Microfluidic single-cell analysis of oxidative stress in Dictyostelium discoideum [post-print]

Microfluidic chemical cytometry is a powerful technique for examining chemical contents of individual cells, but applications have focused on cells from multicellular organisms, especially mammals. We demonstrate the first use of microfluidic chemical cytometry to examine a unicellular organism, the social amoeba Dictyostelium discoideum. We used the reactive oxygen species indicator dichlorodihydrofluorescein diacetate to report on oxidative stress and controlled for variations in indicator loading and retention using carboxyfluorescein diacetate as an internal standard. After optimizing indicator concentration, we investigated the effect of peroxide treatment through single-cell measurements of 353 individual cells. The peak area ratio of dichlorofluorescein to carboxyfluorescein increased from 1.69 ± 0.89 for untreated cells to 5.19 ± 2.72 for cells treated with 40 mM hydrogen peroxide. Interestingly, the variance of the data also increased with oxidative stress. While preliminary, these results are consistent with the hypothesis that heterogeneous stress responses in unicellular organisms may be adaptive

Role of Protein Kinase C in Podocytes and Development of Glomerular Damage in Diabetic Nephropathy

The early glomerular changes in diabetes include a podocyte phenotype with loss of slit diaphragm proteins, changes in the actin cytoskeleton and foot process architecture. This review focusses on the role of the Protein Kinase C family in podocytes and points out the differential roles of classical, novel and atypical PKCs in podocytes. Some PKC-isoforms are indispensable for proper glomerular development and slit diaphragm maintenance whereas others might be harmful when activated in the diabetic milieu. Therefore some might be interesting treatment targets in the early phase of diabetes

MRI of Perfusion-Diffusion Mismatch in Non-Human Primate (Baboon) Stroke: A Preliminary Report

The goal of this study was to develop a clinically relevant non-human primate (baboon) stroke model and multi-parametric MRI protocols on a clinical scanner with long-term goals to better model human stroke and facilitate clinical translations of novel therapeutic strategies. Baboons were chosen because of their relatively large brain volume and that they are evolutionarily close to humans. Middle cerebral artery occlusion (MCAO) was induced using a minimally invasive endovascular approach to guide an inflatable balloon catheter into the MCA and followed by permanently or transiently inflate the balloon. Using multimodal MRI, including perfusion and diffusion imaging, the spatiotemporal dynamic evolution of the ischemic lesions in permanent and transient occlusion experiments in baboons were investigated. Perfusion-diffusion mismatch, which approximates the ischemic penumbra, was detected. In the permanent MCAO group (n = 2), the mean infarct volume was 29 ml (17% of total brain volume) whereas in the transient MCAO group (n = 2, 60 or 90 min of occlusion), the mean infarct volume was 15 ml (9% of total brain volume). Substantial perfusion-diffusion mismatch tissue (~50%) was salvaged by reperfusion compared to permanent MCAO. This baboon stroke model has the potential to become a translational platform to better design clinical studies, guide clinical diagnosis and improve treatment time windows in patients

Augmented Reality Markerless Multi-Image Outdoor Tracking System for the Historical Buildings on Parliament Hill

[EN] Augmented Reality (AR) applications have experienced extraordinary growth recently, evolving into a well-established method for the dissemination and communication of content related to cultural heritage¿including education. AR applications have been used in museums and gallery exhibitions and virtual reconstructions of historic interiors. However, the circumstances of an outdoor environment can be problematic. This paper presents a methodology to develop immersive AR applications based on the recognition of outdoor buildings. To demonstrate this methodology, a case study focused on the Parliament Buildings National Historic Site in Ottawa, Canada has been conducted. The site is currently undergoing a multiyear rehabilitation program that will make access to parts of this national monument inaccessible to the public. AR experiences, including simulated photo merging of historic and present content, are proposed as one tool that can enrich the Parliament Hill visit during the rehabilitation. Outdoor AR experiences are limited by factors, such as variable lighting (and shadows) conditions, caused by changes in the environment (objects height and orientation, obstructions, occlusions), the weather, and the time of day. This paper proposes a workflow to solve some of these issues from a multi-image tracking approach.This work has been developed under the framework of the New Paradigms/New Tools for Heritage Conservation in Canada, a project funded through the Social Sciences and Humanities Research Council of Canada (SSHRC).Blanco-Pons, S.; Carrión-Ruiz, B.; Duong, M.; Chartrand, J.; Fai, S.; Lerma, JL. (2019). Augmented Reality Markerless Multi-Image Outdoor Tracking System for the Historical Buildings on Parliament Hill. Sustainability. 11(16):1-15. https://doi.org/10.3390/su11164268S1151116Bekele, M. K., Pierdicca, R., Frontoni, E., Malinverni, E. S., & Gain, J. (2018). A Survey of Augmented, Virtual, and Mixed Reality for Cultural Heritage. Journal on Computing and Cultural Heritage, 11(2), 1-36. doi:10.1145/3145534Gimeno, J., Portalés, C., Coma, I., Fernández, M., & Martínez, B. (2017). Combining traditional and indirect augmented reality for indoor crowded environments. A case study on the Casa Batlló museum. Computers & Graphics, 69, 92-103. doi:10.1016/j.cag.2017.09.001Kolivand, H., El Rhalibi, A., Shahrizal Sunar, M., & Saba, T. (2018). ReVitAge: Realistic virtual heritage taking shadows and sky illumination into account. Journal of Cultural Heritage, 32, 166-175. doi:10.1016/j.culher.2018.01.020Amakawa, J., & Westin, J. (2017). New Philadelphia: using augmented reality to interpret slavery and reconstruction era historical sites. International Journal of Heritage Studies, 24(3), 315-331. doi:10.1080/13527258.2017.1378909Kim, J.-B., & Park, C. (2011). Development of Mobile AR Tour Application for the National Palace Museum of Korea. Lecture Notes in Computer Science, 55-60. doi:10.1007/978-3-642-22021-0_7Barrile, V., Fotia, A., Bilotta, G., & De Carlo, D. (2019). Integration of geomatics methodologies and creation of a cultural heritage app using augmented reality. Virtual Archaeology Review, 10(20), 40. doi:10.4995/var.2019.10361Analysis of Tracking Accuracy for Single-Camera Square-Marker-Based Tracking. In Third Workshop on Virtual and Augmented Reality of the GI-Fachgruppe VR/AR, Koblenz, Germany, 2006http://campar.in.tum.de/Chair/PublicationDetail?pub=pentenrieder2006giCirulis, A., & Brigmanis, K. B. (2013). 3D Outdoor Augmented Reality for Architecture and Urban Planning. Procedia Computer Science, 25, 71-79. doi:10.1016/j.procs.2013.11.009You, S., Neumann, U., & Azuma, R. (1999). Orientation tracking for outdoor augmented reality registration. IEEE Computer Graphics and Applications, 19(6), 36-42. doi:10.1109/38.799738Wither, J., Tsai, Y.-T., & Azuma, R. (2011). Indirect augmented reality. Computers & Graphics, 35(4), 810-822. doi:10.1016/j.cag.2011.04.010Radkowski, R., & Oliver, J. (2013). Natural Feature Tracking Augmented Reality for On-Site Assembly Assistance Systems. Lecture Notes in Computer Science, 281-290. doi:10.1007/978-3-642-39420-1_30Rao, J., Qiao, Y., Ren, F., Wang, J., & Du, Q. (2017). A Mobile Outdoor Augmented Reality Method Combining Deep Learning Object Detection and Spatial Relationships for Geovisualization. Sensors, 17(9), 1951. doi:10.3390/s17091951Hoppe, H., DeRose, T., Duchamp, T., McDonald, J., & Stuetzle, W. (1993). Mesh optimization. Proceedings of the 20th annual conference on Computer graphics and interactive techniques - SIGGRAPH ’93. doi:10.1145/166117.166119Rossignac, J., & Borrel, P. (1993). Multi-resolution 3D approximations for rendering complex scenes. Modeling in Computer Graphics, 455-465. doi:10.1007/978-3-642-78114-8_29Gross, M. H., Staadt, O. G., & Gatti, R. (1996). Efficient triangular surface approximations using wavelets and quadtree data structures. IEEE Transactions on Visualization and Computer Graphics, 2(2), 130-143. doi:10.1109/2945.506225Botsch, M., Pauly, M., Rossl, C., Bischoff, S., & Kobbelt, L. (2006). Geometric modeling based on triangle meshes. ACM SIGGRAPH 2006 Courses on - SIGGRAPH ’06. doi:10.1145/1185657.1185839Pietroni, N., Tarini, M., & Cignoni, P. (2010). Almost Isometric Mesh Parameterization through Abstract Domains. IEEE Transactions on Visualization and Computer Graphics, 16(4), 621-635. doi:10.1109/tvcg.2009.96Khan, D., Yan, D.-M., Ding, F., Zhuang, Y., & Zhang, X. (2018). Surface remeshing with robust user-guided segmentation. Computational Visual Media, 4(2), 113-122. doi:10.1007/s41095-018-0107-yGuidi, G., Russo, M., Ercoli, S., Remondino, F., Rizzi, A., & Menna, F. (2009). A Multi-Resolution Methodology for the 3D Modeling of Large and Complex Archeological Areas. International Journal of Architectural Computing, 7(1), 39-55. doi:10.1260/147807709788549439Remondino, F., & El-Hakim, S. (2006). Image-based 3D Modelling: A Review. The Photogrammetric Record, 21(115), 269-291. doi:10.1111/j.1477-9730.2006.00383.xBruno, F., Bruno, S., De Sensi, G., Luchi, M.-L., Mancuso, S., & Muzzupappa, M. (2010). From 3D reconstruction to virtual reality: A complete methodology for digital archaeological exhibition. Journal of Cultural Heritage, 11(1), 42-49. doi:10.1016/j.culher.2009.02.006Unity, The Photogrammetry Workflowhttps://unity.com/solutions/photogrammetry.Blanco, S., Carrión, B., & Lerma, J. L. (2016). REVIEW OF AUGMENTED REALITY AND VIRTUAL REALITY TECHNIQUES IN ROCK ART. Proceedings of the ARQUEOLÓGICA 2.0 8th International Congress on Archaeology, Computer Graphics, Cultural Heritage and Innovation. doi:10.4995/arqueologica8.2016.3561Behzadan, A. H., & Kamat, V. R. (2010). Scalable Algorithm for Resolving Incorrect Occlusion in Dynamic Augmented Reality Engineering Environments. Computer-Aided Civil and Infrastructure Engineering, 25(1), 3-19. doi:10.1111/j.1467-8667.2009.00601.xTian, Y., Long, Y., Xia, D., Yao, H., & Zhang, J. (2015). Handling occlusions in augmented reality based on 3D reconstruction method. Neurocomputing, 156, 96-104. doi:10.1016/j.neucom.2014.12.081Tian, Y., Guan, T., & Wang, C. (2010). Real-Time Occlusion Handling in Augmented Reality Based on an Object Tracking Approach. Sensors, 10(4), 2885-2900. doi:10.3390/s10040288

Mice Lacking Gpr37 Exhibit Decreased Expression of the Myelin-Associated Glycoprotein Mag and Increased Susceptibility to Demyelination

GPR37 is an orphan G protein-coupled receptor that is predominantly expressed in the brain and found at particularly high levels in oligodendrocytes. GPR37 has been shown to exert effects on oligodendrocyte differentiation and myelination during development, but the molecular basis of these actions is incompletely understood and moreover nothing is known about the potential role(s) of this receptor under demyelinating conditions. To shed light on the fundamental biology of GPR37, we performed proteomic studies comparing protein expression levels in the brains of mice lacking GPR37 and its close relative GPR37-like 1 (GPR37L1). These studies revealed that one of the proteins most sharply decreased in the brains of Gpr37/Gpr37L1 double knockout mice is the myelin-associated glycoprotein MAG. Follow-up Western blot studies confirmed this finding and demonstrated that genetic deletion of Gpr37, but not Gpr37L1, results in strikingly decreased brain expression of MAG. Further in vitro studies demonstrated that GPR37 and MAG form a complex when expressed together in cells. As loss of MAG has previously been shown to result in increased susceptibility to brain insults, we additionally assessed Gpr37-knockout (Gpr37−/−) vs. wild-type mice in the cuprizone model of demyelination. These studies revealed that Gpr37−/− mice exhibit dramatically increased loss of myelin in response to cuprizone, yet do not show any increased loss of oligodendrocyte precursor cells or mature oligodendrocytes. These findings reveal that loss of GPR37 alters oligodendrocyte physiology and increases susceptibility to demyelination, indicating that GPR37 could be a potential drug target for the treatment of demyelinating diseases such as multiple sclerosis

Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P \u3c 1 × 10−3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases

Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury.

Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans

The impact of cataract surgey on vision-related quality of life for bilateral cataract patients in Ho Chi Minh City, Vietnam: a prospective study

BACKGROUND: To determine the impact of cataract surgery on vision-related quality of life (VRQOL) and examine the association between objective visual measures and change in VRQOL after surgery among bilateral cataract patients in Ho Chi Minh City, Vietnam. METHODS: A cohort of older patients with bilateral cataract was assessed one week before and one to three months after first eye or both eye cataract surgery. Visual measures including visual acuity, contrast sensitivity and stereopsis were obtained. Vision-related quality of life was assessed using the NEI VFQ-25. Descriptive analyses and a generalized linear estimating equation (GEE) analysis were undertaken to measure change in VRQOL after surgery. RESULTS: Four hundred and thirteen patients were assessed before cataract surgery and 247 completed the follow-up assessment one to three months after first or both eye cataract surgery. Overall, VRQOL significantly improved after cataract surgery (p < 0.001) particularly after both eye surgeries. Binocular contrast sensitivity (p < 0.001) and stereopsis (p < 0.001) were also associated with change in VRQOL after cataract surgery. Visual acuity was not associated with VRQOL. CONCLUSIONS: Cataract surgery significantly improved VRQOL among bilateral cataract patients in Vietnam. Contrast sensitivity as well as stereopsis, rather than visual acuity significantly affected VRQOL after cataract surgery