Using Confocal Microscopy to Generate an Accurate Vascular Model for Use in Patient Education Animation.

Hypertension is a condition requiring lifelong medication, where patients often feel well with or without treatment. Uncontrolled hypertension, however, can lead to permanent remodelling processes that occur to the vascular structure, which are seldom understood by the public. As a result, a significant burden is placed on healthcare systems globally as a result of the effects of hypertension and lack of adherence to prescribed treatment.Improving patient education through well-designed interactive applications and animation is a known strategy that can improve adherence rates to medication. In the context of hypertension, little attention has been given to helping patients understand the unseen damage that occurs to vessels exposed to high blood pressure. However, generating an accurate representation of a vessel and the changes that occur can be challenging. Using microscopy data is one way for creating an anatomically correct model, but this often needs careful consideration as data cannot be directly imported. Here we describe methods for creating an accurate 3D model of a small artery using confocal microscopy data. This model can then be animated to demonstrate the substructures and pathological changes that occur in hypertensive conditions to better inform patients about the dangers of uncontrolled blood pressure.

Slow plastic creep of 2D dusty plasma solids.

We report complex plasma experiments, assisted by numerical simulations, providing an alternative qualitative link between the macroscopic response of polycrystalline solid matter to small shearing forces and the possible underlying microscopic processes. In the stationary creep regime we have determined the exponents of the shear rate dependence of the shear stress and defect density, being α=1.15±0.1 and ß=2.4±0.4, respectively. We show that the formation and rapid glide motion of dislocation pairs in the lattice are dominant processes.

Stimulating healthy tissue regeneration by targeting the 5-HT2B receptor in chronic liver disease.

Tissue homeostasis requires an effective, limited wound-healing response to injury. In chronic disease, failure to regenerate parenchymal tissue leads to the replacement of lost cellular mass with a fibrotic matrix. The mechanisms that dictate the balance of cell regeneration and fibrogenesis are not well understood. Here we report that fibrogenic hepatic stellate cells (HSCs) in the liver are negative regulators of hepatocyte regeneration. This negative regulatory function requires stimulation of the 5-hydroxytryptamine 2B receptor (5-HT(2B)) on HSCs by serotonin, which activates expression of transforming growth factor ß1 (TGF-ß1), a powerful suppressor of hepatocyte proliferation, through signaling by mitogen-activated protein kinase 1 (ERK) and the transcription factor JunD. Selective antagonism of 5-HT(2B) enhanced hepatocyte growth in models of acute and chronic liver injury. We also observed similar effects in mice lacking 5-HT(2B) or JunD or upon selective depletion of HSCs in wild-type mice. Antagonism of 5-HT(2B) attenuated fibrogenesis and improved liver function in disease models in which fibrosis was pre-established and progressive. Pharmacological targeting of 5-HT(2B) is clinically safe in humans and may be therapeutic in chronic liver disease.

One-dimensional vertical dust strings in a glass box.

The oscillation spectrum of a one-dimensional vertical dust string formed inside a glass box on top of the lower electrode in a gaseous electronics conference (GEC) reference cell was studied. A mechanism for creating a single vertical dust string is described. It is shown that the oscillation amplitudes, resonance frequencies, damping coefficients, and oscillation phases of the dust particles separate into two distinct groups. One group exhibits low damping coefficients, increasing amplitudes, and decreasing resonance frequencies for dust particles closer to the lower electrode. The other group shows high damping coefficients but anomalous resonance frequencies and amplitudes. At low oscillation frequencies, the two groups are also separated by a π phase difference. One possible cause for the difference in behavior between the two groups is discussed.

Crystallization dynamics of a single layer complex plasma.

We report a series of complex (dusty) plasma experiments, aimed at the study of the detailed time evolution of the recrystallization process following a rapid quench of a two-dimensional dust liquid. The experiments were accompanied by large-scale (million-particle) molecular dynamics simulations, assuming Yukawa-type interparticle interaction. Both experiment and simulation show a ∝t(α) (power-law) dependence of the linear crystallite domain size as measured by the bond-order correlation length, translational correlation length, dislocation (defect) density, and a direct size measurement algorithm. The results show two stages of order formation. On short time scales, individual particle motion dominates; this is a fast process characterized by α=0.93±0.1. At longer time scales, small crystallites undergo collective rearrangement, merging into bigger ones, resulting in a smaller exponent α=0.38±0.06.

Antibody-targeted myofibroblast apoptosis reduces fibrosis during sustained liver injury.

BACKGROUND/AIMS: Myofibroblast apoptosis promotes the resolution of liver fibrosis. However, retaining macrophages may enhance reversal. The effects of specifically stimulating myofibroblast apoptosis in vivo were assessed. METHODS: A single chain antibody (C1-3) to an extracellular domain of a myofibroblast membrane protein was injected as a fluorescent- or gliotoxin conjugate into mice with liver fibrosis. RESULTS: C1-3 specifically targeted alpha-smooth muscle actin positive liver myofibroblasts within scar regions of the liver in vivo and did not co-localise with liver monocytes/macrophages. Injection of free gliotoxin stimulated a 2-fold increase in non-parenchymal cell apoptosis and depleted liver myofibroblasts by 30% and monocytes/macrophages by 50% but had no effect on fibrosis severity in the sustained injury model employed. In contrast, C1-3-targeted gliotoxin stimulated a 5-fold increase in non-parenchymal cell apoptosis, depleted liver myofibroblasts by 60%, did not affect the number of monocytes/macrophages and significantly reduced fibrosis severity. Fibrosis reduction was associated with increased metalloproteinase-13 levels. CONCLUSIONS: These data demonstrate that specific targeting of liver myofibroblast apoptosis is the most effective anti-fibrogenic therapy, supporting a role for liver monocytes and/or macrophages in the promotion of liver fibrosis reduction.

Targeting liver myofibroblasts: a novel approach in anti-fibrogenic therapy.

Chronic liver disease results in a liver-scarring response termed fibrosis. Excessive scarring leads to cirrhosis, which is associated with high morbidity and mortality. The only treatment for liver cirrhosis is liver transplantation; therefore, much attention has been directed toward therapies that will slow or reverse fibrosis. Although anti-fibrogenic therapies have been shown to be effective in experimental animal models, licensed therapies have yet to emerge. A potential problem for any anti-fibrogenic therapy in the liver is the existence of the body's major drug metabolising cell (the hepatocyte) adjacent to the primary fibrosis-causing cell, the myofibroblast. This article reviews the development of a human recombinant single-chain antibody (scAb) that binds to the surface of myofibroblasts. This antibody binds specifically to myofibroblasts in fibrotic mouse livers. When conjugated with a compound that stimulates myofibroblast apoptosis, the antibody directs the specific apoptosis of myofibroblasts with greater specificity and efficacy than the free compound. The antibody also reduces the adverse effect of liver macrophage apoptosis and-in contrast to the free compound-reversed fibrosis in the sustained injury model used. These data suggest that specifically stimulating the apoptosis of liver myofibroblasts using a targeting antibody has potential in the treatment of liver fibrosis.