Red Runaways II: Low mass Hills stars in SDSS Stripe 82

Stars ejected from the Galactic centre can be used to place important constraints on the Milky Way potential. Since existing hypervelocity stars are too distant to accurately determine orbits, we have conducted a search for nearby candidates using full three-dimensional velocities. Since the efficacy of such studies are often hampered by deficiencies in proper motion catalogs, we have chosen to utilize the reliable, high-precision SDSS Stripe 82 proper motion catalog. Although we do not find any candidates which have velocities in excess of the escape speed, we identify 226 stars on orbits that are consistent with Galactic centre ejection. This number is significantly larger than what we would expect for halo stars on radial orbits and cannot be explained by disk or bulge contamination. If we restrict ourselves to metal-rich stars, we find 29 candidates with [Fe/H] > -0.8 dex and 10 with [Fe/H] > -0.6 dex. Their metallicities are more consistent with what we expect for bulge ejecta, and so we believe these candidates are especially deserving of further study. We have supplemented this sample using our own radial velocities, developing an algorithm to use proper motions for optimizing candidate selection. This technique provides considerable improvement on the blind spectroscopic sample of SDSS, being able to identify candidates with an efficiency around 20 times better than a blind search.Comment: 13 pages, accepted for publication in Ap

Nearby Low-Mass Hypervelocity Stars

Hypervelocity stars are those that have speeds exceeding the escape speed and are hence unbound from the Milky Way. We investigate a sample of low-mass hypervelocity candidates obtained using data from the high-precision SDSS Stripe 82 catalogue, which we have combined with spectroscopy from the 200-inch Hale Telescope at Palomar Observatory. We find four good candidates, but without metallicities it is difficult to pin-down their distances and therefore total velocities. Our best candidate has a significant likelihood that it is escaping the Milky Way for a wide-range of metallicities.Comment: 5 pages; Contribution to proceedings for "The Milky Way Unravelled by Gaia" conference, Barcelona, Dec 201

Reproductive Toxicity of Crude oil-Dispersant Mixture in Caenorhabditis elegans

As crude oil remains a vital natural resource for the energy need of the world, environmental crude oil spills continue to be a health risk to human beings and ecological systems. During clean-up efforts, surfactant-like dispersants are used to break down big oil slicks into small droplets. Therefore it is necessary to investigate the health impacts of dispersed oil as a mixture entity rather than based on the toxicological profile of individual chemicals. Since reproductive stages of organisms are generally being more sensitive to the effects of toxicants than other stages, investigation of crude oil/dispersant exposure effects on reproduction is critically important. However, studies on the reproductive effects of crude oil-dispersant mixture exposure and its mechanism remain insufficient. The nematode Caenorhabditis elegans (C. elegans) has been a useful tool for environmental toxicity studies, and it is a well-known animal model to study the reproduction system. Therefore in this study, we employed the nematode C. elegans to test impacts of crude oil/dispersant exposure on basic biological processes growth, reproduction, microRNAs and protein-coding gene expression and its underlying mechanisms. In Chapter 1, we employed parallel experiments to test the effects of crude oil from the DWH oil well, chemical dispersant Corexit 9500A, and dispersant-oil mixture on growth and reproduction in the model organism Caenorhabditis elegans. Both the crude oil and the dispersant significantly inhibited the reproduction of C. elegans. Dose-dependent inhibition of hatched larvae production was observed in worms exposed to both crude oil and dispersant. Importantly, the chemical dispersant Corexit 9500A potentiated crude oil effects; the dispersant-oil mixture induced more significant effects than oil or dispersant-alone exposures. While oil-alone exposure and dispersant-alone exposure have none to moderate inhibitory effects on hatched larvae production, respectively, the mixture of dispersant and oil induced much more significant inhibition of offspring production. The production of hatched larvae was almost completely inhibited by several high concentrations of the dispersant-oil mixture. We also investigated the effects of crude oil/dispersant exposure at the molecular level by measuring the expressions of 31 functional genes. Results showed that the dispersant and the dispersant-oil mixture induced aberrant expressions of 12 protein-coding genes. These 12 genes are associated with a variety of biological processes, including egg-laying, oxidative stress, muscle contraction, and neurological functions. In Chapter 2, we showed that crude oil-dispersant mixture affected reproduction by inducing abnormal sperm during the process of spermatogenesis. Results showed that the abnormal immature sperm were significantly increased in the gonad arms of Dis-Oil mixture treated animals compared to controls (K-medium). We further explored the oil-dispersant mixture toxicity effects on spermatogenesis by using a male C. elegans strain. After 48h exposure to Dis-Oil mixture, spermatids appeared abnormal morphology including irregular shape of the spermatid membrane and unexpected tails induced by dispersed oil. Moreover we utilized puf-8; lip-1 tumor sensitive strain to test the cell fate of immature sperm induced by Dis-Oil mixture treatment. We found increased tumor occurrence in dispersed oil treatments compared to control. Results also suggest that the immature sperm may undergo dedifferentiation and become tumor-like cells in puf-8; lip-1 mutants through the MAPK-independent pathway. Based on the genome-wide investigation of microRNA profile, in Chapter 3, we found that the aberrant expression of miRNAs was induced. The KEGG pathway enrichment analyses indicated that those significantly changed miRNAs regulate many biological processes in C. elegans. Many affected pathways are related to environmental information processing, such as ABC transporters, MAPK signaling pathway, Erbb signaling pathway, JAK-STAT signaling pathway, MTOR signaling pathway and calcium-signaling pathway. Some pathways are related to oil uptake and metabolism, such as endocytosis, fatty acid biosynthesis and phosphatidylinositol signaling system. In summary, based on our studies, both crude oil and dispersant can induce the reproductive toxicity, and the dispersant enhanced the crude oil toxicity. Since the currently identified proteins and microRNAs in C.elegans show remarkable conservation with mammals including humans, the oil/dispersant may also induce similar change at physiological and molecular levels and affect many biological processes in mammals

Genetic polymorphisms in plasminogen activator inhibitor-1 predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese population

BACKGROUND: Steroid usage has been considered as a leading cause of non-traumatic osteonecrosis of the femoral head (ONFH), which is involved in hypo-fibrinolysis and blood supply interruption. Genetic polymorphisms in plasminogen activator inhibitor-1 (PAI-1) have been demonstrated to be associated with ONFH risk in several populations. However, this relationship has not been established in Chinese population. The aim of this study was to investigate the association of PAI-1 gene polymorphisms with steroid-induced ONFH in a large cohort of Chinese population. METHODS: A case–control study was conducted, which included 94 and 106 unrelated patients after steroid administration recruited from 14 provinces in China, respectively. Two SNPs (rs11178 and rs2227631) within PAI-1 were genotyped using Sequenom MassARRAY system. RESULTS: rs2227631 SNP was significantly associated with steroid-induced ONFH group in codominant (P = 0.04) and recessive (P = 0.02) models. However, there were no differences found in genotype frequencies of rs11178 SNP between controls and patients with steroid-induced ONFH (all P > 0.05). CONCLUSIONS: Our data offer the convincing evidence for the first time that rs2227631 SNP of PAI-1 may be associated with the risk of steroid-induced ONFH, suggesting that the genetic variations of this gene may play an important role in the disease development. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1569909986109783

Label-Free Fluorescent Determination of Sunset Yellow in Soft Drinks Based on an Indicator-Displacement Assay

This work reported a fluorescence sensing platform for Sunset Yellow (SY) determination based on competitive host-guest interaction between cucurbit[7]uril (CB7) and signal probe/target molecules. Luteolin/epigallocatechin gallate (EGCG) and SY were selected as the probe and target molecules, respectively. When luteolin or EGCG entered the CB7 host, its fluorescence significantly improved. However, upon the presence of SY in the performed luteolin·CB7 or EGCG·CB7 complex, this led to a remarkable decrease in fluorescence. This result was due to the fact that the binding constant of CB7/SY (4.9×104 M−1) was greater than that of CB7/luteolin (3.2×103 M−1) or CB7/EGCG (4.8×103 M−1). The fluorescence intensities of CB7/luteolin and CB7/EGCG complexes decreased linearly with increased SY concentration ranges of 0.5–50.0 and 2.0–50.0 μM. The proposed method had detection limits of 0.12 and 0.45 μM and was successfully used to determine SY samples with good recoveries ranging from 96.3% to 103.8%. This competitive mode provided a promising fluorescence assay strategy for potential applications in food safety

A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Wu Tou Tang Acting on Rheumatoid Arthritis by Integrating Network Analysis

Aim. To investigate pharmacological mechanisms of Wu Tou Tang acting on rheumatoid arthritis (RA) by integrating network analysis at a system level. Methods and Results. Drug similarity search tool in Therapeutic Targets Database was used to screen 153 drugs with similar structures to compositive compounds of each ingredient in Wu Tou Tang and to identify 56 known targets of these similar drugs as predicted molecules which Wu Tou Tang affects. The recall, precision, accuracy, and F1-score, which were calculated to evaluate the performance of this method, were, respectively, 0.98, 0.61, 59.67%, and 0.76. Then, the predicted effector molecules of Wu Tou Tang were significantly enriched in neuroactive ligand-receptor interaction and calcium signaling pathway. Next, the importance of these predicted effector molecules was evaluated by analyzing their network topological features, such as degree, betweenness, and k-coreness. We further elucidated the biological significance of nine major candidate effector molecules of Wu Tou Tang for RA therapy and validated their associations with compositive compounds in Wu Tou Tang by the molecular docking simulation. Conclusion. Our data suggest the potential pharmacological mechanisms of Wu Tou Tang acting on RA by combining the strategies of systems biology and network pharmacology

The E3 Ubiquitin Ligase SCF(Cyclin F) Transmits AKT Signaling to the Cell-Cycle Machinery

The oncogenic AKT kinase is a key regulator of apoptosis, cell growth, and cell-cycle progression. Despite its important role in proliferation, it remains largely unknown how AKT is mechanistically linked to the cell cycle. We show here that cyclin F, a substrate receptor F-box protein for the SCF (Skp1/Cul1/F-box) family of E3 ubiquitin ligases, is a bona fide AKT substrate. Cyclin F expression oscillates throughout the cell cycle, a rare feature among the 69 human F-box proteins, and all of its known substrates are involved in proliferation. AKT phosphorylation of cyclin F enhances its stability and promotes assembly into productive E3 ligase complexes. Importantly, expression of mutant versions of cyclin F that cannot be phosphorylated by AKT impair cell-cycle entry. Our data suggest that cyclin F transmits mitogen signaling through AKT to the core cell-cycle machinery. This discovery has potential implications for proliferative control in malignancies where AKT is activated

Identification of a novel microRNA-mRNA regulatory biomodule in human prostate cancer

Our recent study identified a list of differentially expressed microRNAs (miRNAs) in human prostate cancer (PCa) tissues compared to adjacent benign prostate tissues. In the current study, to identify the crucial miRNA–mRNA regulatory biomodule involved into prostate carcinogenesis based on the previous miRNA expression profile in PCa, we proposed an integrated systematic approach which combined miRNA-mediated gene expression regulatory network analysis, experimental validations in vitro and in vivo, as well as clinical significance evaluation. As a result, the CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I axis was identified as a bottleneck in the miRNA-mediated gene expression regulatory network of PCa according to network topological analysis. The direct binding relationship between TP73 and PCa downregulated miR-193a-5p, and the direct binding relationship between UBE2I and PCa upregulated miR-188-5p were both experimentally validated. In addition, miR-193a-5p had a more significant regulatory effect on the tumor promoter isoform of TP73-deltaNp73 than on the tumor suppressive isoform of TP73-TAp73. Importantly, the deregulation of either the miR-193a-5p-TP73 or miR-188-5p-UBE2I axes was significantly associated with aggressive progression and poor prognosis in PCa patients. Gain- and loss-of-function experiments showed that miR-193a-5p efficiently inhibited in vitro PCa cell proliferation, migration, and invasion, and in vivo tumor growth, and markedly induced PCa cell apoptosis via regulating TP73 with a corresponding suppression of the CCND1-RNASEL-CDKN1A-MDM2 axis. In contrast, miR-188-5p exerted its tumor promoter roles through targeting UBE2I with a subsequent activation of the CCND1-RNASEL-CDKN1A-MDM2 axis. Taken together, this integrated analysis revealed the potential roles of the miR-193a-5p/TP73 and miR-188-5p/UBE2i negative regulation pairs in PCa. In addition to the significant clinical relevance, miR-193a-5p- and miR-188-5p-regulated CCND1-RNASEL-CDKN1A-TP73-MDM2-UBE2I signaling may be a novel regulatory biomodule in prostate carcinogenesis