Stable water isotopes in HadCM3: isotopic signature of El Nino-Southern Oscillation and the tropical amount effect

Stable water isotopes have been added to the full hydrological cycle of the Hadley Centre Climate model (HadCM3) coupled atmosphere-ocean GCM. Simulations of delta O-18 in precipitation and at the ocean surface compare well with observations for the present-day climate. The model has been used to investigate the isotopic anomalies associated with ENSO; it is found that the anomalous delta O-18 in precipitation is correlated with the anomalous precipitation amount in accordance with the "amount effect.'' The El Nino delta O-18 anomaly at the ocean surface is largest in coastal regions because of the mixing of ocean water and the more depleted runoff from the land surface. Coral delta O-18 anomalies were estimated, using an established empirical relationship, and generally reflect ocean surface delta O-18 anomalies in coastal regions and sea surface temperatures away from the coast. The spatial relationship between tropical precipitation and delta O-18 was investigated for the El Nino anomaly simulated by HadCM3. Weighting the El Nino precipitation anomaly by the precipitation amount at each grid box gave a large increase in the spatial correlation between tropical precipitation and delta O-18. This improvement was most apparent over land points and between 10 and 20 degrees of latitude

An integrated mathematical model of cellular cholesterol biosynthesis and lipoprotein metabolism

Cholesterol regulation is an important aspect of human health. In this work we bring together and extend two recent mathematical models describing cholesterol biosynthesis and lipoprotein endocytosis to create an integrated model of lipoprotein metabolism in the context of a single hepatocyte. The integrated model includes a description of low density lipoprotein (LDL) receptor and cholesterol synthesis, delipidation of very low density lipoproteins (VLDLs) to LDLs and subsequent lipoprotein endocytosis. Model analysis shows that cholesterol biosynthesis produces the majority of intracellular cholesterol. The availability of free receptors does not greatly effect the concentration of intracellular cholesterol, but has a detrimental effect on extracellular VLDL and LDL levels. We test our model by considering its ability to reproduce the known biology of Familial Hypercholesterolaemia and statin therapy. In each case the model reproduces the known biological behaviour. Quantitative differences in response to statin therapy are discussed in the context of the need to extend the work to a more {\it in vivo} setting via the incorporation of more dietary lipoprotein related processes and the need for further testing and parameterisation of {\it in silico} models of lipoprotein metabolism

Mathematics as a tool in the Life Sciences

Teaching mathematics to students in the biological sciences is often fraught with difficulty. Students often discover mathematics to be a very 'dry' subject in which it is difficult to see the motivation of learning it given its often abstract application. In this paper I advocate the use of mathematical modelling as a method for engaging students in understanding the use of mathematics in helping to solve problems in the Biological Sciences. The concept of mathematics as a laboratory tool is introduced and the importance of presenting students with relevant, real-world examples of applying mathematics in the Biological Sciences is discussed

Classifying general nonlinear force laws in cell-based models via the continuum limit

though discrete cell-based frameworks are now commonly used to simulate a whole range of biological phenomena, it is typically not obvious how the numerous different types of model are related to one another, nor which one is most appropriate in a given context. Here we demonstrate how individual cell movement on the discrete scale modeled using nonlinear force laws can be described by nonlinear diffusion coefficients on the continuum scale. A general relationship between nonlinear force laws and their respective diffusion coefficients is derived in one spatial dimension and, subsequently, a range of particular examples is considered. For each case excellent agreement is observed between numerical solutions of the discrete and corresponding continuum models. Three case studies are considered in which we demonstrate how the derived nonlinear diffusion coefficients can be used to (a) relate different discrete models of cell behavior; (b) derive discrete, intercell force laws from previously posed diffusion coefficients, and (c) describe aggregative behavior in discrete simulations

Origin and evolution of osmoregulatory mechanisms in blue-green algae as a function of metabolic and structural complexity: Reflections of precambrian paleobiology

Twenty-four of the twenty-nine cyanobacteria proposed for culture were successfully cultured. Betaines are discussed

Modeling chemotaxis reveals the role of reversed phosphotransfer and a bi-functional kinase-phosphatase

Understanding how multiple signals are integrated in living cells to produce a balanced response is a major challenge in biology. Two-component signal transduction pathways, such as bacterial chemotaxis, comprise histidine protein kinases (HPKs) and response regulators (RRs). These are used to sense and respond to changes in the environment. Rhodobacter sphaeroides has a complex chemosensory network with two signaling clusters, each containing a HPK, CheA. Here we demonstrate, using a mathematical model, how the outputs of the two signaling clusters may be integrated. We use our mathematical model supported by experimental data to predict that: (1) the main RR controlling flagellar rotation, CheY6, aided by its specific phosphatase, the bifunctional kinase CheA3, acts as a phosphate sink for the other RRs; and (2) a phosphorelay pathway involving CheB2 connects the cytoplasmic cluster kinase CheA3 with the polar localised kinase CheA2, and allows CheA3-P to phosphorylate non-cognate chemotaxis RRs. These two mechanisms enable the bifunctional kinase/phosphatase activity of CheA3 to integrate and tune the sensory output of each signaling cluster to produce a balanced response. The signal integration mechanisms identified here may be widely used by other bacteria, since like R. sphaeroides, over 50% of chemotactic bacteria have multiple cheA homologues and need to integrate signals from different sources

Fold-change detection in a whole-pathway model of Escherichia coli chemotaxis

There has been recent interest in sensory systems that are able to display a response which is proportional to a fold change in stimulus concentration, a feature referred to as fold-change detection (FCD). Here, we demonstrate FCD in a recent whole-pathway mathematical model of Escherichia coli chemotaxis. FCD is shown to hold for each protein in the signalling cascade and to be robust to kinetic rate and protein concentration variation. Using a sensitivity analysis, we find that only variations in the number of receptors within a signalling team lead to the model not exhibiting FCD. We also discuss the ability of a cell with multiple receptor types to display FCD and explain how a particular receptor configuration may be used to elucidate the two experimentally determined regimes of FCD behaviour. All findings are discussed in respect of the experimental literature

Theory of commensurable magnetic structures in holmium

The tendency for the period of the helically ordered moments in holmium to lock into values which are commensurable with the lattice is studied theoretically as a function of temperature and magnetic field. The commensurable effects are derived in the mean-field approximation from numerical calculations of the free energy of various commensurable structures, and the results are compared with the extensive experimental evidence collected during the last ten years on the magnetic structures in holmium. In general the stability of the different commensurable structures is found to be in accord with the experiments, except for the tau=5/18 structure observed a few degrees below T_N in a b-axis field. The trigonal coupling recently detected in holmium is found to be the interaction required to explain the increased stability of the tau=1/5 structure around 42 K, and of the tau=1/4 structure around 96 K, when a field is applied along the c-axis.Comment: REVTEX, 31 pages, 7 postscript figure

Modulation of Androgen Receptor by FOXA1 and FOXO1 Factors in Prostate Cancer

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