Human-Centric Functional Modeling of Individual and Collective Biological Systems

Gaining the capacity to coordinate group research so that from observing the functionality of any system converging on a single best understanding of how that functionality is implemented is reliably achievable, requires a process that is able to analyze that system from a common perspective, such as might be achieved through decomposing that system into a common set of functional components. Human-Centric Functional Modeling provides the potential opportunity to decompose biological systems in this way in order to significantly increase collective ability to derive insight about the behavior of a wide range of biological systems, as well as in order to provide the capacity to derive insights from generalizing an understanding of any one biological systems to any other system or collections of such systems where that understanding might apply. This paper explores the methodology.

A covariation analysis reveals elements of selectivity in quorum sensing systems

Many bacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone (AHL) quorum sensing (QS). In these systems, a signal synthase produces an AHL to which its paired receptor selectively responds. Selectivity is fundamental to cell signaling. Despite its importance, it has been challenging to determine how this selectivity is achieved and how AHL QS systems evolve and diversify. We hypothesized that we could use covariation within the protein sequences of AHL synthases and receptors to identify selectivity residues. We began by identifying about 6,000 unique synthase-receptor pairs. We then used the protein sequences of these pairs to identify covariation patterns and mapped the patterns onto the LasI/R system from Pseudomonas aeruginosa PAO1. The covarying residues in both proteins cluster around the ligand-binding sites. We demonstrate that these residues are involved in system selectivity toward the cognate signal and go on to engineer the Las system to both produce and respond to an alternate AHL signal. We have thus demonstrated that covariation methods provide a powerful approach for investigating selectivity in protein-small molecule interactions and have deepened our understanding of how communication systems evolve and diversify.

A covariation analysis reveals elements of selectivity in quorum sensing systems

Many bacteria communicate with kin and coordinate group behaviors through a form of cell-cell signaling called acyl-homoserine lactone (AHL) quorum sensing (QS). In these systems, a signal synthase produces an AHL to which its paired receptor selectively responds. Selectivity is fundamental to cell signaling. Despite its importance, it has been challenging to determine how this selectivity is achieved and how AHL QS systems evolve and diversify. We hypothesized that we could use covariation within the protein sequences of AHL synthases and receptors to identify selectivity residues. We began by identifying about 6,000 unique synthase-receptor pairs. We then used the protein sequences of these pairs to identify covariation patterns and mapped the patterns onto the LasI/R system from Pseudomonas aeruginosa PAO1. The covarying residues in both proteins cluster around the ligand binding sites. We demonstrate that these residues are involved in system selectivity toward the cognate signal and go on to engineer the Las system to both produce and respond to an alternate AHL signal. We have thus demonstrated a new application for covariation methods and have deepened our understanding of how communication systems evolve and diversify.

Facilitating or inhibiting?

Purpose The current research studies are inconclusive about the positive or negative effects of group faultlines, especially in the Chinese context. To address this issue, this study aims to adopt an interactive perspective to explore the group interaction process. Specifically, this study proposes a new construct “interactive faultlines” to integrate overall faultlines and separate faultlines, and based on categorization-elaboration model (CEM), develops an integrated moderated mediation model to examine when and how interactive faultlines facilitate or inhibit group creativity. Design/methodology/approach This study tests the model with the samples of 405 employees from 95 groups in China, carrying out confirmatory factor analysis, regression analysis and process. Findings This study finds that the indirect effect of informational faultlines on group creativity through information elaboration is positive when social faultlines are low, but negative when social faultlines are high. Practical implications This research provides some practical implications on how to manage group compositions and coordinate group interaction process to make full use of the potential benefits of diverse information and avoid the possible detriment from social categorization. Originality/value This study adopts an interactive perspective to consider informational faultlines and social faultlines simultaneously, and constructs a focal concept “interactive faultlines.” Based on CEM, it also offers a fine-grained picture of the double-edged relationship between informational faultlines and group creativity by identifying social faultlines as a moderator and information elaboration as a mediator, which advances knowledge about the linkages between interactive faultlines and group creativity. Particularly, this study is rooted in the Chinese context and brings in indigenous attributes derived from an analysis of Eastern cultures to elucidate the particular effect of informal social connections.

Effective construction of covers of canonical Hom-diagrams for equations over torsion-free hyperbolic groups

We show that, given a finitely generated group G as the coordinate group of a finite system of equations over a torsion-free hyperbolic group Γ, there is an algorithm which constructs a cover of a canonical solution diagram. The diagram encodes all homomorphisms from G to Γ as compositions of factorizations through Γ-NTQ groups and canonical automorphisms of the corresponding NTQ-subgroups. We also give another characterization of Γ-limit groups as iterated generalized doubles over Γ.

The development of social interactions in Corydoras aeneus larvae

Very young animals develop life skills as they mature, and for social animals this includes the acquisition of social abilities such as communication. Many animals exhibit changeable patterns of social behavior based on development, and social experience during the juvenile period can be vital for the development of necessary social behaviors in adulthood. We investigated the development of a distinctive tactile interaction behavior in Corydoras aeneus, the Bronze Cory catfish. Adults use this behavior to coordinate group activities during foraging and flight responses from predators, and the development of this behavior in larvae is of interest in investigating how communication and social behaviors develop as an individual matures, and which factors affect their development. We found that larvae respond to applied tactile stimulation with a flight response far less often as larvae matured, implying that larvae become less sensitive to tactile stimulation with age. Given that adults frequently interact with one another tactilely, this development is consistent with developing appropriate social behavior in adulthood. We also found that social exposure affects the development of the larval response to tactile interactions with conspecifics, and that isolation in the earliest larval stage leads to a greater likelihood of responding to a tactile interaction with a conspecific with a flight response. This suggests that social exposure is important for developing an appropriate response to tactile stimulation in social settings and underscores the particular importance of early life experiences in the development of sociality.

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor inSalmonella entericaserovar Typhimurium

Quorum sensing (QS) allows many common bacterial pathogens to coordinate group behaviors such as virulence factor production, host colonization, and biofilm formation at high population densities. This cell–cell signaling process is regulated byN-acyl L-homoserine lactone (AHL) signals, or autoinducers, and LuxR-type receptors in Gram-negative bacteria. SdiA is an orphan LuxR-type receptor found inEscherichia, Salmonella, Klebsiella, and Enterobactergenera that responds to AHL signals produced by other species and regulates genes involved in several aspects of host colonization. The inhibition of QS using non-native small molecules that target LuxR-type receptors offers a non-biocidal approach for studying, and potentially controlling, virulence in these bacteria. To date, few studies have characterized the features of AHLs and other small molecules capable of SdiA agonism, and no SdiA antagonists have been reported. Herein, we report the screening of a set of AHL analogs to both uncover agonists and antagonists of SdiA and to start to delineate structure–activity relationships (SARs) for SdiA:AHL interactions. Using a cell-based reporter of SdiA inSalmonella entericaserovar Typhimurium, several non-natural SdiA agonists and the first set of SdiA antagonists were identified and characterized. These compounds represent new chemical probes for exploring the mechanisms by which SdiA functions during infection and its role in interspecies interactions. Moreover, as SdiA is highly stable when produced in vitro, these compounds could advance fundamental studies of LuxR-type receptor:ligand interactions that engender both agonism and antagonism.