Mechanical Regulation of Wnt/β-catenin Signaling in Bone Cells

poster abstractThe Wnt/β-catenin signaling pathway is an important regulatory pathway in development and maintenance of various tissues, including bone. Active Wnt interacts with the frizzled/LRP receptor activating dishevelled, which in turn inactivates the GSK-3β complex and allows βcatenin to accumulate in the cytoplasm. β-catenin translocates to the nucleus where it activates a wide number of developmental target genes. Wnt can be sequestered by soluble frizzled related protein causing the inactivation of dishevelled, allowing for activation of the GSK-3β complex. This activated complex binds β-catenin and targets it for degradation. In addition to its other major role as a linker between cadherins and the actin cytoskeleton, β-catenin accumulation in the cytoplasm and subsequent translocation to the nucleus is a key step in the wnt/β-catenin signaling pathway. In bone, wnt/β-catenin signaling regulates skeletal formation, limb development and osteoblast maturation. Both active and inactive wnt/β-catenin signaling regulate bone cell development, active wnt/β-catenin signaling promotes osteoblast formation, while inactive wnt/β-catenin signaling inhibits osteoclast differentiation. Mechanical regulation of bone cells occurs through a process known as mechanotransduction which can be induced by fluid shear stress that occurs across the surfaces of osteoblasts and osteocytes, the effector cells of mechanotransduction. We hypothesize that knocking down β-catenin expression in mouse osteoblasts and osteoprogenitors will change the way these cells respond to fluid shear stress and regulate expression of relevant bone target genes. The future aims of this project are to assess the role of β-catenin during fluid shear stress induced osteoprogenitor cell differentiation by examining the expression of important osteoblast differentiation markers including: runx2, COX2, osteopontin, and osteocalcin and evaluate the significance of β-catenin during differentiation of bone marrow stromal cells

Basal topographic controls on rapid retreat of Humboldt Glacier, northern Greenland

Discharge from marine-terminating outlet glaciers accounts for up to half the recent mass loss from the Greenland ice sheet, yet the causal factors are not fully understood. Here we assess the factors controlling the behaviour of Humboldt Glacier (HG), allowing us to evaluate the influence of basal topography on outlet glacier response to external forcing since part of HG’s terminus occupies a large overdeepening. HG’s retreat accelerated dramatically after 1999, coinciding with summer atmospheric warming of up to 0.19°C a–1 and sea-ice decline. Retreat was an order of magnitude greater in the northern section of the terminus, underlain by a major basal trough, than in the southern section, where the bedrock is comparatively shallow. Velocity change following retreat was spatially non-uniform, potentially due to a pinning point near HG’s northern lateral margin. Consistent with observations, numerical modelling demonstrates an order-of-magnitude greater sensitivity to sea-ice buttressing and crevasse depth (used as a proxy for atmospheric warming) in the northern section. The trough extends up to 72 km inland, so it is likely to facilitate sustained retreat and ice loss from HG during the 21st century

Effects of deformation in the three-body structure of 11Li

11Li is studied within a three-body model 9Li+n+n where the core is allowed to be deformed and/or excite. In particular, we include reorientation couplings and couplings between the two bound states of 9Li. Contrary to the other examples studied within this model, we find that core excitation does not affect the structure of 11Li significantly. Reorientation couplings of the deformed 9Li can change the ground state of 11Li from a predominantly two neutron s1/2^2 configuration into a p1/2^2. In addition, we see no evidence for the existence of significant d-wave strength in its ground state, as opposed to the prediction by shell model. A comparison with shell model is presented.Comment: 13 pages, 9 figure

Retinal toxicity of intravitreal triamcinolone acetonide: a morphological study

Purpose: To evaluate the morphologic effects of intravitreal triamcinolone acetonide (TA) on rabbit retina. Methods: Intravitreal injections of 0.5 mg, 1 mg, 4 mg, 8 mg, and 20 mg of TA (Kenalog-40; Bristol-Myers Squibb, Princeton, NJ) in 0.1 mL were given to pigmented rabbits. For control, 0.1 mL of TA vehicle and saline were injected. Animals were killed on day 14, and retinas were analyzed by light as well as electron microscopy. Results: No ophthalmoscopic change was found. Eyes injected with 0.5 mg and 1 mg of TA did not have morphologic abnormality. Eyes injected with 4 mg, 8 mg, and 20 mg showed destruction of photoreceptor outer segments and migration of macrophage-like cells in the subretinal space. Eyes injected with 20 mg showed more extensive damage and increased pigment granules in the retinal pigment epithelium cells with large oil droplets in the cytoplasm. Electron microscopy also showed loss of photoreceptor/retinal pigment epithelium interdigitations. Eyes injected with vehicle or saline did not show morphologic changes. Conclusion: Single intravitreal injection of 0.5 mg or 1 mg of TA did not produce morphologic retinal changes in pigmented rabbits. However, injections of 4 mg, 8 mg, and 20 mg of TA produced outer retina toxic effects. These findings suggest that long-term retinal toxicity studies should be carried out, using single and repeated injections before this therapy becomes more widely used

On the recurrence and robust properties of Lorenz'63 model

Lie-Poisson structure of the Lorenz'63 system gives a physical insight on its dynamical and statistical behavior considering the evolution of the associated Casimir functions. We study the invariant density and other recurrence features of a Markov expanding Lorenz-like map of the interval arising in the analysis of the predictability of the extreme values reached by particular physical observables evolving in time under the Lorenz'63 dynamics with the classical set of parameters. Moreover, we prove the statistical stability of such an invariant measure. This will allow us to further characterize the SRB measure of the system.Comment: 44 pages, 7 figures, revised version accepted for pubblicatio

Numerical convergence of the block-maxima approach to the Generalized Extreme Value distribution

In this paper we perform an analytical and numerical study of Extreme Value distributions in discrete dynamical systems. In this setting, recent works have shown how to get a statistics of extremes in agreement with the classical Extreme Value Theory. We pursue these investigations by giving analytical expressions of Extreme Value distribution parameters for maps that have an absolutely continuous invariant measure. We compare these analytical results with numerical experiments in which we study the convergence to limiting distributions using the so called block-maxima approach, pointing out in which cases we obtain robust estimation of parameters. In regular maps for which mixing properties do not hold, we show that the fitting procedure to the classical Extreme Value Distribution fails, as expected. However, we obtain an empirical distribution that can be explained starting from a different observable function for which Nicolis et al. [2006] have found analytical results.Comment: 34 pages, 7 figures; Journal of Statistical Physics 201

Inter- and intra-observer reliability of contrast-enhanced magnetic resonance imaging parameters in children with suspected juvenile idiopathic arthritis of the hip

BACKGROUND: Previous work at our institution demonstrated discrepancies between radiologists in interpretation of contrast-enhanced magnetic resonance imaging (MRI) in suspected hip arthritis. OBJECTIVE: To assess inter- and intra-observer reliability of selected MRI parameters (effusion, marrow oedema and synovial thickness and enhancement) used in the diagnosis of juvenile idiopathic arthritis. MATERIALS AND METHODS: A retrospective cohort study was conducted of patients with confirmed or suspected juvenile idiopathic arthritis who underwent hip contrast-enhanced MRI between January 2011 and September 2014. Three pediatric musculoskeletal radiologists independently assessed all scans for effusion, marrow oedema, measurement of synovial thickness, synovial enhancement and subjective assessment of synovium. Categorical variables were analysed using the Cohen κ, and measurement using Bland-Altman plots. RESULTS: Eighty patients were included. Interobserver reliability was moderate for effusion (κ=0.5-0.7), marrow oedema (κ=0.6), subjective synovial assessment (κ=0.4-0.5) and synovial enhancement (κ=0.1-0.5). Intra-observer reliability was highest for marrow oedema (κ=0.6-0.8) and lowest for effusion (κ=0.4-0.7). Intra-observer reliability for synovial enhancement (κ= -0.7-0.8) and subjective synovial assessment (κ=0.4-1.0) ranged from poor to excellent. For synovial thickness, intra- and interobserver Bland-Altman plots were well clustered around the mean suggesting good agreement. CONCLUSION: There were large differences across variables and only moderate agreement between observers. The most reliable parameters were presence of joint effusion and bone marrow oedema and subjective assessment of synovium

Plasmonic excitations in noble metals: The case of Ag

The delicate interplay between plasmonic excitations and interband transitions in noble metals is described by means of {\it ab initio} calculations and a simple model in which the conduction electron plasmon is coupled to the continuum of electron-hole pairs. Band structure effects, specially the energy at which the excitation of the $d$-like bands takes place, determine the existence of a subthreshold plasmonic mode, which manifests itself in Ag as a sharp resonance at 3.8 eV. However, such a resonance is not observed in the other noble metals. Here, this different behavior is also analyzed and an explanation is provided.Comment: 9 pages, 8 figure