An Extended Gene Protein/Products Boolean Network Model Including Post-Transcriptional Regulation

Background: Networks Biology allows the study of complex interactions between biological systems using formal, well structured, and computationally friendly models. Several different network models can be created, depending on the type of interactions that need to be investigated. Gene Regulatory Networks (GRN) are an effective model commonly used to study the complex regulatory mechanisms of a cell. Unfortunately, given their intrinsic complexity and non discrete nature, the computational study of realistic-sized complex GRNs requires some abstractions. Boolean Networks (BNs), for example, are a reliable model that can be used to represent networks where the possible state of a node is a boolean value (0 or 1). Despite this strong simplification, BNs have been used to study both structural and dynamic properties of real as well as randomly generated GRNs. Results: In this paper we show how it is possible to include the post-transcriptional regulation mechanism (a key process mediated by small non-coding RNA molecules like the miRNAs) into the BN model of a GRN. The enhanced BN model is implemented in a software toolkit (EBNT) that allows to analyze boolean GRNs from both a structural and a dynamic point of view. The open-source toolkit is compatible with available visualization tools like Cytoscape and allows to run detailed analysis of the network topology as well as of its attractors, trajectories, and state-space. In the paper, a small GRN built around the mTOR gene is used to demonstrate the main capabilities of the toolkit. Conclusions: The extended model proposed in this paper opens new opportunities in the study of gene regulation. Several of the successful researches done with the support of BN to understand high-level characteristics of regulatory networks, can now be improved to better understand the role of post-transcriptional regulation for example as a network-wide noise-reduction or stabilization mechanism

Expression variability of co-regulated genes differentiates Saccharomyces cerevisiae strains

Background: Saccharomyces cerevisiae (Baker’s yeast) is found in diverse ecological niches and is characterized by high adaptive potential under challenging environments. In spite of recent advances on the study of yeast genome diversity, little is known about the underlying gene expression plasticity. In order to shed new light onto this biological question, we have compared transcriptome profiles of five environmental isolates, clinical and laboratorial strains at different time points of fermentation in synthetic must medium, during exponential and stationary growth phases. Results: Our data unveiled diversity in both intensity and timing of gene expression. Genes involved in glucose metabolism and in the stress response elicited during fermentation were among the most variable. This gene expression diversity increased at the onset of stationary phase (diauxic shift). Environmental isolates showed lower average transcript abundance of genes involved in the stress response, assimilation of nitrogen and vitamins, and sulphur metabolism, than other strains. Nitrogen metabolism genes showed significant variation in expression among the environmental isolates. Conclusions: Wild type yeast strains respond differentially to the stress imposed by nutrient depletion, ethanol accumulation and cell density increase, during fermentation of glucose in synthetic must medium. Our results support previous data showing that gene expression variability is a source of phenotypic diversity among closely related organisms.Fundação para a Ciência e TecnologiaThe authors wish to thank Adega Cooperativa da Bairrada, Cantanhede, Portugal, for providing the commercial strains

An exploratory retrospective assessment of a quantitative measure of diabetes risk: medical management and patient impact in a primary care setting

Maureen R Courtney,1 Edward J Moler,2 John A Osborne,3 Geoff Whitney,4 Scott E Conard5 1College of Nursing, University of Texas Arlington, Arlington, 2Clarient Diagnostics, Aliso Viejo, CA, 3State of the Heart Cardiology, Grapevine, 4WaveTwo, Inc., Irving, 5ACAP Health, Dallas, TX, USA Background: Primary care providers with limited time and resources bear a heavy responsibility for chronic disease prevention or progression. Reliable clinical tools are needed to risk stratify patients for more targeted care. This exploratory study examined the care of patients who had been risk stratified regarding their likelihood of clinically progressing to type 2 diabetes. Methods: This was a retrospective chart review pilot study conducted to assess a primary care provider's use of a risk screening test. In this quality improvement project, the result of the risk screening was examined in relation to its influence on medical management and clinical impact on patients at risk for diabetes. All providers were board certified in family medicine and had more than 10 years clinical experience in managing diabetes and prediabetes. No specific clinical practice guidelines were mandated for patient care in this pilot study. Physicians in the practice group received an orientation to the diabetes risk measure and its availability for use in a pilot study to be conducted over a 6-month period. We identified the 696 nondiabetic adults in family practices who received a risk screening test (PreDx®, a multi-marker blood test that estimates the 5-year likelihood of conversion to type 2 diabetes) between June and November 2011 for a 6-month sample. A comparison group of 2,002 patients from a total database of 3.2 million patients who did not receive the risk test was randomly selected from the same clinical database after matching for age, sex, selected diagnoses, and metabolic risk factors. Patient groups were compared for intensity of care provided and clinical impact. Results: Compared to patients with a similar demographic and diagnostic profile, patients who had the risk test received more intensive primary care and had better clinical outcome than comparison patients. Risk-tested patients were more likely to return for follow-up visits, be monitored for relevant cardio-metabolic risk factors, and receive prescription medications with P<0.001. Further, intensity of care was associated with the level of risk test result: patients with moderate or high scores were more likely to return for follow-up visits and receive prescription medications than patients with low scores. All P-values for comparison patients between the low and moderate groups, low and high groups, and moderate and high groups resulted in P<0.001. Risk-tested patients were more likely than their comparison group counterparts to achieve weight reduction, lowered blood pressure, and improved blood glucose and cholesterol as demonstrated by P-values of <0.001. Conclusion: Use of a risk stratification test in primary care may help providers to more effectively identify high risk patients, manage diabetes risk, increase patient involvement in diabetes risk management, and improve clinical outcomes. A randomized controlled study is the next step to investigate the impact of diabetes risk stratification in primary care. Keywords: patient outcomes, diabetes, diabetes preventio

Structure determination of chemisorbed c(2x2)P/Fe(100) using angle-resolved photoemission extended fine structure and self-consistent-field X α scattered-wave calculations: Comparison with c (2x2)S/Fe(100)

Angle-resolved photoemission extended fine structure (ARPEFS) was used to determine the structure of c(2x2)P/Fe(100). Photoemission data were collected normal to the (100) surface and 45° off-normal along the [011] direction at room temperature. A close analysis of the autoregressive linear-prediction-based Fourier transform indicates that the P atoms adsorb in the high-coordination fourfold hollow sites. Curved-wave multiple-scattering calculations confirmed the fourfold hollow adsorption site. The P atoms were determined to bond 1.02 Å above the first layer of Fe atoms and the Fe-P-Fe bond angle is 140.6°. Additionally, it was determined that there was no expansion of the Fe surface. Self-consistent-field Xα scattered-wave calculations were performed for the c(2x2)P/Fe(100) and the c(2x2)S/Fe(100) systems. These independent results are in excellent agreement with this P/Fe structure and the S/Fe structure previously published, confirming the ARPEFS determination that the Fe 1-Fe 2 interlayer spacing is contracted from the bulk value for S/Fe but not for P/Fe. Finally, this structure is compared to structures from the literature of atomic nitrogen, atomic oxygen, and sulfur adsorbed on the Fe(100) surface.link_to_subscribed_fulltex

The class of microarray games and the relevance index for genes

Coalitional game, Shapley value, Power index, Gene expression, Microarray, 91A12, 91A80, 92B15, 92C40,