HTRA1 variant increases risk to neovascular age-related macular degeneration in Chinese population

AbstractAge-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the world. Advanced AMD can be divided into wet AMD (choroidal neovascularization) and dry AMD (geographic atrophy, GA). Drusen is characterized by deposits in the macula without visual loss and is an early AMD sign in the Caucasian population. rs11200638 in the promoter of HTRA1 has recently been shown to increases the risk for wet AMD in both Caucasian and Hong Kong Chinese populations. In order to replicate these results in a different cohort, we genotyped rs11200638 for 164 Chinese patients (90 wet AMD and 74 drusen) and 106 normal controls in a Han Mainland Chinese cohort. The genotypes were compared using chi square analysis for an additive allelic model. rs11200638 was significantly associated with wet AMD (p=5.00×10−12). Unlike in the Caucasian population, the risk allele of rs11200638 was not associated with drusen in our Chinese population. These findings confirm the association of HTRA1 with wet AMD

Dual regulatory switch through interactions of Tcf7l2/Tcf4 with stage-specific partners propels oligodendroglial maturation

Constitutive activation of Wnt/β-catenin inhibits oligodendrocyte myelination. Tcf7l2/Tcf4, a β-catenin transcriptional partner, is required for oligodendrocyte differentiation. How Tcf7l2 modifies β-catenin signalling and controls myelination remains elusive. Here we define a stage-specific Tcf7l2-regulated transcriptional circuitry in initiating and sustaining oligodendrocyte differentiation. Multistage genome occupancy analyses reveal that Tcf7l2 serially cooperates with distinct co-regulators to control oligodendrocyte lineage progression. At the differentiation onset, Tcf7l2 interacts with a transcriptional co-repressor Kaiso/Zbtb33 to block β-catenin signalling. During oligodendrocyte maturation, Tcf7l2 recruits and cooperates with Sox10 to promote myelination. In that context, Tcf7l2 directly activates cholesterol biosynthesis genes and cholesterol supplementation partially rescues oligodendrocyte differentiation defects in Tcf712 mutants. Together, we identify stage-specific co-regulators Kaiso and Sox10 that sequentially interact with Tcf7l2 to coordinate the switch at the transitions of differentiation initiation and maturation during oligodendrocyte development, and point to a previously unrecognized role of Tcf7l2 in control of cholesterol biosynthesis for CNS myelinogenesis

Performance of Prestressed Anchor Cables Supporting Deep Foundation Pit of a Subway Station during Spring Thaw

Based on the deep foundation pit for a subway station in Changchun (China), a 3D numerical model of water–heat coupling in a prestressed pile anchor system was established to determine its performance in freezing and thawing seasons in alpine areas. Its reliability was confirmed using field monitoring data on the prestressed anchor cables, which demonstrated changes in surface subsidence, anchor cable axial force, and pile horizontal displacement during spring thaw. The results demonstrated different degrees of elevation of the ground surface at the beginning of the spring thaw depending on whether the ground surface was at 2, 5, or 8 m from the pit excavation surface. Moreover, they demonstrated the occurrence of melting and surface subsidence when the temperature rises above 0°C, and that the axial force of the anchor cables fluctuates at the beginning of spring thaw but stabilizes in its middle and late stages. The phenomenon of pile horizontal displacement during the spring thaw could be roughly divided into three stages, with the second stage resulting in the most significant displacement. These results can provide certain reference for deep foundation pit projects in alpine areas

Effect of preparation cooling rate on magnetocaloric effect of Fe(80)P(13)C(7 )amorphous alloy

Effect of preparation cooling rate on magnetocaloric effect of Fe(80)P(13)C(7 )amorphous allo

UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability

Abstract Background Renal interstitial fibrosis is a common pathway for the progressive development of chronic renal diseases (CKD) with different etiology, and is the main pathological basis leading to end-stage renal disease. Although the current research on renal interstitial fibrosis is gradually deepening, the diagnosis and treatment methods are still very lacking. Uncoupling protein 1 (UCP1) is a nuclear encoded protein in mitochondria inner membrane and plays an important role in regulating energy metabolism and mitochondrial homeostasis. However, the biological significance of UCP1 and potential regulatory mechanisms in the development of CKD remain unclear. Methods Unilateral ureteral obstruction (UUO) model was used to construct the animal model of renal fibrosis, and TGF-β1 stimulation of HK2 cells was used to construct the vitro model of renal fibrosis. UCP1 expression was detected by Western blot, immunoblot analysis and immunohistochemistry. UCP1 was upregulated by UCP1 overexpressing lentivirus and UCP1 agonist CL316243. Western blot and immunofluorescence were used to detect epithelial mesenchymal transition (EMT)-related markers, such as collagen I, fibronectin, antioxidant enzyme SOD2 and CAT. Reactive oxygen species (ROS) production was detected by ROS detection kit. SIRT3 knockdown was performed by siRNA. Results This study presents that UCP1 is significantly downregulated in patients with renal fibrosis and UUO model. Further studies discover that UCP1 overexpression and CL316243 treatments (UCP1 agonists) reversed EMT and extracellular matrix (ECM) accumulation in renal fibrosis models in vivo and in vitro. Simultaneously, UCP1 reduced the ROS production by increasing the stability of SIRT3. When SIRT3 was knocked down, the production of ROS decreased. Conclusions Elevating the expression of UCP1 can inhibit the occurrence of oxidative stress by stabilizing SIRT3, thereby reducing EMT and ECM accumulation, and ultimately alleviating renal interstitial fibrosis. It will provide new instructions and targets for the treatment of CKD

Fe(Co)SiBPCCu nanocrystalline alloys with high B-s above 1.83 T

Fe84.75-xCoxSi2B9P3C0.5Cu0.75 (x = 0, 2.5 and 10) nanocrystalline alloys with excellent magnetic properties were successfully developed. The fully amorphous alloy ribbons exhibit wide temperature interval of 145-156 degrees C between the two crystallization events. It is found that the excessive substitution of Co for Fe greatly deteriorates the magnetic properties due to the non-uniform microstructure with coarse grains. The alloys with x = 0 and 2.5 exhibit high saturation magnetization (above 1.83 T), low core loss and relatively low coercivity (below 5.4A/m) after annealing. In addition, the Fe84.75Si2B9P3C0.5Cu0.75 nanocrystalline alloy also exhibits good frequency properties and temperature stability. The excellent magnetic properties were explained by the uniform microstructure with small grain size and the wide magnetic domains of the alloy. Low raw material cost, good manufacturability and excellent magnetic properties will make these nanocrystalline alloys prospective candidates for transformer and motor cores. (C) 2017 Elsevier B.V. All rights reserved