Recombinant PrP and Its Contribution to Research on Transmissible Spongiform Encephalopathies

The misfolding of the cellular prion protein (PrPC) into the disease-associated isoform (PrPSc) and its accumulation as amyloid fibrils in the central nervous system is one of the central events in transmissible spongiform encephalopathies (TSEs). Due to the proteinaceous nature of the causal agent the molecular mechanisms of misfolding, interspecies transmission, neurotoxicity and strain phenomenon remain mostly ill-defined or unknown. Significant advances were made using in vivo and in cellula models, but the limitations of these, primarily due to their inherent complexity and the small amounts of PrPSc that can be obtained, gave rise to the necessity of new model systems. The production of recombinant PrP using E. coli and subsequent induction of misfolding to the aberrant isoform using different techniques paved the way for the development of cell-free systems that complement the previous models. The generation of the first infectious recombinant prion proteins with identical properties of brain-derived PrPSc increased the value of cell-free systems for research on TSEs. The versatility and ease of implementation of these models have made them invaluable for the study of the molecular mechanisms of prion formation and propagation, and have enabled improvements in diagnosis, high-throughput screening of putative anti-prion compounds and the design of novel therapeutic strategies. Here, we provide an overview of the resultant advances in the prion field due to the development of recombinant PrP and its use in cell-free systems

Modelling the skeletal muscle injury recovery using in vivo contrast-enhanced micro-CT : a proof-of-concept study in a rat model

Skeletal muscle injury characterisation during healing supports trauma prognosis. Given the potential interest of computed tomography (CT) in muscle diseases and lack of in vivo CT methodology to image skeletal muscle wound healing, we tracked skeletal muscle injury recovery using in vivo micro-CT in a rat model to obtain a predictive model. Skeletal muscle injury was performed in 23 rats. Twenty animals were sorted into five groups to image lesion recovery at 2, 4, 7, 10, or 14 days after injury using contrast-enhanced micro-CT. Injury volumes were quantified using a semiautomatic image processing, and these values were used to build a prediction model. The remaining 3 rats were imaged at all monitoring time points as validation. Predictions were compared with Bland-Altman analysis. Optimal contrast agent dose was found to be 20 mL/kg injected at 400 μL/min. Injury volumes showed a decreasing tendency from day 0 (32.3 ± 12.0mm 3, mean ± standard deviation) to day 2, 4, 7, 10, and 14 after injury (19.6 ± 12.6, 11.0 ± 6.7, 8.2 ± 7.7, 5.7 ± 3.9, and 4.5 ± 4.8 mm 3, respectively). Groups with single monitoring time point did not yield significant differences with the validation group lesions. Further exponential model training with single follow-up data (R 2 = 0.968) to predict injury recovery in the validation cohort gave a predictions root mean squared error of 6.8 ± 5.4 mm 3. Further prediction analysis yielded a bias of 2.327. Contrast-enhanced CT allowed in vivo tracking of skeletal muscle injury recovery in rat

Headwaters drive streamflow and lowland tracer export in a large‐scale humid tropical catchment

Documento relacionado con el Observatorio del Agua y Cambio GlobalHeadwaters are generally assumed to contribute the majority of water to downstream users, but how much water, of what quality and where it is generated are rarely known in the humid tropics. Here, using monthly monitoring in the data scarce (2,370 km2) San Carlos catchment in northeastern Costa Rica, we determined runoff-area relationships linked to geochemical and isotope tracers. We established 46 monitoring sites covering the full range of climatic, land use and geological gradients in the catchment. Regression and cluster analysis revealed unique spatial patterns and hydrologically functional landscape units. These units were used for seasonal and annual Bayesian tracer mixing models to assess spatial water source contributions to the outlet. Generally, the Bayesian mixing analysis showed that the chemical and isotopic imprint at the outlet is throughout the year dominated by the adjacent lowland catchments (68%) with much less tracer influence from the headwaters. However, the headwater catchments contributed the bulk of water and tracers to the outlet during the dry season (>50%) despite covering less than half of the total catchment area. Additionally, flow volumes seemed to be linearly scaled by area maintaining a link between the headwaters and the outlet particularly during high flows of the rainy season. Stable isotopes indicated mean recharge elevations above the mean catchment altitude, which further supports that headwaters were the primary source of downstream water. Our spatially detailed “snap-shot” sampling enabled a viable alternative source of large-scale hydrological process knowledge in the humid tropics with limited data availability.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI)UCR::Vicerrectoría de Docencia::Ciencias Sociales::Facultad de Ciencias Sociales::Escuela de Geografí