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Molecular & Cellular Proteomics: MCP

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https://www.readbyqxmd.com/read/28232516/differential-protein-expression-marks-the-transition-from-infection-with-opisthorchis-viverrini-to-cholangiocarcinoma
#1
Jarinya Khoontawad, Chawalit Pairojku, Rucksak Rucksaken, Porntip Pinlaor, Chaisiri Wongkham, Puangrat Yongvanit, Ake Pugkhem, Alun Jones, Jordan Plieskatt, Jeremy Potriquet, Jeffery Bethony, Somchai Pinlaor, Jason Mulvenna
Parts of Southeast Asia have the highest incidence of intrahepatic cholangiocarcinoma (CCA) in the world due to infection by the liver fluke Opisthorchis viverrini (Ov). Ov-associated CCA is the culmination of chronic Ov-infection, with the persistent production of the growth factors and cytokines associated with persistent inflammation, which can endure for years in Ov-infected individuals prior to transitioning to CCA. Isobaric labelling and tandem mass spectrometry of liver tissue from a hamster model of CCA was used to compare protein expression profiles from inflammed tissue (Ov-infected but not cancerous) versus cancerous tissue (Ov-induced CCA)...
February 23, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28223351/in-vivo-and-in-vitro-proteome-analysis-of-hiv-1-infected-human-cd4-t-cells
#2
Johannes Nemeth, Valentina Vongrad, Karin J Metzner, Victoria Strouvelle, Rainer Weber, Patrick Pedrioli, Ruedi Aebersold, Huldrych Guenthard, Ben C Collins
Host directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Since HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+ T cells upon HIV-1 infection, both in vitro and in vivo. A SWATH-MS approach was used to measure the proteome of human primary CD4+ T cells infected with HIV-1 in vitro as well as CD4+ T cells from HIV-1 infected patients with paired samples on and off antiretroviral treatment...
February 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28223350/mapping-atheroprotective-functions-and-related-proteins-lipoproteins-in-size-fractionated-human-plasma
#3
Debi K Swertfeger, Hailong Li, Sandra Rebholz, Xiaoting Zhu, Amy S Shah, W Sean Davidson, L Jason Lu
HDL has been shown to possess a variety of cardio-protective functions, including removal of excess cholesterol from the periphery, and inhibition of lipoprotein oxidation. It has been proposed that various HDL subparticles exist, each with distinct protein and lipid compositions, which may be responsible for HDL's many functions. We hypothesized that HDL functions will co-migrate with the operational lipoprotein subspecies when separated by gel filtration chromatography. Plasma from 10 healthy male donors was fractionated and the protein composition of the phospholipid containing fractions was analyzed by mass spectrometry (MS)...
February 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28223349/identification-of-antibody-targets-for-tuberculosis-serology-using-high-density-nucleic-acid-programmable-protein-arrays
#4
Lusheng Song, Garrick Wallstrom, Xiaobo Yu, Marika Hopper, Jennifer Van Duine, Jason Steel, Jin Park, Peter Wiktor, Peter Khan, Al Brunner, Douglas Wilson, Elizabeth R Jenny-Avital, Ji Qiu, Joshua LaBaer, D Mitchell Magee, Jacqueline M Achkar
Better and more diverse biomarkers for the development of simple point-of-care tests for active tuberculosis (TB), a clinically heterogeneous disease, are urgently needed. We generated a proteomic Mycobacterium tuberculosis (Mtb) High-Density Nucleic Acid Programmable Protein Array (HD-NAPPA) that used a novel multiplexed strategy for expedited high-throughput screening for antibody responses to the Mtb proteome. We screened sera from HIV uninfected and co-infected TB patients and controls (n = 120) from the US and South Africa (SA) using the multiplex HD-NAPPA for discovery, followed by deconvolution and validation through single protein HD-NAPPA with biologically independent samples (n=124)...
February 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28196878/global-characterization-of-protein-secretion-from-human-macrophages-following-non-canonical-caspase-4-5-inflammasome-activation
#5
Martina B Lorey, Katariina Rossi, Kari K Eklund, Tuula A Nyman, Sampsa Matikainen
Gram-negative bacteria are associated with a wide spectrum of infectious diseases in humans. Inflammasomes are cytosolic protein complexes that are assembled when the cell encounters pathogens or other harmful agents. The non-canonical caspase-4/5 inflammasome is activated by gram-negative bacteria-derived lipopolysaccharide (LPS) and by endogenous oxidized phospholipids. Protein secretion is a critical component of the innate immune response. Here we have used label-free quantitative proteomics to characterize global protein secretion in response to non-canonical inflammasome activation upon intracellular LPS recognition in human primary macrophages...
February 14, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28196877/using-quantitative-mass-spectrometry-to-better-understand-the-influence-of-genetics-and-nutritional-perturbations-on-the-virulence-potential-of-staphylococcus-aureus
#6
Jessica R Chapman, Divya Balasubramanian, Kayan Tam, Manor Askenazi, Richard Copin, Bo Shopsin, Victor J Torres, Beatrix Ueberheide
Staphylococcus aureus (Sa) is the leading cause of a variety of bacterial infections ranging from superficial skin infections to invasive and life threatening diseases such as septic bacteremia, necrotizing pneumonia, and endocarditis. The success of Sa as a human pathogen is due to its ability to adapt to the environment by changing expression, production, or secretion of virulence factors. Although Sa immune evasion is well-studied, the regulation of virulence factors under different nutrient and growth conditions is still not well understood...
February 14, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28188228/time-resolved-phosphoproteome-analysis-of-paradoxical-raf-activation-reveals-novel-targets-of-erk
#7
Peter Kubiniok, Hugo Lavoie, Marc Therrien, Pierre Thibault
Small molecules targeting aberrant RAF activity, like Vemurafenib (PLX4032), are highly effective against cancers harboring the V600E BRAF mutation, and are now approved for clinical use against metastatic melanoma. However, in tissues showing elevated RAS activity and in RAS-mutant tumors, these inhibitors stimulate RAF dimerization, resulting in inhibitor resistance and downstream paradoxical ERK activation. To understand the global signaling response of cancer cells to RAF inhibitors, we profiled the temporal changes of the phosphoproteome of two colon cancer cell lines (Colo205 and HCT116) that respond differently to Vemurafenib...
February 10, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28188227/the-hla-b27-peptidome-in-vivo-in-spondyloarthritis-susceptible-hla-b27-transgenic-rats-and-the-effect-of-erap1-deletion
#8
Eilon Barnea, Dganit Melamed Kadosh, Yael Haimovich, Nimman Satumtira, Martha L Dorris, Mylinh T Nguyen, Robert E Hammer, Tri M Tran, Robert A Colbert, Joel D Taurog, Arie Admon
HLA-B27 is a class I major histocompatibility (MHC-I) allele that confers susceptibility to the rheumatic disease ankylosing spondylitis (AS) by an unknown mechanism. ERAP1 is an aminopeptidase that trims peptides in the endoplasmic reticulum for binding to MHC-I molecules. ERAP1 shows genetic epistasis with HLA-B27 in conferring susceptibility to AS. Male HLA-B27 transgenic rats develop arthritis and serve as an animal model of AS, whereas female B27 transgenic rats remain healthy. We used large-scale quantitative mass-spectrometry to identify over 15,000 unique HLA-B27 peptide ligands, isolated after immunoaffinity purification of the B27 molecules from the spleens of HLA-B27 transgenic rats...
February 10, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28183815/proteomic-screen-for-cellular-targets-of-the-vaccinia-virus-f10-protein-kinase-reveals-that-phosphorylation-of-mdia-regulates-stress-fiber-formation
#9
Matthew D Greseth, Dominique M Carter, Scott S Terhune, Paula Traktman
Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm of infected cells. While this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. The viral B1 kinase and H1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the F10 kinase. F10 is essential for virion morphogenesis, beginning with the poorly understood process of diversion of membranes from the ER for the purpose of virion membrane biogenesis...
February 9, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28183814/comparative-proteomics-of-purified-pathogen-vacuoles-correlates-intracellular-replication-of-legionella-pneumophila-with-the-small-gtpase-rap1
#10
Johanna Schm Oumllders, Christian Manske, Andreas Otto, Christine Hoffmann, Bernhard Steiner, Amanda Welin, D Oumlrte Becher, Hubert Hilbi
Legionella pneumophila is an opportunistic bacterial pathogen that causes a severe lung infection termed Legionnaires disease. The pathogen replicates in environmental protozoa as well as in macrophages within a unique membrane-bound compartment, the Legionella-containing-vacuole (LCV). LCV formation requires the bacterial Icm/Dot type IV secretion system, which translocates ca. 300 effector proteins into host cells, where they target distinct host factors. The L. pneumophila pentuple mutant (Δpentuple) lacks 5 gene clusters (31% of the effector proteins) and replicates in macrophages but not in Dictyostelium discoideum amoeba...
February 9, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28183813/targeted-proteomics-and-absolute-protein-quantification-for-the-construction-of-a-stoichiometric-host-pathogen-surface-density-model
#11
Kristoffer Sjöholm, Ola Kilsgård, Johan Teleman, Lotta Happonen, Lars Malmström, Johan Malmström
Sepsis is a systemic immune response responsible for considerable morbidity and mortality. Molecular modelling of host-pathogen interactions in the disease state represents a promising strategy to define molecular events of importance for the transition from superficial to invasive infectious diseases. Here we used the gram-positive bacterium Streptococcus pyogenes as a model system to establish a mass spectrometry based workflow for the construction of a stoichiometric surface density model between the S. pyogenes surface, the surface virulence factor M-protein, and adhered human blood plasma proteins...
February 9, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28183812/new-guidelines-for-publication-of-manuscripts-describing-development-and-application-of-targeted-mass-spectrometry-measurements-of-peptides-and-proteins
#12
Susan E Abbatiello, Bradley L Ackermann, Christoph H Borchers, Ralph A Bradshaw, Steven A Carr, Robert J Chalkley, Meena Choi, Eric W Deutsch, Bruno Domon, Andrew N Hoofnagle, Hasmik Keshishian, Eric Kuhn, Daniel C Liebler, Michael J MacCoss, Brendan MacLean, D R Mani, Hendrik Neubert, Derek Smith, Olga Vitek, Lisa Zimmerman
Molecular & Cellular Proteomics is pleased to announce new guidelines and requirements for papers describing the development and application of targeted mass spectrometry measurements of peptides, modified peptides and proteins. These guidelines will be implemented for papers submitted starting June, 2017.
February 9, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28179475/asparagine-linked-glycans-of-cryptosporidium-parvum-contain-a-single-long-arm-are-barely-processed-in-the-er-or-golgi-and-show-a-strong-bias-for-sites-with-threonine
#13
John R Haserick, Deborah R Leon, John Samuelson, Catherine E Costello
Cryptosporidium parvum causes severe diarrhea in infants in developing countries and in immunosuppressed persons, including those with AIDS. We are interested in the Asn-linked glycans (N-glycans) of C. parvum, because 1) the N-glycan precursor is predicted to contain five mannose and two glucose residues on a single long arm versus nine mannose and three glucose residues on the three-armed structure common in host N-glycans, 2) C. parvum is a rare eukaryote that lacks the machinery for N-glycan-dependent quality control of protein folding in the lumen of the Endoplasmic Reticulum (ER), and 3) ER and Golgi mannosidases, as well as glycosyltransferases that build complex N-glycans, are absent from the predicted proteome...
February 8, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28179412/sharpening-host-defenses-during-infection-proteases-cut-to-the-chase
#14
Natalie C Marshall, B Brett Finlay, Christopher M Overall
The human immune system consists of an intricate network of tightly controlled pathways, where proteases are essential regulators and executioners at multiple levels. Invading microbial pathogens also encode proteases that have evolved to manipulate and dysregulate host proteins including host proteases during the course of disease. The identification of pathogen proteases as well as their substrates and mechanisms of action have empowered significant developments in therapeutics for infectious diseases. Yet for many pathogens, there remains a great deal to be discovered...
February 8, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28179408/time-resolved-global-and-chromatin-proteomics-during-herpes-simplex-virus-hsv-1-infection
#15
Katarzyna Kulej, Daphne C Avgousti, Simone Sidoli, Christin Herrmann, Ashley N Della Fera, Eui Tae Kim, Benjamin A Garcia, Matthew D Weitzman
Herpes simplex virus (HSV-1) lytic infection results in global changes to the host cell proteome and the proteins associated with host chromatin. We present a system level characterization of proteome dynamics during infection by performing a multi-dimensional analysis during HSV-1 lytic infection of human foreskin fibroblast (HFF) cells. Our study includes identification and quantification of the host and viral proteomes, phosphoproteomes, chromatin bound proteomes and post-translational modifications (PTMs) on cellular histones during infection...
February 8, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28174230/crispr-cas9-coupled-affinity-purification-mass-spectrometry-analysis-revealed-a-novel-role-of-neurofibromin-in-mtor-signaling
#16
Xu Li, Min Gao, Jong Min Choi, Beom-Jun Kim, Mao-Tian Zhou, Zhen Chen, Antrix N Jain, Sung Yun Jung, Jingsong Yuan, Wenqi Wang, Yi Wang, Junjie Chen
Neurofibromin (NF1) is a well-known tumor suppressor that is commonly mutated in cancer patients. It physically interacts with RAS and negatively regulates RAS GTPase activity. Despite the importance of NF1 in cancer, a high-quality endogenous NF1 interactome has yet to be established. In this study, we combined clustered, regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated gene knockout technology with affinity purification using antibodies against endogenous proteins, followed by mass spectrometry analysis, to sensitively and accurately detect NF1 protein-protein interactions in unaltered in vivo settings...
February 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28174229/effects-of-erbb2-overexpression-on-the-proteome-and-erbb-ligand-specific-phosphosignalling-in-mammary-luminal-epithelial-cells
#17
Jenny Worthington, Georgia Spain, John F Timms
Most breast cancers arise from luminal epithelial cells and 25-30% of these tumours overexpress the ErbB2/HER2 receptor which correlates with disease progression and poor prognosis. The mechanisms of ErbB2 signalling and the effects of its overexpression are not fully understood. Herein, SILAC expression profiling and phosphopeptide enrichment of a relevant, non-transformed, immortalized human mammary luminal epithelial cell model were used to profile ErbB2-dependent differences in protein expression and phosphorylation events triggered via EGFR (EGF treatment) and ErbB3 (HRG1β treatment) in the context of ErbB2 overexpression...
February 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28174228/profiling-subcellular-protein-phosphatase-responses-to-coxsackievirus-b3-infection-of-cardiomyocytes
#18
Millie Shah, Christian M Smolko, Sarah Kinicki, Zachary D Chapman, David L Brautigan, Kevin A Janes
Cellular responses to stimuli involve dynamic and localized changes in protein kinases and phosphatases. Here, we report a generalized functional assay for high-throughput profiling of multiple protein phosphatases with subcellular resolution and apply it to analyze coxsackievirus B3 (CVB3) infection counteracted by interferon signaling. Using on-plate cell fractionation optimized for adherent cells, we isolate protein extracts containing active endogenous phosphatases from cell membranes, the cytoplasm, and the nucleus...
February 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28163258/proteomics-tracing-the-footsteps-of-infectious-disease
#19
Todd M Greco, Ileana M Cristea
Every year, a major cause of human disease and death worldwide is infection with the various pathogens - viruses, bacteria, fungi, and protozoa - that are intrinsic to our ecosystem. In efforts to control the prevalence of infectious disease and develop improved therapies, the scientific community has focused on building a molecular picture of pathogen infection and spread. These studies have been aimed at defining the cellular mechanisms that allow pathogen entry into hosts cells, their replication and transmission, as well as the core mechanisms of host defense against pathogens...
February 5, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28153913/an-anatomically-resolved-mouse-brain-proteome-reveals-parkinson-disease-relevant-pathways
#20
Sung Yun Jung, Jong Min Choi, Maxime W C Rousseaux, Anna Malovannaya, Jean J Kim, Joachim Kutzera, Yi Wang, Yin Huang, Weimin Zhu, Suman Maity, Huda Yahya Zoghbi, Jun Qin
Here we present a mouse brain protein atlas that covers 17 surgically distinct neuroanatomical regions of the adult mouse brain, each less than 1mm3 in size. The protein expression levels are determined for 6,500 to 7,500 gene protein products from each region and over 12,000 gene protein products for the entire brain, documenting the physiological repertoire of mouse brain proteins in an anatomically resolved and comprehensive manner. We explored the utility of our spatially-defined protein profiling methods in a mouse model of Parkinson's disease (PD)...
February 2, 2017: Molecular & Cellular Proteomics: MCP
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