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.     

Florida Red Tide Toxins (Brevetoxins) and Longitudinal Respiratory Effects in Asthmatics

Having demonstrated significant and persistent adverse changes in pulmonary function for asthmatics after 1 h exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols, we assessed the possible longer term health effects in asthmatics from intermittent environmental exposure to brevetoxins over 7 years. 125 asthmatic subjects were assessed for their pulmonary function and reported symptoms before and after 1 h of environmental exposure to Florida red tide aerosols for up to 11 studies over seven years. As a group, the asthmatics came to the studies with normal standardized percent predicted pulmonary function values. The 38 asthmatics who participated in only one exposure study were more reactive compared to the 36 asthmatics who participated in ≥4 exposure studies. The 36 asthmatics participating in ≥4 exposure studies demonstrated no significant change in their standardized percent predicted pre-exposure pulmonary function over the 7 years of the study. These results indicate that stable asthmatics living in areas with intermittent Florida red tides do not exhibit chronic respiratory effects from intermittent environmental exposure to aerosolized brevetoxins over a 7 year period.     

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.     

Essential oil production in shoot cultures versus field-grown plants of Thymus caespititius

Thymus caespititius Brot. is an important aromatic species, due to synthesis and production of essential oils for the pharmaceutical and food industries. In the present study, levels of essential oils from two chemotypes, including carvacrol/thymol (CT) and sabinene/carvacrol (SC), were evaluated in proliferating shoot cultures (6–12 subcultures following establishment) and compared to those from field-grown plants. The essential oils were isolated by hydrodistillation and analysed by gas chromatography (GC) and GC–mass spectrometry (GC–MS). Cultures grown under in vitro culture conditions, evaluated over six subcultures, were found to maintain stable composition of essential oils. For the CT chemotype, carvacrol (42 %) and thymol (23 %) were the main essential oil components detected in field-grown plants; in proliferating shoot cultures the levels detected attained 17–25 % in the case of carvacrol and 18–23 % in that of thymol, closely followed by carvacryl acetate (15–23 %) and thymyl acetate (11–15 %). For the SC chemotype, carvacrol (13–28 %), sabinene (18–45 %), and thymol (9–12 %) were the main essential oil components detected in both field-grown and proliferating shoot cultures. Our experiments showed that the essential oil composition in proliferating shoot cultures was not only stable, but also qualitatively similar to that of field-grown plants, notwithstanding minor quantitative differences.     

Economic impact of exotic insect pests in Brazilian agriculture

Agriculture represents one of the major strengths of the economic sector in Brazil. The need to avoid economic losses because of insect pest populations is one of the greatest challenges faced by this sector. Insect pests have caused annual losses of US$12.0 billion to the Brazilian economy, of which approximately US$1.6 billion are because of exotic pest species. Furthermore, exotic insect species often show greater potential to cause harm than native species. In Brazil, since the late nineteenth century, 24 species of insect pests have been introduced into the country, and they have caused significant economic losses. Many of these species, including Bemisia tabaci, Hypothenemus hampei, Ceratitis capitata, Oryzophagus oryzae and Anthonomus grandis, are major crop pests, and they were accidentally introduced during trading of agricultural products. In this review, we present an overview of Brazilian agriculture, a brief history of the introduction of insect pests in the country and the Brazilian legislation on agricultural defence, and we estimate the economic losses caused to the Brazilian economy by the main insect pest species that have been introduced into Brazil over the last 112 years.     

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.