Systems biology and its potential role in radiobiology

About a century ago, Conrad Röentgen discovered X-rays, and Henri Becquerel discovered a new phenomenon, which Marie and Pierre Curie later coined as radio-activity. Since their seminal work, we have learned much about the physical properties of radiation and its effects on living matter. Alas, the more we discover, the more we appreciate the complexity of the biological processes that are triggered by radiation exposure and eventually lead (or do not lead) to disease. Equipped with modern biological methods of high-throughput experimentation, imaging, and vastly increased computational prowess, we are now entering an era where we can piece some of the multifold aspects of radiation exposure and its sequelae together, and develop a more systemic understanding of radiogenic effects such as radio-carcinogenesis than has been possible in the past. It is evident from the complexity of even the known processes that such an understanding can only be gained if it is supported by mathematical models. At this point, the construction of comprehensive models is hampered both by technical inadequacies and a paucity of appropriate data. Nonetheless, some initial steps have been taken already and the generally increased interest in systems biology may be expected to speed up future progress. In this context, we discuss in this article examples of relatively small, yet very useful models that elucidate selected aspects of the effects of exposure to ionizing radiation and may shine a light on the path before us.     

Habitat-specific clutch size and cost of incubation in eiders reconsidered

The energetic incubation constraint hypothesis (EICH) for clutch size states that birds breeding in poor habitat may free up resources for future reproduction by laying a smaller clutch. The eider (Somateria mollissima) is considered a candidate for supporting this hypothesis. Clutch size is smaller in exposed nests, presumably because of faster heat loss and higher incubation cost, and, hence, smaller optimal clutch size. However, an alternative explanation is partial predation: the first egg(s) are left unattended and vulnerable to predation, which may disproportionately affect exposed nests, so clutch size may be underestimated. We experimentally investigated whether predation on first-laid eggs in eiders depends on nest cover. We then re-evaluated how nesting habitat affects clutch size and incubation costs based on long-term data, accounting for confounding effects between habitat and individual quality. We also experimentally assessed adult survival costs of nesting in sheltered nests. The risk of egg predation in experimental nests decreased with cover. Confounding between individual and habitat quality is unlikely, as clutch size was also smaller in open nests within individuals, and early and late breeders had similar nest cover characteristics. A trade-off between clutch and female safety may explain nest cover variation, as the risk of female capture by us, mimicking predation on adults, increased with nest cover. Nest habitat had no effect on female hatching weight or weight loss, while lower temperature during incubation had an unanticipated positive relationship with hatching weight. There were no indications of elevated costs of incubating larger clutches, while clutch size and colony size were positively correlated, a pattern not predicted by the ‘energetic incubation constraint’ hypothesis. Differential partial clutch predation thus offers the more parsimonious explanation for clutch size variation among habitats in eiders, highlighting the need for caution when analysing fecundity and associated life-history parameters when habitat-specific rates of clutch predation occur.     

A rare sugar xylitol. Part I: the biochemistry and biosynthesis of xylitol

The rare sugar xylitol is a five-carbon polyol (pentitol) that has beneficial health effects. Xylitol has global markets and, therefore, it represents an alternative to current dominant sweeteners. The research on microbial reduction of d-xylose to xylitol has been focused on metabolically engineered Saccharomycess cerevisiae and Candida strains. The Candida strains have an advantage over the metabolically engineered S. cerevisiae in terms of d-xylose uptake and maintenance of the intracellular redox balance. Due to the current industrial scale production of xylitol, it has become an inexpensive starting material for the production of other rare sugar. The first part of this mini-review concentrates on the biochemistry of xylitol biosynthesis and the problems related to intracellular redox balance.     

(4-Piperidinyl)-piperazine: A new platform for acetyl-CoA carboxylase inhibitors

Acetyl-CoA carboxylases (ACCs), the rate limiting enzymes in de novo lipid synthesis, play important roles in modulating energy metabolism. The inhibition of ACC has demonstrated promising therapeutic potential for treating obesity and type 2 diabetes mellitus in transgenic mice and preclinical animal models. We describe herein the synthesis and structure–activity relationships of a series of disubstituted (4-piperidinyl)-piperazine derivatives as a new platform for ACC1/2 non-selective inhibitors.     

Relation between light absorption measured by the quantitative filter technique and attenuation of <Emphasis Type="Italic">Chlorella fusca</Emphasis> cultures of different cell densities: application to estimate the absolute electron transport rate (ETR)

In order to estimate microalgal carbon assimilation or production of Chlorella fusca cultures based on electron transport rate (ETR) as in vivo chlorophyll a fluorescence, it is necessary to determine the photosynthetic yield and the absorbed quanta by measuring the incident irradiance and the fraction of absorbed light, i.e., absorptance or absorption coefficient in the photosynthetic active radiation (PAR) region of the spectra. Due to difficulties associated with the determination of light absorption, ETR is commonly expressed as relative units (rETR) although this is not a good estimator of the photosynthetic production since photobiological responses depend on the absorbed light. The quantitative filter technique (QFT) is commonly used to measure the absorbed quanta of cells retained on a filter (AbQ_f) as estimator of the absorbed quanta of cell suspensions (AbQ_s) determined by using integrating spheres. In this study, light attenuation of thin-layer cell suspensions is determined by using a measuring system designed to reduce the scattering. The light attenuation is related to the absorptance as the fraction of absorbed light by both indoor and outdoor C. fusca cultures of different cell densities. A linear relation between AbQ_f and AbQ_s (R ²?=?0.9902, p?<?0.01) was observed, AbQ_f?=?1.98?×?AbQ_s, being 1.98 an amplification factor to convert AbQ_s values into AbQ_f ones. On the other hand, depending on the culture system, the convenience of the use of the absorptance, light absorption or specific light absorption coefficient expressed per area (thin-layer cascade or flat panel cultivators), volume (cylindrical and tubular photobioreactors), or chlorophyll units (any type of cultivation system) is discussed. The procedure for the measurement of light absorption presented in this study for C. fusca could be applied in other phytoplankton groups. The absorbed quanta as determined in this study can be used to express absolute ETR instead of relative ETR, since the first one provides much more relevant photobiological information of microalgae culture systems.     

Body mass and behavior in Swiss mice subjected to continuous or discontinuous food restriction and refeeding

Food restriction (FR) is hypothesized to decrease body fat content of an animal and thus prevent obesity. However, the response of energy budget to a continuous (CFR) or discontinuous FR (DFR) remains inconsistent. In the present study, effects of CFR or DFR and refeeding on energy budget and behavior were examined in male Swiss mice. CFR significantly decreased the energy expenditure associated with basal metabolic rate (BMR) and activity behavior, but not sufficiently to compensate for energy deficit and thus resulted in lower body mass and fat content. DFR mice had a significantly higher food intake on ad libitum days and showed increases in BMR and activity after 4 weeks’ DFR, which might resulted in lower body mass and less body fat than controls. After being refed ad libitum, both CFR and DFR mice had similar body mass, BMR, and behavioral patterns to controls but had 95% and 75% higher fat content. This suggested that not only CFR but also DFR would be a significant factor in the process of obesity for animals that were refed ad libitum. It also indicated that food restriction interrupted many times by periods of ad libitum feeding had the same long-term effects like continuous underfeeding.     

Callus,shoot and hairy root formation in vitro as affected by the sensitivity to auxin and ethylene in tomato mutants

We analyzed the impact of ethylene and auxin disturbances on callus, shoots and Agrobacterium rhizogenes-induced hairy root formation in tomato (Solanum lycopersicum L.). The auxin low-sensitivity dgt mutation showed little hairy root initiation, whereas the ethylene low-sensitivity Nr mutation did not differ from the control Micro-Tom cultivar. Micro-Tom and dgt hairy roots containing auxin sensitivity/biosynthesis rol and aux genes formed prominent callus onto media supplemented with cytokinin. Under the same conditions, Nr hairy roots did not form callus. Double mutants combining Rg1, a mutation conferring elevated shoot formation capacity, with either dgt or Nr produced explants that formed shoots with little callus proliferation. The presence of rol + aux genes in Rg1 hairy roots prevented shoot formation. Taken together, the results suggest that although ethylene does not affect hairy root induction, as auxin does, it may be necessary for auxin-induced callus formation in tomato. Moreover, excess auxin prevents shoot formation in Rg1.     

A Global History of Australian Trees

Scholars studying the globalization of Australian trees have previously emphasized the rapid natural propagation of Australian trees outside of their native habitats, believing their success to be a reversal of “ecological imperialism” from the “new world” to the “old world.” This article argues that the expansion of Australian trees should not be viewed as a biological phenomenon, but as the result of a long-term attempt by powerful states and state-sponsored scientists to select and breed Australian species that could grow in a variety of climates and ecological conditions. Five non-biological factors largely determined the success of these attempts to grow Australian trees: the abundance or paucity of natural forests, state power, the amount of scientific research directed to planting Australian trees, the cost of labor, and the ability to utilize hardwood timbers and bark. This paper compares the use of Australian trees in Australia, India, and South Africa to demonstrate that biology was not the determining factor in the long-term success of many Australian genera and species.     

Chlorophyll fluorescence images demonstrate variable pathways in the effects of plasma membrane excitation on electron flow in chloroplasts of <Emphasis Type=Italic>Chara</Emphasis> cells

Chlorophyll fluorescence Imaging and Microscopy PAM fluorometry were applied to study spatial dynamics of photosystem II quantum yield ( DF/F_m￠ ) left( {Delta F/F_m^prime } right) and non-photochemical quenching (NPQ) in resting and electrically stimulated Chara corallina cells in the absence and presence of the hydrophilic electron acceptor methyl viologen (MV) in the external medium. Electrical excitation of the plasma membrane temporarily enhanced the heterogeneity of photosynthetic patterns under physiological conditions (in the absence of MV), but irreversibly eliminated these patterns in the presence of MV. These findings suggest that the action potential (AP) of the excitable plant cell affects the spatial patterns of photosynthesis and chlorophyll fluorescence through different pathways operated in the absence and presence of MV. Based on the extent of NPQ as an indicator of MV-dependent electron flow, it is supposed that MV cannot permeate into the chloroplasts of photosynthetically active “acid cell regions” but gains an immediate access to the stroma of these chloroplasts after triggering of an AP. The AP-triggered MV-dependent non-photochemical quenching in the chloroplasts of acidic cell regions was routinely observed at 0.1 mM Ca²⁺ in the medium but not at elevated (2 mM) external Ca²⁺ concentration. The results are interpreted in terms of competition between two permeant divalent ion species, Ca²⁺ and MV²⁺, for their passage through the voltage-gated calcium channels of the plasma membrane. It is proposed that the herbicidal activity of MV in characean cells, here serving as model object, can be manipulated by triggering AP and varying Ca²⁺ concentration in the environmental medium.