Multidrug Resistance-associated Protein 2 (MRP2) mediated transport of Oxaliplatin-derived platinum in membrane vesicles

The platinum-based anticancer drug oxaliplatin is important clinically in cancer treatment. However, the role of multidrug resistance-associated protein 2 (MRP2) in controlling oxaliplatin membrane transport, in vivo handling, toxicity and therapeutic responses is unclear. In the current study, preparations of MRP2-expressing and control membrane vesicles, containing inside-out orientated vesicles, were used to directly characterise the membrane transport of oxaliplatin-derived platinum measured by inductively coupled plasma mass spectrometry. Oxaliplatin inhibited the ATP-dependent accumulation of the model MRP2 fluorescent probe, 5(6)-carboxy-2,'7'-dichlorofluorescein, in MRP2-expressing membrane vesicles. MRP2-expressing membrane vesicles accumulated up to 19-fold more platinum during their incubation with oxaliplatin and ATP as compared to control membrane vesicles and in the absence of ATP. The rate of ATP-dependent MRP2-mediated active transport of oxaliplatin-derived platinum increased non-linearly with increasing oxaliplatin exposure concentration, approaching a plateau value (Vmax) of 2680 pmol Pt/mg protein/10 minutes (95%CI, 2010 to 3360 pmol Pt/mg protein/10 minutes), with the half-maximal platinum accumulation rate (Km) at an oxaliplatin exposure concentration of 301 μM (95% CI, 163 to 438 μM), in accordance with Michaelis-Menten kinetics (r2 = 0.954). MRP2 inhibitors (myricetin and MK571) reduced the ATP-dependent accumulation of oxaliplatin-derived platinum in MRP2-expressing membrane vesicles in a concentration-dependent manner. To identify whether oxaliplatin, or perhaps a degradation product, was the likely substrate for this active transport, HPLC studies were undertaken showing that oxaliplatin degraded slowly in membrane vesicle incubation buffer containing chloride ions and glutathione, with approximately 95% remaining intact after a 10 minute incubation time and a degradation half-life of 2.24 hours (95%CI, 2.08 to 2.43 hours). In conclusion, MRP2 mediates the ATP-dependent active membrane transport of oxaliplatin-derived platinum. Intact oxaliplatin and its anionic monochloro oxalate ring-opened intermediate appear likely candidates as substrates for MRP2-mediated transport

Tamarisk biocontrol using Tamarisk Beetles: Potential consequences for riparian birds in the southwestern United Stains

The tamarisk beetle (Diorhabda spp.), a non-native biocontrol agent, has been introduced to eradicate tamarisk (Tamarix spp.), a genus of non-native tree that has become a dominant component of riparian woodlands in the southwestern United States. Tamarisk beetles have the potential to spread widely and defoliate large expanses of tamarisk habitat, but the effects of such a widespread loss of riparian vegetation on birds remains unknown. We reviewed literature on the effects of other defoliating insects on birds to investigate the potential for tamarisk beetles to affect birds positively or negatively by changing food abundance and vegetation structure. We then combined data on the temporal patterns of tamarisk defoliation by beetles with nest productivity of a well studied riparian obligate, the Southwestern Willow Flycatcher (Empidonax traillii extimus), to simulate the potential demographic consequences of beetle defoliation on breeding riparian birds in both the short and long term. Our results highlight that the effects of tamarisk biocontrol on birds will likely vary by species and population, depending upon its sensitivity to seasonal defoliation by beetles and net loss of riparian habitat due to tamarisk mortality. Species with restricted distributions that include areas dominated by tamarisk may be negatively affected both in the short and long term. The rate of regeneration and/or restoration of native cottonwoods (Populus spp.)and willows (Salix spp.) relative to the rate of tamarisk loss will be critical in determining the long-term effect of this large-scale ecological experiment

Seasonal Variation in Space Use by Nonbreeding Bald Eagles Within the Upper Chesapeake Bay

Access to food resources is essential to self-maintenance and reproduction and, for species of conservation concern, foraging areas are considered critical habitat. Human disturbance is an important factor restricting access to prey resources for Bald Eagles (Haliaeetus leucocephalus) and guidelines in the Chesapeake Bay have been developed to mitigate its impact. However, our ability to implement such guidelines has been limited by a lack of information on important foraging areas. We used Brownian bridge movement modeling to develop a population-wide utilization probability surface for Bald Eagles along shorelines within the upper Chesapeake Bay. We used locations (n  =  320 304) for individuals (n  =  63) tracked with GPS satellite transmitters between 2007 and 2011 in the analysis. We examined seasonal variation by developing utilization surfaces for summer and winter. Although shoreline use was widespread, segments receiving high levels of activity were relatively rare. Shoreline classified as having the highest category of use and accounting for 10% of the total utilization made up 0.41% and 0.55% of the total shoreline for winter and summer, respectively. From a management perspective, there is a clear pattern of diminishing returns in conservation value for including sequentially lower-use shorelines in land-use management plans. Shoreline use shifted dramatically in both location and extent between seasons. During the summer months, use was highly concentrated on shorelines along the main stem of the Chesapeake Bay or along major (\u3e1 km wide) tributaries. During the winter months, use shifted away from the main stem of the bay and was more focused on minor (wide) tributaries and inland ponds. Seasonal shifts in shoreline use suggest the need for season-based management objectives

Use of satellite telemetry to delineate bald eagle activity centers for hazard mitigation and land planning within the upper Chesapeake Bay. Final Report

Sustaining the duel military and environmental stewardship missions on Aberdeen Proving Ground (APG) has become increasingly challenging as the number of eagles using the installation has grown dramatically. Military testing and training activities conducted on APG are vital to national security. APG likely holds the greatest conservation value for bald eagles of any federal property along the Atlantic Coast. The property supports a complex mixture of eagles including a growing breeding population that is rapidly approaching saturation, a large population of non‐breeding residents, and migrant populations from the northeast and southeast. Major activity centers such as active nests, communal roosts and foraging areas are protected under the disturb and sheltering provision of the federal Bald and Golden Eagle Protection Act. The level of site‐specific information on eagles required to tightly integrate their needs into the space requirements of a diverse and dynamic military operation has not been available. The focus of this project has been to collect and provide eagle information that will enable the incorporation of effective environmental planning into the military mission. Between 2007 and 2009 satellite transmitters were deployed on a large (n = 65) cohort of eagles that represent the cross section of populations that use APG. Between 2007 and 2011 transmitters collected nearly 700,000 GPS locations from within every state and Canadian province along the Atlantic Coast confirming APG’s role as a hub of eagle activity within eastern North America. Locations (n \u3e 320,000) within the upper Chesapeake Bay were used in spatial models to develop probability surfaces that identify high‐use activity centers by season within APG. Midnight locations (n \u3e 10,300) were used in separate spatial models to delineate communal roosts. Results of this study provide site‐specific information designed to inform future management decisions. Maps reveal the locations of significant communal roosts, foraging areas, loafing areas and movement corridors used by eagles on APG. Levels of use are quantified by location to facilitate prioritization of sites for management consideration. Seasonal and time‐of‐day patterns are provided to inform the scheduling of activities. The intersection of activity centers with the electrical infrastructure is examined to identify locations with the highest mortality risk. Lines intersecting with high‐use activity centers have produced mortality rates that are 42 times higher than lines intersecting with low‐use areas. Site‐specific information is provided to allow for the phasing of hazard mitigation. This report concludes the largest investigation of space use by bald eagles ever conducted. The project has clarified several aspects of eagle ecology within the upper Chesapeake Bay and has moved the science of eagle management forward in a way that will inform management throughout the species range. The still ongoing tracking database holds a great deal of promise for new ecological discoveries and management solutions

Changes in Producers’ Perceptions of Within-field Yield Variability Following Adoption of Cotton Yield Monitors

Precision Farming, Risk, Yield Monitor, Yield Variability, Yield Perceptions, Spatial Yield Distributions, Within Field Variability, Farm Management, Production Economics, Risk and Uncertainty, Q12, Q16,