Transcriptome analysis of a respiratory Saccharomyces cerevisiae strain suggests the expression of its phenotype is glucose insensitive and predominantly controlled by Hap4, Cat8 and Mig1

BACKGROUND: We previously described the first respiratory Saccharomyces cerevisiae strain, KOY.TM6*P, by integrating the gene encoding a chimeric hexose transporter, Tm6*, into the genome of an hxt null yeast. Subsequently we transferred this respiratory phenotype in the presence of up to 50 g/L glucose to a yeast strain, V5 hxt1-7Delta, in which only HXT1-7 had been deleted. In this study, we compared the transcriptome of the resultant strain, V5.TM6*P, with that of its wild-type parent, V5, at different glucose concentrations. RESULTS: cDNA array analyses revealed that alterations in gene expression that occur when transitioning from a respiro-fermentative (V5) to a respiratory (V5.TM6*P) strain, are very similar to those in cells undergoing a diauxic shift. We also undertook an analysis of transcription factor binding sites in our dataset by examining previously-published biological data for Hap4 (in complex with Hap2, 3, 5), Cat8 and Mig1, and used this in combination with verified binding consensus sequences to identify genes likely to be regulated by one or more of these. Of the induced genes in our dataset, 77% had binding sites for the Hap complex, with 72% having at least two. In addition, 13% were found to have a binding site for Cat8 and 21% had a binding site for Mig1. Unexpectedly, both the up- and down-regulation of many of the genes in our dataset had a clear glucose dependence in the parent V5 strain that was not present in V5.TM6*P. This indicates that the relief of glucose repression is already operable at much higher glucose concentrations than is widely accepted and suggests that glucose sensing might occur inside the cell. CONCLUSION: Our dataset gives a remarkably complete view of the involvement of genes in the TCA cycle, glyoxylate cycle and respiratory chain in the expression of the phenotype of V5.TM6*P. Furthermore, 88% of the transcriptional response of the induced genes in our dataset can be related to the potential activities of just three proteins: Hap4, Cat8 and Mig1. Overall, our data support genetic remodelling in V5.TM6*P consistent with a respiratory metabolism which is insensitive to external glucose concentrations.

The impact of coordination on the effectiveness of last mile relief distribution

Last mile relief distribution is the final stage of humanitarian logistics. It refers to the supply of relief items from local distribution centers to the disaster affected people (Balcik et al., 2008). In the last mile relief distribution literature, researchers have focused on the use of optimisation techniques for determining the exact optimal solution (Liberatore et al., 2014), but there is a need to include behavioural factors with those optimisation techniques in order to obtain better predictive results. This paper will explain how improving the coordination factor increases the effectiveness of the last mile relief distribution process. There are two stages of methodology used to achieve the goal: Interviews: The authors conducted interviews with the Indian Government and with South Asian NGOs to identify the critical factors for final relief distribution. After thematic and content analysis of the interviews and the reports, the authors found some behavioural factors which affect the final relief distribution. Model building: Last mile relief distribution in India follows a specific framework described in the Indian Government disaster management handbook. We modelled this framework using agent based simulation and investigated the impact of coordination on effectiveness. We define effectiveness as the speed and accuracy with which aid is delivered to affected people. We tested through simulation modelling whether coordination improves effectiveness.