Constraints-based genome-scale metabolic simulation for systems metabolic engineering

Random mutagenesis and selection approaches used traditionally for the development of industrial strains have largely been complemented by metabolic engineering, which allows purposeful modification of metabolic and cellular characteristics by using recombinant DNA and other molecular biological techniques. As systems biology advances as a new paradigm of research thanks to the development of genome-scale computational tools and high-throughput experimental technologies including omics, systems metabolic engineering allowing modification of metabolic, regulatory and signaling networks of the cell at the systems-level is becoming possible. In silico genome-scale metabolic model and its simulation play increasingly important role in providing systematic strategies for metabolic engineering. The in silico genome-scale metabolic model is developed using genomic annotation, metabolic reactions, literature information, and experimental data. The advent of in silico genome-scale metabolic model brought about the development of various algorithms to simulate the metabolic status of the cell as a whole. In this paper, we review the algorithms developed for the system-wide simulation and perturbation of cellular metabolism, discuss the characteristics of these algorithms, and suggest future research direction.     

Association of the Ser326Cys polymorphism in the OGG1 gene with type 2 DM

The association of the Ser326Cys polymorphism of the 8-oxoguanine glycosylase 1 (OGG1) gene with type 2 diabetes was examined using a Japanese population (n (M/W): 4585 (2085/2500); age: 62.6 ± 10.9 years). HbA1c levels and frequency of diabetic subjects were significantly higher in subjects with genotypes with Cys allele than in those without (p = 0.032 and 0.037, respectively). Multiple logistic regression analysis showed that genotypes with Cys allele were significantly associated with diabetes (OR: 1.32, p = 0.0289). In subjects whose glucose tolerance was classified by FPG and 2-h PG (n = 1.634), the association was more substantial (genotypes with Cys allele vs. without, OR: 1.70, p = 0.0059; genotypes Cys/Cys vs. Ser/Ser, OR: 2.19, p = 0.0008). In subjects with genotype Ser/Ser, the insulin secretion index, HOMA-β, increased in the subjects with glucose intolerance and decreased in the subjects with diabetes, while, in subjects with genotypes Ser/Cys + Cys/Cys, HOMA-β decreased as the glucose tolerance progressed (p for trend = 0.010).     

Birding and DNA: species for the new millennium

Capsule Based on the 1999 Witherby Memorial Lecture – reviews how developments in molecular and population genetics have led to a reappraisal of species limits in birds.

The taxonomy of birds of the West Palearctic has moved from the comparative stability of the ‘Voous List’ into a period of serious activity, with new data emerging in almost every issue of every evolutionary and avian journal! This activity comes from two directions. Firstly, developments in population genetics, molecular biology, acoustics, behaviour and distributional studies have opened new avenues to measuring differentiation among groups of birds. This, in turn, has led to the recognition that earlier views of what constitutes a ‘species’ are in need of modification (‘improvement’), and the emergence of the ‘lineage concept’ of species. I review some of the species concepts most relevant to avian studies, and attempt to show how and why this change has happened, and its consequences for taxonomy and species limits. Examples are given in the form of ‘case studies’, and include Carrion/Hooded Crows Corvus corone/cornix, Green-winged/Eurasian Teals Anas carolinensis/crecca and Phylloscopus warblers.     

An allometric analysis of the giraffe cardiovascular system

There has been co-evolution of a long neck and high blood pressure in giraffes. How the cardiovascular system (CVS) has adapted to produce a high blood pressure, and how it compares with other similar sized mammals largely is unknown. We have measured body mass and heart structure in 56 giraffes of both genders ranging in body mass from 18 kg to 1500 kg, and developed allometric equations that relate changes in heart dimensions to growth and to cardiovascular function. Predictions made from these equations match measurements made in giraffes. We have found that heart mass increases as body mass increases but it has a relative mass of 0.51 ± 0.7% of body mass which is the same as that in other mammals. The left ventricular and interventricular walls are hypertrophied and their thicknesses are linearly related to neck length. Systemic blood pressure increases as body mass and neck length increase and is twice that of mammals of the same body mass. Cardiac output is the same as, but peripheral resistance double that predicted for similar sized mammals. We have concluded that increasing hydrostatic pressure of the column of blood during neck elongation results in cardiac hypertrophy and concurrent hypertrophy of arteriole walls raising peripheral resistance, with an increase in blood pressure following.     

Regulation of the loss of frost hardiness in Pinus radiata by photoperiod and temperature

Abstract. In controlled environments, the interactive effects of warm (16: 8°C, day: night) and cool (12: 4°C, day: night) temperatures and long (13.5 h) and short (10 h) photoperiods on the dehardening of seedlings of Pinus radiata D. Don were investigated. In another experiment, the effect of four photoperiods from 9 to 14 h was examined. In a third, dehardening at constant temperatures from 5 to 17°C was followed. There was no evidence for an interaction between photoperiod and temperature. Dehardening was temporarily delayed by photoperiods below about 10 h, but there was no other quantitative effect of photoperiod. At constant temperatures, the rate of dehardening was initially constant but declined as the minimum summer frost hardiness was reached. In the initial phase the rate of dehardening was a linear function of temperature, increasing from 0.05°C day⁻¹ at 8°C to 0.30 °C day⁻¹ at 17°C. Temperature controlled the loss of frost hardiness by regulating the rate of dehardening.     

Regional species richness,hydrological characteristics and the local species richness of assemblages of North American stream fishes

1. Local assemblage structure, from a deterministic perspective, is presumably dictated by the regional species pool as well as regulated by local factors. We examined the relationships of the regional species pool and local hydrological characteristics to local species richness of North American freshwater fishes using data sets collected during the National Water Quality Assessment program conducted by the United States Geological Survey. 2. We predicted that local species richness is ultimately constrained by the composition of the regional species pool and further associated with local hydrological factors. Moreover, we predicted that variation in local species richness within major families can be explained by different combinations of hydrological characteristics that represent lineage‐specific responses to the environment. 3. Daily discharge and regional and local species richness data were assembled from 41 stream localities across the United States. Multiple stepwise regressions were conducted to predict local species richness, based on regional species richness, mean discharge and hydrological characteristics quantified by nine variables characterising flow variability. Species richness at each site was calculated for the entire assemblage as well as within the four most species‐rich families in the data set (Catostomidae, Centrarchidae, Cyprinidae and Percidae). 4. Local species richness was best predicted by a combination of regional species richness and discharge magnitude when all species were considered. Regional species richness was a significant explanatory variable of local species richness for three of four families (Catostomidae, Centrarchidae, Cyprinidae), but not for Percidae. Local richness in Centrarchidae and Cyprinidae was positively correlated with temporal flow variability as well as high and low flow duration, respectively, while richness in Catostomidae and Percidae tended to be associated with discharge volume. In addition, local species richness for three of the four major families was positively correlated with species richness of the other families in the assemblage, potentially suggesting the influence of local habitat quality and heterogeneity. 5. Results suggest the importance of the combined influences of the regional species pool and local hydrological characteristics on local richness in freshwater fishes, with variation in richness within each family predicted by different characteristics of flow regimes.