A mathematical model of the stoichiometric control of Smad complex formation in TGF-B signal transducion pathway

Cell fate in multicellular organism is regulated by the diffusible factor from surrounding cells in concentration-dependent manner. TGF-beta is a large protein family of the diffusible proteins secreted from a localized source. The signal of TGF-beta is transduced by Smad family transcription factor. Though it is well known that the stoichiometry of Smads in the transcriptional complex regulates the specificity of target genes of TGF-beta signal, little is known what the stoichiometry of Smads in the transcriptional complex is determined in TGF-beta signal transduction in concentration-dependent manner. To investigate the dynamics of Smad complex formation, we construct a two-compartment model for Smad complex formation in TGF-beta signal transduction. A simplified one-way oligomerization model, which ignores dissociation and well appropriate the full model under high expression levels of R- and Co-Smad, is constructed to analytically investigate the effect of the oligomerization of Smad. Our one-way model reveals that not only shuttling of the Smad from the cytoplasm to the nucleus but also the preferential accumulation of the heteromeric complex in oligomerization can contribute to the predominant production of the heteromeric complex of Smad including both R- and Co-Smad. It is also shown that oligomerization of Smad can contribute to the specificity of signal transduction. In endothelial cells, both Smad-1/5/8 and -2/3 pathways are activated by TGF-beta. The difference of the activity between the two pathways is amplified by trimerization but not by dimerization, suggesting possible importance of trimerization in maintaining the specificity of signal transduction

Optimal Phosphorylation Step Number of Intracellular Signal Transduction Pathway

Eukaryotic cells use signal transduction network to respond in specific ways to external signals from their environment. Several signal transduction pathway are composed of multi-step chemical reactions. We here theoretically study what determines the number of kinase phosphorylation steps composing of the intracellular signal transduction cascade. We examine a simple mathematical model for the association and phosphorylation process of kinases in the signal transduction cascade. We focus on the speed of signal transduction as the criterion for determining the optimal response. The present model first reveals that the initial expression level of kinase in each step of the cascade must be the same in the optimal response under the constraint of the constant total kinase concentration. The second conclusion is that the optimal step number of kinase cascade is primarily determined by the ratio of the target concentration of the final phosphorylated kinase in the cascade to that of input signal molecule, C/S. A multi-step phosphorylation can be optimal when the amplification of the final product concentration C relative to the input signal S is sufficiently large. This suggests that multi-step phosphorylation would have evolved to accelerate the speed of transduction of weak signals

A Mathematical Model for Apoptosome Assembly: The Optimal Cytochrome c/Apaf-1 Ratio

Apoptosis, a highly conserved form of cell suicide, is regulated by apoptotic signals and their transduction with caspases, a family of cystein proteases. Caspases are constantly expressed in the normal cells as inactive pro-enzymes. The activity of caspase is regulated by the proteolysis. Sequential proteolytic reactions of caspases are needed to execute apoptosis. Mitochondrial pathway is one of these apoptotic signal pathways, in which caspases are oligomerized into characteristic heptamer structure, called apoptosome, with caspase-9 that activate the effector caspases for apoptosis. To investigate the dynamics of signal transduction pathway regulated by oligomerization, we construct a mathematical model for Apaf-1 heptamer assembly process. The model first reveals that intermediate products can remain unconverted even after all assemble reactions are completed. The second result of the model is that the conversion efficiency of Apaf-1 heptamer assembly is maximized when the initial concentration of cytochrome c is equal to that of Apaf-1. When the concentration of cytochrome c is sufficiently larger or smaller than that of Apaf-1, the final Apaf-1 heptamer production is decreased, because intermediate Apaf-1 oligomers (tetramers and bigger oligomers), which themselves are unable to form active heptamer, accumulate too fast in the cells, choking a smooth production of Apaf-1 heptamer. Slow activation of Apaf-1 monomers and small oligomers increase the conversion efficiency. We also study the optimal number of subunits comprising an active oligomer that maximize the conversion efficiency in assembly process, and found that the tetramer is the optimum

Newly emerged bumblebees are highly susceptible to gut parasite infection

One factor that can affect infection susceptibility is host age, the effects of which vary in a range of ways. For example, susceptibility may increase with age, due to senescence or decrease with age as a result of maturation of the immune system. If certain ages are more susceptible to infection, populations with contrasting demographics, such as same-age cohorts versus a mixture of ages, will exhibit differing disease prevalence. We use the bumblebee, Bombus terrestris, and its interaction with the gut trypanosome Crithidia sp. as a model system to investigate age-related susceptibility in a social insect. Crithidia sp. are widespread and prevalent parasites of bumblebees that are spread between colonies via faeces on flowers when foraging, and within colonies via contact with infected bees and contaminated surfaces and resources. In the field, Bombus spp. live for approximately three weeks. Here, we inoculated bumblebees at 0, 7, 14 and 21 days of age and measured their infection after one week. We also measured the level of gene expression of two antimicrobial peptides important in the defence against Crithidia bombi in bumblebees. We found that younger bumblebees are more susceptible to infection by Crithidia sp. than their older siblings. Specifically, individuals inoculated on their first day of emergence had infection intensities seven days later that were four-fold higher than bees inoculated at 21 days of age. In contrast, the gene expression of two AMPs known to protect against the trypanosome, abaecin and defensin, did not significantly vary with age. These results suggest that age does affect susceptibility to Crithidia sp. infection in B. terrestris. The higher susceptibility of callows may have implications for the susceptibility of colonies at different stages of their lifecycle, due to the contrasting age demography of workers in the colony

Theoretical Study on Transport Properties of Normal Metal - Zigzag Graphene Nanoribbon - Normal Metal Junctions

We investigate transport properties of the junctions in which the graphene nanoribbon with the zigzag shaped edges consisting of the $N$ legs is sandwiched by the two normal metals by means of recursive Green's function method. The conductance and the transmission probabilities are found to have the remarkable properties depending on the parity of $N$. The singular behaviors close to E=0 with $E$ being the Fermi energy are demonstrated. The channel filtering is shown to occur in the case with $N=$ even.Comment: 4 pages, 5 figure

Spin Currents Induced by Nonuniform Rashba-Type Spin-Orbit Field

We study the spin relaxation torque in nonmagnetic or ferromagnetic metals with nonuniform spin-orbit coupling within the Keldysh Green's function formalism. In non-magnet, the relaxation torque is shown to arise when the spin-orbit coupling is not uniform. In the absence of an external field, the spin current induced by the relaxation torque is proportional to the vector chirality of Rashba-type spin-orbit field (RSOF). In the presence of an external field, on the other hand, spin relaxation torque arises from the coupling of the external field and vector chirality of RSOF. Our result indicates that spin-sink or source effects are controlled by designing RSOF in junctions.Comment: 3 figure

Chiral constituent quark model study of the process γp→ηp\gamma p \to \eta p

A constituent quark model is developed for the reaction, allowing us to investigate all available data for differential cross sections as well as single polarization asymmetries (beam and target) by including {\it all} of the PDG, one to four star, nucleon resonances ($S_{11}$, $P_{11}$, $P_{13}$, $D_{13}$, $D_{15}$, $F_{15}$, $F_{17}$, $G_{17}$, $G_{19}$, $H_{19}$, $I_{1,11}$, and $K_{1,13}$). Issues related to the missing resonances are also briefly discussed by examining possible contributions from several new resonances ($S_{11}$, $P_{11}$, $P_{13}$, $D_{13}$, $D_{15}$, and $H_{1,11}$).Comment: 3 pages,2 figures, presented in NSTAR2007, Bonn, Germany,5 - 8 September 200

Ferroelectric Nanotubes

We report the independent invention of ferroelectric nanotubes from groups in several countries. Devices have been made with three different materials: lead zirconate-titanate PbZr1-xTixO3 (PZT); barium titanate BaTiO3; and strontium bismuth tantalate SrBi2Ta2O9 (SBT). Several different deposition techniques have been used successfully, including misted CSD (chemical solution deposition) and pore wetting. Ferroelectric hysteresis and high optical nonlinearity have been demonstrated. The structures are analyzed via SEM, TEM, XRD, AFM (piezo-mode), and SHG. Applications to trenching in Si dynamic random access memories, ink-jet printers, and photonic devices are discussed. Ferroelectric filled pores as small as 20 nm in diameter have been studied

One-neutron knockout reaction of 17C on a hydrogen target at 70 MeV/nucleon

First experimental evidence of the population of the first 2- state in 16C above the neutron threshold is obtained by neutron knockout from 17C on a hydrogen target. The invariant mass method combined with in-beam gamma-ray detection is used to locate the state at 5.45(1) MeV. Comparison of its populating cross section and parallel momentum distribution with a Glauber model calculation utilizing the shell-model spectroscopic factor confirms the core-neutron removal nature of this state. Additionally, a previously known unbound state at 6.11 MeV and a new state at 6.28(2) MeV are observed. The position of the first 2- state, which belongs to a member of the lowest-lying p-sd cross shell transition, is reasonably well described by the shell-model calculation using the WBT interaction.Comment: 15 pages, 3 figure