Role of connexin40 in the autoregulatory response of the afferent arteriole

Connexins in renal arterioles affect autoregulation of arteriolar tonus and renal blood flow and are believed to be involved in the transmission of the tubuloglomerular feedback (TGF) response across the cells of the juxtaglomerular apparatus. Connexin40 (Cx40) also plays a significant role in the regulation of renin secretion. We investigated the effect of deleting the Cx40 gene on autoregulation of afferent arteriolar diameter in response to acute changes in renal perfusion pressure. The experiments were performed using the isolated blood perfused juxtamedullary nephron preparation in kidneys obtained from wild-type or Cx40 knockout mice. Renal perfusion pressure was increased in steps from 75 to 155 mmHg, and the response in afferent arteriolar diameter was measured. Hereafter, a papillectomy was performed to inhibit TGF, and the pressure steps were repeated. Conduction of intercellular Ca(2+) changes in response to local electrical stimulation was examined in isolated interlobular arteries and afferent arterioles from wild-type or Cx40 knockout mice. Cx40 knockout mice had an impaired autoregulatory response to acute changes in renal perfusion pressure compared with wild-type mice. Inhibition of TGF by papillectomy significantly reduced autoregulation of afferent arteriolar diameter in wild-type mice. In Cx40 knockout mice, papillectomy did not affect the autoregulatory response, indicating that these mice have no functional TGF. Also, Cx40 knockout mice showed no conduction of intercellular Ca(2+) changes in response to local electrical stimulation of interlobular arteries, whereas the Ca(2+) response to norepinephrine was unaffected. These results suggest that Cx40 plays a significant role in the renal autoregulatory response of preglomerular resistance vessels.     

Connexin mimetic peptides fail to inhibit vascular conducted calcium responses in renal arterioles

Vascular conducted responses are believed to play a central role in controlling the microcirculatory blood flow. The responses most likely spread through gap junctions in the vascular wall. At present, four different connexins (Cx) have been detected in the renal vasculature, but their role in transmission of conducted vasoconstrictor signals in the preglomerular arterioles is unknown. Connexin mimetic peptides were previously reported to target and inhibit specific connexins. We, therefore, investigated whether conducted vasoconstriction in isolated renal arterioles could be blocked by the use of mimetic peptides directed against one or more connexins. Preglomerular resistance vessels were microdissected from kidneys of Sprague-Dawley rats and loaded with fura 2. The vessels were stimulated locally by applying electrical current through a micropipette, and the conducted calcium response was measured 500 mum from the site of stimulation. Application of connexin mimetic peptides directed against Cx40, 37/43, 45, or a cocktail with equimolar amounts of each, did not inhibit the propagated response, whereas the nonselective gap junction uncoupler carbenoxolone completely abolished the propagated response. However, the connexin mimetic peptides were able to reduce dye coupling between rat aorta endothelial cells shown to express primarily Cx40. In conclusion, we did not observe any attenuating effects on conducted calcium responses in isolated rat interlobular arteries when exposed to connexin mimetic peptides directed against Cx40, 37/43, or 45. Further studies are needed to determine whether conducted vasoconstriction is mediated via previously undescribed pathways.     

TRPM channels are required for rhythmicity in the ultradian defecation rhythm of <Emphasis Type="Italic">C. elegans</Emphasis>

Background  

Ultradian rhythms, rhythms with a period of less than 24 hours, are a widespread and fundamental aspect of life. The mechanisms underlying the control of such rhythms remain only partially understood. Defecation in C. elegans is a very tightly controlled rhythmic process. Underlying the defecation motor programme is an oscillator which functions in the intestinal cells of the animal. This mechanism includes periodic calcium release and subsequent intercellular calcium waves which in turn regulate the muscle contractions that make up the defecation motor programme. Here we investigate the role of TRPM cation channels in this process.     

Comparison of Worm Control Strategies in Grazing Sheep in Denmark

Control of nematode parasites with reduced reliance on the use of anthelmintics was studied in 16 ewes with suckling twin lambs on contaminated pasture in Denmark. Ewes and lambs were treated with albendazole at turn-out 3 May. Ewes were removed from the groups on 26 July, and lambs were slaughtered on 11 October. The animals were allocated to 4 groups of 8 lambs and their 4 ewes. Group TS was treated with albendazole at weeks 3, 6 and 8 after turnout and set-stocked; group TM was similarly treated but moved to clean pasture in conjunction with the last drenching; group US was untreated and set-stocked, and group UM was left untreated but moved to clean pasture week 8 after turn-out. Supplementary feed was offered in June and August due to scarcity of pasture. Strategic treatments of ewes and lambs weeks 3, 6 and 8 after turn-out, with or without a move to clean pasture, were highly effective in controlling nematode infections for most of the season. This was reflected in better weight gains and carcass characteristics in the treated compared to untreated lambs, resulting in an average increase in the value of the product by 36%. The effect of moving without treatment (UM) on faecal egg counts was limited but peak pasture infectivity was reduced to less than 10% compared to the set-stocked group and weight gains of lambs were significantly better despite poor feed availability in late season. The study showed that under set-stocked conditions repeated anthelmintic treatments of both ewes and lambs in early season may ensure sufficient nematode control whereas moving animals to clean pasture without dosing was less efficient. The latter may, however, still be a viable option in organic and other production systems where routine use of anthelmintics is banned, particularly if weaning and moving are combined or a second move is performed.     

Cross‐validation strategies for data with temporal,spatial, hierarchical,or phylogenetic structure

Ecological data often show temporal, spatial, hierarchical (random effects), or phylogenetic structure. Modern statistical approaches are increasingly accounting for such dependencies. However, when performing cross‐validation, these structures are regularly ignored, resulting in serious underestimation of predictive error. One cause for the poor performance of uncorrected (random) cross‐validation, noted often by modellers, are dependence structures in the data that persist as dependence structures in model residuals, violating the assumption of independence. Even more concerning, because often overlooked, is that structured data also provides ample opportunity for overfitting with non‐causal predictors. This problem can persist even if remedies such as autoregressive models, generalized least squares, or mixed models are used. Block cross‐validation, where data are split strategically rather than randomly, can address these issues. However, the blocking strategy must be carefully considered. Blocking in space, time, random effects or phylogenetic distance, while accounting for dependencies in the data, may also unwittingly induce extrapolations by restricting the ranges or combinations of predictor variables available for model training, thus overestimating interpolation errors. On the other hand, deliberate blocking in predictor space may also improve error estimates when extrapolation is the modelling goal. Here, we review the ecological literature on non‐random and blocked cross‐validation approaches. We also provide a series of simulations and case studies, in which we show that, for all instances tested, block cross‐validation is nearly universally more appropriate than random cross‐validation if the goal is predicting to new data or predictor space, or for selecting causal predictors. We recommend that block cross‐validation be used wherever dependence structures exist in a dataset, even if no correlation structure is visible in the fitted model residuals, or if the fitted models account for such correlations.     

<i>In vitro</i> evaluation of antifungal activity of Agave (<i>Agave scabra</i>, Salm Dyck) extracts against post-harvest mushrooms

The agricultural sector, and particularly the horticultural production, has a singular importance in agriculture, considering that it ranks second on agricultural products, nationally and worldwide. Fungal diseases are one of the major causes of vegetable loss during storage, reducing their nutritional value, quality and sale price. Vegetables are usually exposed to diverse treatments with chemical products before storage; as a result, fungal populations develop an increased resistance over time becoming more difficult to control. Because of this, research efforts toward finding more suitable chemicals to control fungal diseases are needed. Natural extracts may be an alternative solve this problem. In the present investigation the fungicidal activity of aqueous and ethanol extracts of Agave scabra was evaluated on the growth of Botrytis cinerea, Mucor sp., Aspergillus niger, Fusarium sp. and Penicillium sp., whose strains were isolated from potato and tomato. To assess their effects, the agar-dilution and agar-well techniques were performed. The ethanol extract was more effective against Botrytis cinerea and Mucor sp. when the agar-well method was used. However, when using the agar-dilution method the ethanol extract of Agave scabra inhibited the growth of Botrytis cinerea, Mucor sp. and Penicillium sp.     

The mycoflora and toxicity of feedstuffs from a production plant in córdoba, Argentina

Feedstuffs used for poultry nutrition in Argentina were analyzed for fungal flora and natural incidence of mycotoxins. Survey of 120 samples of poultry feeds, taken from May 1998 to April 1999, showed the presence of 15 genera of filamentous fungi. The predominant genera wereFusarium spp. andPenicillium ssp., isolated in 67.5 % of the samples, followed byAspergillus spp. (57.5 %). Yeast, were significantly isolated from most of the samples. Species identification was carried down for the toxigenic genera. Fungal total counts of poultry feeds ranged from 2.0 × 10³ to 3.0 × 10⁵ CFU g^-1 The fungal total counts during two months of sampling, were slightly over the limit value of 1 × 105 CFU g^-1, which ensure the hygienic quality of the feed. Potentially toxicogenic species presented moderate mean colony counts. Many of the fungi isolated from poultry feeds are mycotoxin producers. Fumonisins had the highest incidence, and were found in 97 % of the analyzed samples followed by aflatoxin B₁ (46 %), zearalenone (18 %) and deoxynivalenol (6 %). On the co-occurrence of both carcinogenic mycotoxins, all of the FBs contaminated feed samples were co-contaminated with AFB₁. The results show the relevance of the samples screening for viable fungi propagules and the surveillance of their associated mycotoxins in poultry feeds.