Enzyme localization can drastically affect signal amplification in signal transduction pathways

Push-pull networks are ubiquitous in signal transduction pathways in both prokaryotic and eukaryotic cells. They allow cells to strongly amplify signals via the mechanism of zero-order ultrasensitivity. In a push-pull network, two antagonistic enzymes control the activity of a protein by covalent modification. These enzymes are often uniformly distributed in the cytoplasm. They can, however, also be colocalized in space, for instance, near the pole of the cell. Moreover, it is increasingly recognized that these enzymes can also be spatially separated, leading to gradients of the active form of the messenger protein. Here, we investigate the consequences of the spatial distributions of the enzymes for the amplification properties of push-pull networks. Our calculations reveal that enzyme localization by itself can have a dramatic effect on the gain. The gain is maximized when the two enzymes are either uniformly distributed or colocalized in one region in the cell. Depending on the diffusion constants, however, the sharpness of the response can be strongly reduced when the enzymes are spatially separated. We discuss how our predictions could be tested experimentally.Comment: PLoS Comp Biol, in press. 32 pages including 6 figures and supporting informatio

Forest Carbon Stocks in Woody Plants of Arba Minch Ground Water Forest and its Variations along Environmental Gradients

The role of forests in mitigating the effect of climate change depends on the carbon sequestration potential and management. This study was conducted to estimate the carbon stock and its variation along environmental gradients in Arba Minch Ground Water Forest. The data was collected from the field by measuring plants with a DBH of >5cm in quadrat plots of 10 X 20 m and the carbon stocks of each plant were analyzed by using allometric equations. From this study the mean total carbon stock density of Arba Minch Ground Water Forest was found to be 583.27 t ha-1, of which 829.12 t ha-1, 165.88 t ha-1, 1.28 t ha-1, 83.80 t ha-1 was contained in the above ground carbon, belowground carbon, litter carbon and soil organic carbon (0-30 cm depth) 0respectively. Similarly, the analysis of carbon stock variation of different carbon pools on eight different aspects of the forest area showed a significant variation with the exception of litter carbon stock and this is due to fast decomposition rate of litters and low amount of litter fall in the forest. The amount of carbon stock in above and belowground biomass, soil organic carbon and the total carbon stock was higher on the southern aspect as compared to other aspects. This study concluded that the carbon stock value of Arba Minch Ground Water Forest is large, and this will serve as a potential entry point for the engagement of the forest in REDD project.Keywords: Environmental variables; Ground Water Forest; Climate change; Biomass; Forest carbon stoc

Does export dependency hurt economic development? Empirical evidence from Singapore

A rapid export growth in East Asia was once identified as a source of the sustainable economic development that the region enjoyed. However, the current global recession has turned exports from an economic virtue to a vice. There is a growing awareness that a heavy reliance on exports has caused a serious economic downturn in the region. The present paper chooses Singapore as a case study to examine the relationship between the origin of the East Asian Miracle (i.e. export dependency) and the economic growth. For this purpose, the study employs a causality test developed by Toda and Yamamoto. The empirical findings indicate that despite a negative long-run relationship between export dependency and economic growth, Singapore's heavy reliance on exports does not seem to have produced negative effects on the nation's economic growth. This is because the increase in export dependency was an effect, and not a cause, of the country's output expansion.

When it Pays to Rush: Interpreting Morphogen Gradients Prior to Steady-State

During development, morphogen gradients precisely determine the position of gene expression boundaries despite the inevitable presence of fluctuations. Recent experiments suggest that some morphogen gradients may be interpreted prior to reaching steady-state. Theoretical work has predicted that such systems will be more robust to embryo-to-embryo fluctuations. By analysing two experimentally motivated models of morphogen gradient formation, we investigate the positional precision of gene expression boundaries determined by pre-steady-state morphogen gradients in the presence of embryo-to-embryo fluctuations, internal biochemical noise and variations in the timing of morphogen measurement. Morphogens that are direct transcription factors are found to be particularly sensitive to internal noise when interpreted prior to steady-state, disadvantaging early measurement, even in the presence of large embryo-to-embryo fluctuations. Morphogens interpreted by cell-surface receptors can be measured prior to steady-state without significant decrease in positional precision provided fluctuations in the timing of measurement are small. Applying our results to experiment, we predict that Bicoid, a transcription factor morphogen in Drosophila, is unlikely to be interpreted prior to reaching steady-state. We also predict that Activin in Xenopus and Nodal in zebrafish, morphogens interpreted by cell-surface receptors, can be decoded in pre-steady-state.Comment: 18 pages, 3 figure

Sampling rare switching events in biochemical networks

Bistable biochemical switches are ubiquitous in gene regulatory networks and signal transduction pathways. Their switching dynamics, however, are difficult to study directly in experiments or conventional computer simulations, because switching events are rapid, yet infrequent. We present a simulation technique that makes it possible to predict the rate and mechanism of flipping of biochemical switches. The method uses a series of interfaces in phase space between the two stable steady states of the switch to generate transition trajectories in a ratchet-like manner. We demonstrate its use by calculating the spontaneous flipping rate of a symmetric model of a genetic switch consisting of two mutually repressing genes. The rate constant can be obtained orders of magnitude more efficiently than using brute-force simulations. For this model switch, we show that the switching mechanism, and consequently the switching rate, depends crucially on whether the binding of one regulatory protein to the DNA excludes the binding of the other one. Our technique could also be used to study rare events and non-equilibrium processes in soft condensed matter systems.Comment: 9 pages, 6 figures, last page contains supplementary informatio