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

Top-down control of cortical gamma-band communication via pulvinar induced phase shifts in the alpha rhythm

Selective routing of information between cortical areas is required in order to combine different sources of information according to cognitive demand. Recent experiments have suggested that alpha band activity originating from the pulvinar coordinates this inter-areal cortical communication. Using a computer model we investigated whether top-down induced shifts in the relative alpha phase between two cortical areas could modulate cortical communication, quantified in terms of changes in gamma band coherence between them. The network model was comprised of two uni-directionally connected neuronal populations of spiking neurons, each representing a cortical area. We find that the phase difference of the alpha oscillations modulating the two neuronal populations strongly affected the interregional gamma-band neuronal coherence. We confirmed that a higher gamma band coherence also resulted in more efficient transmission of spiking information between cortical areas, thereby confirming the value of gamma coherence as a proxy for cortical information transmission. In a model where both neuronal populations were connected bi-directionally, the relative alpha phase determined the directionality of communication between the populations. Our results show the feasibility of a physiological realistic mechanism for routing information in the brain based on coupled oscillations. Our model results in a set of testable predictions regarding phase shifts in alpha oscillations under different task demands requiring experimental quantification of neuronal oscillations in different regions in e.g. attention paradigms

Development of phenylthiourea derivatives as allosteric inhibitors of pyoverdine maturation enzyme PvdP tyrosinase

Infections caused by Pseudomonas aeruginosa become increasingly difficult to treat because these bacteria have acquired various mechanisms for antibiotic resistance, which creates the need for mechanistically novel antibiotics. Such antibiotics might be developed by targeting enzymes involved in the iron uptake mechanism because iron is essential for bacterial survival. For P. aeruginosa, pyoverdine has been described as an important virulence factor that plays a key role in iron uptake. Therefore, inhibition of enzymes involved in the pyoverdine synthesis, such as PvdP tyrosinase, can open a new window for the treatment of P. aeruginosa infections. Previously, we reported phenylthiourea as the first allosteric inhibitor of PvdP tyrosinase with high micromolar potency. In this report, we explored structure-activity relationships (SAR) for PvdP tyrosinase inhibition by phenylthiourea derivatives. This enables identification of a phenylthiourea derivative (3c) with a potency in the submicromolar range (IC50 = 0.57 + 0.05 µM). Binding could be rationalized by molecular docking simulation and 3c was proved to inhibit the bacterial pyoverdine production and bacterial growth in P. aeruginosa PA01 cultures

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

Archaeal virus entry and egress

Archaeal viruses display a high degree of structural and genomic diversity. Few details are known about the mechanisms by which these viruses enter and exit their host cells. Research on archaeal viruses has lately made significant progress due to advances in genetic tools and imaging techniques, such as cryo-electron tomography (cryo-ET). In recent years, a steady output of newly identified archaeal viral receptors and egress mechanisms has offered the first insight into how archaeal viruses interact with the archaeal cell envelope. As more details about archaeal viral entry and egress are unravelled, patterns are starting to emerge. This helps to better understand the interactions between viruses and the archaeal cell envelope and how these compare to infection strategies of viruses in other domains of life. Here, we provide an overview of recent developments in the field of archaeal viral entry and egress, shedding light onto the most elusive part of the virosphere.</p