No abstract

We have demonstrated the layer-by-layer growth, via a urea coupling reaction between two bifunctional molecules, ethylenediamine and 1,4-phenylene diisocyanate, to form an ultrathin film on Ge(100)-2 x 1 at room temperature under vacuum conditions. The initial adsorption and subsequent growth of each layer was studied with multiple internal reflection Fourier transform infrared (MIR-FTIR) spectroscopy. Ethylenediamine reacts with Ge(100)-2 x 1 to produce a surface-bound amine group which is available for additional reaction. Subsequent exposure of 1,4-phenylene diisocyanate leads to a spontaneous urea coupling reaction between the surface-bound amine and the highly reactive isocyanate functional group. Three bands at 1665, 1512, and 1306 cm(-)(1) are characteristic of a urea linkage and provide evidence of the coupling reaction. The coupling procedure can be repeated in a binary fashion to create covalently bound ultrathin films at room temperature, and in the present work, we demonstrate the successful growth of four layers. In addition, we have found that an initial exposure of 1,4-phenylene diisocyanate to Ge(100)-2 x 1 produces an isocyanate-functionalized surface which, upon exposure to ethylenediamine, also forms urea linkages. This layer-by-layer deposition method provides a strategy with which to design and produce precisely tailored organic materials at semiconductor interfaces.

Although the unifying hallmark of prion diseases is CNS neurodegeneration caused by conformational corruption of host prion protein (PrP) to its infective counterpart, contagious transmission of chronic wasting disease (CWD) results from shedding of prions produced at high titers in the periphery of diseased cervids. While deer and elk PrP primary structures are equivalent except at residue 226, which is glutamate in elk and glutamine in deer, the effect of this difference on CWD pathogenesis is largely unknown. Using a gene-targeting approach where the mouse PrP coding sequence was replaced with elk or deer PrP, we show that the resulting GtE226 and GtQ226 mice had distinct kinetics of disease onset, prion conformations, and distributions of prions in the brains of diseased mice following intracerebral CWD challenge. These findings indicate that amino acid differences at PrP residue 226 dictate the selection and propagation of divergent strains in deer and elk with CWD. Because prion strain properties largely dictate host-range potential, our findings suggest that prion strains from elk and deer pose distinct risks to sympatric species or humans exposed to CWD. GtE226 and GtQ226 mice were also highly susceptible to CWD prions following intraperitoneal and oral exposures, a characteristic that stood in stark contrast to previously produced transgenic models. Remarkably, disease transmission was effective when infected mice were cohoused with naïve cagemates. Our findings indicate that gene-targeted mice provide unprecedented opportunities to accurately investigate CWD peripheral pathogenesis, CWD strains, and mechanisms of horizontal CWD transmission.