Simulating Granite Emplacement and Deformation with Centrifuge Analogue Modelling

The Greater Himalayan leucogranites are a discontinuous suite of intrusions emplaced in a thickened crust during the Miocene southward ductile extrusion of the Himalayan metamorphic core. Melt-induced weakening is thought to have played a critical role in strain localization that facilitated the extrusion. Recent advancements in centrifuge analogue modelling techniques allow for the replication of a broader range of crustal deformation behaviors, enhancing our understanding of large hot orogens. Polydimethylsiloxane (PDMS) is commonly used in centrifuge experiments to model weak melt zones. Difficulties in handling PDMS had, until now, limited its emplacement in models prior to any deformation. A new modelling technique has been developed where PDMS is emplaced into models that have been subjected to some shortening. This technique aims to better understand the effects of melt on strain localization and potential decoupling between structural levels within an evolving orogenic system. Models are subjected to an early stage of shortening, followed by the introduction of PDMS, and then a final stage of shortening. Theoretical percentages of partial melt and their effect on rock strength are considered when adding a specific percentage of PDMS in each model. Due to the limited size of the models, only PDMS sheets of 3 mm thickness were used, which varied in length and width. Within undeformed packages, minimal surface and internal deformation occurred when PDMS is emplaced in the lower layer of the model, showing a vertical volume increase of ~20% within the package; whereas the emplacement of PDMS into the middle layer showed internal dragging of the middle laminations into the lower layer and a vertical volume increase ~30%. Emplacement of PDMS results in ~7% shortening for undeformed and deformed models. Deformed models undergo ~20% additional shortening after two rounds of deformation. Strain localization and decoupling between units occur in deformed models where the degree of deformation changes based on the amount of partial melt present. Surface deformation visible by the formation of a bulge, mode 1 extension cracks and varying surface strain ellipses varies depending if PDMS is present. Better control during emplacement is exhibited when PDMS is added into cooler models, resulting in reduced internal deformation within the middle layer.

Analysis of Lipoprotein(a) Catabolism

Elevated plasma concentrations of lipoprotein(a) [Lp(a)] have been identified as an independent risk factor for vascular diseases including coronary heart disease and stroke. In the current study, we have examined the binding and degradation of recombinant forms of apolipoprotein(a) [r-apo(a)], the unique kringle-containing moiety of Lp(a), using a cultured cell model. We found that the incubation of human hepatoma (HepG2) cells with an iodinated 17 kringle-containing (17K) recombinant form of apo(a) resulted in a two-component binding system characterized by a high affinity (Kd = 12 nM), low capacity binding site, and a low affinity (Kd = 249 nM), high capacity binding site. We subsequently determined that the high affinity binding site on HepG2 cells corresponds to the LDL receptor. In the HepG2 cell model, association of apo(a) with the LDL receptor was shown to be dependent on the formation of Lp(a) particles from endogenous LDL. Using an apo(a) mutant incapable of binding to the high affinity site through its inability to form Lp(a) particles (17KΔLBS7,8), we further demonstrated that the LDL receptor does not participate in Lp(a) catabolism. The low affinity binding component observed on HepG2 cells, familial hypercholesterolemia (FH) fibroblasts and human embryonic kidney (HEK) 293 cells may correspond to a member(s) of the plasminogen receptor family, as binding to this site(s) was decreased by the addition of the lysine analogue epsilon-aminocaproic acid. The lysine-dependent nature of the low affinity binding site was further confirmed in HepG2 binding studies utilizing r-apo(a) species with impaired lysine binding ability. We observed a reduction maximum binding capacity for 17K r-apo(a) variants lacking the strong lysine binding site (LBS) in kringle IV type 10 (17KΔAsp) and the very weak LBS in kringle V (17KΔV). Degradation of Lp(a)/apo(a) was found to be mediated exclusively by the low affinity component on both HepG2 cells and FH fibroblasts. Fluorescence confocal microscopy, using the 17K r-apo(a) variant fused to green fluorescent protein, further confirmed that degradation by the low affinity component on HepG2 cells does not proceed by the activity of cellular lysosomes. Taken together, these data suggest a potentially significant route for Lp(a)/apo(a) clearance in vivo.