Glycosylation in Indolent,Significant and Aggressive Prostate Cancer by Automated High-Throughput N-Glycan Profiling

The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum N-glycan profiling was carried out on 117 prostate cancer patients’ serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of N-linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.     

Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.     

Multiobjective evaluation of advanced manufacturing system technology investments with risk

Advanced manufacturing system technologies are difficult to evaluate using ordinary financial measures owing to the presence of risk and significant intangible factors. In this paper a methodology is proposed that quantifies financial, strategic, and tactical attributes of each alternative. Attribute values are denned for each period of project life. Both project life and attributes are treated as random variables. Attributes are discounted to the current time and the multiple objectives are combined by composite programming. The distribution of the combined objective is estimated. The procedure is demonstrated on an actual case study.     

Proteine des Bienenhonigs

Zusammenfassung Die Isolierung der Saccharase (E.C. 3.2.1.20) aus den Proteinkonzentraten von Raps-, Tannen- und Zuckerfütterungshonig wird beschrieben. Die Abtrennung von anderen Enzymen, insbesondere von saurer Phosphatase gelingt durch hydrophobe Wechselwirkungschromatographie, von inerten Proteinen durch Gelfiltration. Im Zusammenhang damit wird das Verhalten des Enzyms bei der Chromatographie an Anionenaustauschern, an Hydroxylapatit und an immobilisiertem Weizenkeimlectin untersucht. Dabei ergab sich am Lectin-Gel eine Trennung in zwei multiple Formen.Die Saccharase aus allen drei Honigsorten verhielt sich einheitlich, woraus zu schließen ist, daß sie ausschließlich von der Biene stammt. Ihre Molekül masse wurde gelchromatographisch zu 57000 ermittelt.

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The proteins of honeyVIII. Honey sucrase, isolation, chromatographic behaviour and properties

Summary The isolation of the honey sucrase (E.C. 3.2.1.20) from rape- and fir-honey as well as from honey obtained after sugar feeding is described. The separation from other honey enzymes especially from acid phosphatase succeded by reversed phase chromatography. Separation of other, non-active proteins was accomplished by gel permeation chromatography. The behaviour of the honey sucrase upon chromatography on anion exchangers, on hydroxylapatite and wheat germ lectin was investigated. No differences were found between the sucrases of the three honeys.The molecular weight was determined at 57 000. By affinity chromatography with wheat germ lectin the enzyme could be separated into two multiple forms.

     

Verf?rbung grau und wei? pigmentierter Beschichtungen auf Acrylharzbasis auf Tropenh?lzern

Ohne Zusammenfassung     

Trypsin inhibitor activity of soybean as affected by genotype and fertilisation

The presence of protease inhibitors in soybean prohibits the utilisation of the raw beans for food and feed. However, little information is available about environmental influences and the effects of nitrogen and sulphur supply on the antinutritional constituents of soybean. As these factors may influence protease inhibitors, soybean genotypes segregated according to the presence or absence of the Kunitz trypsin inhibitor have been evaluated for trypsin inhibitor activity (TIA) in field trials. TIA was affected significantly by environment (geographical location), fertilisation treatment and genotype. Environmental means of TIA were between 69.5 and 104.8 mg g^?1. Nitrogen application, which caused an increase in seed protein content, resulted in a reduction in TIA by about 15% as compared with the control. Remarkably, simultaneous application of nitrogen and sulphur in the form of ammonium sulphate had a similar reductive effect on TIA to that of nitrogen application alone, although soybean protease inhibitors are rich in sulphur amino acids. Significant genetic variation in TIA was found both within the genotype class with the Kunitz inhibitor present as well as within the class lacking this inhibitor. The results suggest that TIA of soybean may be modified considerably by genetic improvement and appropriate agronomic management. Copyright © 2003 Society of Chemical Industry