Vasa recta

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Thomas L Pallone - One of the best experts on this subject based on the ideXlab platform.

  • adaptive responses of rat descending Vasa recta to ischemia
    American Journal of Physiology-renal Physiology, 2018
    Co-Authors: Zhong Zhang, Kristie Payne, Thomas L Pallone
    Abstract:

    We tested whether rat descending Vasa recta (DVR) undergo regulatory adaptions after the kidney is exposed to ischemia. Left kidneys (LK) were subjected to 30 minute renal artery cross clamp. After 48 hours, the post-ischemic LK and contralateral right kidney (RK) were harvested for study. When compared to DVR isolated from either sham operated LK or the contralateral RK, post-ischemic LK DVR markedly increased their NO generation. The selective inducible NOS (iNOS) inhibitor, 1400W, blocked the NO response. Immunoblots from outer medullary homogenates showed a parallel 2.6 fold increase in iNOS expression (P=0.01). Microperfused post-ischemic LK DVR exposed to angiotensin II (AngII, 10 nM), constricted less than those from the contralateral RK, and constricted more when exposed to 1400W (10 microM). Resting membrane potentials of pericytes from post-ischemic LK DVR pericytes were hyperpolarized relative to contralateral RK pericytes (62.0±1.6 vs 51.8±2.2 mV, respectively P

  • descending Vasa recta endothelial membrane potential response requires pericyte communication
    PLOS ONE, 2016
    Co-Authors: Zhong Zhang, Kristie Payne, Thomas L Pallone
    Abstract:

    Using dual-cell electrophysiological recording, we examined the routes for equilibration of membrane potential between the pericytes and endothelia that comprise the descending Vasa recta (DVR) wall. We measured equilibration between pericytes in intact vessels, between pericytes and endothelium in intact vessels and between pericytes physically separated from the endothelium. Dual pericyte recording on the abluminal surface of DVR showed that both resting potential and subsequent time-dependent voltage fluctuations after vasoconstrictor stimulation remained closely equilibrated, regardless of the agonist employed (angiotensin II, vasopressin or endothelin 1). When pericytes where removed from the vessel wall but retained physical contact with one another, membrane potential responses were also highly coordinated. In contrast, responses of pericytes varied independently when they were isolated from both the endothelium and from contact with one another. When pericytes and endothelium were in contact, their resting potentials were similar and their temporal responses to stimulation were highly coordinated. After completely isolating pericytes from the endothelium, their mean resting potentials became discordant. Finally, complete endothelial isolation eliminated all membrane potential responses to angiotensin II. We conclude that cell-to-cell transmission through the endothelium is not needed for pericytes to equilibrate their membrane potentials. AngII dependent responses of DVR endothelia may originate from gap junction coupling to pericytes rather than via receptor dependent signaling in the endothelium, per se.

  • syncytial communication in descending Vasa recta includes myoendothelial coupling
    American Journal of Physiology-renal Physiology, 2014
    Co-Authors: Zhong Zhang, Kristie Payne, Thomas L Pallone
    Abstract:

    Using dual cell patch-clamp recording, we examined pericyte, endothelial, and myoendothelial cell-to-cell communication in descending Vasa recta. Graded current injections into pericytes or endothe...

  • descending Vasa recta endothelial cells and pericytes form mural syncytia
    American Journal of Physiology-renal Physiology, 2014
    Co-Authors: Zhong Zhang, Kristie Payne, Thomas L Pallone
    Abstract:

    Using patch clamp, we induced depolarization of descending Vasa recta (DVR) pericytes or endothelia and tested whether it was conducted to distant cells. Membrane potential was measured with the fl...

  • cellular mechanisms underlying nitric oxide induced vasodilation of descending Vasa recta
    American Journal of Physiology-renal Physiology, 2011
    Co-Authors: Aurelie Edwards, Thomas L Pallone
    Abstract:

    It has been observed that vasoactivity of explanted descending Vasa recta (DVR) is modulated by intrinsic nitric oxide (NO) and superoxide (O2−) production (Cao C, Edwards A, Sendeski M, Lee-Kwon W...

Zhong Zhang - One of the best experts on this subject based on the ideXlab platform.

  • adaptive responses of rat descending Vasa recta to ischemia
    American Journal of Physiology-renal Physiology, 2018
    Co-Authors: Zhong Zhang, Kristie Payne, Thomas L Pallone
    Abstract:

    We tested whether rat descending Vasa recta (DVR) undergo regulatory adaptions after the kidney is exposed to ischemia. Left kidneys (LK) were subjected to 30 minute renal artery cross clamp. After 48 hours, the post-ischemic LK and contralateral right kidney (RK) were harvested for study. When compared to DVR isolated from either sham operated LK or the contralateral RK, post-ischemic LK DVR markedly increased their NO generation. The selective inducible NOS (iNOS) inhibitor, 1400W, blocked the NO response. Immunoblots from outer medullary homogenates showed a parallel 2.6 fold increase in iNOS expression (P=0.01). Microperfused post-ischemic LK DVR exposed to angiotensin II (AngII, 10 nM), constricted less than those from the contralateral RK, and constricted more when exposed to 1400W (10 microM). Resting membrane potentials of pericytes from post-ischemic LK DVR pericytes were hyperpolarized relative to contralateral RK pericytes (62.0±1.6 vs 51.8±2.2 mV, respectively P

  • descending Vasa recta endothelial membrane potential response requires pericyte communication
    PLOS ONE, 2016
    Co-Authors: Zhong Zhang, Kristie Payne, Thomas L Pallone
    Abstract:

    Using dual-cell electrophysiological recording, we examined the routes for equilibration of membrane potential between the pericytes and endothelia that comprise the descending Vasa recta (DVR) wall. We measured equilibration between pericytes in intact vessels, between pericytes and endothelium in intact vessels and between pericytes physically separated from the endothelium. Dual pericyte recording on the abluminal surface of DVR showed that both resting potential and subsequent time-dependent voltage fluctuations after vasoconstrictor stimulation remained closely equilibrated, regardless of the agonist employed (angiotensin II, vasopressin or endothelin 1). When pericytes where removed from the vessel wall but retained physical contact with one another, membrane potential responses were also highly coordinated. In contrast, responses of pericytes varied independently when they were isolated from both the endothelium and from contact with one another. When pericytes and endothelium were in contact, their resting potentials were similar and their temporal responses to stimulation were highly coordinated. After completely isolating pericytes from the endothelium, their mean resting potentials became discordant. Finally, complete endothelial isolation eliminated all membrane potential responses to angiotensin II. We conclude that cell-to-cell transmission through the endothelium is not needed for pericytes to equilibrate their membrane potentials. AngII dependent responses of DVR endothelia may originate from gap junction coupling to pericytes rather than via receptor dependent signaling in the endothelium, per se.

  • syncytial communication in descending Vasa recta includes myoendothelial coupling
    American Journal of Physiology-renal Physiology, 2014
    Co-Authors: Zhong Zhang, Kristie Payne, Thomas L Pallone
    Abstract:

    Using dual cell patch-clamp recording, we examined pericyte, endothelial, and myoendothelial cell-to-cell communication in descending Vasa recta. Graded current injections into pericytes or endothe...

  • descending Vasa recta endothelial cells and pericytes form mural syncytia
    American Journal of Physiology-renal Physiology, 2014
    Co-Authors: Zhong Zhang, Kristie Payne, Thomas L Pallone
    Abstract:

    Using patch clamp, we induced depolarization of descending Vasa recta (DVR) pericytes or endothelia and tested whether it was conducted to distant cells. Membrane potential was measured with the fl...

  • membrane current oscillations in descending Vasa recta pericytes
    American Journal of Physiology-renal Physiology, 2008
    Co-Authors: Qingli Zhang, Aurelie Edwards, Zhong Zhang, Gil W Wier, Thomas L Pallone
    Abstract:

    We investigated the origin of spontaneous transient inward current (STIC) oscillations in descending Vasa recta (DVR) pericytes. In cells clamped at −80 mV, angiotensin II (ANG II; 10 nmol/l) induc...

Claire M Peppiattwildman - One of the best experts on this subject based on the ideXlab platform.

  • supplementary material for an intact kidney slice model to investigate Vasa recta properties and function in situ
    2017
    Co-Authors: C Crawford, T Kennedylydon, Scott S P Wildman, C Sprott, Tejal A Desai, L Sawbridge, J Munday, R J Unwin, Claire M Peppiattwildman
    Abstract:

    Background: Medullary blood flow is via Vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending Vasa recta show that pericytes can constrict/dilate descending Vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated Vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in Vasa recta diameter. Results: Pericytes were identified on Vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in Vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E 2 ) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L -NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating Vasa recta function in situ and the role of pericytes as regulators of Vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow.

  • nonsteroidal anti inflammatory drugs alter Vasa recta diameter via pericytes
    American Journal of Physiology-renal Physiology, 2015
    Co-Authors: T Kennedylydon, C Crawford, Scott S P Wildman, Claire M Peppiattwildman
    Abstract:

    We have previously shown that Vasa recta pericytes are known to dilate Vasa recta capillaries in the presence of PGE2 and contract Vasa recta capillaries when endogenous production of PGE2 is inhib...

  • sildenafil and tadalafil act at pericytes to regulate Vasa recta diameter
    The FASEB Journal, 2015
    Co-Authors: Kadeshia Dunn, Claire M Peppiattwildman, Stephen P Kelley, Scott S P Wildman
    Abstract:

    Sildenafil and tadalafil are used clinically for erectile dysfunction [1, 2], yet in addition to their action at sex organs, increasing concentrations of sildenafil citrate have been associated with architectural distortion of kidney vasculature in rats [3], whereas, tadalafil has been reported to provide renoprotective effects against renal ischemic reperfusion injury [4]. Given that it is well established that pericytes regulate Vasa recta diameter to regulate medullary blood flow (MBF), we sought to determine whether sildenafil and tadalafil act at pericytes to modulate Vasa recta capillary diameter and ultimately MBF. Superfusion of live kidney tissue with sildenafil (20 nM, 40 nM and 80 nM) evoked a significantly greater vasodilation of Vasa recta capillaries at pericytes sites (9.10 ± 0.9%, 12.28 ± 1.7% and 25.06 ± 4.4%) than at non-pericyte sites (0.50 ± 0.5%, 1.04 ± 0.3% and 0.95 ± 0.9%; P < 0.01, n=6). Preincubation of tissue with 100 μM L-NNA (nitric oxide synthesis inhibitor) failed to attenuat...

  • sympathetic nerve derived atp regulates renal medullary Vasa recta diameter via pericyte cells a role for regulating medullary blood flow
    Frontiers in Physiology, 2013
    Co-Authors: C Crawford, T Kennedylydon, Scott S P Wildman, Mark C Kelly, Claire M Peppiattwildman
    Abstract:

    Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of Vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending Vasa recta, and therefore may be able to regulate medullary blood flow (MBF). Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesise that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to Vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine) evokes pericyte-mediated vasoconstriction of Vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of Vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is important.

  • an intact kidney slice model to investigate Vasa recta properties and function in situ
    Nephron Physiology, 2012
    Co-Authors: C Crawford, T Kennedylydon, Scott S P Wildman, C Sprott, Tejal A Desai, L Sawbridge, J Munday, R J Unwin, Claire M Peppiattwildman
    Abstract:

    Background: Medullary blood flow is via Vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending Vasa recta show that pericytes can constrict/dilate descending Vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated Vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in Vasa recta diameter. Results: Pericytes were identified on Vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in Vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E2) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating Vasa recta function in situ and the role of pericytes as regulators of Vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow.

Erik P Silldorff - One of the best experts on this subject based on the ideXlab platform.

  • Vasa recta voltage gated na channel nav1 3 is regulated by calmodulin
    American Journal of Physiology-renal Physiology, 2007
    Co-Authors: Whaseon Leekwon, Zhong Zhang, Erik P Silldorff, Thomas L Pallone
    Abstract:

    Rat descending Vasa recta (DVR) express a tetrodotoxin (TTX)-sensitive voltage-operated Na+ (NaV) conductance. We examined expression of NaV isoforms in DVR and tested for regulation of NaV current...

  • descending Vasa recta endothelium is an electrical syncytium
    American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2006
    Co-Authors: Qingli Zhang, Michael Mangano, Zhong Zhang, Erik P Silldorff, Whaseon Leekwon, Kristie Payne, Thomas L Pallone
    Abstract:

    We examined gap junction coupling of descending Vasa recta (DVR). DVR endothelial cells or pericytes were depolarized to record the associated capacitance transients. Virtually all endothelia and s...

  • Vasa recta voltage-gated Na+ channel Nav1.3 is regulated by calmodulin
    American Journal of Physiology-renal Physiology, 2006
    Co-Authors: Whaseon Lee-kwon, Zhong Zhang, Erik P Silldorff, Thomas L Pallone
    Abstract:

    Rat descending Vasa recta (DVR) express a tetrodotoxin (TTX)-sensitive voltage-operated Na+ (NaV) conductance. We examined expression of NaV isoforms in DVR and tested for regulation of NaV current...

  • Descending Vasa recta endothelium is an electrical syncytium
    American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2006
    Co-Authors: Qingli Zhang, Michael Mangano, Zhong Zhang, Erik P Silldorff, Kristie Payne, Whaseon Lee-kwon, Thomas L Pallone
    Abstract:

    We examined gap junction coupling of descending Vasa recta (DVR). DVR endothelial cells or pericytes were depolarized to record the associated capacitance transients. Virtually all endothelia and some pericytes exhibited prolonged transients lasting 10–30 ms. Carbenoxolone (100 μM) and 18β-glycyrrhetinic acid (18βGRA; 100 μM) markedly shortened the endothelial transients. Carbenoxolone and heptanol (2 mM) reduced the pericyte capacitance transients when they were prolonged. Lucifer yellow (LY; 2 mM) was dialyzed into the cytoplasm of endothelial cells and pericytes. LY spread diffusely along the endothelial monolayer, whereas in most pericytes, it was confined to a single cell. In some pericytes, complex patterns of LY spreading were observed. DVR cells were depolarized by voltage clamp as fluorescence of bis(1,3-dibarbituric acid)-trimethine oxanol [DiBAC4([3][1])] was monitored ∼200 μm away. A 40-mV endothelial depolarization was accompanied by a 26.1 ± 5.5-mV change in DiBAC4([3][1]) fluorescence. DiBAC4([3][1]) fluorescence did not change after 18βGRA or when pericytes were depolarized. Similarly, propagated cytoplasmic Ca2+ responses arising from mechanical perturbation of the DVR wall were attenuated by 18βGRA or heptanol. Connexin (Cx) immunostaining showed predominant linear Cx40 and Cx43 in endothelia, whereas Cx37 stained smooth muscle actin-positive pericytes. We conclude that the DVR endothelium is an electrical syncytium and that gap junction coupling in DVR pericytes exists but is less pronounced. [1]: #ref-3

  • katp channel conductance of descending Vasa recta pericytes
    American Journal of Physiology-renal Physiology, 2005
    Co-Authors: Whaseon Leekwon, Erik P Silldorff, Thomas L Pallone
    Abstract:

    Using nystatin-perforated patch-clamp and whole cell recording, we tested the hypothesis that KATP channels contribute to resting conductance of rat descending Vasa recta (DVR) pericytes and are mo...

T L Pallone - One of the best experts on this subject based on the ideXlab platform.

  • Molecular sieving of small solutes by outer medullary descending Vasa recta.
    The American journal of physiology, 1997
    Co-Authors: T L Pallone, M R Turner
    Abstract:

    Molecular sieving of small solutes by outer medullary descending Vasa recta (OMDVR). Descending Vasa recta (DVR) plasma equilibrates with the medullary interstitium by volume efflux (Jv), as well as by influx of solutes. Jv is driven by transmural osmotic pressure gradients due to small hydrophilic solutes (delta pi s), NaCl and urea. DVR endothelium probably contains a "water-only" pathway most likely mediated by the aquaporin-1 (AQP1) water channel. We measured the ability of microperfused OMDVR to concentrate lumenal 22Na and [3H]raffinose when Jv was driven by transmural NaCl gradients. Collectate-to-perfusate ratios of 2 x 10(6) M(r) fluorescein isothiocyanate-labeled dextran volume marker (RDx), 22Na (RNa), and [3H]raffinose (Rraf) were measured in the absence and presence of Jv. During volume efflux (Jv > 0), RDx was 1.37 +/- 0.31. RNa increased from 0.64 +/- 0.03 when Jv = 0 to 0.82 +/- 0.05 when Jv > 0 and Rraf increased from 0.83 +/- 0.03 to 1.13 +/- 0.05: Mathematical simulations predict RNa and Rraf most accurately when the OMDVR reflection coefficient to the tracers is assigned a value near unity. This indicates that the OMDVR wall contains a pathway for osmotic volume flux that excludes small hydrophilic solutes, a behavior consistent with that of aquaporins.

  • molecular sieving of small solutes by outer medullary descending Vasa recta
    American Journal of Physiology-renal Physiology, 1997
    Co-Authors: T L Pallone, M R Turner
    Abstract:

    Molecular sieving of small solutes by outer medullary descending Vasa recta (OMDVR). Descending Vasa recta (DVR) plasma equilibrates with the medullary interstitium by volume efflux (Jv), as well as by influx of solutes. Jv is driven by transmural osmotic pressure gradients due to small hydrophilic solutes (delta pi s), NaCl and urea. DVR endothelium probably contains a "water-only" pathway most likely mediated by the aquaporin-1 (AQP1) water channel. We measured the ability of microperfused OMDVR to concentrate lumenal 22Na and [3H]raffinose when Jv was driven by transmural NaCl gradients. Collectate-to-perfusate ratios of 2 x 10(6) M(r) fluorescein isothiocyanate-labeled dextran volume marker (RDx), 22Na (RNa), and [3H]raffinose (Rraf) were measured in the absence and presence of Jv. During volume efflux (Jv > 0), RDx was 1.37 +/- 0.31. RNa increased from 0.64 +/- 0.03 when Jv = 0 to 0.82 +/- 0.05 when Jv > 0 and Rraf increased from 0.83 +/- 0.03 to 1.13 +/- 0.05: Mathematical simulations predict RNa an...

  • facilitated transport in Vasa recta theoretical effects on solute exchange in the medullary microcirculation
    American Journal of Physiology-renal Physiology, 1997
    Co-Authors: Aurelie Edwards, T L Pallone
    Abstract:

    A new theoretical model describing the exchange of water and solutes between the renal medullary interstitium and the microcirculation was developed to account for the presence of water channels and urea transporters, both of which were recently identified in the descending Vasa recta (DVR) of the renal medulla. Small solutes, which are excluded from the water channels, are freely exchanged through a parallel pathway shared with water. The transcapillary concentration gradients of sodium and urea across the water channels induce water efflux from DVR, whereas classic Starling forces across the shared pathway favor volume uptake by DVR. Because small solute concentration gradients are large in the inner medulla, the model predicts net water removal from DVR, in agreement with experimental observations. The descending and ascending Vasa recta (AVR) function as a countercurrent exchanger, the efficiency of which is inversely related to the net amount of solute taken up by the medullary microcirculation. Our results indicate that net solute removal from the medulla is governed by convective uptake into AVR and thus depends predominantly on the parameters affecting AVR transcapillary volume flux. The simulations also suggest that the urea transporter significantly enhances the exchange of both sodium and urea and might serve to abrogate a reduction in exchanger efficiency imparted by water channels.

  • hydraulic and diffusional permeabilities of isolated outer medullary descending Vasa recta from the rat
    American Journal of Physiology-heart and Circulatory Physiology, 1997
    Co-Authors: M R Turner, T L Pallone
    Abstract:

    Water permeates many microvessel walls via a pathway shared with small hydrophilic solutes and also via an exclusive water pathway. In outer medullary descending Vasa recta (OMDVR), the relationshi...

  • Effect of norepinephrine and acetylcholine on outer medullary descending Vasa recta.
    The American journal of physiology, 1995
    Co-Authors: S Yang, E P Silldorff, T L Pallone
    Abstract:

    To examine their responsiveness to norepinephrine (NE) and acetylcholine (ACh), outer medullary descending Vasa recta (OMDVR) have been dissected from vascular bundles of the rat and perfused in vitro. Abluminal application of NE produced graded vasoconstriction in a concentration range of 10(-9)-10(-6) M. When applied with NE, ACh at concentrations of 10(-8)-10(-5) M dilated NE-preconstricted OMDVR. In contrast, ACh applied in the absence of NE caused vasoconstriction. ACh-induced vasodilation was blocked by addition of the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NNA, 2 x 10(-4) M). L-NNA in the absence of ACh enhanced NE-induced vasoconstriction. Supraphysiological (10(-3) M) L-arginine (L-Arg) reversed the effects of L-NNA, and abluminal application of L-NNA alone resulted in OMDVR vasoconstriction. At concentrations of 10(-6)-10(-3) M, abluminal application of L-Arg produced graded vasodilation of NE-constricted OMDVR. These results suggest that adrenergic and cholinergic innervation could influence OMDVR vasomotor tone to modulate total and regional blood flow to the renal medulla. The data also favor a role for the activity of constitutively expressed nitric oxide synthase to modulate OMDVR vasoactivity.

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