Proton gradient formation in early endosomes from proximal tubules

AbstractHeavy endosomes were isolated from proximal tubules using a combination of magnesium precipitation and wheat-germ agglutinin negative selection techniques. Two small GTPases (Rab4 and Rab5) known to be specifically present in early endosomes were identified in our preparations. Endosomal acidification was followed fluorimetrically using acridine orange. In presence of chloride ions and ATP, the formation of a proton gradient (ΔpH) was observed. This process is due to the activity of an electrogenic V-type ATPase present in the endosomal membrane since specific inhibitors bafilomycin and folimycin effectively prevented or eliminated endosomal acidification. In presence of chloride ions (Km = 30 mM) the formation of the proton gradient was optimal. Inhibitors of chloride channel activity such as DIDS and NPPB reduced acidification. The presence of sodium ions stimulated the dissipation of the proton gradient. This effect of sodium was abolished by amiloride derivative (MIA) but only when loaded into endosomes, indicating the presence of a physiologically oriented Na+/H+-exchanger in the endosomal membrane. Monensin restored the gradient dissipation. Thus three proteins (V-type ATPase, Cl−-channel, Na+/H+-exchanger) present in early endosomas isolated from proximal tubules may regulate the formation, maintenance and dissipation of the proton gradient

Dynamic aid allocation

This paper introduces a framework for studying the optimal dynamic allocation of foreign aid among multiple recipients. We pose the problem as one of weighted global welfare maximization. A donor in the North chooses an optimal path for international transfers, anticipating that consumption and investment decisions will be made by optimizing households in the South, and accounting for limits in the extent to which recipients can effectively absorb aid. We present quantitative results on optimal aid policy by applying our approach to a neoclassical growth model, where the scope for aid-funded growth is determined by the recipients' distance from steady-state

Expression and distribution of adenosine diphosphate-ribosylation factors in the rat kidney111Present address is: Renal Unit & Program in Membrane Biology, Massachusetts General Hospital, Harvard Medical School, 149, 13th Street, 8th Floor, Boston, MA, 02129, USA

Expression and distribution of adenosine diphosphate-ribosylation factors in the rat kidney.BackgroundAdenosine diphosphate (ADP)-ribosylation factors (ARFs) are small guanosine triphosphatases involved in membrane traffic regulation. Aiming to explore the possible involvement of ARF1 and ARF6 in the reabsorptive properties of the nephron, we evaluated their distribution along the different renal epithelial segments.MethodsARFs were detected by immunofluorescence and immunogold cytochemistry on renal sections, using specific anti-ARF antibodies.ResultsARF1 was detected in proximal and distal tubules, thick ascending limbs of Henle's loops, and cortical and medullary collecting ducts. By immunofluorescence, labeling was mostly localized to the cell cytoplasm, particularly in Golgi areas. By electron microscopy, the Golgi apparatus and the endosomal compartment of proximal and distal tubular cells were labeled. ARF6 immunofluorescence was observed in brush border membranes and the cytoplasm of proximal convoluted tubular cells, whereas it was restricted to the apical border of proximal straight tubules. ARF6 immunogold labeling was detected over microvilli and endocytic compartments of proximal tubular cells.ConclusionsThis study demonstrates the following: (a) the heterogeneous distributions of ARF1 and ARF6 along the nephron, (b) the existence of cytosolic and membrane-bound forms for both ARFs, and (c) their association with microvilli and endocytic compartments, suggesting an active participation in renal reabsorption

Effect of valproate on renal metabolism in the intact dog

Effect of valproate on renal metabolism in the intact dog. Valproate is an antiepileptic drug known to induce hyperammonemia in humans. This hyperammonemia might result from a reduced detoxification of ammonium in the liver and/or from an accelerated renal ammoniagenesis. Six dogs with normal acid-base equilibrium and eight dogs with chronic metabolic acidosis were infused with valproate directly into their left renal artery in order to obtain arterial concentrations around 3 to 4mM. The arterial ammonium concentration rose only in chronically acido tic dogs, whereas the lactate concentration and the lactate/pyruvate ratio increased in both groups. The urinary excretion of lactate and pyruvate increased markedly but the urinary excretion of other relevant metabolites remained minimal. Renal glutamine utilization and ammonium production were not changed by valproate administration in normal dogs but increased modestly in acidotic dogs. However, renal lactate utilization was drastically reduced and in fact, changed into a net production of lactate. Valproate strikingly reduced the renal cortical concentrations of glutamine, glutamate, alphaketoglutarate and citrate, and more modestly those of malate, oxaloacetate, aspartate, alanine and ATP. By contrast, the tissue lactate concentration and the lactate/pyruvate ratio were markedly increased. In experiments with brush border membrane vesicles, valproate inhibited the lactate transporter. These results suggest that high concentrations of valproate drastically inhibited the proximal reabsorption and the proximal and distal oxidation of lactate and pyruvate. Valproate probably became itself a significant energetic substrate for the kidney

Modeling Failure of 3D Fiber Reinforced Foam Core Sandwich Structures with Defects

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97072/1/AIAA2012-1863.pd

Relationship between lactate and glutamine metabolism in vitro by the kidney: Differences between dog and rat and importance of alanine synthesis in the dog

Relationship between lactate and glutamine metabolism in vitro by the kidney: Differences between dog and rat and importance of alanine synthesis in the dog. Interaction between lactate (1 or 5 mM) and glutamine (1 or 5 mM) metabolism was studied with renal cortical slices incubated at a pH of 7.0 and obtained from acidotic (ammonium chloride) dogs and rats. The effect of amino-oxyacetate (0.2 mM), dichloroacetate (3 mM), and fluoroacetate (0.05 mM) was also studied. Significant differences were observed between dog and rat. In the dog, lactate had no effect on glutamine uptake and vice versa, but gluconeogenesis increased. Ammonia production, however, decreased by 13 to 21%, whereas a significant increase in alanine production was noted. In the rat, glutamine extraction and ammonia production dropped by 33% with 5 mM lactate. In contrast to the observation in the dog, no production of alanine was noted, but significant accumulation of glutamate took place. Amino-oxyacetate inhibited alanine production in the dog and reestablished ammoniagenesis, and it led to a marked decrement in the uptake of lactate and glucose production in both species. Dichloroacetate in the dog resulted in a reduction in pyruvate, alanine, glucose, and ammonia production while glutamate accumulation was observed. In both species, fluoroacetate stimulated glutamine uptake and ammonia production. With lactate alone, fluoroacetate decreased lactate uptake and glucose production. With both lactate and glutamine in the medium, fluoroacetate prevented any effect of lactate on ammoniagenesis. The present study demonstrates that lactate has a modest depressing effect on renal ammonia production by dog slices through increased synthesis of alanine and redistribution of nitrogen from glutamine. In the rat, the depressing effect of lactate on ammonia production in the alanine aminotransferase deficient kidney occurs through accumulation of glutamate. The data also reveal that oxidation of lactate to carbon dioxide is greater in the dog than it is in the rat, but that gluconeogenesis from lactate is more important in the rat.Relations entre les métabolismes du lactate et de la glutamine in vitro par le rein: Différences entre le chien et le rat et importance de la synthèse d'alanine chez le chien. L'interaction entre le métabolisme du lactate (1 ou 5 mM) et celui de la glutamine (1 ou 5 mM) a été étudiée sur des tranches de cortex rénal incubées à pH 7,0 et obtenues à partir de chiens ou de rats en acidose. L'effet de l'amino-oxyacétate (0,2 mM), du dichloroacétate (3 mM) et du fluoroacétate (0,05 mM) a aussi été étudié. Des différences significatives entre le rat et le chien ont été observées. Chez le chien, le lactate n'a pas d'effet sur la captation de glutamine, et réciproquement, mais la gluconéogenèse augmente. Cependant la production d'ammoniaque est diminuée de 13 à 21% alors qu'une augmentation significative de la production d'alanine est observée. Chez le rat, l'extraction de la glutamine et la production d'ammoniaque diminuent de 33% avec le lactate 5 mM. A l'opposé de ce qui est constaté chez le chien, il n'est pas observé de production d'alanine mais une accumulation significative de glutamate. L'amino-oxyacétate inhibe la production d'alanine chez le chien et restaure l'ammoniogenèse, cependant qu'il détermine une diminution importante de la captation de lactate et de la production de glucose dans les deux espèces. Le dichloroacétate a pour conséquence, chez le chien, une diminution de la production de pyruvate, d'alanine, de glucose et d'ammoniaque, cependant qu'une accumulation de glutamate est observée. Dans les deux espèces le fluoroacétate stimule la captation de glutamine et la production d'ammoniaque. Avec le lactate seul, le fluoroacétate diminue la captation de lactate et la production de glucose. Quand à la fois du lactate et de la glutamine sont ajoutés au milieu, le fluoroacétate empêche les effets du lactate sur l'ammoniogenèse. Ce travail démontre que le lactate a un effet dépresseur modeste sur la production rénale d'ammoniaque par les tranches de rein chez le chien par l'intermédiaire d'une augmentation de la synthèse de l'alanine et de la redistribution de l'azote à partir de la glutamine. Chez le rat, l'effet dépresseur du lactate sur la production d'ammoniaque dans le rein privé d'alanine amino-transférase s'exerce au moyen d'une accumulation de glutamate. Ces résultats révèlent que l'oxydation du lactate en CO2 est plus importante chez le chien que chez le rat alors que la gluconéogenèse à partir du lactate est plus importante chez le rat

Efficient Long-Range Entanglement using Dynamic Circuits

Quantum simulation traditionally relies on unitary dynamics, inherently imposing efficiency constraints on the generation of intricate entangled states. In principle, these limitations can be superseded by non-unitary, dynamic circuits. These circuits exploit measurements alongside conditional feed-forward operations, providing a promising approach for long-range entangling gates, higher effective connectivity of near-term hardware, and more efficient state preparations. Here, we explore the utility of shallow dynamic circuits for creating long-range entanglement on large-scale quantum devices. Specifically, we study two tasks: CNOT gate teleportation between up to 101 qubits by feeding forward 99 mid-circuit measurement outcomes, and the preparation of Greenberger-Horne-Zeilinger (GHZ) states with genuine entanglement. In the former, we observe that dynamic circuits can outperform their unitary counterparts. In the latter, by tallying instructions of compiled quantum circuits, we provide an error budget detailing the obstacles that must be addressed to unlock the full potential of dynamic circuits. Looking forward, we expect dynamic circuits to be useful for generating long-range entanglement in the near term on large-scale quantum devices.Comment: 7 pages, 3 figures (main text) + 11 pages, 6 figures (appendix

Large Scale Semantic Annotation of Radiology Reports

poster abstractThe development and testing of automated information extraction (IE) systems depends on semantically annotated free text. This presentation reports on the results of a large scale annotation project of a radiology corpus, the Roentgen corpus, consisting of 594,000 deidentified radiology reports with 36 million words, and 4.3 million sentences supplied by Indiana University. The presentation highlights the (1) sentence-based approach in defining propositions annotating the corpus, (2) as well as the annotation framework that is incrementally built and refined in order to facilitate the process of annotation

Prospectives

Tiré de: Prospectives, vol. 25, no 1, février 1989Titre de l'écran-titre (visionné le 24 janv. 2013)Le devoir du bonheur et l'engagmeent : pour une éducation à la responsabilité sociale / par Patrick Vinay -- Savoir surtout poser les bonnes questions : l'éducation aux valeurs : un souci / par Madeleine Préclaire -- Du secondaire à l'université, des objectifs partagés : enjeux sociaux et objectifs pédagogiques d'une formation fondamentale de qualité / par Claude Corbo -- Conditions et critères d'une formation fondamentale : formation fondamentale et responsabilité sociale : propos pour un anniversaire / par Pierre Lucier