Evolution of the epithelial sodium channel and the sodium pump as limiting factors of aldosterone action on sodium transport.

Despite large changes in salt intake, the mammalian kidney is able to maintain the extracellular sodium concentration and osmolarity within very narrow margins, thereby controlling blood volume and blood pressure. In the aldosterone-sensitive distal nephron (ASDN), aldosterone tightly controls the activities of epithelial sodium channel (ENaC) and Na,K-ATPase, the two limiting factors in establishing transepithelial sodium transport. It has been proposed that the ENaC/degenerin gene family is restricted to Metazoans, whereas the α- and β-subunits of Na,K-ATPase have homologous genes in prokaryotes. This raises the question of the emergence of osmolarity control. By exploring recent genomic data of diverse organisms, we found that: 1) ENaC/degenerin exists in all of the Metazoans screened, including nonbilaterians and, by extension, was already present in ancestors of Metazoa; 2) ENaC/degenerin is also present in Naegleria gruberi, an eukaryotic microbe, consistent with either a vertical inheritance from the last common ancestor of Eukaryotes or a lateral transfer between Naegleria and Metazoan ancestors; and 3) The Na,K-ATPase β-subunit is restricted to Holozoa, the taxon that includes animals and their closest single-cell relatives. Since the β-subunit of Na,K-ATPase plays a key role in targeting the α-subunit to the plasma membrane and has an additional function in the formation of cell junctions, we propose that the emergence of Na,K-ATPase, together with ENaC/degenerin, is linked to the development of multicellularity in the Metazoan kingdom. The establishment of multicellularity and the associated extracellular compartment ("internal milieu") precedes the emergence of other key elements of the aldosterone signaling pathway.

Sediment budget monitoring of debris-flow and bedload transport in the Manival Torrent, SE France

Steep mountain catchments typically experience large sediment pulses from hillslopes which are stored in headwater channels and remobilized by debris-flows or bedload transport. Event-based sediment budget monitoring in the active Manival debris-flow torrent in the French Alps during a two-year period gave insights into the catchment-scale sediment routing during moderate rainfall intensities which occur several times each year. The monitoring was based on intensive topographic resurveys of low- and high-order channels using different techniques (cross-section surveys with total station and high-resolution channel surveys with terrestrial and airborne laser scanning). Data on sediment output volumes from the main channel were obtained by a sediment trap. Two debris-flows were observed, as well as several bedload transport flow events. Sediment budget analysis of the two debris-flows revealed that most of the debris-flow volumes were supplied by channel scouring (more than 92%). Bedload transport during autumn contributed to the sediment recharge of high-order channels by the deposition of large gravel wedges. This process is recognized as being fundamental for debris-flow occurrence during the subsequent spring and summer. A time shift of scour-and-fill sequences was observed between low- and high-order channels, revealing the discontinuous sediment transfer in the catchment during common flow events. A conceptual model of sediment routing for different event magnitude is proposed.

Official Positions for FRAX® Bone Mineral Density and FRAX® simplification from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Tools to predict fracture risk are useful for selecting patients for pharmacological therapy in order to reduce fracture risk and redirect limited healthcare resources to those who are most likely to benefit. FRAX® is a World Health Organization fracture risk assessment algorithm for estimating the 10-year probability of hip fracture and major osteoporotic fracture. Effective application of FRAX® in clinical practice requires a thorough understanding of its limitations as well as its utility. For some patients, FRAX® may underestimate or overestimate fracture risk. In order to address some of the common issues encountered with the use of FRAX® for individual patients, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) assigned task forces to review the medical evidence and make recommendations for optimal use of FRAX® in clinical practice. Among the issues addressed were the use of bone mineral density (BMD) measurements at skeletal sites other than the femoral neck, the use of technologies other than dual-energy X-ray absorptiometry, the use of FRAX® without BMD input, the use of FRAX® to monitor treatment, and the addition of the rate of bone loss as a clinical risk factor for FRAX®. The evidence and recommendations were presented to a panel of experts at the Joint ISCD-IOF FRAX® Position Development Conference, resulting in the development of Joint ISCD-IOF Official Positions addressing FRAX®-related issues.

Application des méthodes géophysiques à l'étude de deux sites (Kappelen et Grenchen) de l'aquifère poreux complexe du Seeland

L'aquifère du Seeland représente une richesse en ressources hydriques qu'il est impératif de préserver contre tout risque de détérioration. Cet aquifère prolifique est constitué principalement de sédiments alluviaux post-glaciaires (graviers, sables et limons). Il est soumis aux contraintes environnementales des pratiques d'agriculture intensive, du réseau routier, des villes et de leurs activités industrielles. La connaissance optimale de ces ressources est donc primordiale pour leur protection. Dans cette optique, deux sites Kappelen et Grenchen représentatifs de l'aquifère du Seeland ont été étudiés. L'objectif de ce travail est de caractériser d'un point de vue hydrogéophysique l'aquifère au niveau de ces deux sites, c'est-à-dire, comprendre la dynamique des écoulements souterrains par l'application des méthodes électriques de surface associées aux diagraphies en intégrant des méthodes hydrogéologiques. Pour le site de Kappelen, les méthodes électriques de surface ont permis d'identifier les différents faciès géoélectriques en présence et de mettre en évidence leur disposition en une structure tabulaire et horizontale. Il s'agit d'un aquifère libre constitué d'une série de graviers allant jusqu'à 15 m de profondeur reposant sur de la moraine argileuse. Les diagraphies électriques, nucléaires et du fluide ont servis à la détermination des caractéristiques pétrophysiques et hydrauliques de l'aquifère qui contrôlent son comportement hydrodynamique. Les graviers aquifères de Kappelen présentent deux minéraux dominants: quartz et calcite. Les analyses minéralogiques indiquent que ces deux éléments constituent 65 à 75% de la matrice. La porosité totale obtenue par les diagraphies nucléaires varie de 20 à 30 %, et de 22 à 29 % par diagraphies électrique. Avec les faibles valeurs de Gamma Ray ces résultats indiquent que l'aquifère des graviers de Kappelen est dépourvu d'argile minéralogique. La perméabilité obtenue par diagraphies du fluide varie de 3.10-4 à 5.10-2 m/s, et par essais de pompage de 10-4 à 10-2 m/s. Les résultats des analyses granulométriques indiquent une hétérogénéité granulométrique au niveau des graviers aquifères. La fraction de sables, sables très fins, silts et limons constitue de 10 à 40 %. Ces éléments jouent un rôle important dans le comportement hydraulique de l'aquifère. La porosité efficace de 11 à 25% estimée à partir des résultats des analyses granulométriques suppose que les zones les plus perméables correspondent aux zones les plus graveleuses du site. Etablie sur le site de Kappelen, cette méthodologie a été utilisée sur le site de Grenchen. Les méthodes électriques de surface indiquent que l'aquifère captif de Grenchen est constitué des sables silteux comprenant des passages sableux, encadrés par des silts argileux imperméables. L'aquifère de Grenchen est disposé dans une structure relativement tabulaire et horizontale. Son épaisseur totale peut atteindre les 25 m vers le sud et le sud ouest ou les passages sableux sont les plus importants. La détermination des caractéristiques pétrophysiques et hydrauliques s'est faite à l'aide des diagraphies. Les intensités Gamma Ray varient de 30 à 100 cps, les plus fortes valeurs n'indiquent qu'une présence d'éléments argileux mais pas de bancs d'argile. Les porosités totales de 15 à 25% et les densités globales de 2.25 à 2.45 g/cm3 indiquent que la phase minérale (matrice) est composée essentiellement de quartz et de calcaire. Les densités de matrice varient entre 2.65 et 2.75 g/cm3. La perméabilité varie de 2 10-6 à 5 10-4 m/s. La surestimation des porosités totales à partir des diagraphies électriques de 25 à 42% est due à la présence d'argiles. -- The vast alluvial Seeland aquifer system in northwestern Switzerland is subjected to environmental challenges due to intensive agriculture, roads, cities and industrial activities. Optimal knowledge of the hydrological resources of this aquifer system is therefore important for their protection. Two representative sites, Kappelen and Grenchen, of the Seeland aquifer were investigated using surface-based geoelectric methods and geophysical borehole logging methods. By integrating of hydrogeological and hydrogeophysical methods, a reliable characterization of the aquifer system at these two sites can be performed in order to better understand the governing flow and transport process. At the Kappelen site, surface-based geoelectric methods allowed to identify various geoelectric facies and highlighted their tabular and horizontal structure. It is an unconfined aquifer made up of 15 m thick gravels with an important sandy fraction and bounded by a shaly glacial aquitard. Electrical and nuclear logging measurements allow for constraining the petrophysical and hydrological parameters of saturated gravels. Results indicate that in agreement with mineralogical analyses, matrix of the probed formations is dominated by quartz and calcite with densities of 2.65 and 2.71 g/cc, respectively. These two minerals constitute approximately 65 to 75 % of the mineral matrix. Matrix density values vary from 2.60 to 2.75 g/cc. Total porosity values obtained from nuclear logs range from 20 to 30 % and are consistent with those obtained from electrical logs ranging from 22 to 29 %. Together with the inherently low natural gamma radiation and the matrix density values obtained from other nuclear logging measurements, this indicates that at Kappelen site the aquifer is essentially devoid of clay. Hydraulic conductivity values obtained by the Dilution Technique vary between 3.10-4 and 5.10-2 m/s, while pumping tests give values ranging from 10-4 to 10-2 m/s. Grain size analysis of gravel samples collected from boreholes cores reveal significant granulometric heterogeneity of these deposits. Calculations based on these granulometric data have shown that the sand-, silt- and shale-sized fractions constitute between 10 and 40 % of the sample mass. The presence of these fine elements in general and their spatial distribution in particular are important as they largely control the distribution of the total and effective porosity as well as the hydraulic conductivity. Effective porosity values ranging from 11 to 25% estimated from grain size analyses indicate that the zones of higher hydraulic conductivity values correspond to the zones dominated by gravels. The methodology established at the Kappelen site was then applied to the Grenchen site. Results from surface-based geoelectric measurements indicate that it is a confined aquifer made up predominantly of shaly sands with intercalated sand lenses confined impermeable shally clay. The Grenchen confined aquifer has a relatively tabular and horizontal structure with a maximum thickness of 25 m in the south and the southwest with important sand passages. Petrophysical and hydrological characteristics were performed using electrical and nuclear logging. Natural gamma radiation values ranging from 30 to 100 cps indicate presence of a clay fraction but not of pure clay layers. Total porosity values obtained from electrical logs vary form 25 to 42%, whereas those obtained from nuclear logs values vary from 15 to 25%. This over-estimation confirms presences of clays. Density values obtained from nuclear logs varying from 2.25 to 2.45 g/cc in conjunction with the total porosity values indicate that the dominating matrix minerals are quartz and calcite. Matrix density values vary between 2.65 and 2.75 g/cc. Hydraulic conductivity values obtained by the Dilution Technique vary from 2 10-6 to 5 10-4 m/s.

Protease-activated receptor 2 signalling promotes dendritic cell antigen transport and T-cell activation in vivo.

Deficiency of protease-activated receptor-2 (PAR2) modulates inflammation in several models of inflammatory and autoimmune disease, although the underlying mechanism(s) are not understood. PAR2 is expressed on endothelial and immune cells, and is implicated in dendritic cell (DC) differentiation. We investigated in vivo the impact of PAR2 activation on DCs and T cells in PAR2 wild-type (WT) and knockout (KO) mice using a specific PAR2 agonist peptide (AP2). PAR2 activation significantly increased the frequency of mature CD11c(high) DCs in draining lymph nodes 24 hr after AP2 administration. Furthermore, these DCs exhibited increased expression of major histocompatibility complex (MHC) class II and CD86. A significant increase in activated (CD44(+) CD62(-)) CD4(+) and CD8(+) T-cell frequencies was also observed in draining lymph nodes 48 hr after AP2 injection. No detectable change in DC or T-cell activation profiles was observed in the spleen. The influence of PAR2 signalling on antigen transport to draining lymph nodes was assessed in the context of delayed-type hypersensitivity. PAR2 WT mice that were sensitized by skin-painting with fluorescein isothiocyanate (FITC) to induce delayed-type hypersensitivity possessed elevated proportion of FITC(+) DCs in draining lymph nodes 24 hr after FITC painting when compared with PAR2 KO mice (0.95% versus 0.47% of total lymph node cells). Collectively, these results demonstrate that PAR2 signalling promotes DC trafficking to the lymph nodes and subsequent T-cell activation, and thus provides an explanation for the pro-inflammatory effect of PAR2 in animal models of inflammation.

Effect of water velocity on the uptake of polychlorinatedd biphenyls (PCBs) by silicone rubber (SR) and low-density polyethylene (LDPE) passive samplers: an assessment of the efficiency of performance reference compounds (PRCs) in river-like flow conditions

One aim of this study is to determine the impact of water velocity on the uptake of indicator polychlorinated biphenyls (iPCBs) by silicone rubber (SR) and low-density polyethylene (LDPE) passive samplers. A second aim is to assess the efficiency of performance reference compounds (PRCs) to correct for the impact of water velocity. SR and LDPE samplers were spiked with 11 or 12 PRCs and exposed for 6 weeks to four different velocities (in the range of 1.6 to 37.7 cm s−1) in river-like flow conditions using a channel system supplied with river water. A relationship between velocity and the uptakewas found for each iPCB and enables to determine expected changes in the uptake due to velocity variations. For both samplers, velocity increases from 2 to 10 cm s−1, 30 cm s−1 (interpolated data) and 100 cm s−1 (extrapolated data) lead to increases of the uptake which do not exceed a factor of 2, 3 and 4.5, respectively. Results also showed that the influence of velocity decreased with increasing the octanol-water coefficient partition (log Kow) of iPCBs when SR is used whereas the opposite effect was observed for LDPE. Time-weighted average (TWA) concentrations of iPCBs in water were calculated from iPCB uptake and PRC release. These calculations were performed using either a single PRC or all the PRCs. The efficiency of PRCs to correct the impact of velocity was assessed by comparing the TWA concentrations obtained at the four tested velocities. For SR, a good agreement was found among the four TWA concentrations with both methods (average RSD b 10%). Also for LDPE, PRCs offered a good correction of the impact of water velocity (average RSD of about 10 to 20%). These results contribute to the process of acceptance of passive sampling in routine regulatory monitoring programs.

Epithelial sodium transport and its control by aldosterone: the story of our internal environment revisited.

Transcription and translation require a high concentration of potassium across the entire tree of life. The conservation of a high intracellular potassium was an absolute requirement for the evolution of life on Earth. This was achieved by the interplay of P- and V-ATPases that can set up electrochemical gradients across the cell membrane, an energetically costly process requiring the synthesis of ATP by F-ATPases. In animals, the control of an extracellular compartment was achieved by the emergence of multicellular organisms able to produce tight epithelial barriers creating a stable extracellular milieu. Finally, the adaptation to a terrestrian environment was achieved by the evolution of distinct regulatory pathways allowing salt and water conservation. In this review we emphasize the critical and dual role of Na(+)-K(+)-ATPase in the control of the ionic composition of the extracellular fluid and the renin-angiotensin-aldosterone system (RAAS) in salt and water conservation in vertebrates. The action of aldosterone on transepithelial sodium transport by activation of the epithelial sodium channel (ENaC) at the apical membrane and that of Na(+)-K(+)-ATPase at the basolateral membrane may have evolved in lungfish before the emergence of tetrapods. Finally, we discuss the implication of RAAS in the origin of the present pandemia of hypertension and its associated cardiovascular diseases.