Ftsh Sensitizes Methicillin-Resistant Staphylococcus aureus to -Lactam Antibiotics by Degrading YpfP, a Lipoteichoic Acid Synthesis Enzyme

In the Gram-positive pathogen Staphylococcus aureus, FtsH, a membrane-bound metalloprotease, plays a critical role in bacterial virulence and stress resistance. This protease is also known to sensitize methicillin-resistant Staphylococcus aureus (MRSA) to β-lactam antibiotics; however, the molecular mechanism is not known. Here, by the analysis of FtsH substrate mutants, we found that FtsH sensitizes MRSA specifically to β-lactams by degrading YpfP, the enzyme synthesizing the anchor molecule for lipoteichoic acid (LTA). Both the overexpression of FtsH and the disruption of ypfP-sensitized MRSA to β-lactams were observed. The knockout mutation in ftsH and ypfP increased the thickness of the cell wall. The β-lactam sensitization coincided with the production of aberrantly large LTA molecules. The combination of three mutations in the rpoC, vraB, and SAUSA300_2133 genes blocked the β-lactam-sensitizing effect of FtsH. Murine infection with the ypfP mutant could be treated by oxacillin, a β-lactam antibiotic ineffective against MRSA; however, the effective concentration of oxacillin differed depending on the S. aureus strain. Our study demonstrated that the β-lactam sensitizing effect of FtsH is due to its digestion of YpfP. It also suggests that the larger LTA molecules are responsible for the β-lactam sensitization phenotype, and YpfP is a viable target for developing novel anti-MRSA drugs

The older the better: a fourth-order adaptive network model for reward-driven choices of emotion regulation strategies over time

The choice of which emotion regulation strategy to use changes depending on context, which within Psychology is referred to as ‘flexibility’. Besides that, choices of emotion regulation strategies are prone to various other factors, ranging from culture to gender, expectations of their effect, age, etc. This paper considers the phenomenon where choices of emotion regulation strategies change adaptively with age. In addition, the choices within specific age frames are driven by some kind of reward that affects in an adaptive manner the learning of a specific emotion regulation strategy. These adaptive phenomena involve plasticity or metaplasticity of different orders. They have been modeled by a fourth-order adaptive mental network model where the choice of emotion regulation strategies is motivated by reward prediction, and different age phases have their own adaptive influences. Simulation results are discussed for evaluation of the adaptive network model. The fourth-order adaptive network model presented here extends a second-order adaptive network model previously addressed in a paper at the conference COMPLEX NETWORKS 2019

Food desires, negative emotions and behaviour change techniques: A computational analysis

Behaviour change techniques are considered effective means for changing behaviour, and with an increase in their use the interest in their exact working principles has also expanded. This information is required to make informed choices about when to apply which technique. Computational models that describe human behaviour can be helpful for this. In this paper a few behaviour change techniques have been connected with a computational model of emotion and desire regulation. Simulations have been performed to illustrate the effect of the techniques. The results demonstrate the working mechanisms and feasibility of the techniques used in the model

A computational model for flexibility in emotion regulation

Emotion regulation is a vital psychological process that allows people to manage their own emotional states. Recent psychological research has highlighted the importance of flexibility in emotion regulation, such that people can alternative between different emotion regulation strategies. A strategy is chosen depending upon the demands of the situation. This means that healthy emotion regulation is context-sensitive. This paper presents a computational model which models this form of flexible adaptation in emotion regulation in a simplified scenario in which the person has to switch between expressive suppression and attention modulation in managing anger in different work situations. Simulation results are reported that illustrate the capacity of the model to display adaptivity in emotion regulation across different contexts

A Second-Order Adaptive Temporal-Causal Network Model for Age and Gender Differences in Evolving Choice of Emotion Regulation Strategies

Emotion being an essential part of one’s life, its regulation is of utmost importance. The choice of strategies that one employs for regulating their emotions, varies at various stages of their lives and with contexts. Similarly, gender also has an influence in the choice of emotion regulation strategies. This paper presents a second-order adaptive network model for this phenomenon where the choice of strategies varies with age and gender in an adaptive manner. Simulation results for both the genders (male and female) have been provided where for both the genders, choice of emotion regulation strategies changes as age increases. The second-order adaptive network model presented here extends a non-adaptive network model previously introduced at ICCCI’19