Renal nerves and nNOS: roles in natriuresis of acute isovolumetric sodium loading in conscious rats

It was hypothesized that renal sympathetic nerve activity (RSNA) and neuronal nitric oxide synthase (nNOS) are involved in the acute inhibition of renin secretion and the natriuresis following slow NaCl loading (NaLoad) and that RSNA participates in the regulation of arterial blood pressure (MABP). This was tested by NaLoad after chronic renal denervation with and without inhibition of nNOS by S-methyl-thiocitrulline (SMTC). In addition, the acute effects of renal denervation on MABP and sodium balance were assessed. Rats were investigated in the conscious, catheterized state, in metabolic cages, and acutely during anesthesia. NaLoad was performed over 2 h by intravenous infusion of hypertonic solution (50 micromol.min(-1).kg body mass(-1)) at constant body volume conditions. SMTC was coinfused in amounts (20 microg.min(-1).kg(-1)) reported to selectively inhibit nNOS. Directly measured MABPs of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P < 0.005). Plasma renin concentration (PRC) was reduced by renal denervation (14.5 +/- 0.2 vs. 19.3 +/- 1.3 mIU/l, P < 0.005) and by nNOS inhibition (12.4 +/- 2.3 vs. 19.6 +/- 1.6 mlU/l, P < 0.005). NaLoad reduced PRC (P < 0.05) and elevated MABP modestly (P < 0.05) and increased sodium excretion six-fold, irrespective of renal denervation and SMTC. The metabolic data demonstrated that renal denervation lowered sodium balance during the first days after denervation (P < 0.001). These data show that renal denervation decreases MABP and renin secretion. However, neither renal denervation nor nNOS inhibition affects either the renin down-regulation or the natriuretic response to acute sodium loading. Acute sodium-driven renin regulation seems independent of RSNA and nNOS under the present conditions.     

Assessing the agronomic and environmental effects of the application of cattle manure compost on soil by multivariate methods

Multivariate analysis was used for interpreting data from a pot experiment using samples of three Spanish soils. Samples of soil fertilized with compost were compared with untreated control samples. We also compared the effect of adding the compost to soil with a controlled moisture content of 50% of its water holding capacity (WHC), and to a near-saturated soil (95% WHC). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) were used; they perfectly differentiated sample groups both as a function of the treatment applied and by sampling date. The compost samples were characterized by higher pH, electrical conductivity (EC), organic matter (OM) content and cation exchange capacity (CEC), together with nutrient concentrations than the control pots. The pots with a soil–compost mixture at 95% WHC presented lower values of EC, CEC, inorganic N, K, Na and B than the mixtures at 50% WHC. Multivariate methods may therefore be useful for the analysis and interpretation of a large number of data in soil research.     

Discovery of novel 4-amino-6-arylaminopyrimidine-5-carbaldehyde oximes as dual inhibitors of EGFR and ErbB-2 protein tyrosine kinases

We herein disclose a novel series of 4-aminopyrimidine-5-carbaldehyde oximes that are potent and selective inhibitors of both EGFR and ErbB-2 tyrosine kinases, with IC(50) values in the nanomolar range. Structure-activity relationship (SAR) studies elucidated a critical role for the 4-amino and C-6 arylamino moieties. The X-ray co-crystal structure of EGFR with 37 was determined and validated our design rationale.     

The American brine shrimp as an exotic invasive species in the western Mediterranean

The hypersaline environments and salterns present in the western Mediterranean region (including Italy, southern France, the Iberian Peninsula and Morocco) contain autochthonous forms of the brine shrimp Artemia, with parthenogenetic diploid and tetraploid strains coexisting with the bisexual species A. salina. Introduced populations of the American brine shrimp A. franciscana have also been recorded in these Mediterranean environments since the 1980s. Based on brine shrimp cyst samples collected in these countries from 1980 until 2002, we were able to establish the present distribution of autochthonous brine shrimps and of A. franciscana, which is shown to be an expanding invasive species. The results obtained show that A. franciscana is now the dominant Artemia species in Portuguese salterns, along the French Mediterranean coast and in Cadiz bay (Spain). Co-occurrence of autochthonous (parthenogenetic) and American brine shrimp populations was observed in Morocco (Mar Chica) and France (Aigues Mortes), whereas A. franciscana was not found in Italian cyst samples. The results suggest these exotic A. franciscana populations originate as intentional or non-intentional inoculations through aquacultural (hatchery effluents) or pet market activities, and suggest that the native species can be rapidly replaced by the exotic species. This revised version was published online in July 2006 with corrections to the Cover Date.     

Sex, secondary compounds and asymmetry. Effects on plant–herbivore interaction in a dioecious shrub

We analysed the links between herbivory, anthraquinone content and developmental instability of leaves in Rhamnus alpinus, taking into account possible effects of sexual dimorphism. The amount of leaf loss caused by herbivores averaged 3%, rarely exceeding 25%. Leaf losses were evenly distributed in the shrubs, with highest variability among leaves of the same shoot, thus hiding possible shrub, sex or population effects. This pattern of herbivory implies a shifting of caterpillars from one leaf to another before consuming all readily available material. We suggest that this behaviour might be triggered by a short-term change in leaf palatability by means of an increase in the production of secondary compounds. Supporting this hypothesis, we have found a higher anthraquinone content in damaged leaves compared with undamaged ones. The leaves of male plants exhibited a higher concentration of anthraquinones than those of females, which contrasts with classic hypotheses. We relate this to the lower rate of biomass increase in males, which should allow them to allocate more resources to defence. Leaves showed fluctuating asymmetry (FA), but we did not find any relationship between the degree of asymmetry and sex, herbivory or anthraquinone content at any level considered. Therefore, FA cannot be considered as an indicator of susceptibility to damage by herbivores or of the ability to induce the production of defensive compounds in R. alpinus.     

Air- and Dustborne Mycoflora in Houses Free of Water Damage and Fungal Growth

Typically, studies on indoor fungal growth in buildings focus on structures with known or suspected water damage, moisture, and/or indoor fungal growth problems. Reference information on types of culturable fungi and total fungal levels are generally not available for buildings without these problems. This study assessed 50 detached single-family homes in metropolitan Atlanta, Ga., to establish a baseline of “normal and typical” types and concentrations of airborne and dustborne fungi in urban homes which were predetermined not to have noteworthy moisture problems or indoor fungal growth. Each home was visually examined, and samples of indoor and outdoor air and of indoor settled dust were taken in winter and summer. The results showed that rankings by prevalence and abundance of the types of airborne and dustborne fungi did not differ from winter to summer, nor did these rankings differ when air samples taken indoors were compared with those taken outdoors. Water indicator fungi were essentially absent from both air and dust samples. The air and dust data sets were also examined specifically for the proportions of colonies from ecological groupings such as leaf surface fungi and soil fungi. In the analysis of dust for culturable fungal colonies, leaf surface fungi constituted a considerable portion (>20%) of the total colonies in at least 85% of the samples. Thus, replicate dust samples with less than 20% of colonies from leaf surface fungi are unlikely to be from buildings free of moisture or mold growth problems.     

The relationship between habitat permanence and larval development in California spadefoot toads: field and laboratory comparisons of developmental plasticity

We evaluated differences in larval habitats and life history of three species of spadefoot toads, then compared their life histories in a common garden study. Our field work defined the selective regime encountered by each species. Our Great Basin spadefoot (Spea intermontana) bred asynchronously in permanent streams and springs where there was no risk of larval mortality due to drying. The water chemistry remained fairly stable throughout the larval period. The western spadefoot toad, Sp. hammondii, bred fairly synchronously following heavy spring rains in temporary pools that remained filled an average of 81 d. Fifteen % of the breeding pools dried completely on or before the day the first larvae metamorphosed. The desert spadefoot toad, Scaphiopus couchii, bred synchronously after heavy summer showers in very short duration pools; 62% of the breeding pools dried completely on or before the day the first larvae metamorphosed. The concentration of ammonium nitrogen and CaCO₃ increased markedly as the Sp. hammondii and S. couchii pools dried. S. couchii attained metamorphosis at a much earlier age and smaller size than the other two species. S. couchii also showed little variation in the age at metamorphosis but considerable variation in the size at metamorphosis, while the other two species varied in both age and size. The results identify some variables that could serve as cues of pool drying and demonstrate an association between breeding pool duration, breeding synchrony, development rate, and larval development. Our laboratory study yields information about the genetic basis of the differences in development and controlled comparisons of phenotypic plasticity. We manipulated food supply to study the plastic response of age and size at metamorphosis and hence construct the reaction norm for these variables as a function of growth rate. The growth rates ranged from below to above those observed in natural populations. As in the field, in the lab S. couchii attained metamorphosis at an earlier age and smaller size than the other two species. All three species had a similarly shaped reaction norm for size(y‐axis) and age (x‐axis) at metamorphosis, which was a concave upward curve. A consequence of this shape is that age at metamorphosis changes more readily at low levels of food availability and size at metamorphosis changes more readily at high levels of food availability. If we restrict our observations to just those growth rates that are seen in nature, then S. couchii has almost no variation in the age at metamorphosis but considerable variation in size at metamorphosis, while the other two species vary in both age and size at metamorphosis. All three species increased in size at metamorphosis with increased food levels. Our comparative reaction norm approach thus demonstrates that S. couchii has adapted to ephemeral environments by shifting its growth rate reaction norm so that age at metamorphosis is uniformly fast and is not associated with growth rate. The realized variation is concentrated in size rather than age at metamorphosis.     

Association analysis of vitamin D receptor gene polymorphisms with bone mineral density in young women with Graves' disease

Graves' (GD) hyperthyroidism induces accelerated bone turnover that leads to decreased bone mineral density (BMD). The role of the VDR gene in predisposition to primary osteoporosis has been recognized. Recent studies show associations between the VDR gene polymorphisms and susceptibility to autoimmune diseases. Here we analyzed if VDR gene polymorphisms: BsmI, ApaI, TaqI, and FokI may predispose women with Graves' hyperthyroidism to BMD reduction or to disease development. The subjects were 75 premenopausal female Polish patients with GD and 163 healthy women. The genotyping was performed by the use of the restriction fragment length polymorphism analysis (RFLP). We studied the association of the VDR polymorphisms and their haplotypes with patients' BMD and also SNPs and haplotypes association with Graves' disease. We found a strong linkage disequilibrium for the BsmI, ApaI, and TaqI polymorphims that formed three most frequent haplotypes in Graves' women: baT (47.9%), BAt (34.9%), and bAT (16.4%). We did not show statistically significant association of analyzed VDR polymorphisms or haplotypes with decreased bone mineral density in Graves' patients. However, the presence of F allele had a weak tendency to be associated with Graves' disease (with OR=1.93; 95% CI: 0.97-3.84; p=0.058). In conclusion: VDR gene polymorphisms do not predict the risk of decreased BMD in Polish women with Graves'. It may be speculated that the F allele carriers of the VDR-FokI polymorphism are predisposed to Graves' disease development.     

Influence of phosphorohydrazone derivatives of benzopyrones on polymerization and viscosity of fibrin

The synthesis and antitumour and antibacterial activity of coumarin and chromone phosphorohydrazones have been reported. This study describes influence of phosphorohydrazones derivatives of coumarin and chromone on the polymerization and viscosity of fibrin. The fibrin polymerization assay was performed by the Shen and Lorand method and the clot viscosity was measured on the basis of Shen and Lorand and Marchi and coworkers methods. Among the eight compounds tested, one coumarin derivative and two chromone derivatives showed significant activity.