Characterizing Dynamic Changes in the Human Blood Transcriptional Network

Gene expression data generated systematically in a given system over multiple time points provides a source of perturbation that can be leveraged to infer causal relationships among genes explaining network changes. Previously, we showed that food intake has a large impact on blood gene expression patterns and that these responses, either in terms of gene expression level or gene-gene connectivity, are strongly associated with metabolic diseases. In this study, we explored which genes drive the changes of gene expression patterns in response to time and food intake. We applied the Granger causality test and the dynamic Bayesian network to gene expression data generated from blood samples collected at multiple time points during the course of a day. The simulation result shows that combining many short time series together is as powerful to infer Granger causality as using a single long time series. Using the Granger causality test, we identified genes that were supported as the most likely causal candidates for the coordinated temporal changes in the network. These results show that PER1 is a key regulator of the blood transcriptional network, in which multiple biological processes are under circadian rhythm regulation. The fasted and fed dynamic Bayesian networks showed that over 72% of dynamic connections are self links. Finally, we show that different processes such as inflammation and lipid metabolism, which are disconnected in the static network, become dynamically linked in response to food intake, which would suggest that increasing nutritional load leads to coordinate regulation of these biological processes. In conclusion, our results suggest that food intake has a profound impact on the dynamic co-regulation of multiple biological processes, such as metabolism, immune response, apoptosis and circadian rhythm. The results could have broader implications for the design of studies of disease association and drug response in clinical trials

Comparison of Traditional Instruction on Reflection and Rotation in a Nepalese High School with an ICT-Rich, Student-Centered, Investigative Approach

A teacher-centered, examination-driven instructional approach emphasizing knowledge of facts and standard methods through drill-and-practice without use of Information and Communications Technology (ICT) is still dominant in Nepalese high schools. In this article, we present a classroom study in which the traditional instructional approach has been replaced by an ICT-rich, student-centered, investigative approach in the context of teaching and learning basic concepts of reflection and rotation. Here, ICT refers to dynamic geometry software. Through a pretest-posttest control and experimental group research design, we compared the effects of both approaches on students’ understanding. A test was designed and used for investigating students’ alternative conceptions of reflection and rotation. The results showed that the experimental group outperformed the control group and there were indications of a lasting effect. Qualitative analysis indicated that all distinctive aspects of the experimental approach had positive effects on the students’ performance and learning experience. This study can also be considered as an evidence-based example of how one can, with limited ICT facilities, still achieve improvements in teaching and learning at a public high school in a developing country

The institutional and economic foundations of regional proto-federations

In the present paper we analyse the ancient Greek regional proto-federations of free-democratic city-states. We examine their political institutions and policies like common defence, representative federal bodies such as popular assemblies, parliament, state and regional organization, federal finance ministers as well as their economic institutions: common currency, federal budget and federal revenues. We address in more detail the case of the Aetolian League, or Federation, comparing it with some of today's federal states and the European Union and conclude that in some respects, the proto-federation was more advanced than the EU, and thus can serve as a benchmark in addressing current European integration issues