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Sample records for active transport mechanism

  1. Common folds and transport mechanisms of secondary active transporters.

    PubMed

    Shi, Yigong

    2013-01-01

    Secondary active transporters exploit the electrochemical potential of solutes to shuttle specific substrate molecules across biological membranes, usually against their concentration gradient. Transporters of different functional families with little sequence similarity have repeatedly been found to exhibit similar folds, exemplified by the MFS, LeuT, and NhaA folds. Observations of multiple conformational states of the same transporter, represented by the LeuT superfamily members Mhp1, AdiC, vSGLT, and LeuT, led to proposals that structural changes are associated with substrate binding and transport. Despite recent biochemical and structural advances, our understanding of substrate recognition and energy coupling is rather preliminary. This review focuses on the common folds and shared transport mechanisms of secondary active transporters. Available structural information generally supports the alternating access model for substrate transport, with variations and extensions made by emerging structural, biochemical, and computational evidence.

  2. Unraveling fatty acid transport and activation mechanisms in Yarrowia lipolytica.

    PubMed

    Dulermo, Rémi; Gamboa-Meléndez, Heber; Ledesma-Amaro, Rodrigo; Thévenieau, France; Nicaud, Jean-Marc

    2015-09-01

    Fatty acid (FA) transport and activation have been extensively studied in the model yeast species Saccharomyces cerevisiae but have rarely been examined in oleaginous yeasts, such as Yarrowia lipolytica. Because the latter begins to be used in biodiesel production, understanding its FA transport and activation mechanisms is essential. We found that Y. lipolytica has FA transport and activation proteins similar to those of S. cerevisiae (Faa1p, Pxa1p, Pxa2p, Ant1p) but mechanism of FA peroxisomal transport and activation differs greatly with that of S. cerevisiae. While the ScPxa1p/ScPxa2p heterodimer is essential for growth on long-chain FAs, ΔYlpxa1 ΔYlpxa2 is not impaired for growth on FAs. Meanwhile, ScAnt1p and YlAnt1p are both essential for yeast growth on medium-chain FAs, suggesting they function similarly. Interestingly, we found that the ΔYlpxa1 ΔYlpxa2 ΔYlant1 mutant was unable to grow on short-, medium-, or long-chain FAs, suggesting that YlPxa1p, YlPxa2p, and YlAnt1p belong to two different FA degradation pathways. We also found that YlFaa1p is involved in FA storage in lipid bodies and that FA remobilization largely depended on YlFat1p, YlPxa1p and YlPxa2p. This study is the first to comprehensively examine FA intracellular transport and activation in oleaginous yeast.

  3. Active transport of vesicles in neurons is modulated by mechanical tension

    NASA Astrophysics Data System (ADS)

    Ahmed, Wylie W.; Saif, Taher A.

    2014-03-01

    Effective intracellular transport of proteins and organelles is critical in cells, and is especially important for ensuring proper neuron functionality. In neurons, most proteins are synthesized in the cell body and must be transported through thin structures over long distances where normal diffusion is insufficient. Neurons transport subcellular cargo along axons and neurites through a stochastic interplay of active and passive transport. Mechanical tension is critical in maintaining proper function in neurons, but its role in transport is not well understood. To this end, we investigate the active and passive transport of vesicles in Aplysia neurons while changing neurite tension via applied strain, and quantify the resulting dynamics. We found that tension in neurons modulates active transport of vesicles by increasing the probability of active motion, effective diffusivity, and induces a retrograde bias. We show that mechanical tension modulates active transport processes in neurons and that external forces can couple to internal (subcellular) forces and change the overall transport dynamics.

  4. Intraparticle mass transport mechanism in activated carbon adsorption of phenols

    SciTech Connect

    Furuya, E.G.; Miura, Y.; Yokomura, H.; Tajima, S.; Yamashita, S.; Chang, H.T.; Noll, K.E.

    1996-10-01

    Two parallel diffusion mechanisms, pore and surface, can control the rate of contaminant adsorption. The two mechanisms are different functions of temperature and adsorbate concentration. To develop a mechanistic design model for adsorption processes, the two mechanisms must be evaluated separately. In this paper, the authors show that the mechanisms can be separated accurately using a stepwise linearization technique. The technique can easily be incorporated in adsorption diffusion modeling. Two phenolic compounds were used in this study: p-chlorophenol (PCP) and p-nitrophenol (PNP). The application of the linearization technique is illustrated using two types of reactors: a completely mixed batch reactor and a differential reactor. The study results show that pore and surface diffusivity can be determined accurately using the linearization technique. Furthermore, the tortuosity for the absorbent can be estimated from the pore diffusivity. For PCP that is strongly adsorbed by the adsorbent, surface diffusion is the dominant mechanism controlling the intraparticle transport. For weakly adsorbed PNP, neither surface nor pore diffusion is dominant.

  5. Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase

    PubMed Central

    Barber, Kara R.; Sherman, Michael

    2017-01-01

    Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs) and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions. Consistent with a block in axonal transport, we find a decrease in number of active zones and reduced neurotransmission in flies overexpressing Par-1 kinase. Interestingly, we find that Par-1 acts independently of Tau-one of the most well studied substrates of Par-1, revealing a presynaptic function for Par-1 that is independent of Tau. Thus, our study strongly suggests that there are distinct mechanisms that transport components of active zones and that they are tightly regulated. PMID:28222093

  6. A fully resolved active musculo-mechanical model for esophageal transport

    PubMed Central

    Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.

    2015-01-01

    Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multilayered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function. PMID:26190859

  7. A fully resolved active musculo-mechanical model for esophageal transport

    NASA Astrophysics Data System (ADS)

    Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.

    2015-10-01

    Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function.

  8. A fully resolved active musculo-mechanical model for esophageal transport.

    PubMed

    Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E; Pandolfino, John E; Kahrilas, Peter J; Patankar, Neelesh A

    2015-10-01

    Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multilayered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function.

  9. Activation and Proton Transport Mechanism in Influenza A M2 Channel

    PubMed Central

    Wei, Chenyu; Pohorille, Andrew

    2013-01-01

    Molecular dynamics trajectories 2 μs in length have been generated for the pH-activated, tetrameric M2 proton channel of the influenza A virus in all protonation states of the pH sensor located at the His37 tetrad. All simulated structures are in very good agreement with high-resolution structures. Changes in the channel caused by progressive protonation of His37 provide insight into the mechanism of proton transport. The channel is closed at both His37 and Trp41 sites in the singly and doubly protonated states, but it opens at Trp41 upon further protonation. Anions access the charged His37 and by doing so stabilize the protonated states of the channel. The narrow opening at the His37 site, further blocked by anions, is inconsistent with the water-wire mechanism of proton transport. Instead, conformational interconversions of His37 correlated with hydrogen bonding to water molecules indicate that these residues shuttle protons in high-protonation states. Hydrogen bonds between charged and uncharged histidines are rare. The valve at Val27 remains on average quite narrow in all protonation states but fluctuates sufficiently to support water and proton transport. A proton transport mechanism in which the channel, depending on pH, opens at either the histidine or valine gate is only partially supported by the simulations. PMID:24209848

  10. Discovery of a Biological Mechanism of Active Transport through the Tympanic Membrane to the Middle Ear

    PubMed Central

    Kurabi, Arwa; Pak, Kwang K.; Bernhardt, Marlen; Baird, Andrew; Ryan, Allen F.

    2016-01-01

    Otitis media (OM) is a common pediatric disease for which systemic antibiotics are often prescribed. While local treatment would avoid the systemic treatment side-effects, the tympanic membrane (TM) represents an impenetrable barrier unless surgically breached. We hypothesized that the TM might harbor innate biological mechanisms that could mediate trans-TM transport. We used two M13-bacteriophage display biopanning strategies to search for mediators of trans-TM transport. First, aliquots of linear phage library displaying 1010th 12mer peptides were applied on the TM of rats with active bacterial OM. The middle ear (ME) contents were then harvested, amplified and the preparation re-applied for additional rounds. Second, the same naïve library was sequentially screened for phage exhibiting TM binding, internalization and then transit. Results revealed a novel set of peptides that transit across the TM to the ME in a time and temperature dependent manner. The peptides with highest transport capacities shared sequence similarities. Historically, the TM was viewed as an impermeable barrier. However, our studies reveal that it is possible to translocate peptide-linked small particles across the TM. This is the first comprehensive biopanning for the isolation of TM transiting peptidic ligands. The identified mechanism offers a new drug delivery platform into the ME. PMID:26946957

  11. Mechanism of active transport: free energy dissipation and free energy transduction.

    PubMed Central

    Tanford, C

    1982-01-01

    The thermodynamic pathway for "chemiosmotic" free energy transduction in active transport is discussed with an ATP-driven Ca2+ pump as an illustrative example. Two innovations are made in the analysis. (i) Free energy dissipated as heat is rigorously excluded from overall free energy bookkeeping by focusing on the dynamic equilibrium state of the chemiosmotic process. (ii) Separate chemical potential terms for free energy donor and transported ions are used to keep track of the thermodynamic state of each substrate through the reaction cycle. These procedures clarify the mechanism of free energy transduction, even without step-by-step analysis. The results show that free energy exchange must occur in its entirety among protein-bound species. Imposition of conditions for an adequate rate of physiological function further indicates (i) that the standard free energy of hydrolysis of protein-bound ATP (to yield protein-bound products) needs to differ substantially from the standard free energy of hydrolysis in solution and (ii) that binding sites for the transported ions must have different affinities when facing opposite sides of the membrane. The results also demonstrate that step-by-step "basic" free energy changes (often used in the form of free energy level diagrams) are inherently unsuited for analysis of the mechanism of free energy transduction. PMID:6216483

  12. Dissecting the Molecular Mechanism of Nucleotide-Dependent Activation of the KtrAB K+ Transporter

    PubMed Central

    Szollosi, Andras; Vieira-Pires, Ricardo S.; Teixeira-Duarte, Celso M.; Rocha, Rita; Morais-Cabral, João H.

    2016-01-01

    KtrAB belongs to the Trk/Ktr/HKT superfamily of monovalent cation (K+ and Na+) transport proteins that closely resemble K+ channels. These proteins underlie a plethora of cellular functions that are crucial for environmental adaptation in plants, fungi, archaea, and bacteria. The activation mechanism of the Trk/Ktr/HKT proteins remains unknown. It has been shown that ATP stimulates the activity of KtrAB while ADP does not. Here, we present X-ray structural information on the KtrAB complex with bound ADP. A comparison with the KtrAB-ATP structure reveals conformational changes in the ring and in the membrane protein. In combination with a biochemical and functional analysis, we uncover how ligand-dependent changes in the KtrA ring are propagated to the KtrB membrane protein and conclude that, despite their structural similarity, the activation mechanism of KtrAB is markedly different from the activation mechanism of K+ channels. PMID:26771197

  13. Dissecting the Molecular Mechanism of Nucleotide-Dependent Activation of the KtrAB K+ Transporter.

    PubMed

    Szollosi, Andras; Vieira-Pires, Ricardo S; Teixeira-Duarte, Celso M; Rocha, Rita; Morais-Cabral, João H

    2016-01-01

    KtrAB belongs to the Trk/Ktr/HKT superfamily of monovalent cation (K+ and Na+) transport proteins that closely resemble K+ channels. These proteins underlie a plethora of cellular functions that are crucial for environmental adaptation in plants, fungi, archaea, and bacteria. The activation mechanism of the Trk/Ktr/HKT proteins remains unknown. It has been shown that ATP stimulates the activity of KtrAB while ADP does not. Here, we present X-ray structural information on the KtrAB complex with bound ADP. A comparison with the KtrAB-ATP structure reveals conformational changes in the ring and in the membrane protein. In combination with a biochemical and functional analysis, we uncover how ligand-dependent changes in the KtrA ring are propagated to the KtrB membrane protein and conclude that, despite their structural similarity, the activation mechanism of KtrAB is markedly different from the activation mechanism of K+ channels.

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

    NASA Technical Reports Server (NTRS)

    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.

  15. Bundling dynamics regulates the active mechanics and transport in carbon nanotube networks and their nanocomposites

    NASA Astrophysics Data System (ADS)

    Hahm, Myung Gwan; Wang, Hailong; Jung, Hyun Young; Hong, Sanghyun; Lee, Sung-Goo; Kim, Sung-Ryong; Upmanyu, Moneesh; Jung, Yung Joon

    2012-05-01

    High-density carbon nanotube networks (CNNs) continue to attract interest as active elements in nanoelectronic devices, nanoelectromechanical systems (NEMS) and multifunctional nanocomposites. The interplay between the network nanostructure and its properties is crucial, yet current understanding remains limited to the passive response. Here, we employ a novel superstructure consisting of millimeter-long vertically aligned single walled carbon nanotubes (SWCNTs) sandwiched between polydimethylsiloxane (PDMS) layers to quantify the effect of two classes of mechanical stimuli, film densification and stretching, on the electronic and thermal transport across the network. The network deforms easily with an increase in the electrical and thermal conductivities, suggestive of a floppy yet highly reconfigurable network. Insight from atomistically informed coarse-grained simulations uncover an interplay between the extent of lateral assembly of the bundles, modulated by surface zipping/unzipping, and the elastic energy associated with the bent conformations of the nanotubes/bundles. During densification, the network becomes highly interconnected yet we observe a modest increase in bundling primarily due to the reduced spacing between the SWCNTs. The stretching, on the other hand, is characterized by an initial debundling regime as the strain accommodation occurs via unzipping of the branched interconnects, followed by rapid rebundling as the strain transfers to the increasingly aligned bundles. In both cases, the increase in the electrical and thermal conductivity is primarily due to the increase in bundle size; the changes in network connectivity have a minor effect on the transport. Our results have broad implications for filamentous networks of inorganic nanoassemblies composed of interacting tubes, wires and ribbons/belts.High-density carbon nanotube networks (CNNs) continue to attract interest as active elements in nanoelectronic devices, nanoelectromechanical systems

  16. Mechanisms of glutamate transport.

    PubMed

    Vandenberg, Robert J; Ryan, Renae M

    2013-10-01

    L-Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system and plays important roles in a wide variety of brain functions, but it is also a key player in the pathogenesis of many neurological disorders. The control of glutamate concentrations is critical to the normal functioning of the central nervous system, and in this review we discuss how glutamate transporters regulate glutamate concentrations to maintain dynamic signaling mechanisms between neurons. In 2004, the crystal structure of a prokaryotic homolog of the mammalian glutamate transporter family of proteins was crystallized and its structure determined. This has paved the way for a better understanding of the structural basis for glutamate transporter function. In this review we provide a broad perspective of this field of research, but focus primarily on the more recent studies with a particular emphasis on how our understanding of the structure of glutamate transporters has generated new insights.

  17. Uncoupled active transport mechanisms accounting for low selectivity in multidrug carriers: P-glycoprotein and SMR antiporters.

    PubMed

    Krupka, R M

    1999-11-15

    The extraordinarily low substrate specificity of P-glycoprotein conflicts with the notion that specific substrate interactions are required in the control of the reaction path in an active transport system. The difficulty is shown to be overcome by a half-coupled mechanism in which the ATP reaction is linked to carrier transformations, as in a fully coupled system, but in which the transported substrate plays a passive role. The mechanism, which requires no specific interaction with the substrate, brings about uphill transport. A half-coupled mechanism is directly supported by two observations: (i) almost completely uncoupled ATPase activity in purified P-glycoprotein, and (ii) a pattern of substrate specificity like that of passive systems, where maximum rates for different substrates vary little (unlike active systems, where maximum rates vary greatly). The mechanism accommodates other findings: partial inhibition of ATPase activity by an actively transported substrate; simultaneous binding and translocation of more than one substrate molecule; and stimulation or inhibition of the transport of one substrate molecule by another. A half-coupled system associated with an internal competitive inhibitor should behave as if tightly coupled, in agreement with the effects of the synthetic peptide, polytryptophan. The degree of coupling in the intact system is yet to be determined, however. A half-coupled ATPase mechanism could originally have evolved in a flippase, where immersion of the carrier in its substrate, the membrane lipid, precludes uncoupled ATP hydrolysis. These concepts may have wider application. An uncoupled antiport mechanism, driven by a proton gradient rather than ATP, can explain low selectivity in the SMR multidrug carriers of bacteria, and a half-coupled mechanism for the ion-driven cotransport of water (the substrate in which the carrier site is immersed) can explain a recently proposed uphill flow of water.

  18. Vapor transport mechanisms

    NASA Technical Reports Server (NTRS)

    Workman, G. L.

    1978-01-01

    The Raman scattering furnace for investigating vapor transport mechanisms was completed and checked out. Preliminary experiments demonstate that a temperature resolution of plus and minus 5 C is possible with this system operating in a backscatter mode. In the experiments presented with the GeI 4 plus excess Ge system at temperatures up to 600 C, only the GeI4 band at 150 cm superscript minus 1 was observed. Further experiments are in progress to determine if GeI2 does become the major vapor species above 440 C.

  19. Repeat-swap homology modeling of secondary active transporters: updated protocol and prediction of elevator-type mechanisms

    PubMed Central

    Vergara-Jaque, Ariela; Fenollar-Ferrer, Cristina; Kaufmann, Desirée; Forrest, Lucy R.

    2015-01-01

    Secondary active transporters are critical for neurotransmitter clearance and recycling during synaptic transmission and uptake of nutrients. These proteins mediate the movement of solutes against their concentration gradients, by using the energy released in the movement of ions down pre-existing concentration gradients. To achieve this, transporters conform to the so-called alternating-access hypothesis, whereby the protein adopts at least two conformations in which the substrate binding sites are exposed to one or other side of the membrane, but not both simultaneously. Structures of a bacterial homolog of neuronal glutamate transporters, GltPh, in several different conformational states have revealed that the protein structure is asymmetric in the outward- and inward-open states, and that the conformational change connecting them involves a elevator-like movement of a substrate binding domain across the membrane. The structural asymmetry is created by inverted-topology repeats, i.e., structural repeats with similar overall folds whose transmembrane topologies are related to each other by two-fold pseudo-symmetry around an axis parallel to the membrane plane. Inverted repeats have been found in around three-quarters of secondary transporter folds. Moreover, the (a)symmetry of these systems has been successfully used as a bioinformatic tool, called “repeat-swap modeling” to predict structural models of a transporter in one conformation using the known structure of the transporter in the complementary conformation as a template. Here, we describe an updated repeat-swap homology modeling protocol, and calibrate the accuracy of the method using GltPh, for which both inward- and outward-facing conformations are known. We then apply this repeat-swap homology modeling procedure to a concentrative nucleoside transporter, VcCNT, which has a three-dimensional arrangement related to that of GltPh. The repeat-swapped model of VcCNT predicts that nucleoside transport

  20. Chromium activates glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism.

    PubMed

    Chen, Guoli; Liu, Ping; Pattar, Guruprasad R; Tackett, Lixuan; Bhonagiri, Padma; Strawbridge, Andrew B; Elmendorf, Jeffrey S

    2006-04-01

    Evidence suggests that chromium supplementation may alleviate symptoms associated with diabetes, such as high blood glucose and lipid abnormalities, yet a molecular mechanism remains unclear. Here, we report that trivalent chromium in the chloride (CrCl3) or picolinate (CrPic) salt forms mobilize the glucose transporter, GLUT4, to the plasma membrane in 3T3-L1 adipocytes. Concomitant with an increase in GLUT4 at the plasma membrane, insulin-stimulated glucose transport was enhanced by chromium treatment. In contrast, the chromium-mobilized pool of transporters was not active in the absence of insulin. Microscopic analysis of an exofacially Myc-tagged enhanced green fluorescent protein-GLUT4 construct revealed that the chromium-induced accumulation of GLUT4-containing vesicles occurred adjacent to the inner cell surface membrane. With insulin these transporters physically incorporated into the plasma membrane. Regulation of GLUT4 translocation by chromium did not involve known insulin signaling proteins such as the insulin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, and Akt. Consistent with a reported effect of chromium on increasing membrane fluidity, we found that chromium treatment decreased plasma membrane cholesterol. Interestingly, cholesterol add-back to the plasma membrane prevented the beneficial effect of chromium on both GLUT4 mobilization and insulin-stimulated glucose transport. Furthermore, chromium action was absent in methyl-beta-cyclodextrin-pretreated cells already displaying reduced plasma membrane cholesterol and increased GLUT4 translocation. Together, these data reveal a novel mechanism by which chromium may enhance GLUT4 trafficking and insulin-stimulated glucose transport. Moreover, these findings at the level of the cell are consistent with in vivo observations of improved glucose tolerance and decreased circulating cholesterol levels after chromium supplementation.

  1. Laboratory Exercise on Active Transport.

    ERIC Educational Resources Information Center

    Stalheim-Smith, Ann; Fitch, Greg K.

    1985-01-01

    Describes a laboratory exercise which demonstrates qualitatively the specificity of the transport mechanism, including a consideration of the competitive inhibition, and the role of adenosine triphosphate (ATP) in active transport. The exercise, which can be completed in two to three hours by groups of four students, consistently produces reliable…

  2. Tape transport mechanism

    DOEpatents

    Groh, Edward F.; McDowell, William; Modjeski, Norbert S.; Keefe, Donald J.; Groer, Peter

    1979-01-01

    A device is provided for transporting, in a stepwise manner, tape between a feed reel and takeup reel. An indexer moves across the normal path of the tape displacing it while the tape on the takeup reel side of the indexer is braked. After displacement, the takeup reel takes up the displaced tape while the tape on the feed reel side of the indexer is braked, providing stepwise tape transport in precise intervals determined by the amount of displacement caused by the indexer.

  3. Membranes, mechanics, and intracellular transport

    NASA Astrophysics Data System (ADS)

    Parthasarathy, Raghuveer

    2012-10-01

    Cellular membranes are remarkable materials -- self-assembled, flexible, two-dimensional fluids. Understanding how proteins manipulate membrane curvature is crucial to understanding the transport of cargo in cells, yet the mechanical activities of trafficking proteins remain poorly understood. Using an optical-trap based assay involving dynamic deformation of biomimetic membranes, we have examined the behavior of Sar1, a key component of the COPII family of transport proteins. We find that Sar1 from yeast (S. cerevisiae) lowers membrane rigidity by up to 100% as a function of its concentration, thereby lowering the energetic cost of membrane deformation. Human Sar1 proteins can also lower the mechanical rigidity of the membranes to which they bind. However, unlike the yeast proteins, the rigidity is not a monotonically decreasing function of concentration but rather shows increased rigidity and decreased mobility at high concentrations that implies interactions between proteins. In addition to describing this study of membrane mechanics, I'll also discuss some topics relevant to a range of biophysical investigations, such as the insights provided by imaging methods and open questions in the dynamics of multicellular systems.

  4. Divergent mechanisms for the insulin resistant and hyperresponsive glucose transport in adipose cells from fasted and refed rats. Alterations in both glucose transporter number and intrinsic activity.

    PubMed Central

    Kahn, B B; Simpson, I A; Cushman, S W

    1988-01-01

    The effects of fasting and refeeding on the glucose transport response to insulin in isolated rat adipose cells have been examined using 3-O-methylglucose transport in intact cells and cytochalasin B binding and Western blotting in subcellular membrane fractions. After a 72-h fast, basal glucose transport activity decreases slightly and insulin-stimulated activity decreases greater than 85%. Following 48 h of fasting, insulin-stimulated glucose transport activity is diminished from 3.9 +/- 0.5 to 1.3 +/- 0.3 fmol/cell per min (mean +/- SEM). Similarly, the concentrations of glucose transporters are reduced with fasting in both the plasma membranes from insulin-stimulated cells from 38 +/- 5 to 18 +/- 3 pmol/mg of membrane protein and the low density microsomes from basal cells from 68 +/- 8 to 34 +/- 9 pmol/mg of membrane protein. Ad lib. refeeding for 6 d after a 48-h fast results in up to twofold greater maximally insulin-stimulated glucose transport activity compared with the control level (7.1 +/- 0.4 vs. 4.5 +/- 0.2 fmol/cell per min), before returning to baseline at 10 d. However, the corresponding concentration of glucose transporters in the plasma membranes is restored only to the control level (45 +/- 5 vs. 50 +/- 5 pmol/mg of membrane protein). Although the concentration of glucose transporters in the low density microsomes of basal cells remains decreased, the total number is restored to the control level due to an increase in low density microsomal protein. Thus, the insulin-resistant glucose transport in adipose cells from fasted rats can be explained by a decreased translocation of glucose transporters to the plasma membrane due to a depleted intracellular pool. In contrast, the insulin hyperresponsive glucose transport observed with refeeding appears to result from (a) a restored translocation of glucose transporters to the plasma membrane from a repleted intracellular pool and (b) enhanced plasma membrane glucose transporter intrinsic activity

  5. Mechanical approach to chemical transport

    PubMed Central

    Kocherginsky, Nikolai; Gruebele, Martin

    2016-01-01

    Nonequilibrium thermodynamics describes the rates of transport phenomena with the aid of various thermodynamic forces, but often the phenomenological transport coefficients are not known, and the description is not easily connected with equilibrium relations. We present a simple and intuitive model to address these issues. Our model is based on Lagrangian dynamics for chemical systems with dissipation, so one may think of the model as physicochemical mechanics. Using one main equation, the model allows a systematic derivation of all transport and equilibrium equations, subject to the limitation that heat generated or absorbed in the system must be small for the model to be valid. A table with all major examples of transport and equilibrium processes described using physicochemical mechanics is given. In equilibrium, physicochemical mechanics reduces to standard thermodynamics and the Gibbs–Duhem relation, and we show that the First and Second Laws of thermodynamics are satisfied for our system plus bath model. Out of equilibrium, our model provides relationships between transport coefficients and describes system evolution in the presence of several simultaneous external fields. The model also leads to an extension of the Onsager–Casimir reciprocal relations for properties simultaneously transported by many components. PMID:27647899

  6. Toward understanding the mechanism of ion transport activity of neuronal uncoupling proteins UCP2, UCP4, and UCP5.

    PubMed

    Hoang, Tuan; Smith, Matthew D; Jelokhani-Niaraki, Masoud

    2012-05-15

    Neuronal uncoupling proteins (UCP2, UCP4, and UCP5) have crucial roles in the function and protection of the central nervous system (CNS). Extensive biochemical studies of UCP2 have provided ample evidence of its participation in proton and anion transport. To date, functional studies of UCP4 and UCP5 are scarce. In this study, we show for the first time that, despite a low level of amino acid sequence identity with the previously characterized UCPs (UCP1-UCP3), UCP4 and UCP5 share their functional properties. Recombinantly expressed in Escherichia coli, UCP2, UCP4, and UCP5 were isolated and reconstituted into liposome systems, where their conformations and ion (proton and chloride) transport properties were examined. All three neuronal UCPs are able to transport protons across lipid membranes with characteristics similar to those of the archetypal protein UCP1, which is activated by fatty acids and inhibited by purine nucleotides. Neuronal UCPs also exhibit transmembrane chloride transport activity. Circular dichroism spectroscopy shows that these three transporters exist in different conformations. In addition, their structures and functions are differentially modulated by the mitochondrial lipid cardiolipin. In total, this study supports the existence of general conformational and ion transport features in neuronal UCPs. On the other hand, it also emphasizes the subtle structural and functional differences between UCPs that could distinguish their physiological roles. Differentiation between structure-function relationships of neuronal UCPs is essential for understanding their physiological functions in the CNS.

  7. Characterizing mechanisms of extracellular electron transport in sulfur and iron-oxidizing electrochemically active bacteria isolated from marine sediments

    NASA Astrophysics Data System (ADS)

    Rowe, A. R.; Bird, L. J.; Lam, B. R.; Nealson, K. H.

    2014-12-01

    Lithotrophic reactions, including the oxidation of mineral species, are often difficult to detect in environmental systems. This could be due to the nature of substrate or metabolite quantification or the rapid consumption of metabolic end products or intermediates by proximate biological or abiotic processes. Though recently genetic markers have been applied to detecting these processes in environmental systems, our knowledge of lithotrophic markers are limited to those processes catalyzed by organisms that have been cultured and physiologically characterized. Here we describe the use of electrochemical enrichment techniques to isolate marine sediment-dwelling microbes capable of the oxidation or insoluble forms of iron and sulfur including both the elemental species. All the organisms isolated fall within the Alphaproteobacteria and Gammaproteobacteria and are capable of acquiring electrons from an electrode while using either oxygen or nitrate as a terminal electron acceptor. Electrochemical analysis of these microbes has demonstrated that, though they have similar geochemical abilities (either sulfur or iron oxidation), they likely utilize different biochemical mechanisms demonstrated by the variability in dominant electron transfer modes or interactions (i.e., biofilm, planktonic or mediator facilitated interactions) and the wide range of midpoint potentials observed for dominant redox active cellular components (ranging from -293 to +50 mV vs. Ag/AgCl). For example, organisms isolated on elemental sulfur tended to have higher midpoint potentials than iron-oxidizing microbes. A variety of techniques are currently being applied to understanding the different mechanisms of extracellular electron transport for oxidizing an electrode or corresponding insoluble electron donor including both genomic and genetic manipulation experiments. The insight gained from these experiments is not limited to the physiology of the organisms isolated but will also aid in

  8. Phosphorylation mechanisms in dopamine transporter regulation.

    PubMed

    Foster, James D; Vaughan, Roxanne A

    2016-11-09

    The dopamine transporter (DAT) is a plasma membrane phosphoprotein that actively translocates extracellular dopamine (DA) into presynaptic neurons. The transporter is the primary mechanism for control of DA levels and subsequent neurotransmission, and is the target for abused and therapeutic drugs that exert their effects by suppressing reuptake. The transport capacity of DAT is acutely regulated by signaling systems and drug exposure, providing neurons the ability to fine-tune DA clearance in response to specific conditions. Kinase pathways play major roles in these mechanisms, and this review summarizes the current status of DAT phosphorylation characteristics and the evidence linking transporter phosphorylation to control of reuptake and other functions. Greater understanding of these processes may aid in elucidation of their possible contributions to DA disease states and suggest specific phosphorylation sites as targets for therapeutic manipulation of reuptake.

  9. Polar auxin transport: models and mechanisms.

    PubMed

    van Berkel, Klaartje; de Boer, Rob J; Scheres, Ben; ten Tusscher, Kirsten

    2013-06-01

    Spatial patterns of the hormone auxin are important drivers of plant development. The observed feedback between the active, directed transport that generates auxin patterns and the auxin distribution that influences transport orientation has rendered this a popular subject for modelling studies. Here we propose a new mathematical framework for the analysis of polar auxin transport and present a detailed mathematical analysis of published models. We show that most models allow for self-organised patterning for similar biological assumptions, and find that the pattern generated is typically unidirectional, unless additional assumptions or mechanisms are incorporated. Our analysis thus suggests that current models cannot explain the bidirectional fountain-type patterns found in plant meristems in a fully self-organised manner, and we discuss future research directions to address the gaps in our understanding of auxin transport mechanisms.

  10. Respiratory fluid mechanics and transport processes.

    PubMed

    Grotberg, J B

    2001-01-01

    The field of respiratory flow and transport has experienced significant research activity over the past several years. Important contributions to the knowledge base come from pulmonary and critical care medicine, surgery, physiology, environmental health sciences, biophysics, and engineering. Several disciplines within engineering have strong and historical ties to respiration including mechanical, chemical, civil/environmental, aerospace and, of course, biomedical engineering. This review draws from a wide variety of scientific literature that reflects the diverse constituency and audience that respiratory science has developed. The subject areas covered include nasal flow and transport, airway gas flow, alternative modes of ventilation, nonrespiratory gas transport, aerosol transport, airway stability, mucus transport, pulmonary acoustics, surfactant dynamics and delivery, and pleural liquid flow. Within each area are a number of subtopics whose exploration can provide the opportunity of both depth and breadth for the interested reader.

  11. Mechanisms of transport and exocytosis of dense-core granules containing tissue plasminogen activator in developing hippocampal neurons.

    PubMed

    Silverman, Michael A; Johnson, Scooter; Gurkins, Dmitri; Farmer, Meredith; Lochner, Janis E; Rosa, Patrizia; Scalettar, Bethe A

    2005-03-23

    Dense-core granules (DCGs) are organelles found in specialized secretory cells, including neuroendocrine cells and neurons. Neuronal DCGs facilitate many critical processes, including the transport and secretion of proteins involved in learning, and yet their transport and exocytosis are poorly understood. We have used wide-field and total internal reflection fluorescence microscopy, in conjunction with transport theory, to visualize the transport and exocytosis of DCGs containing a tissue plasminogen activator-green fluorescent protein hybrid in cell bodies, neurites, and growth cones of developing hippocampal neurons and to quantify the roles that diffusion, directed motion, and immobility play in these processes. Our results demonstrate that shorter-ranged transport of DCGs near sites of exocytosis in hippocampal neurons and neuroendocrine cells differs markedly. Specifically, the immobile fraction of DCGs within growth cones and near the plasma membrane of hippocampal neurons is small and relatively unaltered by actin disruption, unlike in neuroendocrine cells. Moreover, transport of DCGs in these domains of hippocampal neurons is unusually heterogeneous, being significantly rapid and directed as well as slow and diffusive. Our results also demonstrate that exocytosis is preceded by substantial movement and heterogeneous transport; this movement may facilitate delivery of DCG cargo in hippocampal neurons, given the relatively low abundance of neuronal DCGs. In addition, the extensive mobility of DCGs in hippocampal neurons argues strongly against the hypothesis that cortical actin is a major barrier to membrane-proximal DCGs in these cells. Instead, our results suggest that extended release of DCG cargo from hippocampal neurons arises from heterogeneity in DCG mobility.

  12. Pathogenic forms of tau inhibit kinesin-dependent axonal transport through a mechanism involving activation of axonal phosphotransferases.

    PubMed

    Kanaan, Nicholas M; Morfini, Gerardo A; LaPointe, Nichole E; Pigino, Gustavo F; Patterson, Kristina R; Song, Yuyu; Andreadis, Athena; Fu, Yifan; Brady, Scott T; Binder, Lester I

    2011-07-06

    Aggregated filamentous forms of hyperphosphorylated tau (a microtubule-associated protein) represent pathological hallmarks of Alzheimer's disease (AD) and other tauopathies. While axonal transport dysfunction is thought to represent a primary pathogenic factor in AD and other neurodegenerative diseases, the direct molecular link between pathogenic forms of tau and deficits in axonal transport remain unclear. Recently, we demonstrated that filamentous, but not soluble, forms of wild-type tau inhibit anterograde, kinesin-based fast axonal transport (FAT) by activating axonal protein phosphatase 1 (PP1) and glycogen synthase kinase 3 (GSK3), independent of microtubule binding. Here, we demonstrate that amino acids 2-18 of tau, comprising a phosphatase-activating domain (PAD), are necessary and sufficient for activation of this pathway in axoplasms isolated from squid giant axons. Various pathogenic forms of tau displaying increased exposure of PAD inhibited anterograde FAT in squid axoplasm. Importantly, immunohistochemical studies using a novel PAD-specific monoclonal antibody in human postmortem tissue indicated that increased PAD exposure represents an early pathogenic event in AD that closely associates in time with AT8 immunoreactivity, an early marker of pathological tau. We propose a model of pathogenesis in which disease-associated changes in tau conformation lead to increased exposure of PAD, activation of PP1-GSK3, and inhibition of FAT. Results from these studies reveal a novel role for tau in modulating axonal phosphotransferases and provide a molecular basis for a toxic gain-of-function associated with pathogenic forms of tau.

  13. Transport to Rhebpress activity.

    PubMed

    Garrido, Amanda; Brandt, Marta; Djouder, Nabil

    2016-01-01

    The small GTPases from the rat sarcoma (Ras) superfamily are a heterogeneous group of proteins of about 21 kDa that act as molecular switches, modulating cell signaling pathways and controlling diverse cellular processes. They are active when bound to guanosine triphosphate (GTP) and inactive when bound to guanosine diphosphate (GDP). Ras homolog enriched in brain (Rheb) is a member of the Ras GTPase superfamily and a key activator of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1). We recently determined that microspherule protein 1 (MCRS1) maintains Rheb at lysosomal surfaces in an amino acid-dependent manner. MCRS1 depletion promotes the formation of the GDP-bound form of Rheb, which is then delocalized from the lysosomal platform and transported to endocytic recycling vesicles, leading to mTORC1 inactivation. During this delocalization process, Rheb-GDP remains farnesylated and associated with cellular endomembranes. These findings provide new insights into the regulation of small GTPases, whose activity depends on both their GTP/GDP switch state and their capacity to move between different cellular membrane-bound compartments. Dynamic spatial transport between compartments makes it possible to alter the proximity of small GTPases to their activatory sites depending on the prevailing physiological and cellular conditions.

  14. Energy coupling mechanisms of MFS transporters

    PubMed Central

    Zhang, Xuejun C; Zhao, Yan; Heng, Jie; Jiang, Daohua

    2015-01-01

    Major facilitator superfamily (MFS) is a large class of secondary active transporters widely expressed across all life kingdoms. Although a common 12-transmembrane helix-bundle architecture is found in most MFS crystal structures available, a common mechanism of energy coupling remains to be elucidated. Here, we discuss several models for energy-coupling in the transport process of the transporters, largely based on currently available structures and the results of their biochemical analyses. Special attention is paid to the interaction between protonation and the negative-inside membrane potential. Also, functional roles of the conserved sequence motifs are discussed in the context of the 3D structures. We anticipate that in the near future, a unified picture of the functions of MFS transporters will emerge from the insights gained from studies of the common architectures and conserved motifs. PMID:26234418

  15. Mechanical Forces and Lymphatic Transport

    PubMed Central

    Breslin, Jerome W.

    2014-01-01

    This review examines current understanding of how the lymphatic vessel network can optimize lymph flow in response to various mechanical forces. Lymphatics are organized as a vascular tree, with blind-ended initial lymphatics, precollectors, prenodal collecting lymphatics, lymph nodes, postnodal collecting lymphatics and the larger trunks (thoracic duct and right lymph duct) that connect to the subclavian veins. The formation of lymph from interstitial fluid depends heavily on oscillating pressure gradients to drive fluid into initial lymphatics. Collecting lymphatics are segmented vessels with unidirectional valves, with each segment, called a lymphangion, possessing an intrinsic pumping mechanism. The lymphangions propel lymph forward against a hydrostatic pressure gradient. Fluid is returned to the central circulation both at lymph nodes and via the larger lymphatic trunks. Several recent developments are discussed, including: evidence for the active role of endothelial cells in lymph formation; recent developments on how inflow pressure, outflow pressure, and shear stress affect pump function of the lymphangion; lymphatic valve gating mechanisms; collecting lymphatic permeability; and current interpretations of the molecular mechanisms within lymphatic endothelial cells and smooth muscle. Improved understanding of the physiological mechanisms by lymphatic vessels sense mechanical stimuli, integrate the information, and generate the appropriate response is key for determining the pathogenesis of lymphatic insufficiency and developing treatments for lymphedema. PMID:25107458

  16. Impact of mechanical stress on ion transport in native lung epithelium (Xenopus laevis): short-term activation of Na+, Cl (-) and K+ channels.

    PubMed

    Bogdan, Roman; Veith, Christine; Clauss, Wolfgang; Fronius, Martin

    2008-09-01

    Epithelia, in general, and the lung epithelium, in particular, are exposed to mechanical forces, but little is known about their impact on pulmonary ion transport. In our present study, we employed transepithelial ion transport measurements on Xenopus lung preparations using custom-built Ussing chambers. Tissues were exposed to mechanical stress by increasing the water column (5 cm) at one side of the tissues. Apical exposure to hydrostatic pressure significantly decreased the short circuit current (I (SC): 24 +/- 1%, n = 152), slightly decreased the transepithelial resistance (R (T): 7 +/- 2%, n = 152), but increased the apical membrane capacitance (C (M): 16 +/- 6%, n = 9). The pressure-induced effect was sensitive to Na+ (amiloride), Cl(-) (DIDS, NFA, NPPB) and K+ channel blockers (Ba2+), glibenclamide). Further on, it was accompanied by increased extracellular ATP levels. The results show that mechanical stress leads to an activation of Na+, Cl(-), and K+ conductances in a native pulmonary epithelium resulting in a net decrease of ion absorption. This could be of considerable interest, since an altered ion transport may contribute to pathophysiological conditions, e.g., the formation of pulmonary edema during artificial ventilation.

  17. Molecular mechanisms and regulation of iron transport.

    PubMed

    Chung, Jayong; Wessling-Resnick, Marianne

    2003-04-01

    Iron homeostasis is primarily maintained through regulation of its transport. This review summarizes recent discoveries in the field of iron transport that have shed light on the molecular mechanisms of dietary iron uptake, pathways for iron efflux to and between peripheral tissues, proteins implicated in organellar transport of iron (particularly the mitochondrion), and novel regulators that have been proposed to control iron assimilation. The transport of both transferrin-bound and nontransferrin-bound iron to peripheral tissues is discussed. Finally, the regulation of iron transport is also considered at the molecular level, with posttranscriptional, transcriptional, and posttranslational control mechanisms being reviewed.

  18. Activated transport in AMTEC electrodes

    NASA Technical Reports Server (NTRS)

    Williams, R. M.; Jeffries-Nakamura, B.; Ryan, M. A.; Underwood, M. L.; O'Connor, D.; Kikkert, S.

    1992-01-01

    Transport of alkali, metal atoms through porous cathodes of alkali metal thermal-to-electric converter (AMTEC) cells is responsible for significant reducible losses in the electrical performance of these cells. Experimental evidence for activated transport of metal atoms at grain surfaces and boundaries within some AMTEC electrodes has been derived from temperature dependent studies as well as from analysis of the detailed frequency dependence of ac impedance results for other electrodes, including thin, mature molybdenum electrodes which exhibit transport dominated by free molecular flow of sodium gas at low frequencies or dc conditions. Activated surface transport will almost always exist in parallel with free molecular flow transport, and the process of alkali atom adsorption/desorption from the electrode surface will invariably be part of the transport process, and possibly a dominant part in some cases. The temperature dependence of the diffusion coefficient of the alkali metal through the electrode in several cases provides an activation energy and preexponential, but at least two activated processes may be operative, and the activation parameters should be expected to depend on the alkali metal activity gradient that the electrode experiences. In the case of Pt/W/Mn electrodes operated for 2500 hours, limiting currents varied with electrode thickness, and the activation parameters could be assigned primarily to the surface/grain boundary diffusion process.

  19. Activated transport in AMTEC electrodes

    SciTech Connect

    Williams, R.M.; Jeffries-Nakamura, B.; Ryan, M.A.; Underwood, M.L.; O`Connor, D.; Kikkert, S.

    1992-07-01

    Transport of alkali metal atoms through porous cathodes of alkali metal thermal-to-electric converter (AMTEC) cells is responsible for significant, reducible losses in the electrical performance of these cells. Experimental evidence for activated transport of metal atoms at grain surfaces and boundaries within some AMTEC electrodes has been derived from temperature dependent studies as well as from analysis of the detailed frequency dependence of ac impedance results for other electrodes, including thin, mature molybdenum electrodes which exhibit transport dominated by free molecular flow of sodium gas at low frequencies or dc conditions. Activated surface transport will almost always exist in parallel with free molecular flow transport, and the process of alkali atom adsorption/desorption from the electrode surface will invariably be part of the transport process, and possibly a dominant part in some cases. Little can be learned about the detailed mass transport process from the ac impedance or current voltage curves of an electrode at one set of operating parameters, because the transport process includes a number of important physical parameters that are not all uniquely determined by one experiment. The temperature dependence of diffusion coefficient of the alkali metal through the electrode in several cases provides an activation energy and pre-exponential, but at least two activated processes may be operative, and the activation parameters should be expected to depend on the alkali metal activity gradient that the electrode experiences. In the case of Pt/W/Mn electrodes operated for 2500 hours, limiting currents varied with electrode thickness, and the activation parameters could be assigned primarily to the surface/grain boundary diffusion process. 17 refs.

  20. Activated transport in AMTEC electrodes

    SciTech Connect

    Williams, R.M.; Jeffries-Nakamura, B.; Ryan, M.A.; Underwood, M.L.; O'Connor, D.; Kikkert, S.

    1992-01-01

    Transport of alkali metal atoms through porous cathodes of alkali metal thermal-to-electric converter (AMTEC) cells is responsible for significant, reducible losses in the electrical performance of these cells. Experimental evidence for activated transport of metal atoms at grain surfaces and boundaries within some AMTEC electrodes has been derived from temperature dependent studies as well as from analysis of the detailed frequency dependence of ac impedance results for other electrodes, including thin, mature molybdenum electrodes which exhibit transport dominated by free molecular flow of sodium gas at low frequencies or dc conditions. Activated surface transport will almost always exist in parallel with free molecular flow transport, and the process of alkali atom adsorption/desorption from the electrode surface will invariably be part of the transport process, and possibly a dominant part in some cases. Little can be learned about the detailed mass transport process from the ac impedance or current voltage curves of an electrode at one set of operating parameters, because the transport process includes a number of important physical parameters that are not all uniquely determined by one experiment. The temperature dependence of diffusion coefficient of the alkali metal through the electrode in several cases provides an activation energy and pre-exponential, but at least two activated processes may be operative, and the activation parameters should be expected to depend on the alkali metal activity gradient that the electrode experiences. In the case of Pt/W/Mn electrodes operated for 2500 hours, limiting currents varied with electrode thickness, and the activation parameters could be assigned primarily to the surface/grain boundary diffusion process. 17 refs.

  1. Astrocytic GABA transporter activity modulates excitatory neurotransmission

    PubMed Central

    Boddum, Kim; Jensen, Thomas P.; Magloire, Vincent; Kristiansen, Uffe; Rusakov, Dmitri A.; Pavlov, Ivan; Walker, Matthew C.

    2016-01-01

    Astrocytes are ideally placed to detect and respond to network activity. They express ionotropic and metabotropic receptors, and can release gliotransmitters. Astrocytes also express transporters that regulate the extracellular concentration of neurotransmitters. Here we report a previously unrecognized role for the astrocytic GABA transporter, GAT-3. GAT-3 activity results in a rise in astrocytic Na+ concentrations and a consequent increase in astrocytic Ca2+ through Na+/Ca2+ exchange. This leads to the release of ATP/adenosine by astrocytes, which then diffusely inhibits neuronal glutamate release via activation of presynaptic adenosine receptors. Through this mechanism, increases in astrocytic GAT-3 activity due to GABA released from interneurons contribute to 'diffuse' heterosynaptic depression. This provides a mechanism for homeostatic regulation of excitatory transmission in the hippocampus. PMID:27886179

  2. Secondary metabolites in plants: transport and self-tolerance mechanisms.

    PubMed

    Shitan, Nobukazu

    2016-07-01

    Plants produce a host of secondary metabolites with a wide range of biological activities, including potential toxicity to eukaryotic cells. Plants generally manage these compounds by transport to the apoplast or specific organelles such as the vacuole, or other self-tolerance mechanisms. For efficient production of such bioactive compounds in plants or microbes, transport and self-tolerance mechanisms should function cooperatively with the corresponding biosynthetic enzymes. Intensive studies have identified and characterized the proteins responsible for transport and self-tolerance. In particular, many transporters have been isolated and their physiological functions have been proposed. This review describes recent progress in studies of transport and self-tolerance and provides an updated inventory of transporters according to their substrates. Application of such knowledge to synthetic biology might enable efficient production of valuable secondary metabolites in the future.

  3. Mechanisms of Stratospheric Ozone Transport.

    DTIC Science & Technology

    1982-12-03

    amounts orcur too fat south and about 1 month too late. 92 CHANGE IN (740) (PPM) DIABATIC. cos ( LAT ) 70 50 ~40 (D 30_ _ _ _ _ ) 1 5 Ŗ 2.5 Z. 20 10 0 D...AD-A122 609 MECHANISMS OF STRATOSPHERIC OZONE BRANSPOR(U) NAVAL RESEARCH LAB WASHINGTON DC R B ROOD ET AL 03 DEC 82 UNCLASSIFIED F/G 4/ 1 ...NLIEIIIIEIIII EIIIIIIIIIIIIl IIIEIIIIIEEEEE IIIIIIIIIIIIIl EIIIIIIIIIIIIl EIIIIIIIIIIIIl 1111.0 112 M *0 MIt ROCLt RLS’OLU7ION TLST CHART - - - ,T 1 m -N ;’ V

  4. A general method for determining secondary active transporter substrate stoichiometry.

    PubMed

    Fitzgerald, Gabriel A; Mulligan, Christopher; Mindell, Joseph A

    2017-01-25

    The number of ions required to drive substrate transport through a secondary active transporter determines the protein's ability to create a substrate gradient, a feature essential to its physiological function, and places fundamental constraints on the transporter's mechanism. Stoichiometry is known for a wide array of mammalian transporters, but, due to a lack of readily available tools, not for most of the prokaryotic transporters for which high-resolution structures are available. Here, we describe a general method for using radiolabeled substrate flux assays to determine coupling stoichiometries of electrogenic secondary active transporters reconstituted in proteoliposomes by measuring transporter equilibrium potentials. We demonstrate the utility of this method by determining the coupling stoichiometry of VcINDY, a bacterial Na(+)-coupled succinate transporter, and further validate it by confirming the coupling stoichiometry of vSGLT, a bacterial sugar transporter. This robust thermodynamic method should be especially useful in probing the mechanisms of transporters with available structures.

  5. Molecular Mechanism of Biological Proton Transport

    SciTech Connect

    Pomes, R.

    1998-09-01

    Proton transport across lipid membranes is a fundamental aspect of biological energy transduction (metabolism). This function is mediated by a Grotthuss mechanism involving proton hopping along hydrogen-bonded networks embedded in membrane-spanning proteins. Using molecular simulations, the authors have explored the structural, dynamic, and thermodynamic properties giving rise to long-range proton translocation in hydrogen-bonded networks involving water molecules, or water wires, which are emerging as ubiquitous H{sup +}-transport devices in biological systems.

  6. A Simple Laboratory Exercise Illustrating Active Transport in Yeast Cells.

    ERIC Educational Resources Information Center

    Stambuk, Boris U.

    2000-01-01

    Describes a simple laboratory activity illustrating the chemiosmotic principles of active transport in yeast cells. Demonstrates the energy coupling mechanism of active a-glucoside uptake by Saccaromyces cerevisiae cells with a colorimetric transport assay using very simple equipment. (Contains 22 references.) (Author/YDS)

  7. Generic Transport Mechanisms for Molecular Traffic in Cellular Protrusions

    NASA Astrophysics Data System (ADS)

    Graf, Isabella R.; Frey, Erwin

    2017-03-01

    Transport of molecular motors along protein filaments in a half-closed geometry is a common feature of biologically relevant processes in cellular protrusions. Using a lattice-gas model we study how the interplay between active and diffusive transport and mass conservation leads to localized domain walls and tip localization of the motors. We identify a mechanism for task sharing between the active motors (maintaining a gradient) and the diffusive motion (transport to the tip), which ensures that energy consumption is low and motor exchange mostly happens at the tip. These features are attributed to strong nearest-neighbor correlations that lead to a strong reduction of active currents, which we calculate analytically using an exact moment identity, and might prove useful for the understanding of correlations and active transport also in more elaborate systems.

  8. [Advances in plant anthocyanin transport mechanism].

    PubMed

    Wang, Lu; Dai, Silan; Jin, Xuehua; Huang, He; Hong, Yan

    2014-06-01

    Anthocyanin biosynthesis is one of the thoroughly studied enzymatic pathways in biology, but little is known about the molecular mechanisms of its final stage: the transport of the anthocyanins into the vacuole. A clear picture of the dynamic trafficking of flavonoids is only now beginning to emerge. So far four different models have been proposed to explain the transport of anthocyanins from biosynthetic sites to the central vacuole, and four types of transporters have been found associated with the transport of anthocyanins: glutathione S-transferase, multidrug resistance-associated protein, multidrug and toxic compound extrusion, bilitranslocase-homologue. The functions of these proteins and related genes have also been studied. Although different models have been proposed, cellular and subcellular information is still lacking for reconciliation of different lines of evidence in various anthocyanin sequestration studies. According to the information available, through sequence analysis, gene expression analysis, subcellular positioning and complementation experiments, the function and location of these transporters can be explored, and the anthocyanin transport mechanism can be better understood.

  9. Comparative physiology of renal tubular transport mechanisms.

    PubMed Central

    Long, S.; Giebisch, G.

    1979-01-01

    This manuscript discusses current concepts of glomerular filtration and tubular transport of sodium, water, potassium, and urinary acidification by vertebrate kidneys in a comparative context. Work in mammalian and amphibian nephrons receives major emphasis due to our interest in application of new techniques for investigation of cellular mechanisms; when available, data from other vertebrate classes are discussed. Images FIG. 3 PMID:395765

  10. Thermodynamic evidence for a dual transport mechanism in a POT peptide transporter.

    PubMed

    Parker, Joanne L; Mindell, Joseph A; Newstead, Simon

    2014-12-02

    Peptide transport plays an important role in cellular homeostasis as a key route for nitrogen acquisition in mammalian cells. PepT1 and PepT2, the mammalian proton coupled peptide transporters (POTs), function to assimilate and retain diet-derived peptides and play important roles in drug pharmacokinetics. A key characteristic of the POT family is the mechanism of peptide selectivity, with members able to recognise and transport >8000 different peptides. In this study, we present thermodynamic evidence that in the bacterial POT family transporter PepTSt, from Streptococcus thermophilus, at least two alternative transport mechanisms operate to move peptides into the cell. Whilst tri-peptides are transported with a proton:peptide stoichiometry of 3:1, di-peptides are co-transported with either 4 or 5 protons. This is the first thermodynamic study of proton:peptide stoichiometry in the POT family and reveals that secondary active transporters can evolve different coupling mechanisms to accommodate and transport chemically and physically diverse ligands across the membrane.

  11. Active transport of RB protein from the nucleus to the cytoplasm as one of the development mechanisms of HER2-positive breast cancer.

    PubMed

    Kowalik, Artur; Kopczyński, Janusz; Wypiórkiewicz, Elżbieta; Góźdź, Stanisław; Meżyk, Ryszard; Siedlecki, Janusz Aleksander

    2013-04-01

    HER2-positive breast cancer (HER2+) occurs in approximately 15-20% of all breast cancers. Biologically this cancer subtype is characterized by an aggressive clinical course (often spread to regional lymph nodes at the time of diagnosis), and after successful treatment high risk of recurrence. Deregulation of the cell cycle is the basis for cancer aggressiveness. The RB protein is one of the key regulators of the cell cycle. There are only a few published studies on the expression and localization of RB protein in the cells of HER2-positive breast cancer. The aim of this study was to determine whether there are differences in the expression and localization of RB protein in HER2-positive breast cancers compared to breast cancers showing no expression of HER2. We used 50 tissue samples from HER2 positive breast cancer and 21 tissue samples derived from patients with HER2 negative breast cancer. The RB protein expression was measured by immunohistochemical techniques in tissue microarray format. Cytoplasmic RB expression was observed in 29 out of 50 (58%) HER2 positive breast cancers. In this group only cytoplasmic expression was observed. There was no case with nuclear expression. In contrast, in the HER2-negative breast cancer control group, in no case RB expression was observed in the cytoplasm (0/21, 0%). All 21 samples (100%) showed expression of RB protein in the nucleus (p < 0.0001). We can speculate that lack of expression suggests alternative mechanisms in the development of HER2 positive breast cancer. We hypothesize that HER2 overexpression is in some way associated with active transport of RB protein from the nucleus to the cytoplasm. This may be an indirect mechanism of inactivation of tumor suppressor protein in breast cancer exhibiting overexpression of HER2.

  12. Active cell mechanics: Measurement and theory.

    PubMed

    Ahmed, Wylie W; Fodor, Étienne; Betz, Timo

    2015-11-01

    Living cells are active mechanical systems that are able to generate forces. Their structure and shape are primarily determined by biopolymer filaments and molecular motors that form the cytoskeleton. Active force generation requires constant consumption of energy to maintain the nonequilibrium activity to drive organization and transport processes necessary for their function. To understand this activity it is necessary to develop new approaches to probe the underlying physical processes. Active cell mechanics incorporates active molecular-scale force generation into the traditional framework of mechanics of materials. This review highlights recent experimental and theoretical developments towards understanding active cell mechanics. We focus primarily on intracellular mechanical measurements and theoretical advances utilizing the Langevin framework. These developing approaches allow a quantitative understanding of nonequilibrium mechanical activity in living cells. This article is part of a Special Issue entitled: Mechanobiology.

  13. Mass transport mechanism in porous fuel cell electrodes

    NASA Technical Reports Server (NTRS)

    Jonsson, I.; Lindholm, I.

    1969-01-01

    Results of experiments on hydrogen-oxygen fuel cells show that higher current densities are obtained with cell anodes having a 100 micron thin active layer of porous nickel containing silver electrocatalyst. Increase in current density is attributed to a convective mass transport mechanism.

  14. Transport mechanism of the sarcoplasmic reticulum Ca2+ -ATPase pump.

    PubMed

    Møller, Jesper V; Nissen, Poul; Sørensen, Thomas L-M; le Maire, Marc

    2005-08-01

    The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA1a) belongs to the group of P-type ATPases, which actively transport inorganic cations across membranes at the expense of ATP hydrolysis. Three-dimensional structures of several transport intermediates of SERCA1a, stabilized by structural analogues of ATP and phosphoryl groups, are now available at atomic resolution. This has enabled the transport cycle of the protein to be described, including the coupling of Ca(2+) occlusion and phosphorylation by ATP, and of proton counter-transport and dephosphorylation. From these structures, Ca(2+)-ATPase gradually emerges as a molecular mechanical device in which some of the transmembrane segments perform Ca(2+) transport by piston-like movements and by the transmission of reciprocating movements that affect the chemical reactivity of the cytosolic globular domains.

  15. [Inflammasome: activation mechanisms].

    PubMed

    Suárez, Raibel; Buelvas, Neudo

    2015-03-01

    Inflammation is a rapid biologic response of the immune system in vascular tissues, directed to eliminate stimuli capable of causing damage and begin the process of repair. The macromolecular complexes known as "inflammasomes" are formed by a receptor, either NOD (NLR) or ALR, the receptor absent in melanoma 2 (AIM2). In addition, the inflammasome is formed by the speck-like protein associated to apoptosis (ASC) and procaspase-1, that may be activated by variations in the ionic and intracellular and extracellular ATP concentrations; and the loss of stabilization of the fagolisosomme by internalization of insoluble crystals and redox mechanisms. As a result, there is activation of the molecular platform and the processing of inflammatory prointerleukins to their active forms. There are two modalities of activation of the inflammasome: canonical and non-canonical, both capable of generating effector responses. Recent data associate NLRP 3, IL-1β and IL-18 in the pathogenesis of a variety of diseases, including atherosclerosis, type II diabetes, hyperhomocysteinemia, gout, malaria and hypertension. The inflammasome cascade is emerging as a new chemotherapeutic target in these diseases. In this review we shall discuss the mechanisms of activation and regulation of the inflammasome that stimulate, modulate and resolve inflammation.

  16. Mechanically Activated Ion Channels

    PubMed Central

    Ranade, Sanjeev S.; Syeda, Ruhma; Patapoutian, Ardem

    2015-01-01

    Mechanotransduction, the conversion of physical forces into biochemical signals, is an essential component of numerous physiological processes including not only conscious senses of touch and hearing, but also unconscious senses such as blood pressure regulation. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels. PMID:26402601

  17. Mechanically Activated Ion Channels.

    PubMed

    Ranade, Sanjeev S; Syeda, Ruhma; Patapoutian, Ardem

    2015-09-23

    Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels.

  18. Political activity for physical activity: health advocacy for active transport

    PubMed Central

    2011-01-01

    Effective health advocacy is a priority for efforts to increase population participation in physical activity. Local councils are an important audience for this advocacy. The aim of the current study was to describe features of advocacy for active transport via submissions to city council annual plans in New Zealand, and the impact of an information sheet to encourage the health sector to be involved in this process. Written submissions to city council's annual consultation process were requested for 16 city councils over the period of three years (2007/08, 2008/09, and 2009/10). Submissions were reviewed and categories of responses were created. An advocacy information sheet encouraging health sector participation and summarising some of the evidence-base related to physical activity, active transport and health was released just prior to the 2009/10 submission time. Over the period of the study, city councils received 47,392 submissions, 17% of which were related to active transport. Most submissions came from city residents, with a small proportion (2%) from the health sector. The largest category of submissions was in support of pedestrian and cycling infrastructure, design and maintenance of facilities and additional features to support use of these transport modes. Health arguments featured prominently in justifications for active transport initiatives, including concerns about injury risk, obesity, physical inactivity, personal safety and facilities for people with disabilities. There was evidence that the information sheet was utilised by some health sector submitters (12.5%), providing tentative support for initiatives of this nature. In conclusion, the study provides novel information about the current nature of health advocacy for active transport and informs future advocacy efforts about areas for emphasis, such as health benefits of active transport, and potential alliances with other sectors such as environmental sustainability, transport and urban

  19. Molecular mechanisms for proton transport in membranes.

    PubMed Central

    Nagle, J F; Morowitz, H J

    1978-01-01

    Likely mechanisms for proton transport through biomembranes are explored. The fundamental structural element is assumed to be continuous chains of hydrogen bonds formed from the protein side groups, and a molecular example is presented. From studies in ice, such chains are predicted to have low impedance and can function as proton wires. In addition, conformational changes in the protein may be linked to the proton conduction. If this possibility is allowed, a simple proton pump can be described that can be reversed into a molecular motor driven by an electrochemical potential across the membrane. PMID:272644

  20. Insights into transport mechanism from LeuT engineered to transport tryptophan.

    PubMed

    Piscitelli, Chayne L; Gouaux, Eric

    2012-01-04

    LeuT is a bacterial homologue of the neurotransmitter:sodium symporter (NSS) family and, being the only NSS member to have been structurally characterized by X-ray crystallography, is a model protein for studying transporter structure and mechanism. Transport activity in LeuT was hypothesized to require structural transitions between open-to-out and occluded conformations dependent upon protein:ligand binding complementarity. Here, using crystallographic and functional analysis, we show that binding site modification produces changes in both structure and activity that are consistent with complementarity-dependent structural transitions to the occluded state. The mutation I359Q converts the activity of tryptophan from inhibitor to transportable substrate. This mutation changes the local environment of the binding site, inducing the bound tryptophan to adopt a different conformer than in the wild-type complex. Instead of trapping the transporter open, tryptophan binding now allows the formation of an occluded state. Thus, transport activity is correlated to the ability of the ligand to promote the structural transition to the occluded state, a step in the transport cycle that is dependent on protein:ligand complementarity in the central binding site.

  1. Insights into transport mechanism from LeuT engineered to transport tryptophan

    SciTech Connect

    Piscitelli, Chayne L.; Gouaux, Eric

    2012-01-10

    LeuT is a bacterial homologue of the neurotransmitter:sodium symporter (NSS) family and, being the only NSS member to have been structurally characterized by X-ray crystallography, is a model protein for studying transporter structure and mechanism. Transport activity in LeuT was hypothesized to require structural transitions between open-to-out and occluded conformations dependent upon protein:ligand binding complementarity. Here, using crystallographic and functional analysis, we show that binding site modification produces changes in both structure and activity that are consistent with complementarity-dependent structural transitions to the occluded state. The mutation I359Q converts the activity of tryptophan from inhibitor to transportable substrate. This mutation changes the local environment of the binding site, inducing the bound tryptophan to adopt a different conformer than in the wild-type complex. Instead of trapping the transporter open, tryptophan binding now allows the formation of an occluded state. Thus, transport activity is correlated to the ability of the ligand to promote the structural transition to the occluded state, a step in the transport cycle that is dependent on protein:ligand complementarity in the central binding site.

  2. Energetics of active transport processes.

    PubMed

    Essig, A; Caplan, S R

    1968-12-01

    Discussions of active transport usually assume stoichiometry between the rate of transport J(+) and the metabolic rate J(r). However, the observation of a linear relationship between J(+) and J(r) does not imply a stoichiometric relationship, i.e., complete coupling. Since coupling may possibly be incomplete, we examine systems of an arbitrary degree of coupling q, regarding stoichiometry as a limiting case. We consider a sodium pump, with J(+) and J(r) linear functions of the electrochemical potential difference, -X(+), and the chemical affinity of the metabolic driving reaction, A. The affinity is well defined even for various complex reaction pathways. Incorporation of a series barrier and a parallel leak does not affect the linearity of the composite observable system. The affinity of some region of the metabolic chain may be maintained constant, either by large pools of reactants or by regulation. If so, this affinity can be evaluated by two independent methods. Sodium transport is conveniently characterized by the open-circuit potential (Deltapsi)(I=0) and the natural limits, level flow (J(+))(X+=0), and static head X(0) (+) = (X(+))(J+=0). With high degrees of coupling -X(0) (+)/F approaches the electromotive force E(Na) (Ussing); -X(0) (+)/F cannot be identified with ((RT/F) ln f)(X+=0), where f is the flux ratio. The efficiency eta = -J(+)X(+)/J(r)A is of significance only when appreciable energy is being converted from one form to another. When either J(+) or -X(+) is small eta is low; the significant parameters are then the efficacies epsilon(J+) = J(+)/J(r)A and epsilon(X+) = -X(+)/J(r)A, respectively maximal at level flow and static head. Leak increases both J(+) and epsilon(J+) for isotonic saline reabsorption, but diminishes -X(0) (+) and epsilon(Xfemale symbol). Electrical resistance reflects both passive parameters and metabolism. Various fundamental relations are preserved despite coupling of passive ion and water flows.

  3. Mechanism for alternating access in neurotransmitter transporters.

    PubMed

    Forrest, Lucy R; Zhang, Yuan-Wei; Jacobs, Miriam T; Gesmonde, Joan; Xie, Li; Honig, Barry H; Rudnick, Gary

    2008-07-29

    Crystal structures of LeuT, a bacterial homologue of mammalian neurotransmitter transporters, show a molecule of bound substrate that is essentially exposed to the extracellular space but occluded from the cytoplasm. Thus, there must exist an alternate conformation for LeuT in which the substrate is accessible to the cytoplasm and a corresponding mechanism that switches accessibility from one side of the membrane to the other. Here, we identify the cytoplasmic accessibility pathway of the alternate conformation in a mammalian serotonin transporter (SERT) (a member of the same transporter family as LeuT). We also propose a model for the cytoplasmic-facing state that exploits the internal pseudosymmetry observed in the crystal structure. LeuT contains two structurally similar repeats (TMs1-5 and TMs 6-10) that are inverted with respect to the plane of the membrane. The conformational differences between them result in the formation of the extracellular pathway. Our model for the cytoplasm-facing state exchanges the conformations of the two repeats and thus exposes the substrate and ion-binding sites to the cytoplasm. The conformational change that connects the two states primarily involves the tilting of a 4-helix bundle composed of transmembrane helices 1, 2, 6, and 7. Switching the tilt angle of this bundle is essentially equivalent to switching the conformation of the two repeats. Extensive mutagenesis of SERT and accessibility measurements, using cysteine reagents, are accommodated by our model. These observations may be of relevance to other transporter families, many of which contain internal inverted repeats.

  4. Activity of a sodium-dependent vitamin C transporter (SVCT) in MDCK-MDR1 cells and mechanism of ascorbate uptake

    PubMed Central

    Luo, Shuanghui; Wang, Zhiying; Kansara, Viral; Pal, Dhananjay; Mitra, Ashim. K.

    2008-01-01

    The objective of this research was to functionally characterize sodium-dependent vitamin C transporter (SVCT) in MDCK-MDR1 cells and to study the effect of substituted benzene derivatives on the intracellular accumulation of ascorbic acid (AA). Mechanism of AA uptake and transport was delineated. Uptake of [14C]ascorbic acid ([14C]AA) was studied in the absence and presence of excess unlabelled AA, anion transporter inhibitors, and a series of mono- and di- substituted benzenes. Transepithelial transport of [14C]AA across polarized cell membrane has been studied for the first time. Role of cellular protein kinase mediated pathways on the regulation of AA uptake has been investigated. The cellular localizations of SVCTs were observed using confocal microscopy. Uptake of AA was found to be saturable with a Km of 83.2 μM and Vmax of 94.2 pmol/min/mg protein for SVCT1. The process was pH, sodium, temperature, and energy dependent. It was under the regulation of cellular protein kinase C (PKC) and Ca2+/CaM mediated pathways. [14C]AA uptake was significantly inhibited in the presence of excess unlabelled AA and a series of electron-withdrawing group i.e. halogen- and nitro- substituted benzene derivatives. AA appears to translocate across polarized cell membrane from apical to basal side (A−B) as well as basal to apical side (B−A) at a similar permeability. It appears that SVCT1 was mainly expressed on the apical side and SVCT2 may be located on both apical and basal sides. In conclusion, SVCT has been functionally characterized in MDCK-MDR1 cells. The interference of a series of electrophile substituted benzenes on the AA uptake process may be explained by their structural similarity. SVCT may be targeted to facilitate the delivery of drugs with low bioavailability by conjugating with AA and its structural analogs. MDCK-MDR1 cell line may be utilized as an in vitro model to study the permeability of AA conjugated prodrugs. PMID:18417304

  5. Transport Mechanisms in Dielectric Optical Microcavities

    NASA Astrophysics Data System (ADS)

    Painchaud-April, G.; Poirier, J.; Dubé, L. J.

    2008-05-01

    Optical 2D microcavities have become a source of promising new technologies over the last decades. Applications ranging from high accuracy spectrometry to laser design will benefit from the development of such devices. The versatility of the concept resides in the ray-wave correspondence [1, 2]: the short wavelength limit of the system exhibits properties of well-known billiard systems, which may include Hamiltonian chaos. Therefore, since the wave behaviour of an optical microcavity is influenced by the underlying phase-space structure, a study and characterization of this structure becomes important to predict where the electromagnetic energy will flow out of the cavity. Whereas the correspondence works reasonably well for regular (classically integrable) and completely chaotic systems, partially chaotic systems of mixed phase space show transport properties largely influenced by tunnelling and localization effects with the consequence that the correspondence is all but lost. We will present the results of our investigations, in the ray and wave dynamics, in order to shed some light on the collaborating influence of the different transport mechanisms. [1] H. G. L. Schwefel et al., J. Opt. Soc. Am. B21, 923--934 (2004). [2] J. Wiersig and M. Hentschel, Phys. Rev. Lett, 100, 033901 (2008).

  6. Structure and mechanism of the mammalian fructose transporter GLUT5

    PubMed Central

    Shimamura, Tatsuro; Nomura, Yayoi; Sonoda, Yo; Hussien, Saba Abdul; Qureshi, Aziz Abdul; Coincon, Mathieu; Sato, Yumi; Abe, Hitomi; Nakada-Nakura, Yoshiko; Hino, Tomoya; Arakawa, Takatoshi; Kusano-Arai, Osamu; Iwanari, Hiroko; Murata, Takeshi; Kobayashi, Takuya; Hamakubo, Takao; Kasahara, Michihiro; Iwata, So; Drew, David

    2015-01-01

    The altered activity of the fructose transporter GLUT5, an isoform of the facilitated-diffusion glucose transporter family, has been linked to disorders such as type 2 diabetes and obesity. GLUT5 is also overexpressed in certain tumor cells and inhibitors are potential drugs for these conditions. Here, we describe the crystal structure of GLUT5 from Rattus norvegicus and Bos taurus in open outward- and open inward-facing conformations, respectively. GLUT5 has a major facilitator superfamily fold like other homologous monosaccharide transporters. Based on a comparison of the inward-facing structures of GLUT5 and human GLUT1, a ubiquitous glucose transporter, we show that a single point mutation is enough to switch the substrate binding preference of GLUT5 from fructose to glucose. A comparison of the substrate-free structures of GLUT5 with occluded substrate-bound structures of XylE suggests that, besides global rocker-switch like re-orientation of the bundles, local asymmetric rearrangements of C-terminal bundle helices TMs 7 and 10 underlie a “gated-pore” transport mechanism in such monosaccharide transporters. PMID:26416735

  7. Electrochemical reactivity and proton transport mechanisms in nanostructured ceria

    NASA Astrophysics Data System (ADS)

    Ding, J.; Strelcov, E.; Kalinin, S. V.; Bassiri-Gharb, N.

    2016-08-01

    Electrochemical reactivity and ionic transport at the nanoscale are essential in many energy applications. In this study, time-resolved Kelvin probe force microscopy (tr-KPFM) is utilized for surface potential mapping of nanostructured ceria, in both space and time domains. The fundamental mechanisms of proton injection and transport are studied as a function of environmental conditions and the presence or absence of triple phase boundaries. Finite element modeling is used to extract physical parameters from the experimental data, allowing not only quantification of the observed processes, but also decoupling of their contributions to the measured signal. The constructed phase diagrams of the parameters demonstrate a thermally activated proton injection reaction at the triple phase boundary, and two transport processes that are responsible for the low-temperature proton conductivity of nanostructured ceria.

  8. Flavonoid transport mechanisms: how to go, and with whom.

    PubMed

    Zhao, Jian

    2015-09-01

    Subcellular flavonoid transport and its underlying regulatory mechanisms are still poorly understood, but are fascinating research frontiers in plant science. Recent studies support and further extend previous hypotheses indicating that vacuolar sequestration of flavonoids involves vesicle trafficking, membrane transporters, and glutathione S-transferase (GST). However, the question remains to be addressed of how three distinct but nonexclusive mechanisms are functionally integrated into diverse but redundant transport routes for vacuolar sequestration or extracellular secretion of flavonoids. In this review, I highlight recent progress in understanding flavonoid-transporting vesicle behavior and properties, GST and membrane transporter functions and mechanisms, and flavonoid transport substrate specificity and preference.

  9. Calcium transport in strongly calcifying laying birds: mechanisms and regulation.

    PubMed

    Bar, Arie

    2009-04-01

    Birds that lay long clutches (series of eggs laid sequentially before a "pause day"), among them the high-producing, strongly-calcifying Gallus gallus domesticus (domestic hen) and Coturnix coturnix japonica (Japanese quail), transfer about 10% of their total body calcium daily. They appear, therefore, to be the most efficient calcium-transporters among vertebrates. Such intensive transport imposes severe demands on ionic calcium (Ca2+) homeostasis, and activates at least two extremely effective mechanisms for Ca2+ transfer from food and bone to the eggshell. This review focuses on the development, action and regulation of the mechanisms associated with paracellular and transcellular Ca2+ transport in the intestine and the eggshell gland (ESG); it also considers some of the proteins (calbindin, Ca2+ATPase, Na+/Ca2+ exchange, epithelial calcium channels (TRPVs), osteopontin and carbonic anhydrase (CA) associated with this phenomenon. Calbindins are discussed in some detail, as they appear to be a major component of the transcellular transport system, and as only they have been studied extensively in birds. The review aims to gather old and new knowledge, which could form a conceptual basis, albeit not a completely accepted one, for our understanding of the mechanisms associated with this phenomenon. In the intestine, the transcellular pathway appears to compensate for low Ca2+ intake, but in birds fed adequate calcium the major drive for calcium absorption remains the electrochemical potential difference (ECPD) that facilitates paracellular transport. However, the mechanisms involved in Ca2+ transport into the ESG lumen are not yet established. In the ESG, the presence of Ca2+-ATPase and calbindin--two components of the transcellular transport pathway--and the apparently uphill transport of Ca2+ support the idea that Ca2+ is transported via the transcellular pathway. However, the positive (plasma with respect to mucosa) electrical potential difference (EPD) in the

  10. MDMA causes a redistribution of serotonin transporter from the cell surface to the intracellular compartment by a mechanism independent of phospho-p38-mitogen activated protein kinase activation.

    PubMed

    Kivell, B; Day, D; Bosch, P; Schenk, S; Miller, J

    2010-06-16

    3,4-methylenedioxymethamphetamine (MDMA) causes long-term serotonin depletion and reduced serotonin transporter (SERT) function in humans and in animal models. Using quantitative Western blotting and real-time PCR, we have shown that total SERT protein in the striatum and nucleus accumbens and mRNA levels in the dorsal raphe nucleus were not significantly changed following MDMA exposure in rats (4 x 2 h i.p. injections, 10 mg/kg each). In mouse neuroblastoma (N(2)A) cells transiently expressing green fluorescent protein-tagged human SERT (GFP-hSERT), we have shown redistribution of SERT from the cell surface to intracellular vesicles on exposure to MDMA using cell surface biotinylation, total internal reflection fluorescence microscopy (TIRFM) and live-cell confocal microscopy. To investigate the mechanism responsible for SERT redistribution, we used specific antibodies to phospho-p38-mitogen activated protein kinase (p38 MAPK), a known signalling pathway involved in SERT membrane expression. We found that p38 MAPK activation was not involved in the MDMA-induced redistribution of SERT from the cell-surface to the cell interior. A loss of SERT from the cell surface on acute exposure to MDMA may contribute to the decreased SERT function seen in rats exposed to MDMA.

  11. Transport mechanism and regulatory properties of the human amino acid transporter ASCT2 (SLC1A5).

    PubMed

    Scalise, Mariafrancesca; Pochini, Lorena; Panni, Simona; Pingitore, Piero; Hedfalk, Kristina; Indiveri, Cesare

    2014-11-01

    The kinetic mechanism of the transport catalyzed by the human glutamine/neutral amino acid transporter hASCT2 over-expressed in P. pastoris was determined in proteoliposomes by pseudo-bi-substrate kinetic analysis of the Na(+)-glutamineex/glutaminein transport reaction. A random simultaneous mechanism resulted from the experimental analysis. Purified functional hASCT2 was chemically cross-linked to a stable dimeric form. The oligomeric structure correlated well with the kinetic mechanism of transport. Half-saturation constants (Km) of the transporter for the other substrates Ala, Ser, Asn and Thr were measured both on the external and internal side. External Km were much lower than the internal ones confirming the asymmetry of the transporter. The electric nature of the transport reaction was determined imposing a negative inside membrane potential generated by K(+) gradients in the presence of valinomycin. The transport reaction resulted to be electrogenic and the electrogenicity originated from external Na(+). Internal Na(+) exerted a stimulatory effect on the transport activity which could be explained by a regulatory, not a counter-transport, effect. Native and deglycosylated hASCT2 extracted from HeLa showed the same transport features demonstrating that the glycosyl moiety has no role in transport function. Both in vitro and in vivo interactions of hASCT2 with the scaffold protein PDZK1 were revealed.

  12. Transport Processes from Mechanics: Minimal and Simplest Models

    NASA Astrophysics Data System (ADS)

    Bunimovich, Leonid A.; Grigo, Alexander

    2017-02-01

    We review the current state of a fundamental problem of rigorous derivation of transport processes in classical statistical mechanics from classical mechanics. Such derivations for diffusion and momentum transport (viscosities) were obtained for minimal models of these processes involving one and two particles respectively. However, a minimal model which demonstrates heat conductivity contains three particles. Its rigorous analysis is currently out of reach for existing mathematical techniques. The gas of localized balls is widely accepted as a basis for a simplest model for derivation of Fourier's law. We suggest a modification of the localized balls gas and argue that this gas of localized activated balls is a good candidate to rigorously prove Fourier's law. In particular, hyperbolicity is derived for a reduced version of this model.

  13. Transport Processes from Mechanics: Minimal and Simplest Models

    NASA Astrophysics Data System (ADS)

    Bunimovich, Leonid A.; Grigo, Alexander

    2016-12-01

    We review the current state of a fundamental problem of rigorous derivation of transport processes in classical statistical mechanics from classical mechanics. Such derivations for diffusion and momentum transport (viscosities) were obtained for minimal models of these processes involving one and two particles respectively. However, a minimal model which demonstrates heat conductivity contains three particles. Its rigorous analysis is currently out of reach for existing mathematical techniques. The gas of localized balls is widely accepted as a basis for a simplest model for derivation of Fourier's law. We suggest a modification of the localized balls gas and argue that this gas of localized activated balls is a good candidate to rigorously prove Fourier's law. In particular, hyperbolicity is derived for a reduced version of this model.

  14. Catalytic Mechanism of the Maltose Transporter Hydrolyzing ATP.

    PubMed

    Huang, Wenting; Liao, Jie-Lou

    2016-01-12

    We use quantum mechanical and molecular mechanical (QM/MM) simulations to study ATP hydrolysis catalyzed by the maltose transporter. This protein is a prototypical member of a large family that consists of ATP-binding cassette (ABC) transporters. The ABC proteins catalyze ATP hydrolysis to perform a variety of biological functions. Despite extensive research efforts, the precise molecular mechanism of ATP hydrolysis catalyzed by the ABC enzymes remains elusive. In this work, the reaction pathway for ATP hydrolysis in the maltose transporter is evaluated using a QM/MM implementation of the nudged elastic band method without presuming reaction coordinates. The potential of mean force along the reaction pathway is obtained with an activation free energy of 19.2 kcal/mol in agreement with experiments. The results demonstrate that the reaction proceeds via a dissociative-like pathway with a trigonal bipyramidal transition state in which the cleavage of the γ-phosphate P-O bond occurs and the O-H bond of the lytic water molecule is not yet broken. Our calculations clearly show that the Walker B glutamate as well as the switch histidine stabilizes the transition state via electrostatic interactions rather than serving as a catalytic base. The results are consistent with biochemical and structural experiments, providing novel insight into the molecular mechanism of ATP hydrolysis in the ABC proteins.

  15. Potential fluid mechanic pathways of platelet activation.

    PubMed

    Shadden, Shawn C; Hendabadi, Sahar

    2013-06-01

    Platelet activation is a precursor for blood clotting, which plays leading roles in many vascular complications and causes of death. Platelets can be activated by chemical or mechanical stimuli. Mechanically, platelet activation has been shown to be a function of elevated shear stress and exposure time. These contributions can be combined by considering the cumulative stress or strain on a platelet as it is transported. Here, we develop a framework for computing a hemodynamic-based activation potential that is derived from a Lagrangian integral of strain rate magnitude. We demonstrate that such a measure is generally maximized along, and near to, distinguished material surfaces in the flow. The connections between activation potential and these structures are illustrated through stenotic flow computations. We uncover two distinct structures that may explain observed thrombus formation at the apex and downstream of stenoses. More broadly, these findings suggest fundamental relationships may exist between potential fluid mechanic pathways for mechanical platelet activation and the mechanisms governing their transport.

  16. A general method for determining secondary active transporter substrate stoichiometry

    PubMed Central

    Fitzgerald, Gabriel A; Mulligan, Christopher; Mindell, Joseph A

    2017-01-01

    The number of ions required to drive substrate transport through a secondary active transporter determines the protein’s ability to create a substrate gradient, a feature essential to its physiological function, and places fundamental constraints on the transporter’s mechanism. Stoichiometry is known for a wide array of mammalian transporters, but, due to a lack of readily available tools, not for most of the prokaryotic transporters for which high-resolution structures are available. Here, we describe a general method for using radiolabeled substrate flux assays to determine coupling stoichiometries of electrogenic secondary active transporters reconstituted in proteoliposomes by measuring transporter equilibrium potentials. We demonstrate the utility of this method by determining the coupling stoichiometry of VcINDY, a bacterial Na+-coupled succinate transporter, and further validate it by confirming the coupling stoichiometry of vSGLT, a bacterial sugar transporter. This robust thermodynamic method should be especially useful in probing the mechanisms of transporters with available structures. DOI: http://dx.doi.org/10.7554/eLife.21016.001 PMID:28121290

  17. Mechanism of ochratoxin A transport in kidney

    SciTech Connect

    Sokol, P.P.; Ripich, G.; Holohan, P.D.; Ross, C.R.

    1988-08-01

    The effect of the fungal metabolite (mycotoxin) Ochratoxin A (OTA) on the transport of p-amino(/sup 3/H)hippurate (PAH), a prototypic organic anion, was examined in renal brush border (BBMV) and basolateral membrane vesicles (BLMV). OTA was as effective an inhibitor of PAH uptake in both membranes as probenecid. The dose response curves for OTA in BBMV and BLMV gave IC50 values of 20 +/- 6 and 32 +/- 7 microM, respectively. The effect was specific since the transport of the organic cation N1-methylnicotinamide was not affected. The phenomenon of counterflow was studied to establish that OTA is translocated. OTA produced trans stimulation of PAH transport in both BBMV and BLMV, demonstrating that OTA is transported across both these membranes. The data suggest that OTA interacts with the PAH transport system in both BBMV and BLMV. We conclude that OTA transport in the kidney is mediated via the renal organic anion transport system.

  18. The transport properties of activated carbon fibers

    SciTech Connect

    di Vittorio, S.L. . Dept. of Materials Science and Engineering); Dresselhaus, M.S. . Dept. of Electrical Engineering and Computer Science Massachusetts Inst. of Tech., Cambridge, MA . Dept. of Physics); Endo, M. . Dept. of Electrical Engineering); Issi, J-P.; Piraux, L.

    1990-07-01

    The transport properties of activated isotropic pitch-based carbon fibers with surface area 1000 m{sup 2}/g have been investigated. We report preliminary results on the electrical conductivity, the magnetoresistance, the thermal conductivity and the thermopower of these fibers as a function of temperature. Comparisons are made to transport properties of other disordered carbons. 19 refs., 4 figs.

  19. The Transport Properties of Activated Carbon Fibers

    DOE R&D Accomplishments Database

    di Vittorio, S. L.; Dresselhaus, M. S.; Endo, M.; Issi, J-P.; Piraux, L.

    1990-07-01

    The transport properties of activated isotropic pitch-based carbon fibers with surface area 1000 m{sup 2}/g have been investigated. We report preliminary results on the electrical conductivity, the magnetoresistance, the thermal conductivity and the thermopower of these fibers as a function of temperature. Comparisons are made to transport properties of other disordered carbons.

  20. Active urea transport in lower vertebrates and mammals.

    PubMed

    Bankir, Lise

    2014-01-01

    Some unicellular organisms can take up urea from the surrounding fluids by an uphill pumping mechanism. Several active (energy-dependent) urea transporters (AUTs) have been cloned in these organisms. Functional studies show that active urea transport also occurs in elasmobranchs, amphibians, and mammals. In the two former groups, active urea transport may serve to conserve urea in body fluids in order to balance external high ambient osmolarity or prevent desiccation. In mammals, active urea transport may be associated with the need to either store and/or reuse nitrogen in the case of low nitrogen supply, or to excrete nitrogen efficiently in the case of excess nitrogen intake. There are probably two different families of AUTs, one with a high capacity able to establish only a relatively modest transepithelial concentration difference (renal tubule of some frogs, pars recta of the mammalian kidney, early inner medullary collecting duct in some mammals eating protein-poor diets) and others with a low capacity but able to maintain a high transepithelial concentration difference that has been created by another mechanism or in another organ (elasmobranch gills, ventral skin of some toads, and maybe mammalian urinary bladder). Functional characterization of these transporters shows that some are coupled to sodium (symports or antiports) while others are sodium-independent. In humans, only one genetic anomaly, with a mild phenotype (familial azotemia), is suspected to concern one of these transporters. In spite of abundant functional evidence for such transporters in higher organisms, none have been molecularly identified yet.

  1. An Abiotic Glass-Bead Collector Exhibiting Active Transport

    NASA Astrophysics Data System (ADS)

    Goto, Youhei; Kanda, Masato; Yamamoto, Daigo; Shioi, Akihisa

    2015-09-01

    Animals relocate objects as needed by active motion. Active transport is ubiquitous in living organisms but has been difficult to realize in abiotic systems. Here we show that a self-propelled droplet can gather scattered beads toward one place on a floor and sweep it clean. This is a biomimetic active transport with loadings and unloadings, because the transport was performed by a carrier and the motion of the carrier was maintained by the energy of the chemical reaction. The oil droplet produced fluctuation of the local number density of the beads on the floor, followed by its autocatalytic growth. This mechanism may inspire the technologies based on active transport wherein chemical and physical substances migrate as in living organisms.

  2. Mechanics of soft active materials

    NASA Astrophysics Data System (ADS)

    Zhao, Xuanhe

    Soft active materials, mostly elastomers and polymeric gels, are being developed to mimic a salient feature of life: movement in response to stimuli. For example, when an electric voltage is applied across a layer of a dielectric elastomer, the layer reduces in thickness and expands in area, giving a strain greater than 100%. As another example, in response to a small change of pH or temperature, a hydrogel may absorb a large amount of water and increase its volume over 100 times. The mechanics involved in these processes is important, interesting, and not well understood. This thesis studies large deformations and instabilities in dielectric elastomers and polymeric gels. The thesis first presents a nonlinear field theory for deformable dielectrics. The theory uses measurable quantities to define field variables. The definitions lead to decoupled field equations, and electromechanical coupling enters the theory through material laws. We use the theory to study electromechanical instability and coexistent states in dielectric elastomers. A computational method is also developed to analyze inhomogeneous deformations in complicated structures of dielectric elastomers. The second part of the thesis discusses large deformation and mass transportation in polymeric gels. A gel can undergo large deformation of two modes: local rearrangement and long-range migration. We assume that the local rearrangement is instantaneous, and model the long-range migration by assuming that the solvent molecules diffuse inside the gel. We further study inhomogeneous and anisotropic deformations and instabilities in gels constrained by rigid materials.

  3. Quantum-mechanical transport equation for atomic systems.

    NASA Technical Reports Server (NTRS)

    Berman, P. R.

    1972-01-01

    A quantum-mechanical transport equation (QMTE) is derived which should be applicable to a wide range of problems involving the interaction of radiation with atoms or molecules which are also subject to collisions with perturber atoms. The equation follows the time evolution of the macroscopic atomic density matrix elements of atoms located at classical position R and moving with classical velocity v. It is quantum mechanical in the sense that all collision kernels or rates which appear have been obtained from a quantum-mechanical theory and, as such, properly take into account the energy-level variations and velocity changes of the active (emitting or absorbing) atom produced in collisions with perturber atoms. The present formulation is better suited to problems involving high-intensity external fields, such as those encountered in laser physics.

  4. Berberine acutely activates the glucose transport activity of GLUT1.

    PubMed

    Cok, Alexandra; Plaisier, Christina; Salie, Matthew J; Oram, Daniel S; Chenge, Jude; Louters, Larry L

    2011-07-01

    Berberine, which has a long history of use in Chinese medicine, has recently been shown to have efficacy in the treatment of diabetes. While the hypoglycemic effect of berberine has been clearly documented in animal and cell line models, such as 3T3-L1 adipocytes and L6 myotube cells, the mechanism of action appears complex with data implicating activation of the insulin signaling pathway as well as activation of the exercise or AMP kinase-mediated pathway. There have been no reports of the acute affects of berberine on the transport activity of the insulin-insensitive glucose transporter, GLUT1. Therefore, we examined the acute effects of berberine on glucose uptake in L929 fibroblast cells, a cell line that express only GLUT1. Berberine- activated glucose uptake reaching maximum stimulation of five-fold at >40 μM. Significant activation (P < 0.05) was measured within 5 min reaching a maximum by 30 min. The berberine effect was not additive to the maximal stimulation by other known stimulants, azide, methylene blue or glucose deprivation, suggesting shared steps between berberine and these stimulants. Berberine significantly reduced the K(m) of glucose uptake from 6.7 ± 1.9 mM to 0.55 ± 0.08 mM, but had no effect on the V(max) of uptake. Compound C, an inhibitor of AMP kinase, did not affect berberine-stimulated glucose uptake, but inhibitors of downstream kinases partially blocked berberine stimulation. SB203580 (inhibitor of p38 MAP kinase) did not affect submaximal berberine activation, but did lower maximal berberine stimulation by 26%, while PD98059 (inhibitor of ERK kinase) completely blocked submaximal berberine activation and decreased the maximal stimulation by 55%. It appears from this study that a portion of the hypoglycemic effects of berberine can be attributed to its acute activation of the transport activity of GLUT1.

  5. Molecular Mechanisms of Phosphorus Metabolism and Transport during Leaf Senescence

    PubMed Central

    Stigter, Kyla A.; Plaxton, William C.

    2015-01-01

    Leaf senescence, being the final developmental stage of the leaf, signifies the transition from a mature, photosynthetically active organ to the attenuation of said function and eventual death of the leaf. During senescence, essential nutrients sequestered in the leaf, such as phosphorus (P), are mobilized and transported to sink tissues, particularly expanding leaves and developing seeds. Phosphorus recycling is crucial, as it helps to ensure that previously acquired P is not lost to the environment, particularly under the naturally occurring condition where most unfertilized soils contain low levels of soluble orthophosphate (Pi), the only form of P that roots can directly assimilate from the soil. Piecing together the molecular mechanisms that underpin the highly variable efficiencies of P remobilization from senescing leaves by different plant species may be critical for devising effective strategies for improving overall crop P-use efficiency. Maximizing Pi remobilization from senescing leaves using selective breeding and/or biotechnological strategies will help to generate P-efficient crops that would minimize the use of unsustainable and polluting Pi-containing fertilizers in agriculture. This review focuses on the molecular mechanisms whereby P is remobilized from senescing leaves and transported to sink tissues, which encompasses the action of hormones, transcription factors, Pi-scavenging enzymes, and Pi transporters. PMID:27135351

  6. Berberine stimulates glucose transport through a mechanism distinct from insulin.

    PubMed

    Zhou, Libin; Yang, Ying; Wang, Xiao; Liu, Shangquan; Shang, Wenbin; Yuan, Guoyue; Li, Fengying; Tang, Jinfeng; Chen, Mingdao; Chen, Jialun

    2007-03-01

    Berberine exerts a hypoglycemic effect, but the mechanism remains unknown. In the present study, the effect of berberine on glucose uptake was characterized in 3T3-L1 adipocytes. It was revealed that berberine stimulated glucose uptake in 3T3-L1 adipocytes in a dose- and time-dependent manner with the maximal effect at 12 hours. Glucose uptake was increased by berberine in 3T3-L1 preadipocytes as well. Berberine-stimulated glucose uptake was additive to that of insulin in 3T3-L1 adipocytes, even at the maximal effective concentrations of both components. Unlike insulin, the effect of berberine on glucose uptake was insensitive to wortmannin, an inhibitor of phosphatidylinositol 3-kinase, and SB203580, an inhibitor of p38 mitogen-activated protein kinase. Berberine activated extracellular signal-regulated kinase (ERK) 1/2, but PD98059, an ERK kinase inhibitor, only decreased berberine-stimulated glucose uptake by 32%. Berberine did not induce Ser473 phosphorylation of Akt nor enhance insulin-induced phosphorylation of Akt. Meanwhile, the expression and cellular localization of glucose transporter 4 (GLUT4) were not altered by berberine. Berberine did not increase GLUT1 gene expression. However, genistein, a tyrosine kinase inhibitor, completely blocked berberine-stimulated glucose uptake in 3T3-L1 adipocytes and preadipocytes, suggesting that berberine may induce glucose transport via increasing GLUT1 activity. In addition, berberine increased adenosine monophosphate-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation. These findings suggest that berberine increases glucose uptake through a mechanism distinct from insulin, and activated adenosine monophosphate-activated protein kinase seems to be involved in the metabolic effect of berberine.

  7. Mechanically Active Electrospun Materials

    NASA Astrophysics Data System (ADS)

    Robertson, Jaimee M.

    Electrospinning, a technique used to fabricate small diameter polymer fibers, has been employed to develop unique, active materials falling under two categories: (1) shape memory elastomeric composites (SMECs) and (2) water responsive fiber mats. (1) Previous work has characterized in detail the properties and behavior of traditional SMECs with isotropic fibers embedded in an elastomer matrix. The current work has two goals: (i) characterize laminated anisotropic SMECs and (ii) develop a fabrication process that is scalable for commercial SMEC manufacturing. The former ((i)) requires electrospinning aligned polymer fibers. The aligned fibers are similarly embedded in an elastomer matrix and stacked at various fiber orientations. The resulting laminated composite has a unique response to tensile deformation: after stretching and releasing, the composite curls. This curling response was characterized based on fiber orientation. The latter goal ((ii)) required use of a dual-electrospinning process to simultaneously electrospin two polymers. This fabrication approach incorporated only industrially relevant processing techniques, enabling the possibility of commercial application of a shape memory rubber. Furthermore, the approach had the added benefit of increased control over composition and material properties. (2) The strong elongational forces experienced by polymer chains during the electrospinning process induce molecular alignment along the length of electrospun fibers. Such orientation is maintained in the fibers as the polymer vitrifies. Consequently, residual stress is stored in electrospun fiber mats and can be recovered by heating through the polymer's glass transition temperature. Alternatively, the glass transition temperature can be depressed by introducing a plasticizing agent. Poly(vinyl acetate) (PVAc) is plasticized by water, and its glass transition temperature is lowered below room temperature. Therefore, the residual stress can be relaxed at room

  8. Ratchet transport powered by chiral active particles

    PubMed Central

    Ai, Bao-quan

    2016-01-01

    We numerically investigate the ratchet transport of mixtures of active and passive particles in a transversal asymmetric channel. A big passive particle is immersed in a ‘sea’ of active particles. Due to the chirality of active particles, the longitudinal directed transport is induced by the transversal asymmetry. For the active particles, the chirality completely determines the direction of the ratchet transport, the counterclockwise and clockwise particles move to the opposite directions and can be separated. However, for the passive particle, the transport behavior becomes complicated, the direction is determined by competitions among the chirality, the self-propulsion speed, and the packing fraction. Interestingly, within certain parameters, the passive particle moves to the left, while active particles move to the right. In addition, there exist optimal parameters (the chirality, the height of the barrier, the self-propulsion speed and the packing fraction) at which the rectified efficiency takes its maximal value. Our findings could be used for the experimental pursuit of the ratchet transport powered by chiral active particles. PMID:26795952

  9. Developing Hypothetical Inhibition Mechanism of Novel Urea Transporter B Inhibitor

    NASA Astrophysics Data System (ADS)

    Li, Min; Tou, Weng Ieong; Zhou, Hong; Li, Fei; Ren, Huiwen; Chen, Calvin Yu-Chian; Yang, Baoxue

    2014-07-01

    Urea transporter B (UT-B) is a membrane channel protein that specifically transports urea. UT-B null mouse exhibited urea selective urine concentrating ability deficiency, which suggests the potential clinical applications of the UT-B inhibitors as novel diuretics. Primary high-throughput virtual screening (HTVS) of 50000 small-molecular drug-like compounds identified 2319 hit compounds. These 2319 compounds were screened by high-throughput screening using an erythrocyte osmotic lysis assay. Based on the pharmacological data, putative UT-B binding sites were identified by structure-based drug design and validated by ligand-based and QSAR model. Additionally, UT-B structural and functional characteristics under inhibitors treated and untreated conditions were simulated by molecular dynamics (MD). As the result, we identified four classes of compounds with UT-B inhibitory activity and predicted a human UT-B model, based on which computative binding sites were identified and validated. A novel potential mechanism of UT-B inhibitory activity was discovered by comparing UT-B from different species. Results suggest residue PHE198 in rat and mouse UT-B might block the inhibitor migration pathway. Inhibitory mechanisms of UT-B inhibitors and the functions of key residues in UT-B were proposed. The binding site analysis provides a structural basis for lead identification and optimization of UT-B inhibitors.

  10. Developing Hypothetical Inhibition Mechanism of Novel Urea Transporter B Inhibitor

    PubMed Central

    Li, Min; Tou, Weng Ieong; Zhou, Hong; Li, Fei; Ren, Huiwen; Chen, Calvin Yu-Chian; Yang, Baoxue

    2014-01-01

    Urea transporter B (UT-B) is a membrane channel protein that specifically transports urea. UT-B null mouse exhibited urea selective urine concentrating ability deficiency, which suggests the potential clinical applications of the UT-B inhibitors as novel diuretics. Primary high-throughput virtual screening (HTVS) of 50000 small-molecular drug-like compounds identified 2319 hit compounds. These 2319 compounds were screened by high-throughput screening using an erythrocyte osmotic lysis assay. Based on the pharmacological data, putative UT-B binding sites were identified by structure-based drug design and validated by ligand-based and QSAR model. Additionally, UT-B structural and functional characteristics under inhibitors treated and untreated conditions were simulated by molecular dynamics (MD). As the result, we identified four classes of compounds with UT-B inhibitory activity and predicted a human UT-B model, based on which computative binding sites were identified and validated. A novel potential mechanism of UT-B inhibitory activity was discovered by comparing UT-B from different species. Results suggest residue PHE198 in rat and mouse UT-B might block the inhibitor migration pathway. Inhibitory mechanisms of UT-B inhibitors and the functions of key residues in UT-B were proposed. The binding site analysis provides a structural basis for lead identification and optimization of UT-B inhibitors. PMID:25047372

  11. Active auditory mechanics in mosquitoes.

    PubMed Central

    Göpfert, M. C.; Robert, D.

    2001-01-01

    In humans and other vertebrates, hearing is improved by active contractile properties of hair cells. Comparable active auditory mechanics is now demonstrated in insects. In mosquitoes, Johnston's organ transduces sound-induced vibrations of the antennal flagellum. A non-muscular 'motor' activity enhances the sensitivity and tuning of the flagellar mechanical response in physiologically intact animals. This motor is capable of driving the flagellum autonomously, amplifying sound-induced vibrations at specific frequencies and intensities. Motor-related electrical activity of Johnston's organ strongly suggests that mosquito hearing is improved by mechanoreceptor motility. PMID:11270428

  12. [Sodium ion transportation system and its possible mechanisms in bacteria].

    PubMed

    Yang, Li-Fu; Zhao, Bai-Suo; Yang, Su-Sheng

    2007-12-01

    Sodium ion with high concentration is toxic to living cells, and microorganisms adapt to the environment containing high concentration of salt by the strategies of salt-in-cytoplasm and compatible solutes. The Na+ extrusion system plays important roles in maintaining cytoplasmic Na+ homeostasis and pH level in microbial cells. Two possible mechanisms of Na+ circulation across the cytoplasmic membrane have been proposed, namely primary Na+ pump and secondary Na+/H+ antiporter. Primary sodium pumps coupled the extrusion of Na+ to respiration, and the activity of which was insensitive to uncoupler CCCP ( carbonyl-cyanide m-chlorophenylhydrazone). There were two types of secondary Na+/H+ antiporters-encoding genes designated single gene and multiple subunits, respectively. The types of transportation systems for Na+, possible mechanisms of Na+ extrusion, and projects for further study in bacteria are reviewed.

  13. Stochastic steps in secondary active sugar transport.

    PubMed

    Adelman, Joshua L; Ghezzi, Chiara; Bisignano, Paola; Loo, Donald D F; Choe, Seungho; Abramson, Jeff; Rosenberg, John M; Wright, Ernest M; Grabe, Michael

    2016-07-05

    Secondary active transporters, such as those that adopt the leucine-transporter fold, are found in all domains of life, and they have the unique capability of harnessing the energy stored in ion gradients to accumulate small molecules essential for life as well as expel toxic and harmful compounds. How these proteins couple ion binding and transport to the concomitant flow of substrates is a fundamental structural and biophysical question that is beginning to be answered at the atomistic level with the advent of high-resolution structures of transporters in different structural states. Nonetheless, the dynamic character of the transporters, such as ion/substrate binding order and how binding triggers conformational change, is not revealed from static structures, yet it is critical to understanding their function. Here, we report a series of molecular simulations carried out on the sugar transporter vSGLT that lend insight into how substrate and ions are released from the inward-facing state of the transporter. Our simulations reveal that the order of release is stochastic. Functional experiments were designed to test this prediction on the human homolog, hSGLT1, and we also found that cytoplasmic release is not ordered, but we confirmed that substrate and ion binding from the extracellular space is ordered. Our findings unify conflicting published results concerning cytoplasmic release of ions and substrate and hint at the possibility that other transporters in the superfamily may lack coordination between ions and substrate in the inward-facing state.

  14. Stochastic steps in secondary active sugar transport

    PubMed Central

    Adelman, Joshua L.; Ghezzi, Chiara; Bisignano, Paola; Loo, Donald D. F.; Choe, Seungho; Abramson, Jeff; Rosenberg, John M.; Wright, Ernest M.; Grabe, Michael

    2016-01-01

    Secondary active transporters, such as those that adopt the leucine-transporter fold, are found in all domains of life, and they have the unique capability of harnessing the energy stored in ion gradients to accumulate small molecules essential for life as well as expel toxic and harmful compounds. How these proteins couple ion binding and transport to the concomitant flow of substrates is a fundamental structural and biophysical question that is beginning to be answered at the atomistic level with the advent of high-resolution structures of transporters in different structural states. Nonetheless, the dynamic character of the transporters, such as ion/substrate binding order and how binding triggers conformational change, is not revealed from static structures, yet it is critical to understanding their function. Here, we report a series of molecular simulations carried out on the sugar transporter vSGLT that lend insight into how substrate and ions are released from the inward-facing state of the transporter. Our simulations reveal that the order of release is stochastic. Functional experiments were designed to test this prediction on the human homolog, hSGLT1, and we also found that cytoplasmic release is not ordered, but we confirmed that substrate and ion binding from the extracellular space is ordered. Our findings unify conflicting published results concerning cytoplasmic release of ions and substrate and hint at the possibility that other transporters in the superfamily may lack coordination between ions and substrate in the inward-facing state. PMID:27325773

  15. AXONAL TRANSPORT: CARGO-SPECIFIC MECHANISMS OF MOTILITY AND REGULATION

    PubMed Central

    Maday, Sandra; Twelvetrees, Alison E.; Moughamian, Armen J.; Holzbaur, Erika L. F.

    2014-01-01

    Axonal transport is essential for neuronal function, and many neurodevelopmental and neurodegenerative diseases result from mutations in the axonal transport machinery. Anterograde transport supplies distal axons with newly synthesized proteins and lipids, including synaptic components required to maintain presynaptic activity. Retrograde transport is required to maintain homeostasis by removing aging proteins and organelles from the distal axon for degradation and recycling of components. Retrograde axonal transport also plays a major role in neurotrophic and injury response signaling. This review provides an overview of the axonal transport pathway and discusses its role in neuronal function. PMID:25374356

  16. Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P-Glycoprotein-Mediated Drug Transport.

    PubMed

    Liao, Zheng-Gen; Tang, Tao; Guan, Xue-Jing; Dong, Wei; Zhang, Jing; Zhao, Guo-Wei; Yang, Ming; Liang, Xin-Li

    2016-11-24

    P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and vincristine. Our previous study demonstrated that imperatorin increased the intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated drug efflux. However; the underlying mechanism was not known. The present study investigated the mechanism by which imperatorin promotes P-gp-mediated drug transport. We used molecular docking to predict the binding force between imperatorin and P-gp and the effect of imperatorin on P-gp activity. P-gp efflux activity and P-gp ATPase activity were measured using a rhodamine 123 (Rh-123) accumulation assay and a Pgp-Glo™ assay; respectively. The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess cellular membrane fluidity in MDCK-MDR1 cells. Western blotting was used to analyze the effect of imperatorin on P-gp expression; and P-gp mRNA levels were assessed by qRT-PCR. Molecular docking results demonstrated that the binding force between imperatorin and P-gp was much weaker than the force between P-gp and verapamil (a P-gp substrate). Imperatorin activated P-gp ATPase activity; which had a role in the inhibition of P-gp activity. Imperatorin promoted Rh-123 accumulation in MDCK-MDR1 cells and decreased cellular membrane fluidity. Western blotting demonstrated that imperatorin inhibited P-gp expression; and qRT-PCR revealed that imperatorin down-regulated P-gp (MDR1) gene expression. Imperatorin decreased P-gp-mediated drug efflux by inhibiting P-gp activity and the expression of P-gp mRNA and protein. Our results suggest that imperatorin could down-regulate P-gp expression to overcome multidrug resistance in tumors.

  17. Grain transport mechanics in shallow overland flow

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A physical model based on continuum multiphase flow is described to represent saltating transport of grains in shallow overland flow. The two phase continuum flow of water and sediment considers coupled St.Venant type equations. The interactive cumulative effect of grains is incorporated by a disper...

  18. Grain transport mechanics in shallow flow

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A physical model based on continuum multiphase flow is described to represent saltating transport of grains in shallow overland flows. The two-phase continuum flow of water and sediment considers coupled St.Venant type equations. The interactive cumulative effect of grains is incorporated by a dispe...

  19. Molecular mechanism(s) involved in differential expression of vitamin C transporters along the intestinal tract.

    PubMed

    Subramanian, Veedamali S; Srinivasan, Padmanabhan; Wildman, Alexis J; Marchant, Jonathan S; Said, Hamid M

    2017-04-01

    Mammalian cells utilize two transporters for the uptake of ascorbic acid (AA), Na(+)-dependent vitamin C transporter SVCT-1 and SVCT-2. In the intestine, these transporters are involved in AA absorption and are expressed at the apical and basolateral membrane domains of the polarized epithelia, respectively. Little is known about the differential expression of these two transporters along the anterior-posterior axis of the intestinal tract and the molecular mechanism(s) that dictate this pattern of expression. We used mouse and human intestinal cDNAs to address these issues. The results showed a significantly lower rate of carrier-mediated AA uptake by mouse colon than jejunum. This was associated with a significantly lower level of expression of SVCT-1 and SVCT-2 at the protein, mRNA, and heterogeneous nuclear RNA (hnRNA) levels in the colon than the jejunum, implying the involvement of transcriptional mechanism(s). Similarly, expression levels of SVCT-1 and SVCT-2 mRNA and hnRNA were significantly lower in human colon. We also examined the levels of expression of hepatocyte nuclear factor 1α and specificity protein 1, which drive transcription of the Slc23a1 and Slc23a2 promoters, respectively, and found them to be markedly lower in the colon. Furthermore, significantly lower levels of the activating markers for histone (H3) modifications [H3 trimethylation of lysine 4 (H3K4me3) and H3 triacetylation of lysine 9 (H3K9ac)] were observed in the Slc23a1 and Slc23a2 promoters in the colon. These findings show, for the first time, that SVCT-1 and SVCT-2 are differentially expressed along the intestinal tract and that this pattern of expression is, at least in part, mediated via transcriptional/epigenetic mechanisms.NEW & NOTEWORTHY Our findings show, for the first time, that transporters of the water-soluble vitamin ascorbic acid (i.e., the vitamin C transporters SVCT-1 and SVCT-2) are differentially expressed along the length of the intestinal tract and that the

  20. Activities of the Institute for Mechanical Engineering

    NASA Astrophysics Data System (ADS)

    The Institute of Mechanical Engineering (IME) is part of Canada's National Research Council. Its mission is to undertake, support, promote, and disseminate research and development in the mechanical engineering aspects of three vital sectors of the Canadian economy: transportation, resource industries, and manufacturing. The IME achieves its mission by performing research and development in its own facilities; by developing, providing, and transferring expertise and knowledge; by making its research facilities available to collaborators and clients; and by participating in international liaison and collaborative research activities. Six research programs are conducted in the IME: Advanced Manufacturing Technology; Coastal Zone Engineering; Cold Regions Engineering; Combustion and Fluids Engineering; Ground Transportation Technology; and Machinery and Engine Technology. The rationale and major research thrusts of each program are described, and specific achievements in 1991-92 are reviewed. Lists of technical reports and papers presented by IME personnel are also included.

  1. Development of novel active transport membrande devices

    SciTech Connect

    Laciak, D.V.

    1994-11-01

    Air Products has undertaken a research program to fabricate and evaluate gas separation membranes based upon promising ``active-transport`` (AT) materials recently developed in our laboratories. Active Transport materials are ionic polymers and molten salts which undergo reversible interaction or reaction with ammonia and carbon dioxide. The materials are useful for separating these gases from mixtures with hydrogen. Moreover, AT membranes have the unique property of possessing high permeability towards ammnonia and carbon dioxide but low permeability towards hydrogen and can thus be used to permeate these components from a gas stream while retaining hydrogen at high pressure.

  2. The connexion between active cation transport and metabolism in erythrocytes

    PubMed Central

    Whittam, R.; Ager, Margaret E.

    1965-01-01

    1. A study has been made of the dependence on the concentrations of internal Na+ and external K+ of lactate and phosphate production in human erythrocytes. 2. Lactate production was stimulated by Na+ and K+ but only when they were internal and external respectively. The stimulation was counteracted by ouabain. The production of phosphate was affected in the same way. 3. There is a quantitative correlation between these effects and those previously found for cation movements and the membrane adenosine triphosphatase. 4. It is concluded that the rate of energy production in glycolysis is partly controlled by the magnitude of active transport; the extent of this regulation is shown to vary from 25 to 75% of a basal rate that is independent of active transport. 5. The activity of the membrane adenosine triphosphatase was also compared with rates of Na+ and K+ transport. The latter were varied by altering the concentrations of internal Na+ and external K+, and by inhibiting with ouabain. 6. A threefold variation of active transport rate was accompanied by a parallel change in the membrane adenosine-triphosphatase activity. The results show a constant stoicheiometry for the number of ions moved/mol. of ATP hydrolysed, independent of the electrochemical gradient against which the ions were moved. 7. Calculations show that the amount of ATP hydrolysed would provide enough energy for the osmotic work. The results are discussed in relation to possible mechanisms for active transport. PMID:16749106

  3. Statistical Mechanics of Collective Transport by Ants

    NASA Astrophysics Data System (ADS)

    Pinkoviezky, Itai; Gelblum, Aviram; Fonio, Ehud; Ghosh, Abhijit; Gov, Nir; Feinerman, Ofer

    Collective decisions and cooperation within groups are essential for the survival of many species. Conflicts within the group must be suppressed but conformism may render the system unresponsive to new information. Collective transport by ants is therefore an ideal model system to study how animal groups optimize these opposing requirements. We combine experiments and theory to characterize the collective transport. The ants are modeled as binary Ising spins, representing the two roles ants can perform during transport. It turns out that the ants poise themselves collectively near a critical point where the response to a newly attached ant is maximized. We identify the size as being proportional to an inverse effective temperature and thus the system can exhibit a mesoscopic transition between order and disorder by manipulating the size. Constraining the cargo with a string makes the system behave as a strongly non-linear pendulum. Theoretically we predict that a Hopf bifurcation occurs at a critical size followed by a global bifurcation where full swings emerge. Remarkably, these theoretical predictions were verified experimentally.

  4. Health Impacts of Active Transportation in Europe

    PubMed Central

    Rojas-Rueda, David; de Nazelle, Audrey; Andersen, Zorana J.; Braun-Fahrländer, Charlotte; Bruha, Jan; Bruhova-Foltynova, Hana; Desqueyroux, Hélène; Praznoczy, Corinne; Ragettli, Martina S.; Tainio, Marko; Nieuwenhuijsen, Mark J.

    2016-01-01

    Policies that stimulate active transportation (walking and bicycling) have been related to heath benefits. This study aims to assess the potential health risks and benefits of promoting active transportation for commuting populations (age groups 16–64) in six European cities. We conducted a health impact assessment using two scenarios: increased cycling and increased walking. The primary outcome measure was all-cause mortality related to changes in physical activity level, exposure to fine particulate matter air pollution with a diameter <2.5 μm, as well as traffic fatalities in the cities of Barcelona, Basel, Copenhagen, Paris, Prague, and Warsaw. All scenarios produced health benefits in the six cities. An increase in bicycle trips to 35% of all trips (as in Copenhagen) produced the highest benefits among the different scenarios analysed in Warsaw 113 (76–163) annual deaths avoided, Prague 61 (29–104), Barcelona 37 (24–56), Paris 37 (18–64) and Basel 5 (3–9). An increase in walking trips to 50% of all trips (as in Paris) resulted in 19 (3–42) deaths avoided annually in Warsaw, 11(3–21) in Prague, 6 (4–9) in Basel, 3 (2–6) in Copenhagen and 3 (2–4) in Barcelona. The scenarios would also reduce carbon dioxide emissions in the six cities by 1,139 to 26,423 (metric tonnes per year). Policies to promote active transportation may produce health benefits, but these depend of the existing characteristics of the cities. Increased collaboration between health practitioners, transport specialists and urban planners will help to introduce the health perspective in transport policies and promote active transportation. PMID:26930213

  5. Calcium transport mechanism in molting crayfish revealed by microanalysis

    SciTech Connect

    Mizuhira, V.; Ueno, M.

    1983-01-01

    Crayfish provide a good model in which to study the transport mechanism of Ca ions. During the molting stage, decalcified Ca ions are transferred into the blood and accumulate in the gastrolith epithelium, after which a gastrolith is formed on the surface of the epithelium. The gastrolith is dissolved in the stomach after molting, and the Ca is reabsorbed and redistributed throughout the newly formed exoskeleton. We studied the mechanism of Ca transport by cytochemical precipitation of Ca ions and by electron microanalysis, including X-ray microanalysis (EDX) and electron energy-loss spectroscopy (EELS), with a computer. In EDX analysis, the fine precipitates of K-antimonate in the gastrolith mitochondria clearly defined Ca with antimony; we also observed a large amount of Ca-oxalate in the mitochondria, and Ca-K X-ray pulses were clearly defined. Ca-K X-rays were also detected from fresh freeze-substituted mitochondria. Finally, we succeeded in taking a Ca-L EELS image from the mitochondria of fresh freeze-substituted thin sections. Only a very small amount of Ca was detected from the cell membrane and other organelles. Ca-adenosine triphosphatase (ATPase) and Mg-ATPase activity was also very clearly demonstrated in the mitochondria. These enzymes may play an important role in Ca metabolism.

  6. Regulators of Slc4 bicarbonate transporter activity

    PubMed Central

    Thornell, Ian M.; Bevensee, Mark O.

    2015-01-01

    The Slc4 family of transporters is comprised of anion exchangers (AE1-4), Na+-coupled bicarbonate transporters (NCBTs) including electrogenic Na/bicarbonate cotransporters (NBCe1 and NBCe2), electroneutral Na/bicarbonate cotransporters (NBCn1 and NBCn2), and the electroneutral Na-driven Cl-bicarbonate exchanger (NDCBE), as well as a borate transporter (BTR1). These transporters regulate intracellular pH (pHi) and contribute to steady-state pHi, but are also involved in other physiological processes including CO2 carriage by red blood cells and solute secretion/reabsorption across epithelia. Acid-base transporters function as either acid extruders or acid loaders, with the Slc4 proteins moving HCO−3 either into or out of cells. According to results from both molecular and functional studies, multiple Slc4 proteins and/or associated splice variants with similar expected effects on pHi are often found in the same tissue or cell. Such apparent redundancy is likely to be physiologically important. In addition to regulating pHi, a HCO−3 transporter contributes to a cell's ability to fine tune the intracellular regulation of the cotransported/exchanged ion(s) (e.g., Na+ or Cl−). In addition, functionally similar transporters or splice variants with different regulatory profiles will optimize pH physiology and solute transport under various conditions or within subcellular domains. Such optimization will depend on activated signaling pathways and transporter expression profiles. In this review, we will summarize and discuss both well-known and more recently identified regulators of the Slc4 proteins. Some of these regulators include traditional second messengers, lipids, binding proteins, autoregulatory domains, and less conventional regulators. The material presented will provide insight into the diversity and physiological significance of multiple members within the Slc4 gene family. PMID:26124722

  7. Phloem transport: a review of mechanisms and controls.

    PubMed

    De Schepper, Veerle; De Swaef, Tom; Bauweraerts, Ingvar; Steppe, Kathy

    2013-11-01

    It is generally believed that an osmotically generated pressure gradient drives the phloem mass flow. So far, this widely accepted Münch theory has required remarkably few adaptations, but the debate on alternative and additional hypotheses is still ongoing. Recently, a possible shortcoming of the Münch theory has been pointed out, suggesting that the Münch pressure flow is more suitable for herbs than for trees. Estimation of the phloem resistance indicates that a point might be reached in long sieve tubes where the pressure required to drive the Münch flow cannot be generated. Therefore, the relay hypothesis regained belief as it implies that the sieve tubes are shorter then the plant's axial axis. In the source phloem, three different loading strategies exist which probably result from evolutionary advantages. Passive diffusion seems to be the most primitive one, whereas active loading strategies substantially increase the growth potential. Along the transport phloem, a leakage-retrieval mechanism is observed. Appreciable amounts of carbohydrates are lost from the sieve tubes to feed the lateral sinks, while a part of these lost carbohydrates is subsequently reloaded into the sieve tubes. This mechanism is probably involved to buffer short-term irregularities in phloem turgor and gradient. In the long term, the mechanism controls the replenishment and remobilization of lateral stem storage tissues. As phloem of higher plants has multiple functions in plant development, reproduction, signalling, and growth, the fundamental understanding of the mechanisms behind phloem transport should be elucidated to increase our ability to influence plant growth and development.

  8. Charge transport mechanism in lead oxide revealed by CELIV technique

    PubMed Central

    Semeniuk, O.; Juska, G.; Oelerich, J.-O.; Wiemer, M.; Baranovskii, S. D.; Reznik, A.

    2016-01-01

    Although polycrystalline lead oxide (PbO) belongs to the most promising photoconductors for optoelectronic and large area detectors applications, the charge transport mechanism in this material still remains unclear. Combining the conventional time-of-flight and the photo-generated charge extraction by linear increasing voltage (photo-CELIV) techniques, we investigate the transport of holes which are shown to be the faster carriers in poly-PbO. Experimentally measured temperature and electric field dependences of the hole mobility suggest a highly dispersive transport. In order to analyze the transport features quantitatively, the theory of the photo-CELIV is extended to account for the dispersive nature of charge transport. While in other materials with dispersive transport the amount of dispersion usually depends on temperature, this is not the case in poly-PbO, which evidences that dispersive transport is caused by the spatial inhomogeneity of the material and not by the energy disorder. PMID:27628537

  9. Alternating access mechanisms of LeuT-fold transporters: trailblazing towards the promised energy landscapes.

    PubMed

    Kazmier, Kelli; Claxton, Derek P; Mchaourab, Hassane S

    2016-12-29

    Secondary active transporters couple the uphill translocation of substrates to electrochemical ion gradients. Transporter conformational motion, generically referred to as alternating access, enables a central ligand binding site to change its orientation relative to the membrane. Here we review themes of alternating access and the transduction of ion gradient energy to power this process in the LeuT-fold class of transporters where crystallographic, computational and spectroscopic approaches have converged to yield detailed models of transport cycles. Specifically, we compare findings for the Na(+)-coupled amino acid transporter LeuT and the Na(+)-coupled hydantoin transporter Mhp1. Although these studies have illuminated multiple aspects of transporter structures and dynamics, a number of questions remain unresolved that so far hinder understanding transport mechanisms in an energy landscape perspective.

  10. Fluid transport by active elastic membranes

    NASA Astrophysics Data System (ADS)

    Evans, Arthur A.; Lauga, Eric

    2011-09-01

    A flexible membrane deforming its shape in time can self-propel in a viscous fluid. Alternatively, if the membrane is anchored, its deformation will lead to fluid transport. Past work in this area focused on situations where the deformation kinematics of the membrane were prescribed. Here we consider models where the deformation of the membrane is not prescribed, but instead the membrane is internally forced. Both the time-varying membrane shape and the resulting fluid motion result then from a balance between prescribed internal active stresses, internal passive resistance, and external viscous stresses. We introduce two specific models for such active internal forcing: one where a distribution of active bending moments is prescribed, and one where active inclusions exert normal stresses on the membrane by pumping fluid through it. In each case, we asymptotically calculate the membrane shape and the fluid transport velocities for small forcing amplitudes, and recover our results using scaling analysis.

  11. Substrate regulation of ascorbate transport activity in astrocytes

    SciTech Connect

    Wilson, J.X.; Jaworski, E.M.; Kulaga, A.; Dixon, S.J. )

    1990-10-01

    Astrocytes possess a concentrative L-ascorbate (vitamin C) uptake mechanism involving a Na(+)-dependent L-ascorbate transporter located in the plasma membrane. The present experiments examined the effects of deprivation and supplementation of extracellular L-ascorbate on the activity of this transport system. Initial rates of L-ascorbate uptake were measured by incubating primary cultures of rat astrocytes with L-(14C)ascorbate for 1 min at 37 degrees C. We observed that the apparent maximal rate of uptake (Vmax) increased rapidly (less than 1 h) when cultured cells were deprived of L-ascorbate. In contrast, there was no change in the apparent affinity of the transport system for L-(14C)ascorbate. The increase in Vmax was reversed by addition of L-ascorbate, but not D-isoascorbate, to the medium. The effects of external ascorbate on ascorbate transport activity were specific in that preincubation of cultures with L-ascorbate did not affect uptake of 2-deoxy-D-(3H(G))glucose. We conclude that the astroglial ascorbate transport system is modulated by changes in substrate availability. Regulation of transport activity may play a role in intracellular ascorbate homeostasis by compensating for regional differences and temporal fluctuations in external ascorbate levels.

  12. Allosteric Mechanisms of Molecular Machines at the Membrane: Transport by Sodium-Coupled Symporters.

    PubMed

    LeVine, Michael V; Cuendet, Michel A; Khelashvili, George; Weinstein, Harel

    2016-06-08

    Solute transport across cell membranes is ubiquitous in biology as an essential physiological process. Secondary active transporters couple the unfavorable process of solute transport against its concentration gradient to the energetically favorable transport of one or several ions. The study of such transporters over several decades indicates that their function involves complex allosteric mechanisms that are progressively being revealed in atomistic detail. We focus on two well-characterized sodium-coupled symporters: the bacterial amino acid transporter LeuT, which is the prototype for the "gated pore" mechanism in the mammalian synaptic monoamine transporters, and the archaeal GltPh, which is the prototype for the "elevator" mechanism in the mammalian excitatory amino acid transporters. We present the evidence for the role of allostery in the context of a quantitative formalism that can reconcile biochemical and biophysical data and thereby connects directly to recent insights into the molecular structure and dynamics of these proteins. We demonstrate that, while the structures and mechanisms of these transporters are very different, the available data suggest a common role of specific models of allostery in their functions. We argue that such allosteric mechanisms appear essential not only for sodium-coupled symport in general but also for the function of other types of molecular machines in the membrane.

  13. Transport and biological activities of bile acids.

    PubMed

    Zwicker, Brittnee L; Agellon, Luis B

    2013-07-01

    Bile acids have emerged as important biological molecules that support the solubilization of various lipids and lipid-soluble compounds in the gut, and the regulation of gene expression and cellular function. Bile acids are synthesized from cholesterol in the liver and eventually released into the small intestine. The majority of bile acids are recovered in the distal end of the small intestine and then returned to the liver for reuse. The components of the mechanism responsible for the recycling of bile acids within the enterohepatic circulation have been identified whereas the mechanism for intracellular transport is less understood. Recently, the ileal lipid binding protein (ILBP; human gene symbol FABP6) was shown to be needed for the efficient transport of bile acids from the apical side to the basolateral side of enterocytes in the distal intestine. This review presents an overview of the transport of bile acids between the liver and the gut as well as within hepatocytes and enterocytes. A variety of pathologies is associated with the malfunction of the bile acid transport system.

  14. Transport mechanisms in Schottky diodes realized on GaN

    NASA Astrophysics Data System (ADS)

    Amor, Sarrah; Ahaitouf, Ali; Ahaitouf, Abdelaziz; Salvestrini, Jean Paul; Ougazzaden, Abdellah

    2017-03-01

    This work is focused on the conducted transport mechanisms involved on devices based in gallium nitride GaN and its alloys. With considering all conduction mechanisms of current, its possible to understanded these transport phenomena. Thanks to this methodology the current-voltage characteristics of structures with unusual behaviour are further understood and explain. Actually, the barrier height (SBH) is a complex problem since it depends on several parameters like the quality of the metal-semiconductor interface. This study is particularly interesting as solar cells are made on this material and their qualification is closely linked to their transport properties.

  15. Whisking mechanics and active sensing.

    PubMed

    Bush, Nicholas E; Solla, Sara A; Hartmann, Mitra Jz

    2016-10-01

    We describe recent advances in quantifying the three-dimensional (3D) geometry and mechanics of whisking. Careful delineation of relevant 3D reference frames reveals important geometric and mechanical distinctions between the localization problem ('where' is an object) and the feature extraction problem ('what' is an object). Head-centered and resting-whisker reference frames lend themselves to quantifying temporal and kinematic cues used for object localization. The whisking-centered reference frame lends itself to quantifying the contact mechanics likely associated with feature extraction. We offer the 'windowed sampling' hypothesis for active sensing: that rats can estimate an object's spatial features by integrating mechanical information across whiskers during brief (25-60ms) windows of 'haptic enclosure' with the whiskers, a motion that resembles a hand grasp.

  16. Active and passive calcium transport systems in plant cells

    SciTech Connect

    Sze, H.

    1990-01-01

    The ability to change cytoplasmic Ca{sup 2+} levels ((Ca{sup 2+})) by cells has made this cation a key regulator of many biological processes. Cytoplasmic (Ca{sup 2+}) is determined by the coordination of passive Ca{sup 2+} fluxes which increase cytosolic (Ca{sup 2+}) and active Ca{sup 2+} transport systems that lower cytosolic (Ca{sup 2+}). The mechanisms by which plant cells achieve this is poorly understood. We have initially used isolated vesicles from the plasma membrane or organellar membranes to study Ca{sup 2+} transport systems in oat roots (a monocot) and carrot suspension cells (a dicot). The objectives of the proposal were to identify and characterize active (energy-dependent) and passive calcium transport systems that work together to regulate calcium levels in the cytoplasm of plant cells. 10 figs., 2 tabs.

  17. Active and passive calcium transport systems in plant cells

    SciTech Connect

    Sze, H.

    1991-01-01

    The ability to change cytoplasmic Ca{sup 2+} levels ((Ca{sup 2+})) by cells has made this cation a key regulator of many biological processes. Cytoplasmic (Ca{sup 2+}) is determined by the coordination of passive Ca{sup 2+} fluxes which increase cytosolic (Ca{sup 2+}) and active Ca{sup 2+} transport systems that lower cytosolic (Ca{sup 2+}). The mechanisms by which plant cells achieve this is poorly understood. We have initially used isolated vesicles from the plasma membrane or organellar membranes to study Ca{sup 2+} transport systems in oat roots (a monocot) and carrot suspension cells (a dicot). The objectives of the proposal were to identify and characterize active (energy-dependent) and passive calcium transport systems that work together to regulate calcium levels in the cytoplasm of plant cells.

  18. Drug Transport Mechanism of Oral Antidiabetic Nanomedicines

    PubMed Central

    Gundogdu, Evren; Yurdasiper, Aysu

    2014-01-01

    Context: Over the last few decades, extensive efforts have been made worldwide to develop nanomedicine delivery systems, especially via oral route for antidiabetic drugs. Absorption of insulin is hindered by epithelial cells of gastrointestinal tract, acidic gastric pH and digestive enzymes. Evidence Acquisition: Recent reports have identified and explained the beneficial role of several structural molecules like mucoadhesive polymers (polyacrylic acid, sodium alginate, chitosan) and other copolymers for the efficient transport and release of insulin to its receptors. Results: Insulin nanomedicines based on alginate-dextran sulfate core with a chitosan-polyethylene glycol-albumin shell reduced glycaemia in a dose dependent manner. Orally available exendin-4 formulations exerted their effects in a time dependent manner. Insulin nanoparticles formed by using alginate and dextran sulfate nucleating around calcium and binding to poloxamer, stabilized by chitosan, and subsequently coated with albumin showed a threefold increase of the hypoglycemic effect in comparison to free insulin in animal models. Solid lipid nanoparticles showed an enhancement of the bioavailability of repaglinide (RG) within optimized solid lipid nanoparticle formulations when compared with RG alone. Conclusions: Nanoparticles represent multiparticulate delivery systems designed to obtain prolonged or controlled drug delivery and to improve bioavailability as well as stability. Nanoparticles can also offer advantages like limiting fluctuations within therapeutic range, reducing side effects, protecting drugs from degradation, decreasing dosing frequency, and improving patient compliance and convenience PMID:24696697

  19. Quantum mechanisms of density wave transport

    PubMed Central

    Miller, John H.; Wijesinghe, Asanga I.

    2012-01-01

    We report on new developments in the quantum picture of correlated electron transport in charge and spin density waves. The model treats the condensate as a quantum fluid in which charge soliton domain wall pairs nucleate above a Coulomb blockade threshold field. We employ a time-correlated soliton tunneling model, analogous to the theory of time-correlated single electron tunneling, to interpret the voltage oscillations and nonlinear current-voltage characteristics above threshold. An inverse scaling relationship between threshold field and dielectric response, originally proposed by Grüner, emerges naturally from the model. Flat dielectric and other ac responses below threshold in NbSe3 and TaS3, as well as small density wave phase displacements, indicate that the measured threshold is often much smaller than the classical depinning field. In some materials, the existence of two distinct threshold fields suggests that both soliton nucleation and classical depinning may occur. In our model, the ratio of electrostatic charging to pinning energy helps determine whether soliton nucleation or classical depinning dominates. PMID:22711979

  20. Studies on optical, mechanical and transport properties of NLO active L-alanine formate single crystal grown by modified Sankaranarayanan Ramasamy (SR) method

    NASA Astrophysics Data System (ADS)

    Justin Raj, C.; Dinakaran, S.; Krishnan, S.; Milton Boaz, B.; Robert, R.; Jerome Das, S.

    2008-04-01

    Bulk single crystals of L-alanine formate of 10 mm diameter and 50 mm length have been grown with an aid of modified Sankaranarayanan-Ramasamy (SR) uniaxial crystal growth method within a period of ten days. The optical properties of the grown crystal were calculated from UV transmission spectral analysis. The second harmonic generation efficiency of the grown crystal was confirmed by Kurtz powder test. In order to determine the mechanical strength of the crystal, Vicker's microhardness test was carried along the growth plane (0 0 1). Dielectric studies reveal that both dielectric constant and dielectric loss decreases with increase in frequency. Photoconductivity study confirms the negative photoconducting nature of the crystal.

  1. Mechanisms for the transport of alpha,omega-dicarboxylates through the mitochondrial inner membrane.

    PubMed

    Liu, G; Hinch, B; Beavis, A D

    1996-10-11

    alpha,omega-Dicarboxylates have antibacterial properties, have been used in the treatment of hyperpigmentary disorders, are active against various melanoma cell lines, and can also undergo beta-oxidation. Little, however, is known about their transport. In this paper, we examine the mitochondrial transport of alpha, omega-dicarboxylates ranging from oxalate (DC2) to sebacate (DC10). DC2-DC10 are transported by the inner membrane anion channel (IMAC). DC6-DC10 are also transported by an electroneutral mechanism that appears to reflect transport of the acid through the lipid bilayer. At 37 degrees C and pH 7.0, DC10 is transported very rapidly at 3 micromol/min.mg, and respiring mitochondria swell in the K+ salts of these acids. This transport mechanism is probably the major pathway by which the longer dicarboxylates enter cells, bacteria, and mitochondria. We also demonstrate that DC5-DC10 can also be transported by an electroneutral mechanism mediated by tributyltin, a potent inhibitor of IMAC. The mechanism appears to involve electroneutral exchange of a TBT-dicarboxylate-H complex for TBT-OH. Finally, we present evidence that of all the dicarboxylates tested only DC2-DC4 can be transported by the classical dicarboxylate carrier.

  2. Bursts of Active Transport in Living Cells

    NASA Astrophysics Data System (ADS)

    Wang, Bo; Kuo, James; Granick, Steve

    2013-11-01

    We show, using a large new data set, that the temporally resolved speed of active cargo transport in living cells follows a scaling law over several decades of time and length. The statistical regularities display a time-averaged shape that we interpret to reflect stress buildup, followed by rapid release. The scaling power law agrees quantitatively with those reported in inanimate systems (jammed colloids and granular media, and magnetic Barkhausen noise), suggesting a common origin in pushing through a crowded environment in a weak force regime. The implied regulation of the speed of active cellular transport due to environmental obstruction results in bursts of speed and acceleration. These findings extend the classical notion of molecular crowding.

  3. Bursts of active transport in living cells.

    PubMed

    Wang, Bo; Kuo, James; Granick, Steve

    2013-11-15

    We show, using a large new data set, that the temporally resolved speed of active cargo transport in living cells follows a scaling law over several decades of time and length. The statistical regularities display a time-averaged shape that we interpret to reflect stress buildup, followed by rapid release. The scaling power law agrees quantitatively with those reported in inanimate systems (jammed colloids and granular media, and magnetic Barkhausen noise), suggesting a common origin in pushing through a crowded environment in a weak force regime. The implied regulation of the speed of active cellular transport due to environmental obstruction results in bursts of speed and acceleration. These findings extend the classical notion of molecular crowding.

  4. Neuroinflammation activates efflux transport by NFκB

    PubMed Central

    Yu, Chuanhui; Argyropoulos, George; Zhang, Yan; Kastin, Abba J.; Hsuchou, Hung; Pan, Weihong

    2009-01-01

    Background/aims Although it is known that drug delivery across the blood-brain barrier (BBB) may be hampered by efflux transport activity of the multidrug resistance (mdr) gene product P-glycoprotein, it is not clear how inflammation regulates efflux transporters. In rat brain endothelial (RBE4) cells of BBB origin, the proinflammatory cytokine TNF mainly induces transcriptional upregulation of mdr1b, and to a lesser extent mdr1a, resulting in greater efflux of the substrates (Yu C et al., Cell Physiol Biochem, 2007). This study further determined the mechanisms by which TNF activates mdr1b promoter activity. Methods/Results Luciferase reporter assays and DNA binding studies show that (a) maximal basal promoter activity was conferred by a 476 bp sequence upstream to the mdr1b transcriptional initiation site; (2) TNF induced upregulation of promoter activity by NFkB nuclear translocation; and (3) the NFκB binding site of the mdr1b promoter was solely responsible for basal and TNF-activated gene transcription, whereas the p53 binding site was not involved. Binding of the p65 subunit of NFκB to nuclear DNA from RBE4 cells was shown by electrophoretic mobility shift assay and chromatin immunoprecipitation assays. Conclusion Thus, NFκB mediated TNF-induced upregulation of mdr1b promoter activity, illustrating how inflammation activates BBB efflux transport. PMID:19088456

  5. New mechanism of lenalidomide activity.

    PubMed

    Keevan, Jacob; Figg, William D

    2014-08-01

    Lenalidomide is an immunomodulatory agent (IMiD) that has activity in hematologic cancer (e.g., multiple myeloma). The immunomodulatory and apoptotic properties are readily apparent in therapy. However, the exact mechanism of action has been difficult to quantify until recently when it was shown that another IMiD, thalidomide, binds to an E3 ubiquitin ligase complex constituent, CRBN. The article by Kronke et al. demonstrates that, by binding to CRBN and altering its selectivity, lenalidomide potentiates the ubiquitination and proteolysis of 2 specific proteins, IKZF1 and IKZF3. An article in the same issue, by Lu et al., supports these observations. IKZF1 and IKZF3 are transcription factors that are necessary for multiple myeloma, and repression of these transcription factors is a likely mechanism for lenalidomide activity in this disease.

  6. Mechanisms of dopamine transporter regulation in normal and disease states.

    PubMed

    Vaughan, Roxanne A; Foster, James D

    2013-09-01

    The dopamine (DA) transporter (DAT) controls the spatial and temporal dynamics of DA neurotransmission by driving reuptake of extracellular transmitter into presynaptic neurons. Many diseases such as depression, bipolar disorder, Parkinson's disease (PD), and attention deficit hyperactivity disorder (ADHD) are associated with abnormal DA levels, implicating DAT as a factor in their etiology. Medications used to treat these disorders and many addictive drugs target DAT and enhance dopaminergic signaling by suppressing transmitter reuptake. We now understand that the transport and binding properties of DAT are regulated by complex and overlapping mechanisms that provide neurons with the ability to modulate DA clearance in response to physiological demands. These processes are controlled by endogenous signaling pathways and affected by exogenous transporter ligands, demonstrating their importance for normal neurotransmission, drug abuse, and disease treatments. Increasing evidence supports the disruption of these mechanisms in DA disorders, implicating dysregulation of transport in disease etiologies and suggesting these processes as potential points for therapeutic manipulation of DA availability.

  7. Regulation of amniotic fluid volume: mathematical model based on intramembranous transport mechanisms.

    PubMed

    Brace, Robert A; Anderson, Debra F; Cheung, Cecilia Y

    2014-11-15

    Experimentation in late-gestation fetal sheep has suggested that regulation of amniotic fluid (AF) volume occurs primarily by modulating the rate of intramembranous transport of water and solutes across the amnion into underlying fetal blood vessels. In order to gain insight into intramembranous transport mechanisms, we developed a computer model that allows simulation of experimentally measured changes in AF volume and composition over time. The model included fetal urine excretion and lung liquid secretion as inflows into the amniotic compartment plus fetal swallowing and intramembranous absorption as outflows. By using experimental flows and solute concentrations for urine, lung liquid, and swallowed fluid in combination with the passive and active transport mechanisms of the intramembranous pathway, we simulated AF responses to basal conditions, intra-amniotic fluid infusions, fetal intravascular infusions, urine replacement, and tracheoesophageal occlusion. The experimental data are consistent with four intramembranous transport mechanisms acting in concert: 1) an active unidirectional bulk transport of AF with all dissolved solutes out of AF into fetal blood presumably by vesicles; 2) passive bidirectional diffusion of solutes, such as sodium and chloride, between fetal blood and AF; 3) passive bidirectional water movement between AF and fetal blood; and 4) unidirectional transport of lactate into the AF. Further, only unidirectional bulk transport is dynamically regulated. The simulations also identified areas for future study: 1) identifying intramembranous stimulators and inhibitors, 2) determining the semipermeability characteristics of the intramembranous pathway, and 3) characterizing the vesicles that are the primary mediators of intramembranous transport.

  8. Flexible oligocholate foldamers as membrane transporters and their guest-dependent transport mechanism.

    PubMed

    Zhang, Shiyong; Zhao, Yan

    2012-01-14

    Dimeric, trimeric, and tetrameric oligocholates with flexible 4-aminobutyroyl spacers caused the efflux of hydrophilic molecules such as carboxyfluorescein (CF) and glucose from POPC/POPG liposomes. Transport was greatly suppressed across higher-melting DPPC membranes. Lipid-mixing assays and dynamic light scattering (DLS) indicated that the liposomes were intact during the transport. Kinetic analysis supported the involvement of monomeric species in the rate-limiting step of CF transport, consistent with a carrier-based mechanism. Glucose transport, on the other hand, displayed a highly unusual zero-order dependence on the oligocholate concentration at low loading of the transporter. Different selectivity was observed in the oligocholate transporters depending on the guest involved.

  9. Activation of ion transport systems during cell volume regulation

    SciTech Connect

    Eveloff, J.L.; Warnock, D.G.

    1987-01-01

    This review discusses the activation of transport pathways during volume regulation, including their characteristics, the possible biochemical pathways that may mediate the activation of transport pathways, and the relations between volume regulation and transepithelial transport in renal cells. Many cells regulate their volume when exposed to an anisotonic medium. The changes in cell volume are caused by activation of ion transport pathways, plus the accompanying osmotically driven water movement such that cell volume returns toward normal levels. The swelling of hypertonically shrunken cells is termed regulatory volume increase (RVI) and involves an influx of NaCl into the cell via either activation of Na-Cl, Na-K-2Cl cotransport systems, or Na/sup +/-H/sup +/ and Cl/sup -/-HCO/sub 3//sup -/ exchangers. The reshrinking of hypotonically swollen cells is termed regulatory volume decrease (RVD) and involves an efflux of KCl and water from the cell by activation of either separate K/sup +/ and Cl/sup -/ conductances, a K-Cl cotransport system, or parallel K/sup +/-H/sup +/ and Cl/sup -/-HCO/sub 3//sup -/ exchangers. The biochemical mechanisms involved in the activation of transport systems are largely unknown, however, the phosphoinositide pathway may be implicated in RVI; phorbol esters, cGMP, and Ca/sup 2 +/ affect the process of volume regulation. Renal tubular cells, as well as the blood cells that transverse the medulla, are subjected to increasing osmotic gradients from the corticomedullary junction to the papillary tip, as well as changing interstitial and tubule fluid osmolarity, depending on the diuretic state of the animal. Medullary cells from the loop of Henle and the papilla can volume regulate by activating Na-K-2Cl cotransport or Na/sup +/-H/sup +/ and Cl/sup -/-HCO/sub 3//sup -/ exchange systems.

  10. Transport mechanisms acting in toroidal devices: A theoretician's view

    SciTech Connect

    Carreras, B.A.

    1993-01-01

    Understanding the basic mechanisms of transport in toroidal confinement devices remains one of the more challenging scientific issues in magnetic confinement. At the same time, it is a critical issue for the magnetic fusion program. Recent progress in understanding fluctuations and transport has been fostered by the development and use of new diagnostics, bringing new perspectives on these studies. This has stimulated new theoretical developments. A view of the most recent issues and progress in this area is given. The role of long wavelengths in core transport and the relation between shear flows and turbulence at the plasma edge are the primary topics considered.

  11. Atmospheric transport and diffusion mechanisms in coastal circulation systems

    SciTech Connect

    Kaleel, R.J.; Shearer, D.L.; MacRae, B.L.

    1983-06-01

    This study defines the cyclical aspects of coastal atmospheric behavior that are important to the transport and diffusion (dispersion) of radionuclides. The report is developed around discussions of the meteorological dynamics of the cyclical and (cellular) atmospheric coastal phenomena and the atmospheric transport/diffusion mechanisms along with an assessment of the measurements accompanying both. Further, the efforts directed to modeling both the atmospheric and transport/diffusion processes are summarized and evaluated. Lastly, the review is summarized through a set of conclusions about the current level of understanding of coastal atmospheric phenomena. Recommendations are offered which identify certain aspects of local scale cyclical coastal phenomena that are important to the NRC.

  12. Fluctuation driven active molecular transport in passive channel proteins

    NASA Astrophysics Data System (ADS)

    Kosztin, Ioan

    2006-03-01

    Living cells interact with their extracellular environment through the cell membrane, which acts as a protective permeability barrier for preserving the internal integrity of the cell. However, cell metabolism requires controlled molecular transport across the cell membrane, a function that is fulfilled by a wide variety of transmembrane proteins, acting as either passive or active transporters. In this talk it is argued that, contrary to the general belief, in active cell membranes passive and spatially asymmetric channel proteins can act as active transporters by consuming energy from nonequilibrium fluctuations fueled by cell metabolism. This assertion is demonstrated in the case of the E. coli aquaglyceroporin GlpF channel protein, whose high resolution crystal structure is manifestly asymmetric. By calculating the glycerol flux through GlpF within the framework of a stochastic model, it is found that, as a result of channel asymmetry, glycerol uptake driven by a concentration gradient is enhanced significantly in the presence of non-equilibrium fluctuations. Furthermore, the enhancement caused by a ratchet-like mechanism is larger for the outward, i.e., from the cytoplasm to the periplasm, flux than for the inward one, suggesting that the same non-equilibrium fluctuations also play an important role in protecting the interior of the cell against poisoning by excess uptake of glycerol. Preliminary data on water and sugar transport through aquaporin and maltoporin channels, respectively, are indicative of the universality of the proposed nonequilibrium-fluctuation-driven active transport mechanism. This work was supported by grants from the Univ. of Missouri Research Board, the Institute for Theoretical Sciences and the Department of Energy (DOE Contract W-7405-ENG-36), and the National Science Foundation (FIBR-0526854).

  13. The alternating access mechanism of transport as observed in the sodium-hydantoin transporter Mhp1

    PubMed Central

    Weyand, Simone; Shimamura, Tatsuro; Beckstein, Oliver; Sansom, Mark S. P.; Iwata, So; Henderson, Peter J. F.; Cameron, Alexander D.

    2011-01-01

    Secondary active transporters move molecules across cell membranes by coupling this process to the energetically favourable downhill movement of ions or protons along an electrochemical gradient. They function by the alternating access model of transport in which, through conformational changes, the substrate binding site alternately faces either side of the membrane. Owing to the difficulties in obtaining the crystal structure of a single transporter in different conformational states, relatively little structural information is known to explain how this process occurs. Here, the structure of the sodium-benzylhydantoin transporter, Mhp1, from Microbacterium liquefaciens, has been determined in three conformational states; from this a mechanism is proposed for switching from the outward-facing open conformation through an occluded structure to the inward-facing open state. PMID:21169684

  14. MECHANISM OF GLUCOSE TRANSPORT ACROSS THE YEAST CELL MEMBRANE

    PubMed Central

    Cirillo, Vincent P.

    1962-01-01

    Cirillo, Vincent P. (Seton Hall College of Medicine and Dentistry, Jersey City, N.J.). Mechanism of glucose transport across the yeast cell membrane. J. Bacteriol. 84:485–491. 1962.—The kinetics of d-glucose and l-sorbose transport was studied in Saccharomyces cerevisiae inhibited with iodoacetic acid under nitrogen to prevent glucose metabolism. d-Glucose was found to compete with l-sorbose for a common membrane transport system with an apparent affinity greater than 25 times that of sorbose. A comparison of the net rate of glucose and sorbose transport at 50 and 500 mm external concentration showed that glucose transport is greater than that of sorbose from the lower concentration, but sorbose transport is greater than glucose at the higher concentration. This reversal of transport rate of two sugars with markedly different affinities is predicted by the membrane carrier theory. A further prediction of carrier theory was confirmed by the demonstration that the rate of glucose transport into fructose-loaded cells is greater than into unloaded cells. PMID:14021412

  15. Active learning in transportation engineering education

    NASA Astrophysics Data System (ADS)

    Weir, Jennifer Anne

    The objectives of this research were (1) to develop experimental active-based-learning curricula for undergraduate courses in transportation engineering and (2) to assess the effectiveness of an active-learning-based traffic engineering curriculum through an educational experiment. The researcher developed a new highway design course as a pilot study to test selected active-learning techniques before employing them in the traffic engineering curriculum. Active-learning techniques, including multiple-choice questions, short problems completed by individual students or small groups, and group discussions, were used as active interludes within lectures. The researcher also collected and analyzed student performance and attitude data from control and experimental classes to evaluate the relative effectiveness of the traditional lecture (control) approach and the active-learning (experimental) approach. The results indicate that the active-learning approach adopted for the experimental class did have a positive impact on student performance as measured by exam scores. The students in the experimental class also indicated slightly more positive attitudes at the end of the course than the control class, although the difference was not significant. The author recommends that active interludes similar to those in the experimental curricula be used in other courses in civil engineering.

  16. Fluorescence measurement of chloride transport in monolayer cultured cells. Mechanisms of chloride transport in fibroblasts.

    PubMed

    Chao, A C; Dix, J A; Sellers, M C; Verkman, A S

    1989-12-01

    The methodology has been developed to measure Cl activity and transport in cultured cells grown on a monolayer using the entrapped Cl-sensitive fluorophore 6-methoxy-N-[3-sulfopropyl] quinolinium (SPQ). The method was applied to a renal epithelial cell line, LLC-PKI, and a nonepithelial cell line, Swiss 3T3 fibroblasts. SPQ was nontoxic to cells when present for greater than h in the culture media. To load with SPQ (5 mM), cells were made transiently permeable by exposure to hypotonic buffer (150 mOsm, 4 min). Intracellular fluorescence was monitored continuously by epifluorescence microscopy using low illumination intensity at 360 +/- 5 nm excitation wavelength and photomultiplier detection at greater than 410 nm. Over 60 min at 37 degrees C, there was no photobleaching and less than 10% leakage of SPQ out of cells; intracellular SPQ fluorescence was uniform. SPQ fluorescence was calibrated against intracellular [Cl] using high K solutions containing the ionophores nigericin and tributyltin. The Stern-Volmer constant (Kq) for quenching of intracellular SPQ by Cl was 13 M-1 for fibroblasts and LLC-PKl cells. In the absence of Cl, SPQ lifetime was 26 ns in aqueous solution and 3.7 +/- 0.6 ns in cells, showing that the lower Kq in cells than in free solution (Kq = 118 M-1) was due to SPQ quenching by intracellular anions. To examine Cl transport mechanisms, the time course of intracellular [Cl] was measured in response to rapid Cl addition and removal in the presence of ion or pH gradients. In fibroblasts, three distinct Cl transporting systems were identified: a stilbeneinhibitable Cl/HCO3 exchanger, a furosemide-sensitive Na/K/2Cl cotransporter, and a Ca-regulated Cl conductance. These results establish a direct optical method to measure intracellular [Cl] continuously in cultured cells.

  17. Unveiling the gating mechanism of ECF Transporter RibU

    NASA Astrophysics Data System (ADS)

    Song, Jianing; Ji, Changge; Zhang, John Z. H.

    2013-12-01

    Energy-coupling factor (ECF) transporters are responsible for uptake of micronutrients in prokaryotes. The recently reported crystal structure of an ECF transporter RibU provided a foundation for understanding the structure and transport mechanism of ECF transporters. In the present study, molecular dynamics (MD) was carried out to study the conformational changes of the S component RibU upon binding by riboflavin. Our result and analysis revealed a critically important gating mechanism, in which part of loop5 (L5') (eleven residues, missing in the crystal structure) between TM5 and TM6 is dynamically flexible and serves as a gate. Specifically, the L5' opens a large cavity accessible to riboflavin from the extracellular space in Apo-RibU and closes the cavity upon riboflavin binding through hydrophobic packing with riboflavin. Thus, L5'is proposed to be the gate for riboflavin binding. In addition, steered molecular dynamics (SMD) simulation is employed to investigate the translocation dynamics of RibU during riboflavin transport. The simulation result does not show evidence that the S component alone can carry out the transport function. Since loop regions are very flexible and therefore could not be resolved by crystallography, their dynamics are hard to predict based on crystal structure alone.

  18. Single-molecule detection with active transport

    NASA Astrophysics Data System (ADS)

    Ball, David Allan

    A glass capillary is used near the focal region of a custom-built confocal microscope to investigate the use of active transport for single-molecule detection in solution, with both one and two-photon laser excitation. The capillary tip has a diameter of several microns and is carefully aligned nearby to the sub-micron laser beam waist, collinear to the optical axis, so that a negative pressure-difference causes molecules to be drawn into the capillary, along the laser beam axis. The flow of solution, which is characterized by fluorescence correlation spectroscopy (FCS), can increase the single-molecule detection rate for slowly diffusing proteins by over a factor of 100, while the mean rate of photons during each burst is similar to that for random diffusional transport. Also, the flow is along the longest axis of the ellipsoidally-shaped confocal volume, which results in more collected photons per molecule than that for transverse flow at the same speed. When transport is dominated by flow, FCS can no longer distinguish molecules with differing translational diffusion, and hence a fluorescence fluctuation spectroscopy method based on differences in fluorescence brightness is investigated as a means for assaying different solution components, for applications in pharmaceutical drug discovery. Multi-channel fluctuation spectroscopy techniques can also be used for assays with the flow system and hence this dissertation also reports the characterization of a prototype 4-channel single-photon detector with a two-wavelength polarization-resolved optical set-up.

  19. Morphine Induces Ubiquitin-Proteasome Activity and Glutamate Transporter Degradation*

    PubMed Central

    Yang, Liling; Wang, Shuxing; Sung, Backil; Lim, Grewo; Mao, Jianren

    2008-01-01

    Glutamate transporters play a crucial role in physiological glutamate homeostasis, neurotoxicity, and glutamatergic regulation of opioid tolerance. However, how the glutamate transporter turnover is regulated remains poorly understood. Here we show that chronic morphine exposure induced posttranscriptional down-regulation of the glutamate transporter EAAC1 in C6 glioma cells with a concurrent decrease in glutamate uptake and increase in proteasome activity, which were blocked by the selective proteasome inhibitor MG-132 or lactacystin but not the lysosomal inhibitor chloroquin. At the cellular level, chronic morphine induced the PTEN (phosphatase and tensin homolog deleted on chromosome Ten)-mediated up-regulation of the ubiquitin E3 ligase Nedd4 via cAMP/protein kinase A signaling, leading to EAAC1 ubiquitination and proteasomal degradation. Either Nedd4 or PTEN knockdown with small interfering RNA prevented the morphine-induced EAAC1 degradation and decreased glutamate uptake. These data indicate that cAMP/protein kinase A signaling serves as an intracellular regulator upstream to the activation of the PTEN/Nedd4-mediated ubiquitin-proteasome system activity that is critical for glutamate transporter turnover. Under an in vivo condition, chronic morphine exposure also induced posttranscriptional down-regulation of the glutamate transporter EAAC1, which was prevented by MG-132, and transcriptional up-regulation of PTEN and Nedd4 within the spinal cord dorsal horn. Thus, inhibition of the ubiquitin-proteasome-mediated glutamate transporter degradation may be an important mechanism for preventing glutamate overexcitation and may offer a new strategy for treating certain neurological disorders and improving opioid therapy in chronic pain management. PMID:18539596

  20. Early metabolic effects and mechanism of ammonium transport in yeast

    SciTech Connect

    Pena, A.; Pardo, J.P.; Ramirez, J.

    1987-03-01

    Studies were performed to define the effects and mechanism of NH+4 transport in yeast. The following results were obtained. Glucose was a better facilitator than ethanol-H/sub 2/O/sub 2/ for ammonium transport; low concentrations of uncouplers or respiratory inhibitors could inhibit the transport with ethanol as the substrate. With glucose, respiratory inhibitors showed only small inhibitory effects, and only high concentrations of azide or trifluoromethoxy carbonylcyanide phenylhydrazone could inhibit ammonium transport. Ammonium in the free state could be concentrated approximately 200-fold by the cells. Also, the addition of ammonium produced stimulation of both respiration and fermentation; an increased rate of H+ extrusion and an alkalinization of the interior of the cell; a decrease of the membrane potential, as monitored by fluorescent cyanine; an immediate decrease of the levels of ATP and an increase of ADP, which may account for the stimulation of both fermentation and respiration; and an increase of the levels of inorganic phosphate. Ammonium was found to inhibit 86Rb+ transport much less than K+. Also, while K+ produced a competitive type of inhibition, that produced by NH4+ was of the noncompetitive type. From the distribution ratio of ammonium and the pH gradient, an electrochemical potential gradient of around -180 mV was calculated. The results indicate that ammonium is transported in yeast by a mechanism similar to that of monovalent alkaline cations, driven by a membrane potential. The immediate metabolic effects of this cation seem to be due to an increased (H+)ATPase, to which its transport is coupled. However, the carriers seem to be different. The transport system studied in this work was that of low affinity.

  1. Issues in tokamak/stellarator transport and confinement enhancement mechanisms

    SciTech Connect

    Perkins, F.W.

    1990-08-01

    At present, the mechanism for anomalous energy transport in low-{beta} toroidal plasmas -- tokamaks and stellarators -- remains unclear, although transport by turbulent E {times} B velocities associated with nonlinear, fine-scale microinstabilities is a leading candidate. This article discusses basic theoretical concepts of various transport and confinement enhancement mechanisms as well as experimental ramifications which would enable one to distinguish among them and hence identify a dominant transport mechanism. While many of the predictions of fine-scale turbulence are born out by experiment, notable contradictions exist. Projections of ignition margin rest both on the scaling properties of the confinement mechanism and on the criteria for entering enhanced confinement regimes. At present, the greatest uncertainties lie with the basis for scaling confinement enhancement criteria. A series of questions, to be answered by new experimental/theoretical work, is posed to resolve these outstanding contradictions (or refute the fine-scale turbulence model) and to establish confinement enhancement criteria. 73 refs., 4 figs., 5 tabs.

  2. [Hopping and superexchange mechanisms of charge transport to DNA].

    PubMed

    Lakhno, V D; Sultanov, V B

    2003-01-01

    A theory for charge transport in nucleobase sequences was constructed in which the hole migration proceeds via hopping between guanines. Each hop over the adenine-thymine (A-T) bridge connecting neighboring guanines occurs by means of the superexchange mechanism. The experimental data and theoretical results for various types of nucleobase sequences are compared.

  3. Organic Anion Transporter 1 Is Inhibited by Multiple Mechanisms and Shows a Transport Mode Independent of Exchange.

    PubMed

    Hotchkiss, Adam G; Gao, Tiandai; Khan, Usman; Berrigan, Liam; Li, Mansong; Ingraham, Leslie; Pelis, Ryan M

    2015-12-01

    The mechanism by which drugs inhibit organic anion transporter 1 (OAT1) was examined. OAT1 was stably expressed in Chinese hamster ovary (CHO) cells, and para-aminohippurate (PAH) and 6-carboxyfluorescein were the substrates. Most compounds (10 of 14) inhibited competitively, increasing the Michaelis constant (Km) without affecting the maximal transport rate (Jmax). Others were mixed-type (lowering Jmax and increasing Km) or noncompetitive (lowering Jmax only) inhibitors. The interaction of a noncompetitive inhibitor (telmisartan) with OAT1 was examined further. Binding of telmisartan to OAT1 was observed, but translocation was not. Telmisartan did not alter the plasma membrane expression of OAT1, indicating that it lowers Jmax by reducing the turnover number. PAH transport after telmisartan treatment and its washout recovered faster in the presence of 10% fetal bovine serum in the washout buffer, indicating that binding of telmisartan to OAT1 and its inhibitory effect are reversible. Together, these data suggest that telmisartan binds reversibly to a site distinct from substrate and stabilizes the transporter in a conformation unfavorable for translocation. In the absence of an exchangeable extracellular substrate, PAH efflux from CHO-OAT1 cells was relatively rapid. Telmisartan slowed PAH efflux, suggesting that some transporter-mediated efflux occurs independent of exchange. Although drug-drug interaction predictions at OAT1 assume competitive inhibition, these data show that OAT1 can be inhibited by other mechanisms, which could influence the accuracy of drug-drug interaction predictions at the transporter. Telmisartan was useful for examining how a noncompetitive inhibitor can alter OAT1 transport activity and for uncovering a transport mode independent of exchange.

  4. Transport in active systems crowded by obstacles

    NASA Astrophysics Data System (ADS)

    Huang, Mu-Jie; Schofield, Jeremy; Kapral, Raymond

    2017-02-01

    The reactive and diffusive dynamics of a single chemically powered Janus motor in a crowded medium of moving but passive obstacles is investigated using molecular simulation. It is found that the reaction rate of the catalytic motor reaction decreases in a crowded medium as the volume fraction of obstacles increases as a result of a reduction in the Smoluchowski diffusion-controlled reaction rate coefficient that contributes to the overall reaction rate. A continuum model is constructed and analyzed to interpret the dependence of the steady-state reaction rate observed in simulations on the volume fraction of obstacles in the system. The steady-state concentration fields of reactant and product are shown to be sensitive to the local structure of obstacles around the Janus motor. It is demonstrated that the active motor exhibits enhanced diffusive motion at long times with a diffusion constant that decreases as the volume fraction of crowding species increases. In addition, the dynamical properties of a passive tracer particle in a system containing many active Janus motors is studied to investigate how an active environment influences the transport of non-active species. The diffusivity of a passive tracer particle in an active medium is found to be enhanced in systems with forward-moving Janus motors due to the cooperative dynamics of these motors.

  5. Modeling Transport and Flow Regulatory Mechanisms of the Kidney

    PubMed Central

    Layton, Anita T.

    2013-01-01

    The kidney plays an indispensable role in the regulation of whole-organism water balance, electrolyte balance, and acid-base balance, and in the excretion of metabolic wastes and toxins. In this paper, we review representative mathematical models that have been developed to better understand kidney physiology and pathophysiology, including the regulation of glomerular filtration, the regulation of renal blood flow by means of the tubuloglomerular feedback mechanisms and of the myogenic mechanism, the urine concentrating mechanism, and regulation of renal oxygen transport. We discuss how such modeling efforts have significantly expanded our understanding of renal function in both health and disease. PMID:23914303

  6. Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

    NASA Astrophysics Data System (ADS)

    Appert-Rolland, C.; Ebbinghaus, M.; Santen, L.

    2015-09-01

    Cells are the elementary units of living organisms, which are able to carry out many vital functions. These functions rely on active processes on a microscopic scale. Therefore, they are strongly out-of-equilibrium systems, which are driven by continuous energy supply. The tasks that have to be performed in order to maintain the cell alive require transportation of various ingredients, some being small, others being large. Intracellular transport processes are able to induce concentration gradients and to carry objects to specific targets. These processes cannot be carried out only by diffusion, as cells may be crowded, and quite elongated on molecular scales. Therefore active transport has to be organized. The cytoskeleton, which is composed of three types of filaments (microtubules, actin and intermediate filaments), determines the shape of the cell, and plays a role in cell motion. It also serves as a road network for a special kind of vehicles, namely the cytoskeletal motors. These molecules can attach to a cytoskeletal filament, perform directed motion, possibly carrying along some cargo, and then detach. It is a central issue to understand how intracellular transport driven by molecular motors is regulated. The interest for this type of question was enhanced when it was discovered that intracellular transport breakdown is one of the signatures of some neuronal diseases like the Alzheimer. We give a survey of the current knowledge on microtubule based intracellular transport. Our review includes on the one hand an overview of biological facts, obtained from experiments, and on the other hand a presentation of some modeling attempts based on cellular automata. We present some background knowledge on the original and variants of the TASEP (Totally Asymmetric Simple Exclusion Process), before turning to more application oriented models. After addressing microtubule based transport in general, with a focus on in vitro experiments, and on cooperative effects in the

  7. Insights into the mechanisms of sterol transport between organelles.

    PubMed

    Mesmin, Bruno; Antonny, Bruno; Drin, Guillaume

    2013-09-01

    In cells, the levels of sterol vary greatly among organelles. This uneven distribution depends largely on non-vesicular routes of transfer, which are mediated by soluble carriers called lipid-transfer proteins (LTPs). These proteins have a domain with a hydrophobic cavity that accommodates one sterol molecule. However, a demonstration of their role in sterol transport in cells remains difficult. Numerous LTPs also contain membrane-binding elements, but it is not clear how these LTPs couple their ability to target organelles with lipid transport activity. This issue appears critical, since many sterol transporters are thought to act at contact sites between two membrane-bound compartments. Here, we emphasize that biochemical and structural studies provide precious insights into the mode of action of sterol-binding proteins. Recent studies on START, Osh/ORP and NPC proteins suggest models on how these proteins could transport sterol between organelles and, thereby, influence cellular functions.

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

    PubMed Central

    Sobczak, Iwona; Lolkema, Juke S.

    2005-01-01

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

  9. Small Substrate Transport and Mechanism of a Molybdate ATP Binding Cassette Transporter in a Lipid Environment*

    PubMed Central

    Rice, Austin J.; Harrison, Alistair; Alvarez, Frances J. D.; Davidson, Amy L.; Pinkett, Heather W.

    2014-01-01

    Embedded in the plasma membrane of all bacteria, ATP binding cassette (ABC) importers facilitate the uptake of several vital nutrients and cofactors. The ABC transporter, MolBC-A, imports molybdate by passing substrate from the binding protein MolA to a membrane-spanning translocation pathway of MolB. To understand the mechanism of transport in the biological membrane as a whole, the effects of the lipid bilayer on transport needed to be addressed. Continuous wave-electron paramagnetic resonance and in vivo molybdate uptake studies were used to test the impact of the lipid environment on the mechanism and function of MolBC-A. Working with the bacterium Haemophilus influenzae, we found that MolBC-A functions as a low affinity molybdate transporter in its native environment. In periods of high extracellular molybdate concentration, H. influenzae makes use of parallel molybdate transport systems (MolBC-A and ModBC-A) to take up a greater amount of molybdate than a strain with ModBC-A alone. In addition, the movement of the translocation pathway in response to nucleotide binding and hydrolysis in a lipid environment is conserved when compared with in-detergent analysis. However, electron paramagnetic resonance spectroscopy indicates that a lipid environment restricts the flexibility of the MolBC translocation pathway. By combining continuous wave-electron paramagnetic resonance spectroscopy and substrate uptake studies, we reveal details of molybdate transport and the logistics of uptake systems that employ multiple transporters for the same substrate, offering insight into the mechanisms of nutrient uptake in bacteria. PMID:24722984

  10. [Helicopter transportation of a sedated, mechanically ventilated patient with cervical cord injury].

    PubMed

    Kato, Hideya; Nishiwaki, Yuko; Hosoi, Kunihiko; Shiomi, Naoto; Hirata, Masashi

    2013-09-01

    We report helicopter transportation of a sedated, mechanically ventilated patient with cervical cord injury. A 20-year-old male sustained traumatic injury to the cervical spinal cord during extracurricular activities in a college. On arrival at the hospital, a halo vest was placed on the patient and tracheostomy was performed. On the 38th hospital day, he was transported a distance of 520km by helicopter to a specialized hospital in Fukuoka for medical repatriation. Cabin space was narrow. Since power supply and carrying capacity were limited, battery-driven and portable medical devices were used. In consideration for patient's psychological stress, he was sedated with propofol. RSS (Ramsay sedation scale) scores were recorded to evaluate whether the patient was adequately sedated during helicopter transportation. Prior to transport, we rehearsed the sedation using bispectral index monitoring (BIS) in the hospital to further ensure the patient's safety during the transport.

  11. Coupled ATPase-adenylate kinase activity in ABC transporters

    PubMed Central

    Kaur, Hundeep; Lakatos-Karoly, Andrea; Vogel, Ramona; Nöll, Anne; Tampé, Robert; Glaubitz, Clemens

    2016-01-01

    ATP-binding cassette (ABC) transporters, a superfamily of integral membrane proteins, catalyse the translocation of substrates across the cellular membrane by ATP hydrolysis. Here we demonstrate by nucleotide turnover and binding studies based on 31P solid-state NMR spectroscopy that the ABC exporter and lipid A flippase MsbA can couple ATP hydrolysis to an adenylate kinase activity, where ADP is converted into AMP and ATP. Single-point mutations reveal that both ATPase and adenylate kinase mechanisms are associated with the same conserved motifs of the nucleotide-binding domain. Based on these results, we propose a model for the coupled ATPase-adenylate kinase mechanism, involving the canonical and an additional nucleotide-binding site. We extend these findings to other prokaryotic ABC exporters, namely LmrA and TmrAB, suggesting that the coupled activities are a general feature of ABC exporters. PMID:28004795

  12. Synaptic activation modifies microtubules underlying transport of postsynaptic cargo.

    PubMed

    Maas, Christoph; Belgardt, Dorthe; Lee, Han Kyu; Heisler, Frank F; Lappe-Siefke, Corinna; Magiera, Maria M; van Dijk, Juliette; Hausrat, Torben J; Janke, Carsten; Kneussel, Matthias

    2009-05-26

    Synaptic plasticity, the ability of synapses to change in strength, requires alterations in synaptic molecule compositions over time, and synapses undergo selective modifications on stimulation. Molecular motors operate in sorting/transport of neuronal proteins; however, the targeting mechanisms that guide and direct cargo delivery remain elusive. We addressed the impact of synaptic transmission on the regulation of intracellular microtubule (MT)-based transport. We show that increased neuronal activity, as induced through GlyR activity blockade, facilitates tubulin polyglutamylation, a posttranslational modification thought to represent a molecular traffic sign for transport. Also, GlyR activity blockade alters the binding of the MT-associated protein MAP2 to MTs. By using the kinesin (KIF5) and the postsynaptic protein gephyrin as models, we show that such changes of MT tracks are accompanied by reduced motor protein mobility and cargo delivery into neurites. Notably, the observed neurite targeting deficits are prevented on functional depletion or gene expression knockdown of neuronal polyglutamylase. Our data suggest a previously undescribed concept of synaptic transmission regulating MT-dependent cargo delivery.

  13. The Mechanism of 5-Methyltetrahydrofolate Transport by Human Erythrocytes

    PubMed Central

    Branda, Richard F.; Anthony, Bruce K.; Jacob, Harry S.

    1978-01-01

    The mechanism involved in 5-methyltetrahydrofolate uptake by human cells is poorly understood. To more clearly elucidate this physiologically important process, transport of the vitamin was studied in human erythrocytes. 5-methyltetrahydrofolate uptake was found to increase with reticulocytosis, but measurable incorporation occurred in erythrocyte suspensions depleted of reticulocytes, leukocytes, and platelets, indicating uptake by mature erythrocytes. Incubation of erythrocytes with increasing concentrations of [14C]5-methyltetrahydrofolate resulted in increasing uptake but decreasing percentage incorporation, consistent with saturation of a carrier system. Both influx and efflux phases of uptake were temperature dependent, with almost no transport at 4°C. Uptake of [14C]5-methytetrahydrofolate was effectively inhibited by unlabeled 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, and methotrexate, but not by pteroylglutamic acid. Prior incubation with 5-formyltetrahydrofolate increased uptake of [14C]5-methyltetrahydrofolate, and extracellular 5-formyltetrahydrofolate enhanced efflux of [14C]5-methyltetrahydrofolate. Nearly total depletion of ATP increased uptake of [14C]5-methyltetrahydrofolate, but efflux was unchanged. Column chromatography of membrane-free hemolysate after incubation with [14C]5-methyltetrahydrofolate showed 95% of radioactivity corresponded to marker radioisotope, and no other peak was noted. Thus peripheral erythrocytes incorporate 5-methyltetrahydrofolate by a saturable, temperature-dependent, substrate-specific process which is influenced by counter-transport. This mechanism is qualitatively similar to the carrier-mediated transport of folate compounds previously described in other cell types. Therefore, human erythrocytes should be useful for detailed characterization of this membrane carrier system. PMID:659590

  14. Unveiling the missing transport mechanism inside the valveless micropump.

    PubMed

    Wang, An-Bang; Hsieh, Ming-Che

    2012-09-07

    It has long been held, misleadingly, that the rectifier is the only decisive element for the design of fluid transportation in a valveless micropump. We have shown here that pump performance is also critically dependent on the design of the vibration chamber, a neglected element in micropump design that has drawn almost no attention in the past. Moreover, the generally used in-line design has, surprisingly, the lowest efficiency. The transport mechanism was found to be linked to the hydraulic coupling of two asymmetric vortex pairs inside the vibration chamber. Based upon the discovered flow mechanism, the proposed design inspired by an ancient fish trap has shown extraordinary improvement in micropump performance. It could also be potentially integrated with most existing designs for further energy saving.

  15. Mechanisms of carrier transport induced by a microswimmer bath.

    PubMed

    Kaiser, Andreas; Sokolov, Andrey; Aranson, Igor S; Löwen, Hartmut

    2015-04-01

    It was shown that a wedgelike microparticle (referred to as "carrier") exhibits a directed translational motion along the wedge cusp if it is exposed to a bath of microswimmers. Here we model this effect in detail by resolving the microswimmers explicitly using interaction models with different degrees of mutual alignment. Using computer simulations we study the impact of these interactions on the transport efficiency of a V-shaped carrier. We show that the transport mechanism itself strongly depends on the degree of alignment embodied in the modeling of the individual swimmer dynamics. For weak alignment, optimal carrier transport occurs in the turbulent microswimmer state and is induced by swirl depletion inside the carrier. For strong aligning interactions, optimal transport occurs already in the dilute regime and is mediated by a polar cloud of swimmers in the carrier wake pushing the wedge-particle forward. We also demonstrate that the optimal shape of the carrier leading to maximal transport speed depends on the kind of interaction model used.

  16. Mechanisms of Carrier Transport Induced by a Microswimmer Bath

    SciTech Connect

    Kaiser, Andreas; Sokolov, Andrey; Aranson, Igor S.; Lowen, Hartmut

    2015-04-01

    Recently, it was found that a wedgelike microparticle (referred to as ”carrier”) which is only allowed to translate but not to rotate exhibits a directed translational motion along the wedge cusp if it is exposed to a bath of microswimmers. Here we model this effect in detail by resolving the microswimmers explicitly using interaction models with different degrees of mutual alignment. Using computer simulations we study the impact of these interactions on the transport efficiency of V-shaped carrier. We show that the transport mechanisms itself strongly depends on the degree of alignment embodied in the modelling of the individual swimmer dynamics. For weak alignment, optimal carrier transport occurs in the turbulent microswimmer state and is induced by swirl depletion inside the carrier. For strong aligning interactions, optimal transport occurs already in the dilute regime and is mediated by a polar cloud of swimmers in the carrier wake pushing the wedge-particle forward. We also demonstrate that the optimal shape of the carrier leading to maximal transport speed depends on the kind of interaction model used.

  17. A mirror transport mechanism for use at cryogenic temperatures

    NASA Technical Reports Server (NTRS)

    Stark, Kenneth W.; Wilson, Meredith

    1986-01-01

    The Mirror Transport Mechanism (MTM), which supports a pair of dihedral mirrors and moves them in a very smooth and uniform scanning motion normal to a beamsplitter is described. Each scan is followed by a quick flyback and repeat. Material selection, design, and testing of all major components of the MTM are discussed. Flex pivot failures during vibration testing, excessive dihedral platform sag under one g operation, electronic and fiber optic characteristics, and tolerancing considerations are covered. Development of the mechanism has reached the final phase of thermal and vibration qualification. Environmental testing of the complete FIRAS experiment is just beginning.

  18. Integration of a 'proton antenna' facilitates transport activity of the monocarboxylate transporter MCT4.

    PubMed

    Noor, Sina Ibne; Pouyssegur, Jacques; Deitmer, Joachim W; Becker, Holger M

    2017-01-01

    Monocarboxylate transporters (MCTs) mediate the proton-coupled transport of high-energy metabolites like lactate and pyruvate and are expressed in nearly every mammalian tissue. We have shown previously that transport activity of MCT4 is enhanced by carbonic anhydrase II (CAII), which has been suggested to function as a 'proton antenna' for the transporter. In the present study, we tested whether creation of an endogenous proton antenna by introduction of a cluster of histidine residues into the C-terminal tail of MCT4 (MCT4-6xHis) could facilitate MCT4 transport activity when heterologously expressed in Xenopus oocytes. Our results show that integration of six histidines into the C-terminal tail does indeed increase transport activity of MCT4 to the same extent as did coexpression of MCT4-WT with CAII. Transport activity of MCT4-6xHis could be further enhanced by coexpression with extracellular CAIV, but not with intracellular CAII. Injection of an antibody against the histidine cluster into MCT4-expressing oocytes decreased transport activity of MCT4-6xHis, while leaving activity of MCT4-WT unaltered. Taken together, these findings suggest that transport activity of the proton-coupled monocarboxylate transporter MCT4 can be facilitated by integration of an endogenous proton antenna into the transporter's C-terminal tail.

  19. The maltose ABC transporter: action of membrane lipids on the transporter stability, coupling and ATPase activity.

    PubMed

    Bao, Huan; Dalal, Kush; Wang, Victor; Rouiller, Isabelle; Duong, Franck

    2013-08-01

    The coupling between ATP hydrolysis and substrate transport remains a key question in the understanding of ABC-mediated transport. We show using the MalFGK2 complex reconstituted into nanodiscs, that membrane lipids participate directly to the coupling reaction by stabilizing the transporter in a low energy conformation. When surrounded by short acyl chain phospholipids, the transporter is unstable and hydrolyzes large amounts of ATP without inducing maltose. The presence of long acyl chain phospholipids stabilizes the conformational dynamics of the transporter, reduces its ATPase activity and restores dependence on maltose. Membrane lipids therefore play an essential allosteric function, they restrict the transporter ATPase activity to increase coupling to the substrate. In support to the notion, we show that increasing the conformational dynamics of MalFGK2 with mutations in MalF increases the transporter ATPase activity but decreases the maltose transport efficiency.

  20. Inactivation of the glutamine/amino acid transporter ASCT2 by 1,2,3-dithiazoles: proteoliposomes as a tool to gain insights in the molecular mechanism of action and of antitumor activity

    SciTech Connect

    Oppedisano, Francesca; Catto, Marco; Koutentis, Panayiotis A.; Nicolotti, Orazio; Pochini, Lorena; Koyioni, Maria; Introcaso, Antonellina; Michaelidou, Sophia S.; Carotti, Angelo; Indiveri, Cesare

    2012-11-15

    The ASCT2 transport system catalyses a sodium-dependent antiport of glutamine and other neutral amino acids which is involved in amino acid metabolism. A library of 1,2,3-dithiazoles was designed, synthesized and evaluated as inhibitors of the glutamine/amino acid ASCT2 transporter in the model system of proteoliposomes reconstituted with the rat liver transporter. Fifteen of the tested compounds at concentration of 20 μM or below, inhibited more than 50% the glutamine/glutamine antiport catalysed by the reconstituted transporter. These good inhibitors bear a phenyl ring with electron withdrawing substituents. The inhibition was reversed by 1,4-dithioerythritol indicating that the effect was likely owed to the formation of mixed sulfides with the protein's Cys residue(s). A dose–response analysis of the most active compounds gave IC{sub 50} values in the range of 3–30 μM. Kinetic inhibition studies indicated a non-competitive inhibition, presumably because of a potential covalent interaction of the dithiazoles with cysteine thiol groups that are not located at the substrate binding site. Indeed, computational studies using a homology structural model of ASCT2 transporter, suggested as possible binding targets, Cys-207 or Cys-210, that belong to the CXXC motif of the protein. -- Highlights: ► Non‐competitive inhibition of ASCT2 by 1,2,3-dithiazoles was studied in proteoliposomes. ► Different 1,2,3-dithiazoles were synthesized and evaluated as transporter inhibitors. ► Many compounds potently inhibited the glutamine/glutamine antiport catalyzed by ASCT2. ► The inhibition was reversed by DTE indicating reaction with protein Cys. ► The most active compounds gave IC{sub 50} in the range of 3–30 μM.

  1. How to move an amphipathic molecule across a lipid bilayer: different mechanisms for different ABC transporters?

    PubMed Central

    Theodoulou, Frederica L.; Carrier, David J.; Schaedler, Theresia A.; Baldwin, Stephen A.; Baker, Alison

    2016-01-01

    Import of β-oxidation substrates into peroxisomes is mediated by ATP binding cassette (ABC) transporters belonging to subfamily D. In order to enter the β-oxidation pathway, fatty acids are activated by conversion to fatty acyl-CoA esters, a reaction which is catalysed by acyl-CoA synthetases (ACSs). Here, we present evidence for an unusual transport mechanism, in which fatty acyl-CoA substrates are accepted by ABC subclass D protein (ABCD) transporters, cleaved by the transporters during transit across the lipid bilayer to release CoA, and ultimately re-esterified in the peroxisome lumen by ACSs which interact with the transporter. We propose that this solves the biophysical problem of moving an amphipathic molecule across the peroxisomal membrane, since the intrinsic thioesterase activity of the transporter permits separate membrane translocation pathways for the hydrophobic fatty acid moiety and the polar CoA moiety. The cleavage/re-esterification mechanism also has the potential to control entry of disparate substrates into the β-oxidation pathway when coupled with distinct peroxisomal ACSs. A different solution to the movement of amphipathic molecules across a lipid bilayer is deployed by the bacterial lipid-linked oligosaccharide (LLO) flippase, PglK, in which the hydrophilic head group and the hydrophobic polyprenyl tail of the substrate are proposed to have distinct translocation pathways but are not chemically separated during transport. We discuss a speculative alternating access model for ABCD proteins based on the mammalian ABC transporter associated with antigen processing (TAP) and compare it to the novel mechanism suggested by the recent PglK crystal structures and biochemical data. PMID:27284041

  2. Active and passive transport of drugs in the human placenta.

    PubMed

    Włoch, Stanisław; Pałasz, Artur; Kamiński, Marcin

    2009-10-01

    The human placenta, characterized by the processes of passive transport and facilitated diffusion, contains numerous active transport proteins, usually located in the microvilli of the syncytiotrophoblast or in the endothelium of the capillaries of the villi. These proteins use either the energy from ATP hydrolysis or other mechanisms resulting, among others, from the formation of the maternofetal ion gradient, which facilitates the transfer of various endogenous substances or xenobiotics across the body membranes. The proteins either trigger the efflux of these substances from the fetal tissues via the placenta into the maternal bloodstream, or conversely they accumulate them in the fetal tissues. Both the placenta and the fetus are equipped with independent systems of enzymes of 1st and 2nd phase of substrate metabolism, such as CYP450, glucuronyltransferase or sulphatase. An active therapy with a wide range of drugs, often at high toxicity levels, either shortly before or during pregnancy, has naturally posed a question concerning the degree of impermeability of the placental barrier and how effectively it can be crossed, including any possible negative embryotoxic or teratogenic consequences. Such hazards seem to be quite real, as many drugs are substrates for ABC transporters. Also the placenta itself, including its structure, is subject to vast transformations during pregnancy which may be observed as the thinning of the barrier separating the maternal blood from the fetal one, from 20-30 microm in the first trimester of gestation down to 2-4 microm in the third trimester of gestation.

  3. Psychostimulants affect dopamine transmission through both dopamine transporter-dependent and independent mechanisms.

    PubMed

    dela Peña, Ike; Gevorkiana, Ruzanna; Shi, Wei-Xing

    2015-10-05

    The precise mechanisms by which cocaine and amphetamine-like psychostimulants exert their reinforcing effects are not yet fully defined. It is widely believed, however, that these drugs produce their effects by enhancing dopamine neurotransmission in the brain, especially in limbic areas such as the nucleus accumbens, by inducing dopamine transporter-mediated reverse transport and/or blocking dopamine reuptake though the dopamine transporter. Here, we present the evidence that aside from dopamine transporter, non-dopamine transporter-mediated mechanisms also participate in psychostimulant-induced dopamine release and contribute to the behavioral effects of these drugs, such as locomotor activation and reward. Accordingly, psychostimulants could increase norepinephrine release in the prefrontal cortex, the latter then alters the firing pattern of dopamine neurons resulting in changes in action potential-dependent dopamine release. These alterations would further affect the temporal pattern of dopamine release in the nucleus accumbens, thereby modifying information processing in that area. Hence, a synaptic input to a nucleus accumbens neuron may be enhanced or inhibited by dopamine depending on its temporal relationship to dopamine release. Specific temporal patterns of dopamine release may also be required for certain forms of synaptic plasticity in the nucleus accumbens. Together, these effects induced by psychostimulants, mediated through a non-dopamine transporter-mediated mechanism involving norepinephrine and the prefrontal cortex, may also contribute importantly to the reinforcing properties of these drugs.

  4. The transport mechanism of the integer quantum Hall effect

    NASA Astrophysics Data System (ADS)

    Hui, Tan; LiMing, W.; Liang, Shi-Dong

    2016-11-01

    The integer quantum Hall effect (IQHE) is analysed using a mechanism of the electron transport in the form of semi-classic wave packages in this paper. Due to the confinement of the edges of a slab the Landau levels of electrons in a strong magnetic field go up at large wave-vectors to form energy bands. The slopes of the energy bands give the group velocities of electron wave packages and thus contribute to the current. Certain magnetic fields separate the electron transport in the slab into two branches with opposite and large wave vectors, which are localized at the two edges of the slab, respectively. In this case back scattering of electrons is prohibited due to the localization of these two branches. Thus the slab exhibits zero longitudinal resistance and plateaus of Hall resistance. When the Fermi level is sweeping over a Landau level at some magnetic fields, however, the electron waves locate around the central axis of the slab and overlap each other thus back scattering of electrons takes place frequently. Then longitudinal resistance appears and the Hall resistance goes up from one plateau to a new one. This transport mechanism is much clearer and more intuitive than the conventional explanations to the IQHE.

  5. Evaporation as the transport mechanism of metals in arid regions.

    PubMed

    Lima, Ana T; Safar, Zeinab; Loch, J P Gustav

    2014-09-01

    Soils of arid regions are exposed to drought and drastic temperature oscillations throughout the year. Transport mechanisms in these soils are therefore very different from the ones in temperate regions, where rain dictates the fate of most elements in soils. Due to the low rainfall and high evaporation rates in arid regions, groundwater quality is not threatened and all soil contamination issues tend to be overlooked. But if soil contamination happens, where do contaminants go? This study tests the hypothesis of upward metal movement in soils when evaporation is the main transport mechanism. Laboratory evaporation tests were carried out with heavy metal spiked Saudi soil, using circulation of air as the driving force (Fig. 1). Main results show that loamy soil retains heavy metals quite well while evaporation drives heavy metals to the surface of a sandy soil. Evaporation transports heavy metals upward in sandy soils of arid regions, making them accumulate at the soil surface. Sand being the dominating type of soil in arid regions, soils can then be a potential source of contaminated aerosols and atmospheric pollution - a transboundary problem. Some other repercussions for this problem are foreseen, such as the public ingestion or inhalation of dust.

  6. Transportation as a "Related Service": Issues that Involve Transition Activities.

    ERIC Educational Resources Information Center

    Missouri Univ., Columbia. Missouri LINC.

    The paper discusses transportation as a related service for students with disabilities expecially as related to school-to-work transition activities. First, the legislative and legal basis for providing transportation services is discussed in the form of answers to frequently asked questions: why provide transportation? what is the basis for…

  7. Chill activation of compatible solute transporters in Corynebacterium glutamicum at the level of transport activity.

    PubMed

    Ozcan, Nuran; Krämer, Reinhard; Morbach, Susanne

    2005-07-01

    The gram-positive soil bacterium Corynebacterium glutamicum harbors four osmoregulated secondary uptake systems for compatible solutes, BetP, EctP, LcoP, and ProP. When reconstituted in proteoliposomes, BetP was shown to sense hyperosmotic conditions via the increase in luminal K(+) and to respond by instant activation. To study further putative ways of stimulus perception and signal transduction, we have investigated the responses of EctP, LcoP, and BetP, all belonging to the betaine-carnitine-choline transporter family, to chill stress at the level of activity. When fully activated by hyperosmotic stress, they showed the expected increase of activity at increasing temperature. In the absence of osmotic stress, EctP was not activated by chill and LcoP to only a very low extent, whereas BetP was significantly stimulated at low temperature. BetP was maximally activated at 10 degrees C, reaching the same transport rate as that observed under hyperosmotic conditions at this temperature. A role of cytoplasmic K(+) in chill-dependent activation of BetP was ruled out, since (i) the cytoplasmic K(+) concentration did not change significantly at lower temperatures and (ii) a mutant BetP lacking the C-terminal 25 amino acids, which was previously shown to have lost the ability to be activated by luminal K(+), was fully competent in chill sensing. When heterologously expressed in Escherichia coli, BetP did not respond to chill stress. This may indicate that the membrane in which BetP is inserted plays an important role in chill activation and thus in signal transduction by BetP, different from the previously established K(+)-mediated process.

  8. Cadmium in rice: Transport mechanisms, influencing factors, and minimizing measures.

    PubMed

    Li, Hui; Luo, Na; Li, Yan Wen; Cai, Quan Ying; Li, Hui Yuan; Mo, Ce Hui; Wong, Ming Hung

    2017-05-01

    Cadmium (Cd) accumulation in rice and its subsequent transfer to food chain is a major environmental issue worldwide. Understanding of Cd transport processes and its management aiming to reduce Cd uptake and accumulation in rice may help to improve rice growth and grain quality. Moreover, a thorough understanding of the factors influencing Cd accumulation will be helpful to derive efficient strategies to minimize Cd in rice. In this article, we reviewed Cd transport mechanisms in rice, the factors affecting Cd uptake (including physicochemical characters of soil and ecophysiological features of rice) and discussed efficient measures to immobilize Cd in soil and reduce Cd uptake by rice (including agronomic practices, bioremediation and molecular biology techniques). These findings will contribute to ensuring food safety, and reducing Cd risk on human beings.

  9. Mechanical Fatigue Testing of High Burnup Fuel for Transportation Applications

    SciTech Connect

    Wang, Jy-An John; Wang, Hong

    2015-05-01

    This report describes testing designed to determine the ability of high burnup (HBU) (>45 GWd/MTU) spent fuel to maintain its integrity under normal conditions of transportation. An innovative system, Cyclic Integrated Reversible-bending Fatigue Tester (CIRFT), has been developed at Oak Ridge National Laboratory (ORNL) to test and evaluate the mechanical behavior of spent nuclear fuel (SNF) under conditions relevant to storage and transportation. The CIRFT system is composed of a U-frame equipped with load cells for imposing the pure bending loads on the SNF rod test specimen and measuring the in-situ curvature of the fuel rod during bending using a set up with three linear variable differential transformers (LVDTs).

  10. Electron transport mechanisms in polymer-carbon sphere composites

    NASA Astrophysics Data System (ADS)

    Nieves, Cesar A.; Ramos, Idalia; Pinto, Nicholas J.; Zimbovskaya, Natalya A.

    2016-07-01

    A set of uniform carbon microspheres (CSs) whose diameters have the order of 0.125 μm to 10 μm was prepared from aqueous sucrose solution by means of hydrothermal carbonization of sugar molecules. A pressed pellet was composed by mixing CSs with polyethylene oxide (PEO). Electrical characterization of the pellet was carried out showing Ohmic current-voltage characteristics and temperature-dependent conductivity in the range of 80 K mechanisms of electron transport. It was shown that thermally induced electron tunneling between adjacent spheres may take on an important part in the electron transport through the CS/PEO composites.

  11. Air pollution exposure: An activity pattern approach for active transportation

    NASA Astrophysics Data System (ADS)

    Adams, Matthew D.; Yiannakoulias, Nikolaos; Kanaroglou, Pavlos S.

    2016-09-01

    In this paper, we demonstrate the calculation of personal air pollution exposure during trips made by active transportation using activity patterns without personal monitors. We calculate exposure as the inhaled dose of particulate matter 2.5 μg or smaller. Two modes of active transportation are compared, and they include cycling and walking. Ambient conditions are calculated by combining mobile and stationary monitoring data in an artificial neural network space-time model. The model uses a land use regression framework and has a prediction accuracy of R2 = 0.78. Exposure is calculated at 10 m or shorter intervals during the trips using inhalation rates associated with both modes. The trips are children's routes between home and school. The average dose during morning cycling trips was 2.17 μg, during morning walking trips was 3.19 μg, during afternoon cycling trips was 2.19 μg and during afternoon walking trips was 3.23 μg. The cycling trip dose was significantly lower than the walking trip dose. The air pollution exposure during walking or cycling trips could not be strongly predicted by either the school or household ambient conditions, either individually or in combination. Multiple linear regression models regressing both the household and school ambient conditions against the dose were only able to account for, at most, six percent of the variance in the exposure. This paper demonstrates that incorporating activity patterns when calculating exposure can improve the estimate of exposure compared to its calculation from ambient conditions.

  12. Mechanism of travelling-wave transport of particles

    NASA Astrophysics Data System (ADS)

    Kawamoto, Hiroyuki; Seki, Kyogo; Kuromiya, Naoyuki

    2006-03-01

    Numerical and experimental investigations have been carried out on transport of particles in an electrostatic travelling field. A three-dimensional hard-sphere model of the distinct element method was developed to simulate the dynamics of particles. Forces applied to particles in the model were the Coulomb force, the dielectrophoresis force on polarized dipole particles in a non-uniform field, the image force, gravity and the air drag. Friction and repulsion between particle-particle and particle-conveyer were included in the model to replace initial conditions after mechanical contacts. Two kinds of experiments were performed to confirm the model. One was the measurement of charge of particles that is indispensable to determine the Coulomb force. Charge distribution was measured from the locus of free-fallen particles in a parallel electrostatic field. The averaged charge of the bulk particle was confirmed by measurement with a Faraday cage. The other experiment was measurements of the differential dynamics of particles on a conveyer consisting of parallel electrodes to which a four-phase travelling electrostatic wave was applied. Calculated results agreed with measurements, and the following characteristics were clarified. (1) The Coulomb force is the predominant force to drive particles compared with the other kinds of forces, (2) the direction of particle transport did not always coincide with that of the travelling wave but changed partially. It depended on the frequency of the travelling wave, the particle diameter and the electric field, (3) although some particles overtook the travelling wave at a very low frequency, the motion of particles was almost synchronized with the wave at the low frequency and (4) the transport of some particles was delayed to the wave at medium frequency; the majority of particles were transported backwards at high frequency and particles were not transported but only vibrated at very high frequency.

  13. Curcumin directly inhibits the transport activity of GLUT1.

    PubMed

    Gunnink, Leesha K; Alabi, Ola D; Kuiper, Benjamin D; Gunnink, Stephen M; Schuiteman, Sam J; Strohbehn, Lauren E; Hamilton, Kathryn E; Wrobel, Kathryn E; Louters, Larry L

    2016-06-01

    Curcumin, a major ingredient in turmeric, has a long history of medicinal applications in a wide array of maladies including treatment for diabetes and cancer. Seemingly counterintuitive to the documented hypoglycemic effects of curcumin, however, a recent report indicates that curcumin directly inhibits glucose uptake in adipocytes. The major glucose transporter in adipocytes is GLUT4. Therefore, this study investigates the effects of curcumin in cell lines where the major transporter is GLUT1. We report that curcumin has an immediate inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum inhibition of 80% achieved at 75 μM curcumin. Curcumin also blocks activation of glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine oxide. Inhibition does not increase with exposure time and the inhibitory effects reverse within an hour. Inhibition does not appear to involve a reaction between curcumin and the thiol side chain of a cysteine residue since neither prior treatment of cells with iodoacetamide nor curcumin with cysteine alters curcumin's inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of 2DG transport by about half with little effect on the Km. The inhibitory effects of curcumin are not additive to the effects of cytochalasin B and 75 μM curcumin actually reduces specific cytochalasin B binding by 80%. Taken together, the data suggest that curcumin binds directly to GLUT1 at a site that overlaps with the cytochalasin B binding site and thereby inhibits glucose transport. A direct inhibition of GLUT proteins in intestinal epithelial cells would likely reduce absorption of dietary glucose and contribute to a hypoglycemic effect of curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that overexpress GLUT1 and be another possible mechanism for the documented anticancer effects of curcumin.

  14. Chloride transport in functionally active phagosomes isolated from Human neutrophils

    PubMed Central

    Aiken, Martha L.; Painter, Richard G.; Zhou, Yun; Wang, Guoshun

    2012-01-01

    Chloride anion is critical for hypochlorous acid (HOCl) production and microbial killing in neutrophil phagosomes. However, the molecular mechanism by which this anion is transported to the organelle is poorly understood. In this report, membrane-enclosed and functionally active phagosomes were isolated from human neutrophils by using opsonized paramagnetic latex microspheres and a rapid magnetic separation method. The phagosomes recovered were highly enriched for specific protein markers associated with this organelle such as lysosomal-associated membrane protein-1, myeloperoxidase (MPO), lactoferrin, and NADPH oxidase. When FITC–dextran was included in the phagocytosis medium, the majority of the isolated phagosomes retained the fluorescent label after isolation, indicative of intact membrane structure. Flow cytometric measurement of acridine orange, a fluorescent pH indicator, in the purified phagosomes demonstrated that the organelle in its isolated state was capable of transporting protons to the phagosomal lumen via the vacuolar-type ATPase proton pump (V-ATPase). When NADPH was supplied, the isolated phagosomes constitutively oxidized dihydrorhodamine 123, indicating their ability to produce hydrogen peroxide. The preparations also showed a robust production of HOCl within the phagosomal lumen when assayed with the HOCl-specific fluorescent probe R19-S by flow cytometry. MPO-mediated iodination of the proteins covalently conjugated to the phagocytosed beads was quantitatively measured. Phagosomal uptake of iodide and protein iodination were significantly blocked by chloride channel inhibitors, including CFTRinh-172 and NPPB. Further experiments determined that the V-ATPase-driving proton flux into the isolated phagosomes required chloride cotransport, and the cAMP-activated CFTR chloride channel was a major contributor to the chloride transport. Taken together, the data suggest that the phagosomal preparation described herein retains ion transport

  15. Curcumin directly inhibits the transport activity of GLUT1

    PubMed Central

    Gunnink, Leesha K.; Alabi, Ola D.; Kuiper, Benjamin D.; Gunnink, Stephen M.; Schuiteman, Sam J.; Strohbehn, Lauren E.; Hamilton, Kathryn E.; Wrobel, Kathryn E.; Louters, Larry L.

    2016-01-01

    Curcumin, a major ingredient in turmeric, has a long history of medicinal applications in a wide array of maladies including treatment for diabetes and cancer. Seemingly counterintuitive to the documented hypoglycemic effects of curcumin, however, a recent report indicates that curcumin directly inhibits glucose uptake in adipocytes. The major glucose transporter in adipocytes is GLUT4. Therefore, this study investigates the effects of curcumin in cell lines where the major transporter is GLUT1. We report that curcumin has an immediate inhibitory effect on basal glucose uptake in L929 fibroblast cells with a maximum inhibition of 80% achieved at 75 μM curcumin. Curcumin also blocks activation of glucose uptake by azide, glucose deprivation, hydroxylamine, or phenylarsine oxide. Inhibition does not increase with exposure time and the inhibitory effects reverse within an hour. Inhibition does not appear to involve a reaction between curcumin and the thiol side chain of a cysteine residue since neither prior treatment of cells with iodoacetamide nor curcumin with cysteine alters curcumin’s inhibitory effects. Curcumin is a mixed inhibitor reducing the Vmax of 2DG transport by about half with little effect on the Km. The inhibitory effects of curcumin are not additive to the effects of cytochalasin B and 75 μM curcumin actually reduces specific cytochalasin B binding by 80%. Taken together, the data suggest that curcumin binds directly to GLUT1 at a site that overlaps with the cytochalasin B binding site and thereby inhibits glucose transport. A direct inhibition of GLUT proteins in intestinal epithelial cells would likely reduce absorption of dietary glucose and contribute to a hypoglycemic effect of curcumin. Also, inhibition of GLUT1 activity might compromise cancer cells that overexpress GLUT1 and be another possible mechanism for the documented anticancer effects of curcumin. PMID:27039889

  16. Dopamine Transporter Activity Is Modulated by α-Synuclein.

    PubMed

    Butler, Brittany; Saha, Kaustuv; Rana, Tanu; Becker, Jonas P; Sambo, Danielle; Davari, Paran; Goodwin, J Shawn; Khoshbouei, Habibeh

    2015-12-04

    The duration and strength of the dopaminergic signal are regulated by the dopamine transporter (DAT). Drug addiction and neurodegenerative and neuropsychiatric diseases have all been associated with altered DAT activity. The membrane localization and the activity of DAT are regulated by a number of intracellular proteins. α-Synuclein, a protein partner of DAT, is implicated in neurodegenerative disease and drug addiction. Little is known about the regulatory mechanisms of the interaction between DAT and α-synuclein, the cellular location of this interaction, and the functional consequences of this interaction on the basal, amphetamine-induced DAT-mediated dopamine efflux, and membrane microdomain distribution of the transporter. Here, we found that the majority of DAT·α-synuclein protein complexes are found at the plasma membrane of dopaminergic neurons or mammalian cells and that the amphetamine-mediated increase in DAT activity enhances the association of these proteins at the plasma membrane. Further examination of the interaction of DAT and α-synuclein revealed a transient interaction between these two proteins at the plasma membrane. Additionally, we found DAT-induced membrane depolarization enhances plasma membrane localization of α-synuclein, which in turn increases dopamine efflux and enhances DAT localization in cholesterol-rich membrane microdomains.

  17. [Vesicular intracellular transport in the digestive organs. Membrane vesicle--the universal mechanism of the functional transport].

    PubMed

    Morozov, I A

    2014-01-01

    On the basis of long-term research of the morpho-functional characteristics of the cells of the stomach, small intestine and gallbladder the mechanism and function of membrane vesicles in the implementation of the main functions of these organs sets out in this article: the secretion of hydrochloric acid by parietal cells, the absorption of nutrients in the small intestine and the fluid at a concentration of bile epitheliocytes of gallbladder. Proofs of the intracellular formation of hydrochloric acid in tubulovesicles of the parietal cells and turnover of its secretory membranes in the process of secretory cycle, that has ensured the re-use and explained the extraordinary life of these unique cells are presented. The credible mechanism of HCl output oppression by H(+)-K(+)-ATPase activity blockers has set out on this basis. The article provides detailed endocytosis mechanism of the ions and nutrients absorption by enterocytes. The mechanism of participation of the apical contractile complex of brush border of epithelial cells in the initiation of endocytosis and cytoplasmic microtubules in transport of membrane vesicles in the cytoplasm was analyzed. Based on our research and numerous of the world scientific proceedings the conclusion was done about the existence of two energy dependent types of transport in the absorptive epithelium of the digestive--transmembrane (ionic and nutritive) homeostatic type which is realized by the ATP-system of the basal plasmalemma, and vesicular (endocytosis) type which is impltmented by apical contractile complex of brush border and cytoplasmic microtubules. Both types of transport are interrelated and are under constant cellular control. This observation is relevant to the majority of cells, including those involved in the secretion of various substances: hydrochloric acid by parietal cells, enzymes by main cells of the gastric glands and exocrinocytes of the pancreas, hormone by endocrine cells of the APUD system and, finally

  18. Active transmembrane drug transport in microgravity: a validation study using an ABC transporter model.

    PubMed

    Vaquer, Sergi; Cuyàs, Elisabet; Rabadán, Arnau; González, Albert; Fenollosa, Felip; de la Torre, Rafael

    2014-01-01

    Microgravity has been shown to influence the expression of ABC (ATP-Binding Cassette) transporters in bacteria, fungi and mammals, but also to modify the activity of certain cellular components with structural and functional similarities to ABC transporters. Changes in activity of ABC transporters could lead to important metabolic disorders and undesired pharmacological effects during spaceflights. However, no current means exist to study the functionality of these transporters in microgravity. To this end, a Vesicular Transport Assay (®) (Solvo Biotechnology, Hungary) was adapted to evaluate multi-drug resistance-associated protein 2 (MRP2) trans-membrane estradiol-17-β-glucuronide (E17βG) transport activity, when activated by adenosine-tri-phosphate (ATP) during parabolic flights. Simple diffusion, ATP-independent transport and benzbromarone inhibition were also evaluated. A high accuracy engineering system was designed to perform, monitor and synchronize all procedures. Samples were analysed using a validated high sensitivity drug detection protocol. Experiments were performed in microgravity during parabolic flights, and compared to 1g on ground results using identical equipment and procedures in all cases. Our results revealed that sufficient equipment accuracy and analytical sensitivity were reached to detect transport activity in both gravitational conditions. Additionally, transport activity levels of on ground samples were within commercial transport standards, proving the validity of the methods and equipment used. MRP2 net transport activity was significantly reduced in microgravity, so was signal detected in simple diffusion samples. Ultra-structural changes induced by gravitational stress upon vesicle membranes or transporters could explain the current results, although alternative explanations are possible. Further research is needed to provide a conclusive answer in this regard. Nevertheless, the present validated technology opens new and

  19. Active transmembrane drug transport in microgravity: a validation study using an ABC transporter model

    PubMed Central

    Vaquer, Sergi; Cuyàs, Elisabet; Rabadán, Arnau; González, Albert; Fenollosa, Felip; de la Torre, Rafael

    2014-01-01

    Microgravity has been shown to influence the expression of ABC (ATP-Binding Cassette) transporters in bacteria, fungi and mammals, but also to modify the activity of certain cellular components with structural and functional similarities to ABC transporters. Changes in activity of ABC transporters could lead to important metabolic disorders and undesired pharmacological effects during spaceflights. However, no current means exist to study the functionality of these transporters in microgravity. To this end, a Vesicular Transport Assay ® (Solvo Biotechnology, Hungary) was adapted to evaluate multi-drug resistance-associated protein 2 (MRP2) trans-membrane estradiol-17-β-glucuronide (E17βG) transport activity, when activated by adenosine-tri-phosphate (ATP) during parabolic flights. Simple diffusion, ATP-independent transport and benzbromarone inhibition were also evaluated. A high accuracy engineering system was designed to perform, monitor and synchronize all procedures. Samples were analysed using a validated high sensitivity drug detection protocol. Experiments were performed in microgravity during parabolic flights, and compared to 1g on ground results using identical equipment and procedures in all cases. Our results revealed that sufficient equipment accuracy and analytical sensitivity were reached to detect transport activity in both gravitational conditions. Additionally, transport activity levels of on ground samples were within commercial transport standards, proving the validity of the methods and equipment used. MRP2 net transport activity was significantly reduced in microgravity, so was signal detected in simple diffusion samples. Ultra-structural changes induced by gravitational stress upon vesicle membranes or transporters could explain the current results, although alternative explanations are possible. Further research is needed to provide a conclusive answer in this regard. Nevertheless, the present validated technology opens new and

  20. Mechanism of Paroxetine (Paxil) Inhibition of the Serotonin Transporter

    PubMed Central

    Davis, Bruce A.; Nagarajan, Anu; Forrest, Lucy R.; Singh, Satinder K.

    2016-01-01

    The serotonin transporter (SERT) is an integral membrane protein that exploits preexisting sodium-, chloride-, and potassium ion gradients to catalyze the thermodynamically unfavorable movement of synaptic serotonin into the presynaptic neuron. SERT has garnered significant clinical attention partly because it is the target of multiple psychoactive agents, including the antidepressant paroxetine (Paxil), the most potent selective serotonin reuptake inhibitor known. However, the binding site and orientation of paroxetine in SERT remain controversial. To provide molecular insight, we constructed SERT homology models based on the Drosophila melanogaster dopamine transporter and docked paroxetine to these models. We tested the predicted binding configurations with a combination of radioligand binding and flux assays on wild-type and mutant SERTs. Our data suggest that the orientation of paroxetine, specifically its fluorophenyl ring, in SERT’s substrate binding site directly depends on this pocket’s charge distribution, and thereby provide an avenue toward understanding and enhancing high-affinity antidepressant activity. PMID:27032980

  1. Osmoregulation in zebrafish: ion transport mechanisms and functional regulation

    PubMed Central

    Guh, Ying-Jey; Lin, Chia-Hao; Hwang, Pung-Pung

    2015-01-01

    Fish, like mammals, have to maintain their body fluid ionic and osmotic homeostasis through sophisticated iono-/osmoregulation mechanisms, which are conducted mainly by ionocytes of the gill (the skin in embryonic stages), instead of the renal tubular cells in mammals. Given the advantages in terms of genetic database availability and manipulation, zebrafish is an emerging model for research into regulatory and integrative physiology. At least five types of ionocytes, HR, NaR, NCC, SLC26, and KS cells, have been identified to carry out Na+ uptake/H+ secretion/NH4+ excretion, Ca2+ uptake, Na+/Cl- uptake, K+ secretion, and Cl- uptake/HCO3- secretion, respectively, through distinct sets of transporters. Several hormones, namely isotocin, prolactin, cortisol, stanniocalcin-1, calcitonin, endothelin-1, vitamin D, parathyorid hormone 1, catecholamines, and the renin-angiotensin-system, have been demonstrated to positively or negatively regulate ion transport through specific receptors at different ionocytes stages, at either the transcriptional/translational or posttranslational level. The knowledge obtained using zebrafish answered many long-term contentious or unknown issues in the field of fish iono-/osmoregulation. The homology of ion transport pathways and hormone systems also means that the zebrafish model informs studies on mammals or other animal species, thereby providing insights into related fields. PMID:26600749

  2. A Mirror Transport Mechanism for Use at Cryogenic Temperatures

    NASA Technical Reports Server (NTRS)

    Stark, Kenneth W.; Wilson, Meredith

    1986-01-01

    This report describes the Mirror Transport Mechanism (MTM), which supports a pair of dihedral mirrors and moves them in a very smooth and uniform scanning motion normal to a beamsplitter. Each scan is followed by a quick flyback and repeat. Included in the report will be material selection, design, and testing of all major components of the MTM in order to meet the stringent performance requirements under cryogenic conditions and survive the launch environment of the shuttle. Areas to be discussed in detail will be those in which failures or performance anomalies occurred and their solutions. Typically, this will include (but not to be limited to) flex pivot failures during vibration testing, excessive dihedral platform sag under one "g" operation, electronic and fiber optic characteristics, and tolerancing considerations. As of this writing, development of the mechanism has reached the final phase of thermal and vibration qualification. Environmental testing of the complete FIRAS (Far Infrared Absolute Spectrophotometer) experiment is just beginning.

  3. Molecular dynamics simulations elucidate the mechanism of proton transport in the glutamate transporter EAAT3.

    PubMed

    Heinzelmann, Germano; Kuyucak, Serdar

    2014-06-17

    The uptake of glutamate in nerve synapses is carried out by the excitatory amino acid transporters (EAATs), involving the cotransport of a proton and three Na(+) ions and the countertransport of a K(+) ion. In this study, we use an EAAT3 homology model to calculate the pKa of several titratable residues around the glutamate binding site to locate the proton carrier site involved in the translocation of the substrate. After identifying E374 as the main candidate for carrying the proton, we calculate the protonation state of this residue in different conformations of EAAT3 and with different ligands bound. We find that E374 is protonated in the fully bound state, but removing the Na2 ion and the substrate reduces the pKa of this residue and favors the release of the proton to solution. Removing the remaining Na(+) ions again favors the protonation of E374 in both the outward- and inward-facing states, hence the proton is not released in the empty transporter. By calculating the pKa of E374 with a K(+) ion bound in three possible sites, we show that binding of the K(+) ion is necessary for the release of the proton in the inward-facing state. This suggests a mechanism in which a K(+) ion replaces one of the ligands bound to the transporter, which may explain the faster transport rates of the EAATs compared to its archaeal homologs.

  4. Transporting Radioactive Waste: An Engineering Activity. Grades 5-12.

    ERIC Educational Resources Information Center

    HAZWRAP, The Hazardous Waste Remedial Actions Program.

    This brochure contains an engineering activity for upper elementary, middle school, and high school students that examines the transportation of radioactive waste. The activity is designed to inform students about the existence of radioactive waste and its transportation to disposal sites. Students experiment with methods to contain the waste and…

  5. Characteristics and Possible Functions of Mitochondrial Ca2+ Transport Mechanisms

    PubMed Central

    Gunter, Thomas E.; Sheu, Shey-Shing

    2009-01-01

    Mitochondria produce around 92% of the ATP used in the typical animal cell by oxidative phosphorylation using energy from their electrochemical proton gradient. Intramitochondrial free Ca2+ concentration ([Ca2+]m) has been found to be an important component of control of the rate of this ATP production. In addition, [Ca2+]m also controls the opening of a large pore in the inner mitochondrial membrane, the permeability transition pore (PTP), which plays a role in mitochondrial control of programmed cell death or apoptosis. Therefore, [Ca2+]m can control whether the cell has sufficient ATP to fulfill its functions and survive or is condemned to death. Ca2+ is also one of the most important second messengers within the cytosol, signaling changes in cellular response through Ca2+ pulses or transients. Mitochondria can also sequester Ca2+ from these transients so as to modify the shape of Ca2+ signaling transients or control their location within the cell. All of this is controlled by the action of four or five mitochondrial Ca2+ transport mechanisms and the PTP. The characteristics of these mechanisms of Ca2+ transport and a discussion of how they might function are described in this paper. PMID:19161975

  6. Molecular Mechanisms of Anthracycline Activity

    NASA Astrophysics Data System (ADS)

    Beretta, Giovanni Luca; Zunino, Franco

    On the basis of evidence that anthracyclines are DNA intercalating agents and DNA is the primary target, a large number of analogs and related intercalators have been developed. However, doxorubicin and closely related anthracyclines still remain among the most effective antitumor agents. Multiple mechanisms have been proposed to explain their efficacy. They include inhibition of DNA-dependent functions, free radical formation, and membrane interactions. The primary mechanism of action is now ascribed to drug interference with the function of DNA topoisomerase II. The stabilization of the topoisomerase-mediated cleavable complex results in a specific type of DNA damage (i.e., double-strand protein-associated DNA breaks). The drug-stabilized cleavable complex is a potentially reversible molecular event and its persistence, as a consequence of strong DNA binding, may be recognized as an apoptotic stimulus. Indirect evidence supports the notion that the bioreductive processes of the quinone moiety generating the semiquinone radical with concomitant production of reactive oxygen species may contribute to the drug effects. The cellular defense mechanisms and response to genotoxic/cytotoxic stress appear to be critical determinants of the tumor sensitivity to anthracyclines.

  7. Active Transport of Nanomaterials Using Motor Proteins -Final Report

    SciTech Connect

    Hess, Henry

    2005-09-01

    During the six months of funding we have focused first on the completion of the research begun at the University of Washington in the previous funding cycle. Specifically, we developed a method to polymerize oriented networks of microtubules on lithographically patterned surfaces (M.S. thesis Robert Doot). The properties of active transport have been studied detail, yielding insights into the dispersion mechanisms (Nitta et al.). The assembly of multifunctional structures with a microtubule core has been investigated (Ramachandran et al.). Isaac Luria (B.S. in physics, U. of Florida 2005) worked on the directed assembly of nanoscale, non-equilibrium structures as a summer intern. He is now a graduate student in my group at the University of Florida. T. Nitta and H. Hess: Dispersion in Active Transport by Kinesin-Powered Molecular Shuttles, Nano Letters, 5, 1337-1342 (2005) S. Ramachandran, K.-H. Ernst, G. D. Bachand, V. Vogel, H. Hess*: Selective Loading of Kinesin-Powered Molecular Shuttles with Protein Cargo and its Application to Biosensing, submitted to Small (2005)

  8. Serotonin transporter genotype modulates amygdala activity during mood regulation

    PubMed Central

    Rao, Hengyi; Wang, Jiongjiong; Detre, John A.; Breland, Jessica; Sankoorikal, Geena Mary V.; Brodkin, Edward S.; Farah, Martha J.

    2010-01-01

    Recent studies have implicated the short allele of the serotonin transporter-linked polymorphic region (5-HTTLPR) in depression vulnerability, particularly in the context of stress. Several neuroimaging studies have shown that 5-HTTLPR genotype predicts amygdala reactivity to negatively valenced stimuli, suggesting a mechanism whereby the short allele confers depression risk. The current study investigated whether 5-HTTLPR genotype similarly affects neural activity during an induced sad mood and during recovery from sad mood. Participants were 15 homozygous short (S) and 15 homozygous long (L) individuals. Regional cerebral blood flow was measured with perfusion functional magnetic resonance imaging during four scanning blocks: baseline, sad mood, mood recovery and following return to baseline. Comparing mood recovery to baseline, both whole brain analyses and template-based region-of-interest analyses revealed greater amygdala activity for the S vs the L-group. There were no significant amygdala differences found during the induced sad mood. These results demonstrate the effect of the S allele on amygdala activity during intentional mood regulation and suggest that amygdala hyperactivity during recovery from a sad mood may be one mechanism by which the S allele confers depression risk. PMID:19858108

  9. Mechanisms of calcium transport in human colonic basolateral membrane vesicles.

    PubMed

    Saksena, Seema; Ammar, Mohammad S; Tyagi, Sangeeta; Elsharydah, Ahmed; Gill, Ravinder K; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K

    2002-10-01

    Human colon has been suggested to play an important role in calcium absorption especially after extensive disease or resection of the small intestine. We have previously demonstrated the presence of a carrier-mediated calcium uptake mechanism in the human colonic luminal membrane vesicles. Current studies were, therefore, undertaken to investigate the mechanism(s) of calcium exit across the basolateral membrane domain of the human colon. Human colonic basolateral membrane vesicles (BLMVs) were isolated and purified from mucosal scrapings of organ donor colons, utilizing a technique developed in our laboratory. 45Ca uptake was measured by a rapid filtration technique. 45Ca uptake represented transport into the intravesicular space as evidenced by an osmolarity study and by the demonstration of Ca2' efflux from calcium preloaded vesicles by Ca2+ ionophore A23187. Calcium uptake was stimulated by Mg2+ ATP. The kinetic parameters for ATP-dependent Ca2+ uptake revealed saturation kinetics with Michaelis constant (Km) of 0.22 +/- 0.04 microM and a maximum rate of uptake (Vmax) of 0.38 +/- 0.12 nmol/mg protein/min. The Km of ATP concentration required for half maximal Ca2+ uptake was 0.39 +/- 0.04 mM. ATP-stimulated calcium uptake into these vesicles was further stimulated in the presence of calmodulin and was inhibited by calmodulin antagonist, trifluoperazine. Uptake of 45Ca into BLMVs was markedly inhibited by cis-Na+ but was significantly stimulated by trans-Na+ (40-50% stimulation). Our results demonstrate the presence of a Mg2+/ATP-dependent calmodulin-regulated Ca2+ transport system and a Na+-Ca2+ exchange process in the human colonic basolateral membranes.

  10. Compromising KCC2 transporter activity enhances the development of continuous seizure activity

    PubMed Central

    Kelley, Matthew R.; Deeb, Tarek Z.; Brandon, Nicholas J.; Dunlop, John; Davies, Paul A.; Moss, Stephen J.

    2016-01-01

    Impaired neuronal inhibition has long been associated with the increased probability of seizure occurrence and heightened seizure severity. Fast synaptic inhibition in the brain is primarily mediated by the type A γ-aminobutyric acid receptors (GABAARs), ligand-gated ion channels that can mediate Cl− influx resulting in membrane hyperpolarization and the restriction of neuronal firing. In most adult brain neurons, the K+/Cl− co-transporter-2 (KCC2) establishes hyperpolarizing GABAergic inhibition by maintaining low [Cl−]i. In this study, we sought to understand how decreased KCC2 transport function affects seizure event severity. We impaired KCC2 transport in the 0-Mg2+ ACSF and 4-aminopyridine in vitro models of epileptiform activity in acute mouse brain slices. Experiments with the selective KCC2 inhibitor VU0463271 demonstrated that reduced KCC2 transport increased the duration of SLEs, resulting in non-terminating discharges of clonic-like activity. We also investigated slices obtained from the KCC2-Ser940Ala (S940A) point-mutant mouse, which has a mutation at a known functional phosphorylation site causing behavioral and cellular deficits under hyperexcitable conditions. We recorded from the entorhinal cortex of S940A mouse brain slices in both 0-Mg2+ ACSF and 4-aminopyridine, and demonstrated that loss of the S940 residue increased the susceptibility of continuous clonic-like discharges, an in vitro form of status epilepticus. Our experiments revealed KCC2 transport activity is a critical factor in seizure event duration and mechanisms of termination. Our results highlight the need for therapeutic strategies that potentiate KCC2 transport function in order to decrease seizure event severity and prevent the development of status epilepticus. PMID:27108931

  11. Heat transport in active harmonic chains

    SciTech Connect

    Zheng, Mei C.; Ellis, Fred M.; Kottos, Tsampikos; Fleischmann, Ragnar; Geisel, Theo; Prosen, Tomaz

    2011-08-15

    We show that a harmonic lattice model with amplifying and attenuating elements, when coupled to two thermal baths, exhibits unique heat transport properties. Some of these novel features include anomalous nonequilibrium steady-state heat currents, negative differential thermal conductance, as well as nonreciprocal heat transport. We find that when these elements are arranged in a PT-symmetric manner, the domain of existence of the nonequilibrium steady state is maximized. We propose an electronic experimental setup based on resistive-inductive-capacitive (RLC) transmission lines, where our predictions can be tested.

  12. Jahn-Teller assisted polaronic hole hopping as a charge transport mechanism in CuO nanograins

    NASA Astrophysics Data System (ADS)

    Younas, M.; Nadeem, M.; Idrees, M.; Akhtar, M. J.

    2012-04-01

    Impedance spectroscopy has been employed to investigate the dielectric and electric transport phenomena in sol-gel synthesized CuO nanograins. Semiconducting features of the grains and grain boundaries have been endorsed to the thermal activation of the localized charge carriers. On cooling below 303 K, a transition from Jahn-Teller polaron hopping mechanism to the Mott's variable range hopping mechanism has been observed owing to random potential fluctuations among localized sites. Activation energies for conduction and relaxation processes at grain boundaries provide strong signatures for the involvement of Jahn-Teller adiabatic small polarons as a charge transport mechanism in CuO nanograins.

  13. Opposite-polarity motors activate one another to trigger cargo transport in live cells

    PubMed Central

    Ally, Shabeen; Larson, Adam G.; Barlan, Kari; Rice, Sarah E.

    2009-01-01

    Intracellular transport is typically bidirectional, consisting of a series of back and forth movements. Kinesin-1 and cytoplasmic dynein require each other for bidirectional transport of intracellular cargo along microtubules; i.e., inhibition or depletion of kinesin-1 abolishes dynein-driven cargo transport and vice versa. Using Drosophila melanogaster S2 cells, we demonstrate that replacement of endogenous kinesin-1 or dynein with an unrelated, peroxisome-targeted motor of the same directionality activates peroxisome transport in the opposite direction. However, motility-deficient versions of motors, which retain the ability to bind microtubules and hydrolyze adenosine triphosphate, do not activate peroxisome motility. Thus, any pair of opposite-polarity motors, provided they move along microtubules, can activate one another. These results demonstrate that mechanical interactions between opposite-polarity motors are necessary and sufficient for bidirectional organelle transport in live cells. PMID:20038680

  14. Mechanism of transport and distribution of organic solvents in blood

    NASA Technical Reports Server (NTRS)

    Lam, C. W.; Galen, T. J.; Boyd, J. F.; Pierson, D. L.

    1990-01-01

    Little is known about the mechanism of transport and distribution of volatile organic compounds in blood. Studies were conducted on five typical organic solvents to investigate how these compounds are transported and distributed in blood. Groups of four to five rats were exposed for 2 hr to 500 ppm of n-hexane, toluene, chloroform, methyl isobutyl ketone (MIBK), or diethyl ether vapor; 94, 66, 90, 51, or 49%, respectively, of these solvents in the blood were found in the red blood cells (RBCs). Very similar results were obtained in vitro when aqueous solutions of these solvents were added to rat blood. In vitro studies were also conducted on human blood with these solvents; 66, 43, 65, 49, or 46%, respectively, of the added solvent was taken up by the RBCs. These results indicate that RBCs from humans and rats exhibited substantial differences in affinity for the three more hydrophobic solvents studied. When solutions of these solvents were added to human plasma and RBC samples, large fractions (51-96%) of the solvents were recovered from ammonium sulfate-precipitated plasma proteins and hemoglobin. Smaller fractions were recovered from plasma water and red cell water. Less than 10% of each of the added solvents in RBC samples was found in the red cell membrane ghosts. These results indicate that RBCs play an important role in the uptake and transport of these solvents. Proteins, chiefly hemoglobin, are the major carriers of these compounds in blood. It can be inferred from the results of the present study that volatile lipophilic organic solvents are probably taken up by the hydrophobic sites of blood proteins.

  15. Hyporheic flow and transport processes: Mechanisms, models, and biogeochemical implications

    NASA Astrophysics Data System (ADS)

    Boano, F.; Harvey, J. W.; Marion, A.; Packman, A. I.; Revelli, R.; Ridolfi, L.; Wörman, A.

    2014-12-01

    Fifty years of hyporheic zone research have shown the important role played by the hyporheic zone as an interface between groundwater and surface waters. However, it is only in the last two decades that what began as an empirical science has become a mechanistic science devoted to modeling studies of the complex fluid dynamical and biogeochemical mechanisms occurring in the hyporheic zone. These efforts have led to the picture of surface-subsurface water interactions as regulators of the form and function of fluvial ecosystems. Rather than being isolated systems, surface water bodies continuously interact with the subsurface. Exploration of hyporheic zone processes has led to a new appreciation of their wide reaching consequences for water quality and stream ecology. Modern research aims toward a unified approach, in which processes occurring in the hyporheic zone are key elements for the appreciation, management, and restoration of the whole river environment. In this unifying context, this review summarizes results from modeling studies and field observations about flow and transport processes in the hyporheic zone and describes the theories proposed in hydrology and fluid dynamics developed to quantitatively model and predict the hyporheic transport of water, heat, and dissolved and suspended compounds from sediment grain scale up to the watershed scale. The implications of these processes for stream biogeochemistry and ecology are also discussed.

  16. Transport mechanisms of small molecules through polyamide 12/montmorillonite nanocomposites.

    PubMed

    Alexandre, B; Colasse, L; Langevin, D; Médéric, P; Aubry, T; Chappey, C; Marais, S

    2010-07-15

    The aim of this work is to study the transport of small molecules through the hybrid systems polyamide 12 (PA12)/organo-modified montmorillonite (Cloisite 30B, C30B) prepared by melt blending, using two blending conditions. The transport mechanisms were investigated by using three probe molecules: nitrogen, water, and toluene. While a barrier effect appears clearly with nitrogen, this effect changes with the amount of fillers for water and disappears for toluene. The reduction of permeability for nitrogen is mainly due to the increase of tortuosity. For water and toluene, the permeation kinetics reveals many concomitant phenomena responsible for the permeation behavior. Despite the tortuosity effect, the toluene permeability of nanocomposites increases with C30B fraction. The water and toluene molecules interact differently with fillers according to their hydrophilic/hydrophobic character. Moreover, the plasticization effect of water and toluene in the matrix, involving a concentration-dependent diffusion coefficient, is correctly described by the law D = D(0)e(gammaC). On the basis of Nielsen's tortuosity concept, we suggest a new approach for relative permeability modeling, not only based on the geometrical parameters (aspect ratio, orientation, recovery) but also including phenomenological parameters deduced from structural characterization and permeation kinetics.

  17. Transport Mechanism of Nicotine in Primary Cultured Alveolar Epithelial Cells.

    PubMed

    Takano, Mikihisa; Nagahiro, Machi; Yumoto, Ryoko

    2016-02-01

    Nicotine is absorbed from the lungs into the systemic circulation during cigarette smoking. However, there is little information concerning the transport mechanism of nicotine in alveolar epithelial cells. In this study, we characterized the uptake of nicotine in rat primary cultured type II (TII) and transdifferentiated type I-like (TIL) epithelial cells. In both TIL and TII cells, [(3)H]nicotine uptake was time and temperature-dependent, and showed saturation kinetics. [(3)H]Nicotine uptake in these cells was not affected by Na(+), but was sensitive to extracellular and intracellular pH, suggesting the involvement of a nicotine/proton antiport system. The uptake of [(3)H]nicotine in these cells was potently inhibited by organic cations such as clonidine, diphenhydramine, and pyrilamine, but was not affected by substrates and/or inhibitors of known organic cation transporters such as carnitine, 1-methyl-4-phenylpyridinium, and tetraethylammonium. In addition, the uptake of [(3)H]nicotine in TIL cells was stimulated by preloading the cells with unlabeled nicotine, pyrilamine, and diphenhydramine, but not with tetraethylammonium. These results suggest that a novel proton-coupled antiporter is involved in the uptake of nicotine in alveolar epithelial cells and its absorption from the lungs into the systemic circulation.

  18. Hyporheic flow and transport processes: mechanisms, models, and biogeochemical implications

    USGS Publications Warehouse

    Boano, Fulvio; Harvey, Judson W.; Marion, Andrea; Packman, Aaron I.; Revelli, Roberto; Ridolfi, Luca; Anders, Wörman

    2014-01-01

    Fifty years of hyporheic zone research have shown the important role played by the hyporheic zone as an interface between groundwater and surface waters. However, it is only in the last two decades that what began as an empirical science has become a mechanistic science devoted to modeling studies of the complex fluid dynamical and biogeochemical mechanisms occurring in the hyporheic zone. These efforts have led to the picture of surface-subsurface water interactions as regulators of the form and function of fluvial ecosystems. Rather than being isolated systems, surface water bodies continuously interact with the subsurface. Exploration of hyporheic zone processes has led to a new appreciation of their wide reaching consequences for water quality and stream ecology. Modern research aims toward a unified approach, in which processes occurring in the hyporheic zone are key elements for the appreciation, management, and restoration of the whole river environment. In this unifying context, this review summarizes results from modeling studies and field observations about flow and transport processes in the hyporheic zone and describes the theories proposed in hydrology and fluid dynamics developed to quantitatively model and predict the hyporheic transport of water, heat, and dissolved and suspended compounds from sediment grain scale up to the watershed scale. The implications of these processes for stream biogeochemistry and ecology are also discussed."

  19. Flexible Mechanical Conveyors for Regolith Extraction and Transport

    NASA Technical Reports Server (NTRS)

    Walton, Otis R.; Vollmer, Hubert J.

    2013-01-01

    A report describes flexible mechanical conveying systems for transporting fine cohesive regolith under microgravity and vacuum conditions. They are totally enclosed, virtually dust-free, and can include enough flexibility in the conveying path to enable an expanded range of extraction and transport scenarios, including nonlinear drill-holes and excavation of enlarged subsurface openings without large entry holes. The design of the conveyors is a modification of conventional screw conveyors such that the central screw-shaft and the outer housing or conveyingtube have a degree of bending flexibility, allowing the conveyors to become nonlinear conveying systems that can convey around gentle bends. The central flexible shaft is similar to those used in common tools like a weed whacker, consisting of multiple layers of tightly wound wires around a central wire core. Utilization of compliant components (screw blade or outer wall) increases the robustness of the conveying, allowing an occasional oversized particle to pass hough the conveyor without causing a jam or stoppage

  20. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion

    PubMed Central

    Kouyoumdzian, Nicolás M.; Rukavina Mikusic, Natalia L.; Kravetz, María C.; Lee, Brenda M.; Carranza, Andrea; Del Mauro, Julieta S.; Pandolfo, Marcela; Gironacci, Mariela M.; Gorzalczany, Susana; Toblli, Jorge E.; Fernández, Belisario E.

    2016-01-01

    The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID:27392042

  1. Study of active cooling for supersonic transports

    NASA Technical Reports Server (NTRS)

    Brewer, G. D.; Morris, R. E.

    1975-01-01

    The potential benefits of using the fuel heat sink of hydrogen fueled supersonic transports for cooling large portions of the aircraft wing and fuselage are examined. The heat transfer would be accomplished by using an intermediate fluid such as an ethylene glycol-water solution. Some of the advantages of the system are: (1) reduced costs by using aluminum in place of titanium, (2) reduced cabin heat loads, and (3) more favorable environmental conditions for the aircraft systems. A liquid hydrogen fueled, Mach 2.7 supersonic transport aircraft design was used for the reference uncooled vehicle. The cooled aircraft designs were analyzed to determine their heat sink capability, the extent and location of feasible cooled surfaces, and the coolant passage size and spacing.

  2. Modeling of active transmembrane transport in a mixture theory framework.

    PubMed

    Ateshian, Gerard A; Morrison, Barclay; Hung, Clark T

    2010-05-01

    This study formulates governing equations for active transport across semi-permeable membranes within the framework of the theory of mixtures. In mixture theory, which models the interactions of any number of fluid and solid constituents, a supply term appears in the conservation of linear momentum to describe momentum exchanges among the constituents. In past applications, this momentum supply was used to model frictional interactions only, thereby describing passive transport processes. In this study, it is shown that active transport processes, which impart momentum to solutes or solvent, may also be incorporated in this term. By projecting the equation of conservation of linear momentum along the normal to the membrane, a jump condition is formulated for the mechano-electrochemical potential of fluid constituents which is generally applicable to nonequilibrium processes involving active transport. The resulting relations are simple and easy to use, and address an important need in the membrane transport literature.

  3. CLUB FORMATION MECHANISM FOR TRANSPORT-COMMUNITY CREDIT CARDS

    NASA Astrophysics Data System (ADS)

    Ding, Yue; Kobayashi, Kiyoshi; Nishida, Junji; Yoshida, Mamoru

    In this paper, the roles of transport-community cards jointly issued by a public transport firm and retails are investigated as a means to vitalize an obsolescence shopping center located in a middle of a city. When both the price of goods supplied by the retails and the transport fares affect the consumers' behavior, there exist pecuniary externality between the behaviors of the retails and transport firms. The introduction of a transport-community cards system enables to integrate a basket of goods and transport service into a single commodity; thus, the pecuniary externality can be internalized by price coordination. In addition, the paper clarifies theoretically that the transport firm initiatively decides the price of the transportation service and the retails transfer their incomes to the transport firm so that they are induced to jointly issue the transport-community cards.

  4. [Model of active peristaltic transport in biosystems].

    PubMed

    Klochkov, B N; Romanov, A S

    2013-01-01

    A nonlinear distributed mathematical model of soft vessel with the nonmonotonous static characteristic is proposed and considered. The model describes space-time dynamics of vessel clearance change. Wave phenomena in vessels of different nature and the possibility of peristaltic fluid pumping are discussed and analyzed. The model is rather common in character and represents a description of the whole class of transport phenomena. Lymphatic vessels are particularly considered.

  5. Salmonella infection inhibits intestinal biotin transport: cellular and molecular mechanisms.

    PubMed

    Ghosal, Abhisek; Jellbauer, Stefan; Kapadia, Rubina; Raffatellu, Manuela; Said, Hamid M

    2015-07-15

    Infection with the nontyphoidal Salmonella is a common cause of food-borne disease that leads to acute gastroenteritis/diarrhea. Severe/prolonged cases of Salmonella infection could also impact host nutritional status, but little is known about its effect on intestinal absorption of vitamins, including biotin. We examined the effect of Salmonella enterica serovar Typhimurium (S. typhimurium) infection on intestinal biotin uptake using in vivo (streptomycin-pretreated mice) and in vitro [mouse (YAMC) and human (NCM460) colonic epithelial cells, and human intestinal epithelial Caco-2 cells] models. The results showed that infecting mice with wild-type S. typhimurium, but not with its nonpathogenic isogenic invA spiB mutant, leads to a significant inhibition in jejunal/colonic biotin uptake and in level of expression of the biotin transporter, sodium-dependent multivitamin transporter. In contrast, infecting YAMC, NCM460, and Caco-2 cells with S. typhimurium did not affect biotin uptake. These findings suggest that the effect of S. typhimurium infection is indirect and is likely mediated by proinflammatory cytokines, the levels of which were markedly induced in the intestine of S. typhimurium-infected mice. Consistent with this hypothesis, exposure of NCM460 cells to the proinflammatory cytokines TNF-α and IFN-γ led to a significant inhibition of biotin uptake, sodium-dependent multivitamin transporter expression, and activity of the SLC5A6 promoter. The latter effects appear to be mediated, at least in part, via the NF-κB signaling pathway. These results demonstrate that S. typhimurium infection inhibits intestinal biotin uptake, and that the inhibition is mediated via the action of proinflammatory cytokines.

  6. Salmonella infection inhibits intestinal biotin transport: cellular and molecular mechanisms

    PubMed Central

    Ghosal, Abhisek; Jellbauer, Stefan; Kapadia, Rubina; Raffatellu, Manuela

    2015-01-01

    Infection with the nontyphoidal Salmonella is a common cause of food-borne disease that leads to acute gastroenteritis/diarrhea. Severe/prolonged cases of Salmonella infection could also impact host nutritional status, but little is known about its effect on intestinal absorption of vitamins, including biotin. We examined the effect of Salmonella enterica serovar Typhimurium (S. typhimurium) infection on intestinal biotin uptake using in vivo (streptomycin-pretreated mice) and in vitro [mouse (YAMC) and human (NCM460) colonic epithelial cells, and human intestinal epithelial Caco-2 cells] models. The results showed that infecting mice with wild-type S. typhimurium, but not with its nonpathogenic isogenic invA spiB mutant, leads to a significant inhibition in jejunal/colonic biotin uptake and in level of expression of the biotin transporter, sodium-dependent multivitamin transporter. In contrast, infecting YAMC, NCM460, and Caco-2 cells with S. typhimurium did not affect biotin uptake. These findings suggest that the effect of S. typhimurium infection is indirect and is likely mediated by proinflammatory cytokines, the levels of which were markedly induced in the intestine of S. typhimurium-infected mice. Consistent with this hypothesis, exposure of NCM460 cells to the proinflammatory cytokines TNF-α and IFN-γ led to a significant inhibition of biotin uptake, sodium-dependent multivitamin transporter expression, and activity of the SLC5A6 promoter. The latter effects appear to be mediated, at least in part, via the NF-κB signaling pathway. These results demonstrate that S. typhimurium infection inhibits intestinal biotin uptake, and that the inhibition is mediated via the action of proinflammatory cytokines. PMID:25999427

  7. Nicotine decreases the activity of glutamate transporter type 3.

    PubMed

    Yoon, Hea-Jo; Lim, Young-Jin; Zuo, Zhiyi; Hur, Wonseok; Do, Sang-Hwan

    2014-02-10

    Nicotine, the main ingredient of tobacco, elicits seizures in animal models and cigarette smoking is regarded as a behavioral risk factor associated with epilepsy or seizures. In the hippocampus, the origin of nicotine-induced seizures, most glutamate uptake could be performed primarily by excitatory amino acid transporter type 3 (EAAT3). An association between temporal lobe epilepsy and EAAT3 downregulation has been reported. Therefore, we hypothesized that nicotine may elicit seizures through the attenuation of EAAT3 activity. We investigated chronic nicotine exposure (72 h) cause reduction of the activity of EAAT3 in a Xenopus oocyte expression system using a two-electrode voltage clamp. The roles of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) were also determined. Nicotine (0.001-1 μM) resulted in a time- and dose-dependent decrease in EAAT3 activity with maximal inhibition at nicotine concentrations of 0.03 μM or higher and at an exposure time of 72 h. Vmax on the glutamate response was significantly reduced in the nicotine group (0.03 μM for 72 h), but the Km value of EAAT3 for glutamate was not altered. When nicotine-exposed oocytes (0.03 μM for 72 h) were pretreated with phorbol-12-myristate-13-acetate (PMA, a PKC activator), the nicotine-induced reduction in EAAT3 activity was abolished. PKC inhibitors (staurosporine, chelerythrine, and calphostin C) significantly reduced basal EAAT3 activity, but there were no significant differences among the PKC inhibitors, nicotine, and PKC inhibitors+nicotine groups. Similar response patterns were observed among PI3K inhibitors (wortmannin and LY294002), nicotine, and PI3K inhibitors+nicotine. In conclusion, this study suggests that nicotine decreases EAAT3 activity, and that this inhibition seems to be dependent on PKC and PI3K. Our results may provide an additional mechanism for nicotine-induced seizure.

  8. Thermally activated charge transport in microbial protein nanowires

    NASA Astrophysics Data System (ADS)

    Lampa-Pastirk, Sanela; Veazey, Joshua P.; Walsh, Kathleen A.; Feliciano, Gustavo T.; Steidl, Rebecca J.; Tessmer, Stuart H.; Reguera, Gemma

    2016-03-01

    The bacterium Geobacter sulfurreducens requires the expression of conductive protein filaments or pili to respire extracellular electron acceptors such as iron oxides and uranium and to wire electroactive biofilms, but the contribution of the protein fiber to charge transport has remained elusive. Here we demonstrate efficient long-range charge transport along individual pili purified free of metal and redox organic cofactors at rates high enough to satisfy the respiratory rates of the cell. Carrier characteristics were within the orders reported for organic semiconductors (mobility) and inorganic nanowires (concentration), and resistivity was within the lower ranges reported for moderately doped silicon nanowires. However, the pilus conductance and the carrier mobility decreased when one of the tyrosines of the predicted axial multistep hopping path was replaced with an alanine. Furthermore, low temperature scanning tunneling microscopy demonstrated the thermal dependence of the differential conductance at the low voltages that operate in biological systems. The results thus provide evidence for thermally activated multistep hopping as the mechanism that allows Geobacter pili to function as protein nanowires between the cell and extracellular electron acceptors.

  9. Thermally activated charge transport in microbial protein nanowires.

    PubMed

    Lampa-Pastirk, Sanela; Veazey, Joshua P; Walsh, Kathleen A; Feliciano, Gustavo T; Steidl, Rebecca J; Tessmer, Stuart H; Reguera, Gemma

    2016-03-24

    The bacterium Geobacter sulfurreducens requires the expression of conductive protein filaments or pili to respire extracellular electron acceptors such as iron oxides and uranium and to wire electroactive biofilms, but the contribution of the protein fiber to charge transport has remained elusive. Here we demonstrate efficient long-range charge transport along individual pili purified free of metal and redox organic cofactors at rates high enough to satisfy the respiratory rates of the cell. Carrier characteristics were within the orders reported for organic semiconductors (mobility) and inorganic nanowires (concentration), and resistivity was within the lower ranges reported for moderately doped silicon nanowires. However, the pilus conductance and the carrier mobility decreased when one of the tyrosines of the predicted axial multistep hopping path was replaced with an alanine. Furthermore, low temperature scanning tunneling microscopy demonstrated the thermal dependence of the differential conductance at the low voltages that operate in biological systems. The results thus provide evidence for thermally activated multistep hopping as the mechanism that allows Geobacter pili to function as protein nanowires between the cell and extracellular electron acceptors.

  10. Thermally activated charge transport in microbial protein nanowires

    PubMed Central

    Lampa-Pastirk, Sanela; Veazey, Joshua P.; Walsh, Kathleen A.; Feliciano, Gustavo T.; Steidl, Rebecca J.; Tessmer, Stuart H.; Reguera, Gemma

    2016-01-01

    The bacterium Geobacter sulfurreducens requires the expression of conductive protein filaments or pili to respire extracellular electron acceptors such as iron oxides and uranium and to wire electroactive biofilms, but the contribution of the protein fiber to charge transport has remained elusive. Here we demonstrate efficient long-range charge transport along individual pili purified free of metal and redox organic cofactors at rates high enough to satisfy the respiratory rates of the cell. Carrier characteristics were within the orders reported for organic semiconductors (mobility) and inorganic nanowires (concentration), and resistivity was within the lower ranges reported for moderately doped silicon nanowires. However, the pilus conductance and the carrier mobility decreased when one of the tyrosines of the predicted axial multistep hopping path was replaced with an alanine. Furthermore, low temperature scanning tunneling microscopy demonstrated the thermal dependence of the differential conductance at the low voltages that operate in biological systems. The results thus provide evidence for thermally activated multistep hopping as the mechanism that allows Geobacter pili to function as protein nanowires between the cell and extracellular electron acceptors. PMID:27009596

  11. Molecular Transport Mechanisms for Associating and Solvating Penetrant in Polymers

    DTIC Science & Technology

    2007-11-02

    PIB ) at different vapor activities in order to understand complex diffusion mechanisms and probe molecular structures above the glass tranisition. The...the individual diffusion coefficients can be separated and that they are equal to each other for the acetic acid/ PIB system. The values of the...BOH) mixtures in polyisobutylene ( PIB ) was studied at varying mixture compositions. Diffusion coefficients and hydrogen bonding interactions were

  12. In vitro synthesis of a Major Facilitator Transporter for specific active transport across Droplet Interface Bilayers

    PubMed Central

    Findlay, Heather E.; Harris, Nicola J.; Booth, Paula J.

    2016-01-01

    Nature encapsulates reactions within membrane-bound compartments, affording sequential and spatial control over biochemical reactions. Droplet Interface Bilayers are evolving into a valuable platform to mimic this key biological feature in artificial systems. A major issue is manipulating flow across synthetic bilayers. Droplet Interface Bilayers must be functionalised, with seminal work using membrane-inserting toxins, ion channels and pumps illustrating the potential. Specific transport of biomolecules, and notably transport against a concentration gradient, across these bilayers has yet to be demonstrated. Here, we successfully incorporate the archetypal Major Facilitator Superfamily transporter, lactose permease, into Droplet Interface Bilayers and demonstrate both passive and active, uphill transport. This paves the way for controllable transport of sugars, metabolites and other essential biomolecular substrates of this ubiquitous transporter superfamily in DIB networks. Furthermore, cell-free synthesis of lactose permease during DIB formation also results in active transport across the interface bilayer. This adds a specific disaccharide transporter to the small list of integral membrane proteins that can be synthesised via in vitro transcription/translation for applications of DIB-based artificial cell systems. The introduction of a means to promote specific transport of molecules across Droplet Interface Bilayers against a concentration gradient gives a new facet to droplet networks. PMID:27996025

  13. Decoupling Mechanical and Ion Transport Properties in Polymer Electrolyte Membranes

    NASA Astrophysics Data System (ADS)

    McIntosh, Lucas D.

    Polymer electrolytes are mixtures of a polar polymer and salt, in which the polymer replaces small molecule solvents and provides a dielectric medium so that ions can dissociate and migrate under the influence of an external electric field. Beginning in the 1970s, research in polymer electrolytes has been primarily motivated by their promise to advance electrochemical energy storage and conversion devices, such as lithium ion batteries, flexible organic solar cells, and anhydrous fuel cells. In particular, polymer electrolyte membranes (PEMs) can improve both safety and energy density by eliminating small molecule, volatile solvents and enabling an all-solid-state design of electrochemical cells. The outstanding challenge in the field of polymer electrolytes is to maximize ionic conductivity while simultaneously addressing orthogonal mechanical properties, such as modulus, fracture toughness, or high temperature creep resistance. The crux of the challenge is that flexible, polar polymers best-suited for polymer electrolytes (e.g., poly(ethylene oxide)) offer little in the way of mechanical robustness. Similarly, polymers typically associated with superior mechanical performance (e.g., poly(methyl methacrylate)) slow ion transport due to their glassy polymer matrix. The design strategy is therefore to employ structured electrolytes that exhibit distinct conducting and mechanically robust phases on length scales of tens of nanometers. This thesis reports a remarkably simple, yet versatile synthetic strategy---termed polymerization-induced phase separation, or PIPS---to prepare PEMs exhibiting an unprecedented combination of both high conductivity and high modulus. This performance is enabled by co-continuous, isotropic networks of poly(ethylene oxide)/ionic liquid and highly crosslinked polystyrene. A suite of in situ, time-resolved experiments were performed to investigate the mechanism by which this network morphology forms, and it appears to be tied to the

  14. Simulation of Electrical Transport in Rocks under Mechanical Action

    NASA Astrophysics Data System (ADS)

    Salgueiro da Silva, M. A.; Seixas, T. M.

    2015-12-01

    Rock's electrical properties can be changed by mechanical action, especially when deformation is accompanied by micro-fracturing processes. Knowing how electrical charge is generated in inelastically deformed rocks, the nature and properties of the generated charge carriers, and their spatial distribution and propagation is crucial to gain insight into the origin of seismo-electromagnetic signals. In this work, we describe briefly a model for the numerical simulation of electrical transport in rocks under mechanical action, assuming that high and low mobility charge carriers of opposite signs can be simultaneously generated by micro-fracturing processes and recombine, diffuse and drift across the sample rock. The electrical behavior can then be described using an adaptation of the formalism applied to semiconductors. We provide simulation results on a one-dimensional lattice using finite-difference discretization. Our results show that a large mobility contrast among charge carriers allows charge separation inside the deformation region, which leads to the formation of charged layers of alternate signs. Inside these layers, rapid electric field variations are observed which can lead to the emission of electromagnetic radiation. With proper positioning of current electrodes inside the deformation region, it is possible to collect electrical current even without any applied voltage. We discuss our results in the light of available experimental results on the generation of electrical and electromagnetic signals in deformed rocks.

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

    PubMed

    Melnykov, Artem V

    2016-01-01

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

  16. Amphetamine activates calcium channels through dopamine transporter-mediated depolarization.

    PubMed

    Cameron, Krasnodara N; Solis, Ernesto; Ruchala, Iwona; De Felice, Louis J; Eltit, Jose M

    2015-11-01

    Amphetamine (AMPH) and its more potent enantiomer S(+)AMPH are psychostimulants used therapeutically to treat attention deficit hyperactivity disorder and have significant abuse liability. AMPH is a dopamine transporter (DAT) substrate that inhibits dopamine (DA) uptake and is implicated in DA release. Furthermore, AMPH activates ionic currents through DAT that modify cell excitability presumably by modulating voltage-gated channel activity. Indeed, several studies suggest that monoamine transporter-induced depolarization opens voltage-gated Ca(2+) channels (CaV), which would constitute an additional AMPH mechanism of action. In this study we co-express human DAT (hDAT) with Ca(2+) channels that have decreasing sensitivity to membrane depolarization (CaV1.3, CaV1.2 or CaV2.2). Although S(+)AMPH is more potent than DA in transport-competition assays and inward-current generation, at saturating concentrations both substrates indirectly activate voltage-gated L-type Ca(2+) channels (CaV1.3 and CaV1.2) but not the N-type Ca(2+) channel (CaV2.2). Furthermore, the potency to achieve hDAT-CaV electrical coupling is dominated by the substrate affinity on hDAT, with negligible influence of L-type channel voltage sensitivity. In contrast, the maximal coupling-strength (defined as Ca(2+) signal change per unit hDAT current) is influenced by CaV voltage sensitivity, which is greater in CaV1.3- than in CaV1.2-expressing cells. Moreover, relative to DA, S(+)AMPH showed greater coupling-strength at concentrations that induced relatively small hDAT-mediated currents. Therefore S(+)AMPH is not only more potent than DA at inducing hDAT-mediated L-type Ca(2+) channel currents but is a better depolarizing agent since it produces tighter electrical coupling between hDAT-mediated depolarization and L-type Ca(2+) channel activation.

  17. The Role of Flexible Loops in Folding, Trafficking and Activity of Equilibrative Nucleoside Transporters.

    PubMed

    Aseervatham, Jaya; Tran, Lucky; Machaca, Khaled; Boudker, Olga

    2015-01-01

    Equilibrative nucleoside transporters (ENTs) are integral membrane proteins, which reside in plasma membranes of all eukaryotic cells and mediate thermodynamically downhill transport of nucleosides. This process is essential for nucleoside recycling, and also plays a key role in terminating adenosine-mediated cellular signaling. Furthermore, ENTs mediate the uptake of many drugs, including anticancer and antiviral nucleoside analogues. The structure and mechanism, by which ENTs catalyze trans-membrane transport of their substrates, remain unknown. To identify the core of the transporter needed for stability, activity, and for its correct trafficking to the plasma membrane, we have expressed human ENT deletion mutants in Xenopus laevis oocytes and determined their localization, transport properties and susceptibility to inhibition. We found that the carboxyl terminal trans-membrane segments are essential for correct protein folding and trafficking. In contrast, the soluble extracellular and intracellular loops appear to be dispensable, and must be involved in the fine-tuning of transport regulation.

  18. Identification of an allosteric modulator of the serotonin transporter with novel mechanism of action.

    PubMed

    Kortagere, Sandhya; Fontana, Andreia Cristina Karklin; Rose, Deja Renée; Mortensen, Ole Valente

    2013-09-01

    Serotonin transporters (SERTs) play an essential role in the termination and regulation of serotonin signaling in the brain. SERT is also the target of antidepressants and psychostimulants. Molecules with novel activities and modes of interaction with regard to SERT function are of great scientific and clinical interest. We explored structural regions outside the putative serotonin translocation pathway to identify potential binding sites for allosteric transporter modulators (ATMs). Mutational studies revealed a pocket of amino acids outside the orthosteric substrate binding sites located in the interface between extracellular loops 1 and 3 that when mutated affect transporter function. Using the structure of the bacterial transporter homolog leucine transporter as a template, we developed a structural model of SERT. We performed molecular dynamics simulations to further characterize the allosteric pocket that was identified by site-directed mutagenesis studies and employed this pocket in a virtual screen for small-molecule modulators of SERT function. In functional transport assays, we found that one of the identified molecules, ATM7, increased the reuptake of serotonin, possibly by facilitating the interaction of serotonin with transport-ready conformations of SERT when concentrations of serotonin were low and rate limiting. In addition, ATM7 potentiates 3,4-methylenedioxy-N-methylamphetamine (MDMA, "Ecstasy")-induced reversed transport by SERT. Taking advantage of a conformationally sensitive residue in transmembrane domain 6, we demonstrate that ATM7 mechanistically stabilizes an outward-facing conformation of SERT. Taken together these observations demonstrate that ATM7 acts through a novel mechanism that involves allosteric modulation of SERT function.

  19. Regulation of airway surface liquid volume and mucus transport by active ion transport.

    PubMed

    Tarran, Robert

    2004-01-01

    Mucus clearance is an important component of the lung's innate defense against disease, and the ability of the airways to clear mucus is strongly dependent on the volume of liquid on airway surfaces. Whether airway surface liquid (ASL) volume is maintained by passive surface forces or by active ion transport is controversial yet crucial to the understanding of how this system operates in both health and disease. In support of active ion transport being the major determinant of ASL volume, we have demonstrated that normal airway epithelia sense and autoregulate ASL height (volume) by adjusting the rates of Na+ absorption and Cl- secretion to maintain mucus transport.

  20. Mechanism for the activation of glutamate receptors

    Cancer.gov

    Scientists at the NIH have used a technique called cryo-electron microscopy to determine a molecular mechanism for the activation and desensitization of ionotropic glutamate receptors, a prominent class of neurotransmitter receptors in the brain and spina

  1. Electron transfer activation of a second water channel for proton transport in [FeFe]-hydrogenase

    SciTech Connect

    Sode, Olaseni; Voth, Gregory A.

    2014-12-14

    Hydrogenase enzymes are important because they can reversibly catalyze the production of molecular hydrogen. Proton transport mechanisms have been previously studied in residue pathways that lead to the active site of the enzyme via residues Cys299 and Ser319. The importance of this pathway and these residues has been previously exhibited through site-specific mutations, which were shown to interrupt the enzyme activity. It has been shown recently that a separate water channel (WC2) is coupled with electron transport to the active site of the [FeFe]-hydrogenase. The water-mediated proton transport mechanisms of the enzyme in different electronic states have been studied using the multistate empirical valence bond reactive molecular dynamics method, in order to understand any role WC2 may have in facilitating the residue pathway in bringing an additional proton to the enzyme active site. In a single electronic state A{sup 2−}, a water wire was formed through which protons can be transported with a low free energy barrier. The remaining electronic states were shown, however, to be highly unfavorable to proton transport in WC2. A double amino acid substitution is predicted to obstruct proton transport in electronic state A{sup 2-} by closing a cavity that could otherwise fill with water near the proximal Fe of the active site.

  2. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms.

    PubMed

    Widdows, Kate L; Panitchob, Nuttanont; Crocker, Ian P; Please, Colin P; Hanson, Mark A; Sibley, Colin P; Johnstone, Edward D; Sengers, Bram G; Lewis, Rohan M; Glazier, Jocelyn D

    2015-06-01

    Uptake of system L amino acid substrates into isolated placental plasma membrane vesicles in the absence of opposing side amino acid (zero-trans uptake) is incompatible with the concept of obligatory exchange, where influx of amino acid is coupled to efflux. We therefore hypothesized that system L amino acid exchange transporters are not fully obligatory and/or that amino acids are initially present inside the vesicles. To address this, we combined computational modeling with vesicle transport assays and transporter localization studies to investigate the mechanisms mediating [(14)C]L-serine (a system L substrate) transport into human placental microvillous plasma membrane (MVM) vesicles. The carrier model provided a quantitative framework to test the 2 hypotheses that l-serine transport occurs by either obligate exchange or nonobligate exchange coupled with facilitated transport (mixed transport model). The computational model could only account for experimental [(14)C]L-serine uptake data when the transporter was not exclusively in exchange mode, best described by the mixed transport model. MVM vesicle isolates contained endogenous amino acids allowing for potential contribution to zero-trans uptake. Both L-type amino acid transporter (LAT)1 and LAT2 subtypes of system L were distributed to MVM, with L-serine transport attributed to LAT2. These findings suggest that exchange transporters do not function exclusively as obligate exchangers.

  3. Active transportation safety features around schools in Canada.

    PubMed

    Pinkerton, Bryn; Rosu, Andrei; Janssen, Ian; Pickett, William

    2013-10-31

    The purpose of this study was to describe the presence and quality of active transportation safety features in Canadian school environments that relate to pedestrian and bicycle safety. Variations in these features and associated traffic concerns as perceived by school administrators were examined by geographic status and school type. The study was based on schools that participated in 2009/2010 Health Behaviour in School-aged Children (HBSC) survey. ArcGIS software version 10 and Google Earth were used to assess the presence and quality of ten different active transportation safety features. Findings suggest that there are crosswalks and good sidewalk coverage in the environments surrounding most Canadian schools, but a dearth of bicycle lanes and other traffic calming measures (e.g., speed bumps, traffic chokers). Significant urban/rural inequities exist with a greater prevalence of sidewalk coverage, crosswalks, traffic medians, and speed bumps in urban areas. With the exception of bicycle lanes, the active transportation safety features that were present were generally rated as high quality. Traffic was more of a concern to administrators in urban areas. This study provides novel information about active transportation safety features in Canadian school environments. This information could help guide public health efforts aimed at increasing active transportation levels while simultaneously decreasing active transportation injuries.

  4. Active Transportation Safety Features around Schools in Canada

    PubMed Central

    Pinkerton, Bryn; Rosu, Andrei; Janssen, Ian; Pickett, William

    2013-01-01

    The purpose of this study was to describe the presence and quality of active transportation safety features in Canadian school environments that relate to pedestrian and bicycle safety. Variations in these features and associated traffic concerns as perceived by school administrators were examined by geographic status and school type. The study was based on schools that participated in 2009/2010 Health Behaviour in School-aged Children (HBSC) survey. ArcGIS software version 10 and Google Earth were used to assess the presence and quality of ten different active transportation safety features. Findings suggest that there are crosswalks and good sidewalk coverage in the environments surrounding most Canadian schools, but a dearth of bicycle lanes and other traffic calming measures (e.g., speed bumps, traffic chokers). Significant urban/rural inequities exist with a greater prevalence of sidewalk coverage, crosswalks, traffic medians, and speed bumps in urban areas. With the exception of bicycle lanes, the active transportation safety features that were present were generally rated as high quality. Traffic was more of a concern to administrators in urban areas. This study provides novel information about active transportation safety features in Canadian school environments. This information could help guide public health efforts aimed at increasing active transportation levels while simultaneously decreasing active transportation injuries. PMID:24185844

  5. Entropic Ratchet transport of interacting active Brownian particles

    SciTech Connect

    Ai, Bao-Quan; He, Ya-Feng; Zhong, Wei-Rong

    2014-11-21

    Directed transport of interacting active (self-propelled) Brownian particles is numerically investigated in confined geometries (entropic barriers). The self-propelled velocity can break thermodynamical equilibrium and induce the directed transport. It is found that the interaction between active particles can greatly affect the ratchet transport. For attractive particles, on increasing the interaction strength, the average velocity first decreases to its minima, then increases, and finally decreases to zero. For repulsive particles, when the interaction is very weak, there exists a critical interaction at which the average velocity is minimal, nearly tends to zero, however, for the strong interaction, the average velocity is independent of the interaction.

  6. Interaction of PIN and PGP transport mechanisms in auxin distribution-dependent development.

    PubMed

    Mravec, Jozef; Kubes, Martin; Bielach, Agnieszka; Gaykova, Vassilena; Petrásek, Jan; Skůpa, Petr; Chand, Suresh; Benková, Eva; Zazímalová, Eva; Friml, Jirí

    2008-10-01

    The signalling molecule auxin controls plant morphogenesis via its activity gradients, which are produced by intercellular auxin transport. Cellular auxin efflux is the rate-limiting step in this process and depends on PIN and phosphoglycoprotein (PGP) auxin transporters. Mutual roles for these proteins in auxin transport are unclear, as is the significance of their interactions for plant development. Here, we have analysed the importance of the functional interaction between PIN- and PGP-dependent auxin transport in development. We show by analysis of inducible overexpression lines that PINs and PGPs define distinct auxin transport mechanisms: both mediate auxin efflux but they play diverse developmental roles. Components of both systems are expressed during embryogenesis, organogenesis and tropisms, and they interact genetically in both synergistic and antagonistic fashions. A concerted action of PIN- and PGP-dependent efflux systems is required for asymmetric auxin distribution during these processes. We propose a model in which PGP-mediated efflux controls auxin levels in auxin channel-forming cells and, thus, auxin availability for PIN-dependent vectorial auxin movement.

  7. Mechanism of Orientation-Dependent Asymmetric Charge Transport in Tunneling Junctions Comprising Photosystem I

    PubMed Central

    2016-01-01

    Recently, photoactive proteins have gained a lot of attention due to their incorporation into bioinspired (photo)electrochemical and solar cells. This paper describes the measurement of the asymmetry of current transport of self-assembled monolayers (SAMs) of the entire photosystem I (PSI) protein complex (not the isolated reaction center, RCI), on two different “director SAMs” supported by ultraflat Au substrates. The director SAMs induce the preferential orientation of PSI, which manifest as asymmetry in tunneling charge-transport. We measured the oriented SAMs of PSI using eutectic Ga–In (EGaIn), a large-area technique, and conducting probe atomic force microscopy (CP-AFM), a single-complex technique, and determined that the transport properties are comparable. By varying the temperatures at which the measurements were performed, we found that there is no measurable dependence of the current on temperature from ±0.1 to ±1.0 V bias, and thus, we suggest tunneling as the mechanism for transport; there are no thermally activated (e.g., hopping) processes. Therefore, it is likely that relaxation in the electron transport chain is not responsible for the asymmetry in the conductance of SAMs of PSI complexes in these junctions, which we ascribe instead to the presence of a large, net dipole moment present in PSI. PMID:26057523

  8. An Ekman Transport Mechanism for the Atlantic Multidecadal Oscillation

    NASA Astrophysics Data System (ADS)

    Pratt, V. R.

    2014-12-01

    Multidecadal global climate since 1850 consists of the expected greenhouse warming and two cycles of a fluctuation commonly associated with the AMO that so far has not been satisfactorily explained. In GC53C-06 at AGUFM13 we compared land and sea temperatures during the global warmings of 1860-1880 and 1910-1940 and inferred that heat flowed sea to land, ruling out aerosol-based external forcings and indicating an internal source such as an instability in the AMOC. Length of day during the past century has varied by ~4 ms inversely with the AMO. Noting that the ocean floor is some five times thinner than the continental crust, we propose here that Earth's rotation regulates heat flux through the ocean floor. One mechanism for this is centrifugal force pulling plates apart, particularly along the Mid-Atlantic Ridge and around the Ring of Fire, increasing flux by an amount that would easily pass unnoticed in the 1930s. Another mechanism, perhaps less strong, is stress from rotational acceleration increasing the thermal conductivity of the young rocks comprising the ocean floor. A difficulty is that the ocean would absorb the fluctuations before reaching the surface. We overcome this difficulty via Ekman transport. This mechanism acts on a 50 m deep layer at the surface to drive it polewards from the ITCZ at 3 cm/sec or 1000 km/yr, orders of magnitude faster than the MOC which therefore cannot interfere. This creates a suction at the ITCZ and a downwards pumping action at 30°. In order to close this cycle there must be a flow equal in volume rate towards the ITCZ at depth. We propose that the heat entering the ocean bottom between 30° S and 30° N enters these two "Ekman cells", which carry it to the surface via the ITCZ. To evaluate feasibility, take the area of the participating 50m surface layer to be 1014 m2, making the volume of the top and bottom layers 1016 m3. Only 1022 J of heat is needed to warm or cool this by 1/3.85 = 0.26 °C. Over the 30 years 1910

  9. Calcium transport mechanisms in muskrat and rat hearts.

    PubMed

    McKean, T A

    2001-11-01

    Mammalian hearts experience calcium overload during extreme and prolonged hypoxia and the calcium overload may lead to enzyme activation and cell death. Several calcium transport systems were examined in muskrat hearts and compared to those found in rat hearts to determine if there is a species difference that might be related to the muskrats' superior ability to survive hypoxia. Radiolabeled nitredendipine binding was determined in rat and muskrat hearts to estimate the density of voltage gated calcium channels in surface membranes. There were no species differences. Calcium release channel density in the sarcoplasmic reticulum was estimated by the determination of radiolabeled ryanodine binding in muskrat and rat heart SR membranes. No differences were revealed between species. The SR uptake of calcium was measured in SR membranes from the hearts of the two species. No differences were found in the B(max) values, however, the muskrat SR membranes did have a slightly lower K(m) value. There were large species differences in Na(+)/Ca(2+) exchange in SL membranes with the muskrat heart having approximately 3.5 times the transport capacity of rat SL membranes. During hypoxic conditions in which there is extensive ATP depletion leading to [Na(+)](i) accumulation and discharge of cellular membrane potential, the Na(+)/Ca(2+) exchanger may operate in the reverse mode and import calcium into the cell and accelerate hypoxic damage. Prior to reaching this state a robust Na(+)/Ca(2+) exchange would facilitate the maintenance of normal diastolic calcium levels and calcium cycling. Muskrats hearts are hypoxia tolerant by virtue of their ability to reduce metabolic demand and generate ATP anaerobically thus, maintaining a favorable ATP balance. Therefore, the relative overexpression of Na(+)/Ca(2+) exchangers in muskrat hearts may be beneficial in the preservation of contractile function and calcium homeostasis in this freshwater diving mammal.

  10. Intestinal ammonia transport in freshwater and seawater acclimated rainbow trout (Oncorhynchus mykiss): evidence for a Na+ coupled uptake mechanism.

    PubMed

    Rubino, Julian G; Zimmer, Alex M; Wood, Chris M

    2015-05-01

    In vitro gut sac experiments were performed on freshwater and 60% seawater acclimated trout (Oncorhynchus mykiss) under treatments designed to discern possible mechanisms of intestinal ammonia transport. Seawater acclimation increased ammonia flux rate into the serosal saline (Jsamm) in the anterior intestine, however it did not alter Jsamm in the mid- or posterior intestine suggesting similar mechanisms of ammonia handling in freshwater and seawater fish. Both fluid transport rate (FTR) and Jsamm were inhibited in response to basolateral ouabain treatment, suggesting a linkage of ammonia uptake to active transport, possibly coupled to fluid transport processes via solvent drag. Furthermore, decreases in FTR and Jsamm caused by low Na(+) treatment indicated a Na(+) linked transport mechanism. Mucosal bumetanide (10(-4) M) had no impact on FTR, yet decreased Jsamm in the anterior and mid-intestine, suggesting NH4(+) substitution for K(+) on an apical NKCC, and at least a partial uncoupling of ammonia transport from fluid transport. Additional treatments (amiloride, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), phenamil, bafilomycin, 4',6-diamidino-2-phenylindole (DAPI), high sodium) intended to disrupt alternative routes of Na(+) uptake yielded no change in FTR or Jsamm, suggesting the absence of direct competition between Na(+) and ammonia for transport. Finally, [(14)C]methylamine permeability (PMA) measurements indicated the likely presence of an intestinal Rh-mediated ammonia transport system, as increasing NH4Cl (0, 1, 5 mmol l(-1)) concentrations reduced PMA, suggesting competition for transport through Rh proteins. Overall, the data presented in this paper provide some of the first insights into mechanisms of teleost intestinal ammonia transport.

  11. Caulis Sinomenii extracts activate DA/NE transporter and inhibit 5HT transporter.

    PubMed

    Zhao, Gang; Bi, Cheng; Qin, Guo-Wei; Guo, Li-He

    2009-08-01

    Caulis Sinomenii (QFT) has analgesic, sedative, and anxiolytic-like actions, and is proven effective for improving drug dependence that is known to be associated with abnormal monoaminergic transmission. We assessed whether QFT would be biologically active in functionally regulating monoamine transporters using CHO cells expressing dopamine transporter (DAT), norepinephrine transporter (NET), or serotonin transporter (SERT) (i.e. D8, N1, or S6 cells, respectively). Here, we showed that its primary extracts, such as QA, QC, QE, QD, and QB (QFT ethanol, chloroform, ethyl acetate, alkaloid-free chloroform, and alkaloid-containing chloroform extract, respectively), and secondary extracts, such as QE-2, - 3, - 5, - 7, QD-1, - 2, - 3, - 4, - 5, and QB-1, - 2, - 3, - 4, - 5 (fractioned from QE, QD, and QB, respectively), in differing degrees, either increased DA/ NE uptake by corresponding D8/N1 cells or decreased 5HT uptake by S6 cells; wherein, QE-2, QD-3, and QE-7 were potent DA/NE uptake activators while both QE-7 and QB-5 were potent 5HT uptake inhibitors. Furthermore, the enhancement of DA/NE uptake was dependent of DAT/NET activity, and the inhibition of 5HT uptake was typical of competition. Thus, QFT extracts, especially QE-2 and QE-7 (both with stronger potencies), are novel monoamine transporter modulators functioning as DAT/ NET activators and/or SERT inhibitors, and would likely improve neuropsychological disorders through regulating monoamine transporters.

  12. Hearing molecules, mechanism and transportation: modeled in Drosophila melanogaster.

    PubMed

    Bokolia, Naveen Prakash; Mishra, Monalisa

    2015-02-01

    Mechanosensory transduction underlies the perception of touch, sound and acceleration. The mechanical signals exist in the environment are resensed by the specialized mechanosensory cells, which convert the external forces into the electrical signals. Hearing is a magnificent example that relies on the mechanotransduction mediated by the auditory cells, for example the inner-ear hair cells in vertebrates and the Johnston's organ (JO) in fly. Previous studies have shown the fundamental physiological processes in the fly and vertebrate auditory organs are similar, suggesting that there might be a set of similar molecules underlying these processes. The molecular studies of the fly JO have been shown to be remarkably successful in discovering the developmental and functional genes that provided further implications in vertebrates. Several evolutionarily conserved molecules and signaling pathways have been shown to govern the development of the auditory organs in both vertebrates and invertebrates. The current review describes the similarities and differences between the vertebrate and fly auditory organs at developmental, structural, molecular, and transportation levels.

  13. Robustness of multidimensional Brownian ratchets as directed transport mechanisms

    NASA Astrophysics Data System (ADS)

    González-Candela, Ernesto; Romero-Rochín, Víctor; Del Río, Fernando

    2011-08-01

    Brownian ratchets have recently been considered as models to describe the ability of certain systems to locate very specific states in multidimensional configuration spaces. This directional process has particularly been proposed as an alternative explanation for the protein folding problem, in which the polypeptide is driven toward the native state by a multidimensional Brownian ratchet. Recognizing the relevance of robustness in biological systems, in this work we analyze such a property of Brownian ratchets by pushing to the limits all the properties considered essential to produce directed transport. Based on the results presented here, we can state that Brownian ratchets are able to deliver current and locate funnel structures under a wide range of conditions. As a result, they represent a simple model that solves the Levinthal's paradox with great robustness and flexibility and without requiring any ad hoc biased transition probability. The behavior of Brownian ratchets shown in this article considerably enhances the plausibility of the model for at least part of the structural mechanism behind protein folding process.

  14. Ovariectomy Enhances Mechanical Load-Induced Solute Transport around Osteocytes in Rat Cancellous Bone

    PubMed Central

    Ciani, Cesare; Sharma, Divya; Doty, Stephen B.; Fritton, Susannah P.

    2014-01-01

    To test if osteoporosis alters mechanical load-induced interstitial fluid flow in bone, this study examined the combined effect of estrogen deficiency and external loading on solute transport around osteocytes. An in vivo tracer, FITC-labeled bovine serum albumin, was injected into anaesthetized ovariectomized and control female Sprague Dawley rats before the right tibia was subjected to a controlled, physiological, non-invasive sinusoidal load to mimic walking. Tracer movement through the lacunar-canalicular system surrounding osteocytes was quantified in cortical and cancellous bone from the proximal tibia using confocal microscopy, with the non-loaded tibia serving as internal control. Overall, the application of mechanical loading increased the percentage of osteocyte lacunae labeled with injected tracer, and ovariectomy further enhanced movement of tracer. An analysis of separate regions demonstrated that ovariectomy enhanced in vivo transport of the injected tracer in the cancellous bone of the tibial epiphysis and metaphysis but not in the cortical bone of the metaphysis. These findings show that bone changes due to reduced estrogen levels alter convectional transport around osteocytes in cancellous bone and demonstrate a functional difference of interstitial fluid flow around osteocytes in estrogen-deficient rats undergoing the same physical activity as controls. The altered interstitial fluid flow around osteocytes is likely related to nanostructural matrix-mineral level differences recently demonstrated at the lacunar-canalicular surface of estrogen-deficient rats, which could affect the transmission of mechanical loads to the osteocyte. PMID:24316418

  15. How LeuT shapes our understanding of the mechanisms of sodium-coupled neurotransmitter transporters.

    PubMed

    Penmatsa, Aravind; Gouaux, Eric

    2014-03-01

    Neurotransmitter transporters are ion-coupled symporters that drive the uptake of neurotransmitters from neural synapses. In the past decade, the structure of a bacterial amino acid transporter, leucine transporter (LeuT), has given valuable insights into the understanding of architecture and mechanism of mammalian neurotransmitter transporters. Different conformations of LeuT, including a substrate-free state, inward-open state, and competitive and non-competitive inhibitor-bound states, have revealed a mechanistic framework for the transport and transport inhibition of neurotransmitters. The current review integrates our understanding of the mechanistic and pharmacological properties of eukaryotic neurotransmitter transporters obtained through structural snapshots of LeuT.

  16. Classroom Activities in Transportation: Technology Education.

    ERIC Educational Resources Information Center

    Wisconsin State Dept. of Public Instruction, Madison.

    This curriculum supplement was designed to correlate directly with "A Guide to Curriculum Planning in Technology Education," published by the Wisconsin Department of Public Instruction. It is also a companion book to three other classroom activity compilations, one in each of the other three major systems of technology--manufacturing,…

  17. Thiamine transport in Escherichia coli: the mechanism of inhibition by the sulfhydryl-specific modifier N-ethylmaleimide.

    PubMed

    Hollenbach, Andrew D; Dickson, Kimberly A; Washabaugh, Michael W

    2002-08-31

    Active transport of thiamin (vitamin B(1)) into Escherichia coli occurs through a member of the superfamily of transporters known as ATP-binding cassette (ABC) transporters. Although it was demonstrated that the sulfhydryl-specific modifier N-ethylmaleimide (NEM) inhibited thiamin transport, the exact mechanism of this inhibition is unknown. Therefore, we have carried out a kinetic analysis of thiamin transport to determine the mechanism of inhibition by NEM. Thiamin transport in vivo exhibits Michaelis-Menten kinetics with K(M)=15 nM and V(max)=46 U mg(-1). Treatment of intact E. coli KG33 with saturating NEM exhibited apparent noncompetitive inhibition, decreasing V(max) by approximately 50% without effecting K(M) or the apparent first-order rate constant (k(obsd)). Apparent noncompetitive inhibition is consistent with an irreversible covalent modification of a cysteine(s) that is critical for the transport process. A primary amino acid analysis of the subunits of the thiamin permease combined with our kinetic analysis suggests that inhibition of thiamin transport by NEM is different from other ABC transporters and occurs at the level of protein-protein interactions between the membrane-bound carrier protein and the ATPase subunit.

  18. Effects of surfactants and thermodynamic activity of model active ingredient on transport over plant leaf cuticle.

    PubMed

    Fagerström, Anton; Kocherbitov, Vitaly; Ruzgas, Tautgirdas; Westbye, Peter; Bergström, Karin; Engblom, Johan

    2013-03-01

    The main objective of this study was to investigate the mechanism of molecular transport across the cuticle of Clivia leaves. In vitro diffusion methodology was used to investigate the transport of a systemic fungicide, tebuconazole, over a model silicone membrane, enzymatically isolated cuticle membranes, and dermatomed leaves. It was shown that dermatomed leaves may replace enzymatically isolated cuticles. Furthermore, the effects of two surfactants, C(10)EO(7) and C(8)G(1.6), on the fungicide transport were investigated. Tebuconazole cuticle permeation was described using Fick's first law of diffusion, expressed by the thermodynamic activity of the solute in the membrane. A new method for calculation of diffusion coefficients in the membrane is proposed. To access the thermodynamic activity of the fungicide in the membranes, sorption isotherms of tebuconazole in the membrane materials studied were recorded. The thermodynamic activity of the fungicide in aqueous solutions was calculated from solubility data. For that purpose, the effect of surfactants on tebuconazole solubility was studied. The results show that addition of surfactants allows for higher concentrations of tebuconazole available for penetration. Nonetheless, at a fixed fungicide thermodynamic activity, all formulations produced the same flux over the silicone membrane independently on the fungicide concentration. This shows that the driving force across non-responding membranes is the gradient of thermodynamic activity, rather than the gradient of the fungicide concentration. In case of leaves, surfactants induced the same quantitative increase in both flux and diffusion coefficient of solute in the cuticle, while the cuticle-water partition coefficient was unaffected.

  19. Cerebral ABC transporter-common mechanisms may modulate neurodegenerative diseases and depression in elderly subjects.

    PubMed

    Pahnke, Jens; Fröhlich, Christina; Paarmann, Kristin; Krohn, Markus; Bogdanovic, Nenad; Årsland, Dag; Winblad, Bengt

    2014-11-01

    In elderly subjects, depression and dementia often coincide but the actual reason is currently unknown. Does a causal link exist or is it just a reactive effect of the knowledge to suffer from dementia? The ABC transporter superfamily may represent a causal link between these mental disorders. Since the transporters ABCB1 and ABCC1 have been discovered as major β-amyloid-exporting molecules at the blood-brain barrier and ABCC1 was found to be directly activated by St. John's wort (SJW), depression and dementia certainly share an important pathophysiologic link. It was recognized that herbal anti-depressant formulations made from SJW are at least as effective for the treatment of unipolar depression in old age as classical pharmacotherapy, while having fewer side effects (Cochrane reports, 2008). SJW is known to activate various metabolizing and transport systems in the body, with cytochrome P450 enzymes and ABC transporters being most important. Does the treatment of depression in elderly subjects using pharmacological compounds or phytomedical extracts target a mechanism that also accounts for peptide storage in Alzheimer's disease and perhaps other proteopathies of the brain? In this review we summarize recent data that point to a common mechanism and present the first promising causal treatment results of demented elderly subjects with distinct SJW extracts. Insufficient trans-barrier clearance may indeed present a common problem in all the proteopathies of the brain where toxic peptides are deposited in a location-specific manner. Thus, activation of efflux molecules holds promise for future treatment of this large group of devastating disorders.

  20. Promoting physical activity and reducing climate change: opportunities to replace short car trips with active transportation.

    PubMed

    Maibach, Edward; Steg, Linda; Anable, Jillian

    2009-10-01

    Automobile use is a significant contributor to climate change, local air pollution, pedestrian injuries and deaths, declines in physical activity and obesity. A significant proportion of car use is for short trips that can relatively easily be taken with active transportation options--walking or cycling--or with public transportation. In this commentary, we review a number of immediate, practical opportunities to implement policies and programs that reduce short car trips and increase active transportation.

  1. Center for low-gravity fluid mechanics and transport phenomena

    NASA Technical Reports Server (NTRS)

    Kassoy, D. R.; Sani, R. L.

    1991-01-01

    Research projects in several areas are discussed. Mass transport in vapor phase systems, droplet collisions and coalescence in microgravity, and rapid solidification of undercooled melts are discussed.

  2. Active Transportation to School: Findings from a National Survey

    ERIC Educational Resources Information Center

    Fulton, Janet E.; Shisler, Jessica L.; Yore, Michelle M.; Caspersen, Carl J.

    2005-01-01

    In the past, active transportation to school offered an important source of daily physical activity for youth; more recently, however, factors related to distance, safety, or physical or social environments may have contributed to the proportion of children who travel to school by motorized vehicle. The authors examine the characteristics of…

  3. Electron injection and transport mechanism in organic devices based on electron transport materials

    NASA Astrophysics Data System (ADS)

    Khan, M. A.; Xu, Wei; Khizar-ul-Haq; Zhang, Xiao Wen; Bai, Yu; Jiang, X. Y.; Zhang, Z. L.; Zhu, W. Q.

    2008-11-01

    Electron injection and transport in organic devices based on electron transport (ET) materials, such as 4,7- diphyenyl-1,10-phenanthroline (Bathophenanthroline BPhen), 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (Bathocuproine BCP) and bipyridyl oxadiazole compound 1,3-bis [2-(2,2'-bipyridin-6-yl)-1,3,4-oxadiazol-5-yl]benzene (Bpy-OXD), have been reported. The devices are composed of ITO/ET materials (BPhen, BCP Bpy-OXD)/cathodes, where cathodes = Au, Al and Ca. Current-voltage characteristics of each ET material are performed as a function of cathodes. We have found that Ca and Al exhibit quite different J-V characteristics compared with the gold (Au) cathode. The current is more than one order of magnitude higher for the Al cathode and more than three orders of magnitude higher for Ca compared with that of the Au cathode at ~8 V for all ET materials. This is because of the relatively low energy barrier at the organic/metal interface for Ca and Al cathodes. Electron-only devices with the Au cathode show that the electron transfer limitation is located at the organic/cathode interface and the Fowler-Nordheim mechanism is qualitatively consistent with experimental data at high voltages. With Ca and Al cathodes, electron conduction is preponderant and is bulk limited. A power law dependence J ~ Vm with m > 2 is consistent with the model of trap-charge limited conduction. The total electron trap density is estimated to be ~5 × 1018 cm-3. The critical voltage (Vc) is found to be ~45 V and is almost independent of the materials.

  4. [Activation and inhibitory mechanisms of blood platelets].

    PubMed

    Suzuki-Inoue, Katsue

    2014-07-01

    Exposure of platelets to subendothelial matrices initiates physiological hemostasis and pathological thrombosis. Under high shear stress, von Willebrand factor bridges newly exposed collagen to glycoprotein (GP) Ib on platelets. This initial tethering facilitates association between the collagen receptor GPVI and collagen, which generates tyrosine kinase-dependent activation signals, followed by release of secondary mediators and integrin activation. Activated integrin can bind to their ligands including fibrinogen. The released secondary mediators, ADP and thromboxane A2, activate integrin of flowing platelets, which enables formation of platelet thrombi by binding of activated flowing platelets and adhered platelets to collagen via binding between activated aIIbbeta3 integrin and fibrinogen. Platelets also have inhibitory mechanisms, which help to prevent unwanted platelet activation in vivo.

  5. Spontaneous mechanical activity in depolarized frog ventricle

    PubMed Central

    1976-01-01

    Spontaneous mechanical activity can be produced in depolarized frog ventricle by bathing the tissue in a solution with low Na, Iow Ca, and high K+. The contractions can be inhibited by depleting the tissue of Ca first, but they are relatively insensitive to changes in either extracellular [Ca++] or [Ca++]/[Na+]2. They are terminated very rapidly by raising [Na+] to 40 mM. Local anesthetics enhance the spontaneous activity in proportion to the concentration of their free base form. These contractions occur relatively rhythmically for several hours. Since the preparation is multicellular, this suggests a mechanism for intercellular communication without change in membrane potential. PMID:822122

  6. Measurements Required to Understand the Lunar Dust Environment and Transport Mechanism

    NASA Technical Reports Server (NTRS)

    Spann, James F., Jr.; Abbas, Mian

    2006-01-01

    Going back to the lunar surface offers an opportunity to understand the dust environment and associated transport mechanisms. This talk will explore what measurements are required to understand and characterize the dust-plasma environment in which robotic and human activities will be conducted. The understanding gained with the measurements can be used to make informed decisions on engineering solutions and follow-on investigations. Particular focus will be placed on required measurements of the size, spatial and charge distribution of the suspended lunar regolith.

  7. Amino-acid transporters in T-cell activation and differentiation.

    PubMed

    Ren, W; Liu, G; Yin, J; Tan, B; Wu, G; Bazer, F W; Peng, Y; Yin, Y

    2017-03-02

    T-cell-mediated immune responses aim to protect mammals against cancers and infections, and are also involved in the pathogenesis of various inflammatory or autoimmune diseases. Cellular uptake and the utilization of nutrients is closely related to the T-cell fate decision and function. Research in this area has yielded surprising findings in the importance of amino-acid transporters for T-cell development, homeostasis, activation, differentiation and memory. In this review, we present current information on amino-acid transporters, such as LAT1 (l-leucine transporter), ASCT2 (l-glutamine transporter) and GAT-1 (γ-aminobutyric acid transporter-1), which are critically important for mediating peripheral naive T-cell homeostasis, activation and differentiation, especially for Th1 and Th17 cells, and even memory T cells. Mechanically, the influence of amino-acid transporters on T-cell fate decision may largely depend on the mechanistic target of rapamycin complex 1 (mTORC1) signaling. These discoveries remarkably demonstrate the role of amino-acid transporters in T-cell fate determination, and strongly indicate that manipulation of the amino-acid transporter-mTORC1 axis could ameliorate many inflammatory or autoimmune diseases associated with T-cell-based immune responses.

  8. Ascorbic acid participates in a general mechanism for concerted glucose transport inhibition and lactate transport stimulation.

    PubMed

    Castro, Maite A; Angulo, Constanza; Brauchi, Sebastián; Nualart, Francisco; Concha, Ilona I

    2008-11-01

    In this paper, we present a novel function for ascorbic acid. Ascorbic acid is an important water-soluble antioxidant and cofactor in various enzyme systems. We have previously demonstrated that an increase in neuronal intracellular ascorbic acid is able to inhibit glucose transport in cortical and hippocampal neurons. Because of the presence of sodium-dependent vitamin C transporters, ascorbic acid is highly concentrated in brain, testis, lung, and adrenal glands. In this work, we explored how ascorbic acid affects glucose and lactate uptake in neuronal and non-neuronal cells. Using immunofluorescence and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, the expression of glucose and ascorbic acid transporters in non-neuronal cells was studied. Like neurons, HEK293 cells expressed GLUT1, GLUT3, and SVCT2. With radioisotope-based methods, only intracellular ascorbic acid, but not extracellular, inhibits 2-deoxyglucose transport in HEK293 cells. As monocarboxylates such as pyruvate and lactate, are important metabolic sources, we analyzed the ascorbic acid effect on lactate transport in cultured neurons and HEK293 cells. Intracellular ascorbic acid was able to stimulate lactate transport in both cell types. Extracellular ascorbic acid did not affect this transport. Our data show that ascorbic acid inhibits glucose transport and stimulates lactate transport in neuronal and non-neuronal cells. Mammalian cells frequently present functional glucose and monocarboxylate transporters, and we describe here a general effect in which ascorbic acid functions like a glucose/monocarboxylate uptake switch in tissues expressing ascorbic acid transporters.

  9. Differential Mechanisms of Tenofovir and Tenofovir Disoproxil Fumarate Cellular Transport and Implications for Topical Preexposure Prophylaxis

    PubMed Central

    Crooker, Kerry; Park, Sung Hyun; Su, Jonathan T.; Ott, Adina; Cheshenko, Natalia; Szleifer, Igal; Kiser, Patrick F.; Frank, Bruce; Mesquita, Pedro M. M.

    2015-01-01

    Intravaginal rings releasing tenofovir (TFV) or its prodrug, tenofovir disoproxil fumarate (TDF), are being evaluated for HIV and herpes simplex virus (HSV) prevention. The current studies were designed to determine the mechanisms of drug accumulation in human vaginal and immune cells. The exposure of vaginal epithelial or T cells to equimolar concentrations of radiolabeled TDF resulted in over 10-fold higher intracellular drug levels than exposure to TFV. Permeability studies demonstrated that TDF, but not TFV, entered cells by passive diffusion. TDF uptake was energy independent but its accumulation followed nonlinear kinetics, and excess unlabeled TDF inhibited radiolabeled TDF uptake in competition studies. The carboxylesterase inhibitor bis-nitrophenyl phosphate reduced TDF uptake, suggesting saturability of intracellular carboxylesterases. In contrast, although TFV uptake was energy dependent, no competition between unlabeled and radiolabeled TFV was observed, and the previously identified transporters, organic anion transporters (OATs) 1 and 3, were not expressed in human vaginal or T cells. The intracellular accumulation of TFV was reduced by the addition of endocytosis inhibitors, and this resulted in the loss of TFV antiviral activity. Kinetics of drug transport and metabolism were monitored by quantifying the parent drugs and their metabolites by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Results were consistent with the identified mechanisms of transport, and the exposure of vaginal epithelial cells to equimolar concentrations of TDF compared to TFV resulted in ∼40-fold higher levels of the active metabolite, tenofovir diphosphate. Together, these findings indicate that substantially lower concentrations of TDF than TFV are needed to protect cells from HIV and HSV-2. PMID:26711762

  10. Charge transport mechanisms in organic and microcrystalline silicon field-effect transistors

    NASA Astrophysics Data System (ADS)

    Konezny, S. J.; Bussac, M. N.; Geiser, A.; Zuppiroli, L.

    2007-09-01

    Several organic and inorganic materials have emerged as promising candidates for the active layer of field-effect transistors (FETs) fabricated on flexible substrates. The charge transport models necessary for device optimization in these systems are at different stages of development. The understanding of charge transport in single-crystal and thin-film FETs based on organic materials such as pentacene, rubrene, and other related compounds has advanced considerably in recent years and a clear picture of the relevant transport mechanisms is forming. In contrast, the theoretical description of transport in hydrogenated microcrystalline silicon (μc-Si:H) is not as well known and the published results and theories are often contradictory. We review the paradigms we feel are useful in describing the current understanding of transport in organic and μc-Si:H field-effect transistors. In the case of organic materials these include the polarization and transfer integral fluctuation model [A. Troisi and G. Orlandi, Phys. Rev. Lett. 96, 086601 (2006), J.-D. Picon et al., Phys. Rev. B 75, 235106 (2007)], the Frölich polaron model [I.N. Hulea et al., Nat. Mater. 5, 982 (2006), H. Houilli et al., J. Appl. Phys. 100, 033702 (2006)], and several trapping models [M.E. Gershenson et al., Rev. Mod. Phys. 78, 973 (2006), V. Podzorov et al., Phys Rev. Lett. 95, 226601 (2005)]. Given the heterogeneous composition and structure of microcrystalline silicon thin films, a variety of theories to describe dark conductivity have been applied to μc-Si:H including those based on percolation theory [H. Overhof et al., J. Non-Cryst. Solids 227-230, 992 (1998)], hopping models [A. Dussan and R. H. Buitrago, J. Appl. Phys. 97, 043711 (2005)], thermionic emission, and tunneling. We give a brief overview of these models and present a fluctuation-induced tunneling model that we are developing to describe charge transport in microcrystalline silicon.

  11. Advocacy for active transport: advocate and city council perspectives

    PubMed Central

    2010-01-01

    Background Effective advocacy is an important part of efforts to increase population participation in physical activity. Research about effective health advocacy is scarce, however, the health sector can learn from the experiences and knowledge of community advocates and those who are on the receiving end of this advocacy. The aim of this study is to explore advocacy for active transport from the perspectives of community advocates and representatives from City councils. Methods Cycling and walking advocates were identified from the local contact list of Cycling Advocates Network and Living Streets Aotearoa. Semi-structured telephone interviews were conducted with cycle and walking advocates from throughout New Zealand. Advocates also nominated a suitable council officer at their local City council to be interviewed. Interviews were recorded and transcribed and categories of responses for each of the questions created. Results Several processes were used by advocates to engage with council staff, including formal council submissions, meetings, stakeholder forums and partnership in running community events promoting active transport. Several other agencies were identified as being influential for active transport, some as potential coalition partners and others as potential adversaries. Barriers to improving conditions for active transport included a lack of funding, a lack of will-power among either council staff or councillors, limited council staff capacity (time or training) and a culture of providing infrastructure for motor vehicles instead of people. Several suggestions were made about how the health sector could contribute to advocacy efforts, including encouraging political commitment, engaging the media, communicating the potential health benefits of active transport to the general public and being role models in terms of personal travel mode choice and having workplaces that support participation in active transport. Conclusions There is potential for the

  12. Density and localized states' impact on amorphous carbon electron transport mechanisms

    NASA Astrophysics Data System (ADS)

    Caicedo-Dávila, S.; Lopez-Acevedo, O.; Velasco-Medina, J.; Avila, A.

    2016-12-01

    This work discusses the electron transport mechanisms that we obtained as a function of the density of amorphous carbon (a-C) ultra-thin films. We calculated the density of states (total and projected), degree of electronic states' localization, and transmission function using the density functional theory and nonequilibrium Green's functions method. We generated 25 sample a-C structures using ab-initio molecular dynamics within the isothermal-isobaric ensemble. We identified three transport regimes as a function of the density, varying from semimetallic in low-density samples ( ≤2.4 g/cm3) to thermally activated in high-density ( ≥2.9 g/cm3) tetrahedral a-C. The middle-range densities (2.4 g/cm3 ≤ρ≤ 2.9 g/cm3) are characterized by resonant tunneling and hopping transport. Our findings offer a different perspective from the tight-binding model proposed by Katkov and Bhattacharyya [J. Appl. Phys. 113, 183712 (2013)], and agree with experimental observations in low-dimensional carbon systems [see S. Bhattacharyya, Appl. Phys. Lett. 91, 21 (2007)]. Identifying transport regimes is crucial to the process of understanding and applying a-C thin film in electronic devices and electrode coating in biosensors.

  13. Palmitate stimulates glucose transport in rat adipocytes by a mechanism involving translocation of the insulin sensitive glucose transporter (GLUT4)

    NASA Technical Reports Server (NTRS)

    Hardy, R. W.; Ladenson, J. H.; Henriksen, E. J.; Holloszy, J. O.; McDonald, J. M.

    1991-01-01

    In rat adipocytes, palmitate: a) increases basal 2-deoxyglucose transport 129 +/- 27% (p less than 0.02), b) decreases the insulin sensitive glucose transporter (GLUT4) in low density microsomes and increases GLUT4 in plasma membranes and c) increases the activity of the insulin receptor tyrosine kinase. Palmitate-stimulated glucose transport is not additive with the effect of insulin and is not inhibited by the protein kinase C inhibitors staurosporine and sphingosine. In rat muscle, palmitate: a) does not affect basal glucose transport in either the soleus or epitrochlearis and b) inhibits insulin-stimulated glucose transport by 28% (p less than 0.005) in soleus but not in epitrochlearis muscle. These studies demonstrate a potentially important differential role for fatty acids in the regulation of glucose transport in different insulin target tissues.

  14. On the molecular mechanism of flippase- and scramblase-mediated phospholipid transport.

    PubMed

    Montigny, Cédric; Lyons, Joseph; Champeil, Philippe; Nissen, Poul; Lenoir, Guillaume

    2016-08-01

    Phospholipid flippases are key regulators of transbilayer lipid asymmetry in eukaryotic cell membranes, critical to many trafficking and signaling pathways. P4-ATPases, in particular, are responsible for the uphill transport of phospholipids from the exoplasmic to the cytosolic leaflet of the plasma membrane, as well as membranes of the late secretory/endocytic pathways, thereby establishing transbilayer asymmetry. Recent studies combining cell biology and biochemical approaches have improved our understanding of the path taken by lipids through P4-ATPases. Additionally, identification of several protein families catalyzing phospholipid 'scrambling', i.e. disruption of phospholipid asymmetry through energy-independent bi-directional phospholipid transport, as well as the recent report of the structure of such a scramblase, opens the way to a deeper characterization of their mechanism of action. Here, we discuss the molecular nature of the mechanism by which lipids may 'flip' across membranes, with an emphasis on active lipid transport catalyzed by P4-ATPases. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.

  15. Resolution of parameters in the equivalent electrical circuit of the sodium transport mechanism across toad skin.

    PubMed

    Isaacson, L C

    1977-01-28

    In amphibian epithelia, amiloride reduces net sodium transport by hindering the entry of sodium to the active transport mechanism, that is, by increasing the series resistance (Rser). Theoretically, therefore, analysis of amiloride-induced changes in potential differences and short-circuit current should yield numerical estimates of all the parameters in the equivalent electrical circuit of the sodium transport mechanism. The concept has been explored by analysis of such changes in toad skins (Xenopus laevis) bathed in hypotonic sulphate Ringer's, after exposure to varying doses of amiloride, or to amphotericin, dinitrophenol or Pitressin. The estimated values of Rser, of the electromotive force of the sodium pump (ENa), and of the shunt resistance (Rsh) were independent of the dose of amiloride employed. Skins bathed in hypotonic sulphate Ringer's exhibited a progressive rise in ENa. Amphotericin produced a fall in Rser, while dinitrophenol caused a fall in ENa; washout of the drugs reversed these effects. Pitressin produced a fall in both Rser and Rsh, with a rise in ENa. These results are in accord with earlier suggestions regarding the site(s) of action of these agents.

  16. High Energy Density Nastic Structures Using Biological Transport Mechanisms

    DTIC Science & Technology

    2007-02-28

    permeable membranes . This concept is based on the pressurization of cells similar to the process that plants use to maintain homeostasis and regulate...two chambers separated by a semi-permeable membrane substrate that contains protein transporters suspended in a lipid bilayer. The protein...transporters convert biochemical energy in the form of ATP into a protein gradient across the semi- permeable membrane . The proton gradient, in turn, induces

  17. Structural Insights into the Transport Mechanism of the Human Sodium-dependent Lysophosphatidylcholine Transporter MFSD2A.

    PubMed

    Quek, Debra Q Y; Nguyen, Long N; Fan, Hao; Silver, David L

    2016-04-29

    Major facilitator superfamily domain containing 2A (MFSD2A) was recently characterized as a sodium-dependent lysophosphatidylcholine transporter expressed at the blood-brain barrier endothelium. It is the primary route for importation of docosohexaenoic acid and other long-chain fatty acids into fetal and adult brain and is essential for mouse and human brain growth and function. Remarkably, MFSD2A is the first identified major facilitator superfamily member that uniquely transports lipids, implying that MFSD2A harbors unique structural features and transport mechanism. Here, we present three three-dimensional structural models of human MFSD2A derived by homology modeling using MelB- and LacY-based crystal structures and refined by biochemical analysis. All models revealed 12 transmembrane helices and connecting loops and represented the partially outward-open, outward-partially occluded, and inward-open states of the transport cycle. In addition to a conserved sodium-binding site, three unique structural features were identified as follows: a phosphate headgroup binding site, a hydrophobic cleft to accommodate a hydrophobic hydrocarbon tail, and three sets of ionic locks that stabilize the outward-open conformation. Ligand docking studies and biochemical assays identified Lys-436 as a key residue for transport. It is seen forming a salt bridge with the negative charge on the phosphate headgroup. Importantly, MFSD2A transported structurally related acylcarnitines but not a lysolipid without a negative charge, demonstrating the necessity of a negatively charged headgroup interaction with Lys-436 for transport. These findings support a novel transport mechanism by which lysophosphatidylcholines are "flipped" within the transporter cavity by pivoting about Lys-436 leading to net transport from the outer to the inner leaflet of the plasma membrane.

  18. Molecular mechanisms regulating NLRP3 inflammasome activation

    PubMed Central

    Jo, Eun-Kyeong; Kim, Jin Kyung; Shin, Dong-Min; Sasakawa, Chihiro

    2016-01-01

    Inflammasomes are multi-protein signaling complexes that trigger the activation of inflammatory caspases and the maturation of interleukin-1β. Among various inflammasome complexes, the NLRP3 inflammasome is best characterized and has been linked with various human autoinflammatory and autoimmune diseases. Thus, the NLRP3 inflammasome may be a promising target for anti-inflammatory therapies. In this review, we summarize the current understanding of the mechanisms by which the NLRP3 inflammasome is activated in the cytosol. We also describe the binding partners of NLRP3 inflammasome complexes activating or inhibiting the inflammasome assembly. Our knowledge of the mechanisms regulating NLRP3 inflammasome signaling and how these influence inflammatory responses offers further insight into potential therapeutic strategies to treat inflammatory diseases associated with dysregulation of the NLRP3 inflammasome. PMID:26549800

  19. Dopamine transporter occupancy by RTI-55, inhibition of dopamine transport and stimulation of locomotor activity

    SciTech Connect

    Gatley, S.J.; Gifford, A.N.; Volkow, N.D.

    1997-05-01

    Cocaine analogs such as RTI-55 (or {beta}CIT) with a higher affinity for the DAT are potentially useful as therapeutic drugs in cocaine abuse as well as for radiopharmaceutical use. Previously we showed that in mice RTI-55 (2 mg/Kg, i/p) reduced H-3 cocaine striatum-to-cerebellum ratios (St/Cb, {lg_bullet}) from 1.6 to 1.2 at 3 h after administration, with recovery by 12 h. In the present study we demonstrate a very similar time-course for transport {triangle} measured in striatal homo within 2 min of sacrifice. The maximum inhibition of uptake at about 1 h corresponded to about 80% of the control uptake rate, similar to the percent reduction in St/Cb. The time-course of the effect of this dose of RTI-55 on locomotor activity ({sq_bullet}) was complex, with a drop in the activity measure at 7 h, after a further injection of RTI-55, but activity remained higher than in saline controls. In spite of this complexity, which may be associated with stereotypies and/or exhaustion, the duration of increased activity is consistent with the duration of transporter blockade. These experiments support the notion that PET/SPECT measures of transporter occupancy accurately reflect transporter inhibition.

  20. Exciton transport, charge extraction, and loss mechanisms in organic photovoltaics

    NASA Astrophysics Data System (ADS)

    Scully, Shawn Ryan

    Organic photovoltaics have attracted significant interest over the last decade due to their promise as clean low-cost alternatives to large-scale electric power generation such as coal-fired power, natural gas, and nuclear power. Many believe power conversion efficiency targets of 10-15% must be reached before commercialization is possible. Consequently, understanding the loss mechanisms which currently limit efficiencies to 4-5% is crucial to identify paths to reach higher efficiencies. In this work, we investigate the dominant loss mechanisms in some of the leading organic photovoltaic architectures. In the first class of architectures, which include planar heterojunctions and bulk heterojunctions with large domains, efficiencies are primarily limited by the distance photogenerated excitations (excitons) can be transported (termed the exciton diffusion length) to a heterojunction where the excitons may dissociate. We will discuss how to properly measure the exciton diffusion length focusing on the effects of optical interference and of energy transfer when using fullerenes as quenching layers and show how this explains the variety of diffusion lengths reported for the same material. After understanding that disorder and defects limit exciton diffusion lengths, we suggest some approaches to overcome this. We then extensively investigate the use of long-range resonant energy transfer to increase exciton harvesting. Using simulations and experiments as support, we discuss how energy transfer can be engineered into architectures to increase the distance excitons can be harvested. In an experimental model system, DOW Red/PTPTB, we will show how the distance excitons are harvested can be increased by almost an order of magnitude up to 27 nm from a heterojunction and give design rules and extensions of this concept for future architectures. After understanding exciton harvesting limitations we will look at other losses that are present in planar heterojunctions. One of

  1. Trapping the transition state of an ATP-binding cassette transporter: Evidence for a concerted mechanism of maltose transport

    PubMed Central

    Chen, Jue; Sharma, Susan; Quiocho, Florante A.; Davidson, Amy L.

    2001-01-01

    High-affinity uptake into bacterial cells is mediated by a large class of periplasmic binding protein-dependent transport systems, members of the ATP-binding cassette superfamily. In the maltose transport system of Escherichia coli, the periplasmic maltose-binding protein binds its substrate maltose with high affinity and, in addition, stimulates the ATPase activity of the membrane-associated transporter when maltose is present. Vanadate inhibits maltose transport by trapping ADP in one of the two nucleotide-binding sites of the membrane transporter immediately after ATP hydrolysis, consistent with its ability to mimic the transition state of the γ-phosphate of ATP during hydrolysis. Here we report that the maltose-binding protein becomes tightly associated with the membrane transporter in the presence of vanadate and simultaneously loses its high affinity for maltose. These results suggest a general model explaining how ATP hydrolysis is coupled to substrate transport in which a binding protein stimulates the ATPase activity of its cognate transporter by stabilizing the transition state. PMID:11171984

  2. Transport of active ellipsoidal particles in ratchet potentials

    SciTech Connect

    Ai, Bao-Quan Wu, Jian-Chun

    2014-03-07

    Rectified transport of active ellipsoidal particles is numerically investigated in a two-dimensional asymmetric potential. The out-of-equilibrium condition for the active particle is an intrinsic property, which can break thermodynamical equilibrium and induce the directed transport. It is found that the perfect sphere particle can facilitate the rectification, while the needlelike particle destroys the directed transport. There exist optimized values of the parameters (the self-propelled velocity, the torque acting on the body) at which the average velocity takes its maximal value. For the ellipsoidal particle with not large asymmetric parameter, the average velocity decreases with increasing the rotational diffusion rate, while for the needlelike particle (very large asymmetric parameter), the average velocity is a peaked function of the rotational diffusion rate. By introducing a finite load, particles with different shapes (or different self-propelled velocities) will move to the opposite directions, which is able to separate particles of different shapes (or different self-propelled velocities)

  3. Mechanism of glucocorticoid effect on renal transport of phosphate.

    PubMed

    Turner, S T; Kiebzak, G M; Dousa, T P

    1982-11-01

    We explored whether glucocorticoid administration, a known stimulus of renal gluconeogenesis (GNG), could decrease avid inorganic phosphate (Pi) reabsorption in rats stabilized on low-phosphorus diet (LPD). Rats adapted to LPD were injected with the glucocorticoid (GCD) triamcinolone acetonide (1.25 or 2.5 mg.100 g body wt-1.day-1 ip) for 2 days; they showed a profound increase in urinary excretion of Pi during the injection period. In clearance studies GCD increased the clearance and fractional excretion of Pi but did not change the filtered load of Pi. Initial "uphill" Na+-gradient (Nao+ greater than Nai+)-dependent uptake of 32Pi by luminal brush-border membrane (BBM) vesicles prepared from renal cortex of rats treated with GCD was markedly (greater than 40%) decreased compared with control rats; Na+-gradient-dependent uptake of D-[3H]glucose was not diminished. At the "equilibrium" time interval, measured at 120 min, BBM vesicles from control and GCD-treated rats did not differ in the uptake of 32Pi or D-[3H]glucose. With kinetic analysis, BBM from GCD-treated rats showed a marked decrease (-40%) in the maximum velocity (Vmax) of initial Na+-dependent 32Pi uptake, but the apparent affinity of the BBM transport system for Pi (apparent Km = 0.078 mM Pi) was not different from that of controls. Alkaline phosphatase specific activity was much lower (-40%) in BBM from GCD-treated rats compared with controls, but the activities of three other BBM enzymes (maltase, leucine aminopeptidase, and gamma-glutamyl transferase) were not different. The addition of triamcinolone to BBM in vitro had no effect on either Na+-dependent uptake of 32Pi or alkaline phosphatase activity. The rate of GNG from alpha-ketoglutarate was significantly increased in cortical slices from GCD-treated rats adapted to LPD. Also, the NAD+-to-NADH ratio was higher in the renal cortex of GCD-treated rats, although the total content of NAD [NAD+ + NADH] was not different from controls. Renal excretory

  4. The molecular mechanism of ion-dependent gating in secondary transporters.

    PubMed

    Zhao, Chunfeng; Noskov, Sergei Yu

    2013-10-01

    LeuT-like fold Na-dependent secondary active transporters form a large family of integral membrane proteins that transport various substrates against their concentration gradient across lipid membranes, using the free energy stored in the downhill concentration gradient of sodium ions. These transporters play an active role in synaptic transmission, the delivery of key nutrients, and the maintenance of osmotic pressure inside the cell. It is generally believed that binding of an ion and/or a substrate drives the conformational dynamics of the transporter. However, the exact mechanism for converting ion binding into useful work has yet to be established. Using a multi-dimensional path sampling (string-method) followed by all-atom free energy simulations, we established the principal thermodynamic and kinetic components governing the ion-dependent conformational dynamics of a LeuT-like fold transporter, the sodium/benzyl-hydantoin symporter Mhp1, for an entire conformational cycle. We found that inward-facing and outward-facing states of Mhp1 display nearly the same free energies with an ion absent from the Na2 site conserved across the LeuT-like fold transporters. The barrier separating an apo-state from inward-facing or outward-facing states of the transporter is very low, suggesting stochastic gating in the absence of ion/substrate bound. In contrast, the binding of a Na2 ion shifts the free energy stabilizing the outward-facing state and promoting substrate binding. Our results indicate that ion binding to the Na2 site may also play a key role in the intracellular thin gate dynamics modulation by altering its interactions with the transmembrane helix 5 (TM5). The Potential of Mean Force (PMF) computations for a substrate entrance displays two energy minima that correspond to the locations of the main binding site S1 and proposed allosteric S2 binding site. However, it was found that substrate's binds to the site S1 ∼5 kcal/mol more favorable than that to the

  5. Tau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β

    PubMed Central

    Xu, Jordan C.; Fomenko, Vira; Miyamoto, Takashi; Suberbielle, Elsa; Knox, Joseph A.; Ho, Kaitlyn; Kim, Daniel H.; Yu, Gui-Qiu

    2015-01-01

    Axonal transport deficits in Alzheimer’s disease (AD) are attributed to amyloid β (Aβ) peptides and pathological forms of the microtubule-associated protein tau. Genetic ablation of tau prevents neuronal overexcitation and axonal transport deficits caused by recombinant Aβ oligomers. Relevance of these findings to naturally secreted Aβ and mechanisms underlying tau’s enabling effect are unknown. Here we demonstrate deficits in anterograde axonal transport of mitochondria in primary neurons from transgenic mice expressing familial AD-linked forms of human amyloid precursor protein. We show that these deficits depend on Aβ1–42 production and are prevented by tau reduction. The copathogenic effect of tau did not depend on its microtubule binding, interactions with Fyn, or potential role in neuronal development. Inhibition of neuronal activity, N-methyl-d-aspartate receptor function, or glycogen synthase kinase 3β (GSK3β) activity or expression also abolished Aβ-induced transport deficits. Tau ablation prevented Aβ-induced GSK3β activation. Thus, tau allows Aβ oligomers to inhibit axonal transport through activation of GSK3β, possibly by facilitating aberrant neuronal activity. PMID:25963821

  6. 49 CFR 37.61 - Public transportation programs and activities in existing facilities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Public transportation programs and activities in existing facilities. 37.61 Section 37.61 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Transportation Facilities § 37.61...

  7. 49 CFR 37.61 - Public transportation programs and activities in existing facilities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 1 2014-10-01 2014-10-01 false Public transportation programs and activities in existing facilities. 37.61 Section 37.61 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Transportation Facilities § 37.61...

  8. 49 CFR 37.61 - Public transportation programs and activities in existing facilities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Public transportation programs and activities in existing facilities. 37.61 Section 37.61 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Transportation Facilities § 37.61...

  9. 49 CFR 37.61 - Public transportation programs and activities in existing facilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Public transportation programs and activities in existing facilities. 37.61 Section 37.61 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Transportation Facilities § 37.61...

  10. 49 CFR 37.61 - Public transportation programs and activities in existing facilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Public transportation programs and activities in existing facilities. 37.61 Section 37.61 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Transportation Facilities § 37.61...

  11. Origin of traps and charge transport mechanism in hafnia

    SciTech Connect

    Islamov, D. R. Gritsenko, V. A.; Cheng, C. H.; Chin, A.

    2014-12-01

    In this study, we demonstrated experimentally and theoretically that oxygen vacancies are responsible for the charge transport in HfO{sub 2}. Basing on the model of phonon-assisted tunneling between traps, and assuming that the electron traps are oxygen vacancies, good quantitative agreement between the experimental and theoretical data of current-voltage characteristics was achieved. The thermal trap energy of 1.25 eV in HfO{sub 2} was determined based on the charge transport experiments.

  12. Atomistic mechanisms of rapid energy transport in light-harvesting molecules

    NASA Astrophysics Data System (ADS)

    Ohmura, Satoshi; Koga, Shiro; Akai, Ichiro; Shimojo, Fuyuki; Kalia, Rajiv K.; Nakano, Aiichiro; Vashishta, Priya

    2011-03-01

    Synthetic supermolecules such as π-conjugated light-harvesting dendrimers efficiently harvest energy from sunlight, which is of significant importance for the global energy problem. Key to their success is rapid transport of electronic excitation energy from peripheral antennas to photochemical reaction cores, the atomistic mechanisms of which remains elusive. Here, quantum-mechanical molecular dynamics simulation incorporating nonadiabatic electronic transitions reveals the key molecular motion that significantly accelerates the energy transport based on the Dexter mechanism.

  13. Regional differences in rat conjunctival ion transport activities.

    PubMed

    Yu, Dongfang; Thelin, William R; Rogers, Troy D; Stutts, M Jackson; Randell, Scott H; Grubb, Barbara R; Boucher, Richard C

    2012-10-01

    Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na(+) transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface.

  14. Regional differences in rat conjunctival ion transport activities

    PubMed Central

    Yu, Dongfang; Thelin, William R.; Rogers, Troy D.; Stutts, M. Jackson; Randell, Scott H.; Grubb, Barbara R.

    2012-01-01

    Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na+ transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface. PMID:22814399

  15. Chemically- and mechanically-mediated influences on the transport and mechanical characteristics of rock fractures

    SciTech Connect

    Min, K.-B.; Rutqvist, J.; Elsworth, D.

    2009-02-01

    A model is presented to represent changes in the mechanical and transport characteristics of fractured rock that result from coupled mechanical and chemical effects. The specific influence is the elevation of dissolution rates on contacting asperities, which results in a stress- and temperature-dependent permanent closure. A model representing this pressure-dissolution-like behavior is adapted to define the threshold and resulting response in terms of fundamental thermodynamic properties of a contacting fracture. These relations are incorporated in a stress-stiffening model of fracture closure to define the stress- and temperature-dependency of aperture loss and behavior during stress and temperature cycling. These models compare well with laboratory and field experiments, representing both decoupled isobaric and isothermal responses. The model was applied to explore the impact of these responses on heated structures in rock. The result showed a reduction in ultimate induced stresses over the case where chemical effects were not incorporated, with permanent reduction in final stresses after cooling to ambient conditions. Similarly, permeabilities may be lower than they were in the case where chemical effects were not considered, with a net reduction apparent even after cooling to ambient temperature. These heretofore-neglected effects may have a correspondingly significant impact on the performance of heated structures in rock, such as repositories for the containment of radioactive wastes.

  16. Engineering intracellular active transport systems as in vivo biomolecular tools.

    SciTech Connect

    Bachand, George David; Carroll-Portillo, Amanda

    2006-11-01

    Active transport systems provide essential functions in terms of cell physiology and metastasis. These systems, however, are also co-opted by invading viruses, enabling directed transport of the virus to and from the cell's nucleus (i.e., the site of virus replication). Based on this concept, fundamentally new approaches for interrogating and manipulating the inner workings of living cells may be achievable by co-opting Nature's active transport systems as an in vivo biomolecular tool. The overall goal of this project was to investigate the ability to engineer kinesin-based transport systems for in vivo applications, specifically the collection of effector proteins (e.g., transcriptional regulators) within single cells. In the first part of this project, a chimeric fusion protein consisting of kinesin and a single chain variable fragment (scFv) of an antibody was successfully produced through a recombinant expression system. The kinesin-scFv retained both catalytic and antigenic functionality, enabling selective capture and transport of target antigens. The incorporation of a rabbit IgG-specific scFv into the kinesin established a generalized system for functionalizing kinesin with a wide range of target-selective antibodies raised in rabbits. The second objective was to develop methods of isolating the intact microtubule network from live cells as a platform for evaluating kinesin-based transport within the cytoskeletal architecture of a cell. Successful isolation of intact microtubule networks from two distinct cell types was demonstrated using glutaraldehyde and methanol fixation methods. This work provides a platform for inferring the ability of kinesin-scFv to function in vivo, and may also serve as a three-dimensional scaffold for evaluating and exploiting kinesin-based transport for nanotechnological applications. Overall, the technology developed in this project represents a first-step in engineering active transport system for in vivo applications. Further

  17. Role of different scattering mechanisms on the temperature dependence of transport in graphene

    PubMed Central

    Sarkar, Suman; Amin, Kazi Rafsanjani; Modak, Ranjan; Singh, Amandeep; Mukerjee, Subroto; Bid, Aveek

    2015-01-01

    Detailed experimental and theoretical studies of the temperature dependence of the effect of different scattering mechanisms on electrical transport properties of graphene devices are presented. We find that for high mobility devices the transport properties are mainly governed by completely screened short range impurity scattering. On the other hand, for the low mobility devices transport properties are determined by both types of scattering potentials - long range due to ionized impurities and short range due to completely screened charged impurities. The results could be explained in the framework of Boltzmann transport equations involving the two independent scattering mechanisms. PMID:26608479

  18. A multiscale 3D finite element analysis of fluid/solute transport in mechanically loaded bone.

    PubMed

    Fan, Lixia; Pei, Shaopeng; Lucas Lu, X; Wang, Liyun

    2016-01-01

    The transport of fluid, nutrients, and signaling molecules in the bone lacunar-canalicular system (LCS) is critical for osteocyte survival and function. We have applied the fluorescence recovery after photobleaching (FRAP) approach to quantify load-induced fluid and solute transport in the LCS in situ, but the measurements were limited to cortical regions 30-50 μm underneath the periosteum due to the constrains of laser penetration. With this work, we aimed to expand our understanding of load-induced fluid and solute transport in both trabecular and cortical bone using a multiscaled image-based finite element analysis (FEA) approach. An intact murine tibia was first re-constructed from microCT images into a three-dimensional (3D) linear elastic FEA model, and the matrix deformations at various locations were calculated under axial loading. A segment of the above 3D model was then imported to the biphasic poroelasticity analysis platform (FEBio) to predict load-induced fluid pressure fields, and interstitial solute/fluid flows through LCS in both cortical and trabecular regions. Further, secondary flow effects such as the shear stress and/or drag force acting on osteocytes, the presumed mechano-sensors in bone, were derived using the previously developed ultrastructural model of Brinkman flow in the canaliculi. The material properties assumed in the FEA models were validated against previously obtained strain and FRAP transport data measured on the cortical cortex. Our results demonstrated the feasibility of this computational approach in estimating the fluid flux in the LCS and the cellular stimulation forces (shear and drag forces) for osteocytes in any cortical and trabecular bone locations, allowing further studies of how the activation of osteocytes correlates with in vivo functional bone formation. The study provides a promising platform to reveal potential cellular mechanisms underlying the anabolic power of exercises and physical activities in treating

  19. A multiscale 3D finite element analysis of fluid/solute transport in mechanically loaded bone

    PubMed Central

    Fan, Lixia; Pei, Shaopeng; Lucas Lu, X; Wang, Liyun

    2016-01-01

    The transport of fluid, nutrients, and signaling molecules in the bone lacunar–canalicular system (LCS) is critical for osteocyte survival and function. We have applied the fluorescence recovery after photobleaching (FRAP) approach to quantify load-induced fluid and solute transport in the LCS in situ, but the measurements were limited to cortical regions 30–50 μm underneath the periosteum due to the constrains of laser penetration. With this work, we aimed to expand our understanding of load-induced fluid and solute transport in both trabecular and cortical bone using a multiscaled image-based finite element analysis (FEA) approach. An intact murine tibia was first re-constructed from microCT images into a three-dimensional (3D) linear elastic FEA model, and the matrix deformations at various locations were calculated under axial loading. A segment of the above 3D model was then imported to the biphasic poroelasticity analysis platform (FEBio) to predict load-induced fluid pressure fields, and interstitial solute/fluid flows through LCS in both cortical and trabecular regions. Further, secondary flow effects such as the shear stress and/or drag force acting on osteocytes, the presumed mechano-sensors in bone, were derived using the previously developed ultrastructural model of Brinkman flow in the canaliculi. The material properties assumed in the FEA models were validated against previously obtained strain and FRAP transport data measured on the cortical cortex. Our results demonstrated the feasibility of this computational approach in estimating the fluid flux in the LCS and the cellular stimulation forces (shear and drag forces) for osteocytes in any cortical and trabecular bone locations, allowing further studies of how the activation of osteocytes correlates with in vivo functional bone formation. The study provides a promising platform to reveal potential cellular mechanisms underlying the anabolic power of exercises and physical activities in

  20. Mechanobiocatalysis: Modulating Enzymatic Activity with Mechanical Force

    DTIC Science & Technology

    2015-09-28

    displayed by enzymes and other materials. It was demonstrated that the application of forces to enzymes properly outfitted with polymers resulted in...intrinsic activities displayed by enzymes and other materials. It was demonstrated that the application of forces to enzymes properly outfitted with polymers ...of eYFP-containing polymer composites via the application of mechanical force, as well as showing that the photophysical properties displayed by

  1. Topological mechanics: from metamaterials to active matter

    NASA Astrophysics Data System (ADS)

    Vitelli, Vincenzo

    2015-03-01

    Mechanical metamaterials are artificial structures with unusual properties, such as negative Poisson ratio, bistability or tunable acoustic response, which originate in the geometry of their unit cell. At the heart of such unusual behavior is often a mechanism: a motion that does not significantly stretch or compress the links between constituent elements. When activated by motors or external fields, these soft motions become the building blocks of robots and smart materials. In this talk, we discuss topological mechanisms that possess two key properties: (i) their existence cannot be traced to a local imbalance between degrees of freedom and constraints (ii) they are robust against a wide range of structural deformations or changes in material parameters. The continuum elasticity of these mechanical structures is captured by non-linear field theories with a topological boundary term similar to topological insulators and quantum Hall systems. We present several applications of these concepts to the design and experimental realization of 2D and 3D topological structures based on linkages, origami, buckling meta-materials and lastly active media that break time-reversal symmetry.

  2. Unidirectional Transport Mechanism in an ATP Dependent Exporter

    PubMed Central

    2017-01-01

    ATP-binding cassette (ABC) transporters use the energy of ATP binding and hydrolysis to move a large variety of compounds across biological membranes. P-glycoprotein, involved in multidrug resistance, is the most investigated eukaryotic family member. Although a large number of biochemical and structural approaches have provided important information, the conformational dynamics underlying the coupling between ATP binding/hydrolysis and allocrite transport remains elusive. To tackle this issue, we performed molecular dynamic simulations for different nucleotide occupancy states of Sav1866, a prokaryotic P-glycoprotein homologue. The simulations reveal an outward-closed conformation of the transmembrane domain that is stabilized by the binding of two ATP molecules. The hydrolysis of a single ATP leads the X-loop, a key motif of the ATP binding cassette, to interfere with the transmembrane domain and favor its outward-open conformation. Our findings provide a structural basis for the unidirectionality of transport in ABC exporters and suggest a ratio of one ATP hydrolyzed per transport cycle. PMID:28386603

  3. Price Analysis of Railway Freight Transport under Marketing Mechanism

    NASA Astrophysics Data System (ADS)

    Shi, Ying; Fang, Xiaoping; Chen, Zhiya

    Regarding the problems in the reform of the railway tariff system and the pricing of the transport, by means of assaying the influence of the price elasticity on the artifice used for price, this article proposed multiple regressive model which analyzed price elasticity quantitatively. This model conclude multi-factors which influences on the price elasticity, such as the averagely railway freight charge, the averagely freight haulage of proximate supersede transportation mode, the GDP per capita in the point of origin, and a series of dummy variable which can reflect the features of some productive and consume demesne. It can calculate the price elasticity of different classes in different domains, and predict the freight traffic volume on different rate levels. It can calculate confidence-level, and evaluate the relevance of each parameter to get rid of irrelevant or little relevant variables. It supplied a good theoretical basis for directing the pricing of transport enterprises in market economic conditions, which is suitable for railway freight, passenger traffic and other transportation manner as well. SPSS (Statistical Package for the Social Science) software was used to calculate and analysis the example. This article realized the calculation by HYFX system(Ministry of Railways fund).

  4. The Role of Transport Mechanisms in Mycobacterium Tuberculosis Drug Resistance and Tolerance

    PubMed Central

    Sarathy, Jansy Passiflora; Dartois, Véronique; Lee, Edmund Jon Deoon

    2012-01-01

    In the fight against tuberculosis, cell wall permeation of chemotherapeutic agents remains a critical but largely unsolved question. Here we review the major mechanisms of small molecule penetration into and efflux from Mycobacterium tuberculosis and other mycobacteria, and outline how these mechanisms may contribute to the development of phenotypic drug tolerance and induction of drug resistance. M. tuberculosis is intrinsically recalcitrant to small molecule permeation thanks to its thick lipid-rich cell wall. Passive diffusion appears to account for only a fraction of total drug permeation. As in other bacterial species, influx of hydrophilic compounds is facilitated by water-filled open channels, or porins, spanning the cell wall. However, the diversity and density of M. tuberculosis porins appears lower than in enterobacteria. Besides, physiological adaptations brought about by unfavorable conditions are thought to reduce the efficacy of porins. While intracellular accumulation of selected drug classes supports the existence of hypothesized active drug influx transporters, efflux pumps contribute to the drug resistant phenotype through their natural abundance and diversity, as well as their highly inducible expression. Modulation of efflux transporter expression has been observed in phagocytosed, non-replicating persistent and multi-drug resistant bacilli. Altogether, M. tuberculosis has evolved both intrinsic properties and acquired mechanisms to increase its level of tolerance towards xenobiotic substances, by preventing or minimizing their entry. Understanding these adaptation mechanisms is critical to counteract the natural mechanisms of defense against toxic compounds and develop new classes of chemotherapeutic agents that positively exploit the influx and efflux pathways of mycobacteria. PMID:24281307

  5. Mechanically activated artificial cell by using microfluidics

    PubMed Central

    Ho, Kenneth K. Y.; Lee, Lap Man; Liu, Allen P.

    2016-01-01

    All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner. The microfluidic device is fabricated using multilayer soft lithography technology, and consists of a control layer and a deformable flow channel. Deflections of the PDMS membrane above the main microfluidic flow channels and trapping chamber array are independently regulated pneumatically by two sets of integrated microfluidic valves. We successfully compress and aspirate the double emulsions, which result in transient increase and permanent decrease in oil thickness, respectively. Finally, we demonstrate the influx of calcium ions as a response of our mechanically activated artificial cell through thinning of oil. The development of a microfluidic device to mechanically activate artificial cells creates new opportunities in force-activated synthetic biology. PMID:27610921

  6. Mechanically activated artificial cell by using microfluidics

    NASA Astrophysics Data System (ADS)

    Ho, Kenneth K. Y.; Lee, Lap Man; Liu, Allen P.

    2016-09-01

    All living organisms sense mechanical forces. Engineering mechanosensitive artificial cell through bottom-up in vitro reconstitution offers a way to understand how mixtures of macromolecules assemble and organize into a complex system that responds to forces. We use stable double emulsion droplets (aqueous/oil/aqueous) to prototype mechanosensitive artificial cells. In order to demonstrate mechanosensation in artificial cells, we develop a novel microfluidic device that is capable of trapping double emulsions into designated chambers, followed by compression and aspiration in a parallel manner. The microfluidic device is fabricated using multilayer soft lithography technology, and consists of a control layer and a deformable flow channel. Deflections of the PDMS membrane above the main microfluidic flow channels and trapping chamber array are independently regulated pneumatically by two sets of integrated microfluidic valves. We successfully compress and aspirate the double emulsions, which result in transient increase and permanent decrease in oil thickness, respectively. Finally, we demonstrate the influx of calcium ions as a response of our mechanically activated artificial cell through thinning of oil. The development of a microfluidic device to mechanically activate artificial cells creates new opportunities in force-activated synthetic biology.

  7. Activation energy-activation volume master plots for ion transport behavior in polymer electrolytes and supercooled molten salts.

    PubMed

    Ingram, Malcolm D; Imrie, Corrie T; Stoeva, Zlatka; Pas, Steven J; Funke, Klaus; Chandler, Howard W

    2005-09-08

    We demonstrate the use of activation energy versus activation volume "master plots" to explore ion transport in typical fragile glass forming systems exhibiting non-Arrhenius behavior. These systems include solvent-free salt complexes in poly(ethylene oxide) (PEO) and low molecular weight poly(propylene oxide) (PPO) and molten 2Ca(NO3)2.3KNO3 (CKN). Plots showing variations in apparent activation energy EA versus apparent activation volume VA are straight lines with slopes given by M = DeltaEA/DeltaVA. A simple ion transport mechanism is described where the rate determining step involves a dilatation (expressed as VA) around microscopic cavities and a corresponding work of expansion (EA). The slopes of the master plots M are equated to internal elastic moduli, which vary from 1.1 GPa for liquid PPO to 5.0 GPa for molten CKN on account of differing intermolecular forces in these materials.

  8. Activation of sucrose transport in defoliated Lolium perenne L.: an example of apoplastic phloem loading plasticity.

    PubMed

    Berthier, Alexandre; Desclos, Marie; Amiard, Véronique; Morvan-Bertrand, Annette; Demmig-Adams, Barbara; Adams, William W; Turgeon, Robert; Prud'homme, Marie-Pascale; Noiraud-Romy, Nathalie

    2009-07-01

    The pathway of carbon phloem loading was examined in leaf tissues of the forage grass Lolium perenne. The effect of defoliation (leaf blade removal) on sucrose transport capacity was assessed in leaf sheaths as the major carbon source for regrowth. The pathway of carbon transport was assessed via a combination of electron microscopy, plasmolysis experiments and plasma membrane vesicles (PMVs) purified by aqueous two-phase partitioning from the microsomal fraction. Results support an apoplastic phloem loading mechanism. Imposition of an artificial proton-motive force to PMVs from leaf sheaths energized an active, transient and saturable uptake of sucrose (Suc). The affinity of Suc carriers for Suc was 580 microM in leaf sheaths of undefoliated plants. Defoliation induced a decrease of K(m) followed by an increase of V(max). A transporter was isolated from stubble (including leaf sheaths) cDNA libraries and functionally expressed in yeast. The level of L.perenne SUcrose Transporter 1 (LpSUT1) expression increased in leaf sheaths in response to defoliation. Taken together, the results indicate that Suc transport capacity increased in leaf sheaths of L. perenne in response to leaf blade removal. This increase might imply de novo synthesis of Suc transporters, including LpSUT1, and may represent one of the mechanisms contributing to rapid refoliation.

  9. Transport mechanisms in SnO2(N+)/SiO(x)/Si(n) solar cells

    NASA Astrophysics Data System (ADS)

    Chambouleyron, I.; Marques, F. C.

    This paper refers to the transport mechanisms in SnO2(n+)/SiO(x)/Si(n) solar cells. I vs V curves at dark and under varying illumination conditions were measured in the temperature range 296-372 K. Three transport mechanisms, occurring at different biases, that dominate the electrical behavior of the cells, are identified. At low forward bias the dominant mechanism is thermoionic field emission. At intermediate bias recombination mechanism predominates. Finally at high forward biases the dominant mechanism is diffusion.

  10. Amyloid-β precursor protein: Multiple fragments, numerous transport routes and mechanisms.

    PubMed

    Muresan, Virgil; Ladescu Muresan, Zoia

    2015-05-15

    This review provides insight into the intraneuronal transport of the Amyloid-β Precursor Protein (APP), the prototype of an extensively posttranslationally modified and proteolytically cleaved transmembrane protein. Uncovering the intricacies of APP transport proves to be a challenging endeavor of cell biology research, deserving increased priority, since APP is at the core of the pathogenic process in Alzheimer's disease. After being synthesized in the endoplasmic reticulum in the neuronal soma, APP enters the intracellular transport along the secretory, endocytic, and recycling routes. Along these routes, APP undergoes cleavage into defined sets of fragments, which themselves are transported - mostly independently - to distinct sites in neurons, where they exert their functions. We review the currently known routes and mechanisms of transport of full-length APP, and of APP fragments, commenting largely on the experimental challenges posed by studying transport of extensively cleaved proteins. The review emphasizes the interrelationships between the proteolytic and posttranslational modifications, the intracellular transport, and the functions of the APP species. A goal remaining to be addressed in the future is the incorporation of the various views on APP transport into a coherent picture. In this review, the disease context is only marginally addressed; the focus is on the basic biology of APP transport under normal conditions. As shown, the studies of APP transport uncovered numerous mechanisms of transport, some of them conventional, and others, novel, awaiting exploration.

  11. Mechanism of FGF receptor dimerization and activation

    NASA Astrophysics Data System (ADS)

    Sarabipour, Sarvenaz; Hristova, Kalina

    2016-01-01

    Fibroblast growth factors (fgfs) are widely believed to activate their receptors by mediating receptor dimerization. Here we show, however, that the FGF receptors form dimers in the absence of ligand, and that these unliganded dimers are phosphorylated. We further show that ligand binding triggers structural changes in the FGFR dimers, which increase FGFR phosphorylation. The observed effects due to the ligands fgf1 and fgf2 are very different. The fgf2-bound dimer structure ensures the smallest separation between the transmembrane (TM) domains and the highest possible phosphorylation, a conclusion that is supported by a strong correlation between TM helix separation in the dimer and kinase phosphorylation. The pathogenic A391E mutation in FGFR3 TM domain emulates the action of fgf2, trapping the FGFR3 dimer in its most active state. This study establishes the existence of multiple active ligand-bound states, and uncovers a novel molecular mechanism through which FGFR-linked pathologies can arise.

  12. Active and passive calcium transport systems in plant cells. Progress report, May 1986--January 1991

    SciTech Connect

    Sze, H.

    1991-12-31

    The ability to change cytoplasmic Ca{sup 2+} levels ([Ca{sup 2+}]) by cells has made this cation a key regulator of many biological processes. Cytoplasmic [Ca{sup 2+}] is determined by the coordination of passive Ca{sup 2+} fluxes which increase cytosolic [Ca{sup 2+}] and active Ca{sup 2+} transport systems that lower cytosolic [Ca{sup 2+}]. The mechanisms by which plant cells achieve this is poorly understood. We have initially used isolated vesicles from the plasma membrane or organellar membranes to study Ca{sup 2+} transport systems in oat roots (a monocot) and carrot suspension cells (a dicot). The objectives of the proposal were to identify and characterize active (energy-dependent) and passive calcium transport systems that work together to regulate calcium levels in the cytoplasm of plant cells.

  13. Transport effects due to particle erosion mechanisms. [in planetary rings

    NASA Technical Reports Server (NTRS)

    Durisen, R. H.

    1984-01-01

    Various processes can erode the surfaces of planetary ring particles. Recent estimates for Saturn's rings suggest that a centimeter-thick surface layer could be eroded from an isolated ring particle in less than 1000 yr by meteoroid impacts alone. The atoms, molecules, and chips ejected from ring particles by erosion will arc across the rings along elliptical orbits. For moderate ring optical depths, ejecta will be absorbed or inelastically scattered upon reintersecting the ring plane. Continuous exchange of ejecta between different ring regions can lead to net radial transport of mass and angular momentum, to changes in particle sizes, and to the buildup of chip regoliths several centimeters deep on the surfaces of ring particles. Because most of the erosional ejecta are not lost but merely exchanged over short distances, the net erosion rate of the surfaces of these ring particles will be much less than that estimated for an isolated particle. Numerical solutions for time-dependent ballistic transport under various assumptions suggest pile-up and spillover effects especially near regions of preexisting high optical depth contrast, such as the inner edges of A and B rings. Global redistribution could be significant over billions of years. Other features in planetary ring systems may be influenced by ballistic transport.

  14. Effect of insulin-like factors on glucose transport activity in unweighted rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Henriksen, Erik J.; Ritter, Leslie S.

    1993-01-01

    The effect of 3 or 6 days of unweighting on glucose transport activity, as assessed by 2-deoxyglucose uptake, in soleus strips stimulated by maximally effective concentrations of insulin, IGF-I, vanadate, or phospholipase C (PLC) is examined. Progressively increased responses to maximally effective doses of insulin or insulin-like growth factor were observed after 3 and 6 days of unweighting compared with weight matched control strips. Enhanced maximal responses to vanadate (6 days only) and PLC (3 and 6 days) were also observed. The data provide support for the existance of postreceptor binding mechanisms for the increased action of insulin on the glucose transport system in unweighted rat skeletal muscle.

  15. The bacterial dicarboxylate transporter, VcINDY, uses a two-domain elevator-type mechanism

    PubMed Central

    Mulligan, Christopher; Fenollar-Ferrer, Cristina; Fitzgerald, Gabriel A.; Vergara-Jaque, Ariela; Kaufmann, Desirée; Li, Yan; Forrest, Lucy R.; Mindell, Joseph A.

    2016-01-01

    Secondary transporters use alternating access mechanisms to couple uphill substrate movement to downhill ion flux. Most known transporters utilize a “rocking bundle” motion, where the protein moves around an immobile substrate binding site. However, the glutamate transporter homolog, GltPh, translocates its substrate binding site vertically across the membrane, an “elevator” mechanism. Here, we used the “repeat swap” approach to computationally predict the outward-facing state of the Na+/succinate transporter VcINDY, from Vibrio cholerae. Our model predicts a substantial “elevator”-like movement of vcINDY’s substrate binding site, with a vertical translation of ~15 Å and a rotation of ~43°; multiple disulfide crosslinks which completely inhibit transport provide experimental confirmation and demonstrate that such movement is essential. In contrast, crosslinks across the VcINDY dimer interface preserve transport, revealing an absence of large scale coupling between protomers. PMID:26828963

  16. Drug transport mechanism of P-glycoprotein monitored by single molecule fluorescence resonance energy transfer

    NASA Astrophysics Data System (ADS)

    Ernst, S.; Verhalen, B.; Zarrabi, N.; Wilkens, S.; Börsch, M.

    2011-03-01

    In this work we monitor the catalytic mechanism of P-glycoprotein (Pgp) using single-molecule fluorescence resonance energy transfer (FRET). Pgp, a member of the ATP binding cassette family of transport proteins, is found in the plasma membrane of animal cells where it is involved in the ATP hydrolysis driven export of hydrophobic molecules. When expressed in the plasma membrane of cancer cells, the transport activity of Pgp can lead to the failure of chemotherapy by excluding the mostly hydrophobic drugs from the interior of the cell. Despite ongoing effort, the catalytic mechanism by which Pgp couples MgATP binding and hydrolysis to translocation of drug molecules across the lipid bilayer is poorly understood. Using site directed mutagenesis, we have introduced cysteine residues for fluorescence labeling into different regions of the nucleotide binding domains (NBDs) of Pgp. Double-labeled single Pgp molecules showed fluctuating FRET efficiencies during drug stimulated ATP hydrolysis suggesting that the NBDs undergo significant movements during catalysis. Duty cycle-optimized alternating laser excitation (DCO-ALEX) is applied to minimize FRET artifacts and to select the appropriate molecules. The data show that Pgp is a highly dynamic enzyme that appears to fluctuate between at least two major conformations during steady state turnover.

  17. Sediment transport mechanisms through the sustainable vegetated flow networks

    NASA Astrophysics Data System (ADS)

    Allen, Deonie; Haynes, Heather; Arthur, Scott

    2016-04-01

    Understanding the pollution treatment efficiency of a sustainable urban drainage (SuDS) asset or network requires the influx, transport, detention and discharge of the pollutant within the system. To date event specific monitoring of sediment (primarily total suspended solids) concentrations in the inflow and discharge from SuDS have been monitored. Long term analysis of where the sediment is transported to and the residency time of this pollutant within the SuDS asset or network have not been unraveled due to the difficulty in monitoring specific sediment particulate movement. Using REO tracing methodology, sediment particulate movement has become possible. In tracing sediment movement from an urban surface the internal residency and transportation of this sediment has illustrated SuDS asset differences in multi-event detention. Of key importance is the finding that sediment remains within the SuDS asset for extended periods of time, but that the location sediment detention changes. Thus, over multiple rainfall-runoff events sediment is seen to move through the SuDS assets and network proving the assumption that detained sediment is permanent and stationary to be inaccurate. Furthermore, mass balance analysis of SuDS sediment indicates that there is notable re-suspension and ongoing release of sediment from the SuDS over time and cumulative rainfall-runoff events. Continued monitoring of sediment deposition and concentration in suspension illustrates that sediment detention within SuDS decreases over time/multiple events, without stabilizing within a 12 month period. Repeated experiments show a consistent pattern of detention and release for the three SuDS networks monitored in Scotland. Through consideration of both rainfall and flow factors the drivers of sediment transport within the monitored SuDS have been identified. Within the limitation of this field study the key drivers to SuDS sediment detention efficiency (or transport of sediment through the system

  18. Water transport mechanism through open capillaries analyzed by direct surface modifications on biological surfaces

    NASA Astrophysics Data System (ADS)

    Ishii, Daisuke; Horiguchi, Hiroko; Hirai, Yuji; Yabu, Hiroshi; Matsuo, Yasutaka; Ijiro, Kuniharu; Tsujii, Kaoru; Shimozawa, Tateo; Hariyama, Takahiko; Shimomura, Masatsugu

    2013-10-01

    Some small animals only use water transport mechanisms passively driven by surface energies. However, little is known about passive water transport mechanisms because it is difficult to measure the wettability of microstructures in small areas and determine the chemistry of biological surfaces. Herein, we developed to directly analyse the structural effects of wettability of chemically modified biological surfaces by using a nanoliter volume water droplet and a hi-speed video system. The wharf roach Ligia exotica transports water only by using open capillaries in its legs containing hair- and paddle-like microstructures. The structural effects of legs chemically modified with a self-assembled monolayer were analysed, so that the wharf roach has a smart water transport system passively driven by differences of wettability between the microstructures. We anticipate that this passive water transport mechanism may inspire novel biomimetic fluid manipulations with or without a gravitational field.

  19. Water transport mechanism through open capillaries analyzed by direct surface modifications on biological surfaces.

    PubMed

    Ishii, Daisuke; Horiguchi, Hiroko; Hirai, Yuji; Yabu, Hiroshi; Matsuo, Yasutaka; Ijiro, Kuniharu; Tsujii, Kaoru; Shimozawa, Tateo; Hariyama, Takahiko; Shimomura, Masatsugu

    2013-10-23

    Some small animals only use water transport mechanisms passively driven by surface energies. However, little is known about passive water transport mechanisms because it is difficult to measure the wettability of microstructures in small areas and determine the chemistry of biological surfaces. Herein, we developed to directly analyse the structural effects of wettability of chemically modified biological surfaces by using a nanoliter volume water droplet and a hi-speed video system. The wharf roach Ligia exotica transports water only by using open capillaries in its legs containing hair- and paddle-like microstructures. The structural effects of legs chemically modified with a self-assembled monolayer were analysed, so that the wharf roach has a smart water transport system passively driven by differences of wettability between the microstructures. We anticipate that this passive water transport mechanism may inspire novel biomimetic fluid manipulations with or without a gravitational field.

  20. Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer.

    PubMed

    Wöhlert, David; Grötzinger, Maria J; Kühlbrandt, Werner; Yildiz, Özkan

    2015-12-04

    The common human pathogen Salmonella enterica takes up citrate as a nutrient via the sodium symporter SeCitS. Uniquely, our 2.5 Å x-ray structure of the SeCitS dimer shows three different conformations of the active protomer. One protomer is in the outside-facing state. Two are in different inside-facing states. All three states resolve the substrates in their respective binding environments. Together with comprehensive functional studies on reconstituted proteoliposomes, the structures explain the transport mechanism in detail. Our results indicate a six-step process, with a rigid-body 31° rotation of a helix bundle that translocates the bound substrates by 16 Å across the membrane. Similar transport mechanisms may apply to a wide variety of related and unrelated secondary transporters, including important drug targets.

  1. Mechanism of Na+-dependent citrate transport from the structure of an asymmetrical CitS dimer

    PubMed Central

    Wöhlert, David; Grötzinger, Maria J; Kühlbrandt, Werner; Yildiz, Özkan

    2015-01-01

    The common human pathogen Salmonella enterica takes up citrate as a nutrient via the sodium symporter SeCitS. Uniquely, our 2.5 Å x-ray structure of the SeCitS dimer shows three different conformations of the active protomer. One protomer is in the outside-facing state. Two are in different inside-facing states. All three states resolve the substrates in their respective binding environments. Together with comprehensive functional studies on reconstituted proteoliposomes, the structures explain the transport mechanism in detail. Our results indicate a six-step process, with a rigid-body 31° rotation of a helix bundle that translocates the bound substrates by 16 Å across the membrane. Similar transport mechanisms may apply to a wide variety of related and unrelated secondary transporters, including important drug targets. DOI: http://dx.doi.org/10.7554/eLife.09375.001 PMID:26636752

  2. Buffer transport mechanisms in intentionally carbon doped GaN heterojunction field effect transistors

    SciTech Connect

    Uren, Michael J.; Cäsar, Markus; Kuball, Martin; Gajda, Mark A.

    2014-06-30

    Temperature dependent pulsed and ramped substrate bias measurements are used to develop a detailed understanding of the vertical carrier transport in the buffer layers in a carbon doped GaN power heterojunction field effect transistor. Carbon doped GaN and multiple layers of AlGaN alloy are used in these devices to deliver an insulating and strain relieved buffer with high breakdown voltage capability. However, understanding of the detailed physical mechanism for its operation is still lacking. At the lowest electric fields (<10 MV/m), charge redistribution within the C doped layer is shown to occur by hole conduction in the valence band with activation energy 0.86 eV. At higher fields, leakage between the two-dimensional electron gas and the buffer dominates occurring by a Poole-Frenkel mechanism with activation energy ∼0.65 eV, presumably along threading dislocations. At higher fields still, the strain relief buffer starts to conduct by a field dependent process. Balancing the onset of these leakage mechanisms is essential to allow the build-up of positive rather than negative space charge, and thus minimize bulk-related current-collapse in these devices.

  3. Experimental thermal transport evolution of silane activated nano-clay reinforced styrene butadiene elastomeric nanocomposites

    NASA Astrophysics Data System (ADS)

    Iqbal, S. S.; Iqbal, N.; Jamil, T.; Bashir, A.; Shahid, M.

    2016-08-01

    In this study, silane activated nanoclay was reinforced in styrene butadiene rubber (SBR) to enhance the thermal resistance/stability and mechanical properties of SBR. silane activated nanoclay with variant concentrations was impregnated in the rubber matrix to fabricate polymer nanocomposites under control processing conditions. Experimental thermal transport, thermal oxidation, phase transition study, and mechanical properties of the nanocomposite specimens were carried out. Thermal insulation, thermal stability, and heat flow response were remarkably enhanced with the addition of nanokaolinite in the polymer matrix. Phase transition temperatures, their corresponding enthalpies, tensile strength, elastic modulus, elongation at break and hardness of the rubber composites were positively influenced with the filler incorporation into the host matrix. The Even dispersion of nanoreinforcements, morphological and compositional analyses of the thermal transport tested specimens were performed using scanning electron microscopy and energy dispersive spectroscopy, respectively.

  4. Recent Cooperative Research Activities of HDD and Flexible Media Transport Technologies in Japan

    NASA Astrophysics Data System (ADS)

    Ono, Kyosuke

    This paper presents the recent status of industry-university cooperative research activities in Japan on the mechatronics of information storage and input/output equipment. There are three research committees for promoting information exchange on technical problems and research topics of head-disk interface in hard disk drives (HDD), flexible media transport and image printing processes which are supported by the Japan Society of Mechanical Engineering (JSME), the Japanese Society of Tribologists (JAST) and the Japan Society of Precision Engineering (JSPE). For hard disk drive technology, the Storage Research Consortium (SRC) is supporting more than 40 research groups in various different universities to perform basic research for future HDD technology. The past and present statuses of these activities are introduced, particularly focusing on HDD and flexible media transport mechanisms.

  5. Mechanism of electrodialytic ion transport through solvent extraction membranes

    SciTech Connect

    Moskvin, L.N.; Shmatko, A.G.; Krasnoperov, V.M.

    1987-02-01

    The authors construct a mathematical model for electrodialysis and solvent extraction via an ion-selective ion exchange membrane and accounts for the electrochemical, ion exchange, and diffusional behavior of the processes including their dependence on component concentration and current and voltage. The model is tested against experimental data for the electrodialytic transport of anionic platinum complexes of chlorides from hydrochloric acid solution through tributylphosphate membranes. The platinum concentration in the aqueous solution was determined by gamma spectroscopy obtained via platinum 191 as a radiotracer.

  6. Transport Properties of Melanosomes along Microtubules Interpreted by a Tug-of-War Model with Loose Mechanical Coupling

    PubMed Central

    Bouzat, Sebastián; Levi, Valeria; Bruno, Luciana

    2012-01-01

    In this work, we explored theoretically the transport of organelles driven along microtubules by molecular motors of opposed polarities using a stochastic model that considers a Langevin dynamics for the cargo, independent cargo-motor linkers and stepping motion for the motors. It has been recently proposed that the stiffness of the motor plays an important role when multiple motors collectively transport a cargo. Therefore, we considered in our model the recently reported values for the stiffness of the cargo-motor linker determined in living cells (∼0.01 pN/nm, [1]) which is significantly lower than the motor stiffness obtained in in vitro assays and used in previous studies. Our model could reproduce the multimodal velocity distributions and typical trajectory characteristics including the properties of the reversions in the overall direction of motion observed during melanosome transport along microtubules in Xenopus laevis melanophores. Moreover, we explored the contribution of the different motility states of the cargo-motor system to the different modes of the velocity distributions and could identify the microscopic mechanisms of transport leading to trajectories compatible with those observed in living cells. Finally, by changing the attachment and detachment rates, the model could reproduce the different velocity distributions observed during melanosome transport along microtubules in Xenopus laevis melanophores stimulated for aggregation and dispersion. Our analysis suggests that active tug-of-war processes with loose mechanical coupling can account for several aspects of cargo transport along microtubules in living cells. PMID:22952716

  7. Transport properties of melanosomes along microtubules interpreted by a tug-of-war model with loose mechanical coupling.

    PubMed

    Bouzat, Sebastián; Levi, Valeria; Bruno, Luciana

    2012-01-01

    In this work, we explored theoretically the transport of organelles driven along microtubules by molecular motors of opposed polarities using a stochastic model that considers a Langevin dynamics for the cargo, independent cargo-motor linkers and stepping motion for the motors. It has been recently proposed that the stiffness of the motor plays an important role when multiple motors collectively transport a cargo. Therefore, we considered in our model the recently reported values for the stiffness of the cargo-motor linker determined in living cells (∼0.01 pN/nm,) which is significantly lower than the motor stiffness obtained in in vitro assays and used in previous studies. Our model could reproduce the multimodal velocity distributions and typical trajectory characteristics including the properties of the reversions in the overall direction of motion observed during melanosome transport along microtubules in Xenopus laevis melanophores. Moreover, we explored the contribution of the different motility states of the cargo-motor system to the different modes of the velocity distributions and could identify the microscopic mechanisms of transport leading to trajectories compatible with those observed in living cells. Finally, by changing the attachment and detachment rates, the model could reproduce the different velocity distributions observed during melanosome transport along microtubules in Xenopus laevis melanophores stimulated for aggregation and dispersion. Our analysis suggests that active tug-of-war processes with loose mechanical coupling can account for several aspects of cargo transport along microtubules in living cells.

  8. Mechanisms Underlying Food-Drug Interactions: Inhibition of Intestinal Metabolism and Transport

    PubMed Central

    Won, Christina S.; Oberlies, Nicholas H.; Paine, Mary F.

    2012-01-01

    Food-drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. These interactions often reflect prandial-associated changes in the extent and/or rate of systemic drug exposure. Physiologic and physicochemical mechanisms underlying food effects on drug disposition are well-characterized. However, biochemical mechanisms involving drug metabolizing enzymes and transport proteins remain underexplored. Several plant-derived beverages have been shown to modulate enzymes and transporters in the intestine, leading to altered pharmacokinetic (PK) and potentially negative pharmacodynamic (PD) outcomes. Commonly consumed fruit juices, teas, and alcoholic drinks contain phytochemicals that inhibit intestinal cytochrome P450 and phase II conjugation enzymes, as well as uptake and efflux transport proteins. Whereas myriad phytochemicals have been shown to inhibit these processes in vitro, translation to the clinic has been deemed insignificant or undetermined. An overlooked prerequisite for elucidating food effects on drug PK is thorough knowledge of causative bioactive ingredients. Substantial variability in bioactive ingredient composition and activity of a given dietary substance poses a challenge in conducting robust food-drug interaction studies. This confounding factor can be addressed by identifying and characterizing specific components, which could be used as marker compounds to improve clinical trial design and quantitatively predict food effects. Interpretation and integration of data from in vitro, in vivo, and in silico studies require collaborative expertise from multiple disciplines, from botany to clinical pharmacology (i.e., plant to patient). Development of more systematic methods and guidelines is needed to address the general lack of information on examining drug-dietary substance interactions prospectively. PMID:22884524

  9. Dependence of spontaneous neuronal firing and depolarisation block on astroglial membrane transport mechanisms.

    PubMed

    Øyehaug, Leiv; Østby, Ivar; Lloyd, Catherine M; Omholt, Stig W; Einevoll, Gaute T

    2012-02-01

    Exposed to a sufficiently high extracellular potassium concentration ([K( + )]₀), the neuron can fire spontaneous discharges or even become inactivated due to membrane depolarisation ('depolarisation block'). Since these phenomena likely are related to the maintenance and propagation of seizure discharges, it is of considerable importance to understand the conditions under which excess [K( + )]₀ causes them. To address the putative effect of glial buffering on neuronal activity under elevated [K( + )](o) conditions, we combined a recently developed dynamical model of glial membrane ion and water transport with a Hodgkin-Huxley type neuron model. In this interconnected glia-neuron model we investigated the effects of natural heterogeneity or pathological changes in glial membrane transporter density by considering a large set of models with different, yet empirically plausible, sets of model parameters. We observed both the high [K( + )]₀-induced duration of spontaneous neuronal firing and the prevalence of depolarisation block to increase when reducing the magnitudes of the glial transport mechanisms. Further, in some parameter regions an oscillatory bursting spiking pattern due to the dynamical coupling of neurons and glia was observed. Bifurcation analyses of the neuron model and of a simplified version of the neuron-glia model revealed further insights about the underlying mechanism behind these phenomena. The above insights emphasise the importance of combining neuron models with detailed astroglial models when addressing phenomena suspected to be influenced by the astroglia-neuron interaction. To facilitate the use of our neuron-glia model, a CellML version of it is made publicly available.

  10. Mechanisms underlying food-drug interactions: inhibition of intestinal metabolism and transport.

    PubMed

    Won, Christina S; Oberlies, Nicholas H; Paine, Mary F

    2012-11-01

    Food-drug interaction studies are critical to evaluate appropriate dosing, timing, and formulation of new drug candidates. These interactions often reflect prandial-associated changes in the extent and/or rate of systemic drug exposure. Physiologic and physicochemical mechanisms underlying food effects on drug disposition are well-characterized. However, biochemical mechanisms involving drug metabolizing enzymes and transport proteins remain underexplored. Several plant-derived beverages have been shown to modulate enzymes and transporters in the intestine, leading to altered pharmacokinetic (PK) and potentially negative pharmacodynamic (PD) outcomes. Commonly consumed fruit juices, teas, and alcoholic drinks contain phytochemicals that inhibit intestinal cytochrome P450 and phase II conjugation enzymes, as well as uptake and efflux transport proteins. Whereas myriad phytochemicals have been shown to inhibit these processes in vitro, translation to the clinic has been deemed insignificant or undetermined. An overlooked prerequisite for elucidating food effects on drug PK is thorough knowledge of causative bioactive ingredients. Substantial variability in bioactive ingredient composition and activity of a given dietary substance poses a challenge in conducting robust food-drug interaction studies. This confounding factor can be addressed by identifying and characterizing specific components, which could be used as marker compounds to improve clinical trial design and quantitatively predict food effects. Interpretation and integration of data from in vitro, in vivo, and in silico studies require collaborative expertise from multiple disciplines, from botany to clinical pharmacology (i.e., plant to patient). Development of more systematic methods and guidelines is needed to address the general lack of information on examining drug-dietary substance interactions prospectively.

  11. [Effect of nitrates on active transport of iodine].

    PubMed

    Szökeová, E; Tajtáková, M; Mirossay, L; Mojzis, J; Langer, P; Marcinová, E; Petrovicová, J; Zemberová, E; Bodnár, J

    2001-11-01

    Active iodine transport into the thyrocyte is catalyzed by the transmembrane transport protein Na+/J- symport (NIS) Nitrates can expel iodine from the bond with this transport protein which was found not only in the thyrocyte membrane but also in the cell membrane of the gastric mucosa. The weight of the thyroid gland in mg was significantly greater even when calculated in relation to body weight in the NIT group of rats who were given for 6 days nitrate by gastric tube (100 mg/kg/day) as compared with controls (CON) 17.56 +/- 8.4, 0.07 +/- 0.03/12.10 +/- 9.57, 0.05 +/- 0.03, P < or = 0.01. A lower thyroid activity in per cent calculated per 1 mg of its weight (1.39 +/- 1.0/2.22 +/- 0.9, P < or = 0.01), a higher activity in blood before removal of the thyroid gland (8.54 +/- 4.09/5.45 +/- 2.78) and a lower one after removal of the thyroid gland (1.09 +/- 0.05/0.21 +/- 0.10) before oral administration of I131 in group NIT, suggests a negative effect of nitrates on active iodine transport not only at the level of the thyrocyte but also possible interaction with iodine at the level of the digestive tract. A significantly higher serum level of TT3 in group NIT (0.66 +/- 0.27/0.44 +/- 0.21, P < or = 0.01 regardless of the TSH serum level (2.31 +/- 1.83/2.64 +/- 1.52) and T4 (22.72 +/- 8.2/25 +/- 11.0) suggests a qualitative change in thyroid hormone production in favour of T3 caused even by short-term nitrate administration.

  12. The Asymmetric Active Coupler: Stable Nonlinear Supermodes and Directed Transport

    PubMed Central

    Kominis, Yannis; Bountis, Tassos; Flach, Sergej

    2016-01-01

    We consider the asymmetric active coupler (AAC) consisting of two coupled dissimilar waveguides with gain and loss. We show that under generic conditions, not restricted by parity-time symmetry, there exist finite-power, constant-intensity nonlinear supermodes (NS), resulting from the balance between gain, loss, nonlinearity, coupling and dissimilarity. The system is shown to possess non-reciprocal dynamics enabling directed power transport functionality. PMID:27640818

  13. Active intracellular transport in metastatic cells studied by spatial light interference microscopy

    NASA Astrophysics Data System (ADS)

    Ceballos, Silvia; Kandel, Mikhail; Sridharan, Shamira; Majeed, Hassaan; Monroy, Freddy; Popescu, Gabriel

    2015-11-01

    Spatiotemporal patterns of intracellular transport are very difficult to quantify and, consequently, continue to be insufficiently understood. While it is well documented that mass trafficking inside living cells consists of both random and deterministic motions, quantitative data over broad spatiotemporal scales are lacking. We studied the intracellular transport in live cells using spatial light interference microscopy, a high spatiotemporal resolution quantitative phase imaging tool. The results indicate that in the cytoplasm, the intracellular transport is mainly active (directed, deterministic), while inside the nucleus it is both active and passive (diffusive, random). Furthermore, we studied the behavior of the two-dimensional mass density over 30 h in HeLa cells and focused on the active component. We determined the standard deviation of the velocity distribution at the point of cell division for each cell and compared the standard deviation velocity inside the cytoplasm and the nucleus. We found that the velocity distribution in the cytoplasm is consistently broader than in the nucleus, suggesting mechanisms for faster transport in the cytosol versus the nucleus. Future studies will focus on improving phase measurements by applying a fluorescent tag to understand how particular proteins are transported inside the cell.

  14. 77 FR 71430 - New Agency Information Collection Activity Under OMB Review: Public Transportation Baseline...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-30

    ... SECURITY Transportation Security Administration New Agency Information Collection Activity Under OMB Review: Public Transportation Baseline Assessment for Security Enhancement (BASE) Program AGENCY: Transportation Security Administration, DHS. ACTION: 30-day notice. SUMMARY: This notice announces that the...

  15. Tuning contact transport mechanisms in bilayer MoSe2 transistors up to Fowler-Nordheim regime

    NASA Astrophysics Data System (ADS)

    Mouafo, L. D. N.; Godel, F.; Froehlicher, G.; Berciaud, S.; Doudin, B.; Venkata Kamalakar, M.; Dayen, J.-F.

    2017-03-01

    Atomically thin molybdenum diselenide (MoSe2) is an emerging two-dimensional (2D) semiconductor with significant potential for electronic, optoelectronic, spintronic applications and a common platform for their possible integration. Tuning interface charge transport between such new 2D materials and metallic electrodes is a key issue in 2D device physics and engineering. Here, we report tunable interface charge transport in bilayer MoSe2 field effect transistors with Ti/Au contacts showing high on/off ratio up to 107 at room temperature. Our experiments reveal a detailed map of transport mechanisms obtained by controlling the interface band bending profile via temperature, gate and source-drain bias voltages. This comprehensive investigation leads to demarcating regimes and tuning in transport mechanisms while controlling the interface barrier profile. The careful analysis allows us to identify thermally activated regime at low carrier density, and Schottky barrier driven mechanisms at higher carrier density demonstrating the transition from low-field direct tunneling/ thermionic emission to high-field Fowler-Nordheim tunneling. Furthermore, we show that the transition voltage V trans to Fowler-Nordheim correlates directly to the difference between the chemical potential of the metal electrode and the conduction band minimum in the 2D semiconductor, which opens up opportunities for new theoretical and experimental investigations. Our approach being generic can be extended to other 2D materials, and the possibility of tuning contact transport regimes is promising for designing MoSe2 device applications.

  16. ALMA Binary Data Transport Mechanism using VOTable Headers

    NASA Astrophysics Data System (ADS)

    Wicenec, A.; Meuss, H.; Pisano, J.

    2006-07-01

    ALMA will produce very large data rates and volumes. In full operation the correlator will generate up to 60 MB/s of visibility data. These data have to be transported from the correlator on the high site (5000 m) to the ALMA archive, the telescope calibration and the quick-look subsystems, which are all located at the low site (2500 m) some 40 km away. A dedicated fiber connection between the sites is under construction and the interfaces between the subsystems are under development. The actual transport format produced by the correlator has been defined and implemented and is described in this paper in more detail. The format is derived from the SOAP with attachments [1], but instead of the SOAP XML envelope it is using a slightly modified VOTable [2] to keep the description of the binary data. The VOTable uses content ID pointers (CID, RFC2111 [3]) to refer to the binary parts contained in the same Multipart/Related (RFC2387 [4]) container. Such Multipart/Related containers are constructed for each ALMA integration and sent through a multimedia streaming connection implemented in CORBA (TAO[5, 6]).

  17. Transport mechanisms in conducting polymers: do general behaviours exis

    NASA Astrophysics Data System (ADS)

    Travers, J. P.

    1998-06-01

    We review several studies of transport properties of conducting polymers (CP) as a function of a parameter related to their structure or microstructure. We show that in strongly disordered CP, electron transport is dominated by hopping between conducting grains separated by insulating barriers. Although the nature of the metal-insulator transition is still a controversial topic in weakly disordered CP, several results indicate that heterogeneities play an important role. Thus heterogeneous disorder seems to control the conductivity of a large majority of CP. Plusieurs études sur la conductivité des polymères conducteurs (PC) en relation avec la microstructure sont rassemblées. Dans les PC très désordonnés, les sauts entre grains conducteurs séparés par des barrières isolantes dominent la conduction. Bien que la situation soit moins claire dans les PC peu désordonnés, des résultats indiquent que les hétérogénéités y jouent un rôle important. Ainsi, le désordre de nature hétérogène semble contrôler la conductivité de la grande majorité des PC.

  18. Turbulence elasticity—A new mechanism for transport barrier dynamics

    NASA Astrophysics Data System (ADS)

    Guo, Z. B.; Diamond, P. H.; Kosuga, Y.; Gürcan, Ö. D.

    2014-09-01

    We present a new, unified model of transport barrier formation in "elastic" drift wave-zonal flow (DW-ZF) turbulence. A new physical quantity—the delay time (i.e., the mixing time for the DW turbulence)—is demonstrated to parameterize each stage of the transport barrier formation. Quantitative predictions for the onset of limit-cycle-oscillation (LCO) among DW and ZF intensities (also denoted as I-mode) and I-mode to high-confinement mode (H-mode) transition are also given. The LCO occurs when the ZF shearing rate (|ZF'|) enters the regime Δωk<|ZF'|<τcr-1, where Δωk is the local turbulence decorrelation rate and τcr is the threshold delay time. In the basic predator-prey feedback system, τcr is also derived. The I-H transition occurs when |E ×B'|>τcr-1, where the mean E × B shear flow driven by ion pressure "locks" the DW-ZF system to the H-mode by reducing the delay time below the threshold value.

  19. Angler awareness of aquatic nuisance species and potential transport mechanisms

    USGS Publications Warehouse

    Gates, K.K.; Guy, C.S.; Zale, A.V.; Horton, T.B.

    2009-01-01

    The role anglers play in transporting aquatic nuisance species (ANS) is important in managing infestations and preventing introductions. The objectives of this study were to: (1) quantify angler movement patterns in southwestern Montana, ANS awareness and equipment cleaning practices; and (2) quantify the amount of soil transported on boots and waders. Mean distance travelled by residents from their home to the survey site was 115 km (??17, 95% CI). Mean distance travelled by non-residents was 1738 km (??74). Fifty-one percent of residents and 49% of non-residents reported occasionally, rarely or never cleaning their boots and waders between uses. Mean weight of soil carried on one boot leg was 8.39 g (??1.50). Movement and equipment cleaning practices of anglers in southwestern Montana suggest that future control of ANS dispersal may require restricting the use of felt-soled wading boots, requiring river-specific wading equipment or providing cleaning stations and requiring their use. ?? 2009 Blackwell Publishing Ltd.

  20. Turbulence elasticity—A new mechanism for transport barrier dynamics

    SciTech Connect

    Guo, Z. B.; Diamond, P. H.; Kosuga, Y.; Gürcan, Ö. D.

    2014-09-15

    We present a new, unified model of transport barrier formation in “elastic” drift wave-zonal flow (DW-ZF) turbulence. A new physical quantity—the delay time (i.e., the mixing time for the DW turbulence)—is demonstrated to parameterize each stage of the transport barrier formation. Quantitative predictions for the onset of limit-cycle-oscillation (LCO) among DW and ZF intensities (also denoted as I-mode) and I-mode to high-confinement mode (H-mode) transition are also given. The LCO occurs when the ZF shearing rate (|〈v〉{sub ZF}{sup ′}|) enters the regime Δω{sub k}<|〈V〉{sub ZF}{sup ′}|<τ{sub cr}{sup −1}, where Δω{sub k} is the local turbulence decorrelation rate and τ{sub cr} is the threshold delay time. In the basic predator-prey feedback system, τ{sub cr} is also derived. The I-H transition occurs when |〈V〉{sub E×B}{sup ′}|>τ{sub cr}{sup −1}, where the mean E × B shear flow driven by ion pressure “locks” the DW-ZF system to the H-mode by reducing the delay time below the threshold value.

  1. Molecular Mechanisms of DNA Replication Checkpoint Activation

    PubMed Central

    Recolin, Bénédicte; van der Laan, Siem; Tsanov, Nikolay; Maiorano, Domenico

    2014-01-01

    The major challenge of the cell cycle is to deliver an intact, and fully duplicated, genetic material to the daughter cells. To this end, progression of DNA synthesis is monitored by a feedback mechanism known as replication checkpoint that is untimely linked to DNA replication. This signaling pathway ensures coordination of DNA synthesis with cell cycle progression. Failure to activate this checkpoint in response to perturbation of DNA synthesis (replication stress) results in forced cell division leading to chromosome fragmentation, aneuploidy, and genomic instability. In this review, we will describe current knowledge of the molecular determinants of the DNA replication checkpoint in eukaryotic cells and discuss a model of activation of this signaling pathway crucial for maintenance of genomic stability. PMID:24705291

  2. Mechanism and active variety of allelochemicals

    USGS Publications Warehouse

    Peng, S.-L.; Wen, J.; Guo, Q.-F.

    2004-01-01

    This article summarizes allelochemicals' active variety, its potential causes and function mechanisms. Allelochemicals' activity varies with temperature, photoperiod, water and soils during natural processes, with its initial concentration, compound structure and mixed degree during functional processes, with plant accessions, tissues and maturity within-species, and with research techniques and operation processes. The prospective developmental aspects of allelopathy studies in the future are discussed. Future research should focus on: (1) to identify and purify allelochemicals more effectively, especially for agriculture, (2) the functions of allelopathy at the molecular structure level, (3) using allelopathy to explain plant species interactions, (4) allelopathy as a driving force of succession, and (5) the significance of allelopathy in the evolutionary processes.

  3. Glucose elevates NITRATE TRANSPORTER2.1 protein levels and nitrate transport activity independently of its HEXOKINASE1-mediated stimulation of NITRATE TRANSPORTER2.1 expression.

    PubMed

    de Jong, Femke; Thodey, Kate; Lejay, Laurence V; Bevan, Michael W

    2014-01-01

    Mineral nutrient uptake and assimilation is closely coordinated with the production of photosynthate to supply nutrients for growth. In Arabidopsis (Arabidopsis thaliana), nitrate uptake from the soil is mediated by genes encoding high- and low-affinity transporters that are transcriptionally regulated by both nitrate and photosynthate availability. In this study, we have studied the interactions of nitrate and glucose (Glc) on gene expression, nitrate transport, and growth using glucose-insensitive2-1 (gin2-1), which is defective in sugar responses. We confirm and extend previous work by showing that HEXOKINASE1-mediated oxidative pentose phosphate pathway (OPPP) metabolism is required for Glc-mediated NITRATE TRANSPORTER2.1 (NRT2.1) expression. Treatment with pyruvate and shikimate, two products derived from intermediates of the OPPP that are destined for amino acid production, restores wild-type levels of NRT2.1 expression, suggesting that metabolites derived from OPPP metabolism can, together with Glc, directly stimulate high levels of NRT2.1 expression. Nitrate-mediated NRT2.1 expression is not influenced by gin2-1, showing that Glc does not influence NRT2.1 expression through nitrate-mediated mechanisms. We also show that Glc stimulates NRT2.1 protein levels and transport activity independently of its HEXOKINASE1-mediated stimulation of NRT2.1 expression, demonstrating another possible posttranscriptional mechanism influencing nitrate uptake. In gin2-1 plants, nitrate-responsive biomass growth was strongly reduced, showing that the supply of OPPP metabolites is essential for assimilating nitrate for growth.

  4. Guide to innovative financing mechanisms for mass transportation: an update

    SciTech Connect

    Not Available

    1985-12-01

    The document provides an overview of nonstandard techniques currently being used to finance transit capital and operating expenses. An update of a study, the report focused on six types of mechanisms: assessments, taxes and user charges, use of property and property rights, issuance of debt, contracted services, and voluntary participation programs. A new section, Initiatives and Ideas, discusses local funding of community services like Montgomery County, Maryland's Ride On, franchise approaches, and nonsubsidized bus and vanpool services. The report is structured in two independant parts: the first describes the theoretical background of each technique, and is keyed to a second part, which describes typical applications of the mechanism.

  5. Aromatic isophthalamides aggregate in lipid bilayers: evidence for a cooperative transport mechanism.

    PubMed

    Berry, Stuart N; Busschaert, Nathalie; Frankling, Charlotte L; Salter, Dale; Gale, Philip A

    2015-03-14

    The synthesis and anion transport properties of a series of transmembrane anion transporters based on an isophthalamide scaffold with phenyl, naphthyl or anthracenyl central rings are reported. Anion transport studies using POPC vesicles, showed that the compounds have Hill coefficients >1. This is indicative of higher order complex formation, evidence that leads us to suggest that the compounds are not functioning solely as mobile carriers but rather that a cooperative transport mechanism is being observed. Fluorescence spectroscopy was used to show that the compounds aggregate in the phospholipid bilayer, which provides evidence that these compounds function as a self-assembled anion-conducting aggregate.

  6. Elastic tunneling charge transport mechanisms in silicon quantum dots / Si O 2 thin films and superlattices

    NASA Astrophysics Data System (ADS)

    Illera, S.; Prades, J. D.; Cirera, A.

    2015-05-01

    The role of different charge transport mechanisms in Si / Si O 2 structures has been studied. A theoretical model based on the Transfer Hamiltonian Formalism has been developed to explain experimental current trends in terms of three different elastic tunneling processes: (1) trap assisted tunneling; (2) transport through an intermediate quantum dot; and (3) direct tunneling between leads. In general, at low fields carrier transport is dominated by the quantum dots whereas, for moderate and high fields, transport through deep traps inherent to the SiO2 is the most relevant process. Besides, current trends in Si / Si O 2 superlattice structure have been properly reproduced.

  7. One-dimensional potential of mean force underestimates activation barrier for transport across flexible lipid membranes

    NASA Astrophysics Data System (ADS)

    Kopelevich, Dmitry I.

    2013-10-01

    Transport of a fullerene-like nanoparticle across a lipid bilayer is investigated by coarse-grained molecular dynamics (MD) simulations. Potentials of mean force (PMF) acting on the nanoparticle in a flexible bilayer suspended in water and a bilayer restrained to a flat surface are computed by constrained MD simulations. The rate of the nanoparticle transport into the bilayer interior is predicted using one-dimensional Langevin models based on these PMFs. The predictions are compared with the transport rates obtained from a series of direct (unconstrained) MD simulations of the solute transport into the flexible bilayer. It is observed that the PMF acting on the solute in the flexible membrane underestimates the transport rate by more than an order of magnitude while the PMF acting on the solute in the restrained membrane yields an accurate estimate of the activation energy for transport into the flexible membrane. This paradox is explained by a coexistence of metastable membrane configurations for a range of the solute positions inside and near the flexible membrane. This leads to a significant reduction of the contribution of the transition state to the mean force acting on the solute. Restraining the membrane shape ensures that there is only one stable membrane configuration corresponding to each solute position and thus the transition state is adequately represented in the PMF. This mechanism is quite general and thus this phenomenon is expected to occur in a wide range of interfacial systems. A simple model for the free energy landscape of the coupled solute-membrane system is proposed and validated. This model explicitly accounts for effects of the membrane deformations on the solute transport and yields an accurate prediction of the activation energy for the solute transport.

  8. One-dimensional potential of mean force underestimates activation barrier for transport across flexible lipid membranes.

    PubMed

    Kopelevich, Dmitry I

    2013-10-07

    Transport of a fullerene-like nanoparticle across a lipid bilayer is investigated by coarse-grained molecular dynamics (MD) simulations. Potentials of mean force (PMF) acting on the nanoparticle in a flexible bilayer suspended in water and a bilayer restrained to a flat surface are computed by constrained MD simulations. The rate of the nanoparticle transport into the bilayer interior is predicted using one-dimensional Langevin models based on these PMFs. The predictions are compared with the transport rates obtained from a series of direct (unconstrained) MD simulations of the solute transport into the flexible bilayer. It is observed that the PMF acting on the solute in the flexible membrane underestimates the transport rate by more than an order of magnitude while the PMF acting on the solute in the restrained membrane yields an accurate estimate of the activation energy for transport into the flexible membrane. This paradox is explained by a coexistence of metastable membrane configurations for a range of the solute positions inside and near the flexible membrane. This leads to a significant reduction of the contribution of the transition state to the mean force acting on the solute. Restraining the membrane shape ensures that there is only one stable membrane configuration corresponding to each solute position and thus the transition state is adequately represented in the PMF. This mechanism is quite general and thus this phenomenon is expected to occur in a wide range of interfacial systems. A simple model for the free energy landscape of the coupled solute-membrane system is proposed and validated. This model explicitly accounts for effects of the membrane deformations on the solute transport and yields an accurate prediction of the activation energy for the solute transport.

  9. The promiscuous phosphomonoestearase activity of Archaeoglobus fulgidus CopA, a thermophilic Cu+ transport ATPase.

    PubMed

    Bredeston, Luis M; González Flecha, F Luis

    2016-07-01

    Membrane transport P-type ATPases display two characteristic enzymatic activities: a principal ATPase activity provides the driving force for ion transport across biological membranes, whereas a promiscuous secondary activity catalyzes the hydrolysis of phosphate monoesters. This last activity is usually denoted as the phosphatase activity of P-ATPases. In the present study, we characterize the phosphatase activity of the Cu(+)-transport ATPase from Archaeglobus fulgidus (Af-CopA) and compare it with the principal ATPase activity. Our results show that the phosphatase turnover number was 20 times higher than that corresponding to the ATPase activity, but it is compensated by a high value of Km, producing a less efficient catalysis for pNPP. This secondary activity is enhanced by Mg(2+) (essential activator) and phospholipids (non-essential activator), and inhibited by salts and Cu(+). Transition state analysis of the catalyzed and noncatalyzed hydrolysis of pNPP indicates that Af-CopA enhances the reaction rates by a factor of 10(5) (ΔΔG(‡)=38 kJ/mol) mainly by reducing the enthalpy of activation (ΔΔH(‡)=30 kJ/mol), whereas the entropy of activation is less negative on the enzyme than in solution. For the ATPase activity, the decrease in the enthalpic component of the barrier is higher (ΔΔH(‡)=39 kJ/mol) and the entropic component is small on both the enzyme and in solution. These results suggest that different mechanisms are involved in the transference of the phosphoryl group of p-nitrophenyl phosphate and ATP.

  10. Structure and permeation mechanism of a mammalian urea transporter

    SciTech Connect

    Levin, Elena J.; Cao, Yu; Enkavi, Giray; Quick, Matthias; Pan, Yaping; Tajkhorshid, Emad; Zhou, Ming

    2012-09-17

    As an adaptation to infrequent access to water, terrestrial mammals produce urine that is hyperosmotic to plasma. To prevent osmotic diuresis by the large quantity of urea generated by protein catabolism, the kidney epithelia contain facilitative urea transporters (UTs) that allow rapid equilibration between the urinary space and the hyperosmotic interstitium. Here we report the first X-ray crystal structure of a mammalian UT, UT-B, at a resolution of 2.36 {angstrom}. UT-B is a homotrimer and each protomer contains a urea conduction pore with a narrow selectivity filter. Structural analyses and molecular dynamics simulations showed that the selectivity filter has two urea binding sites separated by an approximately 5.0 kcal/mol energy barrier. Functional studies showed that the rate of urea conduction in UT-B is increased by hypoosmotic stress, and that the site of osmoregulation coincides with the location of the energy barrier.

  11. Examining Changes in Radioxenon Isotope Activity Ratios during Subsurface Transport

    NASA Astrophysics Data System (ADS)

    Annewandter, Robert

    2014-05-01

    The Non-Proliferation Experiment (NPE) has demonstrated and modelled the usefulness of barometric pumping induced gas transport and subsequent soil gas sampling during On-Site inspections. Generally, gas transport has been widely studied with different numerical codes. However, gas transport of radioxenons and radioiodines in the post-detonation regime and their possible fractionation is still neglected in the open peer-reviewed literature. Atmospheric concentrations of the radioxenons Xe-135, Xe-133m, Xe-133 and Xe-131m can be used to discriminate between civilian releases (nuclear power plants or medical isotope facilities), and nuclear explosion sources. It is based on the multiple isotopic activity ratio method. Yet it is not clear whether subsurface migration of the radionuclides, with eventual release into the atmosphere, can affect the activity ratios due to fractionation. Fractionation can be caused by different mass diffusivities due to mass differences between the radionuclides. Cyclical changes in atmospheric pressure can drive subsurface gas transport. This barometric pumping phenomenon causes an oscillatoric flow in upward trending fractures or highly conductive faults which, combined with diffusion into the porous matrix, leads to a net transport of gaseous components - a so-called ratcheting effect. We use a general purpose reservoir simulator (Complex System Modelling Platform, CSMP++) which is recognized by the oil industry as leading in Discrete Fracture-Matrix (DFM) simulations. It has been applied in a range of fields such as deep geothermal systems, three-phase black oil simulations, fracture propagation in fractured, porous media, and Navier-Stokes pore-scale modelling among others. It is specifically designed to account for structurally complex geologic situation of fractured, porous media. Parabolic differential equations are solved by a continuous Galerkin finite-element method, hyperbolic differential equations by a complementary finite

  12. Differences in associations between active transportation and built environmental exposures when expressed using different components of individual activity spaces.

    PubMed

    van Heeswijck, Torbjorn; Paquet, Catherine; Kestens, Yan; Thierry, Benoit; Morency, Catherine; Daniel, Mark

    2015-05-01

    This study assessed relationships between built environmental exposures measured within components of individual activity spaces (i.e., travel origins, destinations and paths in-between), and use of active transportation in a metropolitan setting. Individuals (n=37,165) were categorised as using active or sedentary transportation based on travel survey data. Generalised Estimating Equations analysis was used to test relationships with active transportation. Strength and significance of relationships between exposures and active transportation varied for different components of the activity space. Associations were strongest when including travel paths in expression of the built environment. Land use mix and greenness were negatively related to active transportation.

  13. Mechanism(S) Involved in the Colon-Specific Expression of the Thiamine Pyrophosphate (Tpp) Transporter.

    PubMed

    Nabokina, Svetlana M; Ramos, Mel Brendan; Said, Hamid M

    2016-01-01

    Microbiota of the large intestine synthesizes considerable amount of vitamin B1 (thiamine) in the form of thiamine pyrophosphate (TPP). We have recently demonstrated the existence of an efficient and specific carrier-mediated uptake process for TPP in human colonocytes, identified the TPP transporter (TPPT) involved (product of the SLC44A4 gene), and shown that expression of TPPT along the gastrointestinal (GI) tract is restricted to the colon. Our aim in this study was to determine the molecular basis of the colon-specific expression of TPPT focusing on a possible epigenetic mechanism. Our results showed that the CpG island predicted in the SLC44A4 promoter is non-methylated in the human colonic epithelial NCM460 cells, but is hyper-methylated in the human duodenal epithelial HuTu80 cells (as well as in the human retinal pigment epithelial ARPE19 cells). In the mouse (where TPPT expression in the GI tract is also restricted to the colon), the CpG island predicted in the Slc44a4 promoter is non-methylated in both the jejunum and colon, thus arguing against possible contribution of DNA methylation in the colon-specific expression of TPPT. A role for histone modifications in the tissue-specific pattern of Slc44a4 expression, however, was suggested by the findings that in mouse colon, histone H3 in the 5'-regulatory region of Slc44a4 is tri-methylated at lysine 4 and acetylated at lysine 9, whereas the tri-methylation at lysine 27 modification was negligible. In contrast, in the mouse jejunum, histone H3 is hyper-trimethylated at lysine 27 (repressor mark). Similarly, possible involvement of miRNA(s) in the tissue-specific expression of TPPT was also suggested by the findings that the 3'-UTR of SLC44A4 is targeted by specific miRNAs/RNA binding proteins in non-colonic, but not in colonic, epithelial cells. These studies show, for the first time, epigenetic mechanisms (histone modifications) play a role in determining the tissue-specific pattern of expression of TPPT

  14. Critical review: Radionuclide transport, sediment transport, and water quality mathematical modeling; and radionuclide adsorption/desorption mechanisms

    SciTech Connect

    Onishi, Y.; Serne, R.J.; Arnold, E.M.; Cowan, C.E.; Thompson, F.L.

    1981-01-01

    This report describes the results of a detailed literature review of radionuclide transport models applicable to rivers, estuaries, coastal waters, the Great Lakes, and impoundments. Some representatives sediment transport and water quality models were also reviewed to evaluate if they can be readily adapted to radionuclide transport modeling. The review showed that most available transport models were developed for dissolved radionuclide in rivers. These models include the mechanisms of advection, dispersion, and radionuclide decay. Since the models do not include sediment and radionuclide interactions, they are best suited for simulating short-term radionuclide migration where: (1) radionuclides have small distribution coefficients; (2) sediment concentrations in receiving water bodies are very low. Only 5 of the reviewed models include full sediment and radionuclide interactions: CHMSED developed by Fields; FETRA SERATRA, and TODAM developed by Onishi et al, and a model developed by Shull and Gloyna. The 5 models are applicable to cases where: (1) the distribution coefficient is large; (2) sediment concentrations are high; or (3) long-term migration and accumulation are under consideration. The report also discusses radionuclide absorption/desorption distribution ratios and addresses adsorption/desorption mechanisms and their controlling processes for 25 elements under surface water conditions. These elements are: Am, Sb, C, Ce, Cm, Co, Cr, Cs, Eu, I, Fe, Mn, Np, P, Pu, Pm, Ra, Ru, Sr, Tc, Th, {sup 3}H, U, Zn and Zr.

  15. Mechanism of Highly Synchronized Bilateral Hippocampal Activity

    PubMed Central

    Wang, Y.; Toprani, S.; Tang, Y.; Vrabec, T.; Durand, D.M.

    2014-01-01

    In vivo studies of epileptiform discharges in the hippocampi of rodents have shown that bilateral seizure activity can sometimes be synchronized with very small delays (< 2 ms). This observed small time delay of epileptiform activity between the left and right CA3 regions is unexpected given the physiological propagation time across the hemispheres (> 6 ms). The goal of this study is to determine the mechanisms of this tight synchronization with in-vitro electrophysiology techniques and computer simulations. The hypothesis of a common source was first eliminated by using an in-vitro preparation containing both hippocampi with a functional ventral hippocampal commissure (VHC) and no other tissue. Next, the hypothesis that a noisy baseline could mask the underlying synchronous activity between the two hemispheres was ruled out by low noise in-vivo recordings and computer simulation of the noisy environment. Then we built a novel bilateral CA3 model to test the hypothesis that the phenomenon of very small left-to-right propagation delay of seizure activity is a product of epileptic cell network dynamics. We found that the commissural tract connectivity could decrease the delay between seizure events recorded from two sides while the activity propagated longitudinally along the CA3 layer thereby yielding delays much smaller than the propagation time between the two sides. The modeling results indicate that both recurrent and feedforward inhibition were required for shortening the bilateral propagation delay and depended critically on the length of the commissural fiber tract as well as the number of cells involved in seizure generation. These combined modeling/experimental studies indicate that it is possible to explain near perfect synchronization between the two hemispheres by taking into account the structure of the hippocampal network. PMID:24262205

  16. Coupling mechanical forces to electrical signaling: molecular motors and the intracellular transport of ion channels.

    PubMed

    Barry, Joshua; Gu, Chen

    2013-04-01

    Proper localization of various ion channels is fundamental to neuronal functions, including postsynaptic potential plasticity, dendritic integration, action potential initiation and propagation, and neurotransmitter release. Microtubule-based forward transport mediated by kinesin motors plays a key role in placing ion channel proteins to correct subcellular compartments. PDZ- and coiled-coil-domain proteins function as adaptor proteins linking ionotropic glutamate and GABA receptors to various kinesin motors, respectively. Recent studies show that several voltage-gated ion channel/transporter proteins directly bind to kinesins during forward transport. Three major regulatory mechanisms underlying intracellular transport of ion channels are also revealed. These studies contribute to understanding how mechanical forces are coupled to electrical signaling and illuminating pathogenic mechanisms in neurodegenerative diseases.

  17. Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism.

    PubMed

    Sacchetti, P; Mitchell, T R; Granneman, J G; Bannon, M J

    2001-03-01

    The importance of the nuclear receptor nurr1 for the appropriate development of mesencephalic dopamine-synthesizing neurons has been clearly demonstrated through the targeted disruption of the nurr1 gene. The persistence of nurr1 expression in adult tissue suggests a possible role for this transcription factor in the maintenance, as well as development, of the dopaminergic phenotype. To address this issue, we analyzed the effects of nurr1 on the transcriptional expression of the human dopamine transporter gene (hDAT), one of the most specific phenotypic markers for dopaminergic neurons. Nurr1 enhanced the transcriptional activity of hDAT gene constructs transiently transfected into a newly described cell line (SN4741) that expresses a dopaminergic phenotype, whereas other members of the NGFI-B subfamily of nuclear receptors had lesser or no effects. Nurr1 activation of hDAT was not dependent upon heterodimerization with the retinoid X receptor. Unexpectedly, functional analysis of a series of gene constructs revealed that a region of the hDAT 5'-flanking sequence devoid of NGFI-B response element (NBRE)-like sites mediated nurr1 activation. Additional experiments using a nurr1 mutant construct suggest that nurr1 activates hDAT transcription via a novel NBRE-independent mechanism.

  18. Mechanism of base activation of persulfate.

    PubMed

    Furman, Olha S; Teel, Amy L; Watts, Richard J

    2010-08-15

    Base is the most commonly used activator of persulfate for the treatment of contaminated groundwater by in situ chemical oxidation (ISCO). A mechanism for the base activation of persulfate is proposed involving the base-catalyzed hydrolysis of persulfate to hydroperoxide anion and sulfate followed by the reduction of another persulfate molecule by hydroperoxide. Reduction by hydroperoxide decomposes persulfate into sulfate radical and sulfate anion, and hydroperoxide is oxidized to superoxide. The base-catalyzed hydrolysis of persulfate was supported by kinetic analyses of persulfate decomposition at various base:persulfate molar ratios and an increased rate of persulfate decomposition in D(2)O vs H(2)O. Stoichiometric analyses confirmed that hydroperoxide reacts with persulfate in a 1:1 molar ratio. Addition of hydroperoxide to basic persulfate systems resulted in rapid decomposition of the hydroperoxide and persulfate and decomposition of the superoxide probe hexachloroethane. The presence of superoxide was confirmed with scavenging by Cu(II). Electron spin resonance spectroscopy confirmed the generation of sulfate radical, hydroxyl radical, and superoxide. The results of this research are consistent with the widespread reactivity reported for base-activated persulfate when it is used for ISCO.

  19. Serotonin transporter activity in platelets and canine aggression.

    PubMed

    Rosado, Belén; García-Belenguer, Sylvia; Palacio, Jorge; Chacón, Gema; Villegas, Ainara; Alcalde, Ana I

    2010-10-01

    Several studies have suggested an inhibitory action of the serotonergic system in the regulation of canine aggression, but the role of the serotonin (5-HT) transporter (5-HTT) has not been investigated. Platelet 5-HT uptake has been proposed as a peripheral marker of brain 5-HTT. The aim of the study was to investigate the relationship between platelet 5-HTT activity and canine aggression by measuring the rate of 5-HT uptake mediated by 5-HTT in platelets and serum concentrations of 5-HT in both aggressive (n=14) and non-aggressive dogs (n=17). Aggressive dogs showed significantly higher 5-HT uptake by 5-HTT in platelets and lower serum concentrations of 5-HT, compared with the control group. These results suggested an association between an alteration in the serotonergic system and canine aggression, possibly mediated by an increased 5-HT transport.

  20. Platelet Serotonin Transporter Function Predicts Default-Mode Network Activity

    PubMed Central

    Kasess, Christian H.; Meyer, Bernhard M.; Hofmaier, Tina; Diers, Kersten; Bartova, Lucie; Pail, Gerald; Huf, Wolfgang; Uzelac, Zeljko; Hartinger, Beate; Kalcher, Klaudius; Perkmann, Thomas; Haslacher, Helmuth; Meyer-Lindenberg, Andreas; Kasper, Siegfried; Freissmuth, Michael; Windischberger, Christian; Willeit, Matthäus; Lanzenberger, Rupert; Esterbauer, Harald; Brocke, Burkhard; Moser, Ewald; Sitte, Harald H.; Pezawas, Lukas

    2014-01-01

    Background The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence. Methods A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax) was assessed in blood platelets. We used a mixed-effects multilevel analysis technique (MEMA) to test for linear relationships between whole-brain, blood-oxygen-level dependent (BOLD) activity and platelet Vmax. Results The present study demonstrates that increases in platelet Vmax significantly predict default-mode network (DMN) suppression in healthy subjects independent of genetic variation within SLC6A4. Furthermore, functional connectivity analyses indicate that platelet Vmax is related to global DMN activation and not intrinsic DMN connectivity. Conclusion This study provides evidence that platelet Vmax predicts global DMN activation changes in healthy subjects. Given previous reports on platelet-synaptosomal Vmax coupling, results further suggest an important role of neuronal 5-HT reuptake in DMN regulation. PMID:24667541

  1. Transportation R and D included in thermal and mechanical sciences program

    SciTech Connect

    1995-03-01

    Argonne National Laboratory is a multiprogram research and development laboratory operated by The University of Chicago for the US Department of Energy. At Argonne, applied research in thermal and mechanical sciences is performed within the Thermal and Mechanical Sciences Section of the Energy Technology Division. Current program areas include compact evaporators and condensers for the process and transportation industries, ice slurries for district cooling, advanced fluids for improved heat transfer and reduced pressure drop, flow-induced vibration and flow distribution in shell-and-tube heat exchangers, and dynamics and control of maglev systems. In general, the objective of the research is to extend the technology base in each of these areas and to facilitate its application in solving problems of importance to US industries and utilities. This is accomplished by developing validated design correlations and predictive methods. The staff of the Thermal and Mechanical Sciences Section have extensive experimental and analytical experience in heat transfer, multiphase flow, structural dynamics and control, fluid-structure interaction, transient flow and mixing, thermally driven flows, and flow visualization using ultra-high-speed video. Large, general-purpose test facilities and smaller, single-purpose test apparatuses are available for experiments and component design evaluation. A world-class capability in the study of flow-induced vibrations exists within the Section. Individual fact sheets, describing currently active research program areas, related facilities, and listing, as a contact, the principal investigator, are included.

  2. The Shoelace Antenna: Measurements of Driven Transport and Prospects for Active Edge Control

    NASA Astrophysics Data System (ADS)

    Golfinopoulos, Theodore; Labombard, B.; Brunner, D.; Terry, J. L.; Baek, S. G.; Ennever, P.; Edlund, E.; Han, W.; Burke, W. M.; Wolfe, S. M.; Irby, J. H.; Hughes, J. W.; Fitzgerald, E. W.; Granetz, R. S.; Greenwald, M. J.; Leccacorvi, R.; Marmar, E. S.; Pierson, S. Z.; Porkolab, M.; Vieira, R. F.; Wukitch, S. J.; Alcator C-Mod Team

    2016-10-01

    The Shoelace antenna was built to drive edge fluctuations in the Alcator C-Mod tokamak, matching the wavenumber (k = 1.5/cm) and frequency (50< f<200 kHz) of the Quasi-Coherent Mode (QCM). This fluctuation is responsible for regulating transport across the plasma boundary in the steady-state, ELM-free Enhanced D α(EDA) H-mode; the goal of the Shoelace antenna is to regulate edge transport actively via the same mechanism. Initial experiments demonstrated that the antenna drove a resonant response in the edge plasma in steady-state EDA and transient, non-ELMy H-modes, but transport measurements were unavailable. In 2016, the Shoelace antenna was relocated to enable direct measurements of driven transport by a reciprocating Mirror Langmuir Probe, while also making available gas puff imaging and reflectometer data to provide radial localization of the driven fluctuation. This talk will describe these measurements, and compare them to those of the intrinsic QCM in the context of assessing the feasibility of achieving active control of edge transport using direct coupling to edge modes. This work is supported by USDoE Award DE-FC02-99ER54512.

  3. Mechanism of unassisted ion transport across membrane bilayers

    NASA Technical Reports Server (NTRS)

    Wilson, M. A.; Pohorille, A.

    1996-01-01

    To establish how charged species move from water to the nonpolar membrane interior and to determine the energetic and structural effects accompanying this process, we performed molecular dynamics simulations of the transport of Na+ and Cl- across a lipid bilayer located between two water lamellae. The total length of molecular dynamics trajectories generated for each ion was 10 ns. Our simulations demonstrate that permeation of ions into the membrane is accompanied by the formation of deep, asymmetric thinning defects in the bilayer, whereby polar lipid head groups and water penetrate the nonpolar membrane interior. Once the ion crosses the midplane of the bilayer the deformation "switches sides"; the initial defect slowly relaxes, and a defect forms in the outgoing side of the bilayer. As a result, the ion remains well solvated during the process; the total number of oxygen atoms from water and lipid head groups in the first solvation shell remains constant. A similar membrane deformation is formed when the ion is instantaneously inserted into the interior of the bilayer. The formation of defects considerably lowers the free energy barrier to transfer of the ion across the bilayer and, consequently, increases the permeabilities of the membrane to ions, compared to the rigid, planar structure, by approximately 14 orders of magnitude. Our results have implications for drug delivery using liposomes and peptide insertion into membranes.

  4. Molecular mechanism: the human dopamine transporter histidine 547 regulates basal and HIV-1 Tat protein-inhibited dopamine transport

    PubMed Central

    Quizon, Pamela M.; Sun, Wei-Lun; Yuan, Yaxia; Midde, Narasimha M.; Zhan, Chang-Guo; Zhu, Jun

    2016-01-01

    Abnormal dopaminergic transmission has been implicated as a risk determinant of HIV-1-associated neurocognitive disorders. HIV-1 Tat protein increases synaptic dopamine (DA) levels by directly inhibiting DA transporter (DAT) activity, ultimately leading to dopaminergic neuron damage. Through integrated computational modeling prediction and experimental validation, we identified that histidine547 on human DAT (hDAT) is critical for regulation of basal DA uptake and Tat-induced inhibition of DA transport. Compared to wild type hDAT (WT hDAT), mutation of histidine547 (H547A) displayed a 196% increase in DA uptake. Other substitutions of histidine547 showed that DA uptake was not altered in H547R but decreased by 99% in H547P and 60% in H547D, respectively. These mutants did not alter DAT surface expression or surface DAT binding sites. H547 mutants attenuated Tat-induced inhibition of DA transport observed in WT hDAT. H547A displays a differential sensitivity to PMA- or BIM-induced activation or inhibition of DAT function relative to WT hDAT, indicating a change in basal PKC activity in H547A. These findings demonstrate that histidine547 on hDAT plays a crucial role in stabilizing basal DA transport and Tat-DAT interaction. This study provides mechanistic insights into identifying targets on DAT for Tat binding and improving DAT-mediated dysfunction of DA transmission. PMID:27966610

  5. Evaluation of the physical activity biography: sport and transport.

    PubMed

    Rogen, Sandra; Hofmann, Peter; Bauernhofer, Thomas; Müller, Wolfram

    2014-05-01

    Beside the genetic disposition, physical activity (PA) is one of the major health factors and can play a large role in the prevention and therapy of many diseases (cardiovascular diseases, cancer, obesity-related diseases etc.). In contrast to the genetic disposition, PA can be deliberately influenced by lifestyle. Therefore, it is of high importance to assess PA patterns. In order to assess PA reliably and validly, a new questionnaire (Physical Activity Biography, PAB) was created. The PAB assesses recreational PA (sport and transport) and enables to distinguish between endurance intensity levels and considers strength and high speed activity patterns throughout life. This study aims to evaluate the PAB by means of item analysis, retest-reliability and validity (criteria were physical fitness assessed by the questionnaire FFB-mot and by exercise tests). 141 participants answered the PAB. For deriving retest-reliability, 81 participants completed the PAB after a retest-interval of one month again. 55 participated in exercise tests and answered the FFB-mot to determine construct validity. Retest-reliability (ICC) above 0.7 was found for most items. For the items assessing recent PA, the criteria of convergent and discriminant validity were given. Despite the complexity of the question under study, the results fulfilled the expectations concerning reliability and validity. The PAB enables to assess the amount of sport and locomotion a person has accomplished during different life time frames and, because of the protective effects of PA on various diseases, may become an important tool for risk assessment. Key pointsThe risk of chronic diseases depends largely on physical activity biography.A new questionnaire (PAB) assessing recent and lifetime physical activity was created.The PAB assesses physical activity during sports and transport.The results of the evaluation of the PAB fulfilled the expectations.The PAB enables to determine a person's amount of recreational

  6. Evaluation of the Physical Activity Biography: Sport and Transport

    PubMed Central

    Rogen, Sandra; Hofmann, Peter; Bauernhofer, Thomas; Müller, Wolfram

    2014-01-01

    Beside the genetic disposition, physical activity (PA) is one of the major health factors and can play a large role in the prevention and therapy of many diseases (cardiovascular diseases, cancer, obesity-related diseases etc.). In contrast to the genetic disposition, PA can be deliberately influenced by lifestyle. Therefore, it is of high importance to assess PA patterns. In order to assess PA reliably and validly, a new questionnaire (Physical Activity Biography, PAB) was created. The PAB assesses recreational PA (sport and transport) and enables to distinguish between endurance intensity levels and considers strength and high speed activity patterns throughout life. This study aims to evaluate the PAB by means of item analysis, retest-reliability and validity (criteria were physical fitness assessed by the questionnaire FFB-mot and by exercise tests). 141 participants answered the PAB. For deriving retest-reliability, 81 participants completed the PAB after a retest-interval of one month again. 55 participated in exercise tests and answered the FFB-mot to determine construct validity. Retest-reliability (ICC) above 0.7 was found for most items. For the items assessing recent PA, the criteria of convergent and discriminant validity were given. Despite the complexity of the question under study, the results fulfilled the expectations concerning reliability and validity. The PAB enables to assess the amount of sport and locomotion a person has accomplished during different life time frames and, because of the protective effects of PA on various diseases, may become an important tool for risk assessment. Key points The risk of chronic diseases depends largely on physical activity biography. A new questionnaire (PAB) assessing recent and lifetime physical activity was created. The PAB assesses physical activity during sports and transport. The results of the evaluation of the PAB fulfilled the expectations. The PAB enables to determine a person’s amount of

  7. Mechanisms involved in the transport of mercuric ions in target tissues.

    PubMed

    Bridges, Christy C; Zalups, Rudolfs K

    2017-01-01

    Mercury exists in the environment in various forms, all of which pose a risk to human health. Despite guidelines regulating the industrial release of mercury into the environment, humans continue to be exposed regularly to various forms of this metal via inhalation or ingestion. Following exposure, mercuric ions are taken up by and accumulate in numerous organs, including brain, intestine, kidney, liver, and placenta. In order to understand the toxicological effects of exposure to mercury, a thorough understanding of the mechanisms that facilitate entry of mercuric ions into target cells must first be obtained. A number of mechanisms for the transport of mercuric ions into target cells and organs have been proposed in recent years. However, the ability of these mechanisms to transport mercuric ions and the regulatory features of these carriers have not been characterized completely. The purpose of this review is to summarize the current findings related to the mechanisms that may be involved in the transport of inorganic and organic forms of mercury in target tissues and organs. This review will describe mechanisms known to be involved in the transport of mercury and will also propose additional mechanisms that may potentially be involved in the transport of mercuric ions into target cells.

  8. Quantum-Mechanical Method for the Soliton Transported Bio-energy in Protein

    NASA Astrophysics Data System (ADS)

    Pang, Xiaofeng

    1993-07-01

    The equations of motion of the soliton transported bio-energy in the protein, were heretofore already obtained by a combination of quantum-mechanical and classical methods, but here have been derived based completely on quantum mechanics. And we point out the shortcoming of no self-consistency of the Davydov theory. Some interesting results have also been got.

  9. From Mechanical Motion to Brownian Motion, Thermodynamics and Particle Transport Theory

    ERIC Educational Resources Information Center

    Bringuier, E.

    2008-01-01

    The motion of a particle in a medium is dealt with either as a problem of mechanics or as a transport process in non-equilibrium statistical physics. The two kinds of approach are often unrelated as they are taught in different textbooks. The aim of this paper is to highlight the link between the mechanical and statistical treatments of particle…

  10. Active sodium transport and the electrophysiology of rabbit colon.

    PubMed

    Schultz, S G; Frizzell, R A; Nellans, H N

    1977-05-12

    The electrophysiologic properties of rabbit colonic epithelial cells were investigated employing microelectrode techniques. Under open-circuit conditions, the transepithelial electrical potential difference (PD) averaged 20 mV, serosa positive, and the intracellular electrical potential (psimc) averaged -32 mV, cell interior negative with respect to the mucosal solution; under short-circuit conditions, psimc averaged -46 mV. The addition of amiloride to the mucosal solution abolishes the transepithelial PD and active Na transport, and psimc is hyperpolarized to an average value of -53 mV. These results indicate that Na entry into the mucosal cell is a conductive process which, normally, depolarized psimc. The data obtained were interpreted using a double-membrane equivalent electrical circuit model of the "active Na transport pathway" involving two voltage-independent electromotive forces (emf's) and two voltage-independent resistances arrayed in series. Our observations are consistent with the notions that: (a) The emf's and resistances across the mucosal and baso-lateral membranes are determined predominantly by the emf (64 mV) and resistance of the Na entry process and the emf (53 mV) and resistance of the process responsible for active Na extrusion across the baso-lateral membranes: that is, the electrophysiological properties of the cell appear to be determined solely by the properties and processes responsible for transcellular active Na transport. The emf of the Na entry process is consistent with the notion that the Na activity in the intracellular transport pool is approximately one-tenth that in the mucosal solution or about 14 mM. (b) In the presence of amiloride, the transcellular conductance is essentially abolished and the total tissue conductance is the result of ionic diffusion through paracellular pathways. (c) The negative intracellular potential (with respect to the mucosal solution) is due primarily to the presence of a low resistance

  11. Identification of a Novel Regulatory Mechanism of Nutrient Transport Controlled by TORC1-Npr1-Amu1/Par32

    PubMed Central

    Boeckstaens, Mélanie; Merhi, Ahmad; Llinares, Elisa; Van Vooren, Pascale; Springael, Jean-Yves; Wintjens, René; Marini, Anna Maria

    2015-01-01

    Fine-tuning the plasma-membrane permeability to essential nutrients is fundamental to cell growth optimization. Nutritional signals including nitrogen availability are integrated by the TORC1 complex which notably regulates arrestin-mediated endocytosis of amino-acid transporters. Ammonium is a ubiquitous compound playing key physiological roles in many, if not all, organisms. In yeast, it is a preferred nitrogen source transported by three Mep proteins which are orthologues of the mammalian Rhesus factors. By combining genetic, kinetic, biochemical and cell microscopy analyses, the current study reveals a novel mechanism enabling TORC1 to regulate the inherent activity of ammonium transport proteins, independently of arrestin-mediated endocytosis, identifying the still functional orphan Amu1/Par32 as a selective regulator intermediate. We show that, under poor nitrogen supply, the TORC1 effector kinase' Npr1' promotes phosphorylation of Amu1/Par32 which appears mainly cytosolic while ammonium transport proteins are active. Upon preferred nitrogen supplementation, like glutamine or ammonium addition, TORC1 upregulation enables Npr1 inhibition and Amu1/Par32 dephosphorylation. In these conditions, as in Npr1-lacking cells, hypophosphorylated Amu1/Par32 accumulates at the cell surface and mediates the inhibition of specific ammonium transport proteins. We show that the integrity of a conserved repeated motif of Amu1/Par32 is required for the interaction with these transport proteins. This study underscores the diversity of strategies enabling TORC1-Npr1 to selectively monitor cell permeability to nutrients by discriminating between transporters to be degraded or transiently inactivated and kept stable at the plasma membrane. This study further identifies the function of Amu1/Par32 in acute control of ammonium transport in response to variations in nitrogen availability. PMID:26172854

  12. Saharan Dust, Transport Processes, and Possible Impacts on Hurricane Activities

    NASA Technical Reports Server (NTRS)

    Lau, William K. M.; Kim, K. M.

    2010-01-01

    In this paper, we present observational evidence of significant relationships between Saharan dust outbreak, and African Easterly wave activities and hurricane activities. We found two dominant paths of transport of Saharan dust: a northern path, centered at 25degN associated with eastward propagating 6-19 days waves over northern Africa, and a southern path centered at 15degN, associated with the AEW, and the Atlantic ITCZ. Seasons with stronger dust outbreak from the southern path are associated with a drier atmosphere over the Maximum Development Region (MDR) and reduction in tropical cyclone and hurricane activities in the MDR. Seasons with stronger outbreak from the northern path are associated with a cooler N. Atlantic, and suppressed hurricane in the western Atlantic basin.

  13. Transport and deposition of activation products in a helium cooled fusion power plant

    SciTech Connect

    Bickford, W.E.

    1980-09-01

    The transport and deposition of neutron activation products in a helium cooled tokamak fusion power plant are investigated. Stainless steel is used as coolant channel material for a helium/steam system. The important gamma emitting nuclides /sup 56/Mn, /sup 54/Mn, /sup 57/Co, /sup 58/Co, /sup 60/Co, /sup 51/Cr, and /sup 99/Mo are considered. The dominant release mechanism identified is direct daughter recoil emission from (n,x) type reactions. Corrosion and evaporation are discussed. The radionuclide inventory released by these mechanisms is predicted to exceed 1 x 10/sup 4/ Ci for a reference reactor design after only several days of operation, and approach 3.5 x 10/sup 4/ Ci in equilibrium. A mass transport model is then used to predict the deposition pattern of this inventory in the reactor cooling system.

  14. Modeling of glycerol-3-phosphate transporter suggests a potential 'tilt' mechanism involved in its function.

    PubMed

    Tsigelny, Igor F; Greenberg, Jerry; Kouznetsova, Valentina; Nigam, Sanjay K

    2008-10-01

    Many major facilitator superfamily (MFS) transporters have similar 12-transmembrane alpha-helical topologies with two six-helix halves connected by a long loop. In humans, these transporters participate in key physiological processes and are also, as in the case of members of the organic anion transporter (OAT) family, of pharmaceutical interest. Recently, crystal structures of two bacterial representatives of the MFS family--the glycerol-3-phosphate transporter (GlpT) and lac-permease (LacY)--have been solved and, because of assumptions regarding the high structural conservation of this family, there is hope that the results can be applied to mammalian transporters as well. Based on crystallography, it has been suggested that a major conformational "switching" mechanism accounts for ligand transport by MFS proteins. This conformational switch would then allow periodic changes in the overall transporter configuration, resulting in its cyclic opening to the periplasm or cytoplasm. Following this lead, we have modeled a possible "switch" mechanism in GlpT, using the concept of rotation of protein domains as in the DynDom program17 and membranephilic constraints predicted by the MAPAS program.(23) We found that the minima of energies of intersubunit interactions support two alternate positions consistent with their transport properties. Thus, for GlpT, a "tilt" of 9 degrees -10 degrees rotation had the most favorable energetics of electrostatic interaction between the two halves of the transporter; moreover, this confirmation was sufficient to suggest transport of the ligand across the membrane. We conducted steered molecular dynamics simulations of the GlpT-ligand system to explore how glycerol-3-phosphate would be handled by the "tilted" structure, and obtained results generally consistent with experimental mutagenesis data. While biochemical data remain most consistent with a single-site alternating access model, our results raise the possibility that, while the

  15. Active urea transport by the skin of Bufo viridis: Amiloride- and phloretin-sensitive transport sites

    SciTech Connect

    Rapoport, J.; Abuful, A.; Chaimovitz, C.; Noeh, Z.; Hays, R.M. Albert Einstein College of Medicine, New York, NY )

    1988-09-01

    Urea is actively transported inwardly (J{sub i}) across the skin of the green toad Bufo viridis. J{sub i} is markedly enhanced in toads adapted to hypertonic saline. The authors studied urea transport across the skin of Bufo viridis under a variety of experimental conditions, including treatment with amiloride and phloretin, agents that inhibit urea permeability in the bladder of Bufo marinus. Amiloride (10{sup {minus}4} M) significantly inhibited J{sub i} in both adapted and unadapted animals and was unaffected by removal of sodium from the external medium. Phloretin (10{sup {minus}4} M) significantly inhibited J{sub i} in adapted animals by 23-46%; there was also a reduction in J{sub i} in unadapted toads at 10{sup {minus}4} and 5 {times} 10{sup {minus}4} M phloretin. A dose-response study revealed that the concentration of phloretin causing half-maximal inhibition (K{sub {1/2}}) was 5 {times} 10{sup {minus}4} M for adapted animals. J{sub i} was unaffected by the substitution of sucrose for Ringer solution or by ouabain. They conclude (1) the process of adaptation appears to involve an increase in the number of amiloride- and phloretin-inhibitable urea transport sites in the skin, with a possible increase in the affinity of the sites for phloretin; (2) the adapted skin resembles the Bufo marinus urinary bladder with respect to amiloride and phloretin-inhibitable sites; (3) they confirm earlier observations that J{sub i} is independent of sodium transport.

  16. Structure and Mechanism of the S Component of a Bacterial ECF Transporter

    SciTech Connect

    P Zhang; J Wang; Y Shi

    2011-12-31

    The energy-coupling factor (ECF) transporters, responsible for vitamin uptake in prokaryotes, are a unique family of membrane transporters. Each ECF transporter contains a membrane-embedded, substrate-binding protein (known as the S component), an energy-coupling module that comprises two ATP-binding proteins (known as the A and A' components) and a transmembrane protein (known as the T component). The structure and transport mechanism of the ECF family remain unknown. Here we report the crystal structure of RibU, the S component of the ECF-type riboflavin transporter from Staphylococcus aureus at 3.6-{angstrom} resolution. RibU contains six transmembrane segments, adopts a previously unreported transporter fold and contains a riboflavin molecule bound to the L1 loop and the periplasmic portion of transmembrane segments 4-6. Structural analysis reveals the essential ligand-binding residues, identifies the putative transport path and, with sequence alignment, uncovers conserved structural features and suggests potential mechanisms of action among the ECF transporters.

  17. A mechanism of viral immune evasion revealed by cryo-EM analysis of the TAP transporter

    PubMed Central

    Oldham, Michael L.; Hite, Richard K.; Steffen, Alanna M.; Damko, Ermelinda; Li, Zongli; Walz, Thomas; Chen, Jue

    2015-01-01

    Cellular immunity against viral infection and tumor cells depends on antigen presentation by the major histocompatibility complex class 1 molecules (MHC I). Intracellular antigenic peptides are transported into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP) and then loaded onto the nascent MHC I, which are exported to the cell surface and present peptides to the immune system1. Cytotoxic T lymphocytes recognize non-self peptides and program the infected or malignant cells for apoptosis. Defects in TAP account for immunodeficiency and tumor development. To escape immune surveillance, some viruses have evolved strategies to either down-regulate TAP expression or directly inhibit TAP activity. To date neither the architecture of TAP nor the mechanism of viral inhibition has been elucidated at the structural level. In this study we describe the cryo-electron microscopy (cryo-EM) structure of human TAP in complex with its inhibitor ICP47, a small protein produced by the herpes simplex virus I. We show that the twelve transmembrane helices and two cytosolic nucleotide-binding domains (NBDs) of the transporter adopt an inward-facing conformation with the two NBDs separated. The viral inhibitor ICP47 forms a long helical hairpin, which plugs the translocation pathway of TAP from the cytoplasmic side. Association of ICP47 precludes substrate binding and also prevents NBD closure necessary for ATP hydrolysis. This work illustrates a striking example of immune evasion by persistent viruses. By blocking viral antigens from entering the ER, herpes simplex virus is hidden from cytotoxic T lymphocytes, which may contribute to establishing a lifelong infection in the host. PMID:26789246

  18. Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands

    PubMed Central

    Nakhoul, Hani N.; Kalliny, Medhat I.; Gyftopoulos, Alex; Rabon, Edd; Doetjes, Rienk; Brown, Karen; Nakhoul, Nazih L.

    2011-01-01

    The esophageal submucosal glands (SMG) secrete HCO3− and mucus into the esophageal lumen, where they contribute to acid clearance and epithelial protection. This study characterized the ion transport mechanisms linked to HCO3− secretion in SMG. We localized ion transporters using immunofluorescence, and we examined their expression by RT-PCR and in situ hybridization. We measured HCO3− secretion by using pH stat and the isolated perfused esophagus. Using double labeling with Na+-K+-ATPase as a marker, we localized Na+-coupled bicarbonate transporter (NBCe1) and Cl−-HCO3− exchanger (SLC4A2/AE2) to the basolateral membrane of duct cells. Expression of cystic fibrosis transmembrane regulator channel (CFTR) was confirmed by immunofluorescence, RT-PCR, and in situ hybridization. We identified anion exchanger SLC26A6 at the ducts' luminal membrane and Na+-K+-2Cl− (NKCC1) at the basolateral membrane of mucous and duct cells. pH stat experiments showed that elevations in cAMP induced by forskolin or IBMX increased HCO3− secretion. Genistein, an activator of CFTR, which does not increase intracellular cAMP, also stimulated HCO3− secretion, whereas glibenclamide, a Cl− channel blocker, and bumetanide, a Na+-K+-2Cl− blocker, decreased it. CFTRinh-172, a specific CFTR channel blocker, inhibited basal HCO3− secretion as well as stimulation of HCO3− secretion by IBMX. This is the first report on the presence of CFTR channels in the esophagus. The role of CFTR in manifestations of esophageal disease in cystic fibrosis patients remains to be determined. PMID:21474426

  19. Ion transport mechanisms linked to bicarbonate secretion in the esophageal submucosal glands.

    PubMed

    Abdulnour-Nakhoul, Solange; Nakhoul, Hani N; Kalliny, Medhat I; Gyftopoulos, Alex; Rabon, Edd; Doetjes, Rienk; Brown, Karen; Nakhoul, Nazih L

    2011-07-01

    The esophageal submucosal glands (SMG) secrete HCO(3)(-) and mucus into the esophageal lumen, where they contribute to acid clearance and epithelial protection. This study characterized the ion transport mechanisms linked to HCO(3)(-) secretion in SMG. We localized ion transporters using immunofluorescence, and we examined their expression by RT-PCR and in situ hybridization. We measured HCO(3)(-) secretion by using pH stat and the isolated perfused esophagus. Using double labeling with Na(+)-K(+)-ATPase as a marker, we localized Na(+)-coupled bicarbonate transporter (NBCe1) and Cl(-)-HCO(3)(-) exchanger (SLC4A2/AE2) to the basolateral membrane of duct cells. Expression of cystic fibrosis transmembrane regulator channel (CFTR) was confirmed by immunofluorescence, RT-PCR, and in situ hybridization. We identified anion exchanger SLC26A6 at the ducts' luminal membrane and Na(+)-K(+)-2Cl(-) (NKCC1) at the basolateral membrane of mucous and duct cells. pH stat experiments showed that elevations in cAMP induced by forskolin or IBMX increased HCO(3)(-) secretion. Genistein, an activator of CFTR, which does not increase intracellular cAMP, also stimulated HCO(3)(-) secretion, whereas glibenclamide, a Cl(-) channel blocker, and bumetanide, a Na(+)-K(+)-2Cl(-) blocker, decreased it. CFTR(inh)-172, a specific CFTR channel blocker, inhibited basal HCO(3)(-) secretion as well as stimulation of HCO(3)(-) secretion by IBMX. This is the first report on the presence of CFTR channels in the esophagus. The role of CFTR in manifestations of esophageal disease in cystic fibrosis patients remains to be determined.

  20. Mechanisms of disease: psychomotor retardation and high T3 levels caused by mutations in monocarboxylate transporter 8.

    PubMed

    Friesema, Edith C H; Jansen, Jurgen; Heuer, Heike; Trajkovic, Marija; Bauer, Karl; Visser, Theo J

    2006-09-01

    The actions and the metabolism of thyroid hormone are intracellular events that require the transport of iodothyronines across the plasma membrane. It is increasingly clear that this process does not occur by simple diffusion, but is facilitated by transport proteins. Only recently have iodothyronine transporters been identified at the molecular level, of which organic anion transporting polypeptide 1C1 and monocarboxylate transporter 8 (MCT8) deserve special mention, because of their high activity and specificity for iodothyronines. Organic anion transporting polypeptide 1C1 is almost exclusively expressed in brain capillaries, and may be crucial for the transport of the prohormone T4 across the blood-brain barrier. MCT8 is also expressed in the brain--in particular, in neurons--but also in other tissues. MCT8 seems to be especially important for the uptake of active hormone T3 into neurons, which is essential for optimal brain development. T3 is produced from T4 by type 2 deiodinase in neighboring astrocytes. Neurons express type 3 deiodinase, the enzyme that terminates T3 activity. The SLC16A2 (formerly MCT8) gene is located on chromosome Xq13.2 and has recently been associated with a syndrome combining severe, X-linked, psychomotor retardation and high serum T3 levels. In over 20 families, where affected males have developed this syndrome, several mutations in MCT8 have been identified. The disease mechanism is thought to involve a defect in the neuronal entry of T3 and, therefore, in the action and metabolism of T3 in these cells. This defect results in impaired neurological development and a decrease in T3 clearance.

  1. CFD Model of Water Droplet Transport for ISS Hygiene Activity

    NASA Technical Reports Server (NTRS)

    Son, Chang H.

    2011-01-01

    The goal of the study is to assess the impacts of free water propagation in the Waste and Hygiene Compartment (WHC). Free water can be generated inside the WHC in small quantities due to crew hygiene activity. To mitigate potential impact of free water in Node 3 cabin the WHC doorway is enclosed by a waterproof bump-out, Kabin, with openings at the top and bottom. At the overhead side of the rack, there is a screen that prevents large drops of water from exiting. However, as the avionics fan in the WHC causes airflow toward the deck side of the rack, small quantities of free water may exit at the bottom of the Kabin. A Computational Fluid Dynamics (CFD) analysis of Node 3 cabin airflow made possible to identify the paths of water transport. The Node 3 airflow was computed for several ventilation scenarios. To simulate the droplet transport the Lagrangian discrete phase approach was used. Various initial droplet distributions were considered in the study. The droplet diameter was varied in the range of 2-20 mm. The results of the computations showed that most of the drops fall to the rack surface not far from the WHC curtain. The probability of the droplet transport to the adjacent rack surface with electronic equipment was predicted.

  2. The transport mechanism of integrin αvβ3 receptor targeting nanoparticles in Caco-2 cells.

    PubMed

    Xu, Yining; Xu, Juan; Shan, Wei; Liu, Min; Cui, Yi; Li, Lian; Liu, Chong; Huang, Yuan

    2016-03-16

    As for the existence of epithelium barrier, accelerating the transport remains huge challenges for orally delivered protein and peptide drugs into blood circulation. Modifying nanopaticles (NPs) with targeting peptides can enhance the intestinal absorption of loaded macromolecular drugs. However, the transport process, which mainly means how the NPs pass through the apical membrane and the basolateral side and then enter into blood circulation, is needed comprehensive investigation. In this study, we systemically studied the transport mechanisms in Caco-2 cell model of trimethyl chitosan based NPs (TMC NPs) before and after modification of FQS, an integrin αvβ3 receptor targeting peptide. Our results showed FQS peptide mediated multiple endocytosis pathways and could activate integrin αvβ3 receptor by interacting with FAK and Src-family kinases to induce receptor-mediated endocytosis of the NPs. Then, both endocytosed NPs could transport from early endosome to lysososmes via late endosomes/lysosome pathway, as well as to recycling endosomes and Golgi apparatus through early endosome/recycling endosomes and Golgi apparatus/recycling endosomes/plasma membrane pathways, respectively. After FQS peptide modification, the endocytosis subpathways of NPs have been changed, and more pathways are involved in exocytosis process for FQS-modified NPs compared with non-modified NPs. Our study indicated the ligand modification could enhance the uptake and transport by altering some pathways in whole transport process of NPs.

  3. Systematic characterization of porosity and mass transport and mechanical properties of porous polyurethane scaffolds.

    PubMed

    Wang, Yu-Fu; Barrera, Carlos M; Dauer, Edward A; Gu, Weiyong; Andreopoulos, Fotios; Huang, C-Y Charles

    2017-01-01

    One of the key challenges in porous scaffold design is to create a porous structure with desired mechanical function and mass transport properties which support delivery of biofactors and development of function tissue substitute. In recent years, polyurethane (PU) has become one of the most popular biomaterials in various tissue engineering fields. However, there are no studies fully investigating the relations between porosity and both mass transport and mechanical properties of PU porous scaffolds. In this paper, we fabricated PU scaffolds by combining phase inversion and salt (sodium chloride) leaching methods. The tensile and compressive moduli were examined on PU scaffolds fabricated with different PU concentrations (25%, 20% and 15% w/v) and salt/PU weight ratios (9/1, 6/1, 3/1 and 0/1). The mass transport properties of PU scaffolds including hydraulic permeability and glucose diffusivity were also measured. Furthermore, the relationships between the porosity and mass transport and mechanical properties of porous PU scaffold were systemically investigated. The results demonstrated that porosity is a key parameter which governs both mass transport and mechanical properties of porous PU scaffolds. With similar pore sizes, the mass transport and mechanical properties of porous PU scaffold can be described as single functions of porosity regardless of initial PU concentration. The relationships between scaffold porosity and properties can be utilized to facilitate porous PU scaffold fabrication with specific mass transport and mechanical properties. The systematic approach established in this study can be applied to characterization of other biomaterials for scaffold design and fabrication.

  4. Active urea transport independent of H+ and Na+ transport in frog skin epithelium.

    PubMed

    Lacoste, I; Dunel-Erb, S; Harvey, B J; Laurent, P; Ehrenfeld, J

    1991-10-01

    We investigated the relationship between H+ secretion (JH), Na+ absorption (JNa), and urea transport (Ju) in skin of frogs (Rana esculenta) adapted to running tap water, NaCl (100 mM), and KCl (100 mM). In addition, cell morphological changes, particularly in the mitochondria-rich cells (MRC), were followed. NaCl adaptation stimulated an active Ju, reduced JNa and JH, and caused a decrease in the apical surface of MRC. After KCl adaptation, JNa and JH were increased and highly correlated, with a twofold increase in Ju, whereas the numerous MRC developed infoldings on their apical membranes. No correlation was found between JH and Ju. Clamping the skins in a range of +/- 50 mV or changing the external pH from 7.4 to 5.4 (at high cellular buffering power) had no effect on Ju. Depolarization of the basolateral membranes (serosal KCl-Ringer) had no effect on Ju. Ju was reversibly blocked by acidification of the cells by oxygen-free solution and sulfhydryl reagents (Hg2+, p-chloromercuribenzenesulfonic acid, and N-ethylmaleimide). Diethylstilbestrol, a proton transport blocker, had no effect on Ju. Apical addition of amiloride and derivatives (phenamil and ethylisopropyl amiloride) reversibly blocked Ju, whereas ouabain had no effect. We conclude that a cation (Na+ or H+)-dependent process is unlikely to exist in R. esculenta skin. A primary active transport in a two-step process is the simplest hypothesis to account for the energy-dependent Ju that develops in NaCl-adapted frogs.

  5. Combinatorial pharmacophore modeling of organic cation transporter 2 (OCT2) inhibitors: insights into multiple inhibitory mechanisms.

    PubMed

    Xu, Yuan; Liu, Xian; Li, Shanshan; Zhou, Nannan; Gong, Likun; Luo, Cheng; Luo, Xiaomin; Zheng, Mingyue; Jiang, Hualiang; Chen, Kaixian

    2013-12-02

    Organic cation transporter 2 (OCT2) is responsible for the entry step of many drugs in renal elimination, of which the changing activity may cause unwanted drug-drug interactions (DDIs). To develop drugs with favorable safety profile and provide instruction for rational clinical drug administration, it is of great interest to investigate the multiple mechanisms of OCT2 inhibition. In this study, we designed a combinatorial scheme to screen the optimum combination of pharmacophores from a pool of hypotheses established based on 162 OCT2 inhibitors. Among them, one single pharmacophore hypothesis represents a potential binding mode that may account for one unique inhibitory mechanism, and the obtained pharmacophore combination describes the multimechanisms of OCT2 inhibition. The final model consists of four individual pharmacophores, i.e., DHPR18, APR2, PRR5 and HHR4. Given a query ligand, it is considered as an inhibitor if it matches at least one of the hypotheses, or a noninhibitor if it fails to match any of four hypotheses. Our combinatorial pharmacophore model performs reasonably well to discriminate inhibitors and noninhibitors, yielding an overall accuracy around 0.70 for a test set containing 81 OCT2 inhibitors and 218 noninhibitors. Intriguingly, we found that the number of matched hypotheses was positively correlated with inhibition rate, which coincides with the pharmacophore modeling result of P-gp substrate binding. Further analysis suggested that the hypothesis PRR5 was responsible for competitive inhibition of OCT2, and other hypotheses were important for interaction between the inhibitor and OCT2. In light of the results, a hypothetical model for inhibiting transporting mediated by OCT2 was proposed.

  6. Discovery of an auto-regulation mechanism for the maltose ABC transporter MalFGK2.

    PubMed

    Bao, Huan; Duong, Franck

    2012-01-01

    The maltose transporter MalFGK(2), together with the substrate-binding protein MalE, is one of the best-characterized ABC transporters. In the conventional model, MalE captures maltose in the periplasm and delivers the sugar to the transporter. Here, using nanodiscs and proteoliposomes, we instead find that MalE is bound with high-affinity to MalFGK2 to facilitate the acquisition of the sugar. When the maltose concentration exceeds the transport capacity, MalE captures maltose and dissociates from the transporter. This mechanism explains why the transport rate is high when MalE has low affinity for maltose, and low when MalE has high affinity for maltose. Transporter-bound MalE facilitates the acquisition of the sugar at low concentrations, but also captures and dissociates from the transporter past a threshold maltose concentration. In vivo, this maltose-forced dissociation limits the rate of transport. Given the conservation of the substrate-binding proteins, this mode of allosteric regulation may be universal to ABC importers.

  7. Novel insights in transport mechanisms and kinetics of phenylacetic acid and penicillin-G in Penicillium chrysogenum.

    PubMed

    Douma, Rutger D; Deshmukh, Amit T; de Jonge, Lodewijk P; de Jong, Bouke W; Seifar, Reza M; Heijnen, Joseph J; van Gulik, Walter M

    2012-01-01

    Although penicillin-G (PenG) production by the fungus Penicillium chrysogenum is a well-studied process, little is known about the mechanisms of transport of the precursor phenylacetic acid (PAA) and the product PenG over the cell membrane. To obtain more insight in the nature of these mechanisms, in vivo stimulus response experiments were performed with PAA and PenG in chemostat cultures of P. chrysogenum at time scales of seconds to minutes. The results indicated that PAA is able to enter the cell by passive diffusion of the undissociated acid at a high rate, but is at the same time actively excreted, possibly by an ATP-binding cassette transporter. This results in a futile cycle, dissipating a significant amount of metabolic energy, which was confirmed by increased rates of substrate and oxygen consumption, and carbon dioxide production. To estimate the kinetic properties of passive import and active export of PAA over the cell membrane, a dynamic mathematical model was constructed. With this model, a good description of the dynamic data could be obtained. Also, PenG was found to be rapidly taken up by the cells upon extracellular addition, indicating that PenG transport is reversible. The measured concentration gradient of PenG over the cell membrane corresponded well with facilitated transport. Also, for PenG transport, a dynamic model was constructed and validated with experimental data. The outcome of the model simulations was in agreement with the presence of a facilitated transport system for PenG.

  8. Elementary steps for charge transport in DNA: thermal activation vs. tunneling

    NASA Astrophysics Data System (ADS)

    Berlin, Yuri A.; Burin, Alexander L.; Ratner, Mark A.

    2002-01-01

    Using stacks of Watson-Crick base pairs as an important example of multichromophoric molecular assemblies, we studied charge migration in DNA with special emphasis on the mechanism of hole hopping between neighboring guanines (G) connected by the adenine-thymine (AT) bridge. The tight-binding model proposed for this elementary step shows that for short AT bridges, hole transfer between two G bases proceeds via quantum mechanical tunneling. By contrast, hopping over long bridges requires thermal activation. The condition for crossover between tunneling and thermal activation near room temperature is specified and applies to the analysis of experimental data. We show that thermal activation dominates, if the bridge between two G bases contains more than three AT pairs. Our theoretical findings predict that the replacement of AT base pairs by GC pairs increases the efficiency of hole transport only in the case of short base pair sequences. For long sequences, however, the opposite effect is expected.

  9. Conserved transport mechanisms but distinct auxin responses govern shoot patterning in Selaginella kraussiana.

    PubMed

    Sanders, Heather L; Langdale, Jane A

    2013-04-01

    To provide a comparative framework to understand the evolution of auxin regulation in vascular plants, the effect of perturbed auxin homeostasis was examined in the lycophyte Selaginella kraussiana. Polar auxin transport was measured by tracing tritiated IAA in excised shoots. Shoots were cultured in the presence of auxin efflux inhibitors and exogenous auxin, and developmental abnormalities were documented. Auxin transport in Selaginella shoots is exclusively basipetal, as in angiosperms. Perturbed auxin transport results in the loss of meristem maintenance and abnormal shoot architecture. Dichotomous root branching in Selaginella appears to be regulated by an antagonistic relationship between auxin and cytokinin. The results suggest that basipetal polar auxin transport occurred in the common ancestor of lycophytes and euphyllophytes. Although the mechanisms of auxin transport appear to be conserved across all vascular plants, distinct auxin responses govern shoot growth and development in lycophytes and euphyllophytes.

  10. Evaluation of potential sources and transport mechanisms of fecal indicator bacteria to beach water, Murphy Park Beach, Door County, Wisconsin

    USGS Publications Warehouse

    Juckem, Paul F.; Corsi, Steven R.; McDermott, Colleen; Kleinheinz, Gregory; Fogarty, Lisa R.; Haack, Sheridan K.; Johnson, Heather E.

    2013-01-01

    Fecal Indicator Bacteria (FIB) concentrations in beach water have been used for many years as a criterion for closing beaches due to potential health concerns. Yet, current understanding of sources and transport mechanisms that drive FIB occurrence remains insufficient for accurate prediction of closures at many beaches. Murphy Park Beach, a relatively pristine beach on Green Bay in Door County, Wis., was selected for a study to evaluate FIB sources and transport mechanisms. Although the relatively pristine nature of the beach yielded no detection of pathogenic bacterial genes and relatively low FIB concentrations during the study period compared with other Great Lakes Beaches, its selection limited the number of confounding FIB sources and associated transport mechanisms. The primary sources of FIB appear to be internal to the beach rather than external sources such as rivers, storm sewer outfalls, and industrial discharges. Three potential FIB sources were identified: sand, swash-zone groundwater, and Cladophora mats. Modest correlations between FIB concentrations in these potential source reservoirs and FIB concentrations at the beach from the same day illustrate the importance of understanding transport mechanisms between FIB sources and the water column. One likely mechanism for transport and dispersion of FIB from sand and Cladophora sources appears to be agitation of Cladophora mats and erosion of beach sand due to storm activity, as inferred from storm indicators including turbidity, wave height, current speed, wind speed, sky visibility, 24-hour precipitation, and suspended particulate concentration. FIB concentrations in beach water had a statistically significant relation (p-value ‹0.05) with the magnitude of these storm indicators. In addition, transport of FIB in swash-zone groundwater into beach water appears to be driven by groundwater recharge associated with multiday precipitation and corresponding increased swash-zone groundwater discharge at

  11. Mechanism of ascaridole activation in Leishmania.

    PubMed

    Geroldinger, Gerald; Tonner, Matthias; Hettegger, Hubert; Bacher, Markus; Monzote, Lianet; Walter, Martin; Staniek, Katrin; Rosenau, Thomas; Gille, Lars

    2017-03-02

    values for Art. In a heme association assay Asc demonstrated a lower binding affinity to heme than Art. ICP-OES measurements revealed that in LtP the total iron concentrations were twice as high as values in J774 macrophages. Since low molecular iron was important in Asc activation we studied the influence of Asc on the labile iron pool (LIP) in LtP. Low temperature EPR experiments demonstrated that Asc shifts the redox balance of iron in the LIP to its oxidized state. These data demonstrate that univalent cleavage of Asc/Art in LtP is an essential part of their pharmacological mechanism. The structure of the EP determines whether activation by low molecular iron or heme is favored and the availability of these intracellular activators modulates their cytotoxicity. These findings may be helpful for synthesis of new Asc derivatives and understanding the action of EP in other cell types.

  12. Adult Active Transport in the Netherlands: An Analysis of Its Contribution to Physical Activity Requirements

    PubMed Central

    Fishman, Elliot; Böcker, Lars; Helbich, Marco

    2015-01-01

    Introduction Modern, urban lifestyles have engineered physical activity out of everyday life and this presents a major threat to human health. The Netherlands is a world leader in active travel, particularly cycling, but little research has sought to quantify the cumulative amount of physical activity through everyday walking and cycling. Methods Using data collected as part of the Dutch National Travel Survey (2010 – 2012), this paper determines the degree to which Dutch walking and cycling contributes to meeting minimum level of physical activity of 150 minutes of moderate intensity aerobic activity throughout the week. The sample includes 74,465 individuals who recorded at least some travel on the day surveyed. As physical activity benefits are cumulative, all walking and cycling trips are analysed, including those to and from public transport. These trips are then converted into an established measure of physical activity intensity, known as metabolic equivalents of tasks. Multivariate Tobit regression models were performed on a range of socio-demographic, transport resources, urban form and meteorological characteristics. Results The results reveal that Dutch men and women participate in 24 and 28 minutes of daily physical activity through walking and cycling, which is 41% and 55% more than the minimum recommended level. It should be noted however that some 57% of the entire sample failed to record any walking or cycling, and an investigation of this particular group serves as an important topic of future research. Active transport was positively related with age, income, bicycle ownership, urban density and air temperature. Car ownership had a strong negative relationship with physically active travel. Conclusion The results of this analysis demonstrate the significance of active transport to counter the emerging issue of sedentary lifestyle disease. The Dutch experience provides other countries with a highly relevant case study in the creation of

  13. Active migration and passive transport of malaria parasites.

    PubMed

    Douglas, Ross G; Amino, Rogerio; Sinnis, Photini; Frischknecht, Freddy

    2015-08-01

    Malaria parasites undergo a complex life cycle between their hosts and vectors. During this cycle the parasites invade different types of cells, migrate across barriers, and transfer from one host to another. Recent literature hints at a misunderstanding of the difference between active, parasite-driven migration and passive, circulation-driven movement of the parasite or parasite-infected cells in the various bodily fluids of mosquito and mammalian hosts. Because both active migration and passive transport could be targeted in different ways to interfere with the parasite, a distinction between the two ways the parasite uses to get from one location to another is essential. We discuss the two types of motion needed for parasite dissemination and elaborate on how they could be targeted by future vaccines or drugs.

  14. Directed transport of active particles over asymmetric energy barriers.

    PubMed

    Koumakis, N; Maggi, C; Di Leonardo, R

    2014-08-21

    We theoretically and numerically investigate the transport of active colloids to target regions, delimited by asymmetric energy barriers. We show that it is possible to introduce a generalized effective temperature that is related to the local variance of particle velocities. The stationary probability distributions can be derived from a simple diffusion equation in the presence of an inhomogeneous effective temperature resulting from the action of external force fields. In particular, transition rates over asymmetric energy barriers can be unbalanced by having different effective temperatures over the two slopes of the barrier. By varying the type of active noise, we find that equal values of diffusivity and persistence time may produce strongly varied effective temperatures and thus stationary distributions.

  15. Socioeconomic and regional differences in active transportation in Brazil

    PubMed Central

    de Sá, Thiago Hérick; Pereira, Rafael Henrique Moraes; Duran, Ana Clara; Monteiro, Carlos Augusto

    2016-01-01

    ABSTRACT OBJECTIVE To present national estimates regarding walking or cycling for commuting in Brazil and in 10 metropolitan regions. METHODS By using data from the Health section of 2008’s Pesquisa Nacional por Amostra de Domicílio (Brazil’s National Household Sample Survey), we estimated how often employed people walk or cycle to work, disaggregating our results by sex, age range, education level, household monthly income per capita, urban or rural address, metropolitan regions, and macro-regions in Brazil. Furthermore, we estimated the distribution of this same frequency according to quintiles of household monthly income per capita in each metropolitan region of the country. RESULTS A third of the employed men and women walk or cycle from home to work in Brazil. For both sexes, this share decreases as income and education levels rise, and it is higher among younger individuals, especially among those living in rural areas and in the Northeast region of the country. Depending on the metropolitan region, the practice of active transportation is two to five times more frequent among low-income individuals than among high-income individuals. CONCLUSIONS Walking or cycling to work in Brazil is most frequent among low-income individuals and the ones living in less economically developed areas. Active transportation evaluation in Brazil provides important information for public health and urban mobility policy-making PMID:27355465

  16. Activity ratios of (234)U/(238)U and (226)Ra/(228)Ra for transport mechanisms of elevated uranium in alluvial aquifers of groundwater in south-western (SW) Punjab, India.

    PubMed

    Kumar, A; Karpe, R K; Rout, S; Gautam, Y P; Mishra, M K; Ravi, P M; Tripathi, R M

    2016-01-01

    The concentrations of total dissolved uranium (U), its isotopic composition ((234)U, (235)U, (238)U) and two long lived Ra isotopes ((226)Ra and (228)Ra) in alluvial aquifers of groundwater were determined to investigate the groundwater flow pattern in the south-western (SW) Punjab, India. Particular attention was given to the spatial variability of activity ratios (ARs) of (234)U/(238)U and (226)Ra/(228)Ra to predict the possible sources and supply process of U into the water from the solid phase. The measured groundwater (234)U/(238)U ARs were ∼1 or >1 in the shallow zone (depth < 30 m) with high U concentration and <1 in the deeper zone (depth > 30 m) with relatively low U concentration. The simultaneous elevated U concentration and (234)U/(238)U ARs in waters were possibly due to differences in imprints of rock-water interactions under hydrologic conditions. However, (234)U/(238)U ARs < 1 clearly indicate the lack of recharge from surface water to groundwater leading to (234)U deficit in groundwater. This deficit might be also attributed to alpha recoil processes under strong dissolution. Overall, the decreasing pattern of (234)U/(238)U ARs observed from SE to SW or NW ward clearly indicates a groundwater flow paths from SE to SW/NW. Similarly, (226)Ra/(238)U ARs < 1 for all water samples reflect that the precursor (238)U is fairly mobile relative to (226)Ra. This might be due to unusually high amount of (238)U in groundwaters and subsequently the different geochemistry of the two isotopes. On the other hand, (226)Ra/(228)Ra ARs in groundwaters varied widely and observed about 50-300 times higher than (238)U/(232)Th ARs in granitic rocks or soils. Such elevation in ARs might be attributed to different dissolution properties of their parents during water-rock interactions or lattice damage during decay or local enrichments of uranium in the aquifers.

  17. Transport mechanisms acting in toroidal devices: A theoretician`s view

    SciTech Connect

    Carreras, B.A.

    1993-01-01

    Understanding the basic mechanisms of transport in toroidal confinement devices remains one of the more challenging scientific issues in magnetic confinement. At the same time, it is a critical issue for the magnetic fusion program. Recent progress in understanding fluctuations and transport has been fostered by the development and use of new diagnostics, bringing new perspectives on these studies. This has stimulated new theoretical developments. A view of the most recent issues and progress in this area is given. The role of long wavelengths in core transport and the relation between shear flows and turbulence at the plasma edge are the primary topics considered.

  18. Mechanism and Model of Laser-Driven Mass Transport in Thin Films of Azo Polymers

    DTIC Science & Technology

    2007-11-02

    and Model of Laser-Driven Mass Transport in Thin Films of Azo Polymers by C. J. Barrett, A. Natansohn, and P. Rochon Submitted for publication in...DATE June 23, 1998 Tprhnjr.fil P^nnr I’: 4. TITLE AHO SU3TITLE Mechanism and Model of Laser-Driven Mass Transport in Thin Films of Azo Polymers...TRANSPORT IN THIN FILMS OF AZO POLYMERS Christopher J. Barrett’, Almeria L. Natansohn1, and Paul L. Rochon2. ’Dept. of Chemistry. Queen’s

  19. Slide-and-exchange mechanism for rapid and selective transport through the nuclear pore complex

    PubMed Central

    Raveh, Barak; Karp, Jerome M.; Sparks, Samuel; Rout, Michael P.; Sali, Andrej; Cowburn, David

    2016-01-01

    Nucleocytoplasmic transport is mediated by the interaction of transport factors (TFs) with disordered phenylalanine-glycine (FG) repeats that fill the central channel of the nuclear pore complex (NPC). However, the mechanism by which TFs rapidly diffuse through multiple FG repeats without compromising NPC selectivity is not yet fully understood. In this study, we build on our recent NMR investigations showing that FG repeats are highly dynamic, flexible, and rapidly exchanging among TF interaction sites. We use unbiased long timescale all-atom simulations on the Anton supercomputer, combined with extensive enhanced sampling simulations and NMR experiments, to characterize the thermodynamic and kinetic properties of FG repeats and their interaction with a model transport factor. Both the simulations and experimental data indicate that FG repeats are highly dynamic random coils, lack intrachain interactions, and exhibit significant entropically driven resistance to spatial confinement. We show that the FG motifs reversibly slide in and out of multiple TF interaction sites, transitioning rapidly between a strongly interacting state and a weakly interacting state, rather than undergoing a much slower transition between strongly interacting and completely noninteracting (unbound) states. In the weakly interacting state, FG motifs can be more easily displaced by other competing FG motifs, providing a simple mechanism for rapid exchange of TF/FG motif contacts during transport. This slide-and-exchange mechanism highlights the direct role of the disorder within FG repeats in nucleocytoplasmic transport, and resolves the apparent conflict between the selectivity and speed of transport. PMID:27091992

  20. Evidence for a novel affinity mechanism of motor-assisted transport along microtubules.

    PubMed

    Wada, Y; Hamasaki, T; Satir, P

    2000-01-01

    In microtubule (MT) translocation assays, using colloidal gold particles coupled to monoclonal tubulin antibodies to mark positions along MTs, we found that relative motion is possible between the gold particle and an MT, gliding on dynein or kinesin. Such motion evidently occurred by an affinity release and rebinding mechanism that did not require motor activity on the particle. As the MTs moved, particles drifted to the trailing edge of the MT and then were released. Sometimes the particles transferred from one MT to another, moving orthogonally. Although motion of the particles was uniformly rearward, movement was toward the (-) or (+) end of the MT, depending on whether dynein or kinesin, respectively, was used in the assay. These results open possibilities for physiological mechanisms of organelle and other movement that, although dependent on motor-driven microtubule transport, do not require direct motor attachment between the organelle and the microtubule. Our observations on the direction of particle drift and time of release may also provide confirmation in a dynamic system for the conclusion that beta tubulin is exposed at the (+) end of the MT.

  1. Ca2+ transport in plant cells and mechanisms of transformation of phytochrome-induced photosignals

    NASA Astrophysics Data System (ADS)

    Volotovski, Igor D.

    1995-01-01

    The recent data on the influence of phytochrome on the efficiency of Ca2+ translocation across the membranes of oat protoplasts are given. Ca2+ uptake in the protoplasts was shown to be influenced by the red light (R) illumination. This effect was reverted by the following far-red light (FR) illumination. To elucidate the sensitivity to phytochrome-controlling action the screening between the mechanisms of Ca2+ transport across the plasma membranes of oat protoplasts, Na+/Ca2+ and Ca2+/H+ exchangers, Ca2+-pump and Ca2+-channel was done. It was established that phytochrome modulated the activity of Na+/Ca2+-exchanger and Ca2+-pump. The light-mediated oscillations of cytoplasmic Ca2+ concentration in the oat protoplasts were demonstrated using fluorescence probe quin2 loaded into the cells and laser monitoring of fluorescence signal. The evidences were obtained that the oscillations were not the result of the elevation of cytoplasmic Ca2+ concentration and had no connection with Ca2+ pool of mitochondria. The possibility of the relation between the Ca2+ oscillations and phosphoinositide metabolism in plant cell membranes is analyzed. The mechanisms of transformation of primary phytochrome signal into biological effects were discussed.

  2. An alkaline phosphatase transport mechanism in the pathogenesis of Alzheimer's disease and neurodegeneration.

    PubMed

    Pike, Adrianne F; Kramer, Nynke I; Blaauboer, Bas J; Seinen, Willem; Brands, Ruud

    2015-01-25

    Systemic inflammation is associated with loss of blood-brain barrier integrity and neuroinflammation that lead to the exacerbation of neurodegenerative diseases. It is also associated specifically with the characteristic amyloid-β and tau pathologies of Alzheimer's disease. We have previously proposed an immunosurveillance mechanism for epithelial barriers involving negative feedback-regulated alkaline phosphatase transcytosis as an acute phase anti-inflammatory response that hangs in the balance between the resolution and the progression of inflammation. We now extend this model to endothelial barriers, particularly the blood-brain barrier, and present a literature-supported mechanistic explanation for Alzheimer's disease pathology with this system at its foundation. In this mechanism, a switch in the role of alkaline phosphatase from its baseline duties to a stopgap anti-inflammatory function results in the loss of alkaline phosphatase from cell membranes into circulation, thereby decreasing blood-brain barrier integrity and functionality. This occurs with impairment of both amyloid-β efflux and tau dephosphorylating activity in the brain as alkaline phosphatase is replenished at the barrier by receptor-mediated transport. We suggest systemic alkaline phosphatase administration as a potential therapy for the resolution of inflammation and the prevention of Alzheimer's disease pathology as well as that of other inflammation-related neurodegenerative diseases.

  3. Transport coefficients and mechanical response in hard-disk colloidal suspensions

    NASA Astrophysics Data System (ADS)

    Zhang, Bo-Kai; Li, Jian; Chen, Kang; Tian, Wen-De; Ma, Yu-Qiang

    2016-11-01

    We investigate the transport properties and mechanical response of glassy hard disks using nonlinear Langevin equation theory. We derive expressions for the elastic shear modulus and viscosity in two dimensions on the basis of thermal-activated barrier-hopping dynamics and mechanically accelerated motion. Dense hard disks exhibit phenomena such as softening elasticity, shear-thinning of viscosity, and yielding upon deformation, which are qualitatively similar to dense hard-sphere colloidal suspensions in three dimensions. These phenomena can be ascribed to stress-induced “landscape tilting”. Quantitative comparisons of these phenomena between hard disks and hard spheres are presented. Interestingly, we find that the density dependence of yield stress in hard disks is much more significant than in hard spheres. Our work provides a foundation for further generalizing the nonlinear Langevin equation theory to address slow dynamics and rheological behavior in binary or polydisperse mixtures of hard or soft disks. Project supported by the National Basic Research Program of China (Grant No. 2012CB821500) and the National Natural Science Foundation of China (Grant Nos. 21374073 and, 21574096).

  4. Mechanisms of improvement of intestinal transport of baicalin and puerarin by extracts of Radix Angelicae Dahuricae.

    PubMed

    Liang, Xin-Li; Zhang, Jing; Zhao, Guo-Wei; Li, Zhe; Luo, Yun; Liao, Zheng-Gen; Yan, Dong-Mei

    2015-02-01

    Radix Angelicae Dahuricae is the dried root of Angelicae Dahurica (Fisch.ex Hoffm.)Benth.et Hook.f. var.formosana (Boiss.) Shan et Yuan (Fam.Umbelliferae). The total coumarins (Cou) and volatile oil (VO) were main active components that drived from Radix Angelicae Dahuricae. Our previous studies have shown that Cou and VO could increase intestinal absorption for transmucosal drug delivery with unknown mechanism. The aim of this study was to investigate the molecular mechanism of Radix Angelicae Dahuricae for improving drug intestinal transport. Caco-2 cell model was used to study the effect of Radix Angelicae Dahurica on transepithelial electrical resistance. Western blot was used to study its effect on the expression of the actin and ZO-1, tight junction proteins. The effect of Radix Angelicae Dahurica on the expression of P-gp protein was investigated using flow cytometry. VO (0.036-2.88 μL/mL) and Cou (0.027-0.54 mg/mL) caused a reversible, time- and dose-dependent decrease in transepithelial electrical resistance. VO and/or Cou could inhibit the expression of the tight junction protein, ZO-1 and actin. VO and/or Cou also could inhibit the expression of P-gp. These data suggested that Radix Angelicae Dahurica increased cell permeability by affecting the expression of actin, ZO-1 or P-gp, opening the tight junction or inhibiting the efflux induced by P-gp.

  5. Examining Changes in Radioxenon Isotope Activity Ratios during Subsurface Transport

    NASA Astrophysics Data System (ADS)

    Annewandter, R.

    2013-12-01

    The Non-Proliferation Experiment (NPE) has demonstrated and modelled the usefulness of barometric pumping induced soil gas sampling during On-Site inspections. Gas transport has been widely studied with different numerical codes. However, gas transport of all radioxenons in the post-detonation regime and their possible fractionation is still neglected in the open literature. Atmospheric concentrations of the radioxenons Xe-135, Xe-133m, Xe-133 and Xe-131m can be used to discriminate between civilian releases (nuclear power plants or medical isotope facilities), and nuclear explosion sources. It is based on the isotopic activity ratio method. Yet it is not clear whether subsurface migration of the radioxenons, with eventual release into the atmosphere, can affect the activity ratios due to fractionation. Fractionation can be caused by different diffusivities due to mass differences between the radioxenons. A previous study showed surface arrival time of a chemically inert gaseous tracer is affected by its diffusivity. They observed detectable amount for SF6 50 days after detonation and 375 days for He-3. They predict 50 and 80 days for Xe-133 and Ar-37 respectively. Cyclical changes in atmospheric pressure can drive subsurface gas transport. This barometric pumping phenomenon causes an oscillatoric flow in upward trending fractures which, combined with diffusion into the porous matrix, leads to a net transport of gaseous components - a ratcheting effect. We use a general purpose reservoir simulator (Complex System Modelling Platform, CSMP++) which has been applied in a range of fields such as deep geothermal systems, three-phase black oil simulations , fracture propagation in fractured, porous media, Navier-Stokes pore-scale modelling among others. It is specifically designed to account for structurally complex geologic situation of fractured, porous media. Parabolic differential equations are solved by a continuous Galerkin finite-element method, hyperbolic

  6. Sodium Absorption by Barley Roots: Role of the Dual Mechanisms of Alkali Cation Transport 1

    PubMed Central

    Rains, D. W.; Epstein, Emanuel

    1967-01-01

    Radioactively labeled Na+ absorbed by barley roots was sequestered in an intracellular compartment or compartments (“inner” spaces) in which it was only very slowly exchangeable with exogenous Na+. Absorption of this fraction proceeded at a constant rate for at least 1 hour. When the rate of Na+ absorption was examined over the range of concentrations, 0.005 to 50 mm, the isotherm depicting the relation showed dual kinetics as follows. Over the range, 0.005 to 0.2 mm, a single Michaelis-Menten term describes the relation between the concentration of Na+ and the rate of its absorption. The mechanism of Na+ absorption operating over this range of concentrations, mechanism 1 of alkali cation transport, is severely inhibited in the presence of Ca2+ and virtually rendered inoperative for Na+ transport by the combined presence of Ca2+ and K+. The mechanism is equally effective in Na+ transport whether Cl− or F− is the anion, but is somewhat inhibited when the anion is SO42−. Over the high range of concentrations, 0.5 to 50 mm Na+, a second, low-affinity mechanism of Na+ absorption comes into play. In the presence of Ca2+ and K+, this mechanism 2 is the only one to transport Na+ effectively, since Na+ absorption via mechanism 1 is virtually abolished under these conditions. Anaerobic conditions, low temperature, and the uncoupler, 2,4-dinitrophenol, inhibit Na+ absorption both at low and high Na+ concentrations. PMID:16656509

  7. Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment

    PubMed Central

    Kodama, Hiroko; Fujisawa, Chie; Bhadhprasit, Wattanaporn

    2012-01-01

    Copper is an essential trace element required by all living organisms. Excess amounts of copper, however, results in cellular damage. Disruptions to normal copper homeostasis are hallmarks of three genetic disorders: Menkes disease, occipital horn syndrome, and Wilson’s disease. Menkes disease and occipital horn syndrome are characterized by copper deficiency. Typical features of Menkes disease result from low copper-dependent enzyme activity. Standard treatment involves parenteral administration of copper-histidine. If treatment is initiated before 2 months of age, neurodegeneration can be prevented, while delayed treatment is utterly ineffective. Thus, neonatal mass screening should be implemented. Meanwhile, connective tissue disorders cannot be improved by copper-histidine treatment. Combination therapy with copper-histidine injections and oral administration of disulfiram is being investigated. Occipital horn syndrome characterized by connective tissue abnormalities is the mildest form of Menkes disease. Treatment has not been conducted for this syndrome. Wilson’s disease is characterized by copper toxicity that typically affects the hepatic and nervous systems severely. Various other symptoms are observed as well, yet its early diagnosis is sometimes difficult. Chelating agents and zinc are effective treatments, but are inefficient in most patients with fulminant hepatic failure. In addition, some patients with neurological Wilson’s disease worsen or show poor response to chelating agents. Since early treatment is critical, a screening system for Wilson’s disease should be implemented in infants. Patients with Wilson’s disease may be at risk of developing hepatocellular carcinoma. Understanding the link between Wilson’s disease and hepatocellular carcinoma will be beneficial for disease treatment and prevention. PMID:21838703

  8. Electric Pulse Discharge Activated Carbon Supercapacitors for Transportation Application

    NASA Astrophysics Data System (ADS)

    Nayak, Subhadarshi; Agrawal, Jyoti

    2012-03-01

    ScienceTomorrow is developing a high-speed, low-cost process for synthesizing high-porosity electrodes for electrochemical double-layer capacitors. Four types of coal (lignite, subbituminous, bituminous, and anthracite) were used as precursor materials for spark discharge activation with multiscale porous structure. The final porosity and pore distribution depended, among other factors, on precursor type. The high gas content in low-grade carbon resulted in mechanical disintegration, whereas high capacitance was attained in higher-grade coal. The properties, including capacitance, mechanical robustness, and internal conductivity, were excellent when the cost is taken into consideration.

  9. Influence of mechanical activation of steel powder on its properties

    NASA Astrophysics Data System (ADS)

    Vaulina, O. Yu; Darenskaia, E. A.; Myachin, Y. V.; Vasilyeva, I. E.; Kulkov, S. N.

    2017-02-01

    It has been studied properties of stainless steel based powders after mechanical activation using planetary ball milling technique. It have been shown that after one minute mechanical activation porosity of sintered steel is less than 5%, which is less than the porosity of the sintered steel powder without mechanical activation. The sample without activation has austenite state, which changes after activation toaustenite and ferrite mixtures. X-ray analysis confirmed that the mechanical activation leads to a change in the phase state of the samples: the samples without activation of the FCC structure (γ-Fe), after activation - FCC (γ-Fe) and BCC (α-Fe). The hardness increases at increasing activation time from 800 MPa for the sample without mechanical activation to 1250 MPa for the sample with the activation time of 10 minutes.

  10. Interdisciplinary Research to Elucidate Mechanisms Governing Silver Nanoparticle Fate and Transport in Porous Media

    NASA Astrophysics Data System (ADS)

    Pennell, K. D.; Mittleman, A.; Taghavy, A.; Fortner, J.; Lantagne, D.; Abriola, L. M.

    2014-12-01

    Interdisciplinary Research to Elucidate Mechanisms Governing Silver Nanoparticle Fate and Transport in Porous Media Anjuliee M. Mittelman, Amir Taghavy, Yonggang Wang, John D. Fortner, Daniele S. Lantagne, Linda M. Abriola and Kurt D. Pennell* Detailed knowledge of the processes governing nanoparticle transport and reactivity in porous media is essential for accurate predictions of environmental fate, water and wastewater treatment system performance, and assessment of potential risks to ecosystems and water supplies. To address these issues, an interdisciplinary research team combined experimental and mathematical modeling studies to investigate the mobility, dissolution, and aging of silver nanoparticles (nAg) in representative aquifer materials and ceramic filters. Results of one-dimensional column studies, conducted with water-saturated sands maintained at pH 4 or 7 and three levels of dissolved oxygen (DO), revealed that fraction of silver mass eluted as Ag+ increased with increasing DO level, and that the dissolution of attached nAg decreased over time as a result of surface oxidation. A hybrid Eulerain-Lagragian nanoparticle transport model, which incorporates DO-dependent dissolution kinetics and particle aging, was able to accurately simulate nAg mobility and Ag+ release measured in the column experiments. Model sensitivity analysis indicated that as the flow velocity and particle size decrease, nAg dissolution and Ag+ transport processes increasingly govern silver mobility. Consistent results were obtained in studies of ceramic water filters treated with nAg, where silver elution was shown to be governed by nAg dissolution to form Ag+ and subsequent cation exchange reactions. Recent studies explored the effects of surface coating aging on nAg aggregation, mobility and dissolution. Following ultraviolet light, nAg retention in water saturated sand increased by 25-50%, while up to 50% of the applied mass eluted as Ag+ compared to less than 1% for un-aged n

  11. Interdisciplinary Research to Elucidate Mechanisms Governing Silver Nanoparticle Fate and Transport in Porous Media

    NASA Astrophysics Data System (ADS)

    Pennell, K. D.; Mittleman, A.; Taghavy, A.; Fortner, J.; Lantagne, D.; Abriola, L. M.

    2015-12-01

    Interdisciplinary Research to Elucidate Mechanisms Governing Silver Nanoparticle Fate and Transport in Porous Media Anjuliee M. Mittelman, Amir Taghavy, Yonggang Wang, John D. Fortner, Daniele S. Lantagne, Linda M. Abriola and Kurt D. Pennell* Detailed knowledge of the processes governing nanoparticle transport and reactivity in porous media is essential for accurate predictions of environmental fate, water and wastewater treatment system performance, and assessment of potential risks to ecosystems and water supplies. To address these issues, an interdisciplinary research team combined experimental and mathematical modeling studies to investigate the mobility, dissolution, and aging of silver nanoparticles (nAg) in representative aquifer materials and ceramic filters. Results of one-dimensional column studies, conducted with water-saturated sands maintained at pH 4 or 7 and three levels of dissolved oxygen (DO), revealed that fraction of silver mass eluted as Ag+ increased with increasing DO level, and that the dissolution of attached nAg decreased over time as a result of surface oxidation. A hybrid Eulerain-Lagragian nanoparticle transport model, which incorporates DO-dependent dissolution kinetics and particle aging, was able to accurately simulate nAg mobility and Ag+ release measured in the column experiments. Model sensitivity analysis indicated that as the flow velocity and particle size decrease, nAg dissolution and Ag+ transport processes increasingly govern silver mobility. Consistent results were obtained in studies of ceramic water filters treated with nAg, where silver elution was shown to be governed by nAg dissolution to form Ag+ and subsequent cation exchange reactions. Recent studies explored the effects of surface coating aging on nAg aggregation, mobility and dissolution. Following ultraviolet light, nAg retention in water saturated sand increased by 25-50%, while up to 50% of the applied mass eluted as Ag+ compared to less than 1% for un-aged n

  12. A fully resolved fluid-structure-muscle-activation model for esophageal transport

    NASA Astrophysics Data System (ADS)

    Kou, Wenjun; Bhalla, Amneet P. S.; Griffith, Boyce E.; Johnson, Mark; Patankar, Neelesh A.

    2013-11-01

    Esophageal transport is a mechanical and physiological process that transfers the ingested food bolus from the pharynx to the stomach through a multi-layered esophageal tube. The process involves interactions between the bolus, esophageal wall composed of mucosal, circular muscle (CM) and longitudinal muscle (LM) layers, and neurally coordinated muscle activation including CM contraction and LM shortening. In this work, we present a 3D fully-resolved model of esophageal transport based on the immersed boundary method. The model describes the bolus as a Newtonian fluid, the esophageal wall as a multi-layered elastic tube represented by springs and beams, and the muscle activation as a traveling wave of sequential actuation/relaxation of muscle fibers, represented by springs with dynamic rest lengths. Results on intraluminal pressure profile and bolus shape will be shown, which are qualitatively consistent with experimental observations. Effects of activating CM contraction only, LM shortening only or both, for the bolus transport, are studied. A comparison among them can help to identify the role of each type of muscle activation. The support of grant R01 DK56033 and R01 DK079902 from NIH is gratefully acknowledged.

  13. Quantification of ionic transport within thermally-activated batteries using electron probe micro-analysis

    NASA Astrophysics Data System (ADS)

    Humplik, Thomas; Stirrup, Emily K.; Grillet, Anne M.; Grant, Richard P.; Allen, Ashley N.; Wesolowski, Daniel E.; Roberts, Christine C.

    2016-07-01

    The transient transport of electrolytes in thermally-activated batteries is studied using electron probe micro-analysis (EPMA), demonstrating the robust capability of EPMA as a useful tool for studying and quantifying mass transport within porous materials, particularly in difficult environments where classical flow measurements are challenging. By tracking the mobility of bromine and potassium ions from the electrolyte stored within the separator into the lithium silicon anode and iron disulfide cathode, we are able to quantify the transport mechanisms and physical properties of the electrodes including permeability and tortuosity. Due to the micron to submicron scale porous structure of the initially dry anode, a fast capillary pressure driven flow is observed into the anode from which we are able to set a lower bound on the permeability of 10-1 mDarcy. The transport into the cathode is diffusion-limited because the cathode originally contained some electrolyte before activation. Using a transient one-dimensional diffusion model, we estimate the tortuosity of the cathode electrode to be 2.8 ± 0.8.

  14. Structural insight in the toppling mechanism of an energy-coupling factor transporter

    PubMed Central

    Swier, Lotteke J. Y. M.; Guskov, Albert; Slotboom, Dirk J.

    2016-01-01

    Energy-coupling factor (ECF) transporters mediate uptake of micronutrients in prokaryotes. The transporters consist of an S-component that binds the transported substrate and an ECF module (EcfAA′T) that binds and hydrolyses ATP. The mechanism of transport is poorly understood but presumably involves an unusual step in which the membrane-embedded S-component topples over to carry the substrate across the membrane. In many ECF transporters, the S-component dissociates from the ECF module after transport. Subsequently, substrate-bound S-components out-compete the empty proteins for re-binding to the ECF module in a new round of transport. Here we present crystal structures of the folate-specific transporter ECF–FolT from Lactobacillus delbrueckii. Interaction of the ECF module with FolT stabilizes the toppled state, and simultaneously destroys the high-affinity folate-binding site, allowing substrate release into the cytosol. We hypothesize that differences in the kinetics of toppling can explain how substrate-loaded FolT out-competes apo-FolT for association with the ECF module. PMID:27026363

  15. Structure of Bor1 supports an elevator transport mechanism for SLC4 anion exchangers

    PubMed Central

    Thurtle-Schmidt, Bryan H.; Stroud, Robert M.

    2016-01-01

    Boron is essential for plant growth because of its incorporation into plant cell walls; however, in excess it is toxic to plants. Boron transport and homeostasis in plants is regulated in part by the borate efflux transporter Bor1, a member of the solute carrier (SLC) 4 transporter family with homology to the human bicarbonate transporter Band 3. Here, we present the 4.1-Å resolution crystal structure of Arabidopsis thaliana Bor1. The structure displays a dimeric architecture in which dimerization is mediated by centralized Gate domains. Comparisons with a structure of Band 3 in an outward-open state reveal that the Core domains of Bor1 have rotated inwards to achieve an occluded state. Further structural comparisons with UapA, a xanthine transporter from the nucleobase-ascorbate transporter family, show that the downward pivoting of the Core domains relative to the Gate domains may access an inward-open state. These results suggest that the SLC4, SLC26, and nucleobase-ascorbate transporter families all share an elevator transport mechanism in which alternating access is provided by Core domains that carry substrates across a membrane. PMID:27601653

  16. The direction of water transport on Mars: A possible pumping mechanism

    NASA Astrophysics Data System (ADS)

    James, P. B.

    It is suggested that an atmospheric pumping mechanism might be at work in which water is preferentially transported into the north by a mass outflow wind (due to sublimation from polar cap) that is stronger during southern spring than it is during northern spring. The mechanism is provided by the asymmetric seasonal temperature distribution produced by the eccentric martial orbit and by the associated seasonal asymmetry in the carbon dioxide cycle. The alternating condensation and sublimation of CO2 at the poles produces condensation winds which, in turn, contribute to the meridional transport of water vapor.

  17. The direction of water transport on Mars: A possible pumping mechanism

    NASA Technical Reports Server (NTRS)

    James, P. B.

    1987-01-01

    It is suggested that an atmospheric pumping mechanism might be at work in which water is preferentially transported into the north by a mass outflow wind (due to sublimation from polar cap) that is stronger during southern spring than it is during northern spring. The mechanism is provided by the asymmetric seasonal temperature distribution produced by the eccentric martial orbit and by the associated seasonal asymmetry in the carbon dioxide cycle. The alternating condensation and sublimation of CO2 at the poles produces condensation winds which, in turn, contribute to the meridional transport of water vapor.

  18. Molecular mechanism of serotonin transporter inhibition elucidated by a new flexible docking protocol.

    PubMed

    Gabrielsen, Mari; Kurczab, Rafał; Ravna, Aina W; Kufareva, Irina; Abagyan, Ruben; Chilmonczyk, Zdzisław; Bojarski, Andrzej J; Sylte, Ingebrigt

    2012-01-01

    The two main groups of antidepressant drugs, the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitors (SSRIs), as well as several other compounds, act by inhibiting the serotonin transporter (SERT). However, the binding mode and molecular mechanism of inhibition in SERT are not fully understood. In this study, five classes of SERT inhibitors were docked into an outward-facing SERT homology model using a new 4D ensemble docking protocol. Unlike other docking protocols, where protein flexibility is not considered or is highly dependent on the ligand structure, flexibility was here obtained by side chain sampling of the amino acids of the binding pocket using biased probability Monte Carlo (BPMC) prior to docking. This resulted in the generation of multiple binding pocket conformations that the ligands were docked into. The docking results showed that the inhibitors were stacked between the aromatic amino acids of the extracellular gate (Y176, F335) presumably preventing its closure. The inhibitors interacted with amino acids in both the putative substrate binding site and more extracellular regions of the protein. A general structure-docking-based pharmacophore model was generated to explain binding of all studied classes of SERT inhibitors. Docking of a test set of actives and decoys furthermore showed that the outward-facing ensemble SERT homology model consistently and selectively scored the majority of active compounds above decoys, which indicates its usefulness in virtual screening.

  19. Active transport and obesity prevention - A transportation sector obesity impact scoping review and assessment for Melbourne, Australia.

    PubMed

    Brown, V; Moodie, M; Mantilla Herrera, A M; Veerman, J L; Carter, R

    2017-03-01

    Given the alarming prevalence of obesity worldwide and the need for interventions to halt the growing epidemic, more evidence on the role and impact of transport interventions for obesity prevention is required. This study conducts a scoping review of the current evidence of association between modes of transport (motor vehicle, walking, cycling and public transport) and obesity-related outcomes. Eleven reviews and thirty-three primary studies exploring associations between transport behaviours and obesity were identified. Cohort simulation Markov modelling was used to estimate the effects of body mass index (BMI) change on health outcomes and health care costs of diseases causally related to obesity in the Melbourne, Australia population. Results suggest that evidence for an obesity effect of transport behaviours is inconclusive (29% of published studies reported expected associations, 33% mixed associations), and any potential BMI effect is likely to be relatively small. Hypothetical scenario analyses suggest that active transport interventions may contribute small but significant obesity-related health benefits across populations (approximately 65 health adjusted life years gained per year). Therefore active transport interventions that are low cost and targeted to those most amenable to modal switch are the most likely to be effective and cost-effective from an obesity prevention perspective. The uncertain but potentially significant opportunity for health benefits warrants the collection of more and better quality evidence to fully understand the potential relationships between transport behaviours and obesity. Such evidence would contribute to the obesity prevention dialogue and inform policy across the transportation, health and environmental sectors.

  20. Mechanisms for cellular transport and release of allelochemicals from plant roots into the rhizosphere.

    PubMed

    Weston, Leslie A; Ryan, Peter R; Watt, Michelle

    2012-05-01

    Allelochemicals and other metabolites released by plant roots play important roles in rhizosphere signalling, plant defence and responses to abiotic stresses. Plants use a variety of sequestration and transport mechanisms to move and export bioactive products safely into the rhizosphere. The use of mutants and molecular tools to study gene expression has revealed new information regarding the diverse group of transport proteins and conjugation processes employed by higher plants. Transport systems used for moving secondary products into and out of root cells are similar to those used elsewhere in the plant but are closely linked to soil environmental conditions and local root health. Root cells can rapidly generate and release large quantities of allelochemicals in response to stress or local rhizosphere conditions, so the production and transport of these compounds in cells are often closely linked. Plants need to manage the potentially toxic allelochemicals and metabolites they produce by sequestering them to the vacuole or other membrane-bound vesicles. These compartments provide secure storage areas and systems for safely moving bioactive chemicals throughout the cytosol. Release into the apoplast occurs either by exocytosis or through membrane-bound transport proteins. This review discusses the possible transport mechanisms involved in releasing specific root-produced allelochemicals by combining microscopic observations of the specialized root cells with the physical and chemical properties of the exudates.

  1. Substrate specificity and transport mechanism of amino-acid transceptor Slimfast from Aedes aegypti

    PubMed Central

    Boudko, Dmitri Y.; Tsujimoto, Hitoshi; Rodriguez, Stacy D.; Meleshkevitch, Ella A.; Price, David P.; Drake, Lisa L.; Hansen, Immo A.

    2015-01-01

    Anautogenous mosquitoes depend on vertebrate blood as nutrient source for their eggs. A highly efficient set of membrane transporters mediates the massive movement of nutrient amino acids between mosquito tissues after a blood meal. Here we report the characterization of the amino-acid transporter Slimfast (Slif) from the yellow-fever mosquito Aedes aegypti using codon-optimized heterologous expression. Slif is a well-known component of the target-of-rapamycin signalling pathway and fat body nutrient sensor, but its substrate specificity and transport mechanism were unknown. We found that Slif transports essential cationic and neutral amino acids with preference for arginine. It has an unusual dual-affinity mechanism with only the high affinity being Na+ dependent. Tissue-specific expression and blood meal-dependent regulation of Slif are consistent with conveyance of essential amino acids from gut to fat body. Slif represents a novel transport system and type of transceptor for sensing and transporting essential amino acids during mosquito reproduction. PMID:26449545

  2. SUPG and discontinuity-capturing methods for coupled fluid mechanics and electrochemical transport problems

    NASA Astrophysics Data System (ADS)

    Kler, Pablo A.; Dalcin, Lisandro D.; Paz, Rodrigo R.; Tezduyar, Tayfun E.

    2013-02-01

    Electrophoresis is the motion of charged particles relative to the surrounding liquid under the influence of an external electric field. This electrochemical transport process is used in many scientific and technological areas to separate chemical species. Modeling and simulation of electrophoretic transport enables a better understanding of the physicochemical processes developed during the electrophoretic separations and the optimization of various parameters of the electrophoresis devices and their performance. Electrophoretic transport is a multiphysics and multiscale problem. Mass transport, fluid mechanics, electric problems, and their interactions have to be solved in domains with length scales ranging from nanometers to centimeters. We use a finite element method for the computations. Without proper numerical stabilization, computation of coupled fluid mechanics, electrophoretic transport, and electric problems would suffer from spurious oscillations that are related to the high values of the local Péclet and Reynolds numbers and the nonzero divergence of the migration field. To overcome these computational challenges, we propose a stabilized finite element method based on the Streamline-Upwind/Petrov-Galerkin (SUPG) formulation and discontinuity-capturing techniques. To demonstrate the effectiveness of the stabilized formulation, we present test computations with 1D, 2D, and 3D electrophoretic transport problems of technological interest.

  3. Complex transport behaviors of rectangular graphene quantum dots subject to mechanical vibrations

    NASA Astrophysics Data System (ADS)

    Xu, Mengke; Wang, Yisen; Bao, Rui; Huang, Liang; Lai, Ying-Cheng

    2016-05-01

    Graphene-based mechanical resonators have attracted much attention due to their superior elastic properties and extremely low mass density. We investigate the effects of mechanical vibrations on electronic transport through graphene quantum dots, under the physically reasonable assumption that the time scale associated with electronic transport is much shorter than that with mechanical vibration so that, at any given time, an electron “sees” a static but deformed graphene sheet. We find that, besides periodic oscillation in the quantum transmission at the same frequency as that of mechanical vibrations, structures at finer scales can emerge as an intermediate state, which may lead to spurious higher-frequency components in the current through the device.

  4. Pore scale mechanisms for enhanced vapor transport through partially saturated porous media

    NASA Astrophysics Data System (ADS)

    Shahraeeni, Ebrahim; Or, Dani

    2012-05-01

    Recent theoretical and experimental studies of vapor transport through porous media question the existence and significance of vapor transport enhancement mechanisms postulated by Philip and de Vries. Several enhancement mechanisms were proposed to rectify shortcomings of continuum models and to reconcile discrepancies between predicted and observed vapor fluxes. The absence of direct experimental and theoretical confirmation of these commonly invoked pore scale mechanisms prompted alternate explanations considering the (often neglected) role of transport via capillary connected pathways. The objective of this work was to quantify the specific roles of liquid bridges and of local thermal and capillary gradients on vapor transport at the pore scale. We considered a mechanistic pore scale model of evaporation and condensation dynamics as a building block for quantifying vapor diffusion through partially saturated porous media. Simulations of vapor diffusion in the presence of isolated liquid phase bridges reveal that the so-called enhanced vapor diffusion under isothermal conditions reflects a reduced gaseous diffusion path length. The presence of a thermal gradient may augment or hinder this effect depending on the direction of thermal relative to capillary gradients. As liquid phase saturation increases, capillary transport becomes significant and pore scale vapor enhancement is limited to low water contents as postulated by Philip and deVries. Calculations show that with assistance of a mild thermal gradient water vapor flux could be doubled relative to diffusion of an inert gas through the same system.

  5. Modeling the coupled mechanics, transport, and growth processes in collagen tissues.

    SciTech Connect

    Holdych, David J.; Nguyen, Thao D.; Klein, Patrick A.; in't Veld, Pieter J.; Stevens, Mark Jackson

    2006-11-01

    The purpose of this project is to develop tools to model and simulate the processes of self-assembly and growth in biological systems from the molecular to the continuum length scales. The model biological system chosen for the study is the tendon fiber which is composed mainly of Type I collagen fibrils. The macroscopic processes of self-assembly and growth at the fiber scale arise from microscopic processes at the fibrillar and molecular length scales. At these nano-scopic length scales, we employed molecular modeling and simulation method to characterize the mechanical behavior and stability of the collagen triple helix and the collagen fibril. To obtain the physical parameters governing mass transport in the tendon fiber we performed direct numerical simulations of fluid flow and solute transport through an idealized fibrillar microstructure. At the continuum scale, we developed a mixture theory approach for modeling the coupled processes of mechanical deformation, transport, and species inter-conversion involved in growth. In the mixture theory approach, the microstructure of the tissue is represented by the species concentration and transport and material parameters, obtained from fibril and molecular scale calculations, while the mechanical deformation, transport, and growth processes are governed by balance laws and constitutive relations developed within a thermodynamically consistent framework.

  6. Theory of activated transport in bilayer quantum Hall systems.

    PubMed

    Roostaei, B; Mullen, K J; Fertig, H A; Simon, S H

    2008-07-25

    We analyze the transport properties of bilayer quantum Hall systems at total filling factor nu=1 in drag geometries as a function of interlayer bias, in the limit where the disorder is sufficiently strong to unbind meron-antimeron pairs, the charged topological defects of the system. We compute the typical energy barrier for these objects to cross incompressible regions within the disordered system using a Hartree-Fock approach, and show how this leads to multiple activation energies when the system is biased. We then demonstrate using a bosonic Chern-Simons theory that in drag geometries current in a single layer directly leads to forces on only two of the four types of merons, inducing dissipation only in the drive layer. Dissipation in the drag layer results from interactions among the merons, resulting in very different temperature dependences for the drag and drive layers, in qualitative agreement with experiment.

  7. Investigation of Gas Phase Transport Mechanisms in Unsaturated Zones Under Natural Conditions

    NASA Astrophysics Data System (ADS)

    You, K.; Zhan, H.

    2012-12-01

    Diffusive flux is traditionally treated as the dominant mechanism for gas transport in unsaturated zones without active disturbance. However, some researchers have found that the pressure-driven and density-driven advective flux may also be important under certain conditions. This article conducts a comprehensive study of the diffusive, pressure-driven and density-driven advective fluxes of the gas phase volatile organic compounds (VOCs) in the unsaturated zone under various hydrogeological conditions. The presence of a less or more permeable layer at ground surface in a heterogeneous unsaturated zone is investigated for their influence on the time-averaged advective and diffusive fluxes. Our developed numerical solution is applied to interpret a field study of the trichloroethylene contamination in the unsaturated zone at Picatinny Arsenal in Morris County, New Jersey. Results show that under most of the field conditions the time-averaged advective flux is one to three orders of magnitude smaller than the diffusive flux, and the influence of the density-driven flux on the advective flux is undetectable. The time-averaged advective flux is comparable in magnitude with the diffusive flux only in a deep unsaturated zone (thickness greater than 15 m), or when the gas-filled porosity is less than 0.05, or the magnitude of the water table fluctuation is greater than 0.2 m for the default parameters used in this study. A less permeable layer at ground surface increases the total flux of VOCs under it, while a permeable layer at ground surface increases the total flux in it. The error induced by fixing the water table position but allowing the fluctuation of water table moving velocity is negligible for predicting the gas phase VOCs transport in an unsaturated zone at non-coastal sites.

  8. Complement activation of electrogenic ion transport in isolated rat colon.

    PubMed

    McCole, D F; Otti, B; Newsholme, P; Baird, A W

    1997-11-15

    The complement cascade is an important component in many immune and inflammatory reactions and may contribute to both the diarrhoea and inflammation associated with inflammatory bowel disease. Isolated rat colonic mucosae were voltage clamped in Ussing chambers. Basolateral addition of zymosan-activated whole human serum (ZAS) induced a rapid onset, transient inward short circuit current (SCC). This response was concentration dependent and was significantly attenuated by pre-heating ZAS at 60 degrees C for 30 min. Depletion of complement from normal human serum with cobra venom factor (CVF) significantly lowered SCC responses. Chloride was the primary charge carrying ion as responses to ZAS were abolished in the presence of the loop diuretic bumetanide. The complement component C3a stimulated ion transport but not to the same extent as whole serum. Exogenous C5 was without effect. The cyclooxygenase inhibitor piroxicam significantly attenuated the response to ZAS. These findings support the possibility that complement activation may contribute to the pathophysiology of secretory diarrhoea since activation of electrogenic chloride secretion converts intestinal epithelia to a state of net fluid secretion.

  9. Tubulin transport by IFT is upregulated during ciliary growth by a cilium-autonomous mechanism.

    PubMed

    Craft, Julie M; Harris, J Aaron; Hyman, Sebastian; Kner, Peter; Lechtreck, Karl F

    2015-01-19

    The assembly of the axoneme, the structural scaffold of cilia and flagella, requires translocation of a vast quantity of tubulin into the growing cilium, but the mechanisms that regulate the targeting, quantity, and timing of tubulin transport are largely unknown. In Chlamydomonas, GFP-tagged α-tubulin enters cilia as an intraflagellar transport (IFT) cargo and by diffusion. IFT-based transport of GFP-tubulin is elevated in growing cilia and IFT trains carry more tubulin. Cells possessing both nongrowing and growing cilia selectively target GFP-tubulin into the latter. The preferential delivery of tubulin boosts the concentration of soluble tubulin in the matrix of growing versus steady-state cilia. Cilia length mutants show abnormal kinetics of tubulin transport. We propose that cells regulate the extent of occupancy of IFT trains by tubulin cargoes. During ciliary growth, IFT concentrates soluble tubulin in cilia and thereby promotes elongation of the axonemal microtubules.

  10. Drug metabolism and transport during pregnancy: how does drug disposition change during pregnancy and what are the mechanisms that cause such changes?

    PubMed

    Isoherranen, Nina; Thummel, Kenneth E

    2013-02-01

    There is increasing evidence that pregnancy alters the function of drug-metabolizing enzymes and drug transporters in a gestational-stage and tissue-specific manner. In vivo probe studies have shown that the activity of several hepatic cytochrome P450 enzymes, such as CYP2D6 and CYP3A4, is increased during pregnancy, whereas the activity of others, such as CYP1A2, is decreased. The activity of some renal transporters, including organic cation transporter and P-glycoprotein, also appears to be increased during pregnancy. Although much has been learned, significant gaps still exist in our understanding of the spectrum of drug metabolism and transport genes affected, gestational age-dependent changes in the activity of encoded drug metabolizing and transporting processes, and the mechanisms of pregnancy-induced alterations. In this issue of Drug Metabolism and Disposition, a series of articles is presented that address the predictability, mechanisms, and magnitude of changes in drug metabolism and transport processes during pregnancy. The articles highlight state-of-the-art approaches to studying mechanisms of changes in drug disposition during pregnancy, and illustrate the use and integration of data from in vitro models, animal studies, and human clinical studies. The findings presented show the complex inter-relationships between multiple regulators of drug metabolism and transport genes, such as estrogens, progesterone, and growth hormone, and their effects on enzyme and transporter expression in different tissues. The studies provide the impetus for a mechanism- and evidence-based approach to optimally managing drug therapies during pregnancy and improving treatment outcomes.

  11. Repeated swim impairs serotonin clearance via a corticosterone-sensitive mechanism: organic cation transporter 3, the smoking gun.

    PubMed

    Baganz, Nicole; Horton, Rebecca; Martin, Kathryn; Holmes, Andrew; Daws, Lynette C

    2010-11-10

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with increased extracellular serotonin (5-HT) in limbic brain regions. The mechanism through which this occurs remains unclear. One way could be via HPA axis-dependent impairment of serotonin transporter (SERT) function, the high-affinity uptake mechanism for 5-HT. Consistent with this idea, we found that 5-HT clearance rate in hippocampus was dramatically reduced in mice exposed to repeated swim, a stimulus known to activate the HPA axis. However, this phenomenon also occurred in mice lacking SERT, ruling out SERT as a mechanism. The organic cation transporter 3 (OCT3) is emerging as an important regulator of brain 5-HT. Moreover, corticosterone, which is released upon HPA axis activation, blocks 5-HT uptake by OCT3. Repeated swim produced a persistent elevation in plasma corticosterone, and, consistent with prolonged blockade by corticosterone, we found that OCT3 expression and function were reduced in these mice. Importantly, this effect of repeated swim to reduce 5-HT clearance rate was corticosterone dependent, as evidenced by its absence in adrenalectomized mice, in which plasma corticosterone levels were essentially undetectable. Behaviorally, mice subjected to repeated swim spent less time immobile in the tail suspension test than control mice, but responded similarly to SERT- and norepinephrine transporter-selective antidepressants. Together, these results show that reduced 5-HT clearance following HPA axis activation is likely mediated, at least in part, by the corticosterone-sensitive OCT3, and that drugs developed to selectively target OCT3 (unlike corticosterone) may be candidates for the development of novel antidepressant medications.

  12. Impact of different transport mechanisms of Asian dust and anthropogenic pollutants to Taiwan

    NASA Astrophysics Data System (ADS)

    Lin, C.; Chou, C. C.; Wang, Z.; Lung, S.; Lee, C.; Yuan, C.; Chen, W.; Chang, S.; Hsu, S.; Liu, S. C.

    2012-12-01

    The impacts of long-range transport of Asian dust and anthropogenic air pollutants to Taiwan are strongly associated with the atmospheric conditions and paths of transport. In this study, we identified 16 significant dust events (daily mean mass concentration >= 120 μgm-3) to Taiwan from 2002 to 2008. To investigate transport characteristics associated with long-range transport of Asian dust and anthropogenic air pollutants to Taiwan, significant dust events were further classified into dry (12 cases) and wet (4 cases) types according to atmospheric conditions. We found that the major transport paths for the dry type (DT) dust cases passed through anthropogenic source areas in the low boundary while the major paths for the wet type (WT) dust cases passed over the ocean. After mineral dust, which occupied around 32% of total PM10 mass concentration, anthropogenic ionic pollutants was the second major contributor and occupied 19~ 22% at three sampling stations in Taiwan for DT cases. In the fine particle, the anthropogenic ionic pollutants contributed from 29 to 36% to PM2.5, making it the major contributor. The two most significant cases, one from the DT and one from the WT cases, were selected to study transport mechanisms with the NAQPMS air quality model. Simulation results also suggest that transport paths and boundary atmospheric conditions play important roles in aerosol compositions.;

  13. Research Progress on the Role of ABC Transporters in the Drug Resistance Mechanism of Intractable Epilepsy

    PubMed Central

    Xiong, Jie; Mao, Ding-an; Liu, Li-qun

    2015-01-01

    The pathogenesis of intractable epilepsy is not fully clear. In recent years, both animal and clinical trials have shown that the expression of ATP-binding cassette (ABC) transporters is increased in patients with intractable epilepsy; additionally, epileptic seizures can lead to an increase in the number of sites that express ABC transporters. These findings suggest that ABC transporters play an important role in the drug resistance mechanism of epilepsy. ABC transporters can perform the funcions of a drug efflux pump, which can reduce the effective drug concentration at epilepsy lesions by reducing the permeability of the blood brain barrier to antiepileptic drugs, thus causing resistance to antiepileptic drugs. Given the important role of ABC transporters in refractory epilepsy drug resistance, antiepileptic drugs that are not substrates of ABC transporters were used to obtain ABC transporter inhibitors with strong specificity, high safety, and few side effects, making them suitable for long-term use; therefore, these drugs can be used for future clinical treatment of intractable epilepsy. PMID:26491660

  14. Influence of chemical structure on hydration and gas transport mechanisms of sulfonated poly(aryl ether ketone) membranes.

    PubMed

    Simon, Sandra; Espuche, Eliane; Gouanvé, Fabrice; Chauveau, Edouard; Marestin, Catherine; Mercier, Régis

    2012-10-25

    This work reports the influence of the chemical structure of two sulfonated poly(aryl ether ketone)s (SPAEK) on the hydration and gas transport mechanism of thin membranes made thereupon. For this purpose, two sulfonated poly(aryl ether ketone)s having the same ionic exchange capacity (IEC) but bearing a different repartition of the sulfonic acid groups along the polymer backbone were prepared. These polymers were synthesized by direct copolymerization of two specific sulfonated precursors, bisphenol AF and 4,4'-difluorobenzophenone. The morphology of the membranes was studied by transmission electron microscopy, and the thermal properties of the ionomers were determined from differential scanning calorimetry and thermogravimetric analyses. A detailed analysis of the water sorption isotherms and kinetics was performed. The gas transport properties were also determined for He, H(2), and CO(2) in the full range of water activity. From the detailed analysis of the water sorption isotherm and of the relative contributions of the Fickian diffusion and relaxation phenomena, a water sorption mechanism was proposed in relation with the SPAEK architectures and polymers' chain mobility. This mechanism allowed explaining the different evolution of the gas transport properties observed as a function of the gas nature and hydration rate.

  15. Transport mechanisms and genesis of limestone clast conglomerates with examples from Cambrian of east Tennessee

    SciTech Connect

    Kozar, M.G.; Weber, L.J.; Walker, K.R.

    1986-05-01

    Limestone clast conglomerates are common sedimentary features of most Cambrian strata. Cambrian researchers have considered many of these conglomeratic deposits to have formed from erosion and redeposition of partially lithified sediments by storm currents in shallow subtidal and intertidal environments. Analysis of conglomeratic beds from the Middle and Late Cambrian (Maryville Limestone and Nolichucky Shale) in east Tennessee suggests that other, more dominant, processes were responsible for their genesis and transport. The proposed processes may serve as an alternative explanation for limestone clast conglomerates deposited elsewhere in Cambrian sequences. As the authors gain a greater understanding of transport mechanisms and their resultant sedimentary features, many of the conglomeratic beds that were once thought to be the result of storms may be reinterpreted as mass-gravity flows. Differentiating between these various types of transport mechanisms may be crucial to paleo-environmental interpretation.

  16. Physical Activity Energy Expenditure in Dutch Adolescents: Contribution of Active Transport to School, Physical Education, and Leisure Time Activities

    ERIC Educational Resources Information Center

    Slingerland, Menno; Borghouts, Lars B.; Hesselink, Matthijs K. C.

    2012-01-01

    Background: Detailed knowledge about physical activity energy expenditure (PAEE) can guide the development of school interventions aimed at reducing overweight in adolescents. However, relevant components of PAEE have never been objectively quantified in this population. This study investigated the contribution of active transport to and from…

  17. Silver (Ag) Transport Mechanisms in TRISO coated particles: A Critical Review

    SciTech Connect

    I J van Rooyen; J H Neethling; J A A Engelbrecht; P M van Rooyen; G Strydom

    2012-10-01

    Transport of 110mAg in the intact SiC layer of TRISO coated particles has been studied for approximately 30 years without arriving at a satisfactory explanation of the transport mechanism. In this paper the possible mechanisms postulated in previous experimental studies, both in-reactor and out-of reactor research environment studies are critically reviewed and of particular interest are relevance to very high temperature gas reactor operating and accident conditions. Among the factors thought to influence Ag transport are grain boundary stoichiometry, SiC grain size and shape, the presence of free silicon, nano-cracks, thermal decomposition, palladium attack, transmutation products, layer thinning and coated particle shape. Additionally new insight to nature and location of fission products has been gained via recent post irradiation electron microscopy examination of TRISO coated particles from the DOE’s fuel development program. The combined effect of critical review and new analyses indicates a direction for investigating possible the Ag transport mechanism including the confidence level with which these mechanisms may be experimentally verified.

  18. Vibration-mediated Kondo transport in molecular junctions: conductance evolution during mechanical stretching

    PubMed Central

    Rakhmilevitch, David

    2015-01-01

    Summary The vibration-mediated Kondo effect attracted considerable theoretical interest during the last decade. However, due to lack of extensive experimental demonstrations, the fine details of the phenomenon were not addressed. Here, we analyze the evolution of vibration-mediated Kondo effect in molecular junctions during mechanical stretching. The described analysis reveals the different contributions of Kondo and inelastic transport. PMID:26734532

  19. Silver (Ag) Transport Mechanisms in TRISO Coated Particles: A Critical Review

    SciTech Connect

    IJ van Rooyen; ML Dunzik-Gougar; PM van Rooyen

    2014-05-01

    Transport of 110mAg in the intact SiC layer of TRISO coated particles has been studied for approximately 30 years without arriving at a satisfactory explanation of the transport mechanism. In this paper the possible mechanisms postulated in previous experimental studies, both in-reactor and out-of reactor research environment studies are critically reviewed and of particular interest are relevance to very high temperature gas reactor operating and accident conditions. Among the factors thought to influence Ag transport are grain boundary stoichiometry, SiC grain size and shape, the presence of free silicon, nano-cracks, thermal decomposition, palladium attack, transmutation products, layer thinning and coated particle shape. Additionally new insight to nature and location of fission products has been gained via recent post irradiation electron microscopy examination of TRISO coated particles from the DOE’s fuel development program. The combined effect of critical review and new analyses indicates a direction for investigating possible the Ag transport mechanism including the confidence level with which these mechanisms may be experimentally verified.

  20. Activation of glutamate transport evokes rapid glutamine release from perisynaptic astrocytes

    PubMed Central

    Uwechue, Nneka M; Marx, Mari-Carmen; Chevy, Quentin; Billups, Brian

    2012-01-01

    Stimulation of astrocytes by neuronal activity and the subsequent release of neuromodulators is thought to be an important regulator of synaptic communication. In this study we show that astrocytes juxtaposed to the glutamatergic calyx of Held synapse in the rat medial nucleus of the trapezoid body (MNTB) are stimulated by the activation of glutamate transporters and consequently release glutamine on a very rapid timescale. MNTB principal neurones express electrogenic system A glutamine transporters, and were exploited as glutamine sensors in this study. By simultaneous whole-cell voltage clamping astrocytes and neighbouring MNTB neurones in brainstem slices, we show that application of the excitatory amino acid transporter (EAAT) substrate d-aspartate stimulates astrocytes to rapidly release glutamine, which is detected by nearby MNTB neurones. This release is significantly reduced by the toxins l-methionine sulfoximine and fluoroacetate, which reduce glutamine concentrations specifically in glial cells. Similarly, glutamine release was also inhibited by localised inactivation of EAATs in individual astrocytes, using internal dl-threo-β-benzyloxyaspartic acid (TBOA) or dissipating the driving force by modifying the patch-pipette solution. These results demonstrate that astrocytes adjacent to glutamatergic synapses can release glutamine in a temporally precise, controlled manner in response to glial glutamate transporter activation. Since glutamine can be used by neurones as a precursor for glutamate and GABA synthesis, this represents a potential feedback mechanism by which astrocytes can respond to synaptic activation and react in a way that sustains or enhances further communication. This would therefore represent an additional manifestation of the tripartite relationship between synapses and astrocytes. PMID:22411007

  1. Crystalline, Glassy and Polymeric Electrolytes:. Similarities and Differences in Ionic Transport Mechanisms

    NASA Astrophysics Data System (ADS)

    Souquet, Jean Louis

    2006-06-01

    Ionocovalent crystals or glasses as well as molten salts or salt polymer complexes are currently studied as electrolytes for high energy density batteries. Their large Red/Ox stability range results from their thermodynamic or kinetic characteristics. For all these electrolytes, charge carriers are the consequence of local deviations from electroneutrality, identified as point defects for ionic crystals or partial dissociation in disordered structures. The charge carriers formation derives from a similar activated process. The main difference comes from the migration process, which depends on the dynamic properties of the surrounding medium. When the structural relaxation time is large, an activated process, mainly enthalpic, prevails for charge carriers migration. It is the usual case for ionic crystals or glasses. In the liquid or overcooled liquid states, the structural relaxation time of the medium is shorter that the time required for the activated migration process to occur and a local reorganization of the medium vanishes the energy barrier and provides the free volume necessary to ionic migration. In that case, the migration is mainly an entropic process. The configurational entropy necessary to this process decreases with temperature and vanishes at the so called ideal glass transition temperature which can be estimated by extrapolation of the transport properties or of the thermodynamic characteristics of the medium. However, at the experiment time scale, this configurational entropy disappears at a somewhat higher temperature, the glass transition temperature at which the structural relaxation time corresponds to the measurement time. Some glass forming ionic melts studied in a large temperature scale, over and below the glass transition temperature, evidence the two, enthalpic and entropic, migration mechanisms, allowing the determination of the thermodynamic characteristics of the charge carriers formation and migration. Some recent results indicate

  2. Subpopulations of rat dorsal root ganglion neurons express active vesicular acetylcholine transporter.

    PubMed

    Tata, Ada Maria; De Stefano, M Egle; Tomassy, Giulio Srubek; Vilaró, M Teresa; Levey, Allan I; Biagioni, Stefano

    2004-01-15

    The vesicular acetylcholine transporter (VAChT) is a transmembrane protein required, in cholinergic neurons, for selective storage of acetylcholine into synaptic vesicles. Although dorsal root ganglion (DRG) neurons utilize neuropeptides and amino acids for neurotransmission, we have previously demonstrated the presence of a cholinergic system. To investigate whether, in sensory neurons, the vesicular accumulation of acetylcholine relies on the same mechanisms active in classical cholinergic neurons, we investigated VAChT presence, subcellular distribution, and activity. RT-PCR and Western blot analysis demonstrated the presence of VAChT mRNA and protein product in DRG neurons and in the striatum and cortex, used as positive controls. Moreover, in situ hybridization and immunocytochemistry showed VAChT staining located mainly in the medium/large-sized subpopulation of the sensory neurons. A few small neurons were also faintly labeled by immunocytochemistry. In the electron microscope, immunolabeling was associated with vesicle-like elements distributed in the neuronal cytoplasm and in both myelinated and unmyelinated intraganglionic nerve fibers. Finally, [(3)H]acetylcholine active transport, evaluated either in the presence or in the absence of ATP, also demonstrated that, as previously reported, the uptake of acetylcholine by VAChT is ATP dependent. This study suggests that DRG neurons not only are able to synthesize and degrade ACh and to convey cholinergic stimuli but also are capable of accumulating and, possibly, releasing acetylcholine by the same mechanism used by the better known cholinergic neurons.

  3. Sugar-activated ion transport in canine lingual epithelium. Implications for sugar taste transduction

    PubMed Central

    1988-01-01

    There is good evidence indicating that ion-transport pathways in the apical regions of lingual epithelial cells, including taste bud cells, may play a role in salt taste reception. In this article, we present evidence that, in the case of the dog, there also exists a sugar- activated ion-transport pathway that is linked to sugar taste transduction. Evidence was drawn from two parallel lines of experiments: (a) ion-transport studies on the isolated canine lingual epithelium, and (b) recordings from the canine chorda tympani. The results in vitro showed that both mono- and disaccharides in the mucosal bath stimulate a dose-dependent increase in the short-circuit current over the concentration range coincident with mammalian sugar taste responses. Transepithelial current evoked by glucose, fructose, or sucrose in either 30 mM NaCl or in Krebs-Henseleit buffer (K-H) was partially blocked by amiloride. Among current carriers activated by saccharides, the current response was greater with Na than with K. Ion flux measurements in K-H during stimulation with 3-O-methylglucose showed that the sugar-evoked current was due to an increase in the Na influx. Ouabain or amiloride reduced the sugar-evoked Na influx without effect on sugar transport as measured with tritiated 3-O-methylglucose. Amiloride inhibited the canine chorda tympani response to 0.5 M NaCl by 70-80% and the response to 0.5 M KCl by approximately 40%. This agreed with the percent inhibition by amiloride of the short-circuit current supported in vitro by NaCl and KCl. Amiloride also partially inhibited the chorda tympani responses to sucrose and to fructose. The results indicate that in the dog: (a) the ion transporter subserving Na taste also subserves part of the response to K, and (b) a sugar-activated, Na- preferring ion-transport system is one mechanism mediating sugar taste transduction. Results in the literature indicate a similar sweet taste mechanism for humans. PMID:3171536

  4. Phenylalanine transport in guinea pig jejunum. A general mechanism for organic solute and sodium cotransport.

    PubMed

    Alvarado, F; Lherminier, M

    1982-08-01

    1. Sodium-dependent phenylalanine transport by guinea pig jejunum exhibits apparently pure K-type activation kinetics where Vmaxs is constant but KT decreases as [Na+] increases. At 0, 3 and 6 mM sodium, however, the results deviate from the expected hyperbolic kinetics and give a plateau. 2. This finding is interpreted in terms of the hypothesis that the outer face of the brush border membrane contains enough Na+ to support amino acid and Na+ cotransport at essentially maximal rates, even after preincubation of the tissues in vitro for several minutes in sodium-free buffers. 3. Sodium could move dynamically into this region from tissue stores and across the paracellular pathway. Passage of NaCl directly across the brush border also seems possible by reversal of the (neutral) Na+ and Cl- cotransport system. 4. To reconcile contradictory observations obtained in different laboratories, either with intact-epithelium preparations or with isolated brush border membrane vesicles, we include a theoretical analysis of the kinetics of organic solute and Na+ cotransport. For simplicity, this analysis is limited to cases of 1/2 stoichiometry and to neutral organic solutes such as sugars and monoamino-monocarboxylic amino acids. 5. Cotransport is explained in terms of a general, allosteric mechanism involving one site for S and another for Na+. There is no preferential order for binding, but only the ternary complex S-carrier-Na+ can translocate at quantitatively significant rates (obligatory activation kinetics). Since Na+ crosses the membrane as the free cation, under physiological conditions (inside-negative membrane potential) it will move towards its position of electrical equilibrium, hence unidirectionally. This explains why, with intact-tissue preparations, solute influx exhibits Michaelis-Menten kinetics. 6. By definition, cotransport kinetics are mixed type and involve effects on both KT and Vmaxs. Macroscopic deviations from this expected behaviour can be explained

  5. Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes.

    PubMed

    Setty, Subba Rao Gangi; Tenza, Danièle; Sviderskaya, Elena V; Bennett, Dorothy C; Raposo, Graça; Marks, Michael S

    2008-08-28

    Copper is a cofactor for many cellular enzymes and transporters. It can be loaded onto secreted and endomembrane cuproproteins by translocation from the cytosol into membrane-bound organelles by ATP7A or ATP7B transporters, the genes for which are mutated in the copper imbalance syndromes Menkes disease and Wilson disease, respectively. Endomembrane cuproproteins are thought to incorporate copper stably on transit through the trans-Golgi network, in which ATP7A accumulates by dynamic cycling through early endocytic compartments. Here we show that the pigment-cell-specific cuproenzyme tyrosinase acquires copper only transiently and inefficiently within the trans-Golgi network of mouse melanocytes. To catalyse melanin synthesis, tyrosinase is subsequently reloaded with copper within specialized organelles called melanosomes. Copper is supplied to melanosomes by ATP7A, a cohort of which localizes to melanosomes in a biogenesis of lysosome-related organelles complex-1 (BLOC-1)-dependent manner. These results indicate that cell-type-specific localization of a metal transporter is required to sustain metallation of an endomembrane cuproenzyme, providing a mechanism for exquisite spatial control of metalloenzyme activity. Moreover, because BLOC-1 subunits are mutated in subtypes of the genetic disease Hermansky-Pudlak syndrome, these results also show that defects in copper transporter localization contribute to hypopigmentation, and hence perhaps other systemic defects, in Hermansky-Pudlak syndrome.

  6. Cell-specific ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes

    PubMed Central

    Gangi Setty, Subba Rao; Tenza, Danièle; Sviderskaya, Elena V.; Bennett, Dorothy C.; Raposo, Graça; Marks, Michael S.

    2009-01-01

    SUMMARY Copper is a cofactor for many cellular enzymes and transporters1. To load onto secreted and endomembrane cuproproteins, copper is translocated from the cytosol into membrane-bound organelles by ATP7A or ATP7B transporters, the genes for which are mutated in the copper imbalance syndromes, Menkes and Wilson disease, respectively2. Endomembrane cuproproteins are thought to stably incorporate copper upon transit through the trans Golgi network (TGN), within which ATP7A3 accumulates by dynamic cycling through early endocytic compartments4. Here we show that the pigment cell-specific cuproenzyme tyrosinase acquires copper only transiently and inefficiently within the TGN of melanocytes. To catalyze melanin synthesis, tyrosinase is subsequently reloaded with copper within specialized organelles called melanosomes. Copper is supplied to melanosomes by ATP7A, a cohort of which localizes to melanosomes in a Biogenesis of Lysosome-related Organelles Complex-1 (BLOC-1)-dependent manner. These results indicate that cell type-specific localization of a metal transporter is required to sustain metallation of an endomembrane cuproenzyme, providing a mechanism for exquisite spatial control of metalloenzyme activity. Moreover, as BLOC-1 subunits are mutated in subtypes of the genetic disease, Hermansky-Pudlak syndrome (HPS), these results also show that defects in copper transporter localization contribute to hypopigmentation, and hence perhaps other systemic defects, in HPS. PMID:18650808

  7. Fatty acid transport and activation and the expression patterns of genes involved in fatty acid trafficking.

    PubMed

    Sandoval, Angel; Fraisl, Peter; Arias-Barrau, Elsa; Dirusso, Concetta C; Singer, Diane; Sealls, Whitney; Black, Paul N

    2008-09-15

    These studies defined the expression patterns of genes involved in fatty acid transport, activation and trafficking using quantitative PCR (qPCR) and established the kinetic constants of fatty acid transport in an effort to define whether vectorial acylation represents a common mechanism in different cell types (3T3-L1 fibroblasts and adipocytes, Caco-2 and HepG2 cells and three endothelial cell lines (b-END3, HAEC, and HMEC)). As expected, fatty acid transport protein (FATP)1 and long-chain acyl CoA synthetase (Acsl)1 were the predominant isoforms expressed in adipocytes consistent with their roles in the transport and activation of exogenous fatty acids destined for storage in the form of triglycerides. In cells involved in fatty acid processing including Caco-2 (intestinal-like) and HepG2 (liver-like), FATP2 was the predominant isoform. The patterns of Acsl expression were distinct between these two cell types with Acsl3 and Acsl5 being predominant in Caco-2 cells and Acsl4 in HepG2 cells. In the endothelial lines, FATP1 and FATP4 were the most highly expressed isoforms; the expression patterns for the different Acsl isoforms were highly variable between the different endothelial cell lines. The transport of the fluorescent long-chain fatty acid C(1)-BODIPY-C(12) in 3T3-L1 fibroblasts and 3T3-L1 adipocytes followed typical Michaelis-Menten kinetics; the apparent efficiency (k(cat)/K(T)) of this process increases over 2-fold (2.1 x 10(6)-4.5 x 10(6)s(-1)M(-1)) upon adipocyte differentiation. The V(max) values for fatty acid transport in Caco-2 and HepG2 cells were essentially the same, yet the efficiency was 55% higher in Caco-2 cells (2.3 x 10(6)s(-1)M(-1) versus 1.5 x 10(6)s(-1)M(-1)). The kinetic parameters for fatty acid transport in three endothelial cell types demonstrated they were the least efficient cell types for this process giving V(max) values that were nearly 4-fold lower than those defined form 3T3-L1 adipocytes, Caco-2 cells and HepG2 cells. The

  8. Zinc transporters, mechanisms of action and therapeutic utility: implications for type 2 diabetes mellitus.

    PubMed

    Myers, Stephen A; Nield, Alex; Myers, Mark

    2012-01-01

    Zinc is an essential trace element that plays a vital role in maintaining many biological processes and cellular homeostasis. Dysfunctional zinc signaling is associated with a number of chronic disease states including cancer, cardiovascular disease, Alzheimer's disease, and diabetes. Cellular homeostasis requires mechanisms that tightly control the uptake, storage, and distribution of zinc. This is achieved through the coordinated actions of zinc transporters and metallothioneins. Evidence on the role of these proteins in type 2 diabetes mellitus (T2DM) is now emerging. Zinc plays a key role in the synthesis, secretion and action of insulin in both physiological and pathophysiological states. Moreover, recent studies highlight zinc's dynamic role as a "cellular second messenger" in the control of insulin signaling and glucose homeostasis. This suggests that zinc plays an unidentified role as a novel second messenger that augments insulin activity. This previously unexplored concept would raise a whole new area of research into the pathophysiology of insulin resistance and introduce a new class of drug target with utility for diabetes pharmacotherapy.

  9. Mechanisms of passive tracer interhemispheric transport: An analysis of model-derived and observational interhemispheric transport climatology and interannual variations

    NASA Astrophysics Data System (ADS)

    Lintner, Benjamin Richard

    2003-10-01

    Examination of the distributions of minor atmospheric constituents may provide valuable insight into atmospheric transport processes. Interhemispheric transport (IHT), the cross-equatorial linkage of the Northern and Southern Hemispheres, is an important aspect of transport that can be explored using the properties of passive tracers. In this dissertation, the principal spatial and temporal features of IHT are examined through modeling and observational approaches. Using the Goddard Institute for Space Studies-University of California, Berkeley (GISS-UCB) atmospheric general circulation model (AGCM) and its companion tracer transplant model (TTM), IHT climatology is first described. Means of assessing IHT, including a simple two-box model and transport partitioning, are introduced, and the seasonality of IHT is elaborated. Particular emphasis is placed upon the elucidation of the longitudinal and vertical features of IHT. IHT sensitivity to source emission geometry and convective mixing is also explored using both the TTM and a Lagrangian trajectory model (LTM) approach. This dissertation further addresses the interannual variability (IAV) of IHT within the GISS-UCB AGCM framework. Analysis of several AGCM simulations, including an ensemble of "Identical Forcing" runs, reveals that IHT IAV is small relative to either the mean IHT timescale or its seasonal variations. IHT IAV is linked to both axisymmetric and regional circulations, and both forced and unforced circulation variations contribute significantly to the development of IHT anomalies. Among the mechanisms that modulate IHT on interannual timescales are changes in the intensity/geometry of the Hadley circulation, variations of the strength/displacement of the zonal-mean and regional Intertropical Convergence Zones (ITCZs), the El Nino/Southern Oscillation (ENSO), and the Indian Ocean Monsoon (IOM). The IOM appears to play an especially prominent role in the modulation of IHT. A comparison of AGCM

  10. Atmospheric Compensation of Variations in Tropical Ocean Heat Transport: Understanding Mechanisms and Implications on Tectonic Timescales

    NASA Astrophysics Data System (ADS)

    Rencurrel, M. C.; Rose, B. E. J.

    2015-12-01

    The poleward transport of energy is a key aspect of the climate system, with surface ocean currents presently dominating the transport out of deep tropics. A classic study by Stone (1978) proposed that the total heat transport is determined by astronomical parameters and is highly insensitive to the detailed atmosphere-ocean dynamics. On the other hand, previous modeling work has shown that past continental configurations could have produced substantially different tropical ocean heat transport (OHT). How thoroughly does the atmosphere compensate for changes in ocean transport in terms of the top-of-atmosphere (TOA) radiative budget, what are the relevant mechanisms, and what are the consequences for surface temperature and climate on tectonic timescales? We examine these issues in a suite of aquaplanet GCM simulations subject to large prescribed variations in OHT. We find substantial but incomplete compensation, in which adjustment of the atmospheric Hadley circulation plays a key role. We then separate out the dynamical and thermodynamical components of the adjustment mechanism. Increased OHT tends to warm the mid- to high latitudes without cooling the tropics due asymmetries in radiative feedback processes. The warming is accompanied by hydrological cycle changes that are completely different from those driven by greenhouse gases, suggesting that drivers of past global change might be detectable from combinations of hydroclimate and temperature proxies.

  11. Integrated capture, transport, and magneto-mechanical resonant sensing of superparamagnetic microbeads using magnetic domain walls.

    PubMed

    Rapoport, E; Montana, D; Beach, G S D

    2012-11-07

    An integrated platform for the capture, transport, and detection of individual superparamagnetic microbeads is described for lab-on-a-chip biomedical applications. Magnetic domain walls in magnetic tracks have previously been shown to be capable of capturing and transporting individual beads through a fluid at high speeds. Here it is shown that the strong magnetostatic interaction between a bead and a domain wall leads to a distinct magneto-mechanical resonance that reflects the susceptibility and hydrodynamic size of the trapped bead. Numerical and analytical modeling is used to quantitatively explain this resonance, and the magneto-mechanical resonant response under sinusoidal drive is experimentally characterized both optically and electrically. The observed bead resonance presents a new mechanism for microbead sensing and metrology. The dual functionality of domain walls as both bead carriers and sensors is a promising platform for the development of lab-on-a-bead technologies.

  12. Platelet Activation: The Mechanisms and Potential Biomarkers

    PubMed Central

    Yun, Seong-Hoon; Sim, Eun-Hye; Goh, Ri-Young; Park, Joo-In

    2016-01-01

    Beyond hemostasis and thrombosis, an increasing number of studies indicate that platelets play an integral role in intercellular communication, mediating inflammatory and immunomodulatory activities. Our knowledge about how platelets modulate inflammatory and immunity has greatly improved in recent years. In this review, we discuss recent advances in the pathways of platelet activation and potential application of platelet activation biomarkers to diagnosis and prediction of disease states. PMID:27403440

  13. Mass Transport Deposits in the Santaren Channel: Distribution, Characteristics, and Potential Triggering Mechanisms

    NASA Astrophysics Data System (ADS)

    Schnyder, J.

    2015-12-01

    Submarine slope failures are a likely cause for tsunami generation along the East U.S. coast. A possible source are the large slope failures along western Great Bahama Bank (GBB). Numerical models simulate tsunami generation and propagation through the Straits of Florida, caused by these Pleistocene mass wasting events. In order to estimate the likelihood and extent of future landslides, distribution, characteristics, and possible triggering mechanisms of previous failures and their associated mass transport deposits (MTD) have to be investigated. In 2013, the University of Hamburg acquired 2D high-resolution multichannel seismic data, multibeam data, and subbottom profiles inside the Santaren Channel, along the slopes of western GBB and Cay Sal Bank (CSB). The two platforms are different in two ways. CSB is part of the Cuban Fold and Thrust Belt while GBB is situated in a tectonically quiet zone. In addition, the slopes of western GBB are on the leeward side of the bank, while the eastern slopes of CSB are in a windward position. Differences in nature and size of mass wasting events between the Cay Sal side and the western GBB side of the dataset show how influential the tectonically active Cuban Fold and Thrust Belt is to the generation of large MTDs in this area. In the study area, the slope failures can be divided in two categories; small-scale in situ failures with high frequencies on the slopes, dominant on the western GBB side, and large landslides with a lower frequency, but higher volumes and transport distances on the toe of the slope and in the basin, dominant on the Cay Sal side. The distribution of in situ failures, such as slump and debris flow alternation, shows the interplay between high and low inner strength of the sediment, respectively. On the other hand, large MTDs caused by submarine landslides suggest movement in an unconfined manner. Internal sediment preconditions derived from sea level oscillations are suggested as triggering mechanisms

  14. TRANSPORT

    EPA Science Inventory

    Presentation outline: transport principles, effective solubility; gasoline composition; and field examples (plume diving).
    Presentation conclusions: MTBE transport follows from - phyiscal and chemical properties and hydrology. Field examples show: MTBE plumes > benzene plu...

  15. Transport Mechanisms of Solid Lipid Nanoparticles across Caco-2 Cell Monolayers and their Related Cytotoxicology.

    PubMed

    Chai, Gui-Hong; Xu, Yingke; Chen, Shao-Qing; Cheng, Bolin; Hu, Fu-Qiang; You, Jian; Du, Yong-Zhong; Yuan, Hong

    2016-03-09

    Solid lipid nanoparticles (SLNs) have been extensively investigated and demonstrated to be a potential nanocarriers for improving oral bioavailability of many drugs. However, the molecular mechanisms related to this discovery are not yet understood. Here, the molecular transport mechanisms of the SLNs crossing simulative intestinal epithelial cell monolayers (Caco-2 cell monolayers) were studied. The cytotoxicology results of the SLNs in Caco-2 cells demonstrated that the nanoparticles had low cytotoxicity, had no effect on the integrity of the cell membrane, did not induce oxidative stress, and could significantly reduce cell membrane fluidity. The endocytosis of the SLNs was time-dependent, and their delivery was energy-dependent. For the first time, the transport of the SLNs was directly verified to be a vesicle-mediated process. The internalization of the SLNs was mediated by macropinocytosis pathway and clathrin- and caveolae (or lipid raft)-related routes. Transferrin-related endosomes, lysosomes, endoplasmic reticulum (ER), and Golgi apparatus were confirmed to be the main destinations of the SLNs in Caco-2 cells. As for the transport of the SLNs in Caco-2 cell monolayers, the results demonstrated that the SLNs transported to the basolateral side were intact, and the transport of the nanoparticles did not destroy the structure of tight junctions. The transcytosis of the SLNs across the Caco-2 cell monolayer was demonstrated to be mediated by the same routes as that in the endocytosis study. The ER, Golgi apparatus, and microtubules were confirmed to be important for the transport of the SLNs to both the basolateral and apical membrane sides. This study provides a more thoroughly understand of SLNs transportation crossing intestinal epithelial cell monolayers and could be beneficial for the fabrication of SLNs.

  16. Acid-base transport in pancreatic cancer: molecular mechanisms and clinical potential.

    PubMed

    Kong, Su Chii; Giannuzzo, Andrea; Gianuzzo, Andrea; Novak, Ivana; Pedersen, Stine Falsig

    2014-12-01

    Solid tumors are characterized by a microenvironment that is highly acidic, while intracellular pH (pHi) is normal or even elevated. This is the result of elevated metabolic rates in the highly proliferative cancer cells, in conjunction with often greatly increased rates of net cellular acid extrusion. Studies in various cancers have suggested that while the acid extrusion mechanisms employed are generally the same as those in healthy cells, the specific transporters upregulated vary with the cancer type. The main such transporters include Na(+)/H(+) exchangers, various HCO3(-) transporters, H(+) pumps, and lactate-H(+) cotransporters. The mechanisms leading to their dysregulation in cancer are incompletely understood but include changes in transporter expression levels, trafficking and membrane localization, and posttranslational modifications. In turn, accumulating evidence has revealed that in addition to supporting their elevated metabolic rate, their increased acid efflux capacity endows the cancer cells with increased capacity for invasiveness, proliferation, and chemotherapy resistance. The pancreatic duct exhibits an enormous capacity for acid-base transport, rendering pHi dysregulation a potentially very important topic in pancreatic ductal adenocarcinoma (PDAC). PDAC - accounting for about 90% of all pancreatic cancers - has one of the highest cancer mortality rates known, and new diagnostic and treatment options are highly needed. However, very little is known about whether pH regulation is altered in PDAC and, if so, the possible role of this in cancer development. Here, we review current models for pancreatic acid-base transport and pH homeostasis and summarize current views on acid-base dysregulation in cancer, focusing where possible on the few studies to date in PDAC. Finally, we present new data-mining analyses of acid-base transporter expression changes in PDAC and discuss essential directions for future work.

  17. Drug Release Kinetics and Transport Mechanisms of Non-degradable and Degradable Polymeric Delivery Systems

    PubMed Central

    Fu, Yao; Kao, Weiyuan John

    2010-01-01

    Importance of the field The advancement in material design and engineering has led to the rapid development of novel materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. Areas covered in this review The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literatures published after 1990s. The release kinetics of selected drug compounds from various material systems will be discussed in case studies. Recent progresses in the mathematical models based on different transport mechanisms will be highlighted. What the reader will gain This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drug delivery matrices. Take home message Understanding the structure-function relationship of the material system is key to the successful design of a delivery system for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms. PMID:20331353

  18. Mechanism for Particle Transport and Size Sorting via Low-Frequency Vibrations

    NASA Technical Reports Server (NTRS)

    Sherrit, Stewart; Scott, James S.; Bar-Cohen, Yoseph; Badescu, Mircea; Bao, Xiaoqi

    2010-01-01

    There is a need for effective sample handling tools to deliver and sort particles for analytical instruments that are planned for use in future NASA missions. Specifically, a need exists for a compact mechanism that allows transporting and sieving particle sizes of powdered cuttings and soil grains that may be acquired by sampling tools such as a robotic scoop or drill. The required tool needs to be low mass and compact to operate from such platforms as a lander or rover. This technology also would be applicable to sample handling when transporting samples to analyzers and sorting particles by size.

  19. Boundary conditions for probability density function transport equations in fluid mechanics.

    PubMed

    Valiño, Luis; Hierro, Juan

    2003-04-01

    The behavior of the probability density function (PDF) transport equation at the limits of the probability space is studied from the point of view of fluid mechanics. Different boundary conditions are considered depending on the nature of the variable considered (velocity, scalar, and position). A study of the implications of entrance and exit conditions is performed, showing that a new term should be added to the PDF transport equation to preserve normalization in some nonstationary processes. In practice, this term is taken into account naturally in particle methods. Finally, the existence of discontinuities at the limits is also investigated.

  20. Dioxin mediates downregulation of the reduced folate carrier transport activity via the arylhydrocarbon receptor signalling pathway

    SciTech Connect

    Halwachs, Sandra; Lakoma, Cathleen; Gebhardt, Rolf; Schaefer, Ingo; Seibel, Peter; Honscha, Walther

    2010-07-15

    Dioxins such as 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) are common environmental contaminants known to regulate several genes via activation of the transcription factor aryl hydrocarbon receptor (AhR) associated with the development of numerous adverse biological effects. However, comparatively little is known about the molecular mechanisms by which dioxins display their toxic effects in vertebrates. The 5' untranslated region of the hepatocellular Reduced folate carrier (Rfc1; Slc19a1) exhibits AhR binding sites termed dioxin responsive elements (DRE) that have as yet only been found in the promoter region of prototypical TCDD target genes. Rfc1 mediated transport of reduced folates and antifolate drugs such as methotrexate (MTX) plays an essential role in physiological folate homeostasis and MTX cancer chemotherapy. In order to determine whether this carrier represents a target gene of dioxins we have investigated the influence of TCDD on functional Rfc1 activity in rat liver. Pre-treatment of rats with TCDD significantly diminished hepatocellular Rfc1 uptake activity in a time- and dose-dependent manner. In further mechanistic studies we demonstrated that this reduction was due to TCDD-dependent activation of the AhR signalling pathway. We additionally showed that binding of the activated receptor to DRE motifs in the Rfc1 promoter resulted in downregulation of Rfc1 gene expression and reduced carrier protein levels. As downregulation of pivotal Rfc1 activity results in functional folate deficiency associated with an elevated risk of cardiovascular diseases or carcinogenesis, our results indicate that deregulation of this essential transport pathway represents a novel regulatory mechanism how dioxins display their toxic effects through the Ah receptor.

  1. Comparative Localization and Functional Activity of the Main Hepatobiliary Transporters in HepaRG Cells and Primary Human Hepatocytes

    PubMed Central

    Bachour-El Azzi, Pamela; Sharanek, Ahmad; Burban, Audrey; Li, Ruoya; Guével, Rémy Le; Abdel-Razzak, Ziad; Stieger, Bruno; Guguen-Guillouzo, Christiane; Guillouzo, André

    2015-01-01

    The role of hepatobiliary transporters in drug-induced liver injury remains poorly understood. Various in vivo and in vitro biological approaches are currently used for studying hepatic transporters; however, appropriate localization and functional activity of these transporters are essential for normal biliary flow and drug transport. Human hepatocytes (HHs) are considered as the most suitable in vitro cell model but erratic availability and inter-donor functional variations limit their use. In this work, we aimed to compare localization of influx and efflux transporters and their functional activity in differentiated human HepaRG hepatocytes with fresh HHs in conventional (CCHH) and sandwich (SCHH) cultures. All tested influx and efflux transporters were correctly localized to canalicular [bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), multidrug resistance protein 1 (MDR1), and MDR3] or basolateral [Na+-taurocholate co-transporting polypeptide (NTCP) and MRP3] membrane domains and were functional in all models. Contrary to other transporters, NTCP and BSEP were less abundant and active in HepaRG cells, cellular uptake of taurocholate was 2.2- and 1.4-fold and bile excretion index 2.8- and 2.6-fold lower, than in SCHHs and CCHHs, respectively. However, when taurocholate canalicular efflux was evaluated in standard and divalent cation-free conditions in buffers or cell lysates, the difference between the three models did not exceed 9.3%. Interestingly, cell imaging showed higher bile canaliculi contraction/relaxation activity in HepaRG hepatocytes and larger bile canaliculi networks in SCHHs. Altogether, our results bring new insights in mechanisms involved in bile acids accumulation and excretion in HHs and suggest that HepaRG cells represent a suitable model for studying hepatobiliary transporters and drug-induced cholestasis. PMID:25690737

  2. Species Transport Mechanisms Governing Crossover and Capacity Loss in Vanadium Redox Flow Batteries

    NASA Astrophysics Data System (ADS)

    Agar, Ertan

    Vanadium redox flow batteries (VRFBs) are an emerging energy storage technology that offers unique advantages for grid-scale energy storage due to their flexible design and decoupled power/energy feature. Despite their popularity, a series of technical challenges hinder their widespread implementation. Among these, capacity loss (i.e., loss of energy storage capability) due to the undesired species crossover across the membrane has been identified as the key issue limiting the longevity of these systems. This issue is primarily governed by the properties of the membrane and can be mitigated by using proper membrane architectures with desired features. Presently, identifying proper membrane architectures for VRFB systems is hampered by the lack of a fundamental understanding of the nature of species transport mechanisms and how they are related to the membrane properties and key operating conditions. This Ph.D. study seeks to address this critical challenge by exploring the fundamental mechanisms responsible for species transport within the membrane. The overall objective of this dissertation study is to establish a fundamental understanding of the multi-ionic transport in VRFB membranes by investigating the ionic transport mechanisms responsible for crossover, and utilize this understanding to reveal the role of membrane properties and operating conditions on the capacity loss. To achieve these goals, a combined experimental and computational study was designed. An experimentally validated, 2-D, transient VRFB model that can track the vanadium crossover and capture the related capacity loss was developed. In addition to the model, several electrochemical techniques were used to characterize different types of membrane and study the effects of various operating conditions on the species crossover. Using these computational and experimental tools, an in-depth understanding of the species transport mechanisms within the membrane and how they are related to membrane

  3. The Association between Access to Public Transportation and Self-Reported Active Commuting

    PubMed Central

    Djurhuus, Sune; Hansen, Henning S.; Aadahl, Mette; Glümer, Charlotte

    2014-01-01

    Active commuting provides routine-based regular physical activity which can reduce the risk of chronic diseases. Using public transportation involves some walking or cycling to a transit stop, transfers and a walk to the end location and users of public transportation have been found to accumulate more moderate physical activity than non-users. Understanding how public transportation characteristics are associated with active transportation is thus important from a public health perspective. This study examines the associations between objective measures of access to public transportation and self-reported active commuting. Self-reported time spent either walking or cycling commuting each day and the distance to workplace were obtained for adults aged 16 to 65 in the Danish National Health Survey 2010 (n = 28,928). Access to public transportation measures were computed by combining GIS-based road network distances from home address to public transit stops an integrating their service level. Multilevel logistic regression was used to examine the association between access to public transportation measures and active commuting. Distance to bus stop, density of bus stops, and number of transport modes were all positively associated with being an active commuter and with meeting recommendations of physical activity. No significant association was found between bus services at the nearest stop and active commuting. The results highlight the importance of including detailed measurements of access to public transit in order to identify the characteristics that facilitate the use of public transportation and active commuting. PMID:25489998

  4. The association between access to public transportation and self-reported active commuting.

    PubMed

    Djurhuus, Sune; Hansen, Henning S; Aadahl, Mette; Glümer, Charlotte

    2014-12-05

    Active commuting provides routine-based regular physical activity which can reduce the risk of chronic diseases. Using public transportation involves some walking or cycling to a transit stop, transfers and a walk to the end location and users of public transportation have been found to accumulate more moderate physical activity than non-users. Understanding how public transportation characteristics are associated with active transportation is thus important from a public health perspective. This study examines the associations between objective measures of access to public transportation and self-reported active commuting. Self-reported time spent either walking or cycling commuting each day and the distance to workplace were obtained for adults aged 16 to 65 in the Danish National Health Survey 2010 (n = 28,928). Access to public transportation measures were computed by combining GIS-based road network distances from home address to public transit stops an integrating their service level. Multilevel logistic regression was used to examine the association between access to public transportation measures and active commuting. Distance to bus stop, density of bus stops, and number of transport modes were all positively associated with being an active commuter and with meeting recommendations of physical activity. No significant association was found between bus services at the nearest stop and active commuting. The results highlight the importance of including detailed measurements of access to public transit in order to identify the characteristics that facilitate the use of public transportation and active commuting.

  5. Effect of Mechanical Agitation on Cationic Liposome Transport across an Unstirred Water Layer in Caco-2 Cells.

    PubMed

    Kono, Yusuke; Iwasaki, Ayu; Matsuoka, Kenta; Fujita, Takuya

    2016-01-01

    To develop an effective oral delivery system for plasmid DNA (pDNA) using cationic liposomes, it is necessary to clarify the characteristics of uptake and transport of cationic liposome/pDNA complexes into the intestinal epithelium. In particular, evaluation of the involvement of an unstirred water layer (UWL), which is a considerable permeability barrier, in cationic liposome transport is very important. Here, we investigated the effects of a UWL on the transfection efficiency of cationic liposome/pDNA complexes into a Caco-2 cell monolayer. When Caco-2 cells were transfected with cationic liposome/pDNA complexes in shaking cultures to reduce the thickness of the UWL, gene expression was significantly higher in Caco-2 cells compared with static cultures. We also found that this enhancement of gene expression by shaking was not attributable to activation of transcription factors such as activator protein-1 and nuclear factor-kappaB (NF-κB). In addition, the increase in gene expression by mechanical agitation was observed at all charge ratios (1.5, 2.3, 3.1, 4.5) of cationic liposome/pDNA complexes. Transport experiments using Transwells demonstrated that mechanical agitation increased the uptake of cationic liposome/pDNA complexes by Caco-2 cells, whereas transport of the complexes across a Caco-2 cell monolayer did not occurr. Moreover, the augmentation of the gene expression of cationic liposome/pDNA complexes by shaking was observed in Madin-Darby canine kidney cells. These results indicate that a UWL greatly affects the uptake and transfection efficiency of cationic liposome/pDNA complexes into an epithelial monolayer in vitro.

  6. School Travel Planning: Mobilizing School and Community Resources to Encourage Active School Transportation

    ERIC Educational Resources Information Center

    Buliung, Ron; Faulkner, Guy; Beesley, Theresa; Kennedy, Jacky

    2011-01-01

    Background: Active school transport (AST), school travel using an active mode like walking, may be important to children's overall physical activity. A "school travel plan" (STP) documents a school's transport characteristics and provides an action plan to address school and neighborhood barriers to AST. Methods: We conducted a pilot STP…

  7. Hydraulic mechanism to limit torsional loads between the IUS and space transportation system orbiter

    NASA Technical Reports Server (NTRS)

    Farmer, James R.

    1986-01-01

    The Inertial Upper Stage (IUS) is a two-stage booster used by NASA and the Defense Department to insert payloads into geosynchronous orbit from low-Earth orbit. The hydraulic mechanism discussed here was designed to perform a specific dynamic and static interface function within the Space Transportation System's Orbiter. Requirements, configuration, and application of the hydraulic mechanism with emphasis on performance and methods of achieving zero external hydraulic leakage are discussed. The hydraulic load-leveler mechanism meets the established design requirements for operation in a low-Earth orbit. Considerable testing was conducted to demonstrate system performance and verification that external leakage had been reduced to zero. Following each flight use of an ASE, all hydraulic mechanism components are carefully inspected for leakage. The ASE, including the hydraulic mechanism, has performed without any anomalies during all IUS flights.

  8. Evaluation of organic cation transporter 3 (SLC22A3) inhibition as a potential mechanism of antidepressant action.

    PubMed

    Zhu, Hao-Jie; Appel, David I; Gründemann, Dirk; Richelson, Elliott; Markowitz, John S

    2012-04-01

    Organic cation transporter 3 (OCT3, SLC22A3) is a low-affinity, high-capacity transporter widely expressed in the central nervous system (CNS) and other major organs in both humans and rodents. It is postulated that OCT3 has a role in the overall regulation of neurotransmission and maintenance of homeostasis within the CNS. It is generally believed that all antidepressant drugs in current clinical use exert their primary therapeutic effects through inhibition of one or more of the high-affinity neuronal plasma membrane monoamine transporters, such as the norepinephrine transporter and the serotonin transporter. In the present study, we investigated the inhibitory effects of selected antidepressants on OCT3 activity in OCT3-transfected cells to evaluate whether OCT3 inhibition may at least in part contribute to the pharmacological effects of tested antidepressants. The studies demonstrated that all examined antidepressants inhibited OCT3-mediated uptake of the established OCT3 substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (4-Di-1-ASP) in a concentration-dependent manner. The IC(50) values were determined to be 4.7 μM, 7.4 μM, 12.0 μM, 18.6 μM, 11.2 μM, and 21.9 μM for desipramine, sertraline, paroxetine, amitriptyline, imipramine, and fluoxetine, respectively. Additionally, desipramine had an IC(50) value of 0.7 μM for the uptake of NE by OCT3, while the IC(50) value of sertraline was 2.3 μM for 5-HT uptake. Both desipramine and sertraline appeared to inhibit OCT3 activity via a non-competitive mechanism. In vivo studies are warranted to determine whether such effects on OCT3 inhibition are of sufficient magnitude to contribute to the overall therapeutic effects of antidepressants.

  9. The transepithelial transport mechanism of polybrominated diphenyl ethers in human intestine determined using a Caco-2 cell monolayer.

    PubMed

    Yu, Yingxin; Wang, Mengmeng; Zhang, Kaiqiong; Yang, Dan; Zhong, Yufang; An, Jing; Lei, Bingli; Zhang, Xinyu

    2017-04-01

    Oral ingestion plays an important role in human exposure to polybrominated diphenyl ethers (PBDEs). The uptake of PBDEs primarily occurs in the small intestine. The aim of the present study is to investigate the transepithelial transport characteristics and mechanisms of PBDEs in the small intestine using a Caco-2 cell monolayer model. The apparent permeability coefficients of PBDEs indicated that tri- to hepta-BDEs were poorly absorbed compounds. A linear increase in transepithelial transport was observed with various concentrations of PBDEs, which suggested that passive diffusion dominated their transport at the concentration range tested. In addition, the pseudo-first-order kinetics equation can be applied to the transepithelial transport of PBDEs. The rate-determining step in transepithelial transport of PBDEs was trans-cell transport including the trans-pore process. The significantly lower transepithelial transport rates at low temperature for bidirectional transepithelial transport suggested that an energy-dependent transport mechanism was involved. The efflux transporters (P-glycoprotein, multidrug resistance-associated protein, and breast cancer resistance protein) and influx transporters (organic cation transporters) participated in the transepithelial transport of PBDEs. In addition, the transepithelial transport of PBDEs was pH sensitive; however, more information is required to understand the influence of pH.

  10. Mimicking cellular transport mechanism in stem cells through endosomal escape of new peptide-coated quantum dots

    NASA Astrophysics Data System (ADS)

    Narayanan, Karthikeyan; Yen, Swee Kuan; Dou, Qingqing; Padmanabhan, Parasuraman; Sudhaharan, Thankiah; Ahmed, Sohail; Ying, Jackie Y.; Selvan, Subramanian Tamil

    2013-07-01

    Protein transport is an important phenomenon in biological systems. Proteins are transported via several mechanisms to reach their destined compartment of cell for its complete function. One such mechanism is the microtubule mediated protein transport. Up to now, there are no reports on synthetic systems mimicking the biological protein transport mechanism. Here we report a highly efficient method of mimicking the microtubule mediated protein transport using newly designed biotinylated peptides encompassing a microtubule-associated sequence (MTAS) and a nuclear localization signaling (NLS) sequence, and their final conjugation with streptavidin-coated CdSe/ZnS quantum dots (QDs). Our results demonstrate that these novel bio-conjugated QDs enhance the endosomal escape and promote targeted delivery into the nucleus of human mesenchymal stem cells via microtubules. Mimicking the cellular transport mechanism in stem cells is highly desirable for diagnostics, targeting and therapeutic applications, opening up new avenues in the area of drug delivery.

  11. [Effect of pravastatin on transportation of scutellarin in mouse liver and its mechanism].

    PubMed

    Liu, Jian-Ming; Xiong, Yu-Qing

    2011-03-01

    This study is to investigate the transportation of scutellarin in cell and live models and study on mechanism of absorption and transport of scutellarin in mouse liver. The concentration of scutellarin in plasma and liver from control and pretreated groups was determined by high performance liquid chromatography. The uptake of scutellarin was examined in control hepatocytes group, induced hepatocytes group and induced hepatocytes plus pravastatin group. Pravastatin can affect the pharmacokinetics of scutellarin in mouse: CL is decreased while AUC is increased. The scutellarin absorption of hepatocyte induced group was higher than that of control group, but was decreased in the group with pravastatin added. The research showed that there was potential drug interaction between pravastatin and scutellarin. The drugs may compete for oatp2 mediated transport pathway consisted in the uptake of scutellarin in liver.

  12. Molecular mechanism of ATP-dependent solute transport by multidrug resistance-associated protein 1.

    PubMed

    Chang, Xiu-bao

    2010-01-01

    Millions of new cancer patients are diagnosed each year and over half of these patients die from this devastating disease. Thus, cancer causes a major public health problem worldwide. Chemotherapy remains the principal mode to treat many metastatic cancers. However, occurrence of cellular multidrug resistance (MDR) prevents efficient killing of cancer cells, leading to chemotherapeutic treatment failure. Over-expression of ATP-binding cassette transporters, such as P-glycoprotein, breast cancer resistance protein and/or multidrug resistance-associated protein 1 (MRP1), confers an acquired MDR due to their capabilities of transporting a broad range of chemically diverse anticancer drugs across the cell membrane barrier. In this review, the molecular mechanism of ATP-dependent solute transport by MRP1 will be addressed.

  13. Surface transport properties of reticulopodia: do intracellular and extracellular motility share a common mechanism?

    PubMed

    Bowser, S S; Israel, H A; McGee-Russell, S M; Rieder, C L

    1984-12-01

    The reticulopodial networks of the foraminiferan protozoans Allogromia sp., strain NF, and A. laticollaris display rapid (up to 11 microns/second) and bidirectional saltatory transport of membrane surface markers (polystyrene microspheres). Electron microscopy shows that microspheres adhere directly to the reticulopodial surface glycocalyx. A videomicroscopic analysis of this phenomenon reveals that microsphere movement is typically independent of pseudopod extension/withdrawal and that particles of different sizes and surface properties display similar motile characteristics. The motile properties of surface-associated microspheres appear identical to those of saltating intracellular organelles. Indeed, in some instances the surface-attached microspheres appear transiently linked in motion to these underlying organelles. Our observations suggest that, in reticulopodia, surface transport of microspheres and intracellular transport of organelles are driven by a common mechanism.

  14. Excess white noise to probe transport mechanisms in a membrane channel

    NASA Astrophysics Data System (ADS)

    Queralt-Martín, María; López, M. Lidón; Alcaraz, Antonio

    2015-06-01

    Current fluctuation analysis has been successfully used over the years to investigate the physical properties of different systems. Here, we perform single-channel time-resolved current experiments in a protein channel to evaluate the different transport mechanisms governing the channel function. Using different salts of monovalent and divalent cations in a wide range of concentrations and applied potentials, we analyze current fluctuations focusing on the voltage dependence of the additional white noise that appears in the low-frequency range of the spectra. We demonstrate that the channel displays two characteristic transport regimes: at low salt concentrations (10 mM to 1 M) ion permeation is controlled by the protein fixed charges that induce accumulation or exclusion of ions to preserve local electroneutrality. At high salt concentrations (>1 M ) adsorption processes associated to the binding of cations to the channel charges regulate the transport properties.

  15. The evolvement of the transport mechanism with the ensemble density of Si quantum dots

    SciTech Connect

    Balberg, Isaac

    2014-03-31

    In this review I will try to suggest a comprehensive understanding of the transport mechanisms in three dimensional systems of Si quantum dots (QDs) from the single QD to the very dense ensembles. This understanding is based on our systematic microscopic and macroscopic electrical measurements as a function of the density of Si nanocrystallites. In particular, the role of quantum confinement and Coulomb blockade effects in the transport will be discussed and the concept of QDs' 'touching' will be applied. This consideration will enable to reveal the presence of two transitions, a local carrier deconfinement transition and a percolation transition at which these effects are reminiscent of those found in the single QD. It is hoped that our discussion of the evolvement of the transport with the density of the QDs will provide guidance for the understanding of ensembles of semiconductor QDs in general and ensembles of Si QDs in particular.

  16. Structural mechanism of nuclear transport mediated by importin β and flexible amphiphilic proteins.

    PubMed

    Yoshimura, Shige H; Kumeta, Masahiro; Takeyasu, Kunio

    2014-12-02

    Karyopherin β family proteins mediate the nuclear/cytoplasmic transport of various proteins through the nuclear pore complex (NPC), although they are substantially larger than the size limit of the NPC.To elucidate the molecular mechanism underlying this paradoxical function, we focused on the unique structures called HEAT repeats, which consist of repetitive amphiphilic α helices. An in vitro transport assay and FRAP analyses demonstrated that not only karyopherin β family proteins but also other proteins with HEAT repeats could pass through the NPC by themselves, and serve as transport mediators for their binding partners. Biochemical and spectroscopic analyses and molecular dynamics simulations of purified HEAT-rich proteins revealed that they interact with hydrophobic groups, including phenyl and alkyl groups, and undergo reversible conformational changes in tertiary structures, but not in secondary structures. These results show that conformational changes in the flexible amphiphilic motifs play a critical role in translocation through the NPC.

  17. Are the correlates of active school transport context-specific?

    PubMed Central

    Larouche, R; Sarmiento, O L; Broyles, S T; Denstel, K D; Church, T S; Barreira, T V; Chaput, J-P; Fogelholm, M; Hu, G; Kuriyan, R; Kurpad, A; Lambert, E V; Maher, C; Maia, J; Matsudo, V; Olds, T; Onywera, V; Standage, M; Tremblay, M S; Tudor-Locke, C; Zhao, P; Katzmarzyk, P T

    2015-01-01

    OBJECTIVES: Previous research consistently indicates that children who engage in active school transport (AST) are more active than their peers who use motorized modes (car or bus). However, studies of the correlates of AST have been conducted predominantly in high-income countries and have yielded mixed findings. Using data from a heterogeneous sample of 12 country sites across the world, we investigated the correlates of AST in 9–11-year olds. METHODS: The analytical sample comprised 6555 children (53.8% girls), who reported their main travel mode to school and the duration of their school trip. Potential individual and neighborhood correlates of AST were assessed with a parent questionnaire adapted from previously validated instruments. Multilevel generalized linear mixed models (GLMM) were used to examine the associations between individual and neighborhood variables and the odds of engaging in AST while controlling for the child's school. Site moderated the relationship of seven of these variables with AST; therefore we present analyses stratified by site. RESULTS: The prevalence of AST varied from 5.2 to 79.4% across sites and the school-level intra-class correlation ranged from 0.00 to 0.56. For each site, the final GLMM included a different set of correlates of AST. Longer trip duration (that is, ⩾16 min versus ⩽15 min) was associated with lower odds of AST in eight sites. Other individual and neighborhood factors were associated with AST in three sites or less. CONCLUSIONS: Our results indicate wide variability in the prevalence and correlates of AST in a large sample of children from twelve geographically, economically and culturally diverse country sites. This suggests that AST interventions should not adopt a ‘one size fits all' approach. Future research should also explore the association between psychosocial factors and AST in different countries. PMID:27152191

  18. Solitary waves: a possible mechanism for rapid fluid transport in low permeability porous media

    NASA Astrophysics Data System (ADS)

    Appold, Martin; Joshi, Ajit

    2014-05-01

    Elastic porous media in which the rate of fluid pressure generation is high relative to the rate of fluid pressure diffusion and whose permeabilities are a sensitive function of effective stress may generate solitary waves manifest as discrete pulses of elevated pore pressure and porosity that can travel at velocities that are orders of magnitude greater than the velocities of the pore fluids in the background Darcian flow regime. Solitary waves may thus be important vehicles for fluid transport through porous media whose permeabilities are otherwise too low to allow significant rates of flow. Solitary waves have been hypothesized for diverse geologic settings and processes, including magmatic hydrothermal ore formation, magma transport, fault slip in accretionary wedges and at transform plate boundaries, and primary hydrocarbon migration in sedimentary basins. The present study has focused on solitary waves as agents of oil and methane transport through numerical simulation of their origin and behavior. The results show solitary waves to have limited capacity for transporting oil for several reasons: (1) the rate of fluid pressure generation by typical mechanisms like compaction disequilibrium and hydrocarbon formation is too low to allow solitary waves to form unless permeability is exceptionally low (10-24 to 10-25 m2), (2) solitary waves are only able to ascend no more than 1-2 km before dissipating to ambient pressure and porosity values, (3) the waves are too small and the frequency of their formation is too low to account for the amount of oil observed in the reservoirs that they have been hypothesized to feed. Solitary waves have been found to be more effective at transporting methane because of its lower density and viscosity compared to oil, provided that a mechanism for rapid pressure generation exists and permeabilities are very low. If those conditions exist, then solitary waves can ascend over two kilometers at rates on the order of 100's of meters

  19. Interaction of gatifloxacin with efflux transporters: a possible mechanism for drug resistance

    PubMed Central

    Kwatra, Deep; Vadlapatla, Ramya Krishna; Vadlapudi, Aswani Dutt; Pal, Dhananjay; Mitra, Ashim K.

    2010-01-01

    The purpose of the study is to screen the interactions of fourth generation fluoroquinolone-gatifloxacin with efflux pumps i.e. P-gp, MRP2 and BCRP. Mechanism of gatifloxacin interaction with efflux transporters may explain its acquired resistance. Such clarification may lead to the development of strategies to overcome efflux and enhance its bioavailability at target site. This process will aid in the reduction of dose volume, further eliminating the chances of systemic toxicity from topical gatifloxacin eye drops. MDCK cell lines transfected with the targeted efflux transporters were used for this study. [14C] Erythromycin was selected as a model substrate for P-gp and MRP2 whereas Hoechst 33342 was employed as a substrate for BCRP. Uptake and transport studies of these substrates were performed in the presence of gatifloxacin to delineate its interaction with efflux transporters. Further the efflux ratio in the presence of gatifloxacin was calculated from bidirectional transport studies. The concentration of [14C] erythromycin and Hoechst 33342 were measured using scintillation counter and fluorescence plate reader respectively. A concentration dependent inhibition effect in the presence of gatifloxacin was revealed on [14C] erythromycin uptake. The efflux ratio (BL-AP/AP-BL) of substrates was found to approach unity at higher gatifloxacin concentrations. Increased concentration of gatifloxacin did not elevate uptake of Hoechst 33342. All these studies were validated with known inhibitors as positive control. Uptake and transport studies support the hypothesis that gatifloxacin is a substrate for P-gp, MRP2 but not for BCRP. Possible interactions of gatifloxacin with P-gp and MRP2 may be a possible mechanism for acquired resistance of gatifloxacin. This information can be further extended to design prodrugs or formulations in order to prevent development of acquired resistance and improve therapeutic efficacy with its reduction in side effects. PMID:20573570

  20. Targeting drug transport mechanisms for improving platinum-based cancer chemotherapy

    PubMed Central

    Chen, Helen HW; Chen, Wen-Chung; Liang, Zhang-Dong; Tsai, Wen-Bin; Long, Yan; Aiba, Isamu; Fu, Siqing; Broaddus, Russell; Liu, Jinsong; Feun, Lynn G; Savaraj, Niramol; Kuo, Macus Tien

    2016-01-01

    Introduction Platinum (Pt)-based antitumor agents remain important chemotherapeutic agents for treating many human malignancies. Elevated expression of the human high-affinity copper transporter 1 (hCtr1), resulting in enhanced Pt drug transport into cells, has been shown to be associated with improved treatment efficacy. Thus, targeting hCtr1 upregulation is an attractive strategy for improving the treatment efficacy of Pt-based cancer chemotherapy. Area covered Regulation of hCtr1 expression by cellular copper homeostasis is discussed. Association of elevated hCtr1 expression with intrinsic sensitivity of ovarian cancer to Pt drugs is presented. Mechanism of copper-lowering agents in enhancing hCtr1-mediated cis-diamminedichloroplatinum (II) (cisplatin, cDDP) transport is reviewed. Applications of copper chelation strategy in overcoming cDDP resistance through enhanced hCtr1 expression are evaluated. Expert opinion While both transcriptional and posttranslational mechanisms of hCtr1 regulation by cellular copper bioavailability have been proposed, detailed molecular insights into hCtr1 regulation by copper homeostasis remain needed. Recent clinical study using a copper-lowering agent in enhancing hCtr1-mediated drug transport has achieved incremental improvement in overcoming Pt drug resistance. Further improvements in identifying predictive measures in the subpopulation of patients that can benefit from the treatment are needed. PMID:26004625

  1. Transport capacity and saturation mechanism in a real-space cellular automaton dune model

    NASA Astrophysics Data System (ADS)

    Gao, X.; Zhang, D.; Rozier, O.; Narteau, C.

    2014-04-01

    In a real-space cellular automaton dune model, individual physical processes such as erosion, deposition and transport are implemented by nearest neighbor interactions and a time-dependent stochastic process. Hence, the transport capacity, the saturation mechanism and the characteristic wavelength for the formation of dunes are emergent properties that can only be determined a posteriori from the output of the numerical simulations. Here we propose a simplified version of the model to establish asymptotic relations between the microscopic erosion-deposition-transport rate parameters and the characteristic length and time scales of the flux saturation mechanism. In particular, we show that, in the cellular automaton, the saturation length is a mean transport distance controlled by the deposition of mobile sedimentary cells. Then, we discuss how these results can be used to determine the sediment flux within dune fields and the rate parameters of a new class of discrete models that concentrate on the effect of heterogeneities in grain-size on dune morphodynamics.

  2. Promoter Analysis of the Human Ascorbic Acid Transporters SVCT1 & 2: Mechanisms of Adaptive Regulation in Liver Epithelial Cells

    PubMed Central

    Reidling, Jack C.; Rubin, Stanley A.

    2010-01-01

    Ascorbic acid, the active form of vitamin C, is a vital antioxidant in the human liver, yet the molecular mechanisms involved in the regulation of ascorbic acid transporters (hSVCT1 and hSVCT2) in liver cells are poorly understood. Therefore, we characterized the minimal promoter regions of hSVCT1 & 2 in cultured human liver epithelial cells (HepG2) and examined the effects of ascorbic acid deprivation and supplementation on activity and regulation of the transport systems. Identified minimal promoters required for basal activity were found to include multiple cis-regulatory elements, whereas mutational analysis demonstrated that HNF-1 sites in the hSVCT1 promoter and KLF/Sp1 sites in the hSVCT2 promoter were essential for activities. When cultured in ascorbic acid deficient or supplemented media, HepG2 cells demonstrated significant (P < 0.01) and specific reciprocal changes in [14C]-Ascorbic acid uptake, and in hSVCT1 mRNA and protein levels as well as hSVCT1 promoter activity. However, no significant changes in hSVCT2 expression or promoter activity were observed during ascorbic acid deficient or supplemented conditions. We mapped the ascorbic acid responsive region in the hSVCT1 promoter and determined that HNF-1 sites are important for the adaptive regulation response. The results of these studies further characterize the hSVCT1 and 2 promoters, establish that ascorbic acid uptake by human liver epithelial cells is adaptively regulated, and show that transcriptional mechanisms via HNF-1 in the hSVCT1 promoter may, in part, be involved in this regulation. PMID:20471816

  3. Physiologic mechanism of the ultrasonically activated scalpel.

    PubMed

    McCarus, S D

    1996-08-01

    An ultrasonically activated scalpel was developed and used clinically to provide hemostatic cutting in laparoscopic surgery. Results of experimental work with the ultrasonic scalpel blades were compared with those of electrosurgery and lasers. Some features that distinguish this energy form may confer specific advantages in various surgical procedures.

  4. The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD

    NASA Astrophysics Data System (ADS)

    Calmettes, Charles; Ing, Christopher; Buckwalter, Carolyn M.; El Bakkouri, Majida; Chieh-Lin Lai, Christine; Pogoutse, Anastassia; Gray-Owen, Scott D.; Pomès, Régis; Moraes, Trevor F.

    2015-08-01

    Invading bacteria from the Neisseriaceae, Acinetobacteriaceae, Bordetellaceae and Moraxellaceae families express the conserved outer-membrane zinc transporter zinc-uptake component D (ZnuD) to overcome nutritional restriction imposed by the host organism during infection. Here we demonstrate that ZnuD is required for efficient systemic infections by the causative agent of bacterial meningitis, Neisseria meningitidis, in a mouse model. We also combine X-ray crystallography and molecular dynamics simulations to gain insight into the mechanism of zinc recognition and transport across the bacterial outer-membrane by ZnuD. Because ZnuD is also considered a promising vaccine candidate against N. meningitidis, we use several ZnuD structural intermediates to map potential antigenic epitopes, and propose a mechanism by which ZnuD can maintain high sequence conservation yet avoid immune recognition by altering the conformation of surface-exposed loops.

  5. Flow cytometry analysis of drug transport mechanisms in Haemonchus contortus susceptible or resistant to anthelmintics.

    PubMed

    Kerboeuf, D; Chambrier, P; Le Vern, Y; Aycardi, J

    1999-02-01

    The role of membrane drug-transport mechanisms in resistance to anthelmintics was examined using a flow cytometry method. This method was adapted from assays developed for the study of similar mechanisms in tumor cells. Rhodamine 123, a P-glycoprotein transport probe, associated with the reversal agent verapamil gave a significantly higher level of green fluorescence in Haemonchus contortus-resistant eggs as compared with that of susceptible eggs. In the same way, verapamilbodipy, a new fluorescent probe for the detection of multidrug resistance in cells, showed a significantly higher degree of binding to resistant eggs. The results confirm those obtained with biological drug assays using both anthelmintics and verapamil and provide a quantitative and effective methodology for the functional study of multidrug resistance in nematodes.

  6. The molecular mechanism of Zinc acquisition by the neisserial outer-membrane transporter ZnuD

    PubMed Central

    Calmettes, Charles; Ing, Christopher; Buckwalter, Carolyn M.; El Bakkouri, Majida; Chieh-Lin Lai, Christine; Pogoutse, Anastassia; Gray-Owen, Scott D.; Pomès, Régis; Moraes, Trevor F.

    2015-01-01

    Invading bacteria from the Neisseriaceae, Acinetobacteriaceae, Bordetellaceae and Moraxellaceae families express the conserved outer-membrane zinc transporter zinc-uptake component D (ZnuD) to overcome nutritional restriction imposed by the host organism during infection. Here we demonstrate that ZnuD is required for efficient systemic infections by the causative agent of bacterial meningi