The preconditioning response conferred by a mild uncoupling of the mitochondrial membrane potential (Δψm) has been attributed to altered reactive oxygen species (ROS) production and mitochondrial Ca2 + uptake within the cells. Here we have explored if altered cellular energetics in response to a mild mitochondrial uncoupling stimulus may also contribute to the protection. The addition of 100 nM FCCP for 30 min to cerebellar granule neurons (CGNs) induced a transient depolarization of the Δψm, that was sufficient to significantly reduce CGN vulnerability to the excitotoxic stimulus, glutamate. On investigation, the mild mitochondrial ‘uncoupling’ stimulus resulted in a significant increase in the plasma membrane levels of the glucose transporter isoform 3, with a hyperpolarisation of Δψm and increased cellular ATP levels also evident following the washout of FCCP. Furthermore, the phosphorylation state of AMP-activated protein kinase (AMPK) (Thr 172) was increased within 5 min of the uncoupling stimulus and elevated up to 1 h after washout. Significantly, the physiological changes and protection evident after the mild uncoupling stimulus were lost in CGNs when AMPK activity was inhibited. This study identifies an additional mechanism through which protection is mediated upon mild mitochondrial uncoupling: it implicates increased AMPK signalling and an adaptive shift in energy metabolism as mediators of the preconditioning response associated with FCCP-induced mild mitochondrial uncoupling. 相似文献
In this review, we address the regulatory and toxic role of ·NO along several pathways, from the gut to the brain. Initially, we address the role on ·NO in the regulation of mitochondrial respiration with emphasis on the possible contribution to Parkinson’s disease via mechanisms that involve its interaction with a major dopamine metabolite, DOPAC. In parallel with initial discoveries of the inhibition of mitochondrial respiration by ·NO, it became clear the potential for toxic ·NO-mediated mechanisms involving the production of more reactive species and the post-translational modification of mitochondrial proteins. Accordingly, we have proposed a novel mechanism potentially leading to dopaminergic cell death, providing evidence that NO synergistically interact with DOPAC in promoting cell death via mechanisms that involve GSH depletion. The modulatory role of NO will be then briefly discussed as a master regulator on brain energy metabolism. The energy metabolism in the brain is central to the understanding of brain function and disease. The core role of ·NO in the regulation of brain metabolism and vascular responses is further substantiated by discussing its role as a mediator of neurovascular coupling, the increase in local microvessels blood flow in response to spatially restricted increase of neuronal activity. The many facets of NO as intracellular and intercellular messenger, conveying information associated with its spatial and temporal concentration dynamics, involve not only the discussion of its reactions and potential targets on a defined biological environment but also the regulation of its synthesis by the family of nitric oxide synthases. More recently, a novel pathway, out of control of NOS, has been the subject of a great deal of controversy, the nitrate:nitrite:NO pathway, adding new perspectives to ·NO biology. Thus, finally, this novel pathway will be addressed in connection with nitrate consumption in the diet and the beneficial effects of protein nitration by reactive nitrogen species.
Aim It is a central issue in ecology and biogeography to understand what governs community assembly and the maintenance of biodiversity in tropical rain forest ecosystems. A key question is the relative importance of environmental species sorting (niche assembly) and dispersal limitation (dispersal assembly), which we investigate using a large dataset from diverse palm communities. Location Lowland rain forest, western Amazon River Basin, Peru. Methods We inventoried palm communities, registering all palm individuals and recording environmental conditions in 149 transects of 5 m × 500 m. We used ordination, Mantel tests and indicator species analysis (ISA) to assess compositional patterns, species responses to geographical location and environmental factors. Mantel tests were used to assess the relative importance of geographical distance (as a proxy for dispersal limitation) and environmental differences as possible drivers of dissimilarity in palm species composition. We repeated the Mantel tests for subsets of species that differ in traits of likely importance for habitat specialization and dispersal (height and range size). Results We found a strong relationship between compositional dissimilarity and environmental distance and a weaker but also significant relationship between compositional dissimilarity and geographical distance. Consistent with expectations, relationships with environmental and geographical distance were stronger for understorey species than for canopy species. Geographical distance had a higher correlation with compositional dissimilarity for small‐ranged species compared with large‐ranged species, whereas the opposite was true for environmental distance. The main environmental correlates were inundation and soil nutrient levels. Main conclusions The assembly of palm communities in the western Amazon appears to be driven primarily by species sorting according to hydrology and soil, but with dispersal limitation also playing an important role. The importance of environmental characteristics and geographical distance varies depending on plant height and geographical range size in agreement with functional predictions, increasing our confidence in the inferred assembly mechanisms. 相似文献
The contents of endogenous free and conjugated polyamines, putrescine (Put) and spermidine (Spd), were determined during 9
week of vernalization (at 5 °C) in winter wheat seedlings cultivated on Murashige and Skoog media without (MS0) and with 2
mg dm−3 zearalenone (MSZEN). At the 4th week of chilling treatment, which is sufficient to induce generative development in 30 % of plants, the marked increase in
free and conjugated forms of Put and free Spd were observed. The presence of ZEN in medium significantly accelerated the vernalization.
About 20 % of plants treated with ZEN flowered already after 2 weeks and 40 % after 3 weeks of chilling. Significantly higher
content of free Put was determined in roots grown on MSZEN compared with MS0 during the first 5 weeks of vernalization with
maximum at the 4th week. After germination, a marked decrease in free Spd content was observed both in plants grown on MS0 and MSZEN. Application
of ZEN significantly slowed down the Spd decline in leaves and roots during the first and second week of vernalization. The
content of Spd and its conjugates decreased in vernalized plants after 1 week of cultivation at 20 °C. 相似文献
The thrombopoietic serum activity was examined in rats during thrombocytopenia produced by bleeding or after treatment with antithrombocyte serum (ATS). 6 hours after both treatments the thrombopoietic activity of the serum, i.e. its content of thrombopoietin, is increased. After the ATS treatment of nephrectomized animals a similar increase of thrombopoietic activity as in normal animals could be achieved. In contrast to that, no similar increase of thrombopoietic activity was observed in nephrectomized animals after blood loss. According to the results of the authors the increase of thrombopoietic activity produced by different stimuli can be attributed to different mechanisms. 相似文献
Lactate esters are widely used as food additives, perfume materials, medicine additives, and personal care products. The objective
of this work was to investigate the effect of a series of lactate esters as penetration enhancers on the in vitro skin permeation of four drugs with different physicochemical properties, including ibuprofen, salicylic acid, dexamethasone
and 5-fluorouracil. The saturated donor solutions of the evaluated drugs in propylene glycol were used in order to keep a
constant driving force with maximum thermodynamic activity. The permeability coefficient (Kp), skin concentration of drugs (SC), and lag time (T), as well as the enhancement ratios for Kp and SC were recorded. All results indicated that lactate esters can exert a significant influence on the transdermal delivery
of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement
effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10–12 are more
effective enhancers. Furthermore, the enhancement effect of lactate esters increases with a decrease of the drug lipophilicity,
which suggests that they may be more efficient at enhancing the penetration of hydrophilic drugs than lipophilic drugs. The
influence of the concentration of lactate esters was evaluated and the optimal concentration is in the range of 5∼10 wt.%.
In sum, lactate esters as a penetration enhancer for some drugs are of interest for transdermal administration when the safety
of penetration enhancers is a prime consideration. 相似文献
There is a long tradition of software simulations in theoretical biology to complement pure analytical mathematics which are
often limited to reproduce and understand the self-organization phenomena resulting from the non-linear and spatially grounded
interactions of the huge number of diverse biological objects. Since John Von Neumann and Alan Turing pioneering works on
self-replication and morphogenesis, proponents of artificial life have chosen to resolutely neglecting a lot of materialistic
and quantitative information deemed not indispensable and have focused on the rule-based mechanisms making life possible,
supposedly neutral with respect to their underlying material embodiment. Minimal life begins at the intersection of a series
of processes which need to be isolated, differentiated and duplicated as such in computers. Only software developments and
running make possible to understand the way these processes are intimately interconnected in order for life to appear at the
crossroad. In this paper, I will attempt to set out the history of life as the disciples of artificial life understand it,
by placing these different lessons on a temporal and causal axis, showing which one is indispensable to the appearance of
the next and how does it connect to the next. I will discuss the task of artificial life as setting up experimental software
platforms where these different lessons, whether taken in isolation or together, are tested, simulated, and, more systematically,
analyzed. I will sketch some of these existing software platforms: chemical reaction networks, Varela’s autopoietic cellular
automata, Ganti’s chemoton model, whose running delivers interesting take home messages to open-minded biologists. 相似文献
Changes in the duration and size of the vulnerable period of the myocardium in the presence of respiratory changes were studied in acute experiments on rats. The limits of the vulnerable period were determined by directly stimulating the heart during ventilation via the enlarged respiratory dead space, during hyperventilation and during heart failure. In the control group (normal ventilation without enlargement of the dead space), the vulnerable period lasted 5.7 +/- 0.76 ms. During ventilation via the enlarged dead space, hypercapnic hypoxaemia developed and the vulnerable period was markedly prolonged (18.55 +/- 5.29 ms) by a shift of its inner limit to the left. Hyperventilation caused normoxic to hyperoxic hypocapnia and markedly reduced the duration of the vulnerable period (8.17 +/- 2.21 and 9.31 +/- 2.38 ms respectively). The vulnerable period lengthened the most in heart failure (25.46 +/- 3.93), mainly as a result of a shift of its outer limit. In all the experimental groups there was a shift of the vulnerable period to the right, which was fastest in hypercapnic hypoxaemia and slowest in hyperoxic hypocapnia. The administration of Inderal (3 mg/kg i.p.) or Arfonad (50 mg/kg i.p.) markedly shortened the vulnerable period during hypercapnic hypoxaemia (9.87 +/- 2.78 and 9.32 +/- 2.16 ms respectively), but did not block the shift. Lengthening of the vulnerable period during hypercapnic hypoxaemia was probably due to activation of sympathetic nerves via beta-adrenergic receptors. 相似文献