Hepcidin, interleukin-6 and hematological iron markers in males before and after heart surgery

Anemia of inflammation in patients with acute or chronic acute-phase activation is a common clinical problem. Hepcidin is a peptide shown to be the principal regulator of the absorption and systemic distribution of iron. Main inducers of hepcidin are iron overload, hypoxia and inflammation, where the latter has been linked to hepcidin via increased interleukin-6 (IL-6). This article addresses the impact and time course of postoperative acute-phase reaction in humans following heart surgery on prohepcidin, hepcidin, hematological markers and IL-6 concentrations. Serum concentrations of prohepcidin, hepcidin, IL-6 and hematological iron parameters were studied in five male patients without infection before and after heart surgery. This study, which is the first to report the impact on serum hepcidin and serum prohepcidin concentrations in patients following surgery, clearly demonstrates the induction of hypoferremia due to the postoperative acute-phase reaction. Significant changes were seen for serum iron concentration, transferrin saturation, total iron binding capacity and hemoglobin concentration. A significant increase in ferritin concentration was seen 96-144 h postoperatively. Additionally, there were significant alterations in both serum hepcidin after 96-144 h and serum prohepcidin after 48 h compared with preoperative values. Serum prohepcidin decreased, whereas serum hepcidin increased. In conclusion, changes in serum prohepcidin were followed by an increase in serum hepcidin. This speaks in favor of a chain of action where proteolytic trimming of serum prohepcidin results in increased serum hepcidin. However, hypoferremia appeared prior to the changes in serum prohepcidin and serum hepcidin.     

Phenomics: the next challenge

A key goal of biology is to understand phenotypic characteristics, such as health, disease and evolutionary fitness. Phenotypic variation is produced through a complex web of interactions between genotype and environment, and such a 'genotype-phenotype' map is inaccessible without the detailed phenotypic data that allow these interactions to be studied. Despite this need, our ability to characterize phenomes - the full set of phenotypes of an individual - lags behind our ability to characterize genomes. Phenomics should be recognized and pursued as an independent discipline to enable the development and adoption of high-throughput and high-dimensional phenotyping.     

Carotenoid dynamics in Atlantic salmon

Background  

Carotenoids are pigment molecules produced mainly in plants and heavily exploited by a wide range of organisms higher up in the food-chain. The fundamental processes regulating how carotenoids are absorbed and metabolized in vertebrates are still not fully understood. We try to further this understanding here by presenting a dynamic ODE (ordinary differential equation) model to describe and analyse the uptake, deposition, and utilization of a carotenoid at the whole-organism level. The model focuses on the pigment astaxanthin in Atlantic salmon because of the commercial importance of understanding carotenoid dynamics in this species, and because deposition of carotenoids in the flesh is likely to play an important life history role in anadromous salmonids.     

Catalase and NO CATALASE ACTIVITY1 Promote Autophagy-Dependent Cell Death in Arabidopsis

Programmed cell death often depends on generation of reactive oxygen species, which can be detoxified by antioxidative enzymes, including catalases. We previously isolated catalase-deficient mutants (cat2) in a screen for resistance to hydroxyurea-induced cell death. Here, we identify an Arabidopsis thaliana hydroxyurea-resistant autophagy mutant, atg2, which also shows reduced sensitivity to cell death triggered by the bacterial effector avrRpm1. To test if catalase deficiency likewise affected both hydroxyurea and avrRpm1 sensitivity, we selected mutants with extremely low catalase activities and showed that they carried mutations in a gene that we named NO CATALASE ACTIVITY1 (NCA1). nca1 mutants showed severely reduced activities of all three catalase isoforms in Arabidopsis, and loss of NCA1 function led to strong suppression of RPM1-triggered cell death. Basal and starvation-induced autophagy appeared normal in the nca1 and cat2 mutants. By contrast, autophagic degradation induced by avrRpm1 challenge was compromised, indicating that catalase acted upstream of immunity-triggered autophagy. The direct interaction of catalase with reactive oxygen species could allow catalase to act as a molecular link between reactive oxygen species and the promotion of autophagy-dependent cell death.     

European porphyria initiative (EPI): a platform to develop a common approach to the management of porphyrias and to promote research in the field

Porphyrias are uncommon inherited diseases of haem biosynthesis for which the diagnosis and treatment varies in individual countries. Despite the existence of guidelines recommended by porphyria experts concerning the diagnosis and management of the acute porphyrias, and of specialist centres in most European countries, many clinicians still do not apply these guidelines. The European Porphyia Initiative (EPI) network was formed in 2001 in order to compare experience among countries to attempt to develop a common approach to the management of the porphyrias, particularly concerning recommendation of safe and unsafe drugs, and to facilitate international collaborative clinical and biological research. The main achievements of EPI during this period have been: * Drafting and agreeing to consensus protocols for the diagnosis and management of acute hepatic porphyrias. * Creation of a multilingual website, particularly focusing on guidelines for common prescribing problems in acute porphyria and on providing information for patients that is now available in 10 languages: (www.porphyria-europe.org). EPI's current objectives are to develop the EPI platform, expand to new countries, extend to non-acute porphyrias and design European research and clinical trials in porphyria. The project will focus on: 1. Setting up a European laboratory external quality assurance scheme (EQAS) for biochemical and molecular investigations and their interpretation 2. Establishing a consensus drug list in collaboration with the Nordic porphyria network 3. Improving patient counseling 4. Developing large multi-centre, multi-national research projects. Due to the rarity of the porphyrias, it would be very difficult for any one country to provide this data with a sufficient number of patients and within a reasonable timescale. The progress achieved will facilitate improvements in the treatment and development of new therapeutic strategies. It will set a pattern for establishing, and subsequently harmonising, between countries best clinical practice for a rare but important group of diseases, and will help to develop the optimal therapy and ensure its cost effectiveness.     

The effect of long-chain alkyl betainates on the arylesterase-like activity of bovine serum albumin

The effect of a hydrolyzable cationic surfactant, tetradecyl betainate (tetradecyloxycarbonyl-N,N,N-trimethylmethanaminium chloride), on the arylesterase-like activity of bovine serum albumin (BSA) was investigated. The rate of hydrolysis of p-nitrophenyl hexanoate in the presence of BSA and varying concentrations of the surfactant was followed. The rate was found to be dependent on the concentration of the cationic surfactant and a maximum was found in the curve at ca. 3 m . The Michaelis-Menten constants (K_m/n, where n is the number of active sites) and the “catalytic” rate constants (k₂) were determined for the reactions, and were found to be 11 and 40 times larger, respectively, in the presence of the surfactant. The hydrolysis of radiolabeled tetradecyl betainate in the presence and absence of BSA was also followed. This study, together with a binding study based on gel permeation chromatography, showed that the surfactant binds to the protein, but that no hydrolysis of the betaine ester takes place while bound to BSA. It was thus concluded that the increased value of k₂ in the presence of a cationic surfactant was not, as has been previously suggested, due to an increased local hydroxide concentration resulting from the formation of a new pseudophase.     

Targeted reduction of complex models with time scale hierarchy--a case study

With the increasing flow of biological data there is a growing demand for mathematical tools whereby essential aspects of complex causal dynamic models can be captured and detected by simpler mathematical models without sacrificing too much of the realism provided by the original ones. Given the presence of a time scale hierarchy, singular perturbation techniques represent an elegant method for making such minimised mathematical representations. Any reduction of a complex model by singular perturbation methods is a targeted reduction by the fact that one has to pick certain mechanisms, processes or aspects thought to be essential in a given explanatory context. Here we illustrate how such a targeted reduction of a complex model of melanogenesis in mammals recently developed by the authors provides a way to improve the understanding of how the melanogenic system may behave in a switch-like manner between production of the two major types of melanins. The reduced model is shown by numerical means to be in good quantitative agreement with the original model. Furthermore, it is shown how the reduced model discloses hidden robustness features of the full model, and how the making of a reduced model represents an efficient analytical sensitivity analysis. In addition to yielding new insights concerning the melanogenic system, the paper provides an illustration of a protocol that could be followed to make validated simplifications of complex biological models possessing time scale hierarchies.     

Bamboo as bioresource in Ethiopia: management strategy to improve seedling performance (Oxytenanthera abyssinica)

Seedling emergence and subsequent survival and growth are vital for natural forest restoration or plantation establishment by means of seeds. Such information is lacking for the African bamboo species. Two experiments were carried out in a greenhouse to evaluate the influence of seed orientation and sowing depth of the lowland bamboo Oxytenanthera abyssinica on seedling emergence, survival and growth. A randomised complete block design was used. Seedling emergence in the seed orientation experiment followed the order embryo-end-up>lay-flat>embryo-end-down. Survival rate after 62 days decreased in the order lay-flat>embryo-end-down>embryo-end-up. Mean seedling height and number of leaves per seedling followed a similar pattern. Seeds sown on top of the soil surface and at 2.5 mm depth achieved faster and higher seedling emergence than those sown at 5 and 10 mm depths. However, mean seedling height and number of leaves per seedling were higher in 5 and 2.5 mm depths than surface and 10 mm depths. There were significant quadratic relationships between sowing depth and seedling height (p=0.034) as well as number of leaves per seedling (p=0.032), both peaking around 5 mm soil depth. Lay-flat orientation, which is the most frequent position in broadcast sowing, is recommended at 5 mm sowing depth for the lowland bamboo based on overall performance in seedling emergence, survival and growth.     

A rapid hypersensitive response associated with resistance in the willow Salix viminalis against the gall midge Dasineura marginemtorquens

Great genotypic variation in resistance against the gall midge Dasineura marginemtorquens Bremi (Diptera: Cecidomyiidae) exists within its willow host Salix viminalis L. (Salicaceae). In some resistant genotypes larvae die within 40 h after attempting to initiate galls. The present study tested the hypothesis that the hypersensitive response (HR) is involved in incompatible interactions between D. marginemtorquens and S. viminalis. By means of UV/blue light and visible light microscopy, we verified a rapidly (within 12 h after egg hatch) spreading cell death of an HR-type due to larval attack in resistant willow genotypes. Twelve h after egg hatch, the cell death had spread up to six cell layers in resistant S. viminalis genotypes whereas in susceptible genotypes only up to two cell layers were affected. In the groups of dead cells on the resistant genotypes accumulation of phenolics was observed within 24 h after egg hatch. The rapidity of the cell death induction, the early local accumulation of phenolic compounds, and the strong association of the cell death with larval mortality suggest that the formation of dead cells in resistant willow genotypes should be interpreted as a true HR.