Characterization of Metastasis-Associated Cell Surface Glycoproteins in Prostate Cancer

Prostate cancer (PCa) is a major health problem in males in the United States. Its lethality is mostly attributed to the primary tumor metastasizing to distant sites that are highly resistant to conventional therapies. Serum Prostate Specific Antigen (PSA) is the only protein biomarker used in clinic for prediction of prostate cancer recurrence following local therapies. Nonetheless, PSA lacks the ability to predict the behavior of an individual tumor in an individual patient. Therefore, development of reliable biomarkers for detection of metastatic potential in primary tumors, as well as discovery of new therapeutic targets, is in a great need for improved disease survival and management. Tumor metastasis is a multistep process involving extravasation of a cancer cell subsequent invasion and expression at a site distal to the primary tumors. Cell surface glycoproteins play pivotal roles as recognition molecules in a range of cell communication and adhesion events. Aberrant cell surface glycosylation has been reported in various cancers including PCa, and strongly correlated with prognosis and metastasis. However, the staggering complexity of glycans renders their analysis extraordinarily difficult. This research project aims to develop a mass spectrometry-based glycoproteomic approach for the selective isolation and identification of cell surface glycoproteins from cellular samples, and apply this technology to the discovery of new glycoprotein biomarkers which are indicative of prostate cancer progression and metastasis. To this end, cell surface glycosylation patterns were characterized by lectin flow cytometry and lectin cytochemistry on a human syngeneic PCa cell metastatic model, PC3 and its two variants with different metastatic potentials. It was found that metastatic potentials of PC3 variants were inversely correlated with cell surface α2-6 sialic acid levels. Targeted to cell surface sialoglycoproteins, a new glycoproteomic approach was successfully developed, which combined selective metabolic labeling of cell surface sialyl glycans, chemically probing the labeled sugar with a biotin tag, affinity purification of sialylated proteins, SDS-PAGE separation, and subsequent LC-MS/MS for protein identification. Application of this methodology in our prostate cancer model system resulted in unique identification of a total of 80 putative cell surface sialoglycoproteins differentially expressed between PC3 variants. After prioritization of the candidate biomarkers, one cell-based prioritized biomarker CUB-domain-containing protein 1 (CDCP1) was verified in prostate cancer cell lines and clinical samples, including tissues and body fluids, by immunoassays. Results indicated that expression of CDCP1 protein is dysregulated in prostate cancer and it has potential utility as a therapeutic target and a diagnostic marker for PCa progression. Overall, the data from this research project provided the proof-of-principle evidence for our targeted glycoproteomic approach, which we believe will help expedite the discovery of new cancer biomarkers and therapeutic targets in diseases and delineation of signal transduction pathways on a global scale

Research on Multimedia Teaching Materials of Ergonomics Experiments

AbstractAs important foundation for product design, ergonomics studying has been necessary for most engineering students. Ergonomics experiments can help students obtain perceptual knowledge of human factors. Through research of integrating multimedia technology into ergonomics experiments teaching, the author hopes to improve the teaching effect of ergonomics experiment. By introducing some film shooting technology, the multimedia courseware can clearly present the process of ergonomics experiment and by means of adding more ergonomics related background knowledge, the multimedia courseware can provide students rich useful information for ergonomics study. The development of ergonomics multimedia courseware gives a novel idea is to improve teaching effect

Small-molecule Nucleic-acid-based Gene-silencing Strategies

Gene-targeting strategies based on nucleic acid have opened a new era with the development of potent and effective gene intervention strategies, such as DNAzymes, ribozymes, small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), aptamers, decoys, etc. These technologies have been examined in the setting of clinical trials, and several have recently made the successful transition from basic research to clinical trials. This chapter discusses progress made in these technologies, mainly focusing on Dzs and siRNAs, because these are poised to play an integral role in antigene therapies in the future

A Review on John Fryer’s Scientific Translation in the Late Qing Dynasty

John Fryer was a British missionary in the late Qing Dynasty who came to China and was employed by The Translation Department of Kiangnan Arsenal. He has been engaged in the translation work for over 28 years, not only having translated a great deal of Western scientific works into Chinese, but also having contributed greatly to the standardization of the scientific terminology translation. This paper first attempts to analyze the previous studies on John Fryer, and then tries to analyze the studies on scientific translation in the late Qing Dynasty. Based on the analyses, we come to a conclusion that a detailed and systematic study on John Fryer’s scientific translation and his contribution to the standardization of translated scientific terminologies is greatly worth doing

John Fryer’s Contribution to Standardization of Translated Scientific Terminology in Modern China

John Fryer was a British missionary in the late Qing Dynasty who came to China and was employed by The Translation Department of Kiangnan Arsenal. He has been engaged in the translation work for over 28 years, not only having translated a great deal of Western scientific works into Chinese, but also having contributed greatly to the standardization of the scientific terminology translation. This paper first attempts to probe into Fryer’s scientific translation practice and his translation ideas, and then points out that Fryer’s major contributions to the standardization of the scientific terminology translation in Modern China are that the magazine Ko-chih-hui-pien he established had helped greatly with the popularization of modern scientific knowledge, that the book Mirroring the Origins of Chemistry he translated had paved the way for the term translation of modern chemical elements, and that various lists of bilingual technical terms he made, to a great degree, had standardized the translation of scientific terminology

Morphological Dependence of Star Formation Properties for the Galaxies in the Merging Galaxy Cluster A2255

The merging cluster of galaxies A2255 is covered by the Sloan Digital Sky Survey (SDSS) survey. In this paper we perform a morphological classification on the basis of the SDSS imaging and spectral data, and investigate the morphological dependence of the star formation rates (SFRs) for these member galaxies. As we expect, a tight correlation between the normalized SFR by stellar mass (SFR/M$_*$) and the H$\alpha$ equivalent width is found for the late-type galaxies in A2255. The correlation of SFR/M$_*$ with the continuum break strength at 4000 \AA is also confirmed. The SFR/M$_*$ - M$_*$ correlation is found for both the early- and late-type galaxies, indicating that the star formation activity tends to be suppressed when the assembled stellar mass M$_*$) increases, and this correlation is tighter and steeper for the late-type cluster galaxies. Compared with the mass range of field spiral galaxies, only two massive late-type galaxies with M$_*>10^{11}$ M$_{\odot}$ are survived in A2255, suggesting that the gas disks of massive spiral galaxies could have been tidally stripped during cluster formation. Additionally, the SFR variation with the projected radial distance are found to be heavily dependent upon galaxy morphology: the early-type galaxies have a very weak inner decrease in SFR/M$_*$, while the inner late-type galaxies tend to have higher SFR/M$_*$ values than the outer late-types. This may suggest that the galaxy-scale turbulence stimulated by the merging of subclusters might have played different roles on early- and late-type galaxies, which leads to a suppression of the star formation activity for E/S0 galaxies and a SFR enhancement for spiral and irregular galaxies.Comment: 21 pages, including 7 EPS figures and 1 tables, uses aastex.cls, Accepted by the A

Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes

Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress. mTOR signaling presents both cardioprotective and cardiotoxic effects on the diabetic heart, which interplays with oxidative stress directly or indirectly. Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets. In this review, we will focus on the role of oxidative stress and mTOR signaling in the pathophysiology of MI/R injury in diabetes and discuss potential mechanisms and their interactions in an effort to provide some evidence for cardiometabolic targeted therapies for ischemic heart disease (IHD)