Nanotechnology Applications in Transplantation Medicine.

A recent technological advance that shows promise for applications in health care, including transplantation medicine, is the implementation of nanoparticles. Nanoparticles can be composed of a variety of organic or inorganic materials and confer many advantages over conventional treatments available, such as low toxicity, low-effective dosage required, and a high degree of manipulability. Although also used for imaging and diagnostics, nanoparticles' utility as a drug or genetic delivery system is of particular interest in transplantation medicine. Currently, researchers are exploring options to integrate nanoparticles into both diagnostics and therapy for both grafts ex-situ before transplantation and for patients following transplantation. These studies have demonstrated that nanoparticles can mitigate damage to organs and patients through a large variety of mechanisms-ranging from the induction of cellular genetic changes to the enhancement of immunosuppressive drug delivery. Specifically, with the advent of machine perfusion preservation ex vivo, treatment of the graft became a very attractive approach and nanoparticles have great potential. However, before nanoparticles can be translated into clinical use, their short-term and long-term toxicity must be thoroughly characterized, especially with regards to their interactions with other biological molecules present in the human body.

3D mapping reveals network-specific amyloid progression and subcortical susceptibility in mice.

Alzheimer's disease (AD) is a progressive, neurodegenerative dementia with no cure. Prominent hypotheses suggest accumulation of beta-amyloid (Aß) contributes to neurodegeneration and memory loss, however identifying brain regions with early susceptibility to Aß remains elusive. Using SWITCH to immunolabel intact brain, we created a spatiotemporal map of Aß deposition in the 5XFAD mouse. We report that subcortical memory structures show primary susceptibility to Aß and that aggregates develop in increasingly complex networks with age. The densest early Aß occurs in the mammillary body, septum, and subiculum- core regions of the Papez memory circuit. Previously, early mammillary body dysfunction in AD had not been established. We also show that Aß in the mammillary body correlates with neuronal hyper-excitability and that modulation using a pharmacogenetic approach reduces Aß deposition. Our data demonstrate large-tissue volume processing techniques can enhance biological discovery and suggest that subcortical susceptibility may underlie early brain alterations in AD.