Transmissibility of Atypical Scrapie in Ovine Transgenic Mice: Major Effects of Host Prion Protein Expression and Donor Prion Genotype

Atypical scrapie or Nor98 has been identified as a transmissible spongiform encephalopathy (TSE) that is clearly distinguishable from classical scrapie and BSE, notably regarding the biochemical features of the protease-resistant prion protein PrPres and the genetic factors involved in susceptibility to the disease. In this study we transmitted the disease from a series of 12 French atypical scrapie isolates in a transgenic mouse model (TgOvPrP4) overexpressing in the brain ∼0.25, 1.5 or 6× the levels of the PrPARQ ovine prion protein under the control of the neuron-specific enolase promoter. We used an approach based on serum PrPc measurements that appeared to reflect the different PrPc expression levels in the central nervous system. We found that transmission of atypical scrapie, much more than in classical scrapie or BSE, was strongly influenced by the PrPc expression levels of TgOvPrP4 inoculated mice. Whereas TgOvPrP4 mice overexpressing ∼6× the normal PrPc level died after a survival periods of 400 days, those with ∼1.5× the normal PrPc level died at around 700 days. The transmission of atypical scrapie in TgOvPrP4 mouse line was also strongly influenced by the prnp genotypes of the animal source of atypical scrapie. Isolates carrying the AF141RQ or AHQ alleles, associated with increased disease susceptibility in the natural host, showed a higher transmissibility in TgOvPrP4 mice. The biochemical analysis of PrPres in TgOvPrP4 mouse brains showed a fully conserved pattern, compared to that in the natural host, with three distinct PrPres products. Our results throw light on the transmission features of atypical scrapie and suggest that the risk of transmission is intrinsically lower than that of classical scrapie or BSE, especially in relation to the expression level of the prion protein

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Semi-natural test methods to evaluate fire safety of wall claddings

External walls and their components are subjected to a number of fire safety requirements. Fire resistance and reaction to fire are the harmonised requirements in the EU. These cover two fire scenarios: contribution of internal wall linings to an intermediate-size developing fire inside a fire compartment, and resistance of external walls to post-flashover fire inside a fire compartment (resistance to an external fire may also be required). The spread of fire along the external surface is not part of this European evaluation system and remains subjected to national fire safety codes and regulations. A number of test methods covering this scenario exist in Europe and North America at national levels as well as at the international level (ISO). These test methods and associated criteria differ in fire size, test duration, test specimen size and configuration. This paper presents principles of major existing test methods and comparison of test results on comparable test specimens where they are available

Semi-natural test methods to evaluate fire safety of wall claddings

External walls and their components are subjected to a number of fire safety requirements. Fire resistance and reaction to fire are the harmonised requirements in the EU. These cover two fire scenarios: contribution of internal wall linings to an intermediate-size developing fire inside a fire compartment, and resistance of external walls to post-flashover fire inside a fire compartment (resistance to an external fire may also be required). The spread of fire along the external surface is not part of this European evaluation system and remains subjected to national fire safety codes and regulations. A number of test methods covering this scenario exist in Europe and North America at national levels as well as at the international level (ISO). These test methods and associated criteria differ in fire size, test duration, test specimen size and configuration. This paper presents principles of major existing test methods and comparison of test results on comparable test specimens where they are available

Semi-natural test methods to evaluate fire safety of wall claddings: Update

There are a number of test methods worldwide to evaluate fire safety of facades. An overview of available test methods implemented in fire safety codes was presented at the 1st Conference of Fire Safety of Facades in 2013. [1] Since then, a number of changes and developments occurred. The purpose of this paper is to present the updated global overview of facade fire spread test methods made for building regulations

Semi-natural test methods to evaluate fire safety of wall claddings: Update

There are a number of test methods worldwide to evaluate fire safety of facades. An overview of available test methods implemented in fire safety codes was presented at the 1st Conference of Fire Safety of Facades in 2013. [1] Since then, a number of changes and developments occurred. The purpose of this paper is to present the updated global overview of facade fire spread test methods made for building regulations