Spiral surface growth without desorption

Spiral surface growth is well understood in the limit where the step motion is controlled by the local supersaturation of adatoms near the spiral ridge. In epitaxial thin-film growth, however, spirals can form in a step-flow regime where desorption of adatoms is negligible and the ridge dynamics is governed by the non-local diffusion field of adatoms on the whole surface. We investigate this limit numerically using a phase-field formulation of the Burton-Cabrera-Frank model, as well as analytically. Quantitative predictions, which differ strikingly from those of the local limit, are made for the selected step spacing as a function of the deposition flux, as well as for the dependence of the relaxation time to steady-state growth on the screw dislocation density.Comment: 9 pages, 3 figures, RevTe

Neuromelanin-MRI using 2D GRE and deep learning: considerations for improving the visualization of substantia nigra and locus coeruleus

An optimized clinically feasible neuromelanin-MRI imaging protocol for visualising the SN and LC simultaneously using deep learning reconstruction is presented. We optimize flip-angle for optimal combined SN and LC depiction. We also experimented with combinations of anisotropic and isotropic in-plane resolution, partial vs full echoes and the number of averages. Phantom and in-vivo experiments on three healthy volunteers illustrate that high-resolution imaging combined with deep-learning denoising shows good depiction of the SN and LC with a clinically feasible sequence of around 7 minutes.Comment: An article based on ECR and ISMRM abstracts, with more text & figure

Deletion of the ghrelin receptor GHSR corrects the trabecular, but not the cortical bone changes in the femoral head of ob/ob mice

Background: There exists an intriguing and complex relationship between fat and bone cells with respect to aging and osteoporosis, which is mediated in part by leptin. Genetically obese mice (ob/ob), that lack leptin, have aheterogeneous bone phenotype, with differential effects on cortical and trabecular compartments. Besides its role in bone metabolism, leptin is most well known for its anorexigenic properties. Opposed in action to leptin is ghrelin, a potent orexigenic peptide hormone derived from the stomach. Ghrelin and leptin also act as each other’s antagonists in gonadal and immune system function.Objective: To determine if ghrelin opposes leptin action on bone metabolism.Methods: Characterization of femoral micro-architecture in 6 months old male wild type, ob/ob, ghrelin receptor knockout (Ghsr -/-), and ob/ob.Ghsr-/- mice using micro-computed tomography.Results: Deletion of Ghsr alone did not significantly alter bone micro-architecture in wild type mice. Deletion of leptin reduced cortical volume and thickness in the femoral head of wild type mice, while it increased endocortical volume. Tissue volume remained unaffected. Conversely, deletion of leptin increased trabecular bone volume, trabecular number and connectivity in wild type mice. Additional deletion of Ghsr in ob/ob mice restored the changes to wild type levels in trabecular bone, but not in cortical bone (all not significant).Conclusion: We found that leptin deficiency has a negative effect on cortical and a positive effect on trabecular bone micro-architecture, confirming the heterogeneous skeletal effects observed by others in ob/ob mice. Knocking out ghrelin signaling compensates for the effect of leptin deficiency on trabecular bone. These observations demonstrate the positive activity of ghrelin signaling in bone, and suggest that ghrelin and leptin have opposing actions on bone metabolism

Protein arginine methyltransferases PRMT1, PRMT4/CARM1 and PRMT5 have distinct functions in control of osteoblast differentiation

Osteogenic differentiation of mesenchymal cells is controlled by epigenetic enzymes that regulate post-translational modifications of histones. Compared to acetyl or methyltransferases, the physiological functions of protein arginine methyltransferases (PRMTs) in osteoblast differentiation remain minimally understood. Therefore, we surveyed the expression and function of all nine mammalian PRMT members during osteoblast differentiation. RNA-seq gene expression profiling shows that Prmt1, Prmt4/Carm1 and Prmt5 represent the most prominently expressed PRMT subtypes in mouse calvarial bone and MC3T3 osteoblasts as well as human musculoskeletal tissues and mesenchymal stromal cells (MSCs). Based on effects of siRNA depletion, it appears that PRMT members have different functional effects: (i) loss of Prmt1 stimulates and (ii) loss of Prmt5 decreases calcium deposition of mouse MC3T3 osteoblasts, while (iii) loss of Carm1 is inconsequential for calcium deposition. Decreased Prmt5 suppresses expression of multiple genes involved in mineralization (e.g., Alpl, Ibsp, Phospho1) consistent with a positive role in osteogenesis. Depletion of Prmt1, Carm1 and Prmt5 has intricate but modest time-dependent effects on the expression of a panel of osteoblast differentiation and proliferation markers but does not change mRNA levels for select epigenetic regulators (e.g., Ezh1, Ezh2, Brd2 and Brd4). Treatment with the Class I PRMT inhibitor GSK715 enhances extracellular matrix mineralization of MC3T3 cells, while blocking formation of H3R17me2a but not H4R3me2a marks. In sum, Prmt1, Carm1 and Prmt5 have distinct biological roles during osteoblast differentiation, and different types histone H3 and H4 arginine methylation may contribute to the chromatin landscape during osteoblast differentiation.</p