Using GeneReg to construct time delay gene regulatory networks

<p>Abstract</p> <p>Background</p> <p>Understanding gene expression and regulation is essential for understanding biological mechanisms. Because gene expression profiling has been widely used in basic biological research, especially in transcription regulation studies, we have developed GeneReg, an easy-to-use R package, to construct gene regulatory networks from time course gene expression profiling data; More importantly, this package can provide information about time delays between expression change in a regulator and that of its target genes.</p> <p>Findings</p> <p>The R package GeneReg is based on time delay linear regression, which can generate a model of the expression levels of regulators at a given time point against the expression levels of their target genes at a later time point. There are two parameters in the model, time delay and regulation coefficient. Time delay is the time lag during which expression change of the regulator is transmitted to change in target gene expression. Regulation coefficient expresses the regulation effect: a positive regulation coefficient indicates activation and negative indicates repression. GeneReg was implemented on a real Saccharomyces cerevisiae cell cycle dataset; more than thirty percent of the modeled regulations, based entirely on gene expression files, were found to be consistent with previous discoveries from known databases.</p> <p>Conclusions</p> <p>GeneReg is an easy-to-use, simple, fast R package for gene regulatory network construction from short time course gene expression data. It may be applied to study time-related biological processes such as cell cycle, cell differentiation, or causal inference.</p

Dengue Vaccines Regulatory Pathways: A Report on Two Meetings with Regulators of Developing Countries

Richard Mahoney and colleagues summarize two recent meetings convened by the Pediatric Dengue Vaccine Initiative and the Developing Countries' Vaccine Regulators Network on regulatory issues that need to be addressed before licensing dengue vaccines

Faecal calprotectin: factors affecting levels and its potential role as a surrogate marker for risk of development of Crohn's Disease.

BACKGROUND: Faecal calprotectin (FC) is one of the most widely used non-invasive tests for the diagnosis and assessment of Crohn's disease (CD) activity. Despite this, factors other than disease activity which affect levels have not been extensively reviewed. This is of importance when using FC in the diagnostic setting but also may be of utility in studying the aetiology of disease. OBJECTIVES: Our review outlines environmental risk factors that affect FC levels influencing diagnostic accuracy and how these may be associated with risk of developing CD. FC as a surrogate marker could be used to validate risk factors established in case control studies where prospective studies are not feasible. Proof of this concept is provided by our identification of obesity as being associated with elevated FC, our subsequent confirmation of obesity as risk factor for CD and the subsequent verification in prospective studies, as well as associations of lack of physical activity and dietary fibre intake with elevated FC levels and their subsequent confirmation as risk factors in prospective studies. CONCLUSION: We believe that FC is likely to prove a useful surrogate marker for risk of developing CD. This review has given a theoretical basis for considering the epidemiological determinants of CD which to date has been missing

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Nanostructured Systems Containing Rutin: In Vitro Antioxidant Activity and Photostability Studies

The improvement of the rutin photostability and its prolonged in vitro antioxidant activity were studied by means of its association with nanostructured aqueous dispersions. Rutin-loaded nanocapsules and rutin-loaded nanoemulsion showed mean particle size of 124.30 ± 2.06 and 124.17 ± 1.79, respectively, polydispersity index below 0.20, negative zeta potential, and encapsulation efficiency close to 100%. The in vitro antioxidant activity was evaluated by the formation of free radical ·OH after the exposure of hydrogen peroxide to a UV irradiation system. Rutin-loaded nanostructures showed lower rutin decay rates [(6.1 ± 0.6) 10−3 and (5.1 ± 0.4) 10−3 for nanocapsules and nanoemulsion, respectively] compared to the ethanolic solution [(35.0 ± 3.7) 10−3 min−1] and exposed solution [(40.1 ± 1.7) 10−3 min−1] as well as compared to exposed nanostructured dispersions [(19.5 ± 0.5) 10−3 and (26.6 ± 2.6) 10−3, for nanocapsules and nanoemulsion, respectively]. The presence of the polymeric layer in nanocapsules was fundamental to obtain a prolonged antioxidant activity, even if the mathematical modeling of the in vitro release profiles showed high adsorption of rutin to the particle/droplet surface for both formulations. Rutin-loaded nanostructures represent alternatives to the development of innovative nanomedicines