A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways

Quorum sensing (QS) is an important determinant of bacterial phenotype. Many cell functions are regulated by intricate and multimodal QS signal transduction processes. The LuxS/AI-2 QS system is highly conserved among Eubacteria and AI-2 is reported as a ‘universal' signal molecule. To understand the hierarchical organization of AI-2 circuitry, a comprehensive approach incorporating stochastic simulations was developed. We investigated the synthesis, uptake, and regulation of AI-2, developed testable hypotheses, and made several discoveries: (1) the mRNA transcript and protein levels of AI-2 synthases, Pfs and LuxS, do not contribute to the dramatically increased level of AI-2 found when cells are grown in the presence of glucose; (2) a concomitant increase in metabolic flux through this synthesis pathway in the presence of glucose only partially accounts for this difference. We predict that ‘high-flux' alternative pathways or additional biological steps are involved in AI-2 synthesis; and (3) experimental results validate this hypothesis. This work demonstrates the utility of linking cell physiology with systems-based stochastic models that can be assembled de novo with partial knowledge of biochemical pathways

S -Adenosyl- l -homocysteine in brain

Administration of methionine sulfoximine (MSO) to rats and mice significantly decreased cerebral levels of S -adenosyl- l -homocysteine (AdoHcy). Concurrent administration of methionine prevented this decrease and, when methionine was given alone, significantly elevated AdoHcy levels resulted in both species. Regionally, AdoHcy levels varied from 20 nmol/g in rat cerebellum and spinal cord to about 60 nmol/g in hypothalamus and midbrain. MSO decreased AdoHcy in all regions tested except striatum, midbrain, and spinal cord. AdoMet/AdoHcy ratios (methylation index) varied from 0.48 in hypothalamus to 2.4 in cerebellum, and MSO administration decreased these ratios in all regions except hypothalamus. AdoHcy hydrolase activity was lowest in hypothalamus, highest in brainstem and, generally, varied inversely with regional AdoHcy levels. MSO decreased AdoHcy hydrolase activity in all regions except hypothalamus and spinal cord. Cycloleucine administration resulted in significantly decreased levels of mouse brain AdoHcy, whereas the administration of dihydroxyphenylalanine (DOPA) failed to affect AdoHcy levels. It is concluded that (a) cerebral AdoHcy levels are more tightly regulated than are those of AdoMet after MSO administration, (b) slight fluctuations of AdoHcy levels may be important in regulating AdoHcy hydrolase activity and hence AdoHcy catabolism in vivo, (c) the AdoMet/AdoHcy ratio reflects the absolute AdoMet concentration rather than the transmethylation flux, (d) the decreased AdoMet levels in midbrain, cortex, and striatum after MSO with no corresponding decrease in AdoHcy suggest an enhanced AdoMet utilization, hence an increased transmethylation in the MSO preconvulsant state.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45411/1/11064_2004_Article_BF00966019.pd

Dynamic protein methylation in chromatin biology

Post-translational modification of chromatin is emerging as an increasingly important regulator of chromosomal processes. In particular, histone lysine and arginine methylation play important roles in regulating transcription, maintaining genomic integrity, and contributing to epigenetic memory. Recently, the use of new approaches to analyse histone methylation, the generation of genetic model systems, and the ability to interrogate genome wide histone modification profiles has aided in defining how histone methylation contributes to these processes. Here we focus on the recent advances in our understanding of the histone methylation system and examine how dynamic histone methylation contributes to normal cellular function in mammals

The Impact of a Natural Disaster on Classroom Curricula

This study examines classroom curricula and activities in the academic year sub sequent to a flooding disaster that led to school being canceled five week s before the usual end of the academic year. Fifty- seven elementary school teachers from five schools provided information regarding alterations they ma de in their curriculum in the academic year subsequent to the flood. Curricular adjustments took the form of additional review of information from the previous academic year and integration of flood related information into classroom curricula. Curricular adjustments made by teachers were found to vary as a function of the grade taught. Teachers in the earlies t grades made more alterations in their reading, writing, and expressive language instruction as compared to teachers in the more advanced grades. Teachers in the more advanced grades made more alterations in mathematics instruction than teachers in the earliest grades. Specific ways in which teachers included information regarding the flood into their curriculum included discussion, reading stories, drawing pictures, and writing essays and books on topics which related to floods . It is important to note that these post disaster interventions were unplanned; individual classroom teachers made decisions about if and how they would make alterations in their curriculum in the wake of the disaster the previous year. School districts may find it advantage to us to develop contingency plans in the event that a disaster or another significantly disruptive event does occur. We also recommend that school districts more ca r e fully document post-disaster educational experiences of their students  within and outside of the school district, in order to learn more about what types of academic interventions are helpful to students after the occurrence of disaster