Linking transcriptional regulation and high resolution metabolic fluxes in yeast modulated by the global regulator Gcn4p

Genome sequencing dramatically increased our ability to understand cellular response to perturbation. Integrating system-wide measurements such as gene expression with networks of protein protein interactions and transcription factor binding revealed critical insights into cellular behavior. However, the potential of systems biology approaches is limited by difficulties in integrating metabolic measurements across the functional levels of the cell despite their being most closely linked to cellular phenotype. To address this limitation, we developed a model-based approach to correlate mRNA and metabolic flux data that combines information from both interaction network models and flux determination models. We started by quantifying 5,764 mRNAs, 54 metabolites, and 83 experimental (13)C-based reaction fluxes in continuous cultures of yeast under stress in the absence or presence of global regulator Gcn4p. Although mRNA expression alone did not directly predict metabolic response, this correlation improved through incorporating a network-based model of amino acid biosynthesis (from r = 0.07 to 0.80 for mRNA-flux agreement). The model provides evidence of general biological principles: rewiring of metabolic flux (i.e., use of different reaction pathways) by transcriptional regulation and metabolite interaction density (i.e., level of pairwise metabolite-protein interactions) as a key biosynthetic control determinant. Furthermore, this model predicted flux rewiring in studies of follow-on transcriptional regulators that were experimentally validated with additional (13)C-based flux measurements. As a first step in linking metabolic control and genetic regulatory networks, this model underscores the importance of integrating diverse data types in large-scale cellular models. We anticipate that an integrated approach focusing on metabolic measurements will facilitate construction of more realistic models of cellular regulation for understanding diseases and constructing strains for industrial applications

Stonefly (Plecoptera) fauna in a mountainous area of Central Brazil: composition and adult phenology

A survey of the stonefly (Plecoptera) fauna of streams of the Almas River basin, Pirenópolis, Goiás State, Central Brazil, is presented as well as data of some factors that could affeet the temporal distribution of the adults. For checking adult phenology, light sources were used in three stations from June 1993 to Jully 1994. The sampled individuais were identified to species or morphospecies, as possible. In this study, 301 individuais belonging to the perlid genera Anacroneuria Klapálek, 1909, Kempnyia Klapálek, 1916 and Macrogynoplax Enderlein, 1909 were collected. Adults of most species were collected along the studied period, except for those of Kempnyia that were restricted to the warm-rainy season, the same pattern for this genus in southeastern Brazil. Although adults of most species were collected along most of the studied period, the largest number of adults was collected in the months with larger mean temperatures, showing a clear seasonality in abundance