A Modular Gradient-Sensing Network for Chemotaxis in Escherichia coli Revealed by Responses to Time-Varying Stimuli

The Escherichia coli chemotaxis-signaling pathway computes time derivatives of chemoeffector concentrations. This network features modules for signal reception/amplification and robust adaptation, with sensing of chemoeffector gradients determined by the way in which these modules are coupled in vivo. We characterized these modules and their coupling by using fluorescence resonance energy transfer to measure intracellular responses to time-varying stimuli. Receptor sensitivity was characterized by step stimuli, the gradient sensitivity by exponential ramp stimuli, and the frequency response by exponential sine-wave stimuli. Analysis of these data revealed the structure of the feedback transfer function linking the amplification and adaptation modules. Feedback near steady state was found to be weak, consistent with strong fluctuations and slow recovery from small perturbations. Gradient sensitivity and frequency response both depended strongly on temperature. We found that time derivatives can be computed by the chemotaxis system for input frequencies below 0.006 Hz at 22°C and below 0.018 Hz at 32°C. Our results show how dynamic input–output measurements, time honored in physiology, can serve as powerful tools in deciphering cell-signaling mechanisms.Molecular and Cellular Biolog

Differential Distribution of Ca2+-Activated K+ Channel Splice Variants among Hair Cells along the Tonotopic Axis of the Chick Cochlea

AbstractSummary We have cloned from the receptor epithelium of the chick cochlea a family of alternatively spliced cDNAs derived from cslo, which encodes a Ca2+-activated K+ channel like those shown to help determine the resonant frequency of electrically tuned hair cells. Our results from PCRs using template RNAs from both tonotopically subdivided receptor epithelia and single hair cells demonstrate differential exon usage along the frequency axis of the epithelium at multiple splice sites in cslo. We also show that single hair cells express more than one splice variant at a given splice site. Since channel isoforms encoded by differentially spliced slo transcripts in other species are functionally heterogeneous, these data suggest that differential processing of slo transcripts may account, at least in part, for the systematic variation in hair-cell membrane properties along the frequency axis of electrically tuned auditory receptor epithelia

Escaping from the Filter Bubble? The Effects of Novelty and Serendipity on Users’ Evaluations of Online Recommendations

Recommender systems aim to support users in identifying the most relevant items. However, there are concerns that recommenders may imprison users in a “filter bubble” by recommending items predominantly known to them. On the other hand, providing unconventional items may increase risks of not meeting users’ taste. Given this trade-off, we analyze the effects of consumers’ perceived levels of recommendation novelty and serendipity on perceived preference fit and enjoyment. We find that merely increasing the level of novel recommendations is disadvantageous. Instead, recommenders should provide more serendipitous recommendations as this leads to higher perceived preference fit and enjoyment. In addition, market and recommender technology characteristics must be taken into account, since they partially determine the level of novel and serendipitous recommendations. Our findings have significant implications for research as they add additional insights on users’ evaluations of recommender systems. For practice, our results support online retailers in developing better recommenders