Differential roles of transcriptional and translational negative autoregulations in protein dynamics.

Cells continuously respond to stimuli to function properly by employing a wide variety of regulatory mechanisms that often involve protein up or down regulations. This study focuses on dynamics of a protein with negative autoregulations in , and assumes that the input signal up-regulates the protein, and then the protein down-regulates its own production 2 distinct types of mechanisms. The mathematical models describe the dynamics of mRNA and protein for 3 scenarios: (i) a simplistic model with no regulation, (ii) a model with transcriptional negative autoregulation, and (iii) a model with translational negative autoregulation.

Mathematical modeling reveals differential regulation of MAPK activity by phosphatase proteins in the yeast pheromone response pathway.

To prevent indefinite cellular responses to external signals, cells utilize various adaptation mechanisms. The yeast mating-response pathway is a model cellular system that exhibits adaptation to persistent external signals. This pathway employs a mitogen-activated protein kinase (MAPK) cascade which is composed of two well-known negative feedback inhibitions that involve the yeast phosphatase proteins Ptp3 and Msg5.

Differential transcriptional regulation by alternatively designed mechanisms: A mathematical modeling approach.

Cells maintain cellular homeostasis employing different regulatory mechanisms to respond external stimuli. We study two groups of signal-dependent transcriptional regulatory mechanisms. In the first group, we assume that repressor and activator proteins compete for binding to the same regulatory site on DNA (competitive mechanisms).

Mathematical modeling deciphers the benefits of alternatively-designed conserved activatory and inhibitory gene circuits.

Cells employ a variety of mechanisms as a response to external signals to maintain cellular homeostasis. In this study, we examine four activatory and four inhibitory protein synthesis mechanisms at both population and single cell level that can be triggered by a transient external signal. Activation mechanisms result from the assumption that cells can employ four different modes to temporarily increase the levels of a protein: decreased mRNA degradation, increased mRNA synthesis, decreased protein degradation and increased protein synthesis.

Dynamics matter: differences and similarities between alternatively designed mechanisms.

Cells selectively respond to external stimuli to maintain cellular homeostasis by making use of different regulatory mechanisms. We studied two classes of signal-dependent regulatory inhibition and activation mechanisms in this study. Inhibition mechanisms assume that inhibition can occur in two different ways: either by increasing the degradation rate or decreasing the production rate.

The characteristics of patients with chronic hepatitis B in Turkey.

Aim: To evaluate the characteristics of patients with hepatitis B virus (HBV) infection and summarize the treatment modalities.

Methods: By September 30, 2011 the data of 7871 HBsAg (+) patients were complied and analysed according to demographic and medical records (age, sex, laboratory tests, treatment with antiviral agents) in thirty centres of Turkey.

Results: Of the 7871 patients 3078 (39.

Efficacy and safety of tenofovir disoproxil fumarate in pregnancy for the prevention of vertical transmission of HBV infection.

Aim: To evaluate the effects of tenofovir disoproxil fumarate (TDF) use during late pregnancy to reduce hepatitis B virus (HBV) transmission in highly viremic mothers.

Methods: This retrospective study included 45 pregnant patients with hepatitis B e antigen (+) chronic hepatitis B and HBV DNA levels > 10⁷ copies/mL who received TDF 300 mg/d from week 18 to 27 of gestation (n = 21). Untreated pregnant patients served as controls (n = 24).

Combined computational and experimental analysis reveals mitogen-activated protein kinase-mediated feedback phosphorylation as a mechanism for signaling specificity.

Different environmental stimuli often use the same set of signaling proteins to achieve very different physiological outcomes. The mating and invasive growth pathways in yeast each employ a mitogen-activated protein (MAP) kinase cascade that includes Ste20, Ste11, and Ste7. Whereas proper mating requires Ste7 activation of the MAP kinase Fus3, invasive growth requires activation of the alternate MAP kinase Kss1.

Mathematical modeling of the low and high affinity arabinose transport systems in Escherichia coli.

A mathematical model was developed for the low and high affinity arabinose transport systems in E. coli. The model is a system of three ordinary differential equations and takes the dynamics of mRNAs for the araE and araFGH proteins and the internal arabinose into account.

Deterministic and stochastic simulation and analysis of biochemical reaction networks the lactose operon example.

A brief introduction to mathematical modeling of biochemical regulatory reaction networks is presented. Both deterministic and stochastic modeling techniques are covered with examples from enzyme kinetics, coupled reaction networks with oscillatory dynamics and bistability. The Yildirim-Mackey model for lactose operon is used as an example to discuss and show how deterministic and stochastic methods can be used to investigate various aspects of this bacterial circuit.

beta2-adrenergic receptor signaling and desensitization elucidated by quantitative modeling of real time cAMP dynamics.

G protein-coupled receptor signaling is dynamically regulated by multiple feedback mechanisms, which rapidly attenuate signals elicited by ligand stimulation, causing desensitization. The individual contributions of these mechanisms, however, are poorly understood. Here, we use an improved fluorescent biosensor for cAMP to measure second messenger dynamics stimulated by endogenous beta(2)-adrenergic receptor (beta(2)AR) in living cells.

Mathematical modeling of RGS and G-protein regulation in yeast.

G-protein-activated signaling pathways are capable of adapting to a persistent external stimulus. Desensitization is thought to occur at the receptor level as well as through negative feedback by a family of proteins called regulators of G-protein signaling (RGS). The pheromone response pathway in yeast is a typical example of such a system, and the relative simplicity of this pathway makes it an attractive system in investigating the regulatory role of RGS proteins.

Dynamics and bistability in a reduced model of the lac operon.

It is known that the lac operon regulatory pathway is capable of showing bistable behavior. This is an important complex feature, arising from the nonlinearity of the involved mechanisms, which is essential to understand the dynamic behavior of this molecular regulatory system. To find which of the mechanisms involved in the regulation of the lac operon is the origin of bistability, we take a previously published model which accounts for the dynamics of mRNA, lactose, allolactose, permease and beta-galactosidase involvement and simplify it by ignoring permease dynamics (assuming a constant permease concentration).

Modeling operon dynamics: the tryptophan and lactose operons as paradigms.

Understanding the regulation of gene control networks and their ensuing dynamics will be a critical component in the understanding of the mountain of genomic data being currently collected. This paper reviews recent mathematical modeling work on the tryptophan and lactose operons which are, respectively, the classical paradigms for repressible and inducible operons.

Regulators of G protein signaling and transient activation of signaling: experimental and computational analysis reveals negative and positive feedback controls on G protein activity.

Cellular responses to hormones and neurotransmitters are necessarily transient. The mating pheromone signal in yeast is typical. Signal initiation requires cell surface receptors, a G protein heterotrimer, and down-stream effectors.

Feedback regulation in the lactose operon: a mathematical modeling study and comparison with experimental data.

A mathematical model for the regulation of induction in the lac operon in Escherichia coli is presented. This model takes into account the dynamics of the permease facilitating the internalization of external lactose; internal lactose; beta-galactosidase, which is involved in the conversion of lactose to allolactose, glucose and galactose; the allolactose interactions with the lac repressor; and mRNA. The final model consists of five nonlinear differential delay equations with delays due to the transcription and translation process.