Upstream Regulators and Downstream Effectors of NADPH Oxidases as Novel Therapeutic Targets for Diabetic Kidney Disease

Oxidative stress has been linked to the pathogenesis of diabetic nephropathy, the complication of diabetes in the kidney. NADPH oxidases of the Nox family, and in particular the homologue Nox4, are a major source of reactive oxygen species in the diabetic kidney and are critical mediators of redox signaling in glomerular and tubulointerstitial cells exposed to the diabetic milieu. Here, we present an overview of the current knowledge related to the understanding of the role of Nox enzymes in the processes that control mesangial cell, podocyte and tubulointerstitial cell injury induced by hyperglycemia and other predominant factors enhanced in the diabetic milieu, including the renin-angiotensin system and transforming growth factor-β. The nature of the upstream modulators of Nox enzymes as well as the downstream targets of the Nox NADPH oxidases implicated in the propagation of the redox processes that alter renal biology in diabetes will be highlighted.     

Stress integrated tests and cytological analyses reveal Brassica villosa subsp. drepanensis seed quality decrease upon long-term storage

Under stress integrated germination test (SIGT), seeds undergo osmo-saline stresses, which enable to detect differences in vigour of long-term stored seeds with high germination percentage (G%). The quality of Brassica villosa subsp. drepanensis seeds stored in a genebank (at ? 20°C for 16 years) was compared with seeds at harvest by standard germination tests (GT), SIGT and cytogenetic analysis. No differences were detected in G% and mean germination time under GT. Conversely, SIGT performed with NaCl ? 0.9 MPa osmotic potential did not influence G% at harvest but reduced that of stored seeds, SIGT at ? 1.4 MPa reduced G% of both. Cytogenetic analysis showed reduction of mitotic index, appearance of chromosomal aberrations and smaller nucleoli in stored seeds compared with harvest seeds germinated in water. SIGT at ? 0.9 MPa had no effect on mitotic index, but increased chromosome aberrations and nucleoli number. SIGT at ? 1.4 MPa inhibited G% of harvest and stored seeds, reduced mitoses in harvest and completely prevented it in stored seeds. The results indicate that GT does not faithfully reflect the quality of stored seeds, with misinterpretation of their vigour, whereas SIGT and cytogenetical parameters are sensitive, reliable and inexpensive methods for early prediction of genetic erosion in germplasm banks.     

Ichtyotoxic activity of extracts from Mexican marine macroalgae

Seventy-three species of macroalgae from the Mexican Pacific, Atlantic and Caribbean coast were screened for ichtyotoxic activity. Ethanolic, acetonic and aqueous extracts were prepared and tested against the fish Carassius auratus. The extracts were classified on the basis of their effects as: toxic if the fish died in two hours or less; moderately toxic, if the organism behaved abnormally but death did notoccur, and non-toxic if the fish did not display any change. 79% species were ichtyotoxic to some degree. Extracts of 39 species were toxic, with at least one extract with lethal effects, 19 were moderately toxic and 15 species were non-toxic. Only the extracts ofDictyota bartayresiana, Dictyota cervicornis,Lobophora variegata, Bryothamnion triquetrum and Laurencia obtusa were toxic in all three solvents. The acetone and ethanol extracts were more active, and therefore are more suitable for extraction of toxic substances. This revised version was published online in August 2006 with corrections to the Cover Date.     

Ability of predatory native Australian fishes to learn to avoid toxic larvae of the introduced toad Bufo marinus

Of two native Australian fishes naïve to the introduced toad Bufo marinus most barramundi Lates calcarifer rapidly learned to avoid B. marinus tadpoles, while sooty grunter Hephaestus fuliginosus exhibited considerable intraspecific variation in their learning ability. Some sooty grunter learned to avoid tadpoles after only a few attacks, while other individuals continued to attack and reject tadpoles throughout the entire laboratory trials. Individuals of both species recognized and avoided tadpoles 1 day after their previous encounter. None of the fishes died during the trials. The observed variation in behavioural responses of fishes to B. marinus may be due to differences in (1) learning ability, (2) fish hunger levels, and or (3) tadpole palatability and toxicity. The results demonstrate that most barramundi and sooty grunter learn to avoid B. marinus tadpoles with minimal trauma. Consequently, it is anticipated that the toads are unlikely to have a significant negative impact on wild populations of these fishes through direct toxic effects.     

A comparison of ferric-chelate reductase and chlorophyll and growth ratios as indices of selection of quince,pear and olive genotypes under iron deficiency stress

Quince (Cydonia oblonga Mill.), pear (Pyrus communis L.) and olive (Olea europaea L.) genotypes were evaluated for their tolerance to iron deficiency stress by growing young plants in three types of aerated nutrient solutions: (1) with iron, (2) without iron or (3) low in iron and with 10 mM bicarbonate. Plants were obtained either from rooted softwood cuttings or from germination of seeds. The degree of tolerance was evaluated with several indices: (1) the chlorophyll content, (2) the root Fe³⁺ reducing capacity and (3) the whole plant relative growth. Fifteen hours before Fe³⁺ reducing capacity determination, iron was applied to the roots of plants with iron-stress, since this method resulted in increasing the reductase activity. All quince and pear genotypes increased the root Fe³⁺ reducing capacity when grown in the treatments for iron-stress, in relation to control plants of the same genotypes. In olive cultivars, the Fe³⁺ reducing capacity was lower in the iron-stress treatments than in the control one. Studying the relationship between relative growth and chlorophyll content for each genotype under iron-stress, in relation to both indices in control plants, a classification of species and genotypes was established. According to that, most olive cultivars and some pear rootstocks and cultivars appear more iron-efficient than quince rootstocks. Our study shows that in some woody species, determining root Fe³⁺ reducing capacity is not the best method to establish tolerance to iron deficiency stress.     

Fluid shear stress regulates HepG2 cell migration though time-dependent integrin signaling cascade

Hepatocellular carcinoma (HCC) is a subtype of malignant liver cancer with poor prognosis and limited treatment options. It is noteworthy that mechanical forces in tumor microenvironment play a pivotal role in mediating the behaviors and functions of tumor cells. As an instrumental type of mechanical forces in vivo, fluid shear stress (FSS) has been reported having potent physiologic and pathologic effects on cancer progression. However, the time-dependent mechanochemical transduction in HCC induced by FSS remains unclear. In this study, hepatocellular carcinoma HepG2 cells were exposed to 1.4 dyn/cm² FSS for transient duration (15s and 30s), short duration (5 min, 15 min and 30 min) and long duration (1h, 2h and 4h), respectively. The expression and translocation of Integrins induced FAK-Rho GTPases signaling events were examined. Our results showed that FSS endowed HepG2 cells with higher migration ability via reorganizing cellular F-actin and disrupting intercellular tight junctions. We further demonstrated that FSS regulated the expression and translocation of Integrins and their downstream signaling cascade in time-dependent patterns. The FSS downregulated focal adhesion components (Paxillin, Vinculin and Talin) while upregulated the expression of Rho GTPases (Cdc42, Rac1 and RhoA) in long durations. These results indicated that FSS enhanced tumor cell migration through Integrins-FAK-Rho GTPases signaling pathway in time-dependent manners. Our in vitro findings shed new light on the role of FSS acting in physiologic and pathological processes during tumor progression, which has emerged as a promising clinical strategy for liver carcinoma.     

Hyperthermia Induces the Synthesis of a Heat Shock Protein by Polysomes Isolated from the Fetal and Neonatal Mammalian Brain

Abstract: Analysis of the cell-free translation products of polysomes isolated from fetal brain and other organs indicates that elevation of maternal body temperature induces the synthesis of a heat shock protein of molecular weight 74,000 (74K). The newborn mammal is particularly sensitive to induction of the 74K protein. As early postnatal development proceeds, higher body temperatures are required to induce synthesis of the 74K heat shock protein.     

Co‐occurrence patterns of trees along macro‐climatic gradients and their potential influence on the present and future distribution of Fagus sylvatica L.

Aim During recent and future climate change, shifts in large‐scale species ranges are expected due to the hypothesized major role of climatic factors in regulating species distributions. The stress‐gradient hypothesis suggests that biotic interactions may act as major constraints on species distributions under more favourable growing conditions, while climatic constraints may dominate under unfavourable conditions. We tested this hypothesis for one focal tree species having three major competitors using broad‐scale environmental data. We evaluated the variation of species co‐occurrence patterns in climate space and estimated the influence of these patterns on the distribution of the focal species for current and projected future climates. Location Europe. Methods We used ICP Forest Level 1 data as well as climatic, topographic and edaphic variables. First, correlations between the relative abundance of European beech (Fagus sylvatica) and three major competitor species (Picea abies, Pinus sylvestris and Quercus robur) were analysed in environmental space, and then projected to geographic space. Second, a sensitivity analysis was performed using generalized additive models (GAM) to evaluate where and how much the predicted F. sylvatica distribution varied under current and future climates if potential competitor species were included or excluded. We evaluated if these areas coincide with current species co‐occurrence patterns. Results Correlation analyses supported the stress‐gradient hypothesis: towards favourable growing conditions of F. sylvatica, its abundance was strongly linked to the abundance of its competitors, while this link weakened towards unfavourable growing conditions, with stronger correlations in the south and at low elevations than in the north and at high elevations. The sensitivity analysis showed a potential spatial segregation of species with changing climate and a pronounced shift of zones where co‐occurrence patterns may play a major role. Main conclusions Our results demonstrate the importance of species co‐occurrence patterns for calibrating improved species distribution models for use in projections of climate effects. The correlation approach is able to localize European areas where inclusion of biotic predictors is effective. The climate‐induced spatial segregation of the major tree species could have ecological and economic consequences.     

Effects of ship‐induced waves on littoral benthic invertebrates

1. Ship‐induced waves can affect the physical characteristics of lake and river shorelines, and laboratory studies have shown effects on littoral invertebrates. Here, we explored whether these effects could be observed under field conditions along a natural lake shore affected by wave sequences (trains) produced by boats. 2. Individuals of five invertebrate species (Bithynia tentaculata, Calopteryx splendens, Dikerogammarus villosus, Gammarus roeselii, Laccophilus hyalinus) were exposed to waves with increasing shear stress in five habitats differing in structural complexity. 3. Detachment of invertebrates increased with increasing shear stress and was best modelled using sigmoid response curves. Habitat structural complexity mitigated the effects of shear stress, and detachment rate was influenced more by habitat type than by species. A threshold (90% of the individual invertebrates unaffected) stress level of 0.64 N m^?2 was found for a structurally complex reed habitat, compared to 0.37 N m^?2 for a simple sand habitat. 4. Shear stress associated with wave trains created by recreational boating at a distance of 35 m from the shore and at a speed of 11 km h^?1 resulted in 45% detachment of littoral invertebrates. Decreasing the boat‐to‐shore distance to 20 m increased wave shear stress by 30% and invertebrate detachments up to 75%. 5. Disturbance of littoral habitats and invertebrate assemblages are widespread in inland waters used for recreational and/or commercial navigation. Our findings show that the integrity of littoral zones of navigable surface waters could be much improved by implementing management measures such as physically protecting complex habitats with dense reed belts and tree roots, and reducing boat speeds and increasing their minimum shoreline distance.