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  • Skyline for Small Molecules: A Unifying Software Package for Quantitative Metabolomics
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-27
    Kendra J. Adams; Brian Pratt; Neelanjan Bose; Laura G. Dubois; Lisa St.John-Williams; Kevin M. Perrott; Karina Ky; Pankaj Kapahi; Vagisha Sharma; Michael J. MacCoss; M. Arthur Moseley; Carol A. Colton; Brendan X. MacLean; Birgit Schilling; J. Will Thompson

    Vendor-independent software tools for quantification of small molecules and metabolites are lacking, especially for targeted analysis workflows. Skyline is a freely available, open-source software tool for targeted quantitative mass spectrometry method development and data processing with a ten-year history supporting 6 major instrument vendors. Designed initially for proteomic analysis, we describe the expansion of Skyline to data for small molecule analysis, including selected reaction monitoring (SRM), high-resolution mass spectrometry (HRMS), and calibrated quantification. This fundamental expansion of Skyline from a peptide-sequence centric tool to a molecule-centric tool makes it agnostic to the source of the molecule while retaining Skyline features critical for workflows in both peptide and more general biomolecular research. The data visualization and interrogation features already available in Skyline - such as peak picking, chromatographic alignment, and transition selection - have been adapted to support small molecule data, including metabolomics. Herein, we explain the conceptual workflow for small molecule analysis using Skyline, demonstrate Skyline performance benchmarked against a comparable instrument vendor software tool, and present additional real-world applications. Further, we include step-by-step instructions on using Skyline for small molecule quantitative method development and data analysis on data acquired with a variety of mass spectrometers from multiple instrument vendors.

    更新日期:2020-01-27
  • Identification of ALDH6A1 as a Potential Molecular Signature in Hepatocellular Carcinoma via Quantitative Profiling of the Mitochondrial Proteome
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-27
    Heon Shin; Hyun-Jeong Cha; Min Jung Lee; Keun Na; Donha Park; Chae-Yeon Kim; Dai Hoon Han; Hoguen Kim; Young-Ki Paik

    Various liver diseases, including hepatocellular carcinoma (HCC), have been linked to mitochondrial dysfunction, reduction of reactive oxygen species (ROS) and elevation of nitric oxide (NO). In this study, we subjected the human liver mitochondrial proteome to an extensive quantitative proteomic profiling analysis and molecular characterization to identify potential signatures indicative of cancer cell growth and progression. A sequential proteomic analysis identified 2452 mitochondrial proteins, of which 1464 and 2010 were classified as non-tumor and tumor (HCC) mitochondrial proteins, respectively, with 1022 overlaps. Further metabolic mapping of the HCC mitochondrial proteins narrowed our biological characterization to four proteins, namely ALDH4A1, LRPPRC, ATP5C1 and ALDH6A1. The latter protein, a mitochondrial methylmalonate semialdehyde dehydrogenase (ALDH6A1), was most strongly suppressed in HCC tumor regions (~10-fold decrease) in contrast to LRPPRC (~6-fold increase), and was predicted to present in plasma. Accordingly, we selected ALDH6A1 for a functional analysis and engineered Hep3B cells to overexpress this protein, called ALDH6A1-O/E cells. Since ALDH6A1 is predicted to be involved in mitochondrial respiration, we assessed changes in the levels of NO and ROS in the overexpressed cell lines. Surprisingly, in ALDH6A1-O/E cells, NO was decreased nearly 50% but ROS was increased at the similar level, while the former was restored by treatment with S-nitroso-N-acetyl-penicillamine. The lactate levels were also decreased relative to control cells. Propidium iodine staining suggested that the decrease in NO and increase in ROS in ALDH6A1-O/E cells could be caused by depolarization of the mitochondrial membrane potential (ΔΨ). Taken together, our results suggest that hepatic neoplastic transformation appear to suppress the expression of ALDH6A1, which is accompanied by a respective increase and decrease in NO and ROS in cancer cells. Given the close link between ALDH6A1 suppression and abnormal cancer cell growth, this protein may serve as a potential molecular signature or biomarker of hepatocarcinogenesis and treatment responses. Mass spectrometry data are available via ProteomeXchange with identifier PXD014252.

    更新日期:2020-01-27
  • Spontaneous Glycan Reattachment Following N-Glycanase Treatment of Influenza and HIV Vaccine Antigens
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-24
    Celina L. Keating; Eric Kuhn; Julia Bals; Alexandra R. Cocco; Ashraf S. Yousif; Colette Matysiak; Maya Sangesland; Larance Ronsard; Matthew Smoot; Thalia Bracamonte Moreno; Vintus Okonkwo; Ian Setliff; Ivelin Georgiev; Alejandro B. Balazs; Steven A. Carr; Daniel Lingwood
    更新日期:2020-01-26
  • High Resolution GC-Orbitrap-MS Metabolomics using both Electron Ionization (EI) and Chemical Ionization (CI) for Analysis of Human Plasma
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-24
    Biswapriya B. Misra; Michael Olivier

    Gas chromatography-mass spectrometry (GC-MS) platforms are typically run in electron ionization (EI) mode for mass spectral matching and metabolite annotation. With the advent of high resolution mass spectrometry (HRMS), soft ionization techniques such as chemical ionization (CI) may provide additional coverage for compound identification. We evaluated NIST SRM 1950 pooled plasma reference sample using a HRGC-MS instrument [GC-Orbitrap-MS with electron ionization (EI), positive chemical ionization (PCI), and negative CI (NCI) capabilities) for metabolite annotation and quantification to assess the suitability of the platform for routine discovery metabolomics. Using both open source and vendor workflows, we validated the spectral matches with an in-house spectral library (Wake Forest CPM GC-MS spectral and retention time libraries) of EI-MS and CI-MS/MS spectra obtained from chemical standards. We confidently [metabolomics standards initiative (MSI) confidence level 2] identified 263, 93, and 65 metabolites using EI, PCI, and NCI modes, respectively, of which 270 metabolites (64%) were validated using our Wake Forest CPM GC-MS spectral libraries. When compared to published LC-MS-based efforts using the same NIST SRM 1950 plasma sample, there was only 17% overlap between the two platforms. In addition, the metabolomics analysis of community approved standard human plasma demonstrated the ability of EI- and CI-MS modes of analysis using a HRGC-MS platform to enable reproducible and interoperable spectral matching.

    更新日期:2020-01-26
  • Aspirin Reshapes Acetylomes in Inflammatory and Cancer Cells via CoA-Dependent and CoA-Independent Pathways
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-24
    Lin Guo; Jing Gao; Yang Gao; Zhengjiang Zhu; Yaoyang Zhang
    更新日期:2020-01-24
  • 更新日期:2020-01-24
  • 1H NMR-Based Metabolic Profiles Delineate the Anticancer Effect of Vitamin C and Oxaliplatin on Hepatocellular Carcinoma Cells
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-23
    Caigui Lin; Jiyang Dong; Zhiliang Wei; Kian-Kai Cheng; Jie Li; Song You; Yueyue Liu; Xiaomin Wang; Zhong Chen
    更新日期:2020-01-24
  • Pre-pregnant obesity of mothers in a multi-ethnic cohort is associated with cord blood metabolomic changes in offspring
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-24
    Ryan J. Schlueter; Fadhl M. Alakwaa; Paula A. Benny; Alexandra Gurary; Guoxiang Xie; Wei Jia; Shaw J. Chun; Ingrid Chern; Lana Garmire

    Maternal obesity has become a growing global health concern that may predispose the offspring to medical conditions later in life. However, the metabolic link between maternal pre-pregnant obesity and healthy offspring has not yet been fully elucidated. In this study, we conducted a case-control study using coupled untargeted and targeted metabolomics approach, from the newborn cord blood metabolomes associated with a matched maternal pre-pregnant obesity cohort of 28 cases and 29 controls. The subjects were recruited from multi-ethnic populations in Hawaii, including rarely reported Native Hawaiian and other Pacific Islanders (NHPI). We found that maternal obesity was the most important factor contributing to differences in cord blood metabolomics. Using elastic net regularization based logistic regression model, we identified 29 metabolites as potential early-life biomarkers manifesting intrauterine effect of maternal obesity, with accuracy as high as 0.947 after adjusting for clinical confounding (maternal and paternal age and ethnicity, parity and gravidity). We validated the model results in a subsequent set of samples (N=30) with an accuracy of 0.822. Among the metabolites, six metabolites (galactonic acid, butenylcarnitine, 2-hydroxy-3-methylbutyric acid, phosphatidylcholine diacyl C40:3, 1,5-anhydrosorbitol, and phosphatidylcholine acyl-alkyl 40:3) were individually and significantly different between the maternal obese vs. norm-weight groups. Interestingly, Hydroxy-3-methylbutyric acid showed significnatly higher levels in cord blood from the NHPI group, compared to asian and caucasian groups. In summary, significant associations were observed between maternal pre-pregnant obesity and offspring metabolomics alternation at birth, revealing the inter-generational impact of maternal obesity.

    更新日期:2020-01-24
  • EPIFANY - A method for efficient high-confidence protein inference
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-24
    Julianus Pfeuffer; Timo Sachsenberg; Tjeerd M. H. Dijkstra; Oliver Serang; Knut Reinert; Oliver Kohlbacher

    Accurate protein inference under the presence of shared peptides is still one of the key problems in bottom-up proteomics. Most protein inference tools employing simple heuristic inference strategies are efficient, but exhibit reduced accuracy. More advanced probabilistic methods often exhibit better inference quality but tend to be too slow for large data sets. Here we present a novel protein inference method, EPIFANY, combining a loopy belief propagation algorithm with convolution trees for efficient processing of Bayesian networks. We demonstrate that EPIFANY combines the reliable protein inference of Bayesian methods with significantly shorter runtimes. On the 2016 iPRG protein inference benchmark data EPIFANY is the only tested method which finds all true-positive proteins at a 5% protein FDR without strict pre-filtering on PSM level, yielding an increase in identification performance (+10% in the number of true positives and +14% in partial AUC) compared to previous approaches. Even very large data sets with hundreds of thousands of spectra (which are intractable with other Bayesian and some non-Bayesian tools) can be processed with EPIFANY within minutes. The increased inference quality including shared peptides results in better protein inference results and thus increased robustness of the biological hypotheses generated. EPIFANY is available as open-source software for all major platforms at https://OpenMS.de/epifany.

    更新日期:2020-01-24
  • Comparing 22 popular phosphoproteomics pipelines for peptide identification and site localization
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-24
    Marie Locard-Paulet; David Bouyssie; Carine Froment; Odile Burlet-Schiltz; Lars J. Jensen

    Phosphorylation-driven cell signaling governs most biological functions and is widely studied using mass spectrometry-based phosphoproteomics. Identifying the peptides and localizing the phosphorylation sites within them from the raw data is challenging and can be performed by several algorithms that return scores that are not directly comparable. This increases the heterogeneity among published phosphoproteomics data sets and prevents their direct integration. Here, we compare 22 pipelines implemented in the main software tools used for bottom-up phosphoproteomics analysis (MaxQuant, Proteome Discoverer, PeptideShaker). We test six search engines (Andromeda, Comet, Mascot, MS Amanda, SequestHT, and X!Tandem) in combination with several localization scoring algorithms (delta score, D-score, PTM-score, phosphoRS, and Ascore). We show that these follow very different score distributions, which can lead to different false localization rates for the same threshold. We provide a strategy to discriminate correctly from incorrectly localized phosphorylation sites in a consistent manner across the tested pipelines. The results presented here can help users choose the most appropriate pipeline and cutoffs for their phosphoproteomics analysis.

    更新日期:2020-01-24
  • BLOOD PLASMA METABOLOMICS PREDICTS PREGNANCY IN HOLSTEIN CATTLE TRANSFERRED WITH FRESH AND VITRIFIED/WARMED EMBRYOS PRODUCED IN VITRO
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-24
    Enrique Gómez; Pascal Salvetti; Julie Gatien; Susana Carrocera; David Martin-Gonzalez; Marta Muñoz

    Metabolomics may identify biomarkers in blood that differentiate pregnant from open embryo recipients. Fresh and vitrified/warmed, in-vitro produced embryos, were transferred to Holstein recipients (discovery group). Recipient blood plasma collected on Day-0 (estrus) and Day-7 (before embryo transfer) was analysed by nuclear magnetic resonance, (N=36 metabolites quantified). Metabolites whose concentrations differed between open and pregnant recipients were analysed [(P<0.05); FDR (P<0.05)]. Biomarkers were identified in Day-7 plasma (ROC-AUC>0.650; T-Test P<0.05; Random Forests, mean decrease accuracy) and cross-validated in independent Holstein, beef and crossbred recipients (overall classification accuracy –OCA-; P<0.05). Recipients with fresh embryos showed N=6 biomarkers consistently on Day-40, Day-62 and at birth. Recipients with vitrified embryos showed N=5 biomarkers on Day-40 and Day-62 but only one biomarker at birth. The most predictive biomarkers identified at birth within fresh embryos were Oxoglutaric acid (ROC-AUC=0.709; OCA=0.812) and Ornithine (ROC-AUC=0.731; OCA=0.727), while L-Glycine was identified in vitrified embryos (ROC-AUC=0.796; OCA=0.667) together with other predictive biomarkers not identified at birth (Day-62: L-Glutamine ROC-AUC= 0.757; OCA=0.767) and L-Lysine (Day-62: ROC-AUC=0.680; OCA=0.767). Pathway enrichment analysis distinguished between pregnant recipients for fresh (enriched energy oxidative metabolism from fat) and vitrified embryos (lower lipid metabolism). Metabolomics can select individuals which will become pregnant in a defined cycle.

    更新日期:2020-01-24
  • Quantitative Mitochondrial Proteomics Reveals ANXA7 as a Crucial Factor in Mitophagy
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-24
    Kun Meng; Shaohua Lu; Xin Yan; Yue Sun; Jing Gao; Yang Wang; Xingfeng Yin; Zhenghua Sun; Qing-Yu He

    Mitochondria are involved in many crucial cellular processes. Maintaining healthy mitochondria is essential for cellular homeostasis. Parkin-dependent mitophagy plays an important role in selectively eliminating damaged mitochondria in mammalian cells. However, mechanisms of Parkin-dependent mitophagy remain elusive. In this research, we performed data-independent acquisition (DIA)-based quantitative mitochondrial proteomics to study the proteomic alterations of carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced Parkin-mediated mitophagy. We identified 222 differentially expressed proteins, with 76 up-regulations and 146 down-regulations, which were potentially involved in mitophagy. We then demonstrated that annexin A7 (ANXA7), a calcium-dependent phospholipid-binding protein, can translocate to impaired mitochondria upon CCCP treatment, where it played a pivotal part in the process of Parkin-dependent mitophagy via interacting with BASP1. As a mitochondrial uncoupling agent, CCCP indirectly regulated ANXA7 and BASP1 to induce Parkin-dependent mitophagy. Keywords: mitochondrial proteomics, mitophagy, ANXA7

    更新日期:2020-01-24
  • Gain-Scanning for Protein Microarray Assays
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-23
    Feng Feng; Sila Toksoz Ataca; Mingxuan Ran; Yumei Wang; Michael Breen; Thomas B. Kepler
    更新日期:2020-01-23
  • MDMA hepatotoxicity under heat stress condition: novel insights from in vitro metabolomic studies
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-23
    Ana Margarida Araujo; Maria Enea; Eduarda Fernandes; Félix Carvalho; Maria de Lourdes Bastos; Marcia Carvalho; Paula Guedes de Pinho

    Hyperthermia has been extensively reported as a life-threatening consequence of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) abuse. In this work, we used a sensitive untargeted metabolomic approach based on gas chromatography-mass spectrometry to evaluate the impact of hyperthermia on the hepatic metabolic changes caused by MDMA. For this purpose, primary mouse hepatocytes were exposed to subtoxic (LC01 and LC10) and toxic (LC30) concentrations of MDMA for 24 h, at 37.0 °C or 40.5 °C (simulating body temperature increase after MDMA consumption), and alterations on both intracellular metabolome and extracellular volatilome were evaluated. Multivariate analysis showed that metabolic patterns clearly discriminate MDMA treated cells from control cells, both in normothermic and hyperthermic conditions. Metabolic signature was found to be largely common to MDMA subtoxic and toxic concentrations, although with evident differences in the magnitude of response, with metabolic changes significantly more pronounced at 40.5 °C. Discriminant metabolites associated with MDMA-induced hepatotoxicity are mostly involved in amino acids metabolism, aminoacyl tRNA byosynthesis, glutathione metabolism, tricarboxylic acid cycle and pyruvate metabolism. Moreover, our metabolomic findings were corroborated by classical toxicity parameters, demonstrating the high sensitivity of this omic approach to assess molecular-level effects. Overall, this study indicates that MDMA triggers significant metabolic alterations on hepatic cells, even at low concentrations, that are clearly exacerbated at high temperatures. These findings provide new metabolic pieces to solve the puzzle of MDMA’s hepatotoxicity mechanism and emphasize the increased risks of MDMA abuse due to the thermogenic action of the drug.

    更新日期:2020-01-23
  • NETGE-PLUS: standard and network-based gene enrichment analysis in human and model organisms
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-23
    Samuele Bovo; Pier Luigi Martelli; Pietro Di Lena; Rita Casadio

    Omics techniques provide a spectrum of information at the genomic level, whose analysis can characterize complex traits at a molecular level. The relationship among genotype and phenotype implies that from genome information the molecular pathways and biological processes underlaying a given phenotype are discovered. In dealing with this problem, gene enrichment analysis has become the most widely adopted strategy. Here, we present NETGE-PLUS, a web-server for standard and network-based functional interpretation of gene sets of human and of model organisms, including Sus scrofa, Saccharomyces cerevisiae, Escherichia coli and Arabidopsis thaliana. NETGE-PLUS enables the functional enrichment of both simple and ranked lists of genes, introducing also the possibility of exploring relationships among KEGG pathways. A web interface makes data retrieval complete and user-friendly. NETGE-PLUS is publicly available at http://net-ge2.biocomp.unibo.it

    更新日期:2020-01-23
  • Mass Spectrometry-Based Identification of Phospho-Tyr in Plant Proteomics
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-22
    Nagib Ahsan; Rashaun S. Wilson; R. Shyama Prasad Rao; Fernanda Salvato; Mercy Sabila; Hemayet Ullah; Ján A. Miernyk
    更新日期:2020-01-23
  • Top-Down and Bottom-Up Proteomics of Circulating S100A8/S100A9 in Plasma of Septic Shock Patients
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-22
    Christelle Dubois; Didier Payen; Stéphanie Simon; Christophe Junot; François Fenaille; Nathalie Morel; François Becher
    更新日期:2020-01-23
  • Lipid profiling of serum and lipoprotein fractions in response to pitavastatin using an animal model of familial hypercholesterolemia
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-22
    Hiroaki Takeda; Yoshihiro Izumi; Shohei Tamura; Tomonari Koike; Ying Yu; Masashi Shiomi; Takeshi Bamba

    Statins are widely used for the treatment of atherosclerotic cardiovascular diseases. They inhibit cholesterol biosynthesis in the liver and cause pleiotropic effects including anti-inflammatory and antioxidant effects. To develop novel therapeutic drugs, the effect of blood-borne lipid molecules on the pleiotropic effects of statins must be elucidated. Myocardial-infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for hypercholesterolemia, are suitable for the determination of lipid molecules in blood in response to statins because their lipoprotein metabolism is similar to that of humans. Herein, lipid molecules were investigated by lipidome analysis in response to pitavastatin using WHHLMI rabbits. Various lipid molecules in the blood were measured using a supercritical fluid chromatography triple quadrupole mass spectrometry. Cholesterol and cholesterol ester blood levels decreased by reducing the secretion of very low density lipoproteins from the liver. Independent of the inhibition effects of cholesterol biosynthesis, the concentrations of some lipids with anti-inflammation and antioxidant effects (phospholipid molecules with n-6 fatty acid side chains, lysophosphatidylcholines, phosphatidylethanolamine plasmalogens, and ceramide molecules) were significantly altered. These findings may lead to further investigation of the mechanism of statin action.

    更新日期:2020-01-23
  • Impact of an antifungal insect defensin on the proteome of the phytopathogenic fungus Botrytis cinerea
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-22
    Thomas Aumer; Sebastien Voisin; Thomas Knobloch; Céline Landon; Philippe Bulet

    ETD151, an analogue of the antifungal insect defensin heliomicin, is an antifungal peptide active against yeasts and filamentous fungi. In order to decipher the mechanisms underlying its molecular action on the phytopathogenic fungus Botrytis cinerea, a necrotrophic pathogen responsible for gray mold disease, we investigated the changes in three-day old mycelia upon treatment with different concentrations of ETD151. Optical and fluorescent microscopies were used prior to establishing the peptide/protein profiles through two mass spectrometry approaches: MALDI profiling, to generate molecular mass fingerprints as peptide signatures, and a gel-free bottom-up proteomics approach. Our results show that a concentration of ETD151 above the half-maximal inhibitory concentration can alter the integrity of the mycelial structure of B. cinerea. Furthermore, reproducible modifications of the peptide/protein composition were demonstrated in the presence of ETD151 within a 1,500 – 16,000 mass (m/z) range. After the robustness of LC-ESI-MS/MS analysis on B. cinerea mycelial extracts was confirmed, our analyses highlighted 340 significantly modulated proteins upon treatment with ETD151 within a 4.8 – 466 kDa mass range. Finally, data mapping on KEGG pathways revealed the molecular impact of ETD151 on at least six pathways, namely spliceosome, ribosome, protein processing in endoplasmic reticulum, endocytosis, MAPK signaling pathway and oxidative phosphorylation.

    更新日期:2020-01-23
  • Metabolomic Profiling of the Synergistic Effects of Ginsenoside Rg1 in Combination with Neural Stem Cell Transplantation in Ischemic Stroke Rats
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-22
    Jian Gao; Peng Bai; Yuanyuan Li; Jingzhong Li; Caixia Jia; Tieshan Wang; Haibin Zhao; Yinchu Si; Jianxin Chen

    As the greatest medical and socioeconomic problem in developing countries, stroke is the second or third leading cause of death in China and worldwide. In adult organisms suffering from stroke, transplanted stem cell has the ability to repair damaged tissues by regenerating autologous cells, while ginsenoside Rg1 could promote proliferation and differentiation of stem cells. Although obvious anti-stroke effects of ginsenoside Rg1 and transplanted stem cells have been verified in publications, the mechanism exploration remained challenging. Our study was carried out to investigate the synergistic effects of ginsenoside Rg1 and neural stem cell (NSC) transplantation on MCAO rats with a 1H NMR-based non-targeted metabolomics methods to identify potential biomarkers and protein targets and discover the potential mechanism. NSCs transplantation after MCAO combined with ginsenoside Rg1 administration could significantly improve the cerebral infract and neurological deficits. The treatment significant intervened the levels of ten metabolites, and perturbed energy metabolism, amino acids metabolism and lipids metabolism. And 11 enzymes were identified and verified as the targets of NSCs transplantation and ginsenoside Rg1 administration on MCAO rats. Our findings helped to improve the anti-stroke mechanism of NSCs transplantation and ginsenoside Rg1 and supply a theory basis for the combined research of stem cell and Chinese medicine in future.

    更新日期:2020-01-23
  • 更新日期:2020-01-21
  • Differential Network Analysis Reveals Metabolic Determinants Associated with Mortality in Acute Myocardial Infarction Patients and Suggests Potential Mechanisms Underlying Different Clinical Scores Used To Predict Death
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-17
    Alessia Vignoli; Leonardo Tenori; Betti Giusti; Serafina Valente; Nazario Carrabba; Daniela Balzi; Alessandro Barchielli; Niccolò Marchionni; Gian Franco Gensini; Rossella Marcucci; Anna Maria Gori; Claudio Luchinat; Edoardo Saccenti
    更新日期:2020-01-21
  • Quantitative Characterization of the Neuropeptide Level Changes in Dorsal Horn and Dorsal Root Ganglia Regions of the Murine Itch Models
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-19
    Emily G. Tillmaand; Krishna D.B. Anapindi; Eduardo De La Toba; Changxiong J. Guo; Jessica Krebs; Ashley E. Lenhart; Qin Liu; Jonathan V. Sweedler

    Chronic itch can be extremely devastating and, in many cases, difficult to treat. One challenge in treating itch disorders is the limited understanding of the multitude of chemical players involved in the communication of itch sensation from the peripheral to central nervous system. Neuropeptides are intercellular signaling molecules that are known to be involved in the transmission of itch signals from primary afferent neurons, which detect itch in the skin, to higher-order circuits in the spinal cord and brain. To investigate the role neuropeptides play in transmitting itch signals, we generated two mouse models of chronic itch—Acetone-Ether-Water (AEW, dry skin) and calcipotriol (MC903, atopic dermatitis). For peptide identification and quantitation, we analyzed the peptide content of dorsal root ganglia (DRG) and dorsal horn (DH) tissues from chronically itchy mice using liquid chromatography coupled to tandem mass spectrometry. De novo-assisted database searching facilitated the identification and quantitation of 335 peptides for DH MC903, 318 for DH AEW, 266 for DRG MC903, and 271 for DRG AEW. Of these quantifiable peptides, we detected 30 that were differentially regulated in the tested models, after accounting for multiple testing correction (q<0.1). These include several peptide candidates derived from neuropeptide precursors, such as proSAAS, protachykinin-1, proenkephalin and calcitonin gene-related peptide, some of them previously linked to itch. The peptides identified in this study may help elucidate our understanding about these debilitating disorders. Data are available via ProteomeXchange with identifier PXD015949.

    更新日期:2020-01-21
  • Quantitative Proteome Responses to Oncolytic Reovirus in GM-CSF- and M-CSF-Differentiated Bone Marrow-Derived Cells
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-17
    Michael A. Giacomantonio; Andra M. Sterea; Youra Kim; Joao A. Paulo; Derek R. Clements; Barry E. Kennedy; Moamen J. Bydoun; Ge Shi; David M. Waisman; Steven P. Gygi; Carman A. Giacomantonio; J. Patrick Murphy; Shashi Gujar
    更新日期:2020-01-17
  • 更新日期:2020-01-17
  • IKK-mediated Regulation of the COP9 Signalosome via Phosphorylation of CSN5
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-17
    Jingzi Zhang; Ruoyu Zhao; Clinton Yu; Christine L. N. Bryant; Kenneth Wu; Zhihong Liu; Yibing Ding; YUE ZHAO; Bin Xue; Zhen-Qiang Pan; Chaojun Li; Lan Huang; Lei Fang

    The COP9 signalosome (CSN) is an evolutionarily conserved multi-subunit protein complex, which controls protein degradation through deneddylation and inactivation of cullin-RING ubiquitin E3 ligases (CRLs). Recently, the CSN complex has been linked to the NF-κB signaling pathway due to its association with the IKK complex. However, how the CSN complex is regulated in this signaling pathway remains unclear. Here, we have carried out biochemical experiments and confirmed the interaction between the CSN and IKK complexes. In addition, we have determined that overexpression of IKKα or IKKβ leads to enhanced phosphorylation of CSN5, the catalytic subunit for CSN deneddylase activity. Mutational analyses have revealed that phosphorylation at serine 201 and threonine 205 of CSN5 impairs CSN-mediated deneddylation activity in vitro. Interestingly, TNF-α treatment not only enhances the interaction between CSN and IKK, but also induces an IKK-dependent phosphorylation of CSN5 at serine 201, linking CSN to TNF-α signaling through IKK. Moreover, TNF-α treatment affects CSN interaction network globally, especially the associations of CSN with the proteasome complex, eukaryotic translation initiation factor complex and CRL components. Collectively, our results provide new insights into IKK-mediated regulation of CSN associated with NF-κB signaling pathway.

    更新日期:2020-01-17
  • Global Metabolomic and Lipidomic Analysis Reveal the Synergistic Effect of Bufalin in Combination with Cinobufagin against HepG2 Cells
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-16
    Jinghui Zhang; Yanjun Hong; Lilong Jiang; Xiaojiao Yi; Yang Chen; Li Liu; Zhongjian Chen; Yongjiang Wu; Zongwei Cai

    Chansu, which is prepared from the skin secretions of toad (Bufo bufo gargarizans Cantor), is widely used in traditional Chinese medicine (TCM). Being the principal bioactive constituents of ChanSu, bufalin (BFL) and cinobufagin (CBF), have been shown to possess anticancer properties. TCM confer bioactivities through the synergistic effect between potential active ingredients, so as to interfere with the development of the disease, and ultimately achieve the therapeutic effect. We found that the anticancer effect was significantly potentiated by co-treatment of BFL and CBF as compared to mono-treatment, suggesting their synergistic interaction. To reveal their synergistic mechanisms, metabolomic and lipidomic profiling based on liquid chromatography-mass spectrometry (LC–MS) were utilized to delineate the responses in HepG2 cells after treatment with BFL and CBF individually or in combination. Metabolic pathways including methionine metabolism, energy metabolism, lipid metabolism and amino acid metabolism were modulated and subsequently lead to apoptosis and cell cycle arrest of HepG2 cells. In particular, the discrepant regulation of methionine metabolism between mono-treatment and co-treatment of BFL and CBF may account for their synergistic effect. Our study provided novel insights into the mechanistic links between cellular metabolism and synergistic effect, which may ultimately lead to better treatments for hepatoma.

    更新日期:2020-01-16
  • Alterations of brain quantitative proteomics profiling revealed the molecular mechanisms of diosgenin against cerebral ischemia reperfusion effects
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-15
    Xinxin Zhang; Xingbin Wang; Muhammad Khurm; Guanqun Zhan; Hui Zhang; Yoichiro Ito; Zengjun Guo

    Diosgenin (DIO), the starting material for the synthesis of steroidal anti-inflammatory drugs in pharmaceutical industry, has been previously demonstrated to display pharmaceutical effects against cerebral ischemic reperfusion (I/R). However, the alterations of brain proteome profiles underlying this treatment remain elusive. In the present study, the proteomics analysis of the brain tissues from I/R rats after DIO treatment was performed by an integrated TMT-based quantitative proteomic approach coupled with LC-MS/MS technology. A total of 5043 proteins (ProteomeXchange identifier: PXD016303) were identified, of which 58 common differentially expressed proteins (DEPs) were significantly dysregulated in comparison between Sham verse I/R and I/R verse DIO. The 8 validated proteins including EPG5, STAT2, CPT1A, EIF2AK2, GGCT, HIKESHI, TNFAIP8, and EMC6 by qPCR and Western blotting consistently supported the TMT-based proteomic results, which were mainly associated with autophagy and inflammation response. Considering the anti-inflammatory characters of DIO, the biological functions of STAT2 and HIKESHI that are the probably direct anti-inflammatory targets were further investigated during the course of I/R treated with DIO. In addition, the combination of verified STAT2 and HIKESHI in peripheral blood samples from stroke patients resulted in AUC value of 0.765 with P<0.004 to distinguish stroke patients from healthy controls. Taken together, the current findings firstly mapped comprehensive proteomic changes after I/R treated with DIO to better decipher the molecular mechanisms mainly based on anti-inflammatory aspect underlying this therapeutic effect, providing a foundation for developing potentially therapeutic targets of anti-I/R of DIO and clinically prognostic biomarkers of stroke.

    更新日期:2020-01-16
  • Elucidating proteoform dynamics underlying the senescence associated secretory phenotype
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-15
    Peter F. Doubleday; Luca Fornelli; Neil L Kelleher

    Primary diploid cells exit the cell cycle in response to exogenous stress or oncogene activation through a process known as cellular senescence. This cell-autonomous tumor suppressive mechanism is also a major mechanism operative in organismal aging. To date, temporal aspects of senescence remain understudied. Therefore, we use quantitative proteomics to investigate changes following forced HRASG12V expression and induction of senescence across one week in normal diploid fibroblasts. We demonstrate that global intracellular proteomic changes correlate with the emergence of the senescence associated secretory phenotype (SASP) and the switch to robust cell cycle exit. The senescence secretome reinforces cell cycle exit yet is largely detrimental to tissue homeostasis. Previous studies of secretomes rely on ELISAs, bottom-up proteomics or RNA-seq. To date, no study to date has examined the proteoform complexity of secretomes to elucidate isoform-specific, post-translational modifications or regulated cleavage of signal peptides. Therefore, we use a quantitative top-down proteomics approach to define the molecular complexity of secreted proteins <30 kDa. We identify multiple forms of immune regulators with known activities and affinities such as distinct forms of interleukin-8, as well as GROα and HMGA1, and temporally-resolve secreted proteoform dynamics. Together, our work demonstrates the complexity of the secretome past individual protein accessions and provides motivation for further proteoform-resolved measurements of the secretome.

    更新日期:2020-01-16
  • Glyco-CPLL: An Integrated Method for In-Depth and Comprehensive N-Glycoproteome Profiling of Human Plasma
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-14
    Yong Zhang; Yonghong Mao; Wanjun Zhao; Tao Su; Yi Zhong; Linru Fu; Jingqiang Zhu; Jingqiu Cheng; Hao Yang
    更新日期:2020-01-15
  • HYPERsol: High-Quality Data from Archival FFPE Tissue for Clinical Proteomics
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-14
    Dylan M. Marchione; Ilyana Ilieva; Kyle Devins; Danielle Sharpe; Darryl J. Pappin; Benjamin A. Garcia; John P. Wilson; John B. Wojcik
    更新日期:2020-01-15
  • Systematic Comparison of Label-Free, SILAC, and TMT Techniques to Study Early Adaption toward Inhibition of EGFR Signaling in the Colorectal Cancer Cell Line DiFi
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-14
    Markus Stepath; Birgit Zülch; Abdelouahid Maghnouj; Karin Schork; Michael Turewicz; Martin Eisenacher; Stephan Hahn; Barbara Sitek; Thilo Bracht
    更新日期:2020-01-15
  • Integrating Serum Protein Electrophoresis with Mass Spectrometry, A New Workflow for M-Protein Detection and Quantification
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-14
    Marina Zajec; Joannes F. M. Jacobs; Corrie M. de Kat Angelino; Lennard J. M. Dekker; Christoph Stingl; Theo M. Luider; Yolanda B. De Rijke; Martijn M. VanDuijn
    更新日期:2020-01-15
  • Integrated Univariate, Multivariate, and Correlation-Based Network Analyses Reveal Metabolite-Specific Effects on Bacterial Growth and Biofilm Formation in Necrotizing Soft Tissue Infections
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-14
    Muhammad Afzal; Edoardo Saccenti; Martin Bruun Madsen; Marco Bo Hansen; Ole Hyldegaard; Steinar Skrede; Vitor A. P. Martins dos Santos; Anna Norrby-Teglund; Mattias Svensson
    更新日期:2020-01-14
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  • Proteomic analysis of MYB-regulated secretome identifies functional pathways and biomarkers: potential pathobiological and clinical implications
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-13
    Haseeb Zubair; Girijesh Kumar Patel; Mohammad Aslam Khan; Shafquat Azim; Asif Zubair; Seema Singh; Sanjeev Kumar Srivastava; Ajay Pratap Singh

    Earlier we have shown important roles of MYB in pancreatic tumor pathobiology. To better understand the role of MYB in the tumor microenvironment and identify MYB-associated secreted biomarker proteins, we conducted mass spectrometry analysis of the secretome from MYB-modulated and control pancreatic cancer cell lines. We also performed in silico analyses to determine MYB-associated biofunctions, gene networks and altered biological pathways. Our data demonstrated significant modulation (p < 0.05) of 337 secreted proteins in MYB-silenced MiaPaCa cells whereas 282 proteins were differentially present in MYB-overexpressing BxPC3 cells, compared to their respective control cells. Alteration of several phenotypes such as cellular movement, cell death and survival, inflammatory response, protein synthesis etc. was associated with MYB-induced differentially expressed proteins (DEPs) in secretomes. DEPs from MYB-silenced MiaPaCa PC cells were suggestive of the downregulation of genes primarily associated with glucose metabolism, PI3K/AKT signaling and oxidative stress response, among others. DEPs from MYB-overexpressing BxPC3 cells suggested enhanced release of proteins associated with glucose metabolism and cellular motility. We also observed that MYB positively regulated the expression of four proteins with potential biomarker properties, i.e. FLNB, ENO1, ITGB1 and INHBA. Mining of publicly available databases using Oncomine and UALCAN demonstrated that these genes are overexpressed in pancreatic tumors and associated with reduced patient’s survival. Altogether, these data provide novel avenues for future investigations on diverse biological functions of MYB, specifically in the tumor microenvironment, and could also be exploited for biomarker development.

    更新日期:2020-01-14
  • Comparative Membrane N-Glycomics of Different Breast Cancer Cell Lines To Understand Breast Cancer Brain Metastasis
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-13
    Wenjing Peng; Parvin Mirzaei; Rui Zhu; Shiyue Zhou; Yehia Mechref
    更新日期:2020-01-13
  • Serum Metabolomics Reveals Personalized Metabolic Patterns for Macular Neovascular Disease Patient Stratification
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-09
    Kun Liu; Junwei Fang; Jing Jin; Shaopin Zhu; Xiaoyin Xu; Yupeng Xu; Bin Ye; Shu-Hai Lin; Xun Xu
    更新日期:2020-01-10
  • Discovery of potential serum protein biomarkers in Ankylosing Spondylitis using TMT-based quantitative proteomics
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-09
    Shijia Liu; Wei Ji; Jiawei Lu; Xiaojun Tang; Yunke Guo; Mingde Ji; Tian Xu; Wanjian Gu; Deshun Kong; Qiuxiang Shen; Dandan Wang; Xiangyu Lv; Jue Wang; Tianyao Zhu; Youjuan Zhu; Ping Liu; Jinfeng Su; Lu Wang; Yuhua Li; Pan Gao; Wei Liu; Lingyun Sun; Xiaojian Yin; Wei Zhou

    Ankylosing Spondylitis (AS) is a systemic, chronic and inflammatory rheumatic disease that affects 0.2% of the population. Current diagnostic criteria for disease activity rely on subjective Bath Ankylosing Spondylitis Disease Activity Index scores. Here, we aimed to discover a panel of serum protein biomarkers. First, TMT-based quantitative proteomics was applied to identify differential proteins between 15 pooled active AS and 60 pooled healthy subjects. Second, cohort 1 of 328 humans, including 138 active AS and 190 healthy subjects from 2 independent centers, was used for biomarker discovery and validation. Finally, biomarker panels were applied to differentiate among active AS, stable AS and healthy subjects from cohort 2, which enrolled 28 patients with stable AS, 26 with active AS and 28 healthy subjects. From the proteomics study, a total of 762 proteins were identified, and 46 proteins were up-regulated and 59 proteins were down-regulated in active AS patients compared to healthy persons. Among them, C-reactive protein (CRP), Complement factor H-related protein 3 (CFHR3), alpha-1-acid glycoprotein 2 (ORM2), serum amyloid A1 (SAA1), fibrinogen gamma (FG-γ) and fibrinogen beta (FG-β) were the most significantly up-regulated inflammation-related proteins; S100A8, fatty acid-binding protein 5 (FABP5) and thrombospondin 1 (THBS1) were the most significantly down-regulated inflammation-related proteins. From cohort 1 study, the best panel for diagnosis of active AS vs healthy subjects is combination of CRP and SAA1. The area under the receiver operating characteristic (ROC) curve was nearly 0.900. The sensitivity was 0.970 and the specificity was 0.805 at a 95% confidence interval from 0.811 to 0.977. Using 0.387 as the cut-off value, the predictive values reached 92.00% in the internal validation set (62 with active AS vs 114 healthy subjects) and 97.50% in the external validation phase (40 with active AS vs 40 healthy subjects). From cohort 2 study, a panel of CRP and SAA1 can differentiate well among active AS, stable AS and healthy subjects. For active AS vs stable AS, the area under the ROC curve was 0.951, the sensitivity was 96.43%, the specificity was 88.46% at a 95% confidence interval from 0.891 to 1, and the coincidence rate was 92.30%. For stable AS vs healthy humans, the area under the ROC curve was 0.908, the sensitivity was 89.29%, the specificity was 78.57% at a 95% confidence interval from 0.836 to 0.980, and the coincidence rate was 83.93%. For active AS vs healthy subjects, the predictive value was 94.44%. The results indicated that the CRP and SAA1 combination can potentially diagnose disease status, especially for active or stable AS, which will be conducive to treatment recommendation for patients with AS.

    更新日期:2020-01-10
  • Host Metabolic Response in Early Lyme Disease
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-09
    Bryna L. Fitzgerald; Claudia R. Molins; M. Nurul Islam; Barbara Graham; Petronella R. Hove; Gary P. Wormser; Linden Hu; Laura V. Ashton; John T. Belisle
    更新日期:2020-01-09
  • In Situ Metabolomics of the Honeybee Brain: The Metabolism of l-Arginine through the Polyamine Pathway in the Proboscis Extension Response (PER)
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-09
    Marcel Pratavieira; Anally Ribeiro da Silva Menegasso; Thaisa Roat; Osmar Malaspina; Mario Sergio Palma
    更新日期:2020-01-09
  • Fecal Metabolomics as a Novel Noninvasive Method for Short-Term Stress Monitoring in Beef Cattle
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-09
    Azzurra Valerio; Luca Casadei; Alessandro Giuliani; Mariacristina Valerio
    更新日期:2020-01-09
  • Evaluation of Injury Degree of Adriamycin-Induced Nephropathy in Rats Based on Serum Metabolomics Combined with Proline Marker
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-09
    Ai-Ping Li; Liu Yang; Li-Chao Zhang; Sheng-Sheng He; Jin-Ping Jia; Xue-Mei Qin
    更新日期:2020-01-09
  • Evaluation of Tumor Interstitial Fluid-Extraction Methods for Proteome Analysis: Comparison of Biopsy Elution versus Centrifugation
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-08
    Clara Matas-Nadal; Joan Josep Bech-Serra; Marta Guasch-Vallés; Josep Manel Fernández-Armenteros; Carla Barceló; Josep Manel Casanova; Carolina de la Torre Gómez; Rafael Aguayo Ortiz; Eloi Garí
    更新日期:2020-01-09
  • Comparative Proteomic Analysis of Histone Modifications upon Acridone Derivative 8a-Induced CCRF-CEM Cells by Data Independent Acquisition
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-07
    Yini Wang; Caixia Xu; Bowen Zhong; Dongdong Zhan; Mingwei Liu; Dan Gao; Yi Wang; Jun Qin
    更新日期:2020-01-09
  • Quantitative Analysis of in Vivo Methionine Oxidation of the Human Proteome
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-07
    John Q. Bettinger; Kevin A. Welle; Jennifer R. Hryhorenko; Sina Ghaemmaghami
    更新日期:2020-01-07
  • Ion-Pairing with Triethylammonium Acetate Improves Solid-Phase Extraction of ADP-Ribosylated Peptides
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-07
    Robert Lyle McPherson; Shao-En Ong; Anthony K. L. Leung
    更新日期:2020-01-07
  • TulsiPIN: An Interologous Protein Interactome of Ocimum tenuiflorum
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-06
    Vikram Singh; Gagandeep Singh; Vikram Singh
    更新日期:2020-01-07
  • Quantitative Proteomics Reveal an Altered Pattern of Protein Expression in Brain Tissue from Mice Lacking GPR37 and GPR37L1
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-05
    TrangKimberly Thu Nguyen; Eric B. Dammer; Sharon A Owino; Michelle M Giddens; Nora S Madaras; Duc M. Duong; Nicholas T. Seyfried; Randy A. Hall

    GPR37 and GPR37L1 are glia-enriched GPCRs that have been implicated in several neurological and neurodegenerative diseases. To gain insight into the potential molecular mechanisms by which GPR37 and GPR37L1 regulate cellular physiology, proteomic analyses of whole mouse brain tissue from wild-type (WT) versus GPR37/GPR37L1 double knockout (DKO) mice were performed in order to identify proteins regulated by the absence versus presence of these receptors (data are available via ProteomeXchange with identifier PXD015202). These analyses revealed a number of proteins that were significantly increased or decreased by the absence of GPR37 and GPR37L1. One of the most decreased proteins in the DKO versus WT brain tissue was S100A5, a calcium-binding protein, and the reduction of S100A5 expression in KO brain tissue was validated via Western blot. Co-expression of S100A5 with either GPR37 or GPR37L1 in HEK293T cells did not result in any change in S100A5 expression but did robustly increase secretion of S100A5. To dissect the mechanism by which S100A5 secretion was enhanced, cells co-expressing S100A5 with the receptors were treated with different pharmacological reagents. These studies revealed that calcium is essential for the secretion of S100A5 downstream of GPR37 and GPR37L1 signaling, as treatment with BAPTA-AM, an intracellular Ca2+ chelator, reduced S100A5 secretion from transfected HEK293T cells. Collectively these findings provide a panoramic view of proteomic changes resulting from loss of GPR37 and GPR37L1 and also impart mechanistic insight into the regulation of S100A5 by these receptors, thereby shedding light on the functions of GPR37 and GPR37L1 in brain tissue.

    更新日期:2020-01-06
  • Untargeted Proteomics-Based Profiling for the Identification of Novel Processing-Induced Protein Modifications in Milk
    J. Proteome Res. (IF 3.780) Pub Date : 2020-01-05
    Jasmin Meltretter; Johannes Wüst; Daniel Dittrich; Johannes Lach; Jonas Ludwig; Jutta Eichler; Monika Pischetsrieder

    Nonenzymatic post-translational protein modifications (nePTMs) affect the nutritional, physiological, and technological properties of proteins in food and in vivo. In contrast to the usual targeted analyses, the present study determined nePTMs in processed milk in a truly untargeted proteomic approach. Thus, it was possible to determine to which extent known nePTM structures explain protein modifications in processed milk and to detect and identify novel products. The method combined ultrahigh-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UHPLC–ESI–MS/MS) with bioinformatic data analysis by the software XCMS. The nePTMs detected by untargeted profiling of a β-lactoglobulin–lactose model were incorporated in a sensitive scheduled multiple reaction monitoring (sMRM) method to analyze these modifications in milk samples and to monitor their reaction kinetics during thermal treatment. Additionally, we identified the structures of unknown modifications. Lactosylation, carboxymethylation, formylation of lysine and N-terminus, glycation of arginine, oxidation of methionine, tryptophan and cysteine, oxidative deamination of N-terminus, and deamidation of asparagine and glutamine were the most important reactions of β-lactoglobulin during milk processing. The isomerization of aspartic acid and N-formyllysine were observed for the first time in milk products and N-terminal 4-imidazolidinone was identified as a novel nePTM.

    更新日期:2020-01-06
  • Quantitative Proteomics Reveals the Protective Effects of Huangqi Decoction Against Acute Cholestatic Liver Injury by Inhibiting the NF-κB/IL-6/STAT3 Signaling Pathway
    J. Proteome Res. (IF 3.780) Pub Date : 2019-12-31
    Jia-Sheng Wu; Qian Liu; Shan-Hua Fang; Xing Liu; Min Zheng; Tian-Ming Wang; Hua Zhang; Ping Liu; Hu Zhou; Yue-Ming Ma
    更新日期:2020-01-01
  • Longitudinal transcriptomic, proteomic, and metabolomic analyses of Citrus sinensis (L.) Osbeck graft-inoculated with ‘Candidatus Liberibacter asiaticus’
    J. Proteome Res. (IF 3.780) Pub Date : 2019-12-29
    Elizabeth L Chin; John S. Ramsey; Darya O Mishchuk; Surya Saha; Elizabeth Foster; Juan D. Chavez; Kevin Howe; Xuefei Zhong; MaryLou Polek; Kris E. Godfrey; Lukas Mueller; James E. Bruce; Michelle Heck; Carolyn M Slupsky

    “Candidatus Liberibacter asiaticus” (CLas) is the bacterium associated with the citrus disease Huanglongbing (HLB). Current CLas detection methods are unreliable during presymptomatic infection, and understanding CLas pathogenicity to help develop new detection techniques is challenging because CLas has yet to be isolated in pure culture. To understand how CLas affects citrus metabolism and whether infected plants produce systemic signals that can be used to develop improved detection techniques, leaves from Washington Navel orange (Citrus sinensis (L.) Osbeck) plants were graft-inoculated with CLas and longitudinally studied using transcriptomics (RNA-seq), proteomics (LC-MS/MS), and metabolomics (1H NMR). Photosynthesis gene expression and protein levels were lower in infected plants compared to controls during late infection, and lower levels of photosynthesis proteins were identified as early as 8 weeks post-grafting. These changes coordinated with higher sugar concentrations, which have been shown to accumulate during HLB. Cell wall modification and degradation gene expression and proteins were higher in infected plants during late infection. Changes in gene expression and proteins related to plant defense were observed in infected plants as early as 8 weeks post-grafting. These results reveal coordinated changes in greenhouse navel leaves during CLas infection at the transcript, protein, and metabolite levels, which can inform of biomarkers of early infection.

    更新日期:2019-12-30
  • Bisphenol A Activates an Innate Viral Immune Response Pathway
    J. Proteome Res. (IF 3.780) Pub Date : 2019-12-27
    Mark L. Sowers; Hui Tang; Bing Tian; Randall Goldblum; Terumi Midoro-Horiuti; Kangling Zhang
    更新日期:2019-12-29
  • Using Multiple Analytical Platforms to Investigate the Androgen Depletion Effects on Fecal Metabolites in a Mouse Model of Systemic Lupus Erythematosus
    J. Proteome Res. (IF 3.780) Pub Date : 2019-12-27
    Fang Yuan; James Harder; Jing Ma; Xinmin Yin; Xiang Zhang; Michele M. Kosiewicz
    更新日期:2019-12-29
  • Comparison of Statistical Tests and Power Analysis for Phosphoproteomics Data
    J. Proteome Res. (IF 3.780) Pub Date : 2019-12-26
    Lei J. Ding; Hannah M. Schlüter; Matthew J. Szucs; Rushdy Ahmad; Zheyang Wu; Weifeng Xu
    更新日期:2019-12-27
  • UPLC–QTOF-MS-Based Plasma Lipidomic Profiling Reveals Biomarkers for Inflammatory Bowel Disease Diagnosis
    J. Proteome Res. (IF 3.780) Pub Date : 2019-12-26
    Su Guan; Bingjie Jia; Kang Chao; Xia Zhu; Jian Tang; Miao Li; Lvying Wu; Lei Xing; Kun Liu; Lei Zhang; Xueding Wang; Xiang Gao; Min Huang
    更新日期:2019-12-27
  • Quantitative Proteomics Combined with Two Genetic Strategies for Screening Substrates of Ubiquitin Ligase Hrt3
    J. Proteome Res. (IF 3.780) Pub Date : 2019-12-23
    Qiuyan Lan; Yihao Wang; Zhen Sun; Yanchang Li; Cheng Zhang; Lei Chang; Yue Gao; Junzhu Wu; Fuqiang Wang; Ping Xu
    更新日期:2019-12-23
  • Comparative Proteomics Unravels the Differences in Salt Stress Response of Own-Rooted and 110R-Grafted Thompson Seedless Grapevines
    J. Proteome Res. (IF 3.780) Pub Date : 2019-12-20
    Sucheta Patil; Manisha Shinde; Ramya Prashant; Narendra Kadoo; Anuradha Upadhyay; Vidya Gupta
    更新日期:2019-12-21
  • In Situ Structural Restraints from Cross-Linking Mass Spectrometry in Human Mitochondria
    J. Proteome Res. (IF 3.780) Pub Date : 2019-12-19
    Petra S. J. Ryl; Michael Bohlke-Schneider; Swantje Lenz; Lutz Fischer; Lisa Budzinski; Marchel Stuiver; Marta M. L. Mendes; Ludwig Sinn; Francis J. O’Reilly; Juri Rappsilber
    更新日期:2019-12-19
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