ActinoBase: tools and protocols for researchers working on Streptomyces and other filamentous actinobacteria.

Actinobacteria is an ancient phylum of Gram-positive bacteria with a characteristic high GC content to their DNA. The ActinoBase Wiki is focused on the filamentous actinobacteria, such as Streptomyces species, and the techniques and growth conditions used to study them. These organisms are studied because of their complex developmental life cycles and diverse specialised metabolism which produces many of the antibiotics currently used in the clinic. ActinoBase is a community effort that provides valuable and freely accessible resources, including protocols and practical information about filamentous actinobacteria. It is aimed at enabling knowledge exchange between members of the international research community working with these fascinating bacteria. ActinoBase is an anchor platform that underpins worldwide efforts to understand the ecology, biology and metabolic potential of these organisms. There are two key differences that set ActinoBase apart from other Wiki-based platforms: [1] ActinoBase is specifically aimed at researchers working on filamentous actinobacteria and is tailored to help users overcome challenges working with these bacteria and [2] it provides a freely accessible resource with global networking opportunities for researchers with a broad range of experience in this field.

Discovery of GSK2795039, a Novel Small Molecule NADPH Oxidase 2 Inhibitor.

AIMS: The NADPH oxidase (NOX) family of enzymes catalyzes the formation of reactive oxygen species (ROS). NOX enzymes not only have a key role in a variety of physiological processes but also contribute to oxidative stress in certain disease states. To date, while numerous small molecule inhibitors have been reported (in particular for NOX2), none have demonstrated inhibitory activity in vivo. As such, there is a need for the identification of improved NOX inhibitors to enable further evaluation of the biological functions of NOX enzymes in vivo as well as the therapeutic potential of NOX inhibition. In this study, both the in vitro and in vivo pharmacological profiles of GSK2795039, a novel NOX2 inhibitor, were characterized in comparison with other published NOX inhibitors. RESULTS: GSK2795039 inhibited both the formation of ROS and the utilization of the enzyme substrates, NADPH and oxygen, in a variety of semirecombinant cell-free and cell-based NOX2 assays. It inhibited NOX2 in an NADPH competitive manner and was selective over other NOX isoforms, xanthine oxidase, and endothelial nitric oxide synthase enzymes. Following systemic administration in mice, GSK2795039 abolished the production of ROS by activated NOX2 enzyme in a paw inflammation model. Furthermore, GSK2795039 showed activity in a murine model of acute pancreatitis, reducing the levels of serum amylase triggered by systemic injection of cerulein. INNOVATION AND CONCLUSIONS: GSK2795039 is a novel NOX2 inhibitor that is the first small molecule to demonstrate inhibition of the NOX2 enzyme in vivo.

Repetitive ritalin treatment modulates the diurnal activity pattern of young SD male rats.

Attention Deficit Hyperactivity Disorder (ADHD) is a common behavioral disorder of children and is treated by psychostimulants. Psychostimulant exposure to children at the time of neuronal development can cause behavioral and physiological changes continuing during adulthood. Most of the studies on psychostimulants investigate the acute effects of the drug. The objective of this study was to investigate whether acute or chronic exposure to methylphenidate (MPD), the drug most often used to treat ADHD in children, will modulate the diurnal activity pattern of young rats. Maintaining the diurnal activity pattern is a physiological process that regulates the internal homeostasis. Dose response protocol was used to study the effect of acute and chronic MPD in four young post natal day 40 (P 40) rat groups, (each N=8), as follows: saline (control) group, and 0.6, 2.5, or 10.0 mg/kg i.p. MPD groups, respectively. The experiment was performed over 11 consecutive days of continuous locomotor activity recording using the open field assay. The data evaluation was divided into four phases as follows: acute, induction, washout and expression phases. There was a dose-dependent increase in the average locomotor activity in the first few hours post-injection. Analysis of the diurnal rhythmic pattern of locomotion in the three dose groups compared to control demonstrated that only the 10.0 mg/kg MPD elicited significant changes in diurnal pattern activity in the washout and the expression phase. In addition, this study indicated that chronic MPD treatment elicits dose dependent anticipation and/or withdrawal and behavioral sensitization.

The effects of forestry on Hg bioaccumulation in nemoral/boreal waters and recommendations for good silvicultural practice.

Mercury (Hg) levels are alarmingly high in fish from lakes across Fennoscandia and northern North America. The few published studies on the ways in which silviculture practices influence this problem indicate that forest operations increase Hg in downstream aquatic ecosystems. From these studies, we estimate that between one-tenth and one-quarter of the Hg in the fish of high-latitude, managed forest landscapes can be attributed to harvesting. Forestry, however, did not create the elevated Hg levels in the soils, and waterborne Hg/MeHg concentrations downstream from harvested areas are similar to those from wetlands. Given the current understanding of the way in which silviculture impacts Hg cycling, most of the recommendations for good forest practice in Sweden appear to be appropriate for high-latitude regions, e.g., leaving riparian buffer zones, as well as reducing disturbance at stream crossings and in moist areas. The recommendation to restore wetlands and reduce drainage, however, will likely increase Hg/MeHg loadings to aquatic ecosystems.

Suspended sediment removal by vegetative filter strip treating highway runoff.

Structural best management practices (BMPs) are often used to mitigate the impact of storm water runoff on receiving waters. Vegetative filter strips (VFS) are an example of a structural BMP that has been used to treat storm water and highway runoff. Physical factors affecting the performance of VFS include pollutant characteristics, vegetation composition and density, soil properties, and the physical dimensions of the filter strip. In this study, field-suspended sediment data were collected from an experimental VFS treating highway runoff in eastern North Carolina. Field data were used to test the design concepts of the VFS treatment train and to validate a simulation model for evaluating the impact of these physical factors on sediment removal as a function of filter strip length. It was concluded that the experimental filter strip was effective in removing more than 85% of the incoming total suspended sediment (TSS). Simulation results support field observations that a 10-m or longer filter strip can retain most of the medium and large particles (> 8 microm) transported in runoff. Simulations also indicate infiltration loss is largely responsible for the retention of small-size sediment particles (< 8 microm). Saturated hydraulic conductivity and initial water contents have little effects on TSS removal. The condition of vegetative coverage, in particular vegetation density, is another factor affecting the performance of filter strip.