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The NHE1 isoform of the mammalian [Na.sup.+]/[H.sup.+] exchanger is a ubiquitous plasma membrane protein that regulates intracellular pH in cells by removing one intracellular proton in exchange for one extracellular sodium. Genetic defects in NHE1 have been shown to affect the growth and motor ability of mice, but mutations in humans have not been studied. NHE1 has a cytosolic C-terminal regulatory domain of approximately 300 amino acids. We investigated the functional effects of two human mutations found in the regulatory phosphorylatable amino acids [Ser.sup.703] and [Ser.sup.771]. A Ser703Pro mutant protein had essentially the same activity, expression, and targeting as the wild type NHE1 protein. In contrast, the Ser771Pro protein had reduced activity and expression of NHE1 protein, though cell surface targeting was normal. In dual pulse assays the Ser771Pro mutant was not further activated by sustained intracellular acidosis but displayed an unusual activation by brief pulses of acidosis. The results demonstrate that the Ser771Pro human genetic mutation has significant and detrimental physiological effects on the activity of the NHE1 protein, SLC9A1. Key words: [Na.sup.+]/[H.sup.+] exchanger, pH regulation, genetic mutation, phosphorylation. Resume: L'isoforme NHE1 de l'echangeur [Na.sup.+]/[H.sup.+] de mammifere consiste en une proteine membranaire plasmatique ubiquiste qui regule le pH intracellulaire en enlevant un proton intracellulaire en echange d'un sodium extracellulaire. Il a ete montre que des defauts genetiques de NHE1 affectaient la croissance et les capacites motrices chez la souris, mais les mutations chez l'humain n'ont pas ete etudiees. NHE1 possede une extremite C-terminale cytosolique regulatrice d'environ 300 acides amines. Les auteurs ont examine les effets fonctionnels de deux mutations trouvees chez l'humain sur les acides amines [Ser.sup.703] et [Ser.sup.771] cibles de la phosphorylation. Une proteine mutante Ser703Pro possedait essentiellement les memes activite, expression et ciblage que la proteine NHE1 sauvage. En revanche, la proteine Ser771Pro possedait une activite et une expression reduites, alors que le ciblage a la surface cellulaire etait normal. Lors de dosages realises a la suite d'impulsions doubles, le mutant Ser771Pro n'etait pas active par une acidose intracellulaire soutenue, mais il presentait une activation inhabituelle par des breves impulsions acides. Les resultats demontrent que la mutation humaine Ser771Pro exerce un effet physiologique significatif et nefaste sur l'activite de la proteine NHE1, SLC9A1. [Traduit par la Redaction] Mots-cles: echangeur [Na.sup.+]/[H.sup.+], regulation du pH, mutation genetique, phosphorylation., Introduction In mammalian cells, the maintenance of pH homeostasis in both normal and neoplastic cells is chiefly regulated by the [Na.sup.+]/[H.sup.+] exchanger isoform one (NHE1). NHE1 is an integral plasma [...]

[Na.sup.+]/[H.sup.+] exchanger isoform 1 (NHE1) is the principal plasma membrane [Na.sup.+]/[H.sup.+] exchanger of mammalian cells and functions by exchanging one intracellular proton for one extracellular sodium ion. Critical transmembrane segments of [Na.sup.+]/[H.sup.+] exchangers have discontinuous transmembrane helices, which result in a dipole within the membrane. Amino acid R425 has been suggested to play an important role in neutralizing one such helix dipole. To investigate this hypothesis, R425 was mutated to alanine, glutamine, histidine, or lysine and the mutant NHE1 proteins were expressed and characterized in NHE1-deficient cells. The R425A and R425E mutants exhibited complete loss of expression of mature, fully glycosylated NHE1, reduced expression overall, and greatly reduced cell surface targeting. The cell surface targeting, expression, and activity of the R425H and R425K mutant proteins were also impaired, though residual NHE1 activity remained. When reduced targeting and expression were accounted for, the R425H and R425K mutant proteins had activity similar to that of the wild-type protein. The results suggest that R425 is critical for NHE1 expression, targeting, and activity and that replacement with another basic residue can rescue activity. The findings are consistent with a role for R425 in both neutralizing a helix dipole and maintaining NHE1 structure and function. Key words: [Na.sup.+]/[H.sup.+] exchanger, pH regulation, transmembrane segment, helix dipole. L'isoforme 1 de l'echangeur [Na.sup.+]/[H.sup.+] (NHE1) est le principal echangeur [Na.sup.+]/[H.sup.+] de la membrane plasmique des cellules de mammiferes et elle fonctionne en echangeant un proton intercellulaire pour un sodium extracellulaire. Des segments transmembranaires cruciaux des echangeurs [Na.sup.+]/[H.sup.+] comportent des helices transmembranaires discontinues, ce qui resulte en la formation d'un dipole a l'interieur de la membrane. On a suggere que l'acide amine R425 joue un role important dans la neutralisation d'un tel dipole de l'helice. Afin verifier cette hypothese, le R425 a ete mute en alanine, glutamine, histidine ou lysine, et les mutants de NHE1 ont ete exprimes et caracterises dans des cellules depourvues de NHE-1. Les mutants R425A et R425E presentaient une perte complete d'expression de NHE1 pleinement glycosyle, une reduction globale reduite et un ciblage a la surface cellulaire grandement reduit. Le ciblage a la surface cellulaire, l'expression et l'activite des proteines mutantes R425H et R425K etaient aussi affectes mais une activite NHE1 residuelle demeurait. Apres correction sur le plan de la reduction du ciblage et de l'expression, les proteines mutantes R425H et R425 K presentaient une activite similaire a celle de la proteine sauvage. Les resultats suggerent que le R425 est crucial a l'expression, au ciblage et a l'activite de NHE1, et que son remplacement par un autre residu basique peut preserver l'activite. Ces donnees sont en coherence avec le role du R425 dans la neutralisation du dipole de l'helice et le maintien de la structure et de la fonction de NHE1. [Traduit par la Redaction] Mots-cles: echangeur [Na.sup.+]/[H.sup.+], regulation du pH, segment transmembranaire, dipole de l'helice., Introduction The [Na.sup.+]/[H.sup.+] exchanger is a pH regulatory plasma membrane protein present in all mammalian cells. The NHE1 isoform of the protein is an integral membrane protein. It has a [...]

Coded aperture imaging systems have recently shown great success in recovering scene depth and extending the depth-of-field. Tremendous efforts have been focused on designing good coded patterns. The ideal pattern, however, would have to serve two conflicting purposes: 1) it should be broadband to ensure robust deconvolution and 2) it should have sufficient zero-crossings for a high depth discrepancy. This paper presents a simple but effective scene-adaptive coded aperture solution to bridge this gap. We observe that natural scenes often exhibit a dominant edge direction that can be caused by structure, texture, shading, etc. We therefore apply depth-discriminative codes along the dominant direction and broadband codes along its orthogonal direction. To physically implement this scheme, we adopt a two-shot scheme. Firstly, we capture a scene image with a pinhole aperture and analyze image content to determine the dominant direction. Secondly, we apply the proposed coding scheme using the programmable Liquid Crystal on Silicon (LCoS). Experiments on a broad range of synthetic and real scenes show that our technique is able to combine advantages of the state-of-the-art patterns for recovering better quality depth map and all-focus images. [ABSTRACT FROM AUTHOR]