The ndh gene of Escherichia coli which encodes an NADH dehydrogenase contains a putative FNR-binding site in its upstream non-coding region, and its expression has been investigated using an ndh-lacZ fusion. Expression of the fusion was found to be reduced during anaerobic growth, and experiments with hosts containing an fnr mutation and/or a multicopy fnr+ plasmid indicated that the anaerobic repression of the ndh gene is mediated by the FNR protein. Thus FNR can function as an anaerobic repressor as well as an anaerobic transcriptional activator. The results are consistent with the FNR-binding function attributed to the proposed consensus sequence. Using frdA- and ndh-lacZ fusions exhibiting positive and negative regulation by FNR, it was further shown that the depletion of metal ions in growth media with chelating agents mimics oxygen with respect to the activity of FNR. Possible roles for metal ions in the oxygen-sensing pathway associated with FNR function are discussed.

Understanding life at a systems level is a major aim of biology.The bacterium Escherichia coli offers one of the best opportunities to achieve this goal. It is a metabolically versatile bacterium able to respond to changes in oxygen availability. This ability is a crucial component of its lifestyle, allowing it to thrive in aerobic external environments and under the oxygen-starved conditions of a host gut. The controlled growth conditions of chemostat culture were combined with transcript profiling to investigate transcriptome dynamics during the transition from aerobic to micro-aerobic conditions. In addition to predictable changes in transcripts encoding proteins of central metabolism, the abundances of transcripts involved in homeostasis of redox-reactive metals (Cu and Fe), and cell envelope stress were significantly altered. To gain further insight into the responses of the regulatory networks, the activities of key transcription factors during the transition to micro-aerobic conditions were inferred using a probabilistic modeling approach, which revealed that the response of the direct oxygen sensor FNR was rapid and overshot, whereas the indirect oxygen sensor ArcA reacted more slowly. Similarly, the cell envelope stress sensors RpoE and CpxR reacted rapidly and more slowly, respectively. Thus, it is suggested that combining rapid and slow reacting components in regulatory networks might be a feature of systems in which a signal is perceived by two or more functionally related transcription factors controlling overlapping regulons.Escherichia coli is a metabolically versatile bacterium that is able to grow in the presence and absence of oxygen. To achieve this, it exploits a flexible biochemistry in which aerobic respiration is preferred to anaerobic respiration, which in turn is preferred to fermentation. The preference for aerobic respiration reflects the relative energetic efficiencies of the alternative metabolic modes (1). To exploit the energetic benefits conferred by aerobic respiration, E. coli has two alternative quinol oxidases, cytochrome bo 3 and cytochrome bd (2). Cytochrome bo 3 is a heme-copper protein that is synthesized under aerobic conditions and has a lower affinity for O 2 than the heme protein cytochrome bd, which has a very high affinity for O 2 and is synthesized under micro-aerobic conditions (3-5). In a further adaptation to lower O 2 concentrations, the role of the pyruvate dehydrogenase complex (PDHC), 2 which oxidizes pyruvate to acetyl-CoA and CO 2 , is progressively taken over by pyruvate formate-lyase (PFL), which converts pyruvate to acetyl-CoA and formate (1). These adaptations allow the bacteria to exploit the relatively low levels of O 2 present under micro-aerobic conditions and maintain redox balance.Adaptation to changes in O 2 availability is regulated at the level of transcription by two well characterized systems, FNR and ArcBA (6 -9). FNR is a direct O 2 sensor (10), whereas the ArcBA two-component system senses O 2 availability indirectly by monitoring the redo...

The decreased postprandial bile acid response in obese subjects compared with normal weight subjects may partly explain the suboptimal GLP-1 and PYY responses and could affect appetite, glycaemic control and energy expenditure.

The Escherichia coli hlyE gene (also known as clyA or sheA) codes for a novel pore-forming toxin. Previous work has shown that the global transcription factors FNR and CRP positively regulate hlyE expression by binding at the same site. Here in vivo transcription studies reveal that FNR occupies the hlyE promoter more frequently than CRP, providing a mechanism for the moderate upregulation of hlyE expression in response to two distinct environmental signals (oxygen and glucose starvation). It has been reported that H-NS interacts with two large regions of the hlyE promoter (PhlyE), one upstream of the ؊35 element and one downstream of the ؊10 element. Here we identify two high-affinity H-NS sites, H-NS I, located at the 3 end of the extended upstream footprint, and H-NS II, located at the 5 end of the extended downstream footprint. It is suggested that these high-affinity sites initiate the progressive formation of higher order complexes, allowing a range of H-NS-mediated regulatory effects at PhlyE. Finally, the identification of a SlyA binding site that overlaps the H-NS I site in PhlyE suggests a mechanism to explain how SlyA overproduction enhances hlyE expression by antagonizing the negative effects of H-NS.

SummaryHumans are intrinsically social animals, forming enduring affiliative bonds [1]. However, a striking minority with psychopathic traits, who present with violent and antisocial behaviors, tend to value other people only insofar as they contribute to their own advancement [2, 3]. Extant research has addressed the neurocognitive processes associated with aggression in such individuals, but we know remarkably little about processes underlying their atypical social affiliation. This is surprising, given the importance of affiliation and bonding in promoting social order and reducing aggression [4, 5]. Human laughter engages brain areas that facilitate social reciprocity and emotional resonance, consistent with its established role in promoting affiliation and social cohesion [6, 7, 8]. We show that, compared with typically developing boys, those at risk for antisocial behavior in general (irrespective of their risk of psychopathy) display reduced neural response to laughter in the supplementary motor area, a premotor region thought to facilitate motor readiness to join in during social behavior [9, 10, 11]. Those at highest risk for developing psychopathy additionally show reduced neural responses to laughter in the anterior insula. This region is implicated in auditory-motor processing and in linking action tendencies with emotional experience and subjective feelings [10, 12, 13]. Furthermore, this same group reports reduced desire to join in with the laughter of others—a behavioral profile in part accounted for by the attenuated anterior insula response. These findings suggest that atypical processing of laughter could represent a novel mechanism that impoverishes social relationships and increases risk for psychopathy and antisocial behavior.