Spontaneous cooperation for public goods

Cooperation for public goods poses a dilemma, where individuals are tempted to free ride on others' contributions. Classic solutions involve monitoring, reputation maintenance and costly incentives, but there are important collective actions based on simple and cheap cues only, for example unplanned protests and revolts. This can be explained by an Ising model with the assumption that individuals in uncertain situations tend to conform to the local majority in their network. Among initial defectors, noise such as rumors or opponents' provocations causes some of them to cooperate accidentally. At a critical level of noise, these cooperators trigger a cascade of cooperation. We find an analytic relationship between the phase transition and the asymmetry of the Ising model, which in turn reflects the asymmetry of cooperation and defection. This study thereby shows that in principle, the dilemma of cooperation can be solved by nothing more than a portion of random noise, without rational decision making

Complex Agent Networks explaining the HIV epidemic among homosexual men in Amsterdam

Simulating the evolution of the Human Immunodeficiency Virus (HIV) epidemic requires a detailed description of the population network, especially for small populations in which individuals can be represented in detail and accuracy. In this paper, we introduce the concept of a Complex Agent Network(CAN) to model the HIV epidemics by combining agent-based modelling and complex networks, in which agents represent individuals that have sexual interactions. The applicability of CANs is demonstrated by constructing and executing a detailed HIV epidemic model for men who have sex with men (MSM) in Amsterdam, including a distinction between steady and casual relationships. We focus on MSM contacts because they play an important role in HIV epidemics and have been tracked in Amsterdam for a long time. Our experiments show good correspondence between the historical data of the Amsterdam cohort and the simulation results.Comment: 21 pages, 4 figures, Mathematics and Computers in Simulation, added reference

Increasing risk behaviour can outweigh the benefits of antiretroviral drug treatment on the HIV incidence among men-having-sex-with-men in Amsterdam

Background: The transmission through contacts among MSM (men who have sex with men) is one of the dominating contributors to HIV prevalence in industrialized countries. In Amsterdam, the capital of the Netherlands, the MSM risk group has been traced for decades. This has motivated studies which provide detailed information about MSM's risk behavior statistically, psychologically and sociologically. Despite the era of potent antiretroviral therapy, the incidence of HIV among MSM increases. In the long term the contradictory effects of risk behavior and effective therapy are still poorly understood.Methods: Using a previously presented Complex Agent Network model, we describe steady and casual partnerships to predict the HIV spreading among MSM. Behavior-related parameters and values, inferred from studies on Amsterdam MSM, are fed into the model; we validate the model using historical yearly incidence data. Subsequently, we study scenarios to assess the contradictory effects of risk behavior and effective therapy, by varying corresponding values of parameters. Finally, we conduct quantitative analysis based on the resulting incidence data.R

Engineering a Plant Polyketide Synthase for the Biosynthesis of Methylated Flavonoids

Homoeriodictyol and hesperetin are naturally occurring O-methylated flavonoids with many health-promoting properties. They are produced in plants in low abundance and as complex mixtures of similar compounds that are difficult to separate. Synthetic biology offers the opportunity to produce various flavonoids in a targeted, bottom-up approach in engineered microbes with high product titers. However, the production of O-methylated flavonoids is currently still highly inefficient. In this study, we investigated and engineered a combination of enzymes that had previously been shown to support homoeriodictyol and hesperetin production in Escherichia coli from fed O-methylated hydroxycinnamic acids. We determined the crystal structures of the enzyme catalyzing the first committed step of the pathway, chalcone synthase from Hordeum vulgare, in three ligand-bound states. Based on these structures and a multiple sequence alignment with other chalcone synthases, we constructed mutant variants and assessed their performance in E. coli toward producing methylated flavonoids. With our best mutant variant, HvCHS (Q232P, D234 V), we were able to produce homoeriodictyol and hesperetin at 2 times and 10 times higher titers than reported previously. Our findings will facilitate further engineering of this enzyme toward higher production of methylated flavonoids.</p

Engineering a Plant Polyketide Synthase for the Biosynthesis of Methylated Flavonoids

Homoeriodictyol and hesperetin are naturally occurring O-methylated flavonoids with many health-promoting properties. They are produced in plants in low abundance and as complex mixtures of similar compounds that are difficult to separate. Synthetic biology offers the opportunity to produce various flavonoids in a targeted, bottom-up approach in engineered microbes with high product titers. However, the production of O-methylated flavonoids is currently still highly inefficient. In this study, we investigated and engineered a combination of enzymes that had previously been shown to support homoeriodictyol and hesperetin production in Escherichia coli from fed O-methylated hydroxycinnamic acids. We determined the crystal structures of the enzyme catalyzing the first committed step of the pathway, chalcone synthase from Hordeum vulgare, in three ligand-bound states. Based on these structures and a multiple sequence alignment with other chalcone synthases, we constructed mutant variants and assessed their performance in E. coli toward producing methylated flavonoids. With our best mutant variant, HvCHS (Q232P, D234 V), we were able to produce homoeriodictyol and hesperetin at 2 times and 10 times higher titers than reported previously. Our findings will facilitate further engineering of this enzyme toward higher production of methylated flavonoids.</p

Engineering a Plant Polyketide Synthase for the Biosynthesis of Methylated Flavonoids

Homoeriodictyol and hesperetin are naturally occurring O-methylated flavonoids with many health-promoting properties. They are produced in plants in low abundance and as complex mixtures of similar compounds that are difficult to separate. Synthetic biology offers the opportunity to produce various flavonoids in a targeted, bottom-up approach in engineered microbes with high product titers. However, the production of O-methylated flavonoids is currently still highly inefficient. In this study, we investigated and engineered a combination of enzymes that had previously been shown to support homoeriodictyol and hesperetin production in Escherichia coli from fed O-methylated hydroxycinnamic acids. We determined the crystal structures of the enzyme catalyzing the first committed step of the pathway, chalcone synthase from Hordeum vulgare, in three ligand-bound states. Based on these structures and a multiple sequence alignment with other chalcone synthases, we constructed mutant variants and assessed their performance in E. coli toward producing methylated flavonoids. With our best mutant variant, HvCHS (Q232P, D234 V), we were able to produce homoeriodictyol and hesperetin at 2 times and 10 times higher titers than reported previously. Our findings will facilitate further engineering of this enzyme toward higher production of methylated flavonoids.</p

Engineering a Plant Polyketide Synthase for the Biosynthesis of Methylated Flavonoids

Homoeriodictyol and hesperetin are naturally occurring O-methylated flavonoids with many health-promoting properties. They are produced in plants in low abundance and as complex mixtures of similar compounds that are difficult to separate. Synthetic biology offers the opportunity to produce various flavonoids in a targeted, bottom-up approach in engineered microbes with high product titers. However, the production of O-methylated flavonoids is currently still highly inefficient. In this study, we investigated and engineered a combination of enzymes that had previously been shown to support homoeriodictyol and hesperetin production in Escherichia coli from fed O-methylated hydroxycinnamic acids. We determined the crystal structures of the enzyme catalyzing the first committed step of the pathway, chalcone synthase from Hordeum vulgare, in three ligand-bound states. Based on these structures and a multiple sequence alignment with other chalcone synthases, we constructed mutant variants and assessed their performance in E. coli toward producing methylated flavonoids. With our best mutant variant, HvCHS (Q232P, D234 V), we were able to produce homoeriodictyol and hesperetin at 2 times and 10 times higher titers than reported previously. Our findings will facilitate further engineering of this enzyme toward higher production of methylated flavonoids.</p

Engineering a Plant Polyketide Synthase for the Biosynthesis of Methylated Flavonoids

Homoeriodictyol and hesperetin are naturally occurring O-methylated flavonoids with many health-promoting properties. They are produced in plants in low abundance and as complex mixtures of similar compounds that are difficult to separate. Synthetic biology offers the opportunity to produce various flavonoids in a targeted, bottom-up approach in engineered microbes with high product titers. However, the production of O-methylated flavonoids is currently still highly inefficient. In this study, we investigated and engineered a combination of enzymes that had previously been shown to support homoeriodictyol and hesperetin production in Escherichia coli from fed O-methylated hydroxycinnamic acids. We determined the crystal structures of the enzyme catalyzing the first committed step of the pathway, chalcone synthase from Hordeum vulgare, in three ligand-bound states. Based on these structures and a multiple sequence alignment with other chalcone synthases, we constructed mutant variants and assessed their performance in E. coli toward producing methylated flavonoids. With our best mutant variant, HvCHS (Q232P, D234 V), we were able to produce homoeriodictyol and hesperetin at 2 times and 10 times higher titers than reported previously. Our findings will facilitate further engineering of this enzyme toward higher production of methylated flavonoids.</p