A new method for cancer detection based on diffusion reflection measurements of targeted gold nanorods

This paper presents a new method for cancer detection based on diffusion reflection measurements. This method enables discrimination between cancerous and noncancerous tissues due to the intense light absorption of gold nanorods (GNRs), which are selectively targeted to squamous cell carcinoma head and neck cancer cells. Presented in this paper are tissue-like phantom and in vivo results that demonstrate the high sensitivity of diffusion reflection measurements to the absorption differences between the GNR-targeted cancerous tissue and normal, noncancerous tissue. This noninvasive and nonionizing optical detection method provides a highly sensitive, simple, and inexpensive tool for cancer detection

Characterization of four new monoclonal antibodies against the distal N-terminal region of PrP(c)

Prion diseases are a group of fatal neurodegenerative disorders that affect humans and animals. They are characterized by the accumulation in the central nervous system of a pathological form of the host-encoded prion protein (PrPC). The prion protein is a membrane glycoprotein that consists of two domains: a globular, structured C-terminus and an unstructured N-terminus. The N-terminal part of the protein is involved in different functions in both health and disease. In the present work we discuss the production and biochemical characterization of a panel of four monoclonal antibodies (mAbs) against the distal N-terminus of PrPC using a well-established methodology based on the immunization of Prnp0/0 mice. Additionally, we show their ability to block prion (PrPSc) replication at nanomolar concentrations in a cell culture model of prion infection. These mAbs represent a promising tool for prion diagnostics and for studying the physiological role of the N-terminal domain of PrPC

alpha-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication

The precise molecular mechanism of how misfolded \uce\ub1-synuclein (\uce\ub1-Syn) accumulates and spreads in synucleinopathies is still unknown. Here, we show the role of the cellular prion protein (PrPC) in mediating the uptake and the spread of recombinant \uce\ub1-Syn amyloids. The in vitro data revealed that the presence of PrPC fosters the higher uptake of \uce\ub1-Syn amyloid fibrils, which was also confirmed in vivo in wild type (Prnp +/+) compared to PrP knock-out (Prnp -/-) mice. Additionally, the presence of \uce\ub1-Syn amyloids blocked the replication of scrapie prions (PrPSc) in vitro and ex vivo, indicating a link between the two proteins. Indeed, whilst PrPC is mediating the internalization of \uce\ub1-Syn amyloids, PrPSc is not able to replicate in their presence. This observation has pathological relevance, since several reported case studies show that the accumulation of \uce\ub1-Syn amyloid deposits in Creutzfeldt-Jakob disease patients is accompanied by a longer disease course

Site-specific structural analysis of a yeast prion strain with species-specific seeding activity

Prion proteins misfold and aggregate into multiple infectious strain variants that possess unique abilities to overcome prion species barriers, yet the structural basis for the species-specific infectivities of prion strains is poorly understood. Therefore, we have investigated the site-specific structural properties of a promiscuous chimeric form of the yeast prion Sup35 from Saccharomyces cerevisiae and Candida albicans. The Sup35 chimera forms two strain variants, each of which selectively infect one species but not the other. Importantly, the N-terminal and middle domains of the Sup35 chimera (collectively referred to as Sup35NM) contain two prion recognition elements (one from each species) that regulate the nucleation of each strain. Mutations in either prion recognition element significantly bias nucleation of one strain conformation relative to the other. Here we have investigated the folding of each prion recognition element for the serine-to-arginine mutant at residue 17 of the Sup35NM chimera known to promote nucleation of C. albicans strain conformation. Using cysteine-specific labeling analysis, we find that residues in the C. albicans prion recognition element are solvent-shielded, while those outside the recognition sequence (including most of those in the S. cerevisiae recognition element) are solvent-exposed. Moreover, we find that proline mutations in the C. albicans recognition sequence disrupt the prion templating activity of this strain conformation. Our structural findings reveal that differential folding of complementary and non-complementary prion recognition elements within the prion amyloid core of the Sup35NM chimera is the structural basis for its species-specific templating activity