Laboratory-based evolution and whole-genome sequencing can link genotype and phenotype. We used evolution of acid resistance in exponential phase Escherichia coli to study resistance to a lethal stress. Iterative selection at pH 2.5 generated five populations that were resistant to low pH in early exponential phase. Genome sequencing revealed multiple mutations, but the only gene mutated in all strains was evgS, part of a two-component system that has already been implicated in acid resistance. All these mutations were in the cytoplasmic PAS domain of EvgS, and were shown to be solely responsible for the resistant phenotype, causing strong upregulation at neutral pH of genes normally induced by low pH. Resistance to pH 2.5 in these strains did not require the transporter GadC, or the sigma factor RpoS. We found that EvgS-dependent constitutive acid resistance to pH 2.5 was retained in the absence of the regulators GadE or YdeO, but was lost if the oxidoreductase YdeP was also absent. A deletion in the periplasmic domain of EvgS abolished the response to low pH, but not the activity of the constitutive mutants. On the basis of these results we propose a model for how EvgS may become activated by low pH.

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A squirting wave model of the cochlear amplifier 1 5.1 Introduction 5.2 Squirting waves 5.3 SLR wave in the cochlea 5.4 Dispersion and tonotopic tuning 5.5 The cochlear amplifier as a standing wave 5.6 Derivation of equations governing squirting waves 5.7 Viscosity and the effects of hydrophobicity 5.8 Conclusions This chapter investigates the distinctive properties of symmetric Lloyd-Redwood (SLR) waves -known in ultrasonics as squirting waves -and describes how their unique characteristics make them well-suited for carrying positive feedback between rows of outer hair cells. This could provide standing-wave resonance -in essence a narrow-band cochlear amplifier. Based on known physical properties of the cochlea, such an amplifier can be readily tuned to match the full 10octave range of human hearing. SLR waves propagate in a thin liquid layer enclosed between two thin compliant plates or between a single such plate and a rigid wall, conditions found in the subtectorial space of the cochlea, and rely on the mass of the inter-plate fluid 1 Based on Bell, A. and N. H. Fletcher (2004). The cochlear amplifier as a standing wave: "squirting" waves between rows of outer hair cells? J. Acoust. Soc. Am. 116: 1016-1024.R 5 [2]interacting with the stiffness of the plates to provide extremely low phase velocity and high dispersion. The first property means SLR wavelengths can be as short as the distance between rows of outer hair cells, allowing standing wave formation; the second permits wide-range tuning using only an order-of-magnitude variation in cochlear physical properties, most importantly the inter-row spacing.Theoretically, viscous drag at the two surfaces should hinder SLR wave propagation at low frequencies, but by invoking hydrophobic effects this limitation might be overcome. R 5 [3]respond in unison. Furthermore, since the OHCs are arranged in three parallel rows, positive feedback at a resonance frequency related to the OHC spacing will occur and, as a result, will launch a 'radial' wave in a direction normal to the rows. This mechanism would operate effectively if the response sensitivity of the individual cells were adjusted neurally to be just below the threshold of oscillation.A major difficulty confronting this radial wave hypothesis, however, is the extremely low wave velocity and high dispersion required in order to have the wavelength match the separation between OHC rows over the full frequency range of the human cochlea. In this paper a wave type is identified that meets these requirements: a symmetric Lloyd-Redwood (SLR) wave, known in ultrasonics as a 'squirting' wave. This mechanism would provide the 'self-tuned critical oscillators' by which amplification of small signals takes place at a frequency where there is a dynamic instability (Hopf bifurcation) 5-9 . A feature of Hopf resonance ( §D 9.2/c) when applied to this system is that the tuning is governed by the frequencies of the oscillators, not the stiffness or inertia of the partition, and the oscillators will act as sharply tuned high-ga...

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