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The specific pH values of cellular compartments affect virtually all biochemical processes, including enzyme activity, protein folding and redox state. Accurate, sensitive and compartment-specific measurements of intracellular pH (pHi) dynamics in living cells are therefore crucial to the understanding of stress response and adaptation. We used the pH-sensitive GFP derivative 'ratiometric pHluorin' expressed in the cytosol and in the mitochondrial matrix of growing Saccharomyces cerevisiae to assess the variation in cytosolic pH ([pH.sub.cyt]) and mitochondrial pH ([pH.sub.mit]) in response to nutrient availability, respiratory chain activity, shifts in environmental pH and stress induced by addition of sorbic acid. The in vivo measurement allowed accurate determination of organelle-specific pH, determining a constant [pH.sub.cyt] of 7.2 and a constant [pH.sub.mit] of 7.5 in cells exponentially growing on glucose. We show that [pH.sub.cyt] and [pH.sub.mit] are differentially regulated by carbon source and respiratory chain inhibitors. Upon glucose starvation or sorbic acid stress, [pH.sub.i] decrease coincided with growth stasis. Additionally, pHi and growth coincided similarly in recovery after addition of glucose to glucose-starved cultures or after recovery from a sorbic acid pulse. We suggest a relation between pHi and cellular energy generation, and therefore a relation between [pH.sub.i] and growth.

The weak organic acid sorbic acid is a commonly used food preservative, as it inhibits the growth of bacteria, yeasts, and molds. We have used genome-wide transcriptional profiling of Bacillus subtilis cells during mild sorbic acid stress to reveal the growth-inhibitory activity of this preservative and to identify potential resistance mechanisms. Our analysis demonstrated that sorbic acid-stressed cells induce responses normally seen upon nutrient limitation. This is indicated by the strong derepression of the CcpA, CodY, and Fur regulon and the induction of tricarboxylic acid cycle genes, SigL- and SigH-mediated genes, and the stringent response. Intriguingly, these conditions did not lead to the activation of sporulation, competence, or the general stress response. The fatty acid biosynthesis (fab) genes and BkdR-regulated genes are upregulated, which may indicate plasma membrane remodeling. This was further supported by the reduced sensitivity toward thefab inhibitor cerulenin upon sorbic acid stress. We are the first to present a comprehensive analysis of the transcriptional response of B. subtilis to sorbic acid stress.

This review discusses the recent developments in cell wall biogenesis of yeast in terms of the molecular architecture and composition and biosynthetic genes and their regulation. Also aspects of cell polarity and signal transduction between external and internal stimuli during growth and proliferation are presented.

The article discusses the cellular origin of pacemaker tissues and their molecular control of differentiation and morphogenesis in the heart. It states that pacemaker and conduction system mycoytes play a vitalrole in regulating the cardiac chambers' contraction. The primary pacemaker is the sinoatrial node (SAN) while the atrioventricular node (AVN) and ventricular conduction system are secondary pacemakers. The SAN cells resemble embroyonic mycoytes while AVN consists of various cell types.

The transcriptional responses of yeast cells to a wide variety of stress conditions have been studied extensively. In addition, deletion mutant collections have been widely used to measure the combined effect of gene loss and stress on growth (fitness). Here we present a comparative analysis of 1,095 publicly available transcription and genome-wide fitness profiles in yeast, from different laboratories and experimental platforms. We analyzed these data, using T-profiler, to describe the correlation in behavior of a priori defined functional groups. Two-mode clustering analysis of the fitness T-profiles revealed that functional groups involved in regulating ribosome biogenesis and translation offer general stress resistance. These groups are closely related to growth rate and nutrient availability. General stress sensitivity was found in deletion mutant groups functioning in intracellular vesicular transport, actin cytoskeleton organization, and cell polarity, indicating that they play an key role in maintaining yeast adaptability. Analysis of the phenotypic and transcriptional variability of our a priori defined functional groups showed that the quantitative effect on fitness of both resistant and sensitive groups is highly condition-dependent. Finally, we discuss the implications of our results for combinatorial drug design.