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Journal of Proteome Research

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https://www.readbyqxmd.com/read/28653853/post-translational-modifications-ptms-identified-on-endogenous-huntingtin-cluster-within-proteolytic-domains-between-heat-repeats
#1
Tamara Ratovitski, Robert N O'Meally, Mali Jiang, Raghothama Chaerkady, Ekaterine Chighladze, Jacqueline C Stewart, Xiaofang Wang, Nicolas Arbez, Elaine Roby, Athanasios Alexandris, Wenzhen Duan, Ravi Vijayvargia, Ihn Sik Seong, Daniel J Lavery, Robert N Cole, Christopher A Ross
Post-translational modifications (PTMs) of proteins regulate various cellular processes. PTMs of polyglutamine-expanded huntingtin (Htt) protein, which causes Huntington's disease (HD), are likely modulators of HD pathogenesis. Previous studies have identified and characterized several PTMs on exogenously expressed Htt fragments, but none of them were designed to systematically characterize PTMs on the endogenous full-length Htt protein. We found that full-length endogenous Htt, which was immunoprecipitated from HD knock-in mouse and human postmortem brain, is suitable for detection of PTMs by mass spectrometry...
June 27, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28650662/glucose-restriction-combined-with-autophagy-inhibition-and-chemotherapy-in-hct-116-spheroids-decreases-cell-clonogenicity-and-viability-regulated-by-tumor-suppressor-genes
#2
Monica M Schroll, Gabriel J LaBonia, Katelyn R Ludwig, Amanda B Hummon
Drug resistance is a prevalent phenomenon that decreases the efficacy of cancer treatments and contributes to cancer progression and metastasis. Weakening drug resistant cancer cells prior to chemotherapy is a potential strategy to combat chemoresistance. One approach to damage resistant cancer cells is modulation of nutritional intake. The combination of nutrient restriction with targeted compound treatment results in pronounced molecular changes. This study provides valuable information about augmenting existing chemotherapeutic regimes with simultaneous glucose restriction and autophagy inhibition in colorectal cancer cells...
June 26, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28650171/comprehensive-lipoprotein-characterization-using-lipidomics-analysis-of-human-plasma
#3
Nicolas Christinat, Mojgan Masoodi
Lipoproteins are responsible for the transport of lipids and other nutrients in the circulation and therefore play an important role in lipid metabolism and dyslipidemia. They have also been linked to multiple metabolic disorders including cardiovascular disease, thus understanding their lipid composition is of crucial importance. Characterization of lipoproteins is a challenging task due to their heterogeneity. In particular, their fractionation is often laborious and time-consuming, making large sets of clinical samples difficult to analyze...
June 26, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28648085/specifying-rna-binding-regions-in-proteins-by-peptide-cross-linking-and-affinity-purification
#4
Meeli Mullari, David Lyon, Lars Juhl Jensen, Michael L Nielsen
RNA-binding proteins (RBPs) allow cells to carry out pre-RNA processing and post-transcriptional regulation of gene expression, with aberrations in RBP functions linked to many diseases including neurological disorders and cancer. Human cells encode thousands of RNA-binding proteins with unique RNA-binding properties. These properties are regulated through modularity of a large variety of RNA-binding domains, rendering RNA-protein interactions difficult to study. Recently, the introduction of proteomics methods has provided novel insights into RNA-binding proteins at a systems level...
June 25, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28648079/mass-spectrometry-imaging-microdissection-and-lc-ms-ms-of-the-same-tissue-section
#5
Marialaura Dilillo, Davide Pellegrini, Rima Ait-Belkacem, Erik L de Graaf, Matteo Caleo, Liam A McDonnell
Mass spectrometry imaging (MSI) is able to simultaneously record the distributions of hundreds of molecules directly from tissue. Rapid direct tissue analysis is essential for MSI, in order to maintain spatial localization and acceptable measurement times. The absence of an explicit analyte separation/purification step means MSI lacks the depth-of-coverage of LC-MS/MS. In this work we demonstrate how atmospheric pressure MALDI-MSI enables the same tissue section to be first analyzed by MSI, to identify regions-of-interest that exhibit distinct molecular signatures, followed by localized proteomics analysis using laser capture microdissection isolation and LC-MS/MS...
June 25, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28644030/a-plc-%C3%AE-1-feedback-pathway-regulates-lck-substrate-phosphorylation-at-the-t-cell-receptor-and-slp-76-complex
#6
Judson Belmont, Tao Gu, Ashley Marie Mudd, Arthur R Salomon
Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T cell signaling pathway. While its functions as a regulator of both Ca2+ signaling and PKC-family kinases are well characterized, PLC-γ1's role in the regulation of early T cell receptor signaling events is incompletely understood. Activation of the T cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from SLP-76 to the apical kinase in the pathway, Lck...
June 23, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28641008/hypoxia-induced-changes-in-the-fibroblast-secretome-exosome-and-whole-cell-proteome-using-cultured-cardiac-derived-cells-isolated-from-neonatal-mice
#7
Jake Cosme, Hongbo Guo, Sina Hadipour-Lakmehsari, Andrew Emili, Anthony O Gramolini
Cardiac fibroblasts (CF) represent a major subpopulation of cells in the developing and adult heart. Cardiomyocyte (CM) and CF intercellular communication occurs through paracrine interactions and modulate myocyte development and stress response. Detailed proteomic analysis of the CF secretome in normal and stressed conditions may offer insights into the role of CF in heart development and disease. Primary neonatal mouse CF were isolated and cultured for 24h in 21% (normoxic) or 2% (hypoxic) O2. Conditioned media was separated to obtain EXO and EXO-depleted secretome fractions...
June 22, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28636386/msviz-a-graphical-software-tool-for-in-depth-manual-validation-and-quantitation-of-post-translational-modifications
#8
Trinidad Martin Campos, Roman Mylonas, Alexandre Masselot, Patrice Waridel, Tanja Petricevic, Ioannis Xenarios, Manfredo Quadroni
Mass spectrometry (MS) has become the tool of choice for the large scale identification and quantitation of proteins and their post-translational modifications (PTMs). This development has been enabled by powerful software packages for the automated analysis of MS data. While data on PTM's of thousands of proteins can nowadays be readily obtained, fully deciphering the complexity and combinatorics of modification patterns even on a single protein often remains challenging. Moreover, functional investigation of PTMs on a protein of interest requires validation of the localization and the accurate quantitation of its changes across several conditions, tasks that often still require human evaluation...
June 21, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28633522/molecular-dynamics-information-improves-cis-peptide-based-function-annotation-of-proteins
#9
Sreetama Das, Pratiti Bhadra, Suryanarayanarao Ramakumar, Debnath Pal
Cis-peptide bonds, whose occurrence in proteins is rare but evolutionarily conserved, are implicated to play an important role in protein function. This has led to their previous use in a homology-independent, fragment match-based protein function annotation method. However, proteins are not static molecules; dynamics is integral to their activity. This is nicely epitomized by the geometric isomerization of cis-peptide to trans form for molecular activity. Hence we have incorporated both static (cis-peptide) and dynamics information to improve the prediction of protein molecular function...
June 21, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28613908/metabolomics-analysis-of-effects-of-commercial-soy-based-protein-products-in-red-drum-sciaenops-ocellatus
#10
Fabio Casu, Aaron M Watson, Justin Yost, John W Leffler, Thomas Gibson Gaylord, Frederic T Barrows, Paul A Sandifer, Michael R Denson, Daniel W Bearden
We investigated the metabolic effects of four different commercial soy-based protein products on red drum fish (Sciaenops ocellatus) using nuclear magnetic resonance (NMR) spectroscopy-based metabolomics along with unsupervised principal component analysis (PCA) to evaluate metabolic profiles in liver, muscle, and plasma tissues. Specifically, during a 12 week feeding trial, juvenile red drum maintained in an indoor recirculating aquaculture system were fed four different commercially available soy formulations, containing the same amount of crude protein, and two reference diets as performance controls: a 60% soybean meal diet that had been used in a previous trial in our lab and a natural diet...
June 21, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28631923/influence-of-ingesting-a-flavonoid-rich-supplement-on-the-metabolome-and-concentration-of-urine-phenolics-in-overweight-obese-women
#11
David C Nieman, Sivapriya Ramamoorthy, Colin D Kay, Courtney L Goodman, Christopher R Capps, Zach L Shue, Nicole Heyl, Mary H Grace
This study evaluated the effect of ingesting a flavonoid-rich supplement (329 mg/d) on total urine phenolics and shifts in plasma metabolites in overweight/obese female adults using untargeted metabolomics procedures. Participants (N=103, 18-65 y, BMI ≥ 25 kg/m2) were randomized to flavonoid (F) or placebo (P) groups for 12 weeks, with blood and 24-h urine samples collected pre-study, 4- and 12-weeks in a parallel design. Supplements were prepared as chewable tablets, and included vitamin C, wild bilberry fruit extract, green tea leaf extract, quercetin, caffeine, and omega 3 fatty acids...
June 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28608686/targeted-metabolic-profiling-of-post-mortem-brain-from-infants-who-died-from-sudden-infant-death-syndrome
#12
Stewart F Graham, Onur Turkoglu, Praveen Kumar, Ali Yilmaz, Trent C Bjorndahl, BeomSoo Han, Rupasri Mandal, David S Wishart, Ray O Bahado-Singh
Currently little is known about the underlying pathophysiology associated with SIDS, and no objective biomarkers exist for the accurate identification of those at greatest risk of dying from SIDS. Using targeted metabolomics, we aim to profile the medulla oblongata of infants who have died from SIDS (n = 16) and directly compare their biochemical profile with age matched controls. Combining data acquired using (1)H NMR and targeted DI-LC-MS/MS, we have identified fatty acid oxidation as a pivotal biochemical pathway perturbed in the brains of those infants who have from SIDS (p = 0...
June 20, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28628327/impact-of-the-niemann-pick-c1-gene-mutation-on-the-total-cellular-glycomics-of-cho-cells
#13
Jun-Ichi Furukawa, Minami Soga, Kazue Okada, Ikuko Yokota, Jinhua Piao, Tetsumi Irie, Takumi Era, Yasuro Shinohara
Niemann-Pick disease type C (NPC) is an autosomal recessive lipid storage disorder, and the majority of cases are caused by mutations in the NPC1 gene. In this study, we clarified how a single gene mutation in the NPC1 gene impacts the cellular glycome by analyzing the total glycomic expression profile of Chinese hamster ovary cell mutants defective in the Npc1 gene (Npc1 KO CHO cells). A number of glycomic alterations were identified, including increased expression of lactosylceramide, GM1, GM2, GD1, various neolacto-series glycosphingolipids, and sialyl-T (O-glycan), which was found to be the major sialylated protein-bound glycan, as well as various N-glycans, which were commonly both fucosylated and sialylated...
June 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28627176/correction-to-proteomic-characterization-of-the-cellular-response-to-nitrosative-stress-mediated-by-s-nitrosoglutathione-reductase-inhibition
#14
Matthew W Foster, Zhonghui Yang, David M Gooden, J Will Thompson, Carol H Ball, Meredith E Turner, Yongyong Hou, Jingbo Pi, M Arthur Moseley, Loretta G Que
No abstract text is available yet for this article.
June 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28627174/integrative-analysis-of-renal-ischemia-reperfusion-injury-and-remote-ischemic-preconditioning-in-mice
#15
Kumsun Cho, Sang-Il Min, Sanghyun Ahn, Seung-Kee Min, Curie Ahn, Kyung-Sang Yu, In-Jin Jang, Joo-Youn Cho, Jongwon Ha
Remote ischemic preconditioning (RIPC) is a strategy to induce resistance in a target organ against the oxidative stress and injury caused by ischemia and reperfusion (IR). RIPC harnesses the body's endogenous protective capabilities through brief episodes of IR applied in organs remote from the target. Few studies have analyzed this phenomenon in the kidney. Furthermore, the window of protection representing RIPC efficacy has not been fully elucidated. Here, we performed a multi-omics study to specify those associated with protective effects of RIPC against the IR injury...
June 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28625053/annotation-of-the-domestic-pig-genome-by-quantitative-proteogenomics
#16
Harald Marx, Hannes Hahne, Susanne E Ulbrich, Angelika Schnieke, Oswald Rottmann, Dimitrij Frishman, Bernhard Kuster
The pig is one of the earliest domesticated animals in the history of human civilization and represents one of the most important livestock animals. The recent sequencing of the Sus scrofa genome was a major step towards the comprehensive understanding of porcine biology, evolution and its utility as a promising large animal model for biomedical and xenotransplantation research. However, the functional and structural annotation of the Sus scrofa genome is far from complete. Here, we present mass spectrometry-based quantitative proteomics data of nine juvenile organs and six embryonic stages between 18 to 39 days after gestation...
June 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28608681/activated-ion-electron-transfer-dissociation-enables-comprehensive-top-down-protein-fragmentation
#17
Nicholas M Riley, Michael S Westphall, Joshua J Coon
Here we report the first demonstration of near-complete sequence coverage of intact proteins using activated ion-electron transfer dissociation (AI-ETD), a method that leverages concurrent infrared photoactivation to enhance electron-driven dissociation. AI-ETD produces mainly c/z-type product ions and provides comprehensive (77-97%) protein sequence coverage, outperforming HCD, ETD, and EThcD for all proteins investigated. AI-ETD also maintains this performance across precursor ion charge states, mitigating charge-state dependence that limits traditional approaches...
June 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28374590/binding-site-characterization-of-am1336-a-novel-covalent-inverse-agonist-at-human-cannabinoid-2-receptor-using-mass-spectrometric-analysis
#18
Srikrishnan Mallipeddi, Simion Kreimer, Nikolai Zvonok, Kiran Vemuri, Barry L Karger, Alexander R Ivanov, Alexandros Makriyannis
Cannabinoid 2 receptor (CB2R), a Class-A G-protein coupled receptor (GPCR), is a promising drug target under a wide array of pathological conditions. Rational drug design has been hindered due to our poor understanding of the structural features involved in ligand binding. Binding of a high-affinity biarylpyrazole inverse agonist AM1336 to a library of the human CB2 receptor (hCB2R) cysteine-substituted mutants provided indirect evidence that two cysteines in transmembrane helix-7 (H7) were critical for the covalent attachment...
June 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28287739/application-of-metabolic-profiling-to-abdominal-aortic-aneurysm-research
#19
Mahim I Qureshi, Michele Greco, Panagiotis A Vorkas, Elaine Holmes, Alun H Davies
Abdominal aortic aneurysm (AAA) is a complex disease posing diagnostic and therapeutic challenges. Metabonomics may aid in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis. A systematic review of the diversity and outcomes of existing AAA metabonomic research has been performed. Original research studies applying metabonomics to human aneurysmal disease are included. Seven relevant articles were identified: four studies were based on plasma/serum metabolite profiling, and three studies examined aneurysmal tissue...
June 19, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28621139/coupling-urinary-trihalomethanes-and-metabolomic-profiles-of-type-ii-diabetes-a-case-control-study
#20
Xanthi D Andrianou, Pantelis Charisiadis, Konstantinos Christos Makris
Abiding by the exposome paradigm, incorporation of external and internal exposure metrics using metabolomics tools is warranted to refine the etiology of type II diabetes (T2D). A small (n=51) age- and sex-matched case-control study was conducted in Cyprus coupling urinary trihalomethanes (THM) with T2D. The objectives were to: i) perform a comparative assessment of different deconvolution parameters in compound identification, and ii) evaluate the association between differentially expressed metabolites and either urinary THM or T2D status...
June 16, 2017: Journal of Proteome Research
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