High glucose up-regulates ENaC and SGK1 expression in HCD-cells

Background/Aim: Diabetic nephropathy is associated with progressive renal damage, leading to impaired function and end-stage renal failure. Secondary hypertension stems from a deranged ability of cells within the kidney to resolve and appropriately regulate sodium resorption in response to hyperglycaemia. However, the mechanisms by which glucose alters sodium re-uptake have not been fully characterised. Methods: Here we present RT-PCR, western blot and immunocytochemistry data confirming mRNA and protein expression of the serum and glucocorticoid inducible kinase (SGK1) and the a conducting subunit of the epithelial sodium channel (ENaC) in a model in vitro system of the human cortical collecting duct (HCD). We examined changes in expression of these elements in response to glucose challenge, designed to mimic hyperglycaemia associated with type 2 diabetes mellitus. Changes in Na+ concentration were assessed using single-cell microfluorimetry. Results: Incubation with glucose, the Ca2+-ionophore ionomycin and the cytokine TGF-beta 1 were all found to evoke significant and time-dependent increases in both SGK1 and alpha ENaC protein expression. These molecular changes were correlated to an increase in Na+-uptake at the single-cell level. Conclusion: Together these data offer a potential explanation for glucose-evoked Na+-resorption and a potential contributory role of SGK1 and ENaCs in development of secondary hypertension, commonly linked to diabetic nephropathy

Using continuous measurements of near-surface atmospheric water vapour isotopes to document snow-air interactions

Water stable isotope data from Greenland ice cores provide key paleoclimatic information. However, postdepositional processes linked with snow metamorphism remain poorly documented. For this purpose, a monitoring of the isotopic composition δ18O and δD at several height levels (up to 13 meter) of near-surface water vapor, precipitation and snow in the first 0.5 cm from the surface has been conducted during three summers (2010-2012) at NEEM, NW Greenland. We observe a clear diurnal cycle in both the value and gradient of the isotopic composition of the water vapor above the snow surface. The diurnal amplitude in δD is found to be ~15‰. The diurnal isotopic composition follows the absolute humidity cycle. This indicates a large flux of vapor from the snow surface to the atmosphere during the daily warming and reverse flux during the daily cooling. The isotopic measurements of the flux of water vapor above the snow give new insights into the post depositional processes of the isotopic composition of the snow. During nine 1-5 days periods between precipitation events, our data demonstrate parallel changes of δ18O and d-excess in surface snow and near-surface vapor. The changes in δ18O of the vapor are similar or larger than those of the snow δ18O. It is estimated using the CROCUS snow model that 6 to 20% of the surface snow mass is exchanged with the atmosphere. In our data, the sign of surface snow isotopic changes is not related to the sign or magnitude of sublimation or deposition. Comparisons with atmospheric models show that day-to-day variations in near-surface vapor isotopic composition are driven by synoptic variations and changes in air mass trajectories and distillation histories. We suggest that, in-between precipitation events, changes in the surface snow isotopic composition are driven by these changes in near-surface vapor isotopic composition. This is consistent with an estimated 60% mass turnover of surface snow per day driven by snow recrystallization processes associated with temperature gradients near the snow surface. Our findings have implications for ice core data interpretation and model-data comparisons, and call for further process studies

The conservation status of the world's freshwater molluscs

With the biodiversity crisis continuing unchecked, we need to establish levels and drivers of extinction risk, and reassessments over time, to effectively allocate conservation resources and track progress towards global conservation targets. Given that threat appears particularly high in freshwaters, we assessed the extinction risk of 1428 randomly selected freshwater molluscs using the IUCN Red List Categories and Criteria, as part of the Sampled Red List Index project. We show that close to one-third of species in our sample are estimated to be threatened with extinction, with highest levels of threat in the Nearctic, Palearctic and Australasia and among gastropods. Threat levels were higher in lotic than lentic systems. Pollution (chemical and physical) and the modification of natural systems (e.g. through damming and water abstraction) were the most frequently reported threats to freshwater molluscs, with some regional variation. Given that we found little spatial congruence between species richness patterns of freshwater molluscs and other freshwater taxa, apart from crayfish, new additional conservation priority areas emerged from our study. We discuss the implications of our findings for freshwater mollusc conservation, the adequacy of a sampled approach and important next steps to estimate trends in freshwater mollusc extinction risk over time

Genetic causes of hypercalciuric nephrolithiasis

Renal stone disease (nephrolithiasis) affects 3–5% of the population and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in over 35% of patients and may occur as a monogenic disorder that is more likely to manifest itself in childhood. Studies of these monogenic forms of hypercalciuric nephrolithiasis in humans, e.g. Bartter syndrome, Dent’s disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal disease, is caused by mutations of the bumetanide-sensitive Na–K–Cl (NKCC2) co-transporter, the renal outer-medullary potassium (ROMK) channel, the voltage-gated chloride channel, CLC-Kb, the CLC-Kb beta subunit, barttin, or the calcium-sensing receptor (CaSR). Dent’s disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrolithiasis, is due to mutations of the chloride/proton antiporter 5, CLC-5; ADHH is associated with activating mutations of the CaSR, which is a G-protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium–phosphate co-transporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to hypercalciuria and nephrolithiasis

Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption

To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal principal cells. This triggers an intracellular cAMP signaling cascade, which phosphorylates aquaporin-2 (AQP2) and targets the channel to the apical plasma membrane. Driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels. When water homeostasis is restored, AVP levels decline, and AQP2 is internalized from the plasma membrane, leaving the plasma membrane watertight again. The action of AVP is counterbalanced by several hormones like prostaglandin E2, bradykinin, dopamine, endothelin-1, acetylcholine, epidermal growth factor, and purines. Moreover, AQP2 is strongly involved in the pathophysiology of disorders characterized by renal concentrating defects, as well as conditions associated with severe water retention. This review focuses on our recent increase in understanding of the molecular mechanisms underlying AVP-regulated renal water transport in both health and disease

Bad taxonomy can kill : molecular reevaluation of Unio mancus

International audienc

Phylogeny of African fruit bats (Chiroptera, Pteropodidae) based on complete mitochondrial genomes

Members of the family Pteropodidae, also known as Old World fruit bats, are represented in Africa by 14 genera and 44 species. Here, we sequenced 67 complete mitochondrial genomes from African and Asian pteropodids to better understand the evolutionary history of the subfamily Rousettinae, which includes most of the African species. An increased frequency of guanine to adenine transitions is detected in the mtDNA genomes of Macroglossus sobrinus and all species of Casinycteris and Scotonycteris. Our phylogenetic and molecular dating analyses based on 126 taxa and 15,448 characters indicate a low signal for deep relationships within the family, suggesting a rapid diversification during the Late Oligocene period of "warming." Within the subfamily Rousettinae, most nodes are highly supported by our different analyses (all nucleotide sites, SuperTRI analyses of a sliding window, transversions only, coding genes only, and amino acid sequences). The results indicate the existence of four tribes: Rousettini-distributed from Africa through Mediterranean region and South Asia to South-East Asia; Eonycterini-found in Asia; and Epomophorini and Scotonycterini-restricted to sub-Saharan Africa. Although most interspecies relationships are highly supported, three parts of the Rousettinae mitochondrial tree are still unresolved, suggesting rapid diversification: (a) among the three subtribes Epomophorina (Epomophorus sensu lato, i.e., including Micropteropus, Epomops, Hypsignathus, Nanonycteris), Plerotina (Plerotes), and Myonycterina (Myonycteris, Megaloglossus) in the Late Miocene; (b) among Epomops, Hypsignathus, and other species of Epomophorina at the Pliocene-Pleistocene boundary; and (c) among Myonycteris species in the Early Pleistocene. Within the Epomophorini, Stenonycteris lanosus emerged first, suggesting that lingual echolocation may have appeared in the common ancestor of Epomophorini and Rousettini. Our analyses suggest that multiple events of mtDNA introgression occurred within the Epomophorus species complex during the Pleistocene

Evidence for a three-phase sequence during Heinrich Stadial 4 using a multiproxy approach based on Greenland ice core records

International audienceGlacial climate was characterised by two types of abrupt events. Greenland ice cores record Dansgaard-Oeschger events, marked by abrupt warming in-between cold, stadial phases. Six of these stadials appear related to major Heinrich events (HEs), identified from ice-rafted debris (IRD) and large excursions in carbon-and oxygen-stable isotopic ratios in North Atlantic deep sea sediments, documenting major ice sheet collapse events. This finding has led to the paradigm that glacial cold events are induced by the response of the Atlantic Meridional Overturning Circulation to such massive freshwater inputs, supported by sensitivity studies conducted with climate models of various complexities. These models also simulate synchronous Green-land temperature and lower-latitude hydrological changes. To investigate the sequence of events between climate changes at low latitudes and in Greenland, we provide here the first 17 O-excess record from a Greenland ice core during Dansgaard-Oeschger events 7 to 13, encompassing H4 and H5. Combined with other ice core proxy records, our new 17 O-excess data set demonstrates that stadials are generally characterised by low 17 O-excess levels compared to interstadials. This can be interpreted as synchronous change of high-latitude temperature and lower-latitude hydrological cycle (relative humidity at the oceanic source of evaporation or change in the water mass trajectory/recharge) and/or an influence of local temperature on 17 O-excess through kinetic effect at snow formation. As an exception from this general pattern, stadial 9 consists of three phases, characterised first by Greenland cooling during 550 ± 60 years (as shown by markers of Greenland temperature δ 18 O and δ 15 N), followed by a specific lower-latitude fingerprint as identified from several proxy records (abrupt decrease in 17 O-excess, increase in CO 2 and methane mixing ratio, heavier δD-CH 4 and δ 18 O atm), lasting 740 ± 60 years, itself ending approximately 390 ± 50 years prior to abrupt Greenland warming. We hypothesise that this lower-latitude signal may be the fingerprint of Heinrich event 4 in Greenland ice cores. The proposed decoupling between stable cold Greenland temperature and low-latitude climate variability identified for sta-dial 9 provides new targets for benchmarking climate model simulations and testing mechanisms associated with millen-nial variability