Estimation of the source-by-source effect of autorepression on genetic noise.

Transcriptional autorepression has been thought to be one of the simplest control circuits to attenuate fluctuations in gene expression. Here, we explored the effect of autorepression on fluctuations from different noise sources. We theoretically represent the fluctuations in the copy number of proteins as the sum of several terms, each of which is related to a specific noise source and expressed as the product of the source-specific fluctuations under no autorepression (path gain) and the effect of autorepression on them (loop gain).

A mathematical model of respiratory and biothermal dynamics in brain hypothermia treatment.

Brain hypothermia treatment (BHT) requires proper mechanical ventilation and therapeutic cooling. The cooling strategy for BHT has been mainly discussed in the literature while little information is available on the respiratory management. We first developed a mathematical model that integrates the respiratory and biothermal dynamics to discuss the simultaneous managements of mechanical ventilation and therapeutic cooling.

Mathematical classification of regulatory logics for compound environmental changes.

This paper is concerned with biological regulatory mechanisms in response to the simultaneous occurrence of a huge number of environmental changes. The restricted resources of cells strictly limit the number of their regulatory methods; hence, cells must adopt, as compensation, special mechanisms to deal with the simultaneous occurrence of environmental changes. We hypothesize that cells use various control logics to integrate information about independent environmental changes related to a cell task and represent the resulting effects of the different ways of integration by logical functions.

Simulation of propofol anaesthesia for intracranial decompression using brain hypothermia treatment.

Background: Although propofol is commonly used for general anaesthesia of normothermic patients in clinical practice, little information is available in the literature regarding the use of propofol anaesthesia for intracranial decompression using brain hypothermia treatment. A novel propofol anaesthesia scheme is proposed that should promote such clinical application and improve understanding of the principles of using propofol anaesthesia for hypothermic intracranial decompression.

Methods: Theoretical analysis was carried out using a previously-developed integrative model of the thermoregulatory, hemodynamic and pharmacokinetic subsystems.

Stochastic approach to molecular interactions and computational theory of metabolic and genetic regulations.

The underlying molecular mechanisms of metabolic and genetic regulations are computationally identical and can be described by a finite state Markov process. We establish a common computational model for both regulations based on the stationary distribution of the Markov process with the aim of establishing a unified, quantitative model of general biological regulations. Various existing results regarding intracellular regulations are derived including the classical Michaelis-Menten equation and its generalization to more complex allosteric enzymes in a systematic way.

Modulation of cellular rhythm and photoavoidance by oscillatory irradiation in the Physarum plasmodium.

We studied responses of cellular rhythm and light-induced movement to periodic irradiation in a unicellular amoeboid organism, the Physarum plasmodium. The intrinsic frequency of the contraction rhythm, which is based on biochemical oscillations, became synchronized with the frequency of periodic irradiation with light when both frequencies were close enough. In order to study the role of the synchronization in light-induced movement, periodic irradiation was applied to only part of the plasmodium.

Highly optimised global organisation of metabolic networks.

High-level, mathematically precise descriptions of the global organisation of complex metabolic networks are necessary for understanding the global structure of metabolic networks, the interpretation and integration of large amounts of biologic data (sequences, various -omics) and ultimately for rational design of therapies for disease processes. Metabolic networks are highly organised to execute their function efficiently while tolerating wide variation in their environment. These networks are constrained by physical requirements (e.

Mathematical description of gene regulatory units.

Revealing the control mechanisms responsible for the cell's surprisingly well-organized functions should lead directly to a better understanding of how the cell adapts to extraordinarily changing environments. A general framework for describing models that can represent diverse biochemical regulatory functions systematically would help not only systematic interpretation of the various models proposed for certain systems but also further understanding of the general control mechanism and design principles underlying different biological systems. This article presents a unified mathematical framework for describing gene regulatory units.

An integrated model of thermodynamic-hemodynamic-pharmacokinetic system and its application on decoupling control of intracranial temperature and pressure in brain hypothermia treatment.

Brain hypothermia treatment (BHT) is an intensive care characterized by simultaneous managements of various vital signs, such as intracranial temperature (ICT) and pressure (ICP), of the severe neuropatient. Medical treatments including therapeutic ambient cooling and diuresis are separately carried out based on the experience of the medical staff involved in the clinical management of various pathophysiological processes, such as thermodynamics, hemodynamics and pharmacokinetics. However, no special attention has been paid to the interactions among these subsystems in therapeutic hypothermia because of the lack of theoretical knowledge.

Some protein interaction data do not exhibit power law statistics.

It has been claimed that protein-protein interaction (PPI) networks are scale-free, and that identifying high-degree "hub" proteins reveals important features of PPI networks. In this paper, we evaluate the claims that PPI node degree sequences follow a power law, a necessary condition for networks to be scale-free. We provide two PPI network examples which clearly do not have power laws when analyzed correctly, and thus at least these PPI networks are not scale-free.

A mathematical model of intracranial pressure dynamics for brain hypothermia treatment.

Brain hypothermia treatment is used as a neuroprotectant to decompress the elevated intracranial pressure (ICP) in acute neuropatients. However, a quantitative relationship between decompression and brain hypothermia is still unclear, this makes medical treatment difficult and ineffective. The objective of this paper is to develop a general mathematical model integrating hemodynamics and biothermal dynamics to enable a quantitative prediction of transient responses of elevated ICP to ambient cooling temperature.

Scale-rich metabolic networks.

Recent research in biology has clarified many features of the global organization of metabolic networks, including the biochemical mechanisms responsible for power laws in metabolite degrees. The primary aim of this Letter is to give the simplest possible biochemical explanations and minimal toy models based on a highly optimized tolerance perspective, which show where and why metabolic networks have power laws. A second aim is to further explain why scale-free explanations fail in this case to correctly describe metabolism.

A novel mechanism of intragenic complementation between Phe to Ala calmodulin mutations.

Calmodulin (CaM) performs essential functions in cell proliferation in Saccharomyces cerevisiae. Previously, we isolated fourteen temperature-sensitive Phe-to-Ala mutations of the CaM-encoding gene CMD1. These mutations were classified into four intragenic complementation groups, suggesting that each group represents a loss of CaM interaction with its specific essential target protein.

Binding of calmodulin to Nuf1p is required for karyogamy in Saccharomyces cerevisiae.

The role of calmodulin (CaM) during mating in Saccharomyces cerevisiae was examined by using a set of Phe-to-Ala substitutions. We identified ten CaM mutants that exhibited significantly reduced mating efficiencies when crossed to a strain of the opposite mating type harboring the same CaM mutation. Most of the mating-defective CaM mutants were bilateral, i.

Glial cell line-derived neurotrophic factor up-regulates the expression of tyrosine hydroxylase gene in human neuroblastoma cell lines.

The role of glial cell line-derived neurotrophic factor (GDNF) in the survival of dopaminergic neurons has been well documented, but its effect on dopamine biosynthesis remains to be elucidated. In this study, the effect of GDNF on the gene expression of tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine biosynthesis, was investigated. We found that GDNF elevated the expression of the TH gene at both mRNA and protein levels in TGW cells, a human neuroblastoma cell line.

Manganese-induced apoptosis in PC12 cells.

Manganese has been known to induce neurological disorders similar to parkinsonisms for a long time. Dopamine deficiency has been demonstrated in Parkinson's disease and in chronic manganese poisoning, suggesting that the mechanisms underlying the neurotoxic effects of the metal ion are related to dysfunction of the extrapyramidal system. However, the details of the mechanisms have yet to be elucidated.

Manganese mimics the action of 1-methyl-4-phenylpyridinium ion, a dopaminergic neurotoxin, in rat striatal tissue slices.

Manganese and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are known to induce neurological pathologies similar to that of parkinsonism. Previous studies performed in rat striatal slices have shown that MPTP and related compounds inhibit tyrosine hydroxylation, a rate-limiting step of dopamine biosynthesis. Here, we reported that manganese inhibited tyrosine hydroxylation in rat striatal slices.

Extraction of specific signals with temporal structure.

In this work we develop a very simple batch learning algorithm for semiblind extraction of a desired source signal with temporal structure from linear mixtures. Although we use the concept of sequential blind extraction of sources and independent component analysis, we do not carry out the extraction in a completely blind manner; neither do we assume that sources are statistically independent. In fact, we show that the a priori information about the autocorrelation function of primary sources can be used to extract the desired signals (sources of interest) from their linear mixtures.

Interaction between cell shape and contraction pattern in the Physarum plasmodium.

The relationship between cell shape and rhythmic contractile activity in the large amoeboid organism Physarum polycephalum was studied. The organism develops intricate networks of veins in which protoplasmic sol moved to and fro very regularly. When migrating on plain agar, the plasmodium extends like a sheet and develops dendritic veins toward the rear.

Dependence of GABAergic synaptic areas on the interneuron type and target size.

In the neostriatum, several types of interneuron with distinct firing patterns and expression of neuroactive substances are known to exist. We found two types of neostriatal interneurons, parvalbumin-containing fast-spiking (FS) cells and somatostatin-containing low-threshold spike (LTS) cells to both be immunoreactive for GABA at their axon terminals in immersion-fixed brain slices from rat. To reveal the differences in synaptic connections between these two types of GABAergic interneurons, the postsynaptic target and their synaptic structure were compared by three-dimensional reconstructions from electron microscopic images of intracellularly stained axon terminals.

Diffusion-based learning theory for organizing visuo-motor coordination.

A diffusion-based learning theory is presented and applied to organize the visuomotor coordination of an eye-hand system which has redundant motion degree of freedom (dof). This theory considers the spatial optimality of the coordination: to minimize the end-effector position error of the eye-hand system as well as the differentiation of the joint angles with respect to the end-effector positions over all the bounded work space. By introducing variational methods with respect to the space, we derive a partial differential equation (PDE) of the joint angles with respect to the work space.

Phosphorylation and activation of p70 S6 kinase by manganese in PC12 cells.

Previous study has shown that the treatment of PC12 cells with manganese, a MPTP-like neurotoxin, causes transcription-dependent apoptosis. This is a useful model system for the study of neuronal cell death. Manganese-induced apoptosis is accompanied by the induction of DNA fragmentation, expressions of c-Fos and c-Jun, and activation of the c-Jun N-terminal kinase U(JNK) pathway.

Activation of JNK pathway and induction of apoptosis by manganese in PC12 cells.

Manganese is known to induce neurological disorders similar to parkinsonisms. A dopamine deficiency has been demonstrated in Parkinson's disease and in chronic manganese poisoning, suggesting that the mechanisms underlying the neurotoxic effects of the metal ion are related to a functional abnormality of the extrapyramidal system. However, the details have yet to be elucidated.

Noradrenergic excitation and inhibition of GABAergic cell types in rat frontal cortex.

Noradrenaline (NA) from the locus coeruleus and GABA from intracortical nonpyramidal cells exert strong influences on cortical activity. To assess possible interaction between the two, the effects of noradrenergic agonists on spontaneous GABAergic IPSCs as well as on the activity of identified GABAergic cell types were investigated by in vitro whole-cell recordings from the frontal cortex of 18- to 22-d-old rats. NA (3-50 microM) and an alpha-adrenergic agonist, 6-fluoronorepinephrine (FNE; 30-50 microM), induced an increase of IPSC frequency in pyramidal cells, but a beta-adrenergic agonist did not.