Modelling the growth of prion protein aggregates in the brain in variant Creutzfeldt-Jakob disease

Deposition of insoluble prion protein (PrP) in the brain in the form of protein aggregates or deposits is characteristic of the ‘transmissible spongiform encephalopathies’ (TSEs). Understanding the growth and development of these PrP aggregates is important both in attempting to the elucidate of the pathogenesis of prion disease and in the development of treatments designed to prevent or inhibit the spread of prion pathology within the brain. Aggregation and disaggregation of proteins and the diffusion of substances into the developing aggregates (surface diffusion) are important factors in the development of protein aggregates. Mathematical models suggest that if aggregation/disaggregation or surface diffusion is the predominant factor, the size frequency distribution of the resulting protein aggregates in the brain should be described by either a power-law or a log-normal model respectively. This study tested this hypothesis for two different types of PrP deposit, viz., the diffuse and florid-type PrP deposits in patients with variant Creutzfeldt-Jakob disease (vCJD). The size distributions of the florid and diffuse plaques were fitted by a power-law function in 100% and 42% of brain areas studied respectively. By contrast, the size distributions of both types of plaque deviated significantly from a log-normal model in all brain areas. Hence, protein aggregation and disaggregation may be the predominant factor in the development of the florid plaques. A more complex combination of factors appears to be involved in the pathogenesis of the diffuse plaques. These results may be useful in the design of treatments to inhibit the development of protein aggregates in vCJD.

Growth rates of Rhizocarpon geographicum lichens:A review with new data from Iceland

This paper reviews evidence from previous growth-rate studies on lichens of the yellow-green species of Subgenus Rhizocarpon - the family most commonly used in lichenometric dating. New data are presented from Rhizocarpon section Rhizocarpon thalli growing on a moraine in southern Iceland over a period of 4.33yr. Measurements of 38 lichen thalli, between 2001 and 2005, show that diametral growth rate (DGR, mmyr-1) is a function of thallus size. Growth rates increase rapidly in small thalli (<10 mm diameter), remain high (ca. 0.8 mm yr-1) and then decrease gradually in larger thalli (>50 mm diameter). Mean DGR in southern Iceland, between 2001 and 2005, was 0.64 mm yr-1 (SD = 0.24). The resultant growth-rate curve is parabolic and is best described by a third-order polynomial function. The striking similarity between these findings in Iceland and those of Armstrong (1983) in Wales implies that the shape of the growth-rate curve may be characteristic of Rhizocarpon geographicum lichens. The difference between the absolute growth rate in southern Iceland and Wales (ca. 66% faster) is probably a function of climate and micro-environment between the two sites. These findings have implications for previous lichenometric-dating studies, namely, that those studies which assume constant lichen growth rates over many decades are probably unreliable. © British Geological Survey/ Natural Environment Research Council copyright 2006.

Growth curves of four crustose lichens

The growth curves of four common species of crustose lichens, viz., Buellia aethalea (Ach.) Th. Fr., Lecidea tumida Massai., Rhizocarpon geographicum (L.) DC., and Rhizocarpon reductum Th. Fr. were studied at a site in south Gwynedd, north Wales, UK. Radial growth rates (RGR, mm 1.5 yr-1) were greatest in thalli of R. reductum and least in R. geographicum. Variation in RGR between thalli was greater in B. aethalea and L. tumida than in the species of Rhizocarpon. The relationship between growth rate and thallus diameter was not asymptotic; RGR increasing in smaller thalli to a maximum and then declining in larger diameter thalli. A polynomial curve was fitted to the data; the growth curves being fitted best by a second-order (quadratic) curve, the best fit to this model being shown by B. aethalea. A significant linear regression with a negative slope was also fitted to the growth of the larger thalli of each species. The data suggest that the growth curves of the four crustose lichens differ significantly from the asymptotic curves of foliose lichen species. A phase of declining RGR in larger thalli appears to be characteristic of crustose lichens and is consistent with data from lichenometric studies.

Modelling growth of prion protein aggregates in the brain in variant Creutzfeldt-Jakob disease

Deposition of insoluble prion protein (PrP) in the brain in the form of protein aggregates or deposits is characteristic of the ‘transmissible spongiform encephalopathies’ (TSEs). Understanding the growth and development of PrP aggregates is important both in attempting to elucidate the pathogenesis of prion disease and in the development of treatments designed to inhibit the spread of prion pathology within the brain. Aggregation and disaggregation of proteins and the diffusion of substances into the developing aggregates (surface diffusion) are important factors in the development of protein deposits. Mathematical models suggest that if either aggregation/disaggregation or surface diffusion is the predominant factor, then the size frequency distribution of the resulting protein aggregates will be described by either a power-law or a log-normal model respectively. This study tested this hypothesis for two different populations of PrP deposit, viz., the diffuse and florid-type PrP deposits characteristic of patients with variant Creutzfeldt-Jakob disease (vCJD). The size distributions of the florid and diffuse deposits were fitted by a power-law function in 100% and 42% of brain areas studied respectively. By contrast, the size distributions of both types of aggregate deviated significantly from a log-normal model in all areas. Hence, protein aggregation and disaggregation may be the predominant factor in the development of the florid deposits. A more complex combination of factors appears to be involved in the pathogenesis of the diffuse deposits. These results may be useful in the design of treatments to inhibit the development of PrP aggregates in vCJD.

Memory effects in a non-equilibrium growth model

We study memory effects in a kinetic roughening model. For d=1, a different dynamic scaling is uncovered in the memory dominated phases; the Kardar-Parisi-Zhang scaling is restored in the absence of noise. dc=2 represents the critical dimension where memory is shown to smoothen the roughening front (a=0). Studies on a discrete atomistic model in the same universality class reconfirm the analytical results in the large time limit, while a different scaling behavior shows up for tcharacteristic of the atomistic model. Results can be generalized for other nonconservative systems.

Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability

Increased vascular permeability is an early event characteristic of tissue ischemia and angiogenesis. Although VEGF family members are potent promoters of endothelial permeability the role of placental growth factor (PlGF) is hotly debated. Here we investigated PlGF isoforms 1 and 2 and present in vitro and in vivo evidence that PlGF-1, but not PlGF-2, can inhibit VEGF-induced permeability but only during a critical window post-VEGF exposure. PlGF-1 promotes VE-cadherin expression via the trans-activating Sp1 and Sp3 interaction with the VE-cadherin promoter and subsequently stabilizes transendothelial junctions, but only after activation of endothelial cells by VEGF. PlGF-1 regulates vascular permeability associated with the rapid localization of VE-cadherin to the plasma membrane and dephosphorylation of tyrosine residues that precedes changes observed in claudin 5 tyrosine phosphorylation and membrane localization. The critical window during which PlGF-1 exerts its effect on VEGF-induced permeability highlights the importance of the translational significance of this work in that PLGF-1 likely serves as an endogenous anti-permeability factor whose effectiveness is limited to a precise time point following vascular injury. Clinical approaches that would pattern nature's approach would thus limit treatments to precise intervals following injury and bring attention to use of agents only during therapeutic windows.

Epitaxial growth and magnetic properties of half-metallic Fe3O4 on GaAs(100)

The growth and magnetic properties of epitaxial magnetite Fe3O4 on GaAs(100) have been studied by reflection high-energy electron diffraction, x-ray photoelectron spectroscopy, magneto-optical Kerr effect, and x-ray magnetic circular dichroism. The epitaxial Fe3O4 films were synthesized by in situ post growth annealing of ultrathin epitaxial Fe films at 500K in an oxygen partial pressure of 5×10−5mbar. The XMCD measurements show characteristic contributions from different sites of the ferrimagnetic magnetite unit cell, namely, Fetd3+, Feoh2+, and Feoh3+. The epitaxial relationship was found to be Fe3O4(100)⟨011⟩∕∕GaAs(100)⟨010⟩ with the unit cell of Fe3O4 rotated by 45° to match that of GaAs(100) substrate. The films show a uniaxial magnetic anisotropy in a thickness range of about 2.0–6.0nm with the easy axes along the [011] direction of the GaAs(100) substrate.