Effect of mineralocorticoid deficiency on ion and urea transporters and aquaporin water channels in the rat

Mineralocorticoid deficiency is associated with impaired urinary concentration and dilution. The present investigation was undertaken to determine the effects of selective mineralocorticoid deficiency on renal sodium and urea transporters and aquaporin water channels and whether these perturbations can be reversed by maintenance of extracellular fluid volume. Mineralocorticoid deficiency was induced by bilateral adrenalectomies with glucocorticoid replacement. Mineralocorticoid deficient rats receiving plain drinking water (MDW) were compared with mineralocorticoid deficient rats receiving saline-drinking water (MDS) in order to maintain extracellular fluid volume, and with controls (CTL). In MDW rats, there was a significant decrease in renal outer medulla Na-K-2Cl co-transporter and outer medulla Na-K-ATPase as well as an increase in inner medulla aquaporins 2 and 3. There were no significant changes in aquaporin-1, aquaporin-4, or urea transporters. These alterations were reversed with maintenance of extracellular fluid volume in MDS rats. Our findings indicate that mineralocorticoid deficiency in the rat is associated with alterations in factors involved in the countercurrent concentrating mechanism (Na-K-2Cl, Na-K-ATPase) and osmotic water equilibration in the collecting duct (AQP2, AQP3). Maintenance of sodium balance and extracellular fluid volume is associated with normalization of these perturbations.     

Soybean polar lipids differently impact adipose tissue inflammation and the endotoxin transporters LBP and sCD14 in flaxseed vs. palm oil-rich diets

Obesity and type 2 diabetes are nutritional pathologies, characterized by a subclinical inflammatory state. Endotoxins are now well recognized as an important factor implicated in the onset and maintain of this inflammatory state during fat digestion in high-fat diet. As a preventive strategy, lipid formulation could be optimized to limit these phenomena, notably regarding fatty acid profile and PL emulsifier content. Little is known about soybean polar lipid (SPL) consumption associated to oils rich in saturated FA vs. anti-inflammatory omega-3 FA such as α-linolenic acid on inflammation and metabolic endotoxemia. We then investigated in mice the effect of different synthetic diets enriched with two different oils, palm oil or flaxseed oil and containing or devoid of SPL on adipose tissue inflammation and endotoxin receptors. In both groups containing SPL, adipose tissue (WAT) increased compared with groups devoid of SPL and an induction of MCP-1 and LBP was observed in WAT. However, only the high-fat diet in which flaxseed oil was associated with SPL resulted in both higher WAT inflammation and higher circulating sCD14 in plasma. In conclusion, we have demonstrated that LPS transporters LBP and sCD14 and adipose tissue inflammation can be modulated by SPL in high fat diets differing in oil composition. Notably high-flaxseed oil diet exerts a beneficial metabolic impact, however blunted by PL addition. Our study suggests that nutritional strategies can be envisaged by optimizing dietary lipid sources in manufactured products, including fats/oils and polar lipid emulsifiers, in order to limit the inflammatory impact of palatable foods.     

Serum hormone levels and tissue metabolism in pair-fed lean and obese Zucker rats.

Obese Zucker rats were either pair-fed to their lean litter-mates or fed ad lib, to determine the effect of hyperphagia on serum hormone levels and tissue metabolism as indicated by enzyme activities and in vitro metabolite flux. Hyperphagia was shown to be non-essential for the elevation in serum insulin and suppression in serum growth hormone and prolactin in the genetically obese rat. It was also shown that the increased liver cell lipogenic rate was not dependent on hyperphagia in the obese rat and that adipose cell lipogenesis was not significantly altered in the pair-fed obese rat. The utilization of alanine for glucose synthesis in vitro was similar for both lean and obese rats, but its utilization for fatty acid synthesis was higher in the obese rat. Data is presented which suggest that the inhibitory effect of glucagon on liver lipogenesis is blunted in the obese rat.     

Molecular determinants of ammonia and urea conductance in plant aquaporin homologs

Aquaporins and/or aquaglyceroporins regulate the permeability of plant membranes to water and small, uncharged molecules. Using molecular simulations with a plant plasma membrane aquaporin tetramer, the residues in the channel constriction region were identified as the crucial determinants of ammonia and urea conductance. The impact of these residues was experimentally verified using AtPIP2;1 pore mutants. Several, but not all, mutants with a NIP-like selectivity filter promoted yeast growth on urea or ammonia as sole sources of nitrogen. TIP-like mutants conducted urea but not NH(3), and a residue without direct contact to the pore lumen was critical for conduction in the mutants.     

Benzodiazepines differently modulate EAAT1/GLAST and EAAT2/GLT1 glutamate transporters expressed in CHO cells.

It has been described recently that low concentrations of benzodiazepines stimulate the transport activity of the neuronal glutamate transporter EAAT3, whereas high concentrations inhibit it. The present study is aimed to investigate whether benzodiazepines have similar effects on the two glial glutamate transporter, EAAT1 and EAAT2. To this end, the transporters were transiently expressed in CHO cells and transport activity was determined by isotope fluxes using D-aspartate as non-metabolizable homologue of L-glutamate. At low D-aspartate concentrations (1 micromol/l) EAAT1-mediated uptake was reduced significantly by low concentrations of oxazepam (1 micromol/l) and diazepam (1 and 10 micromol/l). At 100 micromol/l D-aspartate oxazepam stimulated EAAT1-mediated uptake up to 150% in a dose dependent manner, whereas the inhibition by low concentrations of diazepam was attenuated. In contrast, a significant effect of diazepam on EAAT2-mediated uptake was only observed at 1000 micromol/l where uptake was inhibited by 60%. A similar inhibition was observed for EAAT1. These studies demonstrate a different modulation of EAAT1 and EAAT2 by benzodiazepines. Furthermore the glial transporters differ from the neuronal glutamate transporter. Thus, a complex in vivo response of the various transporters to benzodiazepines can be expected.     

Expression breadth and expression abundance behave differently in correlations with evolutionary rates

Background  

One of the main objectives of the molecular evolution and evolutionary systems biology field is to reveal the underlying principles that dictate protein evolutionary rates. Several studies argue that expression abundance is the most critical component in determining the rate of evolution, especially in unicellular organisms. However, the expression breadth also needs to be considered for multicellular organisms.     

Protective effects of mesenchymal stromal cells on adriamycin-induced minimal change nephrotic syndrome in rats and possible mechanisms

Background aimsMinimal change nephrotic syndrome is the most frequent cause of nephrotic syndrome in childhood. Current treatment regimes, which include glucocorticoid hormones and immunosuppressive therapy, are effective and have fast response. However, because of the side effects, long treatment course, poor patient compliance and relapse, novel approaches for the disease are highly desired.MethodsThe adriamycin-induced nephrotic rat model was established. Rats were allocated to a model group, a prednisone group or mesenchymal stromal cell (MSC) group. Clinical parameters in each treatment group were determined at 2 weeks, 4 weeks and 8 weeks. The messenger RNA (mRNA) levels of synaptopodin, p21 and monocyte chemoattractant protein-1 were determined through the use of quantitative real-time–polymerase chain reaction. Protein levels were determined by means of Western blot or enzyme-linked immunosorbent assay. Podocytes were isolated and apoptotic rate after adriamycin with or without MSC treatment was analyzed by means of flow cytometry.ResultsMSC intervention improved renal function as assessed by urinary protein, blood creatinine and triglyceride levels. MSC intervention reduced adriamycin-induced renal tissue damage visualized by immunohistochemistry and light and electron microscopic analysis and reduced adriamycin-induced podocyte apoptosis. After MSC intervention, mRNA and protein levels of synaptopodin and p21 in renal cortex were significantly increased. MSCs also restored synaptopodin mRNA and protein expression in isolated podocytes. In addition, monocyte chemoattractant protein-1 mRNA in renal cortex and protein level in serum of the MSC treatment group were significantly decreased compared with that in the adriamycin-induced nephropathy model group.ConclusionsOur data indicate that MSCs could protect rats from adriamycin-induced minimal change nephrotic syndrome, and the protective effects of MSCs are mediated through multiple actions.     

Protein interactions with urea and guanidinium chloride. A calorimetric study.

The interaction of urea and guanidinium chloride with proteins has been studied calorimetrically by titrating protein solutions with denaturants at various fixed temperatures, and by scanning them with temperature at various fixed concentrations of denaturants. It has been shown that the observed heat effects can be described in terms of a simple binding model with independent and similar binding sites. Using the calorimetric data, the number of apparent binding sites for urea and guanidinium chloride have been estimated for three proteins in their unfolded and native states (ribonuclease A, hen egg white lysozyme and cytochrome c). The intrinsic and total thermodynamic characteristics of their binding (the binding constant, the Gibbs energy, enthalpy, entropy and heat capacity effect of binding) have also been determined. It is found that the binding of urea and guanidinium chloride by protein is accompanied by a significant decrease of enthalpy and entropy. At all concentrations of denaturants the enthalpy term slightly dominates the entropy term in the Gibbs energy function. Correlation analysis of the number of binding sites and structural characteristics of these proteins suggests that the binding sites for urea and guanidinium chloride are likely to be formed by several hydrogen bonding groups. This type of binding of the denaturant molecules should lead to a significant restriction of conformational freedom within the polypeptide chain. This raises a doubt as to whether a polypeptide chain in concentrated solutions of denaturants can be considered as a standard of a random coil conformation.     

Water guns affect abundance and behavior of bigheaded carp and native fish differently

Water guns have shown the potential to repel nuisance aquatic organisms. This study examines the effects of exposure to a 1966.4 cm³ seismic water gun array (two guns) on the abundance and behavior of Bighead Carp Hypophthalmichthys nobilis, Silver Carp H. molitrix (collectively referred to as bigheaded carp) and native fishes (e.g., Smallmouth Buffalo Ictiobus bubalus). Water guns were deployed in a channel that connects the Illinois River to backwater quarry pits that contained a large transient population of bigheaded carp. To evaluate the effect of water guns, mobile side-looking split-beam hydroacoustic surveys were conducted before, during and between replicated water gun firing periods. Water guns did not affect abundance of bigheaded carp, but abundance of native fish detected during the firing treatment was 43 and 34% lower than the control and water guns off treatments, respectively. The proximity of bigheaded carp to the water gun array was similar between the water guns on and water guns off treatments. In contrast, the closest detected native fish were detected farther from the water guns during the water guns on treatment (mean ± SE, 32.38 ± 3.32 m) than during the water guns off treatment (15.04 ± 1.59 m). The water gun array had a greater impact on native fish species than on bigheaded carp. Caution should be taken to the extrapolation of these results to other fish species and to fish exposed to water guns in different environments (e.g., reduced shoreline interaction) or exposure to a larger array of water guns, or for use of water guns for purposes other than a barrier.     

Abundance and abundance change in the world's parrots

Estimates of population density and abundance change (differences in density or encounter rates across land uses or time periods) form the cornerstone of much of our knowledge of species' responses to environmental conditions, extinction risks and potential conservation actions. Gathering baseline data on abundance of the world's c. 10 000 bird species and monitoring trends in the light of rapidly changing environmental and harvest pressures is a daunting prospect. With this in mind, we review literature on population densities and abundance changes across habitats in one of the world's largest and most threatened bird families, the parrots (Psittaciformes), to identify gaps in knowledge, model phylogenetic and other influences on abundance, and seek patterns that might guide thinking for data‐deficient taxa and situations. Density estimates were found for only 25% of 356 parrot species. Abundance change data were similarly limited and most came from logged forest, with very few comparisons across different anthropogenic habitats. Threatened species were no more likely to have a density estimate than non‐threatened species, and were less likely to have estimates of abundance change. Exploratory generalized linear mixed models indicated that densities are most influenced by genus, and are generally higher within protected areas than outside. It is unclear whether the latter effect stems from habitat protection, a reduction in poaching or both, but protected areas appear to be beneficial for parrots. Individual members of the ‘parakeet’ genera (e.g. Pyrrhura and Eos) were predictably abundant, whereas within larger‐bodied genera such as Ara (macaws), species were predictably uncommon (< 10 individuals per km²) and there was a long tail of extreme rarity. Responses of parrots to habitat change were highly variable, with natural variation in parrot abundance across different primary forests as great as that between primary forest and human‐altered forests. The speed at which environmental change is affecting the world's parrots far outstrips that of our current capacity to track their abundance and we assess the likely scale of data deficiency in this and other bird groups. Developments in survey and analysis methods such as variants of distance sampling and the integration of niche modelling with point density estimation may increase our effectiveness in monitoring parrots and other important and threatened bird groups.