A novel, resistance-linked ovine PrP variant and its equivalent mouse variant modulate the in vitro cell-free conversion of rPrP to PrPres

Prion diseases are associated with the conversion of the normal cellular prion protein, PrPc, to the abnormal, disease-associated form, PrPSc. This conversion can be mimicked in vitro by using a cell-free conversion assay. It has recently been shown that this assay can be modified to use bacterial recombinant PrP as substrate and mimic the in vivo transmission characteristics of rodent scrapie. Here, it is demonstrated that the assay replicates the ovine polymorphism barriers of scrapie transmission. In addition, the recently identified ovine PrP variant ARL168Q, which is associated with resistance of sheep to experimental BSE, modulates the cell-free conversion of ovine recombinant PrP to PrPres by three different types of PrPSc, reducing conversion efficiencies to levels similar to those of the ovine resistance-associated ARR variant. Also, the equivalent variant in mice (L164) is resistant to conversion by 87V scrapie. Together, these results suggest a significant role for this position and/or amino acid in conversion

A gene-targeted mouse model of P102L Gerstmann-Sträussler-Scheinker syndrome

Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177Item not available from this repository.https://doi.org/10.1016/S0272-2712(02)00067-723

Two Neural Circuits to Point Towards Home Position After Passive Body Displacements

International audienceA challenge in motor control research is to understand the mechanisms underlying the transformation of sensory information into arm motor commands. Here, we investigated these transformation mechanisms for movements whose targets were defined by information issued from body rotations in the dark (i.e., idiothetic information). Immediately after being rotated, participants reproduced the amplitude of their perceived rotation using their arm (Experiment 1). The cortical activation during movement planning was analyzed using electroencephalography and source analyses. Task-related activities were found in regions of interest (ROIs) located in the prefrontal cortex (PFC), dorsal premotor cortex, dorsal region of the anterior cingulate cortex (ACC) and the sensorimotor cortex. Importantly, critical regions for the cognitive encoding of space did not show significant task-related activities. These results suggest that arm movements were planned using a sensorimotor-type of spatial representation. However, when a 8 s delay was introduced between body rotation and the arm movement (Experiment 2), we found that areas involved in the cognitive encoding of space [e.g., ventral premotor cortex (vPM), rostral ACC, inferior and superior posterior parietal cortex (PPC)] showed task-related activities. Overall, our results suggest that the use of a cognitive-type of representation for planning arm movement after body motion is necessary when relevant spatial information must be stored before triggering the movement

Unlocking Access to Health Care: A Federalist Approach to Reforming Occupational Licensing

Several features of the existing occupational licensing system impede access to health care without providing appreciable protections for patients. Licensing restrictions prevent health care providers from offering services to the full extent of their competency, obstruct the adoption of telehealth, and deter foreign-trained providers from practicing in the United States. Scholars and policymakers have proposed a number of reforms to this system over the years, but these proposals have had a limited impact for political and institutional reasons. Still, there are grounds for optimism. In recent years, the federal government has taken a range of initial steps to reform licensing requirements for health care providers, and these steps have the potential to improve access to health care. Together, they illustrate a federalist approach to licensing reform, in which the federal government encourages the states to reform their licensing regimes, while largely preserving states’ control over the system. These steps include: (1) easing federal licensing restrictions for health care providers in certain areas where the federal government possesses regulatory authority; (2) creating incentives for states and professional bodies to experiment with reforms; (3) intensifying the Federal Trade Commission’s focus on licensing boards’ anti-competitive conduct; and (4) generating additional pressure for state-level reforms through expanding health insurance and promoting delivery system reforms under the Affordable Care Act. This article argues that a federalist approach represents the most promising path toward reforming occupational licensing in health care. Federal intervention in licensing is necessary, due to states’ lack of incentives to experiment with licensing reforms, the externalities of their licensing regimes, and their inability to resolve their own collective action problems. Nevertheless, large-scale federal preemption of state licensing laws is unlikely, due to a combination of interest group politics, Congress’s tendency toward incrementalism, and its reliance on the states to administer federal policies. A federalist approach also has functional advantages over outright federal preemption: it allows for more experimentation in constructing new licensing regimes, and it enables the federal government to take advantage of states’ institutional expertise in regulating occupations. Finally, this approach presents a model for how the federal government can play a constructive role in occupational licensing in other fields besides health care, and in other areas of state regulatory policy

Human stem cell-derived astrocytes replicate human prions in a PRNP genotype-dependent manner.

Prions are infectious agents that cause neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD). The absence of a human cell culture model that replicates human prions has hampered prion disease research for decades. In this paper, we show that astrocytes derived from human induced pluripotent stem cells (iPSCs) support the replication of prions from brain samples of CJD patients. For experimental exposure of astrocytes to variant CJD (vCJD), the kinetics of prion replication occur in a prion protein codon 129 genotype-dependent manner, reflecting the genotype-dependent susceptibility to clinical vCJD found in patients. Furthermore, iPSC-derived astrocytes can replicate prions associated with the major sporadic CJD strains found in human patients. Lastly, we demonstrate the subpassage of prions from infected to naive astrocyte cultures, indicating the generation of prion infectivity in vitro. Our study addresses a long-standing gap in the repertoire of human prion disease research, providing a new in vitro system for accelerated mechanistic studies and drug discovery