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Marian Christoph Neidert, Daniel Johannes Kowalewski, Manuela Silginer, Konstantina Kapolou, Linus Backert, Lena Katharina Freudenmann, Janet Kerstin Peper, Ana Marcu, Sophie Shih-Yüng Wang, Juliane Sarah Walz, Fabian Wolpert, Hans-Georg Rammensee, Reinhard Henschler, Katrin Lamszus, Manfred Westphal, Patrick Roth, Luca Regli, Stefan Stevanović, Michael Weller, Günter Eisele
Glioblastoma is the most frequent malignant primary brain tumor. In a hierarchical tumor model, glioblastoma stem-like cells (GSC) play a major role in tumor initiation and maintenance as well as in therapy resistance and recurrence. Thus, targeting this cellular subset may be key to effective immunotherapy. Here, we present a mass spectrometry-based analysis of HLA-presented peptidomes of GSC and glioblastoma patient specimens. Based on the analysis of patient samples (n = 9) and GSC (n = 3), we performed comparative HLA peptidome profiling against a dataset of normal human tissues...
March 20, 2018: Acta Neuropathologica
Laura Santambrogio
This review will highlight our current understanding of the formation, circulation, and immunological role of lymphatic fluid. The formation of the extracellular fluid depends on the net balance between the hydrostatic and osmotic pressure gradients effective in the capillary beds. Lymph originates from the extracellular fluid and its composition combines the ultrafiltrated plasma proteins with the proteome generated by the metabolic activities of each parenchymal tissue. Several analyses have indicated how the lymph composition reflects the organs' physiological and pathological states...
2018: International Review of Cell and Molecular Biology
Zhao-Lian Lu, Ying-Jian Chen, Xin-Yan Jing, Na-Na Wang, Ting Zhang, Cheng-Jin Hu
BACKGROUND Papillary thyroid cancer (PTC) is currently the most commonly diagnosed endocrine malignancy. In addition, the sex- and age-adjusted incidence of PTC has exhibited a greater increase over the last 2 decades than in many other malignancies. Thus, discovering noninvasive specific serum biomarker to distinguish PTC from cancer-free controls in its early stages remains an important goal. MATERIAL AND METHODS Serum samples from 88 PTC patients and 80 cancer-free controls were randomly allocated into training or validation sets...
March 17, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Tao Liu, Karin D Rodland, Richard D Smith
Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of the tumor peptidome has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the tumors peptidome information in cancer research have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing...
2018: Vitamins and Hormones
Rattiyaporn Kanlaya, Visith Thongboonkerd
TGF-β1 is a key fibrotic factor mediating epithelial mesenchymal transition (EMT) of epithelial cells through various signaling pathways. However, roles of proteolytic cleavage and endogenous peptide dynamics in TGF-β1-induced EMT remain unknown. We therefore performed quantitative peptidomics of TGF-β1-induced EMT in renal tubular epithelial cells. The acquired mesenchymal characteristics were confirmed, including morphological change (from cobblestone-like to fibroblast-like), decreased epithelial marker (ZO-1), and increased mesenchymal marker (vimentin)...
December 2018: Cell Death Discovery
Aleksandra E Lewandowska, Katarzyna Macur, Paulina Czaplewska, Joanna Liss, Krzysztof Łukaszuk, Stanisław Ołdziej
Analysis of proteomic composition of human follicular fluid (hFF) has been previously proposed as a potential tool of oocyte quality evaluation. In order to develop an efficient method to investigate the hFF proteome and peptidome components, we applied and tested a few prefractionation schemes of hFF material consisting of ultrafiltration, optional immunodepletion, and high pH RP-HPLC separation by building spectral libraries and comparing their quantification capabilities of unfractionated samples. Low Molecular-Weight Fraction peptides (LMWF, <10 kDa) and High Molecular-Weight Fraction proteins (HMWF, >10 kDa) resulting from ultrafiltration were analyzed separately...
March 9, 2018: Journal of Proteomics
Mehdi Moini
In the past few years, there has been a significant effort by the forensic science community to develop new scientific techniques for the analysis of forensic evidence. Forensic chemists have been spearheaded to develop information-rich confirmatory technologies and techniques and apply them to a broad array of forensic challenges. The purpose of these confirmatory techniques is to provide alternatives to presumptive techniques that rely on data such as color changes, pattern matching, or retention time alone, which are prone to more false positives...
March 12, 2018: Electrophoresis
Florian Erhard, Anne Halenius, Cosima Zimmermann, Anne L'Hernault, Daniel J Kowalewski, Michael P Weekes, Stefan Stevanovic, Ralf Zimmer, Lars Dölken
Ribosome profiling has been used to predict thousands of short open reading frames (sORFs) in eukaryotic cells, but it suffers from substantial levels of noise. PRICE ( is a computational method that models experimental noise to enable researchers to accurately resolve overlapping sORFs and noncanonical translation initiation. We experimentally validated translation using major histocompatibility complex class I (MHC I) peptidomics and observed that sORF-derived peptides efficiently enter the MHC I presentation pathway and thus constitute a substantial fraction of the antigen repertoire...
March 12, 2018: Nature Methods
Andrew E Christie, Micah G Pascual, Andy Yu
Peptides are the largest/most diverse class of molecules used by animals for chemical communication, and with their cognate receptors, are key players in modulating physiological/behavioral control systems, including those involved in adaptation to environmental change. Crustaceans have long served as models for investigating peptidergic control of physiology/behavior, and members of Notostraca, an ancient branchiopod order, have recently been proposed as models for investigating the genetic/physiological underpinnings of ecoresponsiveness; nothing is currently known about the genes/proteins underlying peptidergic signaling in any member of this crustacean taxon...
March 8, 2018: Marine Genomics
Dominic Agyei, Apollinaire Tsopmo, Chibuike C Udenigwe
There are emerging advancements in the strategies used for the discovery and development of food-derived bioactive peptides because of their multiple food and health applications. Bioinformatics and peptidomics are two computational and analytical techniques that have the potential to speed up the development of bioactive peptides from bench to market. Structure-activity relationships observed in peptides form the basis for bioinformatics and in silico prediction of bioactive sequences encrypted in food proteins...
March 7, 2018: Analytical and Bioanalytical Chemistry
Fabio Marino
Mass spectrometry (MS)-based immunopeptidomics has developed as one of the leading methodologies for comprehensive characterization of in vivo presented Human Leukocyte Antigen (HLA)-bound peptides. Unveiling the identity of HLA-bound peptides derived from diseased cells is crucial to gain knowledge on the constitution of efficient disease-specific T cell responses. The HLA-presented peptidome reflects the status of the cellular proteome, hence disease-related aberrations of post-translational modifications (PTMs) might lead to presentation of peptides harboring PTMs...
March 7, 2018: Proteomics
Simona Arena, Andrea Scaloni
Hen egg is a raw material widely used for preparation of food, pharmaceutical and cosmetoceutical products. Dedicated proteomic studies on egg fractions identified most abundant proteins. No similar studies have been performed at the peptidomic level so far. This study fills this gap and provides a comprehensive picture of the peptides present in the yolk plasma of different hen egg types after 24 and 264 h of laying, using a two-step fractionation followed by combined MALDI-TOF-TOF-MS and nanoLC-ESI-Q-Orbitrap-MS/MS analysis...
March 7, 2018: Journal of Agricultural and Food Chemistry
Jia Qi Wu, Jiu Hui Jiang, Li Xu, Cheng Liang, Xiu Jing Wang, Yunyang Bai
OBJECTIVE: To identify a panel of differentially expressed candidate biomarkers for patients undergoing accelerated osteogenic orthodontics (AOO). METHODS: This study included 36 saliva samples taken from six Class III surgical patients at six time points: the date before the corticotomy procedure (T1) and at 1 week, 2 weeks, 1 month, 2 months and 6 months after the procedure (T2, T3, T4, T5 and T6, respectively). After the maxillary dental arch was aligned and levelled, AOO procedures were performed in the maxillary alveolar bone...
2018: Chinese Journal of Dental Research
Krishna D B Anapindi, Elena V Romanova, Bruce R Southey, Jonathan V Sweedler
Characterization of endogenous neuropeptides produced from post-translational proteolytic processing of precursor proteins is a demanding task. A variety of complex prohormone processing steps generate molecular diversity from neuropeptide prohormones, making in silico neuropeptide discovery difficult. In addition, the wide range of endogenous peptide concentrations as well as significant peptide complexity further challenge the structural characterization of neuropeptides. Liquid chromatography-mass spectrometry (MS), performed in conjunction with bioinformatics, allows for high-throughput characterization of peptides...
May 15, 2018: Talanta
Michael P Greenwood, Mingkwan Greenwood, Elena V Romanova, Andre S Mecawi, Alex Paterson, Olivera Sarenac, Nina Japundžić-Žigon, José Antunes-Rodrigues, Julian F R Paton, Jonathan V Sweedler, David Murphy
Elderly people exhibit a diminished capacity to cope with osmotic challenges such as dehydration. We have undertaken a detailed molecular analysis of arginine vasopressin (AVP) biosynthetic processes in the supraoptic nucleus (SON) of the hypothalamus and secretory activity in the posterior pituitary of adult (3 months) and aged (18 months) rats, to provide a comprehensive analysis of age-associated changes to the AVP system. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, we identified differences in pituitary peptides, including AVP, in adult and aged rats under both basal and dehydrated states...
January 31, 2018: Neurobiology of Aging
P S Zeiner, J Zinke, D J Kowalewski, S Bernatz, J Tichy, M W Ronellenfitsch, F Thorsen, A Berger, M T Forster, A Muller, J P Steinbach, R Beschorner, J Wischhusen, H M Kvasnicka, K H Plate, S Stefanović, B Weide, M Mittelbronn, P N Harter
Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity.We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival...
March 1, 2018: Acta Neuropathologica Communications
Sven Van Bael, Jan Watteyne, Kurt Boonen, Wouter De Haes, Gerben Menschaert, Niels Ringstad, H Robert Horvitz, Liliane Schoofs, Steven Husson, Liesbet Temmerman
Neuropeptides constitute a vast and functionally diverse family of neurochemical signaling molecules, and are widely involved in the regulation of various physiological processes. The nematode C. elegans is well-suited for the study of neuropeptide biochemistry and function, as neuropeptide biosynthesis enzymes are not essential for C. elegans viability. This permits the study of neuropeptide biosynthesis in mutants lacking certain neuropeptide-processing enzymes. Mass spectrometry has been used to study the effects of proprotein convertase and carboxypeptidase mutations on proteolytic processing of neuropeptide precursors and on the peptidome in C...
February 27, 2018: Journal of Biological Chemistry
Jaimie Dufresne, Angelique Florentinus-Mefailoski, Pete Bowden, John G Marshall
The proteins identified from endogenous peptides agreed between serum versus plasma, and tryptic versus non-tryptic peptides, collected by C18 alone and analyzed by liquid chromatography electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS) including amyloids, apolipoproteins, haptoglobin, complements, fibrinogens, hemopexin, antitrypsin and alpha 2 macroglobulin. Precipitation of polypeptides from plasma in 9 vol of 100% organic solvent followed by stepwise extraction of the insoluble pellet with an increasing fraction of water identified thousands of proteins...
February 24, 2018: Analytical Biochemistry
Andrea Padoan
The successful use of proteomic technology for the discovery of clinically-relevant, new candidate biomarkers, especially in the low molecular weight range (peptidome), calls for a careful consideration of standardized operating procedures (SOP) for pre-analytical variables, including samples handling and storage. The current lack of standardization, widely considered a relevant source of random and systematic errors, underlies the uncertainty of analytical results and poor comparability, especially in multi-centric or inter-laboratory studies...
February 24, 2018: Proteomics. Clinical Applications
Peter D E M Verhaert
In this final chapter I project my personal perspective on the future of peptidomics. A bird's eye view is shed on the discipline and a bid is made to frame it in the broader arena of the life sciences of tomorrow. Inferring from its present state-of-the-art and from the general direction of some evolutionary trends which are to be discerned, a case is made that peptidomics enjoys full ripeness as a young branch of science today, from which a bright future for the discipline can be predicted.
2018: Methods in Molecular Biology
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