Cholesterol crystallization in human atherosclerosis is triggered in smooth muscle cells during the transition from fatty streak to fibroatheroma.

Recent studies have shown that in addition to being major constituents of the atheromatous core, solid cholesterol crystals (CCs) promote atherosclerotic lesion development and rupture by causing mechanical damage and exerting cytotoxic and pro-inflammatory effects. These findings suggest that targeting CCs might represent a therapeutic strategy for plaque stabilization. However, little is known about how cholesterol crystallization is initiated in human atherothrombotic disease. Here, we investigated these mechanisms. We performed a thorough immunohistological analysis of non-embedded, minimally processed human aortic tissues, combining polarized light and fluorescence microscopy. We found that CC formation was initiated during the fatty streak to fibroatheroma transition in tight association with the death of intralesional smooth muscle cells (SMCs). Cholesterol-loaded human SMCs were capable of producing CCs in vitro, a process that was enhanced by type I collagen and by inhibition of autophagy and cholesterol esterification. The fibrous transition, which was characterized by increased type I collagen expression, was associated with changes in the expression of autophagy and cholesterol flux-related genes, including a decrease in the autophagic adapter p62 and an increase in the cholesterol intracellular transporter Niemann-Pick C1. Collagen was identified as a potent inducer of these changes in SMCs. Collagen-induced changes in cholesterol metabolism and autophagy flux in smooth muscle foam cells at the fibrolipid transition likely contribute to initiate cholesterol crystallization in human atherosclerosis. Also, our data are in support of a protective role of autophagy against CC formation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Computational optical distortion correction using a radial basis function-based mapping method.

A distortion mapping and computational image unwarping method based on a network interpolation that uses radial basis functions is presented. The method is applied to correct distortion in an off-axis head-worn display (HWD) presenting up to 23% highly asymmetric distortion over a 27°x21° field of view. A 10(-5) mm absolute error of the mapping function over the field of view was achieved. The unwarping efficacy was assessed using the image-rendering feature of optical design software. Correlation coefficients between unwarped images seen through the HWD and the original images, as well as edge superimposition results, are presented. In an experiment, images are prewarped using radial basis functions for a recently built, off-axis HWD with a 20° diagonal field of view in a 4:3 ratio. Real-time video is generated by a custom application with 2 ms added latency and is demonstrated.

Syndecan-1 Is Overexpressed in Human Thoracic Aneurysm but Is Dispensable for the Disease Progression in a Mouse Model.

Glycosaminoglycans (GAGs) pooling has long been considered as one of the histopathological characteristics defining thoracic aortic aneurysm (TAA) together with smooth muscle cells (SMCs) apoptosis and elastin fibers degradation. However, little information is known about GAGs composition or their potential implication in TAA pathology. Syndecan-1 (SDC-1) is a heparan sulfate proteoglycan that is implicated in extracellular matrix (ECM) interaction and assembly, regulation of SMCs phenotype, and various aspects of inflammation in the vascular wall. Therefore, the aim of this study was to determine whether SDC-1 expression was regulated in human TAA and to analyze its role in a mouse model of this disease. In the current work, the regulation of SDC-1 was examined in human biopsies by RT-qPCR, ELISA, and immunohistochemistry. In addition, the role of SDC-1 was evaluated in descending TAA in vivo using a mouse model combining both aortic wall weakening and hypertension. Our results showed that both SDC-1 mRNA and protein are overexpressed in the media layer of human TAA specimens. RT-qPCR experiments revealed a 3.6-fold overexpression of SDC-1 mRNA (p = 0.0024) and ELISA assays showed that SDC-1 protein was increased 2.3 times in TAA samples compared with healthy counterparts (221 ± 24 vs. 96 ± 33 pg/mg of tissue, respectively, p = 0.0012). Immunofluorescence imaging provided evidence that SMCs are the major cell type expressing SDC-1 in TAA media. Similarly, in the mouse model used, SDC-1 expression was increased in TAA specimens compared to healthy samples. Although its protective role against abdominal aneurysm has been reported, we observed that SDC-1 was dispensable for TAA prevalence or rupture. In addition, SDC-1 deficiency did not alter the extent of aortic wall dilatation, elastin degradation, collagen deposition, or leukocyte recruitment in our TAA model. These findings suggest that SDC-1 could be a biomarker revealing TAA pathology. Future investigations could uncover the underlying mechanisms leading to regulation of SDC-1 expression in TAA.

Airy beams: a geometric optics perspective.

Theoretically formulated in the 1970s within the context of nonrelativistic quantum mechanics, Airy beams have been experimentally realized for the first time only recently, paving the way to innovative optical techniques. While their remarkable features, a non-diffracting property and a transverse shift of the intensity maximum during propagation, are currently theoretically described from the wave optics viewpoint, here their exact relation to rays and geometric wavefront aberrations is revealed using a wavefront family that includes two-dimensional Airy beams. Several members of this family are computationally and experimentally implemented here. The lateral shift of Airy beams during propagation is presented in the context of the three-dimensional caustic representation. This new description allows re-emphasizing the use of "Airy-like" beams in computational imaging for depth of focus extension.

Reversing binding sensitivity to A147T translocator protein.

The translocator protein (TSPO) is a target for the development of neuroinflammation imaging agents. Clinical translation of TSPO PET ligands, such as [11C]DPA-713, has been hampered by the presence of a common polymorphism (A147T TSPO), at which all second-generation TSPO ligands lose affinity. Little is known about what drives binding at A147T compared to WT TSPO. This study aimed to identify moieties in DPA-713, and related derivatives, that influence binding at A147T compared to WT TSPO. We found changes to the nitrogen position and number in the heterocyclic core influences affinity to WT and A147T to a similar degree. Hydrogen bonding groups in molecules with an indole core improve binding at A147T compared to WT, a strategy that generated compounds that possess up to ten-times greater affinity for A147T. These results should inform the future design of compounds that bind both A147T and WT TSPO for use in neuroinflammation imaging.

Application of radial basis functions to shape description in a dual-element off-axis magnifier.

We previously demonstrated that radial basis functions may be preferred as a descriptor of free-form shape for a single mirror magnifier when compared to other conventional descriptions such as polynomials [Opt. Express 16, 1583 (2008)]. A key contribution is the application of radial basis functions to describe and optimize the shape of a free-form mirror in a dual-element magnifier with the specific goal of optimizing the pupil size given a 20 degrees field of view. We demonstrate a 12 mm exit pupil, 20 degrees diagonal full field of view, 15.5 mm eye clearance, 1.5 arc min resolution catadioptric dual-element magnifier design operating across the photopic visual regime. A second contribution is the explanation of why it is possible to approximate any optical mirror shape using radial basis functions.