Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis

Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis. We studied the possibility that tubule fluid iron could be involved in the pathogenesis of the tubulo-interstitial injury associated with primary glomerular disease. Tubule fluid iron is determined by the magnitude of the glomerular leak for transferrin and the iron saturation of transferrin. To minimize tubule fluid iron in an experimental model of glomerulonephritis, iron deficiency was induced in rats prior to the induction of nephrotoxic serum nephritis. Iron deficiency did not effect the development of glomerular disease as determined by proteinuria, but had a marked effect on preventing the development of tubulo-interstitial disease and renal functional deterioration. There was also a strong correlation between the amount of functional deterioration and extent of tubulo-interstitial disease and urinary iron excretion in both the control and iron deficient animals. It is proposed that injury results from iron being dissociated from transferrin at the more acid pH of the tubule fluid. Iron, a transition element, is able to catalyze the Haber-Weiss reaction with the formation of free hydroxyl radicals which causes renal tubule cell injury. This tubulo-interstitial injury is the major determinate of progressive renal functional deterioration in this experimental model of glomerulonephritis

Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate

Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate. Clinical and experimental studies have shown that citrate markedly enhances the intestinal absorption of aluminum (Al), but the site and mechanism of enhanced absorption are unknown. To determine where in the gastrointestinal tract aluminum citrate (Alcitr) was absorbed, Alcitr was gavaged with D-[1-3H] glucose in male Sprague-Dawley rats. Plasma Al levels increased rapidly and simultaneously peaked with D-[1-3G] glucose, suggesting early proximal bowel absorption. In in vitro duodenal and jejunal everted gut preparations, Alcitr incubation resulted in increased tissue Al levels and markedly enhanced transmural transport of Al and citr. Unlike citr, the transmural movement of Al was independent of temperature (37°C vs. 4°C). On the other hand, Al lactate (al Lac) increased tissue associated Al levels but had no effect on transmural Al movement. To determine if this large flux of Al following Alcitr administration was due to paracellular movement, ruthenium red and Ussing chamber studies were used to evaluate the morphologic and functional integrity of cellular tight junctions. Alcitr, as opposed to A1C13, markedly increased ruthenium red deposits in intercellular spaces, especially around goblet cells, and induced a prolonged significant reduction in transmural resistance. Alcitr also resulted in rapid and nearly complete (99.7%) chelation of free calcium, an event known to disrupt cellular tight junction integrity. Taken together, these data suggest that enhanced Al absorption following administration of Alcitr occurs in the proximal bowel via the paracellular pathway due to the opening of cellular tight junctions

Developpement d'un système de dopage "PM" : premiers essais

National audienceThe participation to inter-laboratory exercises is a key step for any ambient air quality monitoring network. To guarantee the interest of such campaigns, participants need a large range of concentration, including regulatory limits. As far as PM10 is concerned, the 1996 European directive implement a 24h hours limit of 50 micro g/m3 with a maximum relative uncertainty of 25%. In the frame of the French National Air Quality Laboratory (LCSQA), INERIS -in relation with LNI Inc.- is developing a special PM generator. The objective is to distribute to all participants an ambient air enriched with PM10 or PM2,5 particles. Preliminary results show that our prototype is able to distribute to 4 TEOM and TEOM-FDMS microbalances air in a range from the background up to 100 micro g/m3 and more. The set-up and the results will be presented.La reconnaissance d'une compétence en matière de mesurage passe par la participation à des exercices d'intercomparaison, ou " exercices inter-laboratoires ". Ce type d'exercice est organisé dans le cadre de la surveillance réglementaire " air ambiant " française. Afin de garantir l'efficacité d'une telle session, il est essentiel de bénéficier d'un spectre large de concentration, et tout particulièrement d'inclure les valeurs limites pour lesquelles il existe des exigences en matière d'incertitude. C'est le cas de la surveillance des PM10, pour lesquels une incertitude maximale de 25% est exigée à 50 micro g/m3 (mesure journalière). Il est en pratique impossible de garantir a priori un tel niveau de concentration. C'est pourquoi dans le cadre du LCSQA, l'INERIS a entrepris de développer des systèmes d'enrichissement, appelés aussi " systèmes de dopage ". La présente communication est consacrée au développement d'un tel dispositif pour les particules de type PM10 et PM 2,5. Les objectifs, le montage expérimental, ainsi que les premiers résultats, seront rapportés dans le cas de microbalances TEOM et TEOM-FDMS, pour des concentrations allant du niveau de fond à plus de 100 micro g/m3. Une attention particulière sera portée sur les contraintes et les résultats obtenus en matière de représentativité de la matrice, ainsi qu'en matière d'équivalence des échantillons fournis à chaque analyseur participant

Imaging along-strike variations in mechanical properties of the Gofar transform fault, East Pacific Rise

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 119 (2014): 7175–7194, doi:10.1002/2014JB011270.A large part of global plate motion on mid-ocean ridge transform faults (RTFs) is not accommodated as major earthquakes. When large earthquakes do occur, they often repeat quasiperiodically. We focus here on the high slip rate (∼14 cm/yr) Gofar transform fault on the equatorial East Pacific Rise. This fault is subdivided into patches that slip during Mw 5.5–6 earthquakes every 5 to 6 years. These patches are separated by rupture barriers that accommodate slip through swarms of smaller events and/or aseismic creep. We performed an imaging study to investigate which spatiotemporal variations of the fault zone properties control this segmentation in mechanical behavior and could explain the specific behavior of RTFs at the global scale. We adopt a double-difference approach in a joint inversion of active air gun shots and microseismicity recorded for 1 year. This data set includes the 2008 Mw 6 Gofar earthquake. The along-strike P wave velocity structure reveals an abrupt transition between the barrier area, characterized by a damaged fault zone of 10–20% reduced Vp and a nearly intact fault zone in the asperity area. The importance of the strength of the damage zone on the mechanical behavior is supported by the temporal S wave velocity changes which suggest increased damage within the barrier area, during the week preceding the Mw 6 earthquake. Our results support the conclusion that extended highly damaged zones are the key factor in limiting the role of major earthquakes to accommodate plate motion along RTFs.The material presented here is based on work supported by the National Science Foundation grants 1232725 and 0242117.2015-03-2

Expanding Duplication of Free Fatty Acid Receptor-2 (GPR43) Genes in the Chicken Genome

International audienceFree fatty acid receptors (FFAR) belong to a family of five G-protein coupled receptors that are involved in the regulation of lipidmetabolism, so that their loss of function increases the risk of obesity. The aim of this study was to determine the expansion of genesencoding paralogs of FFAR2 in the chicken, considered as amodel organism for developmental biology and biomedical research. Byestimating the gene copy number using quantitative polymerase chain reaction, genomic DNA resequencing, and RNA sequencingdata, we showed the existence of 23 ±1.5 genes encoding FFAR2 paralogs in the chicken genome. The FFAR2 paralogs shared anidentity from 87.2%up to 99%. Extensive gene conversion was responsible for this high degree of sequence similarities betweenthese genes, and this concerned especially the four amino acids known to be critical for ligand binding. Moreover, elevated nonsynonymous/synonymous substitutionratios onsomeamino acids withinor inclose-vicinity of the ligand-bindinggroove suggest thatpositive selectionmay have reduced the effective rate of gene conversion in this region, thus contributing to diversify the function ofsome FFAR2 paralogs. All the FFAR2 paralogs were located on a microchromosome in a same linkage group. FFAR2 genes wereexpressed in different tissues and cells such as spleen, peripheral blood mononuclear cells, abdominal adipose tissue, intestine, andlung, with the highest rate of expression in testis. Further investigations are needed to determine whether these chicken-specificevents along evolution are the consequence of domestication and may play a role in regulating lipid metabolism in this species

Effects of natural selection and gene conversion on the evolution of human glycophorins coding for MNS blood polymorphisms in malaria-endemic African populations

Malaria has been a very strong selection pressure in recent human evolution, particularly in Africa. Of the one million deaths per year due to malaria, more than 90% are in sub-Saharan Africa, a region with high levels of genetic variation and population substructure. However, there have been few studies of nucleotide variation at genetic loci that are relevant to malaria susceptibility across geographically and genetically diverse ethnic groups in Africa. Invasion of erythrocytes by Plasmodium falciparum parasites is central to the pathology of malaria. Glycophorin A (GYPA) and B (GYPB), which determine MN and Ss blood types, are two major receptors that are expressed on erythrocyte surfaces and interact with parasite ligands. We analyzed nucleotide diversity of the glycophorin gene family in 15 African populations with different levels of malaria exposure. High levels of nucleotide diversity and gene conversion were found at these genes. We observed divergent patterns of genetic variation between these duplicated genes and between different extracellular domains of GYPA. Specifically, we identified fixed adaptive changes at exons 3-4 of GYPA. By contrast, we observed an allele frequency spectrum skewed toward a significant excess of intermediate-frequency alleles at GYPA exon 2 in many populations; the degree of spectrum distortion is correlated with malaria exposure, possibly because of the joint effects of gene conversion and balancing selection. We also identified a haplotype causing three amino acid changes in the extracellular domain of glycophorin B. This haplotype might have evolved adaptively in five populations with high exposure to malaria