Computer Simulation of Assembly and Co-operativity of Hexameric AAA ATPases

AAA ATPases form a functionally diverse superfamily of proteins. Most members form homo-hexameric ring complexes, are catalytically active only in the fully assembled state, and show co-operativity among the six subunits. The mutual dependence among the subunits is clearly evidenced by the fact that incorporation of mutated, inactive subunits can decrease the activity of the remaining wild type subunits. For the first time, we develop here models to describe this form of allostery, evaluate them in a simulation study, and test them on experimental data. We show that it is important to consider the assembly reactions in the kinetic model, and to define a formal inhibition scheme. We simulate three inhibition scenarios explicitly, and demonstrate that they result in differing outcomes. Finally, we deduce fitting formulas, and test them on real and simulated data. A non-competitive inhibition formula fitted experimental and simulated data best. To our knowledge, our study is the first one that derives and tests formal allosteric schemes to explain the inhibitory effects of mutant subunits on oligomeric enzymes.     

Effect of Feed Restriction on Performance and Postprandial Nutrient Metabolism in Pigs Co-Infected with Mycoplasma hyopneumoniae and Swine Influenza Virus

As nutritional status and inflammation are strongly connected, feeding and nutritional strategies could be effective to improve the ability of pigs to cope with disease. The aims of this study were to investigate the impact of a feed restriction on the ability of pigs to resist and be tolerant to a coinfection with Mycoplasma hyopneumoniae (Mhp) and the European H1N1 swine influenza virus, and the consequences for nutrient metabolism, with a focus on amino acids. Two groups of specific pathogen-free pigs were inoculated with Mhp and H1N1 21 days apart. One group was fed ad libitum, the other group was subjected to a two-week 40% feed restriction starting one week before H1N1 infection. The two respective mock control groups were included. Three days post-H1N1 infection, 200 g of feed was given to pigs previously fasted overnight and serial blood samples were taken over 4 hours to measure plasma nutrient concentrations. Throughout the study, clinical signs were observed and pathogens were detected in nasal swabs and lung tissues. Feed-restricted pigs presented shorter hyperthermia and a positive mean weight gain over the 3 days post-H1N1 infection whereas animals fed ad libitum lost weight. Both infection and feed restriction reduced postprandial glucose concentrations, indicating changes in glucose metabolism. Post-prandial plasma concentrations of the essential amino acids histidine, arginine and threonine were lower in co-infected pigs suggesting a greater use of those amino acids for metabolic purposes associated with the immune response. Altogether, these results indicate that modifying feeding practices could help to prepare animals to overcome an influenza infection. Connections with metabolism changes are discussed.     

The transient and constitutive inflammatory signaling in tumorigenesis

Comment on: Rokavec M, et al. Mol Cell 2012; 45:777-89.     

Modulation of slow and fast elbow extensor EMG tonic activity by stretch reflexes in man

Reflex EMG responses to sudden passive flexion of the elbow were recorded from anconeus and triceps brachii in 5 human volunteers. While the subjects were required not to resist the flexion movement, they were required to maintain an extension torque of 3.5 or 7.0 Nm prior to its onset. Under these isotonic conditions, the latency and amplitude of the reflex activities from anconeus and triceps brachii did not differ significantly, in contrast to the findings of Le Bozec (1986) in actively relaxed subjects. The myotatic/postmyotatic EMG amplitude ratio did not provide a further quantitative way to distinguish between these muscles. The absence of a difference between the reflex activities of a slow (anconeus) and a fast (triceps brachii) muscle is interpreted as resulting from a strong drive of spindle activity on the whole extensor motoneuron pool, which outweights the differences in recruitment due to the differing relative amounts of type I and type II fibres in the two muscles. Differences like those described between finger and calf muscles by other authors are thought to be due to the relative degree of corticalization of these muscles. All short and long latency responses of the muscles increased in magnitude and decreased in latency with increasing background EMG activity as well as with increasing initial length. The position and tonic activity dependency of these responses is explained in terms of alpha-gamma coactivation.     

Flood Risk Analysis Based on Information Diffusion Theory

Due to the fact that the flood data series of small drainage basins is relatively short, available data are often not sufficient for flood risk analysis. This presents the problem of risk analysis using very small data samples. One method that can be applied is to regard the available small samples as fuzzy information and optimize them using information diffusion technology to yield analytical results with greater reliability. In this article a risk analysis method based on information diffusion theory is applied to create a new flood risk analysis model. Application of the model is illustrated taking the Jinhuajiang and Qujiang drainage basins as examples. This is a new attempt at applying information diffusion theory in flood risk analysis. Computations based on this analytical flood risk model can yield an estimated flood damage value that is relatively accurate. This study indicates that the aforementioned model exhibits fairly stable analytical results, even when using a small set of sample data. The results also indicate that information diffusion technology is highly capable of extracting useful information and therefore improves system recognition accuracy. This method can be easily applied and the analytical results produced are easy to understand. Results are accurate enough to act as a guide in disaster situations.