Cardiolipin externalization mediates prion protein (PrP) peptide 106–126-associated mitophagy and mitochondrial dysfunction

Proper mitochondrial performance is imperative for the maintenance of normal neuronal function to prevent the development of neurodegenerative diseases. Persistent accumulation of damaged mitochondria plays a role in prion disease pathogenesis, which involves a chain of events that culminate in the generation of reactive oxygen species and neuronal death. Our previous studies have demonstrated that PINK1/Parkin-mediated mitophagy induced by PrP106−126 is defective and leads to an accumulation of damaged mitochondria after PrP106−126 treatment. Externalized cardiolipin (CL), a mitochondria-specific phospholipid, has been reported to play a role in mitophagy by directly interacting with LC3II at the outer mitochondrial membrane. The involvement of CL externalization in PrP106−126-induced mitophagy and its significance in other physiological processes of N2a cells treated with PrP106−126 remain unknown. We demonstrate that the PrP106−126 peptide caused a temporal course of mitophagy in N2a cells, which gradually increased and subsequently decreased. A similar trend in CL externalization to the mitochondrial surface was seen, resulting in a gradual decrease in CL content at the cellular level. Inhibition of CL externalization by knockdown of CL synthase, responsible for de novo synthesis of CL, or phospholipid scramblase-3 and NDPK-D, responsible for CL translocation to the mitochondrial surface, significantly decreased PrP106−126-induced mitophagy in N2a cells. Meanwhile, the inhibition of CL redistribution significantly decreased PINK1 and DRP1 recruitment in PrP106−126 treatment but had no significant decrease in Parkin recruitment. Furthermore, the inhibition of CL externalization resulted in impaired oxidative phosphorylation and severe oxidative stress, which led to mitochondrial dysfunction. Our results indicate that CL externalization induced by PrP106−126 on N2a cells plays a positive role in the initiation of mitophagy, leading to the stabilization of mitochondrial function

Amniocytes can serve a dual function as a source of iPS cells and feeder layers

Clinical barriers to stem-cell therapy include the need for efficient derivation of histocompatible stem cells and the zoonotic risk inherent to human stem-cell xenoculture on mouse feeder cells. We describe a system for efficiently deriving induced pluripotent stem (iPS) cells from human and mouse amniocytes, and for maintaining the pluripotency of these iPS cells on mitotically inactivated feeder layers prepared from the same amniocytes. Both cellular components of this system are thus autologous to a single donor. Moreover, the use of human feeder cells reduces the risk of zoonosis. Generation of iPS cells using retroviral vectors from short- or long-term cultured human and mouse amniocytes using four factors, or two factors in mouse, occurs in 5–7 days with 0.5% efficiency. This efficiency is greater than that reported for mouse and human fibroblasts using similar viral infection approaches, and does not appear to result from selective reprogramming of Oct4+ or c-Kit+ amniocyte subpopulations. Derivation of amniocyte-derived iPS (AdiPS) cell colonies, which express pluripotency markers and exhibit appropriate microarray expression and DNA methylation properties, was facilitated by live immunostaining. AdiPS cells also generate embryoid bodies in vitro and teratomas in vivo. Furthermore, mouse and human amniocytes can serve as feeder layers for iPS cells and for mouse and human embryonic stem (ES) cells. Thus, human amniocytes provide an efficient source of autologous iPS cells and, as feeder cells, can also maintain iPS and ES cell pluripotency without the safety concerns associated with xenoculture

Spatial distribution estimation of malaria in northern China and its scenarios in 2020, 2030, 2040 and 2050

© 2016 The Author(s). Background: Malaria is one of the most severe parasitic diseases in the world. Spatial distribution estimation of malaria and its future scenarios are important issues for malaria control and elimination. Furthermore, sophisticated nonlinear relationships for prediction between malaria incidence and potential variables have not been well constructed in previous research. This study aims to estimate these nonlinear relationships and predict future malaria scenarios in northern China. Methods: Nonlinear relationships between malaria incidence and predictor variables were constructed using a genetic programming (GP) method, to predict the spatial distributions of malaria under climate change scenarios. For this, the examples of monthly average malaria incidence were used in each county of northern China from 2004 to 2010. Among the five variables at county level, precipitation rate and temperature are used for projections, while elevation, water density index, and gross domestic product are held at their present-day values. Results: Average malaria incidence was 0.107 per annum in northern China, with incidence characteristics in significant spatial clustering. A GP-based model fit the relationships with average relative error (ARE) = 8.127 % for training data (R2 = 0.825) and 17.102 % for test data (R2 = 0.532). The fitness of GP results are significantly improved compared with those by generalized additive models (GAM) and linear regressions. With the future precipitation rate and temperature conditions in Special Report on Emission Scenarios (SRES) family B1, A1B and A2 scenarios, spatial distributions and changes in malaria incidences in 2020, 2030, 2040 and 2050 were predicted and mapped. Conclusions: The GP method increases the precision of predicting the spatial distribution of malaria incidence. With the assumption of varied precipitation rate and temperature, and other variables controlled, the relationships between incidence and the varied variables appear sophisticated nonlinearity and spatially differentiation. Using the future fluctuated precipitation and the increased temperature, median malaria incidence in 2020, 2030, 2040 and 2050 would significantly increase that it might increase 19 to 29 % in 2020, but currently China is in the malaria elimination phase, indicating that the effective strategies and actions had been taken. While the mean incidences will not increase even reduce due to the incidence reduction in high-risk regions but the simultaneous expansion of the high-risk areas

Design, construction and modeling of a small-scale high temperature field rotor test rig

In-field validation of radiation thermometer performance is time consuming and expensive, especially when prototype experiments are performed. This study focuses on the development of a novel small-scale high temperature field simulation test rig for measuring turbine blade surface temperatures under changing environmental conditions. When developing and testing a radiation thermometer, the testing is typically performed directly on a test rig that can simultaneously provide a standardized environment and compare temperature data. This apparatus allows for static and dynamic temperature testing in a hostile environment by combining temperature, particle, and atmospheric effects. In the present study, a test rig will be utilized to analyze and validate the radiation thermometer, which will be subjected to harsh combined environmental variables with a temperature range of up to 2000K. Notably, the rotating head structure of the two materials allows for the application of a vast range of temperature measurements (700–2000 K), which is a distinctive characteristic of the design. The requirements of the test rig are defined based on the specimens to be tested. The necessity for the combined complete test setup, as well as its design and functionality, are discussed in this paper. Finally, validation experiments are conducted to demonstrate the test rig's accuracy in measuring turbine blade surface temperature, which is 0.25%

The Effect of Lycii Radicis Cortex Extract on Bone Formation in Vitro and in Vivo

Osteoporosis is a common skeletal disease caused by decreased bone mass; it enhances the risk of bone fracture. This study aimed to discover novel herbal extract(s) for the treatment of osteoporosis. We screened 64 ethanol extracts of edible plants native to Korea for their ability to increase the cellular proliferation and differentiation of two osteoblastic cell lines: C3H10T1/2 and MC3T3-E1. We selected a Lycii Radicis Cortex (LRC), Lycium Chinese root bark as the primary candidate. Treatment with LRC extract showed enhanced alkaline phosphatase activity and increased expression of bone metabolic markers Alpl, Runx2, and Bglap genes in both osteoblastic cell lines. There was no effect on the osteoclastic differentiation of primary-cultured monocytes from the mouse bone marrows. Furthermore, the study examined the effect of LRC extract in vivo in ovariectomizd (OVX) mice for 8 weeks and 16 weeks, respectively. Bone mineral density (BMD) was significantly higher in LRC extract-administered group than in the non-LRC-administered OVX control group. The results indicated that LRC extract prevented the OVX-induced BMD loss in mice via promoting the differentiation of osteoblast linage cells. These results suggest that LRC extract may be a good natural herbal medicine candidate for the treatment of osteoporosis