Cover Image: Foreground image taken from Tongzhong Ju et al., (pp. 618–631): IgA1 has normalO-glycans with a core 1 O-glycan decorated with sialic acids (purple diamonds) in either mono- or disiaylated structures. But in IgA1 from IgA nephropathy (IgAN) patients it is proposed that Tn and STn antigens lacking the core 1 O-glycan accumulate and contribute to IgAN. IgAN is the most common glomerulonephritis and results in renal failure in 20–40% of patients over 25 years of age. Deposition of IgA1 in the glomerular mesangium is thought to drive the disease. Background image, kindly provided by Tongzhong Ju, Richard D. Cummings, et al.: Human primary colorectal adenocarcinoma cells highly express Tn antigen. A formalin fixed paraffin-embedded tissue section of human primary colorectal adenocarcinoma was immunohistochemically stained with anti-Tn monoclonal antibody (Red) and counter staining with Haemotoxylin (Blue). The tumor cells are highly stained with anti-TnmAb. Cover design by SCHULZGrafik-Design.
Oxidatively modified ApoA1: The left-hand side of the figure depicts an HDL particle with bound ApoA1 that has not undergone oxidative damage, and as shown, is able to function normally interacting with LCAT, peripheral ABCA1 and SRB-1. The righthand side of the figure displays an HDL particle that has undergone extensive oxidative modification on ApoA1, a process that has been shown to negatively affect the ability of the HDL particle to interact peripherally with ABCA1, LCAT, and SRB-1. This loss of function of ApoA1 has many consequences such as impaired ABCA1 signaling and cholesterol deposition to HDL, impaired cholesterol to cholesteryl conversion by LCAT, and the inability to dock with SRB-1. For further details see article in this issue by Jeriel Keeney et al., Apolipoprotein A-I: Insights from redox proteomics for its role in neurodegeneration, Proteomics Clin. Appl. 2013, 7, 109-122 (DOI: 10.1002/prca.201200087). Cover image created by Jeriel Keeney and Aaron Swomley (Prof. D. Allan Butterfield Group, Chemistry Department, University of Kentucky, Lexington. KY, USA); cover design by SCHULZ Grafik-Design. 相似文献
In this issue of Proteomics – Clinical Applications you will find the following highlighted articles: Looking through the leftovers The magic in conditioned medium has been recognized for decades but exactly what it was and how it worked has only begun to come to light more recently. Byproducts of metabolic activity are easy to spot, more challenging are the secreted growth factors and other types of communication molecules. Ogura et al. looked at the litter that surrounded various cancer cells as a potential gold mine. It took only a bit of RP‐HPLC and MALDI‐TOF panning to turn up nuggets of pro‐ and pre‐proneurotensin/neuromedin N (pre‐proNT/NTN), good candidates for small‐cell lung cancer biomarkers. Pre‐proNT/NTN was found in medium from 4 out of 7 different small‐cell lung carcinomas but 0 out of 8 non‐small‐cell carcinomas. Ogura, S.‐i. et al., Proteomics Clin. Appl. 2008, 2, 1620–1627. Hunting for Huntington's Creating animal models of inherited human diseases is not always a simple issue of replacing an animal gene with the human equivalent. Huntington's Disease (HD), caused at least in part by the development of expanded polyglutamine (CAG)n sequences in the huntingtin gene, has been modeled in mice with n>60 (CAG)n sequences but this leads to expression as a juvenile form of the disease. Nguyen et al. have developed transgenic rats that come much closer to the pattern of adult human HD in the character and time of appearance of motor deficits, cognitive decline, and emotional disturbance. After thorough micro array evaluation of the rat model at ages 3 and 12 months, these researchers argue that they are much closer to a system suitable for selection and application of biomarkers and potential therapeutics. Nguyen, H. P. et al., Proteomics Clin. Appl. 2008, 2, 1638–1650. Bifunctional assay means less work To be able to have your cake and eat it, too, is one of those things economists tell us is impossible. Don't tell Rader et al. though. They are investigating methods to simplify and speed up human papilloma virus (HPV) biomarker screening from the same sample. This would be very useful for cervical cancer staging, still a problem despite the recent introduction and growing use of a vaccine for the most frequent cancer‐causing HPV types. Cervical samples were collected into a tube containing an RNA stabilizing reagent, from which proteins could be extracted and freed of cervical mucus. RNA could be extracted from the same samples with Trizol reagent according to the manufacturer's directions. Proteins recovered were cleanly analyzed by 2‐D DIGE and Western blots; total RNA could be analyzed on human cDNA arrays. Rader, J. S. et al., Proteomics Clin. Appl. 2008, 2, 1658–1669. 相似文献
Over recent years, advances in proteomic technologies have led to the rapid generation of vast volumes of data regarding many clinical applications, acquired from cells through to patients. High-throughput analysis of protein-protein interactions, quantification of protein abundance, global analysis of posttranslational modifications and other approaches have addressed the complexity of cellular regulation in health and disease, which has opened the way to systems-level clinical research. The dysregulation of cell adhesion plays a key role in many disease states. The image represents a systematic analysis of integrin adhesion complexes, which were isolated from erythroleukemia cells and analyzed bymass spectrometry (see Byron et al., Science Signaling 2011, 4, pt2). To understand how specific adhesion complexes may function, the composition of different complexes was compared using hierarchical clustering, and a protein-protein interaction network model of the core receptor-bound subcomplex was constructed. Data-driven, global investigations such as this could pave the road to new therapeutic targets and personalized medicines. Cover image created by Adam Byron (University of Manchester,Manchester, UK); cover design by SCHULZ Grafik-Design. 相似文献