Iron-induced Complement Dysregulation in the Retinal Pigment Epithelium: Implications for Age-Related Macular Degeneration

Age-related macular degeneration (AMD), typically manifesting as a loss of central vision in elderly persons, is a leading cause of blindness in highly developed nations. AMD is a multifactorial disease associated with aging, oxidative stress, complement dysregulation, dsRNA toxicity, among many other possible factors. The formation of extracellular deposits, termed drusen, below the retinal pigment epithelial (RPE) cell layer in the outer retina is a pathognomonic hallmark of AMD. The composition of drusen is complex, but identified elements include iron, complement components, and amyloid protein derivatives. This suggests that iron may be involved in the pathophysiology of AMD. Further support for this hypothesis comes from mice lacking ferroxidases Ceruloplasmin (Cp) and Hephaestin (Heph), which have a primary genetic defect in iron homeostasis. These mice develop some AMD-like morphological features and a telling molecular feature: activated complement component 3 (C3) fragment deposition at the basolateral aspect of the RPE (the location of drusen in AMD). In our studies, we investigated the molecular mechanisms by which C3 is up-regulated by iron in RPE cells. ERK1/2, SMAD3, and CCAAT/enhancer-binding protein-δ (C/EBP-δ) are part of a non-canonical TGF-β signaling pathway that is responsible for iron-induced C3 expression. Pharmacologic inhibition of either ERK1/2 or SMAD3 phosphorylation decreased iron-induced C3 expression levels. Knockdown of SMAD3 blocked the iron-induced up-regulation and nuclear accumulation of C/EBP-δ, a transcription factor known to promote C3 expression by binding to the basic leucine zipper (bZIP1) domain of the gene promoter. We show herein that mutation of this domain reduced iron-induced C3 promoter activity. The molecular events in the iron-C3 pathway represent therapeutic targets for AMD. To better understand the relative contribution of systemic iron and local dysregulation of iron homeostasis to RPE iron accumulation, we used Bmp6 KO mice and WT mice and found that retinal hepcidin levels are not changed, but in fact may be slightly greater in KO compared to WT mice. As such, systemic iron overload by genetic KO or intravenous supplementation in WT mice resulted in increased RPE labile iron and oxidative stress, suggesting that systemic iron overload may lead to retinal iron overload despite the presence of an intact blood retinal barrier. Systemic iron status appears to be a leading determinant of retinal iron status

LAMP: a micro-satellite based soft X-ray polarimeter for astrophysics

The Lightweight Asymmetry and Magnetism Probe (LAMP) is a micro-satellite mission concept dedicated for astronomical X-ray polarimetry and is currently under early phase study. It consists of segmented paraboloidal multilayer mirrors with a collecting area of about 1300 cm^2 to reflect and focus 250 eV X-rays, which will be detected by position sensitive detectors at the focal plane. The primary targets of LAMP include the thermal emission from the surface of pulsars and synchrotron emission produced by relativistic jets in blazars. With the expected sensitivity, it will allow us to detect polarization or place a tight upper limit for about 10 pulsars and 20 blazars. In addition to measuring magnetic structures in these objects, LAMP will also enable us to discover bare quark stars if they exist, whose thermal emission is expected to be zero polarized, while the thermal emission from neutron stars is believed to be highly polarized due to plasma polarization and the quantum electrodynamics (QED) effect. Here we present an overview of the mission concept, its science objectives and simulated observational results

Operational Modal Analysis of Wind Turbine Speed-increase Gearbox

Speed increase transmission gear box is the primary vibration and noise source of wind turbine, Operational modal method was adopted to collect impact data and response data of each point based on the gearbox test model. ANSYS finite element model is established to simulate the wind turbine gearbox. Then the modal frequencies of the two methods were compared to ensure the test model is correct. The results show that operational modal method can be applied in wind turbine gearbox modal analysis and it has important guiding significance to gearbox fault diagnosis and reliability and maintainability improving. DOI: http://dx.doi.org/10.11591/telkomnika.v11i11.3518

Novel Multifunctional Materials Based on Oxide Thin Films and Artificial Heteroepitaxial Multilayers

Transition metal oxides show fascinating physical properties such as high temperature superconductivity, ferro- and antiferromagnetism, ferroelectricity or even multiferroicity. The enormous progress in oxide thin film technology allows us to integrate these materials with semiconducting, normal conducting, dielectric or non-linear optical oxides in complex oxide heterostructures, providing the basis for novel multi-functional materials and various device applications. Here, we report on the combination of ferromagnetic, semiconducting, metallic, and dielectric materials properties in thin films and artificial heterostructures using laser molecular beam epitaxy. We discuss the fabrication and characterization of oxide-based ferromagnetic tunnel junctions, transition metal-doped semiconductors, intrinsic multiferroics, and artificial ferroelectric/ferromagetic heterostructures - the latter allow for the detailed study of strain effects, forming the basis of spin-mechanics. For characterization we use X-ray diffraction, SQUID magnetometry, magnetotransport measurements, and advanced methods of transmission electron microscopy with the goal to correlate macroscopic physical properties with the microstructure of the thin films and heterostructures.Comment: 21 pages, 21 figures (2 figures added, typos corrected

Preparation and Photocatalytic Activity of Fe3+ - doped TiO2 Modified

Photocatalytic materials of TiO2 / coarse silica gel microspheres were prepared by sol-gel impregnation method and doped with transition metal ions Fe3+ to form Fe3+ modified TiO2 / coarse silica gel microspheres. The surface of the Fe modified photocatalytic materials were analyzed by XRD and surface scanning. Degradation of reactive dyes using X-3B dye wastewater water samples for validation tests. The results show that the photocatalytic activity of the photocatalytic material reaches the best when the Fe doping amount is 0.5%, and the most photocatalyst amount is 10g / L. The degradation rate of COD under this dosage was 72.32%. At the same time, according to the characterization analysis, it was found that Fe did not react with the photocatalytic material of TiO2 / coarse silica microspheres in the reaction, Fe increased the defect structure of TiO2 surface and promoted the formation of anatase, A red shift occurred and the corresponding range of the spectrum expanded toward the visible region. The results show that the doping of Fe affects the formation of TiO2 crystals, but increases the photocatalytic efficiency of TiO2

Landscape of intestinal microbiota in patients with IgA nephropathy, IgA vasculitis and Kawasaki disease

ObjectiveTo explore the common differential flora of IgAN, Kawasaki disease and IgA vasculitis by screening and analyzing the differential intestinal flora between the three disease groups of IgAN, Kawasaki disease and IgA vasculitis and their healthy controls.MethodsPapers on 16srRNA sequencing-related intestinal flora of IgAN, Kawasaki disease and IgA vasculitis were searched in databases, the literature was systematically collated and analysed, the original data was download from the relevant databases, and then the operational taxonomic unit and species classification analysis were performed. Besides, Alpha diversity analysis and Beta diversity analysis were performed to screen for IgAN, Kawasaki disease and I1gA vasculitis groups and finally compare the common intestinal differential flora among the three groups.ResultsAmong the common differential flora screened, Lachnospiracea_incertae_sedis was lower in both the IgAN and Kawasaki disease groups than in the respective healthy controls; Coprococcus was low in the IgAN group but high in the IgA vasculitis group. Fusicatenibacter was lower in both the Kawasaki disease and IgA vasculitis groups than in their respective healthy controls, and Intestinibacter was low in the Kawasaki disease group, but its expression was high in the IgA vasculitis group.ConclusionThe dysbiosis of the intestinal flora in the three groups of patients with IgAN, Kawasaki disease and IgA vasculitis, its effect on the immunity of the organism and its role in the development of each disease group remain unclear, and the presence of their common differential flora may further provide new ideas for the association of the pathogenesis of the three diseases