Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.     

Effects of long-term livestock grazing and habitat on understory vegetation

The herbaceous understory stratum contains most of the plant diversity in ponderosa pine ( Pinus ponderosa P. & C. Lawson var. scopulorum Engelm.) forests of the American Southwest and provides critical food and habitat for many wildlife species. During the last century, this stratum has been affected by livestock grazing and by increased dominance of overstory trees. We sampled a unique grazing exclosure to examine the relative importance of long-term livestock grazing (grazed or ungrazed) and habitat (park or tree) on the understory community. We sampled 3 plots of 192 contiguous quadrats (each quadrat 0.5 m 2 ) in each of the 4 treatment combinations, for a total of 2304 quadrats. Species-area curves were generated by aggregating quadrats into nonoverlapping areas at grain sizes of 0.5 to 576 m 2 . The effects of habitat and grazing on species density were evident at very different scales. Species density was higher in park than tree plots at scales ≤32 m 2 but did not differ between habitats at larger scales. Species density differed minimally between grazed and ungrazed treatments at small grains, but grazed plots contained more species than ungrazed plots at larger grains. Grazing treatments differed at smaller grains (to 4–8 m 2 ) than did habitats (to 32 m 2 ), with respect to density of native species and graminoids. Grazed plots had more exotic species than ungrazed plots at all grain sizes, though few exotics were present. Twenty-two species were identified as indicator species associated with habitats and/or grazing treatments. Evaluations of plant community response to treatments would be improved by accounting for the grain at which data have been collected and analyzed and by identifying indicator species associated with various treatments. These data would enable more-informed conservation and management decisions.     

The knockout mouse project

Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain.     

Hormonal manipulation of carrageenin-induced pyresis in rats

Summary The intensity of the hyperthermic response in rats promoted by subplantar injection of 1 mg of carrageenin is directly related to the irritant properties of the type of carrageenin. The overall pyretic response is more dramatic in female rats than in male rats. Subtle changes in the time-course hyperthermic profiles are seen after hormonal modifications.This work was supported by NIH, MBS research grant No. RR08111.