Tubuloglomerular feedback responses of the downstream efferent resistance: Unmasking a role for adenosine?

This Commentary aims to integrate or interrelate the available in vivo data with the in vitro study by Ren and co-workers, which comes to the somewhat surprising conclusion that tubuloglomerular feedback activation vasodilates the efferent arteriole by an adenosine-dependent mechanism

Renal Effects of the Novel Selective Adenosine A1 Receptor Blocker SLV329 in Experimental Liver Cirrhosis in Rats

Liver cirrhosis is often complicated by an impaired renal excretion of water and sodium. Diuretics tend to further deteriorate renal function. It is unknown whether chronic selective adenosine A1 receptor blockade, via inhibition of the hepatorenal reflex and the tubuloglomerular feedback, might exert diuretic and natriuretic effects without a reduction of the glomerular filtration rate. In healthy animals intravenous treatment with the novel A1 receptor antagonist SLV329 resulted in a strong dose-dependent diuretic (up to 3.4-fold) and natriuretic (up to 13.5-fold) effect without affecting creatinine clearance. Male Wistar rats with thioacetamide-induced liver cirrhosis received SLV329, vehicle or furosemide for 12 weeks. The creatinine clearance of cirrhotic animals decreased significantly (−36.5%, p<0.05), especially in those receiving furosemide (−41.9%, p<0.01). SLV329 was able to prevent this decline of creatinine clearance. Mortality was significantly lower in cirrhotic animals treated with SLV329 in comparison to animals treated with furosemide (17% vs. 54%, p<0.05). SLV329 did not relevantly influence the degree of liver fibrosis, kidney histology or expression of hepatic or renal adenosine receptors. In conclusion, chronic treatment with SLV329 prevented the decrease of creatinine clearance in a rat model of liver cirrhosis. Further studies will have to establish whether adenosine A1 receptor antagonists are clinically beneficial at different stages of liver cirrhosis

HCl and ClO in activated Arctic air; first retrieved vertical profiles from TELIS submillimetre limb spectra

The first profile retrieval results of the Terahertz and submillimeter Limb Sounder (TELIS) balloon instrument are presented. The spectra are recorded during a 13-h balloon flight on 24 January 2010 from Kiruna, Sweden. The TELIS instrument was mounted on the MIPAS-B2 gondola and shared this platform with the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) and the mini- Differential Optical Absorption Spectroscopy (mini-DOAS) instruments. The flight took place within the Arctic vortex at an altitude of ≈34 km in chlorine activated air, and both active (ClO) and inactive chlorine (HCl) were measured over an altitude range of respectively ≈16–32 km and ≈10– 32 km. In this altitude range, the increase of ClO concentration levels during sunrise has been recorded with a temporal resolution of one minute. During the daytime equilibrium, a maximum ClO level of 2.1±0.3 ppbv has been observed at an altitude of 23.5 km. This equilibrium profile is validated against the ClO profile by the satellite instrument Microwave Limb Sounder (MLS) aboard EOS Aura. HCl profiles have been determined from two different isotopes – H35Cl and H37Cl – and are also validated againstMLS. The precision of all profiles is well below 0.01 ppbv and the overall accuracy is therefore governed by systematic effects. The total uncertainty of these effects is estimated to be maximal 0.3 ppbv for ClO around its peak value at 23.5 km during the daytime equilibrium, and for HCl it ranges from 0.05 to 0.4 ppbv, depending on altitude. In both cases the main uncertainty stems from a largely unknown non-linear response in the detector

P2Y2 receptor activation inhibits the expression of the sodium-chloride cotransporter NCC in distal convoluted tubule cells

Luminal nucleotide stimulation is known to reduce Na+ transport in the distal nephron. Previous studies suggest that this mechanism may involve the thiazide-sensitive Na+-Cl− cotransporter (NCC), which plays an essential role in NaCl reabsorption in the cells lining the distal convoluted tubule (DCT). Here we show that stimulation of mouse DCT (mDCT) cells with ATP or UTP promoted Ca2+ transients and decreased the expression of NCC at both mRNA and protein levels. Specific siRNA-mediated silencing of P2Y2 receptors almost completely abolished ATP/UTP-induced Ca2+ transients and significantly reduced ATP/UTP-induced decrease of NCC expression. To test whether local variations in the intracellular Ca2+ concentration ([Ca2+]i) may control NCC transcription, we overexpressed the Ca2+-binding protein parvalbumin selectively in the cytosol or in the nucleus of mDCT cells. The decrease in NCC mRNA upon nucleotide stimulation was abolished in cells overexpressing cytosolic PV but not in cells overexpressing either a nuclear-targeted PV or a mutated PV unable to bind Ca2+. Using a firefly luciferase reporter gene strategy, we observed that the activity of NCC promoter region from −1 to −2,200bp was not regulated by changes in [Ca2+]i. In contrast, high cytosolic calcium level induced instability of NCC mRNA. We conclude that in mDCT cells: (1) P2Y2 receptor is essential for the intracellular Ca2+ signaling induced by ATP/UTP stimulation; (2) P2Y2-mediated increase of cytoplasmic Ca2+ concentration down-regulates the expression of NCC; (3) the decrease of NCC expression occurs, at least in part, via destabilization of its mRNA

Synergistic interaction of hypertension and diabetes in promoting kidney injury and the role of endoplasmic reticulum stress

Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella