Essential Role of MFG-E8 for Phagocytic Properties of Microglial Cells

Milk fat globule factor-E8 (MFG-E8) has been regarded as a key factor involved in the phagocytosis of apoptotic cells. We induced a lentivirus into the microglial cells for the augmentation or abrogation of MFG-E8 expression in mouse microglial cells, and investigated phagocytosis of phosphatidylserine tagged human red blood cells (hRBCs) in co-cultures. Increased MFG-E8 levels were associated with a significant increase in phagocytic activity compared to the controls. Conversely, phagocytosis dramitically decreased due to the abrogation of MFG-E8. In addition, the expression of the inflammatory cytokines, TNF-α and IL-1β, also increased or decreased in the microglial cells with the augmentation or abrogation of MFG-E8, respectively. Our findings indicate that the enhanced expression of MFG-E8 could increase phagocytosis of apoptotic cells; conversely, the rate of phagocytosis and the expression of inflammatory cytokines decreased when MFG-E8 expression was knocked down. Our results confirm that MFG-E8 plays an important role in phagocytosis, and possibly serves as an essential signal molecule for microglial cells

Aero Engine Fault Diagnosis Using an Optimized Extreme Learning Machine

A new extreme learning machine optimized by quantum-behaved particle swarm optimization (QPSO) is developed in this paper. It uses QPSO to select optimal network parameters including the number of hidden layer neurons according to both the root mean square error on validation data set and the norm of output weights. The proposed Q-ELM was applied to real-world classification applications and a gas turbine fan engine diagnostic problem and was compared with two other optimized ELM methods and original ELM, SVM, and BP method. Results show that the proposed Q-ELM is a more reliable and suitable method than conventional neural network and other ELM methods for the defect diagnosis of the gas turbine engine

Correlation of Cytokine Levels and Microglial Cell Infiltration during Retinal Degeneration in RCS Rats

Microglial cells, which are immunocompetent cells, are involved in all diseases of the central nervous system. During their activation in various diseases, a variety of soluble factors are released. In the present study, the correlation between cytokine levels and microglial cell migration in the course of retinal degeneration of Royal College of Surgeons (RCS) rats was evaluated. MFG-E8 and CD11b were used to confirm the microglial cells. In the retina of RCS rats, the mRNA expression of seven genes (MFG-E8 and its integrins αυ and ß5, CD11b and the cytokines TNF-α, IL-1ß, and MCP-1) formed almost similar bimodal peak distributions, which were centred at P7 and P45 to P60. In contrast, in rdy rats, which comprised the control group, a unimodal peak distribution centred at P14 was observed. The gene expression accompanied the activation and migration of microglial cells from the inner to the outer layer of the retina during the process of degeneration. Principal component analysis and discriminant function analysis revealed that the expression of these seven genes, especially TNF-α and CD11b, positively correlated with retinal degeneration and microglial activity during retinal degeneration in RCS rats, but not in the control rats. Furthermore, linear regression analysis demonstrated a significant correlation between the expression of these genes and the activation of microglial cells in the dystrophic retina. Our findings suggest that the suppression of microglial cells and the blockade of their cytotoxic effects may constitute a novel therapeutic strategy for treating photoreceptor death in various retinal disorders

Investigation of surface integrity of selective laser melting additively manufactured AlSi10Mg alloy under ultrasonic elliptical vibration-assisted ultra-precision cutting

Additive manufacturing technology has been widely used in aviation, aerospace, automobiles and other fields due to the fact that near-net-shaped components with unprecedented geometric freedom can be fabricated. Additively manufactured aluminum alloy has received a lot of attention, due to its excellent material properties. However, the finished surface of additively manufactured aluminum alloy with nanoscale surface roughness is quite challenging and rarely addressed. In this paper, a novel machining technology known as ultrasonic elliptical vibration-assisted cutting (UEVC) was adopted to suppress the generation of cracks, improve the surface integrity and reduce tool wear during the ultra-precision machining of selective laser melting (SLM) additively manufactured AlSi10Mg alloy. The experimental results revealed that, in the conventional cutting (CC) process, surface defects, such as particles, pores and grooves, appeared on the machined surface, and the machined surface rapidly deteriorated with the increase in cumulative cutting area. In contrast, an almost flawless machined surface was obtained in the UEVC process, and its roughness value was less than 10 nm. Moreover, the tool wear of the CC tool was remarkably greater than that of the UEVC tool, and the standard flank wear width of the CC tool was more than twice that of the UEVC tool. Therefore, the UEVC technology is considered to be a feasible method for the ultra-precision machining of SLM additively manufactured AlSi10Mg alloy

A Novel Statistic for Genome-Wide Interaction Analysis

Although great progress in genome-wide association studies (GWAS) has been made, the significant SNP associations identified by GWAS account for only a few percent of the genetic variance, leading many to question where and how we can find the missing heritability. There is increasing interest in genome-wide interaction analysis as a possible source of finding heritability unexplained by current GWAS. However, the existing statistics for testing interaction have low power for genome-wide interaction analysis. To meet challenges raised by genome-wide interactional analysis, we have developed a novel statistic for testing interaction between two loci (either linked or unlinked). The null distribution and the type I error rates of the new statistic for testing interaction are validated using simulations. Extensive power studies show that the developed statistic has much higher power to detect interaction than classical logistic regression. The results identified 44 and 211 pairs of SNPs showing significant evidence of interactions with FDR<0.001 and 0.001<FDR<0.003, respectively, which were seen in two independent studies of psoriasis. These included five interacting pairs of SNPs in genes LST1/NCR3, CXCR5/BCL9L, and GLS2, some of which were located in the target sites of miR-324-3p, miR-433, and miR-382, as well as 15 pairs of interacting SNPs that had nonsynonymous substitutions. Our results demonstrated that genome-wide interaction analysis is a valuable tool for finding remaining missing heritability unexplained by the current GWAS, and the developed novel statistic is able to search significant interaction between SNPs across the genome. Real data analysis showed that the results of genome-wide interaction analysis can be replicated in two independent studies

A Combination of Nutriments Improves Mitochondrial Biogenesis and Function in Skeletal Muscle of Type 2 Diabetic Goto–Kakizaki Rats

BACKGROUND: Recent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis/function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that defect of glucose and lipid metabolism is associated with low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle of the diabetic Goto-Kakizaki rats. The treatment of combination of R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid (FFA), and prevented the reduction of mitochondrial biogenesis in skeletal muscle. The nutrients treatment also significantly increased mRNA levels of genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-alpha (Ppar alpha), peroxisome proliferator-activated receptor-delta (Ppar delta), and carnitine palmitoyl transferase-1 (Mcpt-1) and activity of mitochondrial complex I and II in skeletal muscle. All of these effects of mitochondrial nutrients are comparable to that of the antidiabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone, did not cause body weight gain. CONCLUSIONS/SIGNIFICANCE: These data suggest that a combination of mitochondrial targeting nutrients may improve skeletal mitochondrial dysfunction and exert hypoglycemic effects, without causing weight gain

Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985–2008

BACKGROUND: Pneumonia is a leading infectious disease killer worldwide, yet the burden in China is not well understood as much of the data is published in the non-English literature. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed the Chinese- and English-language literature for studies with primary data on pneumonia incidence and mortality in mainland China. Between 1985 and 2008, 37 studies met the inclusion criteria. The quality of the studies was highly variable. For children <5 years, incidence ranged from 0.06-0.27 episodes per person-year and mortality ranged from 184-1,223 deaths per 100,000 population. Overall incidence and mortality were stable or decreased over the study period and were higher in rural compared to urban areas. CONCLUSIONS/SIGNIFICANCE: Pneumonia continues to be a major public health challenge in young children in China, and estimates of pneumonia incidence and mortality vary widely. Reliable surveillance data and new prevention efforts may be needed to achieve and document additional declines, especially in areas with higher incidence and mortality such as rural settings