Creatine kinase in energy metabolic signaling in muscle

There has been much debate on the mechanism of regulation of mitochondrial ATP synthesis to balance ATP consumption during changing cardiac workloads. A key role of creatine kinase (CK) isoenzymes in this regulation of oxidative phosphorylation and in intracellular energy transport had been proposed, but has in the mean time been disputed for many years. It was hypothesized that high-energy phosphoryl groups are obligatorily transferred via CK; this is termed the phosphocreatine shuttle. The other important role ascribed to the CK system is its ability to buffer ADP concentration in cytosol near sites of ATP hydrolysis. 

Almost all of the experiments to determine the role of CK had been done in the steady state, but recently the dynamic response of oxidative phosphorylation to quick changes in
cytosolic ATP hydrolysis has been assessed at various levels of inhibition of CK. Steady state models of CK function in energy transfer existed but were unable to explain the dynamic response with CK inhibited.

The aim of this study was to explain the mode of functioning of the CK system in heart, and in particular the role of different CK isoenzymes in the dynamic response to workload steps. For this purpose we used a mathematical model of cardiac muscle cell energy metabolism containing the kinetics of the key processes of energy production, consumption and transfer pathways. The model underscores that CK plays indeed a dual role in the cardiac cells. The buffering role of CK system is due to the activity of myofibrillar CK (MMCK) while the energy transfer role depends on the activity of mitochondrial CK (MiCK). We propose that this may lead to the differences in regulation mechanisms and energy transfer modes in species with relatively low MiCK activity such as rabbit in comparison with species with high MiCK activity such as rat.

The model needed modification to explain the new type of experimental data on the dynamic response of the mitochondria. We submit that building a Virtual Muscle Cell is not possible without continuous experimental tests to improve the model. In close interaction with experiments we are developing a model for muscle energy metabolism and transport mediated by the creatine kinase isoforms which now already can explain many different types of experiments

Exploring pathways for sustainable water management in river deltas in a changing environment

Exploring adaptation pathways into an uncertain future can support decisionmaking in achieving sustainable water management in a changing environment. Our objective is to develop and test a method to identify such pathways by including dynamics from natural variability and the interaction between the water system and society. Present planning studies on long-term water management often use a few plausible futures for one or two projection years, ignoring the dynamic aspect of adaptation through the interaction between the water system and society. Our approach is to explore pathways using multiple realisations of transient scenarios with an Integrated Assessment Meta Model (IAMM). This paper presents the first application of the method using a hypothetical case study. The case study shows how to explore and evaluate adaptation pathways. With the pathways it is possible to identify opportunities, threats, timing and sequence of policy options, which can be used by policymakers to develop water management roadmaps into the future. By including the dynamics between the water system and society, the influence of uncertainties in both systems becomes clearer. The results show, among others, that climate variability rather than climate change appears to be important for taking decisions in water management

Effect analysis of transient scenarios for successful water management strategies

Recent scenario studies on water management focus on one or two projection years and the effects on the water system and functions. The future is however more complex and dynamic. Therefore, we analyse transient scenarios in order to evaluate the performance of water management strategies. Current available simulation tools are not suitable for this purpose. Therefore, we have developed and used a tool to simulate 50-100 year long time series and that is good and fast enough to simulate the effects of these scenarios and strategies on the water system and the interaction with the human system. We present the first step by means of a case study

Water movement in layered soils-a simulation model.

The simulation model is written in "continuous system modelling Program" and is applied to ploughed and unplowed soils with layers of different conductivity. (Abstract retrieved from CAB Abstracts by CABI’s permission

Climatology of daily rainfall semi-variance in The Netherlands

Rain gauges can offer high quality rainfall measurements at their locations. Networks of rain gauges can offer better insight into the space-time variability of rainfall, but they tend to be too widely spaced for accurate estimates between points. While remote sensing systems, such as radars and networks of microwave links, can offer good insight in the spatial variability of rainfall they tend to have more problems in identifying the correct rain amounts at the ground. A way to estimate the variability of rainfall between gauge points is to interpolate between them using fitted variograms. If a dense rain gauge network is lacking it is difficult to estimate variograms accurately. In this paper a 30-year dataset of daily rain accumulations gathered at 29 automatic weather stations operated by KNMI (Royal Netherlands Meteorological Institute) and a one-year dataset of 10 gauges in a network with a radius of 5 km around CESAR (Cabauw Experimental Site for Atmospheric Research) are employed to estimate variograms. Fitted variogram parameters are shown to vary according to season, following simple cosine functions. Semi-variances at short ranges during winter and spring tend to be underestimated, but semi-variances during summer and autumn are well predicted

Nutrient loss pathways from grazed grasslands and the effects of decreasing inputs: experimental results for three soil types

Agriculture is a main contributor of diffuse emissions of N and P to the environment. For N the main loss pathways are NH3-volatilization, leaching to ground and surface water and N-2(O) emissions. Currently, imposing restraints on farm inputs are used as policy tool to decrease N and P leaching to ground water and to surface water, and the same measure is suggested to combat emissions of N2O. The response, however, to these measures largely depends on the soil type. In this study nutrient flows of three dairy farms in The Netherlands with comparable intensity on sand, peat and clay soils were monitored for at least 2 years. The first aim was to provide quantitative data on current nutrient loss pathways. The second aim was to explore the responses in partitioning of the nutrient loss pathways when farm inputs were altered. Mean denitrification rates ranged from 103 kg N ha(-1) year(-1) for the sandy soil to 170 kg N ha(-1) year(-1) for the peat soil and leaching to surface water was about 73 kg N ha(-1) year(-1) for the sandy soil, 15 kg N ha(-1) year(-1) for the clay soil and 38 kg N ha(-1) year(-1) for the peat soil. For P, leaching to surface water ranged from 2 kg P ha(-1) year(-1) for the sandy site to 5 kg P ha(-1) year(-1) for the peat site. The sandy soil was most responsive to changes in N surpluses on leaching to surface water, followed by the peat soil and least responsive was the clay soil. For P, a similar sequence was found. This article demonstrates that similar reductions of N and P inputs result in different responses in N and P loss pathways for different soil types. These differences should be taken into account when evaluating measures to improve environmental performance of (dairy) farm

FluxSimulator: An R Package to Simulate Isotopomer Distributions in Metabolic Networks

The representation of biochemical knowledge in terms of fluxes (transformation rates) in a metabolic network is often a crucial step in the development of new drugs and efficient bioreactors. Mass spectroscopy (MS) and nuclear magnetic resonance spectroscopy (NMRS) in combination with ^13C labeled substrates are experimental techniques resulting in data that may be used to quantify fluxes in the metabolic network underlying a process. The massive amount of data generated by spectroscopic experiments increasingly requires software which models the dynamics of the underlying biological system. In this work we present an approach to handle isotopomer distributions in metabolic networks using an object-oriented programming approach, implemented using S4 classes in R. The developed package is called FluxSimulator and provides a user friendly interface to specify the topological information of the metabolic network as well as carbon atom transitions in plain text files. The package automatically derives the mathematical representation of the formulated network, and assembles a set of ordinary differential equations (ODEs) describing the change of each isotopomer pool over time. These ODEs are subsequently solved numerically. In a case study FluxSimulator was applied to an example network. Our results indicate that the package is able to reproduce exact changes in isotopomer compositions of the metabolite pools over time at given flux rates.

Giant coronary aneurysms: three-dimensional reconstruction

A 31 year old man was referred for the evaluation of chest pain. Cardiac CT reconstruction revealed multiple calcified giant coronary aneurysms. Most likely this patient suffered from subclinical Kawasaki’s disease in his childhood