Essential requirement of cytochrome c release for caspase activation by procaspase-activating compound defined by cellular models

Mitochondrial cytochrome c (cyt. c) release and caspase activation are often impaired in tumors with Bcl-2 overexpression or Bax and Bak-defective status. Direct triggering of cell death downstream of Bax and Bak is an attractive strategy to kill such cancers. Small molecule compounds capable of direct caspase activation appear to be the best mode for killing such tumors. However, there is no precise model to screen such compounds. The currently employed cell-free systems possess the inherent drawback of lacking cellular contents and organelles that operate in integrating cell death signaling. We have developed highly refined cell-based approaches to validate direct caspase activation in cancer cells. Using this approach, we show that PAC-1 (first procaspase-activating compound), the first direct activator of procaspases identified in a cell-free system, in fact requires mitochondrial cyt. c release for triggering caspase activation similar to other antitumor agents. It can induce significant caspase activation and cell death in the absence of Bax and Bak, and in cells overexpressing Bcl-2 and Bcl-xL. This study for the first time defines precise criteria for the validation of direct caspase-activating compounds using specialized cellular models that is expected to accelerate the discovery of potential direct caspase activators.     

Complications in postbariatric body contouring: strategies for assessment and prevention

Massive weight loss patients present specific challenges to the plastic surgeon. Review of these issues may be valuable for the surgeon who does not specialize in this area. Obtaining excellent results involves a comprehensive perioperative approach, beginning with proper patient selection and appropriate expectations. Operative considerations such as hypothermia prevention and thromboembolic prophylaxis can play a role in improving outcomes and reducing morbidity. Appropriately focused postoperative care completes the surgical plan, leading to satisfying results for both patient and surgeon.     

Stopover habitats of spring migrating surf scoters in southeast Alaska

Habitat conditions and nutrient reserve levels during spring migration have been suggested as important factors affecting population declines in waterfowl, emphasizing the need to identify key sites used during spring and understand habitat features and resource availability at stopover sites. We used satellite telemetry to identify stopover sites used by surf scoters migrating through southeast Alaska during spring. We then contrasted habitat features of these sites to those of random sites to determine habitat attributes corresponding to use by migrating scoters. We identified 14 stopover sites based on use by satellite tagged surf scoters from several wintering sites. We identified Lynn Canal as a particularly important stopover site for surf scoters originating throughout the Pacific winter range; approximately half of tagged coastally migrating surf scoters used this site, many for extended periods. Stopover sites were farther from the mainland coast and closer to herring spawn sites than random sites, whereas physical shoreline habitat attributes were generally poor predictors of site use. The geography and resource availability within southeast Alaska provides unique and potentially critical stopover habitat for spring migrating surf scoters. Our work identifies specific sites and habitat resources that deserve conservation and management consideration. Aggregations of birds are vulnerable to human activity impacts such as contaminant spills and resource management decisions. This information is of value to agencies and organizations responsible for emergency response planning, herring fisheries management, and bird and ecosystem conservation. © 2010 The Wildlife Society     

NADPH-dependent sulfite reductase flavoprotein adopts an extended conformation unique to this diflavin reductase

This is the first X-ray crystal structure of the monomeric form of sulfite reductase (SiR) flavoprotein (SiRFP-60) that shows the relationship between its major domains in an extended position not seen before in any homologous diflavin reductases. Small angle neutron scattering confirms this novel domain orientation also occurs in solution. Activity measurements of SiR and SiRFP variants allow us to propose a novel mechanism for electron transfer from the SiRFP reductase subunit to its oxidase metalloenzyme partner that, together, make up the SiR holoenzyme. Specifically, we propose that SiR performs its 6-electron reduction via intramolecular or intermolecular electron transfer. Our model explains both the significance of the stoichiometric mismatch between reductase and oxidase subunits in the holoenzyme and how SiR can handle such a large volume electron reduction reaction that is at the heart of the sulfur bio-geo cycle.     

Long-Term Carriage of Medicopsis romeroi,an Agent of Black-Grain Mycetoma,Presenting as Phaeohyphomycosis in a Renal Transplant Patient

Mycopathologia - Medicopsis species are rare fungal pathogens that frequently resist common antifungal therapies and are difficult to identify morphologically as conidia are produced in pycnidia, a...     

Comparing clustered sampling designs for spatially explicit estimation of population density

Spatially explicit capture–recapture methods do not assume that animals have equal access to sampling devices (e.g., detectors), which allows for gaps in the sampling extent and nonuniform (e.g., clustered) sampling designs. However, the performance (i.e., relative root mean squared error [RRMSE], confidence interval coverage, relative bias and relative standard error) of clustered detector arrays has not been thoroughly evaluated. I used simulations to evaluate the performance of various detector and cluster spacings, cluster configurations (i.e., number of detectors arranged in a square grid), sampling extents and number of sampling occasions for estimating population density, the relationship between detection rate and distance to a detector from the animal's center of activity (σ) and base detection rates, using American black bears (Ursus americanus) as a case study. My simulations indicated that a wide range of detector configurations can provide reliable estimates if spacing between detectors in clusters is ≥1σ and ≤3σ. A number of cluster configurations and occasion lengths produced estimates that were unbiased, resulted in good spatial coverage, and were relatively precise. Moreover, increasing the duration of sampling, establishing large study areas, increasing detection rates and spacing clusters so that cross-cluster sampling of individuals can occur could help ameliorate deficiencies in the detector layout. These results have application for a wide array of species and sampling methods (e.g., DNA sampling, camera trapping, mark-resight and search-encounter) and suggest that clustered sampling can significantly reduce the effort necessary to provide reliable estimates of population density across large spatial extents that previously would have been infeasible with nonclustered sampling designs.