A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

Specialists in ancient trees are more affected by climate than generalists

Ancient trees are considered one of the most important habitats for biodiversity in Europe and North America. They support exceptional numbers of specialized species, including a range of rare and endangered wood-living insects. In this study, we use a dataset of 105 sites spanning a climatic gradient along the oak range of Norway and Sweden to investigate the importance of temperature and precipitation on beetle species richness in ancient, hollow oak trees. We expected that increased summer temperature would positively influence all wood-living beetle species whereas precipitation would be less important with a negligible or negative impact. Surprisingly, only oak-specialist beetles with a northern distribu- tion increased in species richness with temperature. Few specialist beetles and no generalist beetles responded to the rise of 4°C in summer as covered by our cli- matic gradient. The negative effect of precipitation affected more specialist species than did temperature, whereas the generalists remained unaffected. In summary, we suggest that increased summer temperature is likely to benefit a few specialist beetles within this dead wood community, but a larger number of specialists are likely to decline due to increased precipitation. In addition, generalist species will remain unaffected. To minimize adverse impacts of climate change on this impor- tant community, long-term management plans for ancient trees are important

Multiscale Drivers of Water Chemistry of Boreal Lakes and Streams

The variability in surface water chemistry within and between aquatic ecosystems is regulated by many factors operating at several spatial and temporal scales. The importance of geographic, regional-, and local-scale factors as drivers of the natural variability of three water chemistry variables representing buffering capacity and the importance of weathering (acid neutralizing capacity, ANC), nutrient concentration (total phosphorus, TP), and importance of allochthonous inputs (total organic carbon, TOC) were studied in boreal streams and lakes using a method of variance decomposition. Partial redundancy analysis (pRDA) of ANC, TP, and TOC and 38 environmental variables in 361 lakes and 390 streams showed the importance of the interaction between geographic position and regional-scale variables. Geographic position and regional-scale factors combined explained 15.3% (streams) and 10.6% (lakes) of the variation in ANC, TP, and TOC. The unique variance explained by geographic, regional, and local-scale variables alone was <10%. The largest amount of variance was explained by the pure effect of regional-scale variables (9.9% for streams and 7.8% for lakes), followed by local-scale variables (2.9% and 5.8%) and geographic position (1.8% and 3.7%). The combined effect of geographic position, regional-, and local-scale variables accounted for between 30.3% (lakes) and 39.9% (streams) of the variance in surface water chemistry. These findings lend support to the conjecture that lakes and streams are intimately linked to their catchments and have important implications regarding conservation and restoration (management) endeavors

Planktonic events may cause polymictic-dimictic regime shifts in temperate lakes

Water transparency affects the thermal structure of lakes, and within certain lake depth ranges, it can determine whether a lake mixes regularly (polymictic regime) or stratifies continuously (dimictic regime) from spring through summer. Phytoplankton biomass can influence transparency but the effect of its seasonal pattern on stratification is unknown. Therefore we analysed long term field data from two lakes of similar depth, transparency and climate but one polymictic and one dimictic, and simulated a conceptual lake with a hydrodynamic model. Transparency in the study lakes was typically low during spring and summer blooms and high in between during the clear water phase (CWP), caused when zooplankton graze the spring bloom. The effect of variability of transparency on thermal structure was stronger at intermediate transparency and stronger during a critical window in spring when the rate of lake warming is highest. Whereas the spring bloom strengthened stratification in spring, the CWP weakened it in summer. The presence or absence of the CWP influenced stratification duration and under some conditions determined the mixing regime. Therefore seasonal plankton dynamics, including biotic interactions that suppress the CWP, can influence lake temperatures, stratification duration, and potentially also the mixing regime

Surface Covering of Downed Logs: Drivers of a Neglected Process in Dead Wood Ecology

Many species use coarse woody debris (CWD) and are disadvantaged by the forestry-induced loss of this resource. A neglected process affecting CWD is the covering of the surfaces of downed logs caused by sinking into the ground (increasing soil contact, mostly covering the underside of the log), and dense overgrowth by ground vegetation. Such cover is likely to profoundly influence the quality and accessibility of CWD for wood-inhabiting organisms, but the factors affecting covering are largely unknown. In a five-year experiment we determined predictors of covering rate of fresh logs in boreal forests and clear-cuts. Logs with branches were little covered because they had low longitudinal ground contact. For branchless logs, longitudinal ground contact was most strongly related to estimated peat depth (positive relation). The strongest predictor for total cover of branchless logs was longitudinal ground contact. To evaluate the effect on cover of factors other than longitudinal ground contact, we separately analyzed data from only those log sections that were in contact with the ground. Four factors were prominent predictors of percentage cover of such log sections: estimated peat depth, canopy shade (both increasing cover), potential solar radiation calculated from slope and slope aspect, and diameter of the log (both reducing cover). Peat increased cover directly through its low resistance, which allowed logs to sink and soil contact to increase. High moisture and low temperatures in pole-ward facing slopes and under a canopy favor peat formation through lowered decomposition and enhanced growth of peat-forming mosses, which also proved to rapidly overgrow logs. We found that in some boreal forests, peat and fast-growing mosses can rapidly cover logs lying on the ground. When actively introducing CWD for conservation purposes, we recommend that such rapid covering is avoided, thereby most likely improving the CWD's longevity as habitat for many species

Turbulence and Fossil Turbulence in Oceans and Lakes

Turbulence is defined as an eddy-like state of fluid motion where the inertial-vortex forces of the eddies are larger than any of the other forces that tend to damp the eddies out. Energy cascades of irrotational flows from large scales to small are non-turbulent, even if they supply energy to turbulence. Turbulent flows are rotational and cascade from small scales to large, with feedback. Viscous forces limit the smallest turbulent eddy size to the Kolmogorov scale. In stratified fluids, buoyancy forces limit large vertical overturns to the Ozmidov scale and convert the largest turbulent eddies into a unique class of saturated, non-propagating, internal waves, termed fossil-vorticity-turbulence. These waves have the same energy but different properties and spectral forms than the original turbulence patch. The Gibson (1980, 1986) theory of fossil turbulence applies universal similarity theories of turbulence and turbulent mixing to the vertical evolution of an isolated patch of turbulence in a stratified fluid as its growth is constrained and fossilized by buoyancy forces. These theories apply to the dynamics of atmospheric, astrophysical and cosmological turbulence.Comment: 31 pages, 11 figures, 2 tables, see http://www-acs.ucsd.edu/~ir118 Accepted for publication by the Chinese Journal of Oceanology and Limnolog

Pathways between Primary Production and Fisheries Yields of Large Marine Ecosystems

The shift in marine resource management from a compartmentalized approach of dealing with resources on a species basis to an approach based on management of spatially defined ecosystems requires an accurate accounting of energy flow. The flow of energy from primary production through the food web will ultimately limit upper trophic-level fishery yields. In this work, we examine the relationship between yield and several metrics including net primary production, chlorophyll concentration, particle-export ratio, and the ratio of secondary to primary production. We also evaluate the relationship between yield and two additional rate measures that describe the export of energy from the pelagic food web, particle export flux and mesozooplankton productivity. We found primary production is a poor predictor of global fishery yields for a sample of 52 large marine ecosystems. However, chlorophyll concentration, particle-export ratio, and the ratio of secondary to primary production were positively associated with yields. The latter two measures provide greater mechanistic insight into factors controlling fishery production than chlorophyll concentration alone. Particle export flux and mesozooplankton productivity were also significantly related to yield on a global basis. Collectively, our analyses suggest that factors related to the export of energy from pelagic food webs are critical to defining patterns of fishery yields. Such trophic patterns are associated with temperature and latitude and hence greater yields are associated with colder, high latitude ecosystems