FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2032081130> ?p ?o ?g. }

• W2032081130 endingPage "1416" @default.
• W2032081130 startingPage "1413" @default.
• W2032081130 abstract "It is well established that cotransporters transport water, but how they do it is debated. Two mechanisms have been suggested: cotransport of water along with the nonaqueous substrates, and osmosis where the cotransporters simply act as water channels. In a recent article, Charron et al. investigated this question for the Na+-coupled glucose transporter expressed in Xenopus laevis oocytes. They focused upon the posttransport period, i.e., when external sugar was removed after a period of inwardly directed Na+ and sugar transport, and argued, on partly empirical grounds, that the data could be explained exclusively by osmosis. In this Comment to the Editor, we have reinterpreted these data by a numerical model of the oocyte which reflects the physical transport processes taking place: cotransport and/or osmosis across the membrane and diffusion and mass balance of the nonaqueous substrates in the cytoplasm. We find that the experiments and analysis as performed in Charron et al. are inadequate with respect to distinguishing between the cotransport hypothesis and the osmotic hypothesis for water transport in cotransporters. It is now generally accepted that cotransporters of the symport type transport water (1.Agre P. Nielsen S. Ottersen O.P. Towards a molecular understanding of water homeostasis in the brain.Neuroscience. 2004; 12: 849-850Google Scholar, 2.King L.S. Kozono D. Agre P. From structure to disease: the evolving tale of aquaporin biology.Nat. Rev. Mol. Cell Biol. 2004; 5: 687-698Google Scholar). Cotransporters such as the KCC, NKCC1, and a variety of Na+-coupled cotransporters have capacities for water transport, which, per molecule, range between that of AQP0 and AQP1 (3.Loo D.F. Hirayama B.A. Meinild A.-K. Chandy G. Zeuthen T. Wright E. Passive water and ion transport by cotransporters.J. Physiol. 1999; 518.1: 195-202Google Scholar, 4.MacAulay N. Hamann S. Zeuthen T. Water transport in the brain: role of cotransporters.Neuroscience. 2004; 129: 1031-1044Google Scholar, 5.Hamann S. Herrera-Perez J.J. Bundgaard M. Alvarez-Leefmans F.J. Zeuthen T. Water permeability of Na+-K+-2Cl− cotransporters in mammalian epithelial cells.J. Physiol. 2005; 568.1: 123-135Google Scholar, 6.Loo D.D.F. Zeuthen T. Chandy G. Wright E.M. Cotransport of water by the Na+/glucose cotransporter.Proc. Natl. Acad. Sci. USA. 1996; 93: 13367-13370Google Scholar). The nature of the transport mechanism, however, has been the subject of an intense debate, which has focused mainly on the water transport properties of the Na+-coupled glucose transporter (SGLT1) expressed in Xenopus oocytes. Two principally different transport mechanisms have been proposed. We have presented the cotransport hypothesis in which a large fraction of the transported water moves along with Na+ and glucose by a molecular mechanism within the cotransporter itself. Accordingly, this water flux is energized by the Na+ flux and can proceed independent of the transmembrane osmotic gradient (6.Loo D.D.F. Zeuthen T. Chandy G. Wright E.M. Cotransport of water by the Na+/glucose cotransporter.Proc. Natl. Acad. Sci. USA. 1996; 93: 13367-13370Google Scholar, 7.Meinild A.-K. Klaerke D.A. Loo D.D.F. Wright E.M. Zeuthen T. The human Na+/glucose cotransporter is a molecular water pump.J. Physiol. 1998; 508.1: 15-21Google Scholar, 8.Zeuthen T. Meinild A.-K. Loo D.D.F. Wright E.M. Klaerke D.A. Isotonic transport by the Na+-glucose cotransporter SGLT1.J. Physiol. 2001; 531.3: 631-644Google Scholar, 9.Zeuthen T. Zeuthen E. Klaerke D.A. Mobility of ions, sugar, and water in the cytoplasm of Xenopus oocytes expressing Na+-coupled sugar transporters (SGLT1).J. Physiol. 2002; 542.1: 71-87Google Scholar, 10.Zeuthen T. Belhage B. Zeuthen E. Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution.J. Physiol. 2006; 570.3: 485-499Google Scholar). In opposition to this, Charron and co-workers (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar, 12.Duquette P.-P. Bisonnette P. Lapointe J.-Y. Local osmotic gradients drive the water flux associated with Na+/glucose cotransport.Proc. Natl. Acad. Sci. USA. 2001; 98: 3796-3801Google Scholar, 13.Gagnon M.P. Bissonnette P. Deslandes L.M. Wallendorff B. Lapointe J.Y. Glucose accumulation can account for the initial water flux triggered by Na+/glucose cotransport.Biophys. J. 2004; 86: 125-133Google Scholar) have argued that the SGLT1 acts entirely as a water channel and that all water transport is osmotic. In this osmotic hypothesis, the driving force for the water transport is proposed to arise as an unstirred layer effect: the diffusion of Na+ and sugar inside the oocyte is assumed to be so slow that significant concentrations build up at the inside of the membrane. This, in turn, leads to water transport by osmosis. It can be estimated that the intracellular diffusion coefficients need to be about three orders of magnitude lower than the free solution values for sufficient concentrations to build up (10.Zeuthen T. Belhage B. Zeuthen E. Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution.J. Physiol. 2006; 570.3: 485-499Google Scholar). It will be of significant physiological relevance to decide between the two hypotheses. In the case of cotransport, water transport can proceed uphill, against the water chemical potential, energized by the (downhill) flux of Na+. This would present a direct solution to several physiological problems, for example, how water can move uphill, from lumen into plasma, across the small intestine (14.Reid E.W. Report on experiments upon “absorption without osmosis”.BMJ. 1892; 1: 323-326Google Scholar) and other epithelial cell layers (15.Zeuthen T. General models for water transport across leaky epithelia.Int. Rev. Cytol. 2002; 215: 285-317Google Scholar). In a recent article, Charron and co-workers used the human isoform hSGLT and focused upon the volume changes that took place immediately after a period of Na+-coupled sugar transport in combination with an osmotic challenge (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar). They employed the nonmetabolizable glucose-analog methyl-α-D-glucopyranoside (αMDG). The underlying assumptions were that only the osmotic hypothesis would explain an increase in intracellular osmolarity and osmotic water transport during the sugar stimulation, and that “this contrasts with the prediction of the water cotransport hypothesis, which purports that 0% of the water transport would be passive during the first minute of transport”(11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar). Thus, the osmotic hypothesis would predict a significant poststimulation swelling, whereas the cotransport hypothesis would not. In addition, the authors argued that the differences between the two hypotheses would be more pronounced for oocytes in which the passive water permeability had been increased by coexpression of AQP1, since the effects of the changes in intracellular osmolarities would be amplified. To analyze their data, the authors used two different numerical models. One was empirical and employed up to six arbitrary constants. Such models, however, do not reflect physical mechanisms. The other model described only central symmetrical diffusion in a sphere but did not incorporate the possibility of cotransport of water. We would question these assumptions and argue that the numerical models used in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar) are inadequate. First, the assumption that the osmotic hypothesis predicts significantly larger changes in intracellular osmolarity during sugar transport than the cotransport hypothesis is untenable. This is particularly relevant for the experiments where sugar transport is combined with an increase in external osmolarity since water is removed by osmosis. Second, it appears that neither of the two numerical models used in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar) incorporates the correct equations to describe cotransport of water. In fact, the principle of mass balance seems to be violated in the test between the osmotic and the cotransport hypotheses shown (Fig. 4 in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar)). Accordingly, we would like to reinterpret the experiments presented in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar) by a numerical model we have developed to describe transport of water in the Xenopus oocyte (10.Zeuthen T. Belhage B. Zeuthen E. Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution.J. Physiol. 2006; 570.3: 485-499Google Scholar). This model is based on the physical mechanism involved and designed to distinguish clearly between osmosis and cotransport of water. In our numerical model, SGLT1 was present in the plasma membrane where it mediated the coupled influx of Na+, sugar, and possibly water. Application of sugar to the external surface of the oocyte under voltage clamp conditions initiated an inward clamp current, IC, which was carried by two Na+ ions and followed by one molecule of αMDG. To describe the cotransport hypothesis, this was accompanied obligatorily by a number of water molecules given by a coupling ratio (CR). Accordingly, the cotransported fluxes of Na+, sugar, and water were, respectively, as follows:JNa+=ICF−1(1) JαMDG=0.5⁡ICF−1(2) JH2O,CO=0.5⁡CR⁡VwICF−,(3) where F is Faraday's constant and Vw is the molar volume of water (18 cm3 mol−1). To comply with the analysis in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar), we used a CR of 250 for the hSGLT1. When the osmotic hypothesis was tested, CR was set to zero. For both hypotheses, water also crosses the membrane by osmosis (JH2O,OS), determined by the transmembrane osmotic gradient (osmi - osmo) and the passive osmotic water permeability Lp:JH2O,OS=Lp⁡A⁡Vw(osmi−osmo),(4) where A is the true surface area of the oocyte, ∼0.4 cm2. The external osmolarity (osmo) was given by the experiment, but the osmolarity at the inside of the membrane (osmi) depended on how fast the oocyte filled up with substrates and how readily they diffused in the cytoplasm. This is a function of the free fraction of the oocyte volume (VF), in these calculations taken as 50% of the total volume (10.Zeuthen T. Belhage B. Zeuthen E. Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution.J. Physiol. 2006; 570.3: 485-499Google Scholar, 11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar), and of the intracellular diffusion coefficient Di. In accordance with Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar), we used a Di of 0.15 × 10−5 cm2 s−1 for both the Na+ and αMDG, which, incidentally, agrees with our previous estimates (9.Zeuthen T. Zeuthen E. Klaerke D.A. Mobility of ions, sugar, and water in the cytoplasm of Xenopus oocytes expressing Na+-coupled sugar transporters (SGLT1).J. Physiol. 2002; 542.1: 71-87Google Scholar). This value is about one-fifth of the diffusion coefficient for glucose in free solution. To describe the time course of substrate transport through the cytoplasm, the model oocyte was divided into 100 shells of equal thickness (division into 1000 shells gave the same results). Transport between shells was described by Fick's equation. Calculations were each performed for 0.01 s (for further details, see Zeuthen et al. (10.Zeuthen T. Belhage B. Zeuthen E. Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution.J. Physiol. 2006; 570.3: 485-499Google Scholar)). For both the cotransport hypothesis and the osmotic hypothesis, the Lp of the SGLT1-expressing oocytes consists of roughly equal contributions from the native oocyte membrane and from the SGLT1s (3.Loo D.F. Hirayama B.A. Meinild A.-K. Chandy G. Zeuthen T. Wright E. Passive water and ion transport by cotransporters.J. Physiol. 1999; 518.1: 195-202Google Scholar). Coexpression of AQP1 can be used to increase the Lp of the membrane further by about one order of magnitude (8.Zeuthen T. Meinild A.-K. Loo D.D.F. Wright E.M. Klaerke D.A. Isotonic transport by the Na+-glucose cotransporter SGLT1.J. Physiol. 2001; 531.3: 631-644Google Scholar, 11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar). In the analysis here, we used Lps similar to those presented in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar). The Xenopus oocyte was assumed to be spherical, with an initial diameter of 1.2 mm. It is noted that clamp currents in the microelectrodes do not give rise to any significant changes in intracellular osmolarity as was ascertained both theoretically and experimentally in Zeuthen et al. (9.Zeuthen T. Zeuthen E. Klaerke D.A. Mobility of ions, sugar, and water in the cytoplasm of Xenopus oocytes expressing Na+-coupled sugar transporters (SGLT1).J. Physiol. 2002; 542.1: 71-87Google Scholar). The question raised in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar) was which volume changes can be expected after a period of sugar transport? In Fig. 1 we simulated these volume changes for oocytes with relatively low passive water permeability (expression of hSGLT1 alone, Fig. 1, A and B) and for oocytes with high passive water permeability (coexpression of AQP1 and hSGLT1, Fig. 1, C and D). As outlined above, we used data and parameters from Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar). In the cases where sugar transport was combined with an increase in external osmolarity (Fig. 1, B and D), the simulations showed clearly that the rates of posttransport swellings predicted by the cotransport hypothesis and the osmotic hypothesis were similar. This is due to two factors. First, the intracellular hyperosmolarities predicted by the two hypotheses are quite close at the time of substrate removal. This can be calculated from the integrated fluxes (Eqs. 1 and 2) and the final oocyte volumes. For the oocytes expressing only hSGLT1 (Fig. 1 B) the cotransport hypothesis predicted an intracellular hyperosmolarity of 1.5 mOsm l−1. The osmotic hypothesis predicted a slightly higher hyperosmolarity of 2 mOsm l−1, since the oocyte, on this model, has shrunk relatively more during the osmotic challenge, which results in an up-concentration of the intracellular contents. Second, the noninstantaneous wash-out of sugar from the external solution caused a gradual decline of the clamp current. This residual current contributed an additional swelling in the case of the cotransport scenario. For the oocytes expressing both hSGLT1 and AQP1 (Fig. 1 D), it was calculated that the cotransport hypothesis predicted an increase of 1.4 mOsm l−1 and the osmotic hypothesis an increase of 1.5 mOsm l−1 during the stimulation with sugar and hyperosmolarity. Here the currents were terminated abruptly by application of phlorizin, in analogy to the experiments in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar). This would avoid any ambiguities in regard to noninstantaneous removal of external sugar. The results of these simulations conflict with Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar), who assumed that only the osmotic hypothesis would give rise to significant increases in intracellular osmolarity and swellings after a period of sugar transport combined with an osmotic challenge. Our simulations underscore that the cotransport hypothesis also predicts significant changes in the intracellular osmolarity and rates of swelling. This is not surprising as the cotransport of 250 water molecules, 2 Na+ ions, and 1 αMDG represent a hypertonic solution and, importantly, the imposed osmotic gradient removes water from the oocyte. In fact, a comparison between our simulations (Fig. 1) and the measurements presented in Figs. 1 and 4 in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar) shows that the cotransport hypothesis predicts the measurements better than the osmotic hypothesis. In general, the volumes predicted by the cotransport hypothesis are always higher and change faster than those predicted by the osmotic hypothesis (10.Zeuthen T. Belhage B. Zeuthen E. Water transport by Na+-coupled cotransporters of glucose (SGLT1) and of iodide (NIS). The dependence of substrate size studied at high resolution.J. Physiol. 2006; 570.3: 485-499Google Scholar). If the Lp was increased by coexpression of AQP1, the difference between the predictions of the cotransport hypothesis and the osmotic hypothesis became smaller, and not larger as argued in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar). This follows from the fact that the relative importance of the cotransport component of water transport is diminished when the Lp and the capacity for passive water transport are increased. Finally, it should be noted that after the removal of sugar, the volumes predicted by the cotransport and the osmotic hypotheses must approach the same value asymptotically. This follows from the principle of mass balance. During exposure to sugar, the amounts of Na+ and αMDG transported into the oocyte are the same in either hypothesis. Accordingly, the number of osmotic active particles trapped inside the oocyte will be the same when sugar is removed. It follows that the final isosmotic steady-state volumes predicted by the osmotic and the cotransport hypotheses must be identical. The final steady state will be reached faster in the case of high water permeability (see Fig. 1). A comparison between the cotransport and osmotic components of water transport in the SGLT1, the ion channel gramicidin, and the glucose monoport GLUT2 obtained by high resolution experiments has recently been presented (16.Zeuthen T. Zeuthen E. MacAulay N. Water transport by GLUT2 expressed in Xenopus laevis oocytes.J. Physiol. 2007; 579: 345-361Google Scholar). Our analysis contrasts with that of Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar) on four accounts. First, we find that at the termination of sugar transport combined with an osmotic challenge, the cotransport hypothesis and the osmotic hypothesis predict roughly the same rate of swelling. Second, the cotransport hypothesis gives the best fit to the recorded volume changes. Third, any increase in the passive water permeability by coexpression of AQP1 will minimize rather than maximize the differences between the changes predicted by the two hypotheses. In fact, lower Lps (and higher clamp currents) will facilitate the distinction between cotransport and osmosis. See, for example, Loo et al. (6.Loo D.D.F. Zeuthen T. Chandy G. Wright E.M. Cotransport of water by the Na+/glucose cotransporter.Proc. Natl. Acad. Sci. USA. 1996; 93: 13367-13370Google Scholar) where we used oocytes with Lps of ∼2 × 10−4 cm s−1 (∼1/3; of those employed in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar)) and currents in the range 1320–2980 nA. Finally, the problems with the numerical analysis in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar) are perhaps best illustrated by Fig. 4 in Charron et al. (11.Charron F.M. Blanchard M.G. Lapointe J.-Y. Intracellular hypertonicity is responsible for water flux associated with Na+/glucose cotransport.Biophys. J. 2006; 90: 3546-3554Google Scholar). Here the posttransport volumes calculated on the basis of the osmotic hypothesis are much larger than those calculated on the cotransport hypothesis, and the final steady states are different. This conflicts with the principle of mass balance as described above." @default.
• W2032081130 created "2016-06-24" @default.
• W2032081130 creator A5042786766 @default.
• W2032081130 creator A5080118751 @default.
• W2032081130 date "2007-08-01" @default.
• W2032081130 modified "2023-10-14" @default.
• W2032081130 title "The Mechanism of Water Transport in Na+-Coupled Glucose Transporters Expressed in Xenopus Oocytes" @default.
• W2032081130 cites W1521522718 @default.
• W2032081130 cites W1525861304 @default.
• W2032081130 cites W1570517521 @default.
• W2032081130 cites W1984579875 @default.
• W2032081130 cites W1991078537 @default.
• W2032081130 cites W2001093549 @default.
• W2032081130 cites W2006749910 @default.
• W2032081130 cites W2009703891 @default.
• W2032081130 cites W2017968105 @default.
• W2032081130 cites W2021692248 @default.
• W2032081130 cites W2050804557 @default.
• W2032081130 cites W2059573547 @default.
• W2032081130 cites W2079582937 @default.
• W2032081130 cites W2093069407 @default.
• W2032081130 cites W2121826300 @default.
• W2032081130 cites W2159732216 @default.
• W2032081130 doi "https://doi.org/10.1529/biophysj.106.095380" @default.
• W2032081130 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1929053" @default.
• W2032081130 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17513358" @default.
• W2032081130 hasPublicationYear "2007" @default.
• W2032081130 type Work @default.
• W2032081130 sameAs 2032081130 @default.
• W2032081130 citedByCount "17" @default.
• W2032081130 countsByYear W20320811302012 @default.
• W2032081130 countsByYear W20320811302014 @default.
• W2032081130 countsByYear W20320811302015 @default.
• W2032081130 countsByYear W20320811302017 @default.
• W2032081130 countsByYear W20320811302020 @default.
• W2032081130 countsByYear W20320811302023 @default.
• W2032081130 crossrefType "journal-article" @default.
• W2032081130 hasAuthorship W2032081130A5042786766 @default.
• W2032081130 hasAuthorship W2032081130A5080118751 @default.
• W2032081130 hasBestOaLocation W20320811301 @default.
• W2032081130 hasConcept C104317684 @default.
• W2032081130 hasConcept C121332964 @default.
• W2032081130 hasConcept C12554922 @default.
• W2032081130 hasConcept C134018914 @default.
• W2032081130 hasConcept C149011108 @default.
• W2032081130 hasConcept C161573976 @default.
• W2032081130 hasConcept C185592680 @default.
• W2032081130 hasConcept C2779306644 @default.
• W2032081130 hasConcept C2779535977 @default.
• W2032081130 hasConcept C2988574769 @default.
• W2032081130 hasConcept C2992163139 @default.
• W2032081130 hasConcept C39432304 @default.
• W2032081130 hasConcept C55493867 @default.
• W2032081130 hasConcept C62520636 @default.
• W2032081130 hasConcept C86803240 @default.
• W2032081130 hasConcept C87717796 @default.
• W2032081130 hasConcept C89611455 @default.
• W2032081130 hasConcept C95444343 @default.
• W2032081130 hasConceptScore W2032081130C104317684 @default.
• W2032081130 hasConceptScore W2032081130C121332964 @default.
• W2032081130 hasConceptScore W2032081130C12554922 @default.
• W2032081130 hasConceptScore W2032081130C134018914 @default.
• W2032081130 hasConceptScore W2032081130C149011108 @default.
• W2032081130 hasConceptScore W2032081130C161573976 @default.
• W2032081130 hasConceptScore W2032081130C185592680 @default.
• W2032081130 hasConceptScore W2032081130C2779306644 @default.
• W2032081130 hasConceptScore W2032081130C2779535977 @default.
• W2032081130 hasConceptScore W2032081130C2988574769 @default.
• W2032081130 hasConceptScore W2032081130C2992163139 @default.
• W2032081130 hasConceptScore W2032081130C39432304 @default.
• W2032081130 hasConceptScore W2032081130C55493867 @default.
• W2032081130 hasConceptScore W2032081130C62520636 @default.
• W2032081130 hasConceptScore W2032081130C86803240 @default.
• W2032081130 hasConceptScore W2032081130C87717796 @default.
• W2032081130 hasConceptScore W2032081130C89611455 @default.
• W2032081130 hasConceptScore W2032081130C95444343 @default.
• W2032081130 hasFunder F4320332676 @default.
• W2032081130 hasIssue "4" @default.
• W2032081130 hasLocation W20320811301 @default.
• W2032081130 hasLocation W20320811302 @default.
• W2032081130 hasLocation W20320811303 @default.
• W2032081130 hasLocation W20320811304 @default.
• W2032081130 hasOpenAccess W2032081130 @default.
• W2032081130 hasPrimaryLocation W20320811301 @default.
• W2032081130 hasRelatedWork W1529178114 @default.
• W2032081130 hasRelatedWork W1814989644 @default.
• W2032081130 hasRelatedWork W1947515666 @default.
• W2032081130 hasRelatedWork W2027162538 @default.
• W2032081130 hasRelatedWork W2032081130 @default.
• W2032081130 hasRelatedWork W2069407345 @default.
• W2032081130 hasRelatedWork W2081356126 @default.
• W2032081130 hasRelatedWork W2408756964 @default.
• W2032081130 hasRelatedWork W3048353462 @default.
• W2032081130 hasRelatedWork W763194022 @default.
• W2032081130 hasVolume "93" @default.
• W2032081130 isParatext "false" @default.
• W2032081130 isRetracted "false" @default.
• W2032081130 magId "2032081130" @default.

• next