Project description:The most commonly studied prokaryotic sensory signal transduction systems include the one-component systems, phosphosignaling systems, extracytoplasmic function (ECF) sigma factor systems, and the various types of second messenger systems. Recently, we described the regulatory role of two separate sensory systems in Streptococcus mutans that jointly control bacteriocin gene expression, natural competence development, as well as a cell death pathway, yet they do not function via any of the currently recognized signal transduction paradigms. These systems, which we refer to as LytTR Regulatory Systems (LRS), minimally consist of two proteins, a transcription regulator from the LytTR Family and a transmembrane protein inhibitor of this transcription regulator. Here, we provide evidence suggesting that LRS are a unique uncharacterized class of prokaryotic sensory system. LRS exist in a basal inactive state. However, when LRS membrane inhibitor proteins are inactivated, an autoregulatory positive feedback loop is triggered due to LRS regulator protein interactions with direct repeat sequences located just upstream of the -35 sequences of LRS operon promoters. Uncharacterized LRS operons are widely encoded by a vast array of Gram positive and Gram negative bacteria as well as some archaea. These operons also contain unique direct repeat sequences immediately upstream of their operon promoters indicating that positive feedback autoregulation is a globally conserved feature of LRS. Despite the surprisingly widespread occurrence of LRS operons, the only characterized examples are those of S. mutans. Therefore, the current study provides a useful roadmap to investigate LRS function in the numerous other LRS-encoding organisms.
Project description:Vocal identity processing depends on the ability to tell apart two instances of different speakers whilst also being able to tell together two instances of the same speaker. Whilst previous research has examined these voice processing capabilities under relatively common listening conditions, it has not yet tested the limits of these capabilities. Here, two studies are presented that employ challenging listening tasks to determine just how good we are at these voice processing tasks. In Experiment 1, 54 university students were asked to distinguish between very similar sounding, yet different speakers (celebrity targets and their impersonators). Participants completed a 'Same/Different' task and a 'Which is the Celebrity?' task to pairs of speakers, and a 'Real or Not?' task to individual speakers. In Experiment 2, a separate group of 40 university students was asked to pair very different sounding instances of the same speakers (speaking and singing). Participants were presented with an array of voice clips and completed a 'Pairs Task' as a variant of the more traditional voice sorting task. The results of Experiment 1 suggested that significantly more mistakes were made when distinguishing celebrity targets from their impersonators than when distinguishing the same targets from control voices. Nevertheless, listeners were significantly better than chance in all three tasks despite the challenge. Similarly, the results of Experiment 2 suggested that it was significantly more difficult to pair singing and speaking clips than to pair two speaking clips, particularly when the speakers were unfamiliar. Again, however, the performance was significantly above zero, and was again better than chance in a cautious comparison. Taken together, the results suggest that vocal identity processing is a highly adaptable task, assisted by familiarity with the speaker. However, the fact that performance remained above chance in all tasks suggests that we had not reached the limit of our listeners' capability, despite the considerable listening challenges introduced. We conclude that voice processing is far better than previous research might have presumed.
Project description:Most bacterial response regulators (RRs) make contact with DNA through a recognition α-helix in their DNA-binding domains. An emerging class of RRs interacts with DNA via a relatively novel type of binding domain, called the LytTR domain, which is mainly composed of β-strands. YpdB belongs to this latter class, is part of a nutrient-sensing network in Escherichia coli and triggers expression of its only target gene, yhjX, in response to extracellular pyruvate. Expression of yhjX mainly occurs in the late exponential growth phase, and in a pulsed manner. Although the DNA-binding sites for YpdB are well defined, exactly how YpdB initiates pulsed gene expression has remained elusive. To address this question, we measured the binding kinetics of wild-type YpdB and the phosphomimetic variant YpdB-D53E to the yhjX promoter region (PyhjX) using surface plasmon resonance (SPR) spectroscopy combined with interaction map® (IM) analysis. Both YpdB and YpdB-D53E bound as monomers to the tandem-repeat sequences in the promoter, with YpdB-D53E displaying a higher maximal binding rate than YpdB. Furthermore, we identified a high-affinity (A-site) and a low-affinity binding site (B-site) within the yhjX promoter. Only YpdB-D53E utilizes an 'AB-BA' DNA-binding mechanism, involving sequential and cooperative promoter binding, and rapid, successive promoter clearance. We propose that response regulator phosphorylation, in combination with the cycle of cooperative DNA binding and rapid promoter clearance just described, can account for pulsed gene expression.
Project description:IntroductionImproving maternal health outcomes remains a priority in Low and Middle Income Countries. With the rapid proliferation of mobile health technologies, there is an increased interest in understanding how these technologies can effectively improve maternal health outcomes particularly maternal health seeking knowledge and behaviors. However, few studies present clear explanations of the program developers' rationale (theory of change) and contextual factors that could influence program outcomes. This mixed-methods study assesses Mobile for Mothers, a community health workers (CHW) utilized maternal mHealth intervention. We present the program developers' rationale and utilize it as a framework to guide our study that aimed to identify intervention-related and contextual factors, which influence the observed outcomes of a CHW, utilized mHealth intervention.Materials and methodsQuantitative methods (a questionnaire with 740 women who received the intervention and survey of 57 CHWs who utilized the intervention) and qualitative methods (12 interviews and 4 group discussions with CHWs and 20 interviews and 5 group discussions with pregnant and lactating women and 15 interviews and 2 group discussions with men) were conducted. These were used to understand how the mHealth intervention was implemented and to gain insight into contextual factors that potentially influenced the observed intervention outcomes.ResultsResults were grouped following three categories: (1) perceptions and experiences of CHWs utilizing the mHealth technology; (2) CHW-related outcomes; and (3) contextual factors that influence maternal health-seeking behavior. The overall response of CHWs and community members to the intervention was positive. However, contextual factors like the relationship between the CHWs and their respective communities, the pregnant women's decision-making power and lack of access due to financial influenced the observed outcomes.ConclusionMobile health applications are promising interventions for improving the performance of CHWs and health-seeking behavior of pregnant women. However, the contextual factors play a crucial role in intervention outcomes and need to be explicated by program developers during intervention design and implementation.
Project description:Fortune telling is a widespread phenomenon, yet little is known about the extent to which people are affected by it-including those who consider themselves non-believers. The present research has investigated the power of a positive fortune telling outcome (vs. neutral vs. negative) on people's financial risk taking. In two online experiments (n1 = 252; n2 = 441), we consistently found that positive fortune telling enhanced financial risk taking particularly among men. Additionally, we used a real online gambling game in a lab setting (n3 = 193) and found that positive fortune telling enhanced the likelihood that college students gambled for money. Furthermore, a meta-analysis of these three studies demonstrated that the effect of positive fortune telling versus neutral fortune telling was significant for men, but virtually absent for women. Thus, positive fortune telling can yield increased financial risk taking in men, but not (or less so) in women.
Project description:This study explores whether an oath to honesty can reduce both shirking and lying among crowd-sourced internet workers. Using a classic coin-flip experiment, we first confirm that a substantial majority of Mechanical Turk workers both shirk and lie when reporting the number of heads flipped. We then demonstrate that lying can be reduced by first asking each worker to swear voluntarily on his or her honor to tell the truth in subsequent economic decisions. Even in this online, purely anonymous environment, the oath significantly reduced the percent of subjects telling "big" lies (by roughly 27%), but did not affect shirking. We also explore whether a truth-telling oath can be used as a screening device if implemented after decisions have been made. Conditional on flipping response, MTurk shirkers and workers who lied were significantly less likely to agree to an ex-post honesty oath. Our results suggest oaths may help elicit more truthful behavior, even in online crowd-sourced environments.
Project description:Bacterial histidine kinase/response regulator systems operate at the interface between environmental cues and physiological states. Escherichia coli contains two LytS/LytTR-type histidine kinase/response regulator systems, BtsS/BtsR (formerly YehU/YehT) and YpdA/YpdB, which have been identified as pyruvate-responsive two-component systems. Since they exhibit remarkable similarity, we analyzed their phylogenetic distribution within the γ-proteobacteria, and experimentally characterized them in a set of representative species. We found that BtsS/BtsR is the predominant LytS/LytTR-type two-component system among γ-proteobacteria, whereas YpdA/YpdB primarily appears in a supplementary role. Based on our observations in E. coli, we used the highly conserved DNA-binding motifs to test the in vivo functionality of both systems in various genera, including Salmonella, Enterobacter, Citrobacter, Xenorhabdus, Yersinia, Aeromonas and Vibrio. The results suggest that, in all cases tested, BtsS/BtsR and YpdA/YpdB respond to different levels of pyruvate in the environment.
Project description:Clostridium difficile binary toxin (CDT) is an actin-specific ADP-ribosyltransferase that is produced by various C. difficile isolates, including the "hypervirulent" NAP1/027 epidemic strains. In contrast to the two major toxins from C. difficile, toxin A and toxin B, little is known about the role of CDT in virulence or how C. difficile regulates its production. In this study we have shown that in addition to the cdtA and cdtB toxin structural genes, a functional cdt locus contains a third gene, here designated cdtR, which is predicted to encode a response regulator. By introducing functional binary toxin genes into cdtR(+) and cdtR-negative strains of C. difficile, it was established that the CdtR protein was required for optimal expression of binary toxin. Significantly increased expression of functional binary toxin was observed in the presence of a functional cdtR gene; an internal deletion within cdtR resulted in a reduction in binary toxin production to basal levels. Strains that did not carry intact cdtAB genes or cdtAB pseudogenes also did not have cdtR, with the entire cdt locus, or CdtLoc, being replaced by a conserved 68-bp sequence. These studies have shown for the first time that binary toxin production is subject to strict regulatory control by the response regulator CdtR, which is a member of the LytTR family of response regulators and is related to the AgrA protein from Staphylococcus aureus.
Project description:Ecologists have been compiling ecological networks for over a century, detailing the interactions between species in a variety of ecosystems. To this end, they have built networks for mutualistic (e.g., pollination, seed dispersal) as well as antagonistic (e.g., herbivory, parasitism) interactions. The type of interaction being represented is believed to be reflected in the structure of the network, which would differ substantially between mutualistic and antagonistic networks. Here, we put this notion to the test by attempting to determine the type of interaction represented in a network based solely on its structure. We find that, although it is easy to separate different kinds of nonecological networks, ecological networks display much structural variation, making it difficult to distinguish between mutualistic and antagonistic interactions. We therefore frame the problem as a challenge for the community of scientists interested in computational biology and machine learning. We discuss the features a good solution to this problem should possess and the obstacles that need to be overcome to achieve this goal.