A Computational Model of Liver Iron Metabolism

Iron is essential for all known life due to its redox properties; however, these same properties can also lead to its toxicity in overload through the production of reactive oxygen species. Robust systemic and cellular control are required to maintain safe levels of iron, and the liver seems to be where this regulation is mainly located. Iron misregulation is implicated in many diseases, and as our understanding of iron metabolism improves, the list of iron-related disorders grows. Recent developments have resulted in greater knowledge of the fate of iron in the body and have led to a detailed map of its metabolism; however, a quantitative understanding at the systems level of how its components interact to produce tight regulation remains elusive. A mechanistic computational model of human liver iron metabolism, which includes the core regulatory components, is presented here. It was constructed based on known mechanisms of regulation and on their kinetic properties, obtained from several publications. The model was then quantitatively validated by comparing its results with previously published physiological data, and it is able to reproduce multiple experimental findings. A time course simulation following an oral dose of iron was compared to a clinical time course study and the simulation was found to recreate the dynamics and time scale of the systems response to iron challenge. A disease state simulation of haemochromatosis was created by altering a single reaction parameter that mimics a human haemochromatosis gene (HFE) mutation. The simulation provides a quantitative understanding of the liver iron overload that arises in this disease. This model supports and supplements understanding of the role of the liver as an iron sensor and provides a framework for further modelling, including simulations to identify valuable drug targets and design of experiments to improve further our knowledge of this system.     

Differential Resistance to Oxidants and Production of Hydrolytic Enzymes in <Emphasis Type="Italic">Candida albicans</Emphasis>

Resistance to the toxic effects of reactive oxygen species produced by phagocytes and production of hydrolytic enzymes are important aspects of Candida albicans virulence. In this report, we compared twelve C. albicans isolates for their in vitro capacity to resist oxidants—hydrogen peroxide, menadione and paraquat; and to produce hydrolytic enzymes—phospholipase and protease. Different C. albicans isolates showed different degrees of resistance to oxidants as well as differences in production of hydrolytic enzymes. Resistance to oxidative stress did not correlate with production of hydrolytic enzymes. This reinforces the view that C. albicans differentially regulates the expression of virulence factors in response to local environmental conditions.     

A new regulatory principle for in vivo biochemistry: Pleiotropic low affinity regulation by the adenine nucleotides – Illustrated for the glycolytic enzymes of Saccharomyces cerevisiae

Enzymology tends to focus on highly specific effects of substrates, allosteric modifiers, and products occurring at low concentrations, because these are most informative about the enzyme’s catalytic mechanism. We hypothesized that at relatively high in vivo concentrations, important molecular monitors of the state of living cells, such as ATP, affect multiple enzymes of the former and that these interactions have gone unnoticed in enzymology.     

New species and new data on Protrinemuridae and Nicoletiidae (Zygentoma) from Eastern Asia and Pacific islands

Four new genera and eleven new species of Zygentoma thysanurans (families Protrinemuridae and Nicoletiidae) are described and some faunistic novelties reported from Oriental and Australian Regions, viz.: Protrinemura leclerci n. sp., from northern Thailand, Protrinemurella allacrotelsoides n. gen. n. sp., from southern Thailand, and Protrinemuroides celebensis n. gen. n. sp., from the Celebes islands (Protrinemuridae), Lepidospora (L.) digitata n. sp., from northern Thailand, L. (L.) deharvengi n. sp., from the Celebes, and Pseudobrinckina anempodiata n. gen. n. sp., from northern Thailand (Nicoletiidae: Coletiniinae), Gastrotheus (G.) papuanus n. sp., from Papua-New Guinea (Nicoletiidae: Atelurinae), and Metrinura celebensis n. sp., from the Celebes, Trinemurodes anomalocoxa n. sp., from southern Thailand, T. bedosae n. sp., from northern Thailand, and Allotrinemurodes thai n.gen. n. sp., from northern Thailand (Nicoletiidae: Subnicoletiinae). Bharatatelura malabarica Mendes is reported for the first time off the Indian sub-continent (in Suva). Proatelura jacobsoni Silvestri is recorded in Macao (southern China) and in the Moluccas islands and notes are presented on its male sex. Gastrotheus (Lasiotheus) nanus (Escherich) is found for the very first time in Macao, in Cook islands and in Niue. Identification keys are provided to Protrinemuridae genera and to species of Trinemurodes, and modifications are suggested to previously presented keys to Nicoletiidae genera and to Lepidospora and Metrinura species.     

Proteome analysis of the plasma protein layer adsorbed to a rough titanium surface

In this study a label-free proteomic approach was used to investigate the composition of the layer of protein adsorbed to rough titanium (Ti) after exposure to human blood plasma. The influence of the protein layer on the surface free energy (SFE) of the Ti was evaluated by contact angle measurements. Ti discs were incubated with blood plasma for 180?min at 37?°C, and the proteins recovered were subjected to liquid chromatography coupled to tandem mass spectrometry analysis. A total of 129 different peptides were identified and assigned to 25 distinct plasma proteins. The most abundant proteins were fibronectin, serum albumin, apolipoprotein A-I, and fibrinogen, comprising 74.54% of the total spectral counts. Moreover, the protein layer increased the SFE of the Ti (p?<?0.05). The layer adsorbed to the rough Ti surface was composed mainly of proteins related to cell adhesion, molecule transportation, and coagulation processes, creating a polar and hydrophilic interface for subsequent interactions with host cells.     

TDZ pulsing evaluation on the in vitro morphogenesis of peach palm

Peach palm (Bactris gasipaes Kunth.) cropping is an excellent alternative to native species exploitation; nevertheless, the problems with seed germination and conventional propagation justify the use of in vitro culturing. Aiming to asses TDZ pulsing effect on B. gasipaes morphogenesis, explants obtained from unarmed microplants were maintained in two treatments, half of them in MS free medium (without growth regulator) and the other half in MS with TDZ (0.36 μM). Both groups were transferred to growth regulator-free MS medium following 14 days of culture. After 84 days of culture, TDZ pulsing increased the growth and development of the shoots, restricted the growth and development of the roots, with no influence on adventitious bud induction or somatic embryogenesis. Furthermore, development of prickles, thickening of roots and chlorotic leaves were noted under TDZ pulsing. Leaf sheath histological analysis showed an epidermal origin and no vascularization of these prickles.     

Breeding plumage honestly signals likelihood of tapeworm infestation in females of a long-distance migrating shorebird, the bar-tailed godwit

The indicator mechanism for sexual selection proposed by Hamilton and Zuk (i.e. that sexually selected ornaments signal parasite resistance) has received rather little observational support, and none in the case of long-distance migrant birds. Here we present a test by examining the association between helminth infestations and breeding plumage quality in bar-tailed godwits Limosa lapponica taymyrensis during their spring staging period in the Wadden Sea, The Netherlands. After a non-stop flight from West Africa, these shorebirds refuel in the Wadden Sea in preparation for a second flight to the central Siberian Arctic breeding grounds. Earlier studies have shown that only relatively heavy and well ornamented birds carry out a "top-up" moult during stopover, in which part of the contour feathers recently grown in West Africa are replaced by even fresher ones. Active body moult was therefore taken as the primary indicator of ornament quality. Of 78 birds collected between 1992 and 1997, 42% carried helminths, including four species of digenean trematodes (flukes), three species of cestodes (tapeworms) and an acanthocephalan (spiny-headed worm). Faecal samples examined for helminth eggs in another 92 birds in 1998 and 2000 showed similar rates of infestation. Actively moulting bar-tailed godwits were confirmed to be heavier and to show more extensive breeding plumage than non-moulting birds. In females, but not in males, active moult was associated with fewer cestodes and acanthocephalans. Also, breeding plumage and presence of cestodes were negatively associated in females. We argue that the quality of the breeding plumage reliably indicates parasite resistance in female godwits. The repeatability of plumage scores of females between years is consistent with such resistance having a heritable component. In contrast, male ornaments may demonstrate other qualities, e.g. an ability to combine adequate fuelling and flight performances with moult during the time-stress of migration.     

A SHIFT FROM MAGNITUDE TO SIGN EPISTASIS DURING ADAPTIVE EVOLUTION OF A BACTERIAL SOCIAL TRAIT

Although the importance of epistasis in evolution has long been recognized, remarkably little is known about the processes by which epistatic interactions evolve in real time in specific biological systems. Here, we have characterized how the epistatic fitness relationship between a social gene and an adapting genome changes radically over a short evolutionary time frame in the social bacterium Myxococcus xanthus. We show that a highly beneficial effect of this social gene in the ancestral genome is gradually reduced—and ultimately reversed into a deleterious effect—over the course of an experimental adaptive trajectory in which a primitive form of novel cooperation evolved. This reduction and reversal of a positive social allelic effect is driven solely by changes in the genetic context in which the gene is expressed as new mutations are sequentially fixed during adaptive evolution, and explicitly demonstrates a significant evolutionary change in the genetic architecture of an ecologically important social trait.