Oxygen-dependent hydroxylation by Factor Inhibiting HIF (FIH) regulates the TRPV3 ion channel

Factor Inhibiting HIF (FIH) is an oxygen-dependent asparaginyl hydroxylase that regulates the hypoxia-inducible factors (HIFs). Several proteins containing ankyrin repeat domains have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ankyrin repeat domain. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygendependent asparaginyl hydroxylation is likely to extend to other ion channels.

Synaptic vesicle glycoprotein 2A modulates vesicular release and calcium channel function at peripheral sympathetic synapses

Synaptic vesicle glycoprotein (SV)2A is a transmembrane protein found in secretory vesicles and is critical for Ca2+-dependent exocytosis in central neurons, although its mechanism of action remains uncertain. Previous studies have proposed, variously, a role of SV2 in the maintenance and formation of the readily releasable pool (RRP) or in the regulation of Ca2+ responsiveness of primed vesicles. Such previous studies have typically used genetic approaches to ablate SV2 levels; here, we used a strategy involving small interference RNA (siRNA) injection to knockdown solely presynaptic SV2A levels in rat superior cervical ganglion (SCG) neuron synapses. Moreover, we investigated the effects of SV2A knockdown on voltage-dependent Ca2+ channel (VDCC) function in SCG neurons. Thus, we extended the studies of SV2A mechanisms by investigating the effects on vesicular transmitter release and VDCC function in peripheral sympathetic neurons. We first demonstrated an siRNA-mediated SV2A knockdown. We showed that this SV2A knockdown markedly affected presynaptic function, causing an attenuated RRP size, increased paired-pulse depression and delayed RRP recovery after stimulus-dependent depletion. We further demonstrated that the SV2A–siRNA-mediated effects on vesicular release were accompanied by a reduction in VDCC current density in isolated SCG neurons. Together, our data showed that SV2A is required for correct transmitter release at sympathetic neurons. Mechanistically, we demonstrated that presynaptic SV2A: (i) acted to direct normal synaptic transmission by maintaining RRP size, (ii) had a facilitatory role in recovery from synaptic depression, and that (iii) SV2A deficits were associated with aberrant Ca2+ current density, which may contribute to the secretory phenotype in sympathetic peripheral neurons.

Efficient incorporation of channel cross-section geometry uncertainty into regional and global scale flood inundation models

This paper investigates the challenge of representing structural differences in river channel cross-section geometry for regional to global scale river hydraulic models and the effect this can have on simulations of wave dynamics. Classically, channel geometry is defined using data, yet at larger scales the necessary information and model structures do not exist to take this approach. We therefore propose a fundamentally different approach where the structural uncertainty in channel geometry is represented using a simple parameterization, which could then be estimated through calibration or data assimilation. This paper first outlines the development of a computationally efficient numerical scheme to represent generalised channel shapes using a single parameter, which is then validated using a simple straight channel test case and shown to predict wetted perimeter to within 2% for the channels tested. An application to the River Severn, UK is also presented, along with an analysis of model sensitivity to channel shape, depth and friction. The channel shape parameter was shown to improve model simulations of river level, particularly for more physically plausible channel roughness and depth parameter ranges. Calibrating channel Manning’s coefficient in a rectangular channel provided similar water level simulation accuracy in terms of Nash-Sutcliffe efficiency to a model where friction and shape or depth were calibrated. However, the calibrated Manning coefficient in the rectangular channel model was ~2/3 greater than the likely physically realistic value for this reach and this erroneously slowed wave propagation times through the reach by several hours. Therefore, for large scale models applied in data sparse areas, calibrating channel depth and/or shape may be preferable to assuming a rectangular geometry and calibrating friction alone.

The efficacy of potassium sorbate-coated packaging to control postharvest gray mold in raspberries, blackberries, and blueberries

The aim of this work is to build on the success of in vitro studies of an active packaging, produced by coating the surface of post-consumer recycled polyethylene terephthalate (PCRPET) package with an aqueous silicone solution (2%, v/v) containing an antifungal agent (potassium sorbate, KS). Antifungal efficacy was evaluated, in vivo, during the storage of raspberries, blackberries and blueberries by examining their shelf life extension. The packaging effectively delayed the growth of Botrytis by extending its lag-phase, which, in turn, extended the shelf life of the berries by up to 3d. Among the three berries tested, the packaging proved to be more advantageous in the case of raspberries, due to their physiological characteristics and shorter shelf life. Based on sensory panel evaluations, it was shown that the coating, containing KS, did not influence the packaging appearance and transparency, and the fruit did not suffer from any off-flavor development.

The Mesolithic-Neolithic transition in the Channel Islands: maritime and terrrestrial perspectives

This paper investigates the Mesolithic-Neolithic transition in the Channel Islands. It presents a new synthesis of all known evidence from the islands c. 5000-4300 BC, including several new excavations as well as find spot sites that have not previously been collated. It also summarises – in English – a large body of contemporary material from north-west France. The paper presents a new high-resolution sea level model for the region, shedding light on the formation of the Channel Islands from 9000-4000 BC. Through comparison with contemporary sites in mainland France, an argument is made suggesting that incoming migrants from the mainland and the small indigenous population of the islands were both involved in the transition. It is also argued that, as a result of the fact the Channel Islands witnessed a very different trajectory of change to that seen in Britain and Ireland c. 5000-3500 BC, this small group of islands has a great deal to tell us about the arrival of the Neolithic more widely.

The housing market channel of monetary policy transmission in the Euro area

Purpose – The purpose of this paper is to explore the role of the housing market in the monetary policy transmission to consumption among euro area member states. It has been argued that the housing market in one country is then important when its mortgage market is well developed. The countries in the euro area follow unitary monetary policy, however, their housing and mortgage markets show some heterogeneity, which may lead to different policy effects on aggregate consumption through the housing market. Design/methodology/approach – The housing market can act as a channel of monetary policy shocks to household consumption through changes in house prices and residential investment – the housing market channel. We estimate vector autoregressive models for each country and conduct a counterfactual analysis in order to disentangle the housing market channel and assess its importance across the euro area member states. Findings – We find little evidence for heterogeneity of the monetary policy transmission through house prices across the euro area countries. Housing market variations in the euro area seem to be better captured by changes in residential investment rather than by changes in house prices. As a result we do not find significantly large house price channels. For some of the countries however, we observe a monetary policy channel through residential investment. The existence of a housing channel may depend on institutional features of both the labour market or with institutional factors capturing the degree of household debt as is the LTV ratio. Originality/value – The study contributes to the existing literature by assessing whether a unitary monetary policy has a different impact on consumption across the euro area countries through their housing and mortgage markets. We disentangle monetary-policy-induced effects on consumption associated with variations on the housing markets due to either house price variations or residential investment changes. We show that the housing market can play a role in the monetary transmission mechanism even in countries with less developed mortgage markets through variations in residential investment.

Eddies and variability in the Mozambique Channel

Between 1995 and 2000, on average 4 eddies per year are observed from satellite altimetry to propagate southward through the Mozambique Channel, into the upstream Agulhas region. Further south, these eddies have been found to control the timing and frequenc yof Agulhas ring shedding. Within the Mozambique Channel, anomalous SSH amplitudes rise to 30 cm ; in agreement with in situ measured velocities. Comparison of an observed velocit ysection with GCM model results shows that the Mozambique Channel eddies in these models are too surface intensified. Also, the number of eddies formed in the models is in disagreement with our observational analysis. Moored current meter measurements observing the passage of three eddies in 2000 are extended to a 5-year time series b yreferencing the anomalous surface currents estimated from altimeter data to a s ynoptic LADCP velocit y measurement. The results show intermittent edd ypassage at the mooring location. A statistical analysis of SSH observations in different parts of the Mozambique Channel shows a southward decrease of the dominant frequency of the variability, going from 7 per year in the extension of the South Equatorial Current north of Madagascar to 4 per year south of Madagascar. The observations suggest that frequency reduction is related to the Rossb ywaves coming in from the east

Relationship Between Expression of Voltage-Dependent Anion Channel (VDAC) Isoforms and Type of Hexokinase Binding Sites on Brain Mitochondria

Voltage-dependent anion channels (VDAC) are pore-forming proteins found in the outer mitochondrial membrane of eukaryotes. VDACs are known to play an essential role in cellular metabolism and in early stages of apoptosis. In mammals, three VDAC isoforms have been identified. A proteomic approach was exploited to study the expression of VDAC isoforms in rat, bovine, and chicken brain mitochondria. Given the importance of mitochondrially bound hexokinase in regulation of aerobic glycolysis in brain, we studied the possibility that differences in the relative expression of VDAC isoforms may be a factor in determining the species-dependent ratio of type A/type B hexokinase binding sites on brain mitochondria. The spots were characterized, and the signal intensities among spots were compared. VDAC1 was the most abundantly expressed of the three isoforms. Moreover the expression of VDAC1 plus VDAC2 was significantly higher in bovine than in rat brain. Chicken brain mitochondria showed the highest VDAC1 expression and the lowest of VDAC2. Bovine brain mitochondria had the highest VDAC2 levels. We concluded that the nature of hexokinase binding site is not determined by the expression of a single VDAC isoform.

Rosiglitazone prevents sirolimus-induced hypomagnesemia, hypokalemia, and downregulation of NKCC2 protein expression

Alexandre CS, Braganca AC, Shimizu MH, Sanches TR, Fortes MA, Giorgi RR, Andrade L, Seguro AC. Rosiglitazone prevents sirolimus-induced hypomagnesemia, hypokalemia, and downregulation of NKCC2 protein expression. Am J Physiol Renal Physiol 297: F916-F922, 2009. First published August 5, 2009; doi:10.1152/ajprenal.90256.2008.-Sirolimus, an antiproliferative immunosuppressant, induces hypomagnesemia and hypokalemia. Rosiglitazone activates renal sodiumand water-reabsorptive pathways. We evaluated whether sirolimus induces renal wasting of magnesium and potassium, attempting to identify the tubule segments in which this occurs. We tested the hypothesis that reduced expression of the cotransporter NKCC2 forms the molecular basis of this effect and evaluated the possible association between increased urinary excretion of magnesium and renal expression of the epithelial Mg(2+) channel TRPM6. We then analyzed whether rosiglitazone attenuates these sirolimus-induced tubular effects. Wistar rats were treated for 14 days with sirolimus (3 mg/kg body wt in drinking water), with or without rosiglitazone (92 mg/kg body wt in food). Protein abundance of NKCC2, aquaporin2 (AQP2), and TRPM6 was assessed using immunoblotting. Sirolimus-treated animals presented no change in glomerular filtration rate, although there were marked decreases in plasma potassium and magnesium. Sirolimus treatment reduced expression of NKCC2, and this was accompanied by greater urinary excretion of sodium, potassium, and magnesium. In sirolimus-treated animals, AQP2 expression was reduced. Expression of TRPM6 was increased, which might represent a direct stimulatory effect of sirolimus or a compensatory response. The finding that rosiglitazone prevented or attenuated all sirolimus-induced renal tubular defects has potential clinical implications.

Aquaporin 2 expression increased by glucagon in normal rat inner medullary collecting ducts

Yano Y, Cesar KR, Araujo M, Rodrigues Jr. AC, Andrade LC, Magaldi AJ. Aquaporin 2 expression increased by glucagon in normal rat inner medullary collecting ducts. Am J Physiol Renal Physiol 296: F54-F59, 2009. First published October 1, 2008; doi: 10.1152/ajprenal.90367.2008.-It is well known that Glucagon (Gl) is released after a high protein diet and participates in water excretion by the kidney, principally after a protein meal. To study this effect in in vitro perfused inner medullary collecting ducts (IMCD), the osmotic water permeability (Pf; mu m/s) at 37 degrees C and pH 7.4 in normal rat IMCDs (n = 36) perfused with Ringer/HCO(3) was determined. Gl (10(-7) M) in absence of Vasopressin (AVP) enhanced the Pf from 4.38 +/- 1.40 to 11.16 +/- 1.44 mu m/s (P < 0.01). Adding 10(-8), 10(-7), and 10(-6) M Gl, the Pf responded in a dose-dependent manner. The protein kinase A inhibitor H8 blocked the Gl effect. The specific Gl inhibitor, des-His(1)-[Glu(9)] glucagon (10(-7) M), blocked the Gl-stimulated Pf but not the AVP-stimulated Pf. There occurred a partial additional effect between Gl and AVP. The cAMP level was enhanced from the control 1.24 +/- 0.39 to 59.70 +/- 15.18 fm/mg prot after Gl 10(-7) M in an IMCD cell suspension. The immunoblotting studies indicated an increase in AQP2 protein abundance of 27% (cont 100.0 +/- 3.9 vs. Gl 127.53; P = 0.0035) in membrane fractions extracted from IMCD tubule suspension, incubated with 10(-6) M Gl. Our data showed that 1) Gl increased water absorption in a dose-dependent manner; 2) the anti-Gl blocked the action of Gl but not the action of AVP; 3) Gl stimulated the cAMP generation; 4) Gl increased the AQP2 water channel protein expression, leading us to conclude that Gl controls water absorption by utilizing a Gl receptor, rather than a AVP receptor, increasing the AQP2 protein expression.

Caesium, potassium and ammonium distributions in different organs of tropical plants

In the present work the distribution of ions in aboveground plant parts was studied in order to establish the suitability of using radiocaesium as a tracer for the plant absorption of nutrients, such as potassium (K(+)) and ammonium (NH(4)(+)). We present the results for the distributions of (137)Cs, (40)K and NH(4)(+) from four tropical plant species: lemon (Citrus aurantifolia), orange (Citrus sinensis), guava (Psidium guajava) and chili pepper (Capsicum frutescens). Activity concentrations of (137)Cs and (40)K were measured by gamma spectrometry and concentrations of free NH(4)(+) ions by a colorimetric method. Similarly to potassium and ammonium, caesium showed a high mobility within the plants, exhibiting the highest values of concentration in the growing parts of the tree (fruits, new leaves, twigs, and barks). A significant correlation between activity concentrations of (137)Cs and (40)K was observed in these tropical plants. The K/Cs discrimination ratios were approximately equal to unity in different compartments of each individual plant, suggesting that caesium could be a good tracer for (40)K in tropical woody fruit species. Despite the similarity observed for the behaviour of caesium and ammonium in the newly grown plant compartments, (137)Cs was not well correlated with NH(4)(+). Significant temporal changes in the NH(4)(+) concentrations were observed during the development of fruits, while the (137)Cs activity concentration alterations were not of great importance, indicating, therefore, that Cs(+) and free NH(4)(+) ions could have distinct concentration ratios for each particular plant organ. (C) 2008 Elsevier B.V. All rights reserved.