is therefore proposed that naturally occurring lupeol and their analogues might reduce blood glucose, at least in part, through stimulating glucose utilization by skeletal muscles.

  15. Silicate mineral impacts on the uptake and storage of arsenic and plant nutrients in rice ( Oryza sativa L.).

    Science.gov (United States)

    Seyfferth, Angelia L; Fendorf, Scott

    2012-12-18

    Arsenic-contaminated rice grain may threaten human health globally. Since H₃AsO₃⁰ is the predominant As species found in paddy pore-waters, and H₄SiO₄⁰ and H₃AsO₃⁰ share an uptake pathway, silica amendments have been proposed to decrease As uptake and consequent As concentrations in grains. Here, we evaluated the impact of two silicate mineral additions differing in solubility (+Si(L), diatomaceous earth, 0.29 mM Si; +Si(H), Si-gel, 1.1 mM Si) to soils differing in mineralogy on arsenic concentration in rice. The +Si(L) addition either did not change or decreased As concentration in pore-water but did not change or increased grain-As levels relative to the (+As--Si) control. The +Si(H) addition increased As in pore-water, but it significantly decreased grain-As relative to the (+As--Si) control. Only the +Si(H) addition resulted in significant increases in straw- and husk-Si. Total grain- and straw-As was negatively correlated with pore-water Si, and the relationship differed between two soils exhibiting different mineralogy. These differing results are a consequence of competition between H₄SiO₄⁰ and H₃AsO₃⁰ for adsorption sites on soil solids and subsequent plant-uptake, and illustrate the importance of Si mineralogy on arsenic uptake.

  16. Pathway analysis of IMC

    DEFF Research Database (Denmark)

    Skrypnyuk, Nataliya; Nielson, Flemming; Pilegaard, Henrik

    2009-01-01

    We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced into the......We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced...

  17. Explaining variation in the uptake of HPV vaccination in England

    Directory of Open Access Journals (Sweden)

    Whynes David K

    2011-03-01

    Full Text Available Abstract Background In England, two national programmes of HPV vaccination for girls have been instituted, a routine programme for 12- and 13-year-olds and a catch-up programme for 17- and 18-year-olds. Uptake rates across the country have been far from uniform, and this research sought to identify factors explaining the variation in uptake by locality. Methods An association between uptake, deprivation and ethnic background had been established in pilot research. The present analysis was conducted at an aggregate, Primary Care Trust (PCT, level for the first year of the programmes. Published measures of HPV vaccination uptake, material deprivation, ethnic composition of PCT populations, primary care quality, and uptake of cervical screening and of other childhood immunisations were collated. Strong evidence of collinearity amongst the explanatory variables required a factor analysis to be undertaken. This provided four independent factors, used thereafter in regression models to explain uptake by PCT. Results The factor analysis revealed that ethnic composition was associated with attitudes towards cervical screening and other childhood vaccinations, whilst material deprivation and quality of primary care were orthogonal. Ethnic composition, early childhood vaccination, cervical screening and primary care quality were found to be influential in predicting uptake in both the routine and the catch-up cohorts, although with a lower degree of confidence in the case of the last two independent variables. Lower primary care quality was significant in explaining a greater fall in vaccination uptake between the first two doses in the catch-up cohort. Greater deprivation was a significant explanatory factor for both uptake and the fall in uptake between doses for the catch-up cohort but not for uptake in the routine cohort. Conclusion These results for uptake of the first year of the national programme using aggregate data corroborate findings from

  18. Cellular arsenic transport pathways in mammals.

    Science.gov (United States)

    Roggenbeck, Barbara A; Banerjee, Mayukh; Leslie, Elaine M

    2016-11-01

    Natural contamination of drinking water with arsenic results in the exposure of millions of people world-wide to unacceptable levels of this metalloid. This is a serious global health problem because arsenic is a Group 1 (proven) human carcinogen and chronic exposure is known to cause skin, lung, and bladder tumors. Furthermore, arsenic exposure can result in a myriad of other adverse health effects including diseases of the cardiovascular, respiratory, neurological, reproductive, and endocrine systems. In addition to chronic environmental exposure to arsenic, arsenic trioxide is approved for the clinical treatment of acute promyelocytic leukemia, and is in clinical trials for other hematological malignancies as well as solid tumors. Considerable inter-individual variability in susceptibility to arsenic-induced disease and toxicity exists, and the reasons for such differences are incompletely understood. Transport pathways that influence the cellular uptake and export of arsenic contribute to regulating its cellular, tissue, and ultimately body levels. In the current review, membrane proteins (including phosphate transporters, aquaglyceroporin channels, solute carrier proteins, and ATP-binding cassette transporters) shown experimentally to contribute to the passage of inorganic, methylated, and/or glutathionylated arsenic species across cellular membranes are discussed. Furthermore, what is known about arsenic transporters in organs involved in absorption, distribution, and metabolism and how transport pathways contribute to arsenic elimination are described.

  19. Enhancing the receptor-mediated cell uptake of PLGA nanoparticle for targeted drug delivery by incorporation chitosan onto the particle surface

    Science.gov (United States)

    Jiang, Guoqiang; Tang, Shifu; Chen, Xuelan; Ding, Fuxin

    2014-06-01

    Cationic polymer chitosan (CS) and target ligand were both incorporated onto nanoparticles (NPs) to enhance the cell uptake by integration of electrostatic interaction and receptor-mediated internalization. CS and biotin-contained amphipathic polymer biotin-poly(ethylene glycol)-poly(lactic acid) (biotin-PEG-PLA) were simultaneously decorated on the poly(lactic- co-glycolic acid) (PLGA) NPs surface in one step during the o/w solvent evaporation procedure. The incorporation of CS increased the zeta potential of the NPs to positive value and showed little impacts on particle size and biotin density. Cell uptake was investigated in vitro using human hepatic carcinoma cell lines SMMC-7721. The CS and biotin co-decorated NPs (CS-B-NPs) presented significantly higher cell uptake than that of the mono biotin-decorated NPs (B-NPs). In acid environment, as CS-B-NPs are more positive charged, cell uptake of CS-B-NPs is further increased, which is 3.8-fold as much as that of the undecorated NPs (U-NPs) and 1.9-fold higher than that of B-NPs at pH 6.6. When either the ligand density was reduced within limited or the particle size was slightly increased, cell uptake of CS-B-NPs remained almost the same. The cell uptake mechanism study demonstrated that the internalization due to the electrostatic interaction would contribute more to the cell uptake when the internalization based on clathrin-mediated endocytosis and other ATP-dependent pathways were blocked. The co-decoration of CS and target ligand is an effective approach for improving the specific cell uptake of NPs.

  20. A new paradigm for aptamer therapeutic AS1411 action: uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism.

    Science.gov (United States)

    Reyes-Reyes, E Merit; Teng, Yun; Bates, Paula J

    2010-11-01

    AS1411 is a first-in-class anticancer agent, currently in phase II clinical trials. It is a quadruplex-forming oligodeoxynucleotide that binds to nucleolin as an aptamer, but its mechanism of action is not completely understood. Mechanistic insights could lead to clinically useful markers for AS1411 response and to novel targeted therapies. Previously, we proposed a model where cell surface nucleolin serves as the receptor for AS1411, leading to selective uptake in cancer cells. Here, we compare uptake of fluorophore-labeled AS1411 (FL-AS1411) in DU145 prostate cancer cells (sensitive to AS1411) and Hs27 nonmalignant skin fibroblasts (resistant to AS1411). Uptake of FL-AS1411 occurred by endocytosis in both cell types and was much more efficient than an inactive, nonquadruplex oligonucleotide. Unexpectedly, uptake of FL-AS1411 was lower in cancer cells compared with Hs27 cells. However, the mechanism of uptake was different, occurring by macropinocytosis in cancer cells, but by a nonmacropinocytic pathway in Hs27 cells. Additionally, treatment of various cancer cells with AS1411 caused hyperstimulation of macropinocytosis, provoking an increase in its own uptake, whereas no stimulation was observed for nonmalignant cells. Nucleolin was not required for initial FL-AS1411 uptake in DU145 cells but was necessary for induced macropinocytosis and FL-AS1411 uptake at later times. Our results are inconsistent with the previous mechanistic model but confirm that nucleolin plays a role in mediating AS1411 effects. The data suggest a new model for AS1411 action as well as a new role for nucleolin in stimulating macropinocytosis, a process with potential applications in drug delivery.

  1. Regulation of Dopamine Uptake by Vasoactive Peptides in the Kidney

    Directory of Open Access Journals (Sweden)

    N. L. Rukavina Mikusic

    2016-01-01

    Full Text Available Considering the key role of renal dopamine in tubular sodium handling, we hypothesized that c-type natriuretic peptide (CNP and Ang-(1-7 may regulate renal dopamine availability in tubular cells, contributing to Na+, K+-ATPase inhibition. Present results show that CNP did not affect either 3H-dopamine uptake in renal tissue or Na+, K+-ATPase activity; meanwhile, Ang-(1-7 was able to increase 3H-dopamine uptake and decreased Na+, K+-ATPase activity in renal cortex. Ang-(1-7 and dopamine together decreased further Na+, K+-ATPase activity showing an additive effect on the sodium pump. In addition, hydrocortisone reversed Ang-(1-7-dopamine overinhibition on the enzyme, suggesting that this inhibition is closely related to Ang-(1-7 stimulation on renal dopamine uptake. Both anantin and cANP (4-23-amide did not modify CNP effects on 3H-dopamine uptake by tubular cells. The Mas receptor antagonist, A-779, blocked the increase elicited by Ang-(1-7 on 3H-dopamine uptake. The stimulatory uptake induced by Ang-(1-7 was even more pronounced in the presence of losartan, suggesting an inhibitory effect of Ang-(1-7 on AT1 receptors on 3H-dopamine uptake. By increasing dopamine bioavailability in tubular cells, Ang-(1-7 enhances Na+, K+-ATPase activity inhibition, contributing to its natriuretic and diuretic effects.

  2. Regulation of Dopamine Uptake by Vasoactive Peptides in the Kidney.

    Science.gov (United States)

    Rukavina Mikusic, N L; Kouyoumdzian, N M; Rouvier, E; Gironacci, M M; Toblli, J E; Fernández, B E; Choi, M R

    2016-01-01

    Considering the key role of renal dopamine in tubular sodium handling, we hypothesized that c-type natriuretic peptide (CNP) and Ang-(1-7) may regulate renal dopamine availability in tubular cells, contributing to Na(+), K(+)-ATPase inhibition. Present results show that CNP did not affect either (3)H-dopamine uptake in renal tissue or Na(+), K(+)-ATPase activity; meanwhile, Ang-(1-7) was able to increase (3)H-dopamine uptake and decreased Na(+), K(+)-ATPase activity in renal cortex. Ang-(1-7) and dopamine together decreased further Na(+), K(+)-ATPase activity showing an additive effect on the sodium pump. In addition, hydrocortisone reversed Ang-(1-7)-dopamine overinhibition on the enzyme, suggesting that this inhibition is closely related to Ang-(1-7) stimulation on renal dopamine uptake. Both anantin and cANP (4-23-amide) did not modify CNP effects on (3)H-dopamine uptake by tubular cells. The Mas receptor antagonist, A-779, blocked the increase elicited by Ang-(1-7) on (3)H-dopamine uptake. The stimulatory uptake induced by Ang-(1-7) was even more pronounced in the presence of losartan, suggesting an inhibitory effect of Ang-(1-7) on AT1 receptors on (3)H-dopamine uptake. By increasing dopamine bioavailability in tubular cells, Ang-(1-7) enhances Na(+), K(+)-ATPase activity inhibition, contributing to its natriuretic and diuretic effects.

  3. Night-time ozone uptake by Mediterranean species

    Directory of Open Access Journals (Sweden)

    S. Mereu

    2009-02-01

    Full Text Available Due to the evident tropospheric ozone impact on plant productivity, an accurate ozone risk assessment for the vegetation has become an issue. There is a growing evidence that ozone stomatal uptake may also take place at night and that the night-time uptake may be more damaging than diurnal uptake. Estimation of night-time uptake in the field is complicated because of instrumental difficulties. Eddy covariance technology is not always reliable because of the low turbulence at night. Leaf level porometry is defective at relative humidity above 70% which often takes place at night. Improved sap flow technology allows to estimate also slow flows that usually take place at night and hence may be, at present, the most trustworthy technology to measure night-time transpiration and hence to derive canopy stomatal conductance and ozone uptake at night. Based on micrometeorological data and the sap flow of three Mediterranean woody species, the night-time ozone uptake of these species was evaluated during a summer season as drought increased. Night-time ozone uptake was 10% of the total when plants were exposed to a weak drought, but increased up to 24% as the drought became more pronounced. The percentage increase is due to a stronger reduction of diurnal stomatal conductance than night-time stomatal conductance.

  4. Mitochondrial Ca(2+) uptake in skeletal muscle health and disease.

    Science.gov (United States)

    Zhou, Jingsong; Dhakal, Kamal; Yi, Jianxun

    2016-08-01

    Muscle uses Ca(2+) as a messenger to control contraction and relies on ATP to maintain the intracellular Ca(2+) homeostasis. Mitochondria are the major sub-cellular organelle of ATP production. With a negative inner membrane potential, mitochondria take up Ca(2+) from their surroundings, a process called mitochondrial Ca(2+) uptake. Under physiological conditions, Ca(2+) uptake into mitochondria promotes ATP production. Excessive uptake causes mitochondrial Ca(2+) overload, which activates downstream adverse responses leading to cell dysfunction. Moreover, mitochondrial Ca(2+) uptake could shape spatio-temporal patterns of intracellular Ca(2+) signaling. Malfunction of mitochondrial Ca(2+) uptake is implicated in muscle degeneration. Unlike non-excitable cells, mitochondria in muscle cells experience dramatic changes of intracellular Ca(2+) levels. Besides the sudden elevation of Ca(2+) level induced by action potentials, Ca(2+) transients in muscle cells can be as short as a few milliseconds during a single twitch or as long as minutes during tetanic contraction, which raises the question whether mitochondrial Ca(2+) uptake is fast and big enough to shape intracellular Ca(2+) signaling during excitation-contraction coupling and creates technical challenges for quantification of the dynamic changes of Ca(2+) inside mitochondria. This review focuses on characterization of mitochondrial Ca(2+) uptake in skeletal muscle and its role in muscle physiology and diseases.

  5. Thymidine phosphorylase influences [(18)F]fluorothymidine uptake in cancer cells and patients with non-small cell lung cancer.

    Science.gov (United States)

    Lee, Seung Jin; Yeo, Jeong Seok; Lee, Haeng Jung; Lee, Eun Jung; Kim, Seog Young; Jang, Se Jin; Lee, Jong Jin; Ryu, Jin-Sook; Moon, Dae Hyuk

    2014-07-01

    Thymidine phosphorylase (TP), a key enzyme in the pyrimidine nucleoside salvage pathway, catalyses the reversible phosphorylation of thymidine, thereby generating thymine and 2-deoxy-D-ribose-1-phosphate. By regulating the levels of endogenous thymidine, TP may influence [(18)F]fluorothymidine ([(18)F]FLT) uptake. We investigated the effect of TP activity on [(18)F]FLT uptake by tumours. Uptake of [(3)H]FLT and [(3)H]thymidine ([(3)H]Thd) and the activities of TP, thymidine kinase 1 (TK1), and equilibrative nucleoside transporter 1 (ENT1) were determined in exponentially growing A431, A549, HT29, HOP92, ACHN, and SKOV3 cells in the presence or absence of tipiracil hydrochloride, a TP inhibitor. Eighty-five non-small cell lung cancer tissues from a patient cohort that was previously studied with [(18)F]FLT positron emission tomography (PET) were retrieved and subjected to immunohistochemical analysis of TP expression. Factors that affected the maximum standardised uptake value (SUVmax) of [(18)F]FLT-PET were identified by multiple linear regression analysis. A431 cells had the highest TP activity; A549 and HT29 cells had moderate TP activity; and ACHN, SKOV3, and HOP92 cells had little detectable TP activity. Cell lines with high TP activity took up more [(3)H]FLT than [(3)H]Thd, whereas cells with little TP activity took up more [(3)H]Thd than [(3)H]FLT. In cells with high TP activity, TP inhibition decreased [(3)H]FLT uptake and increased [(3)H]Thd uptake. However, TP inhibition had no effect on ACHN, SKOV3, and HOP92 cells. TP inhibition did not change TK1 or ENT1 activity, but did increase the intracellular level of thymidine. The SUVmax of [(18)F]FLT was affected by three independent factors: Ki-67 expression (P < 0.001), immunohistochemical TP score (P < 0.001), and tumour size (P = 0.015). TP activity influences [(18)F]FLT uptake, and may explain preferential uptake of [(18)F]FLT over [(3)H]Thd. These results provide important insights into the

  6. Pathways to School Success

    Science.gov (United States)

    University of Pittsburgh Office of Child Development, 2012

    2012-01-01

    In 2006, the University of Pittsburgh Office of Child Development began implementing a multi-year school readiness project in several area schools. Evidence from both research and the field point to several key elements that foster school readiness and create pathways to school success for all children. This paper presents components of a…

  7. Policies built upon pathways

    NARCIS (Netherlands)

    S. Musterd; Z. Kovács

    2013-01-01

    After the general introductions, the first substantive part of this volume (Part II) provides concise research-based discussions of policies developed in recognition of the important role played by the pathways along which city-regions have travelled. Our research has shown that it is highly importa

  8. Dexter energy transfer pathways.

    Science.gov (United States)

    Skourtis, Spiros S; Liu, Chaoren; Antoniou, Panayiotis; Virshup, Aaron M; Beratan, David N

    2016-07-19

    Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor-acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways.

  9. Controls on thallium uptake during hydrothermal alteration of the upper ocean crust

    Science.gov (United States)

    Coggon, Rosalind M.; Rehkämper, Mark; Atteck, Charlotte; Teagle, Damon A. H.; Alt, Jeffrey C.; Cooper, Matthew J.

    2014-11-01

    , a correlation between the Tl and S concentrations of upper crustal basalts from Holes U1301B, 504B and 896A indicates that Tl is primarily incorporated into secondary sulfides. Given that some of these secondary sulfides formed as a result of microbial sulfate reduction, microbial action is at least indirectly responsible for Tl-uptake. Thallium-enrichment of ridge flank basalts requires a Tl-bearing fluid and physical, chemical and microbial conditions that favor secondary sulfide formation. Uptake of Tl occurs in reducing environments in the background rocks away from fluid flow pathways during early 'open' circulation of oxidizing seawater but more pervasively throughout the system during later 'restricted' circulation of reducing fluids. The Tl-isotope system is therefore a useful tracer of the fluid flux through both the 'open' and 'restricted' ridge flank hydrothermal regimes.

  10. Vesicular uptake of macromolecules by human placental amniotic epithelial cells.

    Science.gov (United States)

    Sharshiner, Rita; Brace, Robert A; Cheung, Cecilia Y

    2017-09-01

    Studies in animal models have shown that unidirectional vesicular transport of amniotic fluid across the amnion plays a primary role in regulating amniotic fluid volume. Our objective was to explore vesicle type, vesicular uptake and intracellular distribution of vesicles in human amnion cells using high- and super-resolution fluorescence microscopy. Placental amnion was obtained at cesarean section and amnion cells were prepared and cultured. At 20%-50% confluence, the cells were incubated with fluorophore conjugated macromolecules for 1-30 min at 22 °C or 37 °C. Fluorophore labeled macromolecules were selected as markers of receptor-mediated caveolar and clathrin-coated vesicular uptake as well as non-specific endocytosis. After fluorophore treatment, the cells were fixed, imaged and vesicles counted using Imaris(®) software. Vesicular uptake displayed first order saturation kinetics with half saturation times averaging 1.3 min at 37 °C compared to 4.9 min at 22 °C, with non-specific endocytotic uptake being more rapid at both temperatures. There was extensive cell-to-cell variability in uptake rate. Under super-resolution microscopy, the pattern of intracellular spatial distribution was distinct for each macromolecule. Co-localization of fluorescently labeled macromolecules was very low at vesicular dimensions. In human placental amnion cells, 1) vesicular uptake of macromolecules is rapid, consistent with the concept that vesicular transcytosis across the amnion plays a role in the regulation of amniotic fluid volume; 2) uptake is temperature dependent and variable among individual cells; 3) the unique intracellular distributions suggest distinct functions for each vesicle type; 4) non-receptor mediated vesicular uptake may be a primary vesicular uptake mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Multiple internalization pathways of polyelectrolyte multilayer capsules into mammalian cells.

    Science.gov (United States)

    Kastl, Lena; Sasse, Daniel; Wulf, Verena; Hartmann, Raimo; Mircheski, Josif; Ranke, Christiane; Carregal-Romero, Susana; Martínez-López, José Antonio; Fernández-Chacón, Rafael; Parak, Wolfgang J; Elsasser, Hans-Peter; Rivera Gil, Pilar

    2013-08-27

    Polyelectrolyte multilayer (PEM) capsules are carrier vehicles with great potential for biomedical applications. With the future aim of designing biocompatible, effective therapeutic delivery systems (e.g., for cancer), the pathway of internalization (uptake and fate) of PEM capsules was investigated. In particular the following experiments were performed: (i) the study of capsule co-localization with established endocytic markers, (ii) switching-off endocytotic pathways with pharmaceutical/chemical inhibitors, and (iii) characterization and quantification of capsule uptake with confocal and electron microscopy. As result, capsules co-localized with lipid rafts and with phagolysosomes, but not with other endocytic vesicles. Chemical interference of endocytosis with chemical blockers indicated that PEM capsules enter the investigated cell lines through a mechanism slightly sensitive to electrostatic interactions, independent of clathrin and caveolae, and strongly dependent on cholesterol-rich domains and organelle acidification. Microscopic characterization of cells during capsule uptake showed the formation of phagocytic cups (vesicles) to engulf the capsules, an increased number of mitochondria, and a final localization in the perinuclear cytoplasma. Combining all these indicators we conclude that PEM capsule internalization in general occurs as a combination of different sequential mechanisms. Initially, an adsorptive mechanism due to strong electrostatic interactions governs the stabilization of the capsules at the cell surface. Membrane ruffling and filopodia extensions are responsible for capsule engulfing through the formation of a phagocytic cup. Co-localization with lipid raft domains activates the cell to initiate a lipid-raft-mediated macropinocytosis. Internalization vesicles are very acidic and co-localize only with phagolysosome markers, excluding caveolin-mediated pathways and indicating that upon phagocytosis the capsules are sorted to

  12. Connexin 43 impacts on mitochondrial potassium uptake

    Directory of Open Access Journals (Sweden)

    Kerstin eBoengler

    2013-06-01

    Full Text Available In cardiomyocytes, connexin 43 (Cx43 forms gap junctions and unopposed hemichannels at the plasma membrane, but the protein is also present at the inner membrane of subsarcolemmal mitochondria. Both inhibition and genetic ablation of Cx43 reduce ADP-stimulated complex 1 respiration. Since mitochondrial potassium influx impacts on oxygen consumption, we investigated whether or not inhibition or ablation of mitochondrial Cx43 alters mitochondrial potassium uptake.Subsarcolemmal mitochondria were isolated from rat left ventricular (LV myocardium and loaded with the potassium-sensitive dye PBFI. Intramitochondrial potassium was replaced by TEA (tetraethylammonium. Mitochondria were incubated under control conditions or treated with 250 µM Gap19, a peptide that specifically inhibits Cx43-dependent hemichannels at plasma membranes. Subsequently, 140 mM KCl was added and the slope of the increase in PBFI fluorescence over time was calculated. The slope of the PBFI fluorescence of the control mitochondria was set to 100%. In the presence of Gap19, the mitochondrial potassium influx was reduced from 100±11.6 % in control mitochondria to 65.5±10.7 % (n=6, p<0.05. In addition to the pharmacological inhibition of Cx43, potassium influx was studied in mitochondria isolated from conditional Cx43 knockout mice. Here, the ablation of Cx43 was achieved by the injection of 4-hydroxytamoxifen (Cx43Cre-ER(T/fl + 4-OHT. The mitochondria of the Cx43Cre-ER(T/fl + 4-OHT mice contained 3±1% Cx43 (n=6 of that in control mitochondria (100±11%, n=8, p<0.05. The ablation of Cx43 (n=5 reduced the velocity of the potassium influx from 100±11.2 % in control mitochondria (n=9 to 66.6±5.5 % (p<0.05.Taken together, our data indicate that both pharmacological inhibition and genetic ablation of Cx43 reduce mitochondrial potassium influx.

  13. Oxygen uptake during repeated-sprint exercise.

    Science.gov (United States)

    McGawley, Kerry; Bishop, David J

    2015-03-01

    Repeated-sprint ability appears to be influenced by oxidative metabolism, with reductions in fatigue and improved sprint times related to markers of aerobic fitness. The aim of the current study was to measure the oxygen uptake (VO₂) during the first and last sprints during two, 5 × 6-s repeated-sprint bouts. Cross-sectional study. Eight female soccer players performed two, consecutive, 5 × 6-s maximal sprint bouts (B1 and B2) on five separate occasions, in order to identify the minimum time (trec) required to recover total work done (Wtot) in B1. On a sixth occasion, expired air was collected during the first and last sprint of B1 and B2, which were separated by trec. The trec was 10.9 ± 1.1 min. The VO₂ during the first sprint was significantly less than the last sprint in each bout (psprint (measured in kJ) was significantly related to VO₂max in both B1 (r=0.81, p=0.015) and B2 (r=0.93, p=0.001). In addition, the VO₂ attained in the final sprint was not significantly different from VO₂max in B1 (p=0.284) or B2 (p=0.448). The current study shows that the VO₂ increases from the first to the last of 5 × 6-s sprints and that VO₂max may be a limiting factor to performance in latter sprints. Increasing V˙O₂max in team-sport athletes may enable increased aerobic energy delivery, and consequently work done, during a bout of repeated sprints. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  14. Evolution of plant sucrose uptake transporters (SUTs

    Directory of Open Access Journals (Sweden)

    Anke eReinders

    2012-02-01

    Full Text Available In angiosperms, sucrose uptake transporters (SUTs have important functions especially in vascular tissue. Here we explore the evolutionary origins of SUTs by analysis of angiosperm SUTs and homologous transporters in a vascular early land plant, Selaginella moellendorffii, and a non-vascular plant, the bryophyte Physcomitrella patens, the charophyte algae Chlorokybus atmosphyticus, several red algae and fission yeast, Schizosaccharomyces pombe. Plant SUTs cluster into three types by phylogenetic analysis. Previous studies using angiosperms had shown that Types I and II are localized to plasma membrane while type III SUTs are associated with vacuolar membrane. SUT homologs were not found in the chlorophyte algae Chlamydomonas reinhardtii and Volvox carterii. However, the characean algae Chlorokybus atmosphyticus contains a SUT homolog (CaSUT1 and phylogenetic analysis indicated that it is basal to all other streptophyte SUTs analyzed. SUTs are present in both red algae and S. pombe but are less related to plant SUTs than CaSUT1. Both Selaginella and Physcomitrella encode type II and III SUTs suggesting that both plasma membrane and vacuolar sucrose transporter activities were present in early land plants. It is likely that SUT transporters are important for scavenging sucrose from the environment and intracellular compartments in charophyte and non-vascular plants. Type I SUTs were only found in eudicots and we conclude that they evolved from type III SUTs, possibly through loss of a vacuolar targeting sequence. Eudicots utilize type I SUTs for phloem (vascular tissue loading while monocots use type II SUTs for phloem loading. We show that HvSUT1 from barley, a type II SUT, reverted the growth defect of the Arabidopsis atsuc2 (type I mutant. This indicates that SUTs evolved similar (and interchangeable phloem loading transporter capabilities independently.

  15. Ensemble learned vaccination uptake prediction using web search queries

    DEFF Research Database (Denmark)

    Hansen, Niels Dalum; Lioma, Christina; Mølbak, Kåre

    2016-01-01

    We present a method that uses ensemble learning to combine clinical and web-mined time-series data in order to predict future vaccination uptake. The clinical data is official vaccination registries, and the web data is query frequencies collected from Google Trends. Experiments with official...... vaccine records show that our method predicts vaccination uptake eff?ectively (4.7 Root Mean Squared Error). Whereas performance is best when combining clinical and web data, using solely web data yields comparative performance. To our knowledge, this is the ?first study to predict vaccination uptake...

  16. ERp57 modulates mitochondrial calcium uptake through the MCU.

    Science.gov (United States)

    He, Jingquan; Shi, Weikang; Guo, Yu; Chai, Zhen

    2014-06-01

    ERp57 participates in the regulation of calcium homeostasis. Although ERp57 modulates calcium flux across the plasma membrane and the endoplasmic reticulum membrane, its functions on mitochondria are largely unknown. Here, we found that ERp57 can regulate the expression of the mitochondrial calcium uniporter (MCU) and modulate mitochondrial calcium uptake. In ERp57-silenced HeLa cells, MCU was downregulated, and the mitochondrial calcium uptake was inhibited, consistent with the effect of MCU knockdown. When MCU was re-expressed in the ERp57 knockdown cells, mitochondrial calcium uptake was restored. Thus, ERp57 is a potent regulator of mitochondrial calcium homeostasis.

  17. Effect of different biochars on Nitrogen uptake in poplar trees

    Science.gov (United States)

    George, Elizabeth; Tonon, Giustino; Scandellari, Francesca

    2014-05-01

    Influence of biochar on soil nitrogen transformation and plant uptake has been reported. This paper presents preliminary results of plant N uptake in poplars by using 15N isotope tracer approach Two types of biochar were applied to two sets of pots containing only sand and each pot received a pre-rooted poplar cutting. Half of the pots were inoculated with commercial mycorrhizal gel and the other half were left without. It is intended to provide information on how biochar, mycorrhiza and root interaction mediate nitrogen uptake and organ allocation.

  18. Mining biological pathways using WikiPathways web services.

    Directory of Open Access Journals (Sweden)

    Thomas Kelder

    Full Text Available WikiPathways is a platform for creating, updating, and sharing biological pathways [1]. Pathways can be edited and downloaded using the wiki-style website. Here we present a SOAP web service that provides programmatic access to WikiPathways that is complementary to the website. We describe the functionality that this web service offers and discuss several use cases in detail. Exposing WikiPathways through a web service opens up new ways of utilizing pathway information and assisting the community curation process.

  19. Mining biological pathways using WikiPathways web services.

    Science.gov (United States)

    Kelder, Thomas; Pico, Alexander R; Hanspers, Kristina; van Iersel, Martijn P; Evelo, Chris; Conklin, Bruce R

    2009-07-30

    WikiPathways is a platform for creating, updating, and sharing biological pathways [1]. Pathways can be edited and downloaded using the wiki-style website. Here we present a SOAP web service that provides programmatic access to WikiPathways that is complementary to the website. We describe the functionality that this web service offers and discuss several use cases in detail. Exposing WikiPathways through a web service opens up new ways of utilizing pathway information and assisting the community curation process.

  20. Possible Pathways for Increasing Natural Gas Use for Transportation (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Zigler, B.

    2014-10-01

    A collaborative partnership of DOE National Laboratories is working with DOE to identify critical RD&D needs to significantly increase the speed and breadth of NG uptake into the transportation sector. Drivers for increased utilization of natural gas for transportation are discussed. Key needs in research, development, and deployment are proposed, as well as possible pathways to address those needs. This presentation is intended to serve as a catalyst to solicit input from stakeholders regarding what technical areas they deem the most important.

  1. Uptake and Processing of the Cytolethal Distending Toxin by Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Joseph M. DiRienzo

    2014-10-01

    Full Text Available The cytolethal distending toxin (Cdt is a heterotrimeric holotoxin produced by a diverse group of Gram-negative pathogenic bacteria. The Cdts expressed by the members of this group comprise a subclass of the AB toxin superfamily. Some AB toxins have hijacked the retrograde transport pathway, carried out by the Golgi apparatus and endoplasmic reticulum (ER, to translocate to cytosolic targets. Those toxins have been used as tools to decipher the roles of the Golgi and ER in intracellular transport and to develop medically useful delivery reagents. In comparison to the other AB toxins, the Cdt exhibits unique properties, such as translocation to the nucleus, that present specific challenges in understanding the precise molecular details of the trafficking pathway in mammalian cells. The purpose of this review is to present current information about the mechanisms of uptake and translocation of the Cdt in relation to standard concepts of endocytosis and retrograde transport. Studies of the Cdt intoxication process to date have led to the discovery of new translocation pathways and components and most likely will continue to reveal unknown features about the mechanisms by which bacterial proteins target the mammalian cell nucleus. Insight gained from these studies has the potential to contribute to the development of novel therapeutic strategies.

  2. Uptake and processing of the cytolethal distending toxin by mammalian cells.

    Science.gov (United States)

    DiRienzo, Joseph M

    2014-10-31

    The cytolethal distending toxin (Cdt) is a heterotrimeric holotoxin produced by a diverse group of Gram-negative pathogenic bacteria. The Cdts expressed by the members of this group comprise a subclass of the AB toxin superfamily. Some AB toxins have hijacked the retrograde transport pathway, carried out by the Golgi apparatus and endoplasmic reticulum (ER), to translocate to cytosolic targets. Those toxins have been used as tools to decipher the roles of the Golgi and ER in intracellular transport and to develop medically useful delivery reagents. In comparison to the other AB toxins, the Cdt exhibits unique properties, such as translocation to the nucleus, that present specific challenges in understanding the precise molecular details of the trafficking pathway in mammalian cells. The purpose of this review is to present current information about the mechanisms of uptake and translocation of the Cdt in relation to standard concepts of endocytosis and retrograde transport. Studies of the Cdt intoxication process to date have led to the discovery of new translocation pathways and components and most likely will continue to reveal unknown features about the mechanisms by which bacterial proteins target the mammalian cell nucleus. Insight gained from these studies has the potential to contribute to the development of novel therapeutic strategies.

  3. Electrochemistry suggests proton access from the exit site to the binuclear center in Paracoccus denitrificans cytochrome c oxidase pathway variants.

    Science.gov (United States)

    Meyer, Thomas; Melin, Frédéric; Richter, Oliver-M H; Ludwig, Bernd; Kannt, Aimo; Müller, Hanne; Michel, Hartmut; Hellwig, Petra

    2015-02-27

    Two different pathways through which protons access cytochrome c oxidase operate during oxygen reduction from the mitochondrial matrix, or the bacterial cytoplasm. Here, we use electrocatalytic current measurements to follow oxygen reduction coupled to proton uptake in cytochrome c oxidase isolated from Paracoccus denitrificans. Wild type enzyme and site-specific variants with defects in both proton uptake pathways (K354M, D124N and K354M/D124N) were immobilized on gold nanoparticles, and oxygen reduction was probed electrochemically in the presence of varying concentrations of Zn(2+) ions, which are known to inhibit both the entry and the exit proton pathways in the enzyme. Our data suggest that under these conditions substrate protons gain access to the oxygen reduction site via the exit pathway. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. Problems in evaluating radiation dose via terrestrial and aquatic pathways.

    Science.gov (United States)

    Vaughan, B E; Soldat, J K; Schreckhise, R G; Watson, E C; McKenzie, D H

    1981-12-01

    This review is concerned with exposure risk and the environmental pathways models used for predictive assessment of radiation dose. Exposure factors, the adequacy of available data, and the model subcomponents are critically reviewed from the standpoint of absolute error propagation. Although the models are inherently capable of better absolute accuracy, a calculated dose is usually overestimated by from two to six orders of magnitude, in practice. The principal reason for so large an error lies in using "generic" concentration ratios in situations where site specific data are needed. Major opinion of the model makers suggests a number midway between these extremes, with only a small likelihood of ever underestimating the radiation dose. Detailed evaluations are made of source considerations influencing dose (i.e., physical and chemical status of released material); dispersal mechanisms (atmospheric, hydrologic and biotic vector transport); mobilization and uptake mechanisms (i.e., chemical and other factors affecting the biological availability of radioelements); and critical pathways. Examples are shown of confounding in food-chain pathways, due to uncritical application of concentration ratios. Current thoughts of replacing the critical pathways approach to calculating dose with comprehensive model calculations are also shown to be ill-advised, given present limitations in the comprehensive data base. The pathways models may also require improved parametrization, as they are not at present structured adequately to lend themselves to validation. The extremely wide errors associated with predicting exposure stand in striking contrast to the error range associated with the extrapolation of animal effects data to the human being.

  5. Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

    Science.gov (United States)

    Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

    2007-09-01

    Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

  6. Involvement of Rac1 and the actin cytoskeleton in insulin- and contraction-stimulated intracellular signaling and glucose uptake in mature skeletal muscle

    DEFF Research Database (Denmark)

    Sylow, Lykke

    by exercise is therefore an important alternative way to maintain whole body glucose homeostasis in insulin resistant states such as Type 2 Diabetes. Although the insulin- and exercise-stimulated signaling pathways to glucose uptake have been studied extensively, the underlying mechanisms are not well...... understood. The aim of the current PhD was therefore to investigate the involvement of Rac1 and the actin cytoskeleton in the regulation of insulin- and contraction-stimulated glucose uptake in mature skeletal muscle. The central findings of this PhD thesis was that Rac1 was activated by both insulin...... and muscle contraction in mouse and human skeletal muscle. Most importantly, Rac1 was involved in the regulation of both insulin- and contraction-stimulated glucose uptake. Interestingly, Rac1 signaling was defective in skeletal muscle of insulin resistant obese and T2D human subjects as well as in obese...

  7. Gallium-67 uptake in cutaneous lesions of mycosis fungoides

    Energy Technology Data Exchange (ETDEWEB)

    Nishimi, L.; Chen, D.C.; Ansari, A.N.; Siegel, M.E.

    1988-02-01

    The literature on gallium imaging in mycosis fungoides is limited and conflicting. A case of mycosis fungoides with increased uptake of Ga-67 in clinically noninfected skin lesions is reported. The literature regarding mycosis fungoides and gallium imaging is reviewed.

  8. Factors Contributing to Low Uptake of Cervical Screening in a ...

    African Journals Online (AJOL)

    Results: About 212 (78.2%) of the respondents have heard about cancer ... Discussion: The respondents in this study have demonstrated a high level of awareness of cervical cancer but low uptake of cervical cancer screening ... Article Metrics.

  9. Knowledge, Attitude and Uptake among Female Medical and Dental ...

    African Journals Online (AJOL)

    adedamla

    Conclusion. The knowledge and uptake of HPV vaccination among these students was generally poor though most of them had ... knowledge and attitude of female medical students towards ..... Asian Pacific Journal ... International Journal of.

  10. Off-season uptake of nitrogen in temperate heath vegetation

    DEFF Research Database (Denmark)

    Andresen, Louise C.; Michelsen, Anders

    2005-01-01

    , and the graminoids Carex arenaria and Deschampsia flexuosa, showed high root uptake of both forms of nitrogen, both 1 day after labelling and after a month, in species specific temporal patterns. Plant uptake of 13C was not significant, providing no further evidence of intact uptake of glycine. Translocation......In this field study we show that temperate coastal heath vegetation has a significant off-season uptake potential for nitrogen, both in the form of ammonium and as glycine, throughout winter. We injected 15N-ammonium and 15N 2x(13C)-glycine into the soil twice during winter and once at spring...... of the labelled nitrogen to shoots was generally evident after 1 month and increased as spring approached, with different translocation strategies in the three plant functional types. Furthermore, only the graminoids showed shoot growth during winter. Increasing plant nitrogen concentration from fall to spring...

  11. nutrient uptake efficiency and growth of two aquatic macrophyte ...

    African Journals Online (AJOL)

    Preferred Customer

    Key words/phrases: Constructed wetlands, Cyperus papyrus, nutrient uptake, Phragmites karka, wastewater treatment ... treatment wetlands in Ethiopia with different wastewater ..... cultivated on artificial floating beds in China's rural area. Ecol.

  12. Effect of rhamnolipids on the uptake of PAHs by ryegrass

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Lizhong [Department of Environmental Science, Zhejiang University, Hangzhou, Zhejiang 310028 (China); Ministry of Education Key Laboratory of Environmental Remediation and Ecological Health, Zhejiang University, Hangzhou, Zhejiang 310029 (China)], E-mail: zlz@zju.edu.cn; Zhang Ming [Department of Environmental Science, Zhejiang University, Hangzhou, Zhejiang 310028 (China)], E-mail: zhangming@zju.edu.cn

    2008-11-15

    A hydroponic experiment was conducted to investigate the effect of rhamnolipids, a biosurfactant, on the uptake of polycyclic aromatic hydrocarbons (PAHs) by ryegrass. Results showed that rhamnolipids could enhance the uptake of PAHs by ryegrass roots. With increasing concentration of rhamnolipids, the PAH content in ryegrass roots initially increased and then decreased, while the PAH content in ryegrass shoots did not change. Batch studies also showed that the sorption of phenanthrene by fresh ryegrass roots was dependent on rhamnolipid concentration and showed the same trends as the uptake experiment. The increase of permeability of ryegrass root cells with the increase of rhamnolipid concentration may lead to the initial enhancement of PAH content in ryegrass roots, and the decrease of PAH adsorption onto the root surface with further increase of rhamnolipids led to the decrease of PAH content in ryegrass roots. - Rhamnolipids, a biosurfactant, can promote the uptake of PAHs by ryegrass, which indicates a potential application of surfactant-enhanced phytoremediation.

  13. Cataract surgical uptake among older adults in Ghana | Ackuaku ...

    African Journals Online (AJOL)

    ... measures and chi square for associations in categorical outcome measures. ... Regional differences in cataract surgical uptake existed; was less than 60% in all ten ... Further investigations to garner equity in national eye care efforts are ...

  14. Serotonin uptake in blood platelets of psychiatric patients

    Energy Technology Data Exchange (ETDEWEB)

    Meltzer, H.Y.; Arora, R.C.; Baber, R.; Tricou, B.J.

    1981-12-01

    Platelet serotonin (5-HT) uptake was determined in 72 newly admitted, unmedicated psychiatric patients. Decreased maximum velocity (Vmax) of 5-HT uptake was present in unipolar and bipolar depressed patients as well as schizoaffective depressed patients. The apparent Michaelis constant (km) of 5-HT uptake was normal in these groups, as was Vmax and Km in manic-depressive and chronic schizophrenic patients. Treatment of depressed patients with notriptyline hydrochloride or imipramine hydrochloride increased Km significantly. There was a trend for the increase in Km in the nortriptyline-treated patients to correlate with clinical improvement. Decreased 5-HT uptake in platelets provides additional evidence for the role of 5-HT in the pathophysiologic process of some forms of depression.

  15. Estimating plant root water uptake using a neural network approach

    DEFF Research Database (Denmark)

    Qiao, D M; Shi, H B; Pang, H B

    2010-01-01

    and plant characteristics, and how to model it has been of interest for many years. Most macroscopic models for water uptake operate at soil profile scale under the assumption that the uptake rate depends on root density and soil moisture. Whilst proved appropriate, these models need spatio-temporal root...... density distributions, which is tedious to measure in situ and prone to uncertainty because of the complexity of root architecture hidden in the opaque soils. As a result, developing alternative methods that do not explicitly need the root density to estimate the root water uptake is practically useful......Water uptake by plant roots is an important process in the hydrological cycle, not only for plant growth but also for the role it plays in shaping microbial community and bringing in physical and biochemical changes to soils. The ability of roots to extract water is determined by combined soil...

  16. Growth, yield and NPK uptake by maize with complementary organic ...

    African Journals Online (AJOL)

    Growth, yield and NPK uptake by maize with complementary organic and inorganic fertilizers. ... African Journal of Food, Agriculture, Nutrition and Development ... The mixture of organic and inorganic fertilizer treatment consisted of half the ...

  17. Uptake of crude petroleum hydrocarbons by mudflat bacteria ...

    African Journals Online (AJOL)

    Uptake of crude petroleum hydrocarbons by mudflat bacteria exposed to ... spills is enhanced by the 'continuous' input of nitrogenous fertilizer (NPK) components. ... The net result is the increased recovery potential of this estuarine ...

  18. Understanding and predicting trends in north Atlantic CO2 uptake

    Science.gov (United States)

    Halloran, Paul; Lebehot, Alice; Watson, Andy; McNeall, Doug; Ford, David; Schuster, Ute

    2017-04-01

    To determine the maximum carbon dioxide (CO2) emissions society must commit to, to remain below a given atmospheric CO2 threshold, the scientific community must robustly quantify what proportion of human emitted CO2 will be taken up by the land and marine carbon reservoirs. The North Atlantic Ocean is the most intense marine sink of anthropogenic CO2 on the planet, accounting for about a fifth of the global oceanic anthropogenic CO2 uptake, despite covering just 15% of the global ocean area. Carefully assessing uncertainties, we quantify the real-world trend in North Atlantic CO2 uptake over the past two decades. Comparing this to results from state-of-the-art climate models, we find that models are systematically underestimating the observed CO2 uptake trend. By performing a set of targeted climate model simulations, we diagnose and account for this bias, and produce the first set of observation-informed future ocean CO2 uptake predictions.

  19. biodegradation and moisture uptake modified starch-filled linear low ...

    African Journals Online (AJOL)

    CHEMISTRY

    Key words: Starch-LLDPE blends, Calcium chloride, D-glucose, Chloroform and Alumina. INTRODUCTION .... rate of diffusion into the composites this is because moisture uptakes in ... prepared with oxidized potato starch. Food engineering ...

  20. Growth and nutrient uptake of Citrus rootstock varieties as affected ...

    African Journals Online (AJOL)

    Growth and nutrient uptake of Citrus rootstock varieties as affected poultry manure and NPK fertilizer in Ibadan, Southwestern Nigeria. ... Since plant height and stem diameter determine the quality of rootstock seedlings, poultry manure at 9 ...

  1. Game over? What hampers a major uptake of serious games?

    NARCIS (Netherlands)

    Nadolski, Rob; Baalsrud Hauge, Jannicke; Boyle, Liz; Riedel, Johann; Luccini, Marco

    2011-01-01

    Nadolski, R. J., Baalsrud Hauge, J., Boyle, L., Riedel, J., & Luccini, M. (2011, 2 December). Game over? What hampers the major uptake of serious games? Discussion session at Online Educa Berlin, Berlin, Germany.

  2. Insulin and insulin mutants stimulate glucose uptake in rat adipocytes

    Institute of Scientific and Technical Information of China (English)

    姚矢音; 张新堂; 许英镐; 张信娜; 朱尚权

    1999-01-01

    A simple method to determine the in vitro biological activity of insulin by measuring glucose uptake in the rat adipocytes is presented here. In the presence of insulin, the glucose uptake is 5-6 times more than the basal control. And the uptake of D-[3-3H]-glucose is linear as the logarithm of insulin concentration from 0.2 μg/L to 1.0 μg/L. Glucose and 3-O-methyl-glucose inhibit D-[3-3H]-glucose uptake into adipocytes. By this method, the in vitro biological activity of [B2-Lys]-insulin and [B3-Lys]-insulin was measured to be 61.6% and 154% respectively, relative to that of insulin.

  3. Catecholamines influence myocardial 123I MIBG uptake in neuroblastoma patients

    NARCIS (Netherlands)

    Palen, R.L.F. van der; Bulten, B.F.; Mavinkurve-Groothuis, A.M.C.; Bellersen, L.; Laarhoven, H.W.M. van; Kapusta, L.; Geus-Oei, L.F. de

    2013-01-01

    Aim: Cardiac 123I metaiodobenzylguanidine (MIBG) imaging can be influenced by several factors. We evaluated the relationship between catecholamine measurements and cardiac 123I MIBG uptake in neuroblastoma patients. Patients, methods:30 neuroblastoma patients were retrospectively assessed on cardiac

  4. Facilitation of phosphorus uptake in maize plants by mycorrhizosphere bacteria

    DEFF Research Database (Denmark)

    Battini, Fabio; Grønlund, Mette; Agnolucci, Monica

    2017-01-01

    availability of soil P. This study investigated whether biofertilizers and bioenhancers, such as arbuscular mycorrhizal fungi (AMF) and their associated bacteria could enhance growth and P uptake in maize. Plants were grown with or without mycorrhizas in compartmented pots with radioactive P tracers and were...... inoculated with each of 10 selected bacteria isolated from AMF spores. Root colonization by AMF produced large plant growth responses, while seven bacterial strains further facilitated root growth and P uptake by promoting the development of AMF extraradical mycelium. Among the tested strains, Streptomyces...... sp. W94 produced the largest increases in uptake and translocation of 33P, while Streptomyces sp. W77 highly enhanced hyphal length specific uptake of 33P. The positive relationship between AMF-mediated P absorption and shoot P content was significantly influenced by the bacteria inoculants...

  5. Uptake of Space Technologies - An Educational Programme

    Science.gov (United States)

    Bacai, Hina; Zolotikova, Svetlana; Young, Mandy; Cowsill, Rhys; Wells, Alan; Monks, Paul; Archibald, Alexandra; Smith, Teresa

    2013-04-01

    demonstrated. The results from these workshops and awareness building campaigns will show the end-user 'pull' in the uptake of remote sensing and Earth Observation data to implement successful Local Authority action plans and projects developing innovative solutions to critical Local Authority issues.

  6. Biomechanics and thermodynamics of nanoparticle interactions with plasma and endosomal membrane lipids in cellular uptake and endosomal escape.

    Science.gov (United States)

    Peetla, Chiranjeevi; Jin, Shihua; Weimer, Jonathan; Elegbede, Adekunle; Labhasetwar, Vinod

    2014-07-01

    To be effective for cytoplasmic delivery of therapeutics, nanoparticles (NPs) taken up via endocytic pathways must efficiently transport across the cell membrane and subsequently escape from the secondary endosomes. We hypothesized that the biomechanical and thermodynamic interactions of NPs with plasma and endosomal membrane lipids are involved in these processes. Using model plasma and endosomal lipid membranes, we compared the interactions of cationic NPs composed of poly(D,L-lactide-co-glycolide) modified with the dichain surfactant didodecyldimethylammonium bromide (DMAB) or the single-chain surfactant cetyltrimethylammonium bromide (CTAB) vs anionic unmodified NPs of similar size. We validated our hypothesis in doxorubicin-sensitive (MCF-7, with relatively fluid membranes) and resistant breast cancer cells (MCF-7/ADR, with rigid membranes). Despite their cationic surface charges, DMAB- and CTAB-modified NPs showed different patterns of biophysical interaction: DMAB-modified NPs induced bending of the model plasma membrane, whereas CTAB-modified NPs condensed the membrane, thereby resisted bending. Unmodified NPs showed no effects on bending. DMAB-modified NPs also induced thermodynamic instability of the model endosomal membrane, whereas CTAB-modified and unmodified NPs had no effect. Since bending of the plasma membrane and destabilization of the endosomal membrane are critical biophysical processes in NP cellular uptake and endosomal escape, respectively, we tested these NPs for cellular uptake and drug efficacy. Confocal imaging showed that in both sensitive and resistant cells DMAB-modified NPs exhibited greater cellular uptake and escape from endosomes than CTAB-modified or unmodified NPs. Further, paclitaxel-loaded DMAB-modified NPs induced greater cytotoxicity even in resistant cells than CTAB-modified or unmodified NPs or drug in solution, demonstrating the potential of DMAB-modified NPs to overcome the transport barrier in resistant cells. In

  7. Uptake of gold nanoparticles in primary human endothelial cells

    DEFF Research Database (Denmark)

    Klingberg, Henrik; Oddershede, Lene B.; Löschner, Katrin

    2015-01-01

    Gold nanoparticles (AuNPs) are relevant in nanomedicine for drug delivery in the vascular system, where endothelial cells are the first point of contact. We investigated the uptake of 80 nm AuNPs in primary human umbilical vein endothelial cells (HUVECs) by flow cytometry, 3D confocal microscopy....... Uptake of AuNPs in HUVECs occurred mainly by clathrin-mediated endocytosis and trafficking to membrane enclosures in the form of single particles and agglomerates of 2–3 particles....

  8. Traits affecting early season nitrogen uptake in nine legume species

    Directory of Open Access Journals (Sweden)

    Elana Dayoub

    2017-02-01

    Full Text Available Legume crops are known to have low soil N uptake early in their life cycle, which can weaken their ability to compete with other species, such as weeds or other crops in intercropping systems. However, there is limited knowledge on the main traits involved in soil N uptake during early growth and for a range of species. The objective of this research was to identify the main traits explaining the variability among legume species in soil N uptake and to study the effect of the soil mineral N supply on the legume strategy for the use of available N sources during early growth. Nine legume species were grown in rhizotrons with or without N supply. Root expansion, shoot and root biomass, nodule establishment, N2 fixation and mineral soil N uptake were measured. A large interspecific variability was observed for all traits affecting soil N uptake. Root lateral expansion and early biomass in relation to seed mass were the major traits influencing soil N uptake regardless of the level of soil N availability. Fenugreek, lentil, alfalfa, and common vetch could be considered weak competitors for soil N due to their low plant biomass and low lateral root expansion. Conversely, peanut, pea, chickpea and soybean had a greater soil N uptake. Faba bean was separated from other species having a higher nodule biomass, a higher N2 fixation and a lower seed reserve depletion. Faba bean was able to simultaneously fix N2 and take up soil N. This work has identified traits of seed mass, shoot and root biomass, root lateral expansion, N2 fixation and seed reserve depletion that allowing classification of legume species regarding their soil N uptake ability during early growth.

  9. Regional uptake of iodine-125-metaiodobenzylguanidine in the rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Matsunari, Ichiro (Dept. of Radiology, Fukui Prefectural Hospital, Fukui-City (Japan)); Bunko, Hisashi (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Taki, Junichi (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Nakajima, Kenichi (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Muramori, Akira (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Kuji, Ichiei (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Miyauchi, Tsutomu (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Tonami, Norihisa (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan)); Hisada, Kinichi (Dept. of Nuclear Medicine, Kanazawa Univ., School of Medicine (Japan))

    1993-11-01

    Regional uptake of iodine-125-metoiodobenzylguanidine was evaluated in normal (n=12) and reserpinized (n=12) rat hearts. At 15 min and 1, 3 and 6 h after injection of [sup 125]IMIBG, tissue activities were calculated for the right ventricular myocardium (RV), the whole left ventricular myocardium (whole LV), the epicardial layer of the left ventricular myocardium (Ep LV), the endocardial layer of the left ventricular myocardium (En LV), the basal segment of the left ventricular myocardium and the apical segment of the left ventricular myocardium. The uptake of [sup 125]IMIBG at 6 h after injection in the normal rat heart was higher in RV than in whole LV (0.45 [+-]0.09% vs 0.03 [+-]0.06% kg dose/g), and in Ep LV than in En LV (0.32 [+-]0.07% vs 0.25 [+-]0.05%). In the reserpinized rat heart, the difference in the uptake between Ep LV and En LV was smaller. This suggests that the difference in the regional [sup 125]IMIBG uptake might reflect different intravesicular uptake in the layers of the heart. To our knowledge, the low uptake in the endocardial layer was a new finding which seems to indicate a difference in innervation between the epicardial and endocardial layers of the left ventricle in the rat heart. Autoradiographic study also showed the low uptake of [sup 125]IMIBG in the endocardial layer, while homogeneous perfusion was observed with thallium-201, supporting the tissue uptake study. Thus, the endocardial and epicardial layers of the left ventricle in the rat heart were considered to be differently innervated. (orig.)

  10. Cataract Surgical Uptake Among Older Adults in Ghana.

    Science.gov (United States)

    Ackuaku-Dogbe, E M; Yawson, A E; Biritwum, R B

    2015-06-01

    In sub-Saharan Africa, cataract surgical services are highly inadequate and surgical uptake for cataract is low. This paper describes cataract surgical uptake among older adults in Ghana. This work was based on World Health Organization's multi-country Study on global Ageing and adult health (SAGE), conducted in six countries including Ghana. Wave one of SAGE in Ghana was conducted in 2007-2008 as collaboration between WHO and Department of Community Health, University of Ghana Medical School. A nationally representative sample of 5571 older adults (≥50 years) and a small sample of persons 18-49 years were interviewed. Data was obtained on uptake of cataract surgery in older adults and analyzed using descriptive measures and chi square for associations in categorical outcome measures. Overall surgical uptake was 48.9% among older adults and was slightly higher among older men (49.1%) than women (48%). Cataract surgical uptake was relatively higher in the 60-69 years group (55%), urban residents (52.6%) and those living without partners (50%). Educational and income levels of older persons did not affect cataract surgical uptake. Regional differences in cataract surgical uptake existed; was less than 60% in all ten regions (except one), and the two regions with most self-reported cataracts (Ashanti and Greater Accra) had less than 50% uptake. Intensive public education, engagement of community groups and increased access to cataract surgery at health facilities and outreach services need consideration at national/sub-national levels. Further investigations to garner equity in national eye care efforts are recommended.

  11. Quantification of radionuclide uptake levels for primary bone tumors

    Directory of Open Access Journals (Sweden)

    Hasford Francis

    2015-04-01

    Full Text Available The purpose of the study is to quantify the level of uptake of administered radionuclide in primary bone tumors for patients undergoing bone scintigraphy. Retrospective study on 48 patient's scintigrams to quantify the uptake levels of administered radiopharmaceuticals was performed in a nuclear medicine unit in Ghana. Patients were administered with activity ranging between 0.555 and 1.110 MBq (15–30 mCi, and scanned on Siemens e.cam SPECT system. Analyses on scintigrams were performed with Image J software by drawing regions of interest (ROIs over identified hot spots (pathologic sites. Nine skeletal parts namely cranium, neck, shoulder, sacrum, sternum, vertebra, femur, ribcage, and knee were considered in the study, which involved 96 identified primary tumors. Radionuclide uptakes were quantified in terms of the estimated counts of activity per patient for identified tumor sites. Average normalized counts of activity (nGMC per patient ranged from 5.2759 ± 0.6590 cts/mm2/MBq in the case of cranium tumors to 72.7569 ± 17.8786 cts/mm2/MBq in the case of ribcage tumors. The differences in uptake levels could be attributed to different mechanisms of Tc-99m MDP uptake in different types of bones, which is directly related to blood flow and degree of osteoblastic activity. The overall normalized count of activity for the 96 identified tumors was estimated to be 23.0350 ± 19.5424 cts/mm2/MBq. The study revealed highest uptake of activity in ribcage and least uptake in cranium. Quantification of radionuclide uptakes in tumors is important and recommended in assessing patient's response to therapy, doses to critical organs and in diagnosing tumors.

  12. Ensemble Learned Vaccination Uptake Prediction using Web Search Queries

    OpenAIRE

    Hansen, Niels Dalum; Lioma, Christina; Mølbak, Kåre

    2016-01-01

    We present a method that uses ensemble learning to combine clinical and web-mined time-series data in order to predict future vaccination uptake. The clinical data is official vaccination registries, and the web data is query frequencies collected from Google Trends. Experiments with official vaccine records show that our method predicts vaccination uptake eff?ectively (4.7 Root Mean Squared Error). Whereas performance is best when combining clinical and web data, using solely web data yields...

  13. Constitutive uptake and degradation of fatty acids by Yersinia pestis.

    OpenAIRE

    Moncla, B. J.; Hillier, S L; Charnetzky, W T

    1983-01-01

    Yersinia pestis was found to utilize palmitic acid as a primary carbon and energy source. No inhibition of growth by palmitic acid was observed. Comparison of palmitic acid uptake by cells pregrown either with or without palmitic acid demonstrated that fatty acid uptake was constitutive. High basal levels of two enzymes of beta-oxidation, beta-hydroxyacyl-coenzyme A dehydrogenase and thiolase, and the two enzymes of the glyoxylate shunt, isocitrate lyase and malate synthase, were found in cel...

  14. Extracellular Enzymes Facilitate Electron Uptake in Biocorrosion and Bioelectrosynthesis

    OpenAIRE

    2015-01-01

    ABSTRACT Direct, mediator-free transfer of electrons between a microbial cell and a solid phase in its surrounding environment has been suggested to be a widespread and ecologically significant process. The high rates of microbial electron uptake observed during microbially influenced corrosion of iron [Fe(0)] and during microbial electrosynthesis have been considered support for a direct electron uptake in these microbial processes. However, the underlying molecular mechanisms of direct elec...

  15. Uptake of I-131 MIBG by medullary thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Endo, K.; Koizumi, M.; Sakahara, H.; Nakashima, T.; Ohta, H.; Kasagi, K.; Konishi, J.; Miyauchi, A.; Kuma, K.; Torizuka, K.

    1985-05-01

    I-131 MIBG scans are useful for the localization of pheochromocytoma and neuroblastoma with high catecholamine levels. Recently the authors have found that medullary thyroid cancer also showed an uptake of I-131 MIBG in both primary neck tumors and metastatic sites. Up to now scintigraphic studies were performed in 5 patients with medullary thyroid cancer. Scintigraphy was done at 24 and 48 hours after the administration of 0.5 mCi of I-131 MIBG, thyroid uptake of dissociated I-131 being prevented by Lugol's solution. Four out of 5 cases were familial type and uptake of I-131 MIBG was similarly observed in medullary thyroid cancer as well as in pheochromocytoma. Bone metastasis of medullary thyroid cancer was also detected with I-131 MIBG. However, one case of sporadic form was negative with I-131 MIBG, whereas there was a high uptake of Tc(V)-99m dimercaptosuccinic acid: a newly developed radiopharmaceutical for medullary thyroid cancer, visualizing a different uptake mechanism of both reagents (J Nucl Med 25: 323-325, 1984). After adrenalectomy high uptake of I-131 MIBG was still observed in medullary thyroid cancer, in spite of normal catecholamine levels. The tumor to blood ratio was estimated in vivo to be about several hundreds at 24 hours after the administration. These cells are of neural crest origin and the mechanism of uptake of I-131 MIBG may not be related to the catechamine uptake mechanism. This paper concludes that I-131 MIBG is useful not only for the localization but also for the treatment of medullary thyroid cancer, as preliminary performed in pheochromocytoma and neuroblastoma.

  16. Root uptake of organic contaminants into plants: Species differences

    OpenAIRE

    Orita, Naho

    2012-01-01

    Trace amounts of xenobiotic organic contaminants have been frequently identified in the environment, including surface water and wastewater streams, and some are even in drinking water. The concern of unintended ingestion by humans or wildlife of such compounds resulting from the uptake by plants has risen in recent years. Although the uptake of a variety of xenobiotic organic contaminants by plants has been reported and the contaminants are found in the fruits in some cases, the differences ...

  17. Older adults' uptake and adherence to exercise classes: Instructors' perspectives.

    OpenAIRE

    Hawley-Hague, Helen; Horne, Maria; Skelton, Dawn A; Todd, Chris

    2016-01-01

    Exercise classes provide a range of benefits for older adults, but adherence levels are poor. We know little of instructors' experiences of delivering exercise classes to older adults. Semistructured interviews, informed by the Theory of Planned Behavior (TPB), were conducted with instructors (n = 19) delivering multicomponent exercise classes to establish their perspectives on older adults' uptake and adherence to exercise classes. Analysis revealed 'barriers' to uptake related to identity, ...

  18. The role of calcium in intracellular pathways of rutin in rat pancreatic islets: potential insulin secretagogue effect.

    Science.gov (United States)

    Kappel, Virginia D; Frederico, Marisa J S; Postal, Bárbara G; Mendes, Camila P; Cazarolli, Luisa H; Silva, Fátima R M B

    2013-02-28

    Rutin is a flavonol glycoside with multiple biological activities and it has been demonstrated that rutin modulates glucose homeostasis. In pancreatic β-cell, an increase in intracellular calcium concentration triggers exocytosis and thus insulin secretion. The aim of the study reported herein was to investigate the effect of rutin associated intracellular pathways on Ca(2+) uptake in isolated rat pancreatic islets. We focused on the acute effects of rutin on in vivo insulin secretion and the in vitro cellular signaling of pancreatic islets related to this effect. The results show that rutin significantly increased glucose-induced insulin secretion in an in vivo treatment. Moreover, it was demonstrated that rutin stimulated Ca(2+) uptake after 10 min of incubation compared with the respective control group. The involvement of L-type voltage-dependent Ca(2+) channels (L-VDCCs) was evidenced using nifedipine, while the use of glibenclamide and diazoxide demonstrated that the ATP-sensitive potassium (KATP) channels are not involved in the rutin action in pancreatic islets. In conclusion, rutin diminish glycemia, potentiate insulin secretion in vivo and significantly stimulates Ca(2+) uptake in rat pancreatic islets. A novel cellular mechanism of action of rutin in Ca(2+) uptake on pancreatic β-cells was elucidated. Rutin modulates Ca(2+) uptake in pancreatic islets by opening L-VDCCs, alter intracellular Ca(2+), PLC and PKC signaling pathways, characterizing KATP channel-independent pathways. These findings highlight rutin, a dietary adjuvant, as a potential insulin secretagogue contributing to glucose homeostasis.

  19. The role of iron uptake in pathogenicity and symbiosis in Photorhabdus luminescens TT01

    Directory of Open Access Journals (Sweden)

    Joyce Susan A

    2010-06-01

    Full Text Available Abstract Background Photorhabdus are Gram negative bacteria that are pathogenic to insect larvae whilst also having a mutualistic interaction with nematodes from the family Heterorhabditis. Iron is an essential nutrient and bacteria have different mechanisms for obtaining both the ferrous (Fe2+ and ferric (Fe3+ forms of this metal from their environments. In this study we were interested in analyzing the role of Fe3+ and Fe2+ iron uptake systems in the ability of Photorhabdus to interact with its invertebrate hosts. Results We constructed targeted deletion mutants of exbD, feoABC and yfeABCD in P. luminescens TT01. The exbD mutant was predicted to be crippled in its ability to obtain Fe3+ and we show that this mutant does not grow well in iron-limited media. We also show that this mutant was avirulent to the insect but was unaffected in its symbiotic interaction with Heterorhabditis. Furthermore we show that a mutation in feoABC (encoding a predicted Fe2+ permease was unaffected in both virulence and symbiosis whilst the divalent cation transporter encoded by yfeABCD is required for virulence in the Tobacco Hornworm, Manduca sexta (Lepidoptera but not in the Greater Wax Moth, Galleria mellonella (Lepidoptera. Moreover the Yfe transporter also appears to have a role during colonization of the IJ stage of the nematode. Conclusion In this study we show that iron uptake (via the TonB complex and the Yfe transporter is important for the virulence of P. luminescens to insect larvae. Moreover this study also reveals that the Yfe transporter appears to be involved in Mn2+-uptake during growth in the gut lumen of the IJ nematode. Therefore, the Yfe transporter in P. luminescens TT01 is important during colonization of both the insect and nematode and, moreover, the metal ion transported by this pathway is host-dependent.

  20. Effect of Sulfate on Selenium Uptake And Chemical Speciation in Convolvulus Arvensis L

    Energy Technology Data Exchange (ETDEWEB)

    Cruz-Jimenez, G.; Peralta-Video, J.R.; Rosa, G.de la; Meitzner, G.; Parson, J.G.; Gardea-Torresdey, J.L.

    2007-08-08

    Hydroponic experiments were performed to study several aspects of Se uptake by C. arvensis plants. Ten day old seedlings were exposed for eight days to different combinations of selenate (SeO{sub 4}{sup 2-}), sulfate (SO{sub 4}{sup 2-}), and selenite (SeO{sub 3}{sup 2-}). The results showed that in C. arvensis, SO{sub 4}{sup 2-} had a negative effect (P < 0.05) on SeO{sub 4}{sup 2-} uptake. However, a positive interaction produced a significant increase in SO{sub 4}{sup 2-} uptake when SeO{sub 4}{sup 2-} was at high concentration in the media. X-ray absorption spectroscopy studies showed that C. arvensis plants converted more than 70% of the supplied SeO{sub 3}{sup 2-} into organoselenium compounds. However, only approximately 50% of the supplied SeO{sub 4}{sup 2-} was converted into organoselenium species while the residual 50% remained in the inorganic form. Analysis using LC-XANES fittings confirmed that the S metabolic pathway was affected by the presence of Se. The main Se compounds that resembled those Se species identified in C. arvensis were Se-cystine, Se-cysteine, SeO{sub 3}{sup 2-}, and SeO{sub 4}{sup 2-}, whereas for S the main compounds were cysteine, cystine, oxidized glutathione, reduced glutathione, and SO{sub 4}{sup 2-}. The results of these studies indicated that C. arvensis could be considered as a possible option for the restoration of soil moderately contaminated with selenium even in the presence of sulfate.

  1. Nonendosomal cellular uptake of ligand-free, positively charged gold nanoparticles.

    Science.gov (United States)

    Taylor, Ulrike; Klein, Sabine; Petersen, Svea; Kues, Wilfried; Barcikowski, Stephan; Rath, Detlef

    2010-05-01

    Gold nanoparticles (GNPs) have interesting optical properties, such as exceptionally high quantum yields and virtually limitless photostability. Therefore, they show the potential for applications as biomarkers especially suitable for in vivo and long-term studies. The generation of GNPs using pulsed laser light rather than chemical means provides nanoparticles, which are remarkably stable in a variety of media without the need of stabilizing agents or ligands. This stabilization is achieved by partial oxidation of the gold surface resulting in positively charged GNPs. However, little is known about cellular uptake of such ligand-free nanoparticles, their intracellular fate, or cell viability after nanoparticle contact. The current work is aimed to explore the response of a bovine cell line to GNP exposure mainly using laser scanning confocal microscopy (LSCM) supported by other techniques. Cultured bovine immortalized cells (GM7373) were coincubated with GNP (average diameter 15 nm, 50 microM Au) for 2, 24, and 48 h. The detection of GNP-associated light scattering by the LSCM facilitated a clear distinction between GNP-containing cells and the negative controls. After 48 h, 75% of cells had visibly incorporated nanoparticles. No colocalization was detected with either Rab5a or Lamp1-positive structures, i.e., endosomes or lysosomes, respectivley. However, transmission electron microscope analysis of GNP-coincubated cells indicated the nanoparticles to be positioned within electron-dense structures. Coincubation at 4 degrees C did not inhibit nanoparticle uptake, suggesting diffusion as possible entrance mechanism. Although the assessment of cell morphology, membrane integrity, and apoptosis revealed no GNP-related loss of cell viability at a gold concentration of 25 microM or below, a cytotoxic effect was observed in a proliferation assay after exposing low cell numbers to 50 microM Au and above. In conclusion, this study confirmed the cellular uptake of ligand

  2. Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.

    Science.gov (United States)

    Eijkelkamp, Bart A; Morey, Jacqueline R; Ween, Miranda P; Ong, Cheryl-lynn Y; McEwan, Alastair G; Paton, James C; McDevitt, Christopher A

    2014-01-01

    Streptococcus pneumoniae requires manganese for colonization of the human host, but the underlying molecular basis for this requirement has not been elucidated. Recently, it was shown that zinc could compromise manganese uptake and that zinc levels increased during infection by S. pneumoniae in all the niches that it colonized. Here we show, by quantitative means, that extracellular zinc acts in a dose dependent manner to competitively inhibit manganese uptake by S. pneumoniae, with an EC50 of 30.2 µM for zinc in cation-defined media. By exploiting the ability to directly manipulate S. pneumoniae accumulation of manganese, we analyzed the connection between manganese and superoxide dismutase (SodA), a primary source of protection for S. pneumoniae against oxidative stress. We show that manganese starvation led to a decrease in sodA transcription indicating that expression of sodA was regulated through an unknown manganese responsive pathway. Intriguingly, examination of recombinant SodA revealed that the enzyme was potentially a cambialistic superoxide dismutase with an iron/manganese cofactor. SodA was also shown to provide the majority of protection against oxidative stress as a S. pneumoniae ΔsodA mutant strain was found to be hypersensitive to oxidative stress, despite having wild-type manganese levels, indicating that the metal ion alone was not sufficiently protective. Collectively, these results provide a quantitative assessment of the competitive effect of zinc upon manganese uptake and provide a molecular basis for how extracellular zinc exerts a 'toxic' effect on bacterial pathogens, such as S. pneumoniae.

  3. Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Bart A Eijkelkamp

    Full Text Available Streptococcus pneumoniae requires manganese for colonization of the human host, but the underlying molecular basis for this requirement has not been elucidated. Recently, it was shown that zinc could compromise manganese uptake and that zinc levels increased during infection by S. pneumoniae in all the niches that it colonized. Here we show, by quantitative means, that extracellular zinc acts in a dose dependent manner to competitively inhibit manganese uptake by S. pneumoniae, with an EC50 of 30.2 µM for zinc in cation-defined media. By exploiting the ability to directly manipulate S. pneumoniae accumulation of manganese, we analyzed the connection between manganese and superoxide dismutase (SodA, a primary source of protection for S. pneumoniae against oxidative stress. We show that manganese starvation led to a decrease in sodA transcription indicating that expression of sodA was regulated through an unknown manganese responsive pathway. Intriguingly, examination of recombinant SodA revealed that the enzyme was potentially a cambialistic superoxide dismutase with an iron/manganese cofactor. SodA was also shown to provide the majority of protection against oxidative stress as a S. pneumoniae ΔsodA mutant strain was found to be hypersensitive to oxidative stress, despite having wild-type manganese levels, indicating that the metal ion alone was not sufficiently protective. Collectively, these results provide a quantitative assessment of the competitive effect of zinc upon manganese uptake and provide a molecular basis for how extracellular zinc exerts a 'toxic' effect on bacterial pathogens, such as S. pneumoniae.

  4. Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Ekhtear [Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan); Ota, Akinobu, E-mail: aota@aichi-med-u.ac.jp [Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan); Karnan, Sivasundaram; Damdindorj, Lkhagvasuren [Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan); Takahashi, Miyuki [Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan); Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan); Konishi, Yuko; Konishi, Hiroyuki; Hosokawa, Yoshitaka [Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan)

    2013-12-15

    Although chronic arsenic exposure is a well-known risk factor for cardiovascular diseases, including atherosclerosis, the molecular mechanism underlying arsenic-induced atherosclerosis remains obscure. Therefore, this study aimed to elucidate this molecular mechanism. We examined changes in the mRNA level of the lectin-like oxidized LDL (oxLDL) receptor (LOX-1) in a mouse aortic endothelial cell line, END-D, after sodium arsenite (SA) treatment. SA treatment significantly upregulated LOX-1 mRNA expression; this finding was also verified at the protein expression level. Flow cytometry and fluorescence microscopy analyses showed that the cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with SA treatment. In addition, an anti-LOX-1 antibody completely abrogated the augmented uptake of Dil-oxLDL. We observed that SA increased the levels of the phosphorylated forms of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB)/p65. SA-induced upregulation of LOX-1 protein expression was clearly prevented by treatment with an antioxidant, N-acetylcysteine (NAC), or an NF-κB inhibitor, caffeic acid phenethylester (CAPE). Furthermore, SA-augmented uptake of Dil-oxLDL was also prevented by treatment with NAC or CAPE. Taken together, our results indicate that arsenic upregulates LOX-1 expression through the reactive oxygen species-mediated NF-κB signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of the aberrant LOX-1 signaling pathway in the pathogenesis of arsenic-induced atherosclerosis. - Highlights: • Sodium arsenite (SA) increases LOX-1 expression in mouse aortic endothelial cells. • SA enhances cellular uptake of oxidized LDL in dose-dependent manner. • SA-induced ROS generation enhances phosphorylation of NF-κB. • SA upregulates LOX-1 expression through ROS-activated NF-κB signaling pathway.

  5. DMPD: Antiviral innate immunity pathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16474426 Antiviral innate immunity pathways. Seth RB, Sun L, Chen ZJ. Cell Res. 200...6 Feb;16(2):141-7. (.png) (.svg) (.html) (.csml) Show Antiviral innate immunity pathways. PubmedID 16474426 ...Title Antiviral innate immunity pathways. Authors Seth RB, Sun L, Chen ZJ. Publication Cell Res. 2006 Feb;16

  6. The effect of hydrate promoters on gas uptake.

    Science.gov (United States)

    Xu, Chun-Gang; Yu, Yi-Song; Ding, Ya-Long; Cai, Jing; Li, Xiao-Sen

    2017-08-16

    Gas hydrate technology is considered as a promising technology in the fields of gas storage and transportation, gas separation and purification, seawater desalination, and phase-change thermal energy storage. However, to date, the technology is still not commercially used mainly due to the low gas hydrate formation rate and the low gas uptake. In this study, the effect of hydrate promoters on gas uptake was systematically studied and analyzed based on hydrate-based CH4 storage and CO2 capture from CO2/H2 gas mixture experiments. Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR) and gas chromatography (GC) were employed to analyze the microstructures and gas compositions. The results indicate that the effect of the hydrate promoter on the gas uptake depends on the physical and chemical properties of the promoter and gas. A strong polar ionic promoter is not helpful towards obtaining the ideal gas uptake because a dense hydrate layer is easily formed at the gas-liquid interface, which hinders gas diffusion from the gas phase to the bulk solution. For a weak polar or non-polar promoter, the gas uptake depends on the dissolution characteristics among the different substances in the system. The lower the mutual solubility among the substances co-existing in the system, the higher the independence among the substances in the system; this is so that each phase has an equal chance to occupy the hydrate cages without or with small interactions, finally leading to a relatively high gas uptake.

  7. Uptake of {sup 64}Cu-oxine by marine phytoplankton

    Energy Technology Data Exchange (ETDEWEB)

    Croot, P.L.; Karson, B.; Elteren, J.T. van; Kroon, J.J.

    1999-10-15

    Short-term uptake experiments using fie phytoplankton species (Synechococcus clone DC2, Amphidinium carterae, Chrysochromulina polylepis, Ditylum brightwelli, and Prorocentrum micans) demonstrated rapid uptake of the lipophilic complex {sup 64}Cu-oxine, presumably by diffusion of the complex across the plasma membrane. This passive uptake mechanism was extremely rapid and significantly faster than facilitated uptake by the free metal ion. Measured values of the observed permeability, P{sub obs}, ranged from 0.55 to 18.6 x 10{sup {minus}4} cm s{sup {minus}1}, showing only small differences between the various algal species. Removal rate constants, k{sup bio}, varied much more widely, 0.009--570 x 10{sup {minus}9} L cell{sup {minus}1} h{sup {minus} 1}, between the algae, indicating the influence of surface area on the uptake kinetics. Maximum internal Cu levels were reached after approximately 2 h, showing that a major limiting factor in the uptake of Cu from Cu-oxine is the concentration of intracellular Cu binding sites.

  8. Acoustic trauma increases cochlear and hair cell uptake of gentamicin.

    Directory of Open Access Journals (Sweden)

    Hongzhe Li

    Full Text Available BACKGROUND: Exposure to intense sound or high doses of aminoglycoside antibiotics can increase hearing thresholds, induce cochlear dysfunction, disrupt hair cell morphology and promote hair cell death, leading to permanent hearing loss. When the two insults are combined, synergistic ototoxicity occurs, exacerbating cochlear vulnerability to sound exposure. The underlying mechanism of this synergism remains unknown. In this study, we tested the hypothesis that sound exposure enhances the intra-cochlear trafficking of aminoglycosides, such as gentamicin, leading to increased hair cell uptake of aminoglycosides and subsequent ototoxicity. METHODS: Juvenile C57Bl/6 mice were exposed to moderate or intense sound levels, while fluorescently-conjugated or native gentamicin was administered concurrently or following sound exposure. Drug uptake was then examined in cochlear tissues by confocal microscopy. RESULTS: Prolonged sound exposure that induced temporary threshold shifts increased gentamicin uptake by cochlear hair cells, and increased gentamicin permeation across the strial blood-labyrinth barrier. Enhanced intra-cochlear trafficking and hair cell uptake of gentamicin also occurred when prolonged sound, and subsequent aminoglycoside exposure were temporally separated, confirming previous observations. Acute, concurrent sound exposure did not increase cochlear uptake of aminoglycosides. CONCLUSIONS: Prolonged, moderate sound exposures enhanced intra-cochlear aminoglycoside trafficking into the stria vascularis and hair cells. Changes in strial and/or hair cell physiology and integrity due to acoustic overstimulation could increase hair cell uptake of gentamicin, and may represent one mechanism of synergistic ototoxicity.

  9. Characterization of cadmium uptake by the water lily Nymphaea aurora.

    Science.gov (United States)

    Schor-Fumbarov, Tamar; Keilin, Zvika; Tel-Or, Elisha

    2003-01-01

    This study characterizes cadmium (Cd) uptake by the waterlily Nymphaea aurora, (Nymphaeaceae) in two systems: a model hydroponic Cd solution and heavily polluted sludge from two sites in Israel. The uptake of Cd from hydroponic solution resulted in Cd storage in petioles and laminae of Nymphaea, as well as in the roots. The pH of the solution affected Cd solubility and availability, with pH 5.5 yielding maximum Cd content in the plant (140 mg Cd per g DW). Cd uptake was reduced by the addition of EDTA to the hydroponic growth medium, although EDTA enhanced heavy metal uptake by terrestrial plants. Nymphaea efficiently reduced the concentration of Cd in heavy metal polluted urban and industrial sludge and the amount of Cd uptake was enhanced by the addition of KCl to the sludge and by adjustment of the pH to 5.5. The inherent growth patterns of Nymphaea plants allowed Cd uptake by the shoot and root, and resulted in maximum contact between the various plant parts and the growth media. Thus, Nymphaea has potential as an optimal, highly effective phytoremediation tool for the removal of Cd from polluted waste sources.

  10. Lung damage and pulmonary uptake of serotonin in intact dogs

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, C.A.; Christensen, C.W.; Rickaby, D.A.; Linehan, J.H.; Johnston, M.R.

    1985-06-01

    The authors examined the influence of glass bead embolization and oleic acid, dextran, and imipramine infusion on the pulmonary uptake of trace doses of (/sup 3/H)serotonin and the extravascular volume accessible to (/sup 14/C)antipyrine in anesthetized dogs. Embolization and imipramine decreased serotonin uptake by 53 and 61%, respectively, but no change was observed with oleic acid or dextran infusion. The extravascular volume accessible to the antipyrine was reduced by 77% after embolization and increased by 177 and approximately 44% after oleic acid and dextran infusion, respectively. The results suggest that when the perfused endothelial surface is sufficiently reduced, as with embolization, the uptake of trace doses of serotonin will be depressed. In addition, decreases in serotonin uptake in response to imipramine in this study and in response to certain endothelial toxins in other studies suggest that serotonin uptake can reveal certain kinds of changes in endothelial function. However, the lack of a response to oleic acid-induced damage in the present study suggests that serotonin uptake is not sensitive to all forms of endothelial damage.

  11. Uptake of SPECT radiopharmaceuticals in neocortical brain cultures

    Energy Technology Data Exchange (ETDEWEB)

    Jong, B.M. de; Royen, E.A. van

    1989-01-01

    The uptake, retention and uptake antagonism of /sup 201/Tl-DDC, /sup 201/Tl-Cl, /sup 123/I-IMP, /sup 99m/Tc-HMPAO and /sup 99m/Tc-O4/sup -/ were compared in rat neocortex cultures. /sup 201/Tl-DDC and /sup 123/I-IP revealed the highest uptake of radioactivity in the cultures. /sup 99m/Tc-HMPAO and /sup 123/I-IMP showed the highest retention of radioactivity within the tissue in washout experiments. Blocking of bioelectric activity by tetrodotoxin did not significantly affect the uptake of the radiopharmaceuticals (RPHA). Inhibition of Na K ATPase by ouabain inhibited the uptake of /sup 201/Tl-Cl (77%) and /sup 201/Tl-DDC (27%). Imipramine showed a significantly stronger inhibitory effect on /sup 123/I-IMP uptake in comparison with the effect on other RPHA. /sup 99m/Tc-O4/sup -/ was not concentrated within the cultured tissue. Under the in vitro conditions used in this study, the various RPHA were characterised by distinct differences in their interaction with cortical brain tissue.

  12. Does copper reduce cadmium uptake by different rice genotypes?

    Institute of Scientific and Technical Information of China (English)

    CUI Yujing; ZHANG Xuhong; ZHU Yongguan

    2008-01-01

    A hydroponics experiment was conducted to investigate the effect of copper (Cu) on cadmium (Cd),calcium (Ca),iron (Fe),and zinc (Zn) uptake by several rice genotypes.The experiment was carried out as a 2×2×4 factorial with four rice genotypes and two levels of Cu and Cd in nutrient solution.Plants were grown in a growth chamber with controlled environment.The results showed a significant difference between the biomass of different rice genotypes (P<0.001).The Cd and Cu concentration in the solution had no significant effect on the biomass.The addition of Cu significantly decreased Cd uptake by shoots and roots of rice (P<0.001).The Cd concentration did not significantly influence Ca uptake by plants,whereas the Cu concentration did (P=0.034).There was a significant influence of Cd on Fe uptake by shoots and roots (P<0.001,P=0.003,respectively).Zn uptake decreased significantly as the addition of Cd and Cu increased in shoots.We concluded that Cu had significant influence on Cd uptake.The possible mechanisms were discussed.

  13. Uptake of HNO3 to deliquescent sea-salt particles

    Directory of Open Access Journals (Sweden)

    H. W. Gäggeler

    2002-06-01

    Full Text Available The uptake of HNO3 to deliquescent airborne sea-salt particles (RH = 55%, P = 760 torr, T = 300 K at concentrations from 2 to 575 ppbv is measured in an aerosol flow tube using 13N as a tracer. Small particles (~ 70 nm diameter are used in order to minimize the effect of diffusion in the gas phase on the mass transfer. Below 100 ppbv, an uptake coefficient (gupt of 0.50 ± 0.20 is derived. At higher concentrations, the uptake coefficient decreases along with the consumption of aerosol chloride. Data interpretation is further supported by using the North American Aerosol Inorganics Model (AIM, which predicts the aqueous phase activities of ions and the gas-phase partial pressures of H2O, HNO3, and HCl at equilibrium for the NaCl/HNO3/H2O system. These simulations show that the low concentration data are obtained far from equilibrium, which implies that the uptake coefficient derived is equal to the mass accommodation coefficient under these conditions. The observed uptake coefficient can serve as input to modeling studies of atmospheric sea-salt aerosol chemistry. The main sea-salt aerosol burden in the marine atmosphere is represented by coarse mode particles (> 1 mm diameter. This implies that diffusion in the gas-phase is the limiting step to HNO3 uptake until the sea-salt has been completely processed.

  14. Muscle contraction increases carnitine uptake via translocation of OCTN2.

    Science.gov (United States)

    Furuichi, Yasuro; Sugiura, Tomoko; Kato, Yukio; Takakura, Hisashi; Hanai, Yoshiteru; Hashimoto, Takeshi; Masuda, Kazumi

    2012-02-24

    Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL(uptake)) of l-[(3)H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL(uptake) of [(14)C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL(uptake) of l-[(3)H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (pmuscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (pmuscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.

  15. Modeling uptake kinetics of cadmium by field-grown lettuce

    Energy Technology Data Exchange (ETDEWEB)

    Chen Weiping [Department of Environmental Sciences, University of California, 900 University Avenue, Riverside, CA 92521 (United States)], E-mail: chenweip@yahoo.com.cn; Li Lianqing [Institute of Resources, Ecosystem and Environment of Agriculture, Nanjing Agricultural University, Nanjing 210095 (China); Chang, Andrew C.; Wu Laosheng [Department of Environmental Sciences, University of California, 900 University Avenue, Riverside, CA 92521 (United States); Kwon, Soon-Ik [Agricultural Environmental and Ecology Division, National Institute of Agricultural Science and Technology, Suwon 441-707 (Korea, Republic of); Bottoms, Rick [Desert Research and Extension Center, 1004 East Holton Road, El Centro, CA 92243 (United States)

    2008-03-15

    Cadmium uptake by field grown Romaine lettuce treated with P-fertilizers of different Cd levels was investigated over an entire growing season. Results indicated that the rate of Cd uptake at a given time of the season can be satisfactorily described by the Michaelis-Menten kinetics, that is, plant uptake increases as the Cd concentration in soil solution increases, and it gradually approaches a saturation level. However, the rate constant of the Michaelis-Menten kinetics changes over the growing season. Under a given soil Cd level, the cadmium content in plant tissue decreases exponentially with time. To account for the dynamic nature of Cd uptake, a kinetic model integrating the time factor was developed to simulate Cd plant uptake over the growing season: C{sub Plant} = C{sub Solution} . PUF{sub max} . exp[-b . t], where C{sub Plant} and C{sub Solution} refer to the Cd content in plant tissue and soil solution, respectively, PUF{sub max} and b are kinetic constants. - A kinetic model was developed to evaluate the uptake of Cd under field conditions.

  16. Simple and robust method for estimation of the split between the oxidative pentose phosphate pathway and the Embden- Meyerhof-Parnas pathway in microorganisms

    DEFF Research Database (Denmark)

    Christensen, J.; Christiansen, Torben; Gombert, Andreas Karoly

    2001-01-01

    that includes the entire central carbon metabolism. Setting the glucose uptake rate to 100, the algebraic expression yielded estimates of the PP pathway flux in B. clausii, S. cerevisiae, and P. chrysogenum of 20, 42, and 75, respectively. These results are in accordance with the results from the numerical......The flux through the oxidative pentose phosphate (PP) pathway was estimated in Bacillus clausii, Saccharomyces cerevisiae, and Penicillium chrysogenum growing in chemostats with [1-C- 13]glucose as the limiting substrate. The flux calculations were based on a simple algebraic expression...... that is valid irrespective of isotope rearrangements arising from reversibilities of the reactions in the PP pathway and the upper part of the Embden-Meyerhof-Parnas pathway. The algebraically calculated fluxes were validated by comparing the results with estimates obtained using a numerical method...

  17. Toxicological effects of multi-walled carbon nanotubes on Saccharomyces cerevisiae: The uptake kinetics and mechanisms and the toxic responses

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Song; Zhu, Bin; Huang, Aiguo [College of Animal Science and Technology, Northwest A& F University, Yangling 712100 (China); Hu, Yang [College of Science, Northwest A& F University, Yangling 712100 (China); Wang, Gaoxue, E-mail: wanggaoxue@126.com [College of Animal Science and Technology, Northwest A& F University, Yangling 712100 (China); Ling, Fei, E-mail: feiling@nwsuaf.edu.cn [College of Animal Science and Technology, Northwest A& F University, Yangling 712100 (China)

    2016-11-15

    Highlights: • MWCNTs (<100 mg/L) were not toxic to S. cerevisiae. • MWCNTs were internalized in S. cerevisiae cells by three pathways. • The uptake kinetics and the subcellular distribution of MWCNTs in S. cerevisiae cells were shown. • S. cerevisiae cells were undergoing apoptosis by mitochondrial impairment pathway. - Abstract: Using Saccharomyces cerevisiae as an experimental model, the potential toxicological effects of oxidized multi-walled carbon nanotubes (MWCNTs) were investigated following exposure to 0–600 mg/L for 24 h. Results indicated that MWCNTs (>100 mg/L) had adverse effects on the cell proliferation. MWCNTs were clearly visible in lysosome, vacuole, endosome, mitochondria, multivesicular body and localization in the perinuclear region. The uptake kinetics data demonstrated that the maximum MWCNTs content (209.61 mg/g) was reached at 3 h, and a steady state was reached after 18 h. Based on the combined results of transmission electron microscope, endocytosis inhibition experiments and endocytosis-related genes (END3, END6, Sla2 and Rsp5) expression analysis, we elucidated MWCNTs uptake mechanism: (i) via a direct penetration of single MWCNTs; (ii) via endocytosis of single MWCNTs; and (iii) via endocytosis of MWCNTs aggregates. The percentage of apoptosis was significant increased at 600 mg/L. The decrease of mitochondrial transmembrane potential and the leakage of cytochrome c shown dose-dependent manners. Interestingly, there was no significant increase of reactive oxygen species (ROS). The apoptosis-related genes (SOD1, SOD2, Yca1, Nma111 and Nuc1) were significant changed. These results obtained in our study demonstrated that oxidized MWCNTs induce Saccharomyces cerevisiae apoptosis via mitochondrial impairment pathway.

  18. Metabolic pathways of trichothecenes.

    Science.gov (United States)

    Wu, Qinghua; Dohnal, Vlastimil; Huang, Lingli; Kuca, Kamil; Yuan, Zonghui

    2010-05-01

    Trichothecenes are a group of mycotoxins mainly produced by the fungi of Fusarium genus. Consumers are particularly concerned over the toxicity and food safety of trichothecenes and their metabolites from food-producing animals. The metabolism of T-2 toxin, deoxynivalenol (DON), nivalenol (NIV), fusarenon-X (FX), diacetoxyscirpenol (DAS), 3-acetyldeoxy-nivalenol (3-aDON), and 15-acetyldeoxynivalenol (15-aDON) in rodents, swine, ruminants, poultry, and humans are reviewed in this article. Metabolic pathways of these mycotoxins are very different. The major metabolic pathways of T-2 toxin in animals are hydrolysis, hydroxylation, de-epoxidation, and conjugation. After being transformed to HT-2 toxin, it undergoes further hydroxylation at C-3' to yield 3'-hydroxy-HT-2 toxin, which is considered as an activation pathway, whereas transformation from T-2 to T-2 tetraol is an inactivation pathway in animals. The typical metabolites of T-2 toxin in animals are HT-2 toxin, T-2 triol, T-2 tetraol, neosolaniol (NEO), 3'-hydroxy-HT-2, and 3'-hydroxy-T-2, whereas HT-2 toxin is the main metabolite in humans. De-epoxidation is an important pathway for detoxification in animals. De-epoxy products, DOM-1, and de-epoxy-NIV are the main metabolites of DON and NIV in most animals, respectively. However, the two metabolites are not found in humans. Deacetyl can occur rapidly on the acetyl derivatives, 3-aDON, 15-aDON, and FX. DAS is metabolized in animals to 15-monoacetoxyscirpenol (15-MAS) via C-4 deacetylation and then transformed to scirpentriol (SCP) via C-15 deacetylation. Finally, the epoxy is lost, yielding de-epoxy-SCP. De-epoxy-15-MAS is also the main metabolite of DAS. 15-MAS is the main metabolite in human skin. The review on the metabolism of trichothecenes will help one to well understand the fate of these toxins' future in animals and humans, as well as provide basic information for the risk assessment of them for food safety.

  19. Visualization of custom-tailored iron oxide nanoparticles chemistry, uptake, and toxicity

    Science.gov (United States)

    Wilkinson, Kai; Ekstrand-Hammarström, Barbro; Ahlinder, Linnea; Guldevall, Karolin; Pazik, Robert; Kępiński, Leszek; Kvashnina, Kristina O.; Butorin, Sergei M.; Brismar, Hjalmar; Önfelt, Björn; Österlund, Lars; Seisenbaeva, Gulaim A.; Kessler, Vadim G.

    2012-11-01

    Nanoparticles of iron oxide generated by wearing of vehicles have been modelled with a tailored solution of size-uniform engineered magnetite particles produced by the Bradley reaction, a solvothermal metal-organic approach rendering hydrophilic particles. The latter does not bear any pronounced surface charge in analogy with that originating from anthropogenic sources in the environment. Physicochemical properties of the nanoparticles were thoroughly characterized by a wide range of methods, including XPD, TEM, SEM, DLS and spectroscopic techniques. The magnetite nanoparticles were found to be sensitive for transformation into maghemite under ambient conditions. This process was clearly revealed by Raman spectroscopy for high surface energy magnetite particles containing minor impurities of the hydromaghemite phase and was followed by quantitative measurements with EXAFS spectroscopy. In order to assess the toxicological effects of the produced nanoparticles in humans, with and without surface modification with ATP (a model of bio-corona formed in alveolar liquid), a pathway of potential uptake and clearance was modelled with a sequence of in vitro studies using A549 lung epithelial cells, lymphocyte 221-B cells, and 293T embryonal kidney cells, respectively. Raman microscopy unambiguously showed that magnetite nanoparticles are internalized within the A549 cells after 24 h co-incubation, and that the ATP ligand is retained on the nanoparticles throughout the uptake process. The toxicity of the nanoparticles was estimated using confocal fluorescence microscopy and indicated no principal difference for unmodified and modified particles, but revealed considerably different biochemical responses. The IL-8 cytokine response was found to be significantly lower for the magnetite nanoparticles compared to TiO2, while an enhancement of ROS was observed, which was further increased for the ATP-modified nanoparticles, implicating involvement of the ATP signalling pathway in

  20. Substrate uptake, phosphorus repression, and effect of seed culture on glycopeptide antibiotic production

    DEFF Research Database (Denmark)

    Maiti, Soumen K.; Singh, Kamaleshwar P.; Eliasson Lantz, Anna

    2010-01-01

    Actinomycetes, the soil borne bacteria which exhibit filamentous growth, are known for their ability to produce a variety of secondary metabolites including antibiotics. Industrial scale production of such antibiotics is typically carried out in a multi-substrate medium where the product formation...... may experience catabolite repression by one or more of the substrates. Availability of reliable process models is a key bottleneck in optimization of such processes. Here we present a structured kinetic model to describe the growth, substrate uptake and product formation for the glycopeptide...... antibiotic producer strain Amycolatopsis balhimycina DSM5908. The model is based on the premise that the organism is an optimal strategist and that the various metabolic pathways are regulated via key rate limiting enzymes. Further, the model accounts for substrate inhibition and catabolite repression...