Time-delayed models of gene regulatory networks

We discuss different mathematical models of gene regulatory networks as relevant to the onset and development of cancer. After discussion of alternativemodelling approaches, we use a paradigmatic two-gene network to focus on the role played by time delays in the dynamics of gene regulatory networks. We contrast the dynamics of the reduced model arising in the limit of fast mRNA dynamics with that of the full model. The review concludes with the discussion of some open problems

Bulletin of Mathematical Biology - facts, figures and comparisons

The Society for Mathematical Biology (SMB) owns the Bulletin of Mathematical Biology (BMB). This is an international journal devoted to the interface of mathematics and biology. At the 2003 SMB annual meeting in Dundee the Society asked the editor of the BMB to produce an analysis of impact factor, subject matter of papers, submission rates etc. Other members of the society were interested in the handling times of articles and wanted comparisons with other (appropriate) journals. In this article we present a brief history of the journal and report on how the journal impact factor has grown substantially in the last few years. We also present an analysis of subject areas of published papers over the past two years. We finally present data on times from receipt of paper to acceptance, acceptance to print (and to online publication) and compare these data with some other journals

Metallochaperones regulate intracellular copper levels.

Copper (Cu) is an important enzyme co-factor that is also extremely toxic at high intracellular concentrations, making active efflux mechanisms essential for preventing Cu accumulation. Here, we have investigated the mechanistic role of metallochaperones in regulating Cu efflux. We have constructed a computational model of Cu trafficking and efflux based on systems analysis of the Cu stress response of Halobacterium salinarum. We have validated several model predictions via assays of transcriptional dynamics and intracellular Cu levels, discovering a completely novel function for metallochaperones. We demonstrate that in addition to trafficking Cu ions, metallochaperones also function as buffers to modulate the transcriptional responsiveness and efficacy of Cu efflux. This buffering function of metallochaperones ultimately sets the upper limit for intracellular Cu levels and provides a mechanistic explanation for previously observed Cu metallochaperone mutation phenotypes

Antismoking campaigns’ perception and gender differences: a comparison among EEG Indices

Human factors’ aim is to understand and evaluate the interactions between people and tasks, technologies, and environment. Among human factors, it is possible then to include the subjective reaction to external stimuli, due to individual’s characteristics and states of mind. These processes are also involved in the perception of antismoking public service announcements (PSAs), the main tool for governments to contrast the first cause of preventable deaths in the world: tobacco addiction. In the light of that, in the present article, it has been investigated through the comparison of different electroencephalographic (EEG) indices a typical item known to be able of influencing PSA perception, that is gender. In order to investigate the neurophysiological underpinnings of such different perception, we tested two PSAs: one with a female character and one with a male character. Furthermore, the experimental sample was divided into men and women, as well as smokers and nonsmokers. The employed EEG indices were the mental engagement (ME: the ratio between beta activity and the sum of alpha and theta activity); the approach/withdrawal (AW: the frontal alpha asymmetry in the alpha band); and the frontal theta activity and the spectral asymmetry index (SASI: the ratio between beta minus theta and beta plus theta). Results suggested that the ME and the AW presented an opposite trend, with smokers showing higher ME and lower AW than nonsmokers. The ME and the frontal theta also evidenced a statistically significant interaction between the kind of the PSA and the gender of the observers; specifically, women showed higher ME and frontal theta activity for the male character PSA. This study then supports the usefulness of the ME and frontal theta for purposes of PSAs targeting on the basis of gender issues and of the ME and the AW and for purposes of PSAs targeting on the basis of smoking habits

Attention-dependent modulation of cortical taste circuits revealed by granger causality with signal-dependent noise

We show, for the first time, that in cortical areas, for example the insular, orbitofrontal, and lateral prefrontal cortex, there is signal-dependent noise in the fMRI blood-oxygen level dependent (BOLD) time series, with the variance of the noise increasing approximately linearly with the square of the signal. Classical Granger causal models are based on autoregressive models with time invariant covariance structure, and thus do not take this signal-dependent noise into account. To address this limitation, here we describe a Granger causal model with signal-dependent noise, and a novel, likelihood ratio test for causal inferences. We apply this approach to the data from an fMRI study to investigate the source of the top-down attentional control of taste intensity and taste pleasantness processing. The Granger causality with signal-dependent noise analysis reveals effects not identified by classical Granger causal analysis. In particular, there is a top-down effect from the posterior lateral prefrontal cortex to the insular taste cortex during attention to intensity but not to pleasantness, and there is a top-down effect from the anterior and posterior lateral prefrontal cortex to the orbitofrontal cortex during attention to pleasantness but not to intensity. In addition, there is stronger forward effective connectivity from the insular taste cortex to the orbitofrontal cortex during attention to pleasantness than during attention to intensity. These findings indicate the importance of explicitly modeling signal-dependent noise in functional neuroimaging, and reveal some of the processes involved in a biased activation theory of selective attention