Different Transport Mechanisms in Plant and Human AMT/Rh-type Ammonium Transporters

The conserved family of AMT/Rh proteins facilitates ammonium transport across animal, plant, and microbial membranes. A bacterial homologue, AmtB, forms a channel-like structure and appears to function as an NH3 gas channel. To evaluate the function of eukaryotic homologues, the human RhCG glycoprotein and the tomato plant ammonium transporter LeAMT1;2 were expressed and compared in Xenopus oocytes and yeast. RhCG mediated the electroneutral transport of methylammonium (MeA), which saturated with Km = 3.8 mM at pHo 7.5. Uptake was strongly favored by increasing the pHo and was inhibited by ammonium. Ammonium induced rapid cytosolic alkalinization in RhCG-expressing oocytes. Additionally, RhCG expression was associated with an alkali-cation conductance, which was not significantly permeable to NH4+ and was apparently uncoupled from the ammonium transport. In contrast, expression of the homologous LeAMT1;2 induced pHo-independent MeA+ uptake and specific NH4+ and MeA+ currents that were distinct from endogenous currents. The different mechanisms of transport, including the RhCG-associated alkali-cation conductance, were verified by heterologous expression in appropriate yeast strains. Thus, homologous AMT/Rh-type proteins function in a distinct manner; while LeAMT1;2 carries specifically NH4+, or cotransports NH3/H+, RhCG mediates electroneutral NH3 transport

Defective Urinary Concentrating Ability Due to a Complete Deficiency of Aquaporin-1

Aquaporin-1, the archetypal water-channel protein,1 was initially identified in red cells and renal proximal tubular epithelium.2 The gene for aquaporin-1 (AQP1) on chromosome 7 colocalizes with the Colton blood-group antigen,3,4 and the Colton blood-group antigen polymorphism was identified as a substitution of a single amino acid in an extracellular domain of aquaporin-1.5 The International Blood Group Reference Laboratory has confirmed the existence of only six kindreds who lack the Colton blood group. Members of three of these kindreds were found to be homozygous for different mutations in the AQP1 gene, and their red-cell membranes had a complete absence or a marked reduction of aquaporin-1.6,7 Surprisingly, aquaporin-1 deficiency had no obvious clinical consequence in these people. Since aquaporin-1 is abundant in renal proximal tubular epithelium, the thin descending limb of the loop of Henle, and the descending vasa recta of the kidney,8,9 we hypothesized that people with a deficiency of aquaporin-1 have defects in water homeostasis in the kidneys that can be identified only under conditions of stress. We studied two unrelated subjects with a deficiency of aquaporin-1 and found that they had impaired urinary concentrating ability, suggesting that aquaporin-1 has a physiologic role in renal function

Kidd Blood Group and Urea Transport Function of Human Erythrocytes Are Carried by the Same Protein

International audienc

Deep-Learning Assessed Muscular Hypodensity Independently Predicts Mortality in DLBCL Patients Younger Than 60 Years.

[en] BACKGROUND: Muscle depletion (MD) assessed by computed tomography (CT) has been shown to be a predictive marker in solid tumors, but has not been assessed in non-Hodgkin's lymphomas. Despite software improvements, MD measurement remains highly time-consuming and cannot be used in clinical practice. METHODS: This study reports the development of a Deep-Learning automatic segmentation algorithm (DLASA) to measure MD, and investigate its predictive value in a cohort of 656 diffuse large B cell lymphoma (DLBCL) patients included in the GAINED phase III prospective trial (NCT01659099). RESULTS: After training on a series of 190 patients, the DLASA achieved a Dice coefficient of 0.97 ± 0.03. In the cohort, the median skeletal muscle index was 50.2 cm2/m2 and median muscle attenuation (MA) was 36.1 Hounsfield units (HU). No impact of sarcopenia was found on either progression free survival (PFS) or overall survival (OS). Muscular hypodensity, defined as MA below the tenth percentile according to sex, was associated with a lower OS and PFS, respectively (HR = 2.80 (95% CI 1.58-4.95), p < 0.001, and HR = 2.22 (95% CI 1.43-3.45), p < 0.001). Muscular hypodensity appears to be an independent risk factor for mortality in DLBCL and because of DLASA can be estimated in routine practice

ETUDE DE LA COREGULATION DE L'EXPRESSION DES GENES XG ET MIC2 ET ANALYSE DES BASES MOLECULAIRES DU POLYMORPHISME XG(A+)/XG(A-)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

SYSTEME DE GROUPE SANGUIN KIDD. STRUCTURE ET FONCTION DU TRANSPORTEUR D'UREE DU GLOBULE ROUGE ET HETEROGENEITE MOLECULAIRE DU PHENOTYPE JK N U L L

LE TRANSPORTEUR D'UREE DU GLOBULE ROUGE EST LE PRODUIT DU GENE DE GROUPE SANGUIN KIDD, LOCALISE SUR LE CHROMOSOME 18 EN Q12-Q21. LE SYSTEME KIDD EST CARACTERISE PAR LES ALLELES CODOMINANTS JK*A ET JK*B, QUI DEFINISSENT TROIS PHENOTYPES COURANTS JK(A+B+), JK(A+B), JK(AB+) ET UN PHENOTYPE RARE JK(AB) AUSSI APPELE JK N U L L. NOUS AVONS TOUT D'ABORD CARACTERISE LA STRUCTURE DU GENE JK ISOLE A PARTIR D'UNE BANQUE D'ADNG LEUCOCYTAIRE HUMAINE. IL COMPORTE ONZE EXONS, DONT LES TROIS PREMIERS SONT NON-CODANTS, REPARTIS SUR UN FRAGMENT D'ENVIRON 30 KB. CES INFORMATIONS ONT PERMIS DE DEFINIR LES BASES MOLECULAIRES DES MECANISMES A L'ORIGINE DE LA DEFICIENCE DU TRANSPORT FACILITE D'UREE DES HEMATIES DE SUJETS JK N U L L. LE PHENOTYPE JK(6), CARACTERISE PAR LA MUTATION DU SITE D'EPISSAGE DE L'EXON 6, A ETE IDENTIFIE DANS LA POPULATION POLYNESIENNE. LE PHENOTYPE JK(S291P) DEFINI PAR LA SUBSTITUTION S291P EST PRESENT EN FINLANDE. LE PHENOTYPE JK(7), CARACTERISE PAR LA MUTATION DU SITE D'EPISSAGE DE L'EXON 7, ET LE PHENOTYPE JK(4,5), DEFINI PAR LA DELETION DES EXONS 4 ET 5 ONT ETE IDENTIFIES RESPECTIVEMENT CHEZ UN FRANCAIS ET UN TUNISIEN. DES TESTS DE DETECTION PAR PCR DE CES EVENEMENTS ONT ETE MIS AU POINT ET PERMETTRONT DE RECHERCHER CES MUTATIONS DANS LES DIVERSES POPULATIONS HUMAINES. PARALLELEMENT, NOUS AVONS IDENTIFIE, A PARTIR D'ARN DE RETICULOCYTES HUMAINS, UN NOUVEAU CLONE HUT-B1 (HUT11A) CODANT UNE PROTEINE CARACTERISEE PAR LA PRESENCE DE DEUX MOTIFS VG APRES LA POSITION 227. NOUS AVONS MONTRE QUE CETTE PROTEINE REPRESENTE LE TRANSPORTEUR D'UREE PHYSIOLOGIQUE DES HEMATIES HUMAINES. NOUS AVONS MIS EN EVIDENCE QU'ELLE EST GLYCOSYLEE SUR L'ASPARAGINE-211, LOCALISEE DANS LA 3 E M E BOUCLE EXTRACELLULAIRE, QU'ELLE PORTE LES DETERMINANTS ANTIGENIQUES ABO ET QUE SES EXTREMITES N ET C TERMINALES ONT UNE ORIENTATION INTRACYTOPLASMIQUE. DES EXPERIENCES D'EXPRESSION DANS DES OVOCYTES DE XENOPE ONT MONTRE QUE LORSQUE LA PROTEINE HUT-B1 EST EXPRIMEE A UN NIVEAU PHYSIOLOGIQUE, ELLE TRANSPORTE SPECIFIQUEMENT L'UREE, MAIS NI L'EAU, NI LES SOLUTES DE PETITE TAILLE. DANS CE SYSTEME D'EXPRESSION, UNE ETUDE DES RELATIONS STRUCTURE-FONCTION A REVELE LE ROLE CRITIQUE DE L'EXTREMITE N-TERMINALE DANS LE TRAFIC OU L'INSERTION DE LA PROTEINE TRONQUEE A LA MEMBRANE ET MONTRE QUE LA N-GLYCOSYLATION DE LA PROTEINE N'EST PAS NECESSAIRE A LA FONCTION.PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF