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https://www.readbyqxmd.com/read/29165427/sphingolipids-and-their-metabolism-in-physiology-and-disease
#1
REVIEW
Yusuf A Hannun, Lina M Obeid
Studies of bioactive lipids in general and sphingolipids in particular have intensified over the past several years, revealing an unprecedented and unanticipated complexity of the lipidome and its many functions, which rivals, if not exceeds, that of the genome or proteome. These results highlight critical roles for bioactive sphingolipids in most, if not all, major cell biological responses, including all major cell signalling pathways, and they link sphingolipid metabolism to key human diseases. Nevertheless, the fairly nascent field of bioactive sphingolipids still faces challenges in its biochemical and molecular underpinnings, including defining the molecular mechanisms of pathway and enzyme regulation, the study of lipid-protein interactions and the development of cellular probes, suitable biomarkers and therapeutic approaches...
November 22, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/29163891/identification-of-new-quorum-sensing-autoinducer-binding-partners-in-pseudomonas-aeruginosa-using-photoaffinity-probes
#2
Y R Baker, J T Hodgkinson, B I Florea, E Alza, W R J D Galloway, L Grimm, S M Geddis, H S Overkleeft, M Welch, D R Spring
Many bacterial species, including the human pathogen Pseudomonas aeruginosa, employ a mechanism of intercellular communication known as quorum sensing (QS), which is mediated by signalling molecules termed autoinducers. The Pseudomonas Quinolone Signal (PQS) and 2-Heptyl-3H-4-Quinolone (HHQ) are autoinducers in P. aeruginosa, and they are considered important factors in the progress of infections by this clinically relevant organism. Herein, we report the development of HHQ and PQS photoaffinity-based probes for chemical proteomic studies...
November 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29162636/quantitative-proteomic-profiling-reveals-novel-plasmodium-falciparum-surface-antigens-and-possible-vaccine-candidates
#3
Sandra K Nilsson Bark, Rushdy Ahmad, Kathleen Dantzler, Amanda K Lukens, Mariana De Niz, Matthew J Szucs, Xiaojing Jin, Joanne Cotton, Dietmar Hoffmann, Eva Bric-Furlong, Ray Oomen, Mark Parrington, Dan Milner, Daniel E Neafsey, Steven A Carr, Dyann F Wirth, Matthias Marti
Despite recent efforts towards control and elimination, malaria remains a major public health problem worldwide. Plasmodium falciparum resistance against artemisinin, used in front line combination drugs, is on the rise, and the only approved vaccine shows limited efficacy. Combinations of novel and tailored drug and vaccine interventions are required to maintain the momentum of the current malaria elimination program. Current evidence suggests that strain-transcendent protection against malaria infection can be achieved using whole organism vaccination or with a polyvalent vaccine covering multiple antigens or epitopes...
November 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29161012/top-down-proteomics-ready-for-prime-time
#4
Bifan Chen, Kyle A Brown, Ziqing Lin, Ying Ge
In the post-genomics era, the study of proteins is critical for understanding cellular functions at the molecular level.1-5 Beyond the genetic code, the human proteome is greatly diversified by various genetic variations, alternative splicing of RNA transcripts, and post-translational modifi-cations (PTMs).6,7 In 2013, the term "proteoform" was designated to describe "all of the different molecular forms in which the protein product of a single gene can be found",6 clearing up the confusion in nomenclature and joining research efforts to develop methodologies for pro-teoform characterization...
November 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29161009/a-sensitive-microbead-based-organic-media-assisted-method-for-proteomics-sample-preparation-from-dilute-and-denaturing-solutions
#5
Masato Taoka, Michihiko Fujii, Masahiro Tsuchiya, Takamasa Uekita, Tohru Ichimura
We developed a robust and sensitive sample preparation method for proteomics termed microbead-based and organic-media-assisted proteolysis strategy (BOPs). BOPs combine two advantages of current techniques, (1) unbiased binding of reversed-phase polymeric microbeads to any type of protein and (2) enhanced trypsin digestion efficiency in CH3CN-aqueous solvent systems, into a single-tube workflow. Compared with conventional techniques, this method effectively concentrates proteins and improves proteolytic digestion, and can be used with submicromolar protein samples in dilute and/or denaturing solutions such as 70 % formic acid, 8 M urea, or 7 M guanidine hydrochloride without any sample pretreatment...
November 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29158831/identification-and-validation-of-a-salivary-protein-panel-to-detect-heart-failure-early
#6
Xi Zhang, Terry Walsh, John J Atherton, Karam Kostner, Benjamin Schulz, Chamindie Punyadeera
BACKGROUND: Over 26 million people suffer from heart failure (HF) globally. Current diagnosis of HF relies on clinical evaluation, blood assays and imaging techniques. Our aim is to develop a diagnostic assay to detect HF in at risk individuals within the community using human saliva as a medium, potentially leading to a simple, safe early warning system. METHODS: Saliva samples were collected from healthy controls (n=36) and HF patients (n=75). Salivary proteome profiles were analysed by Sequential Window Acquisition of All Theoretical fragment ion spectra - Mass Spectrometry (SWATH-MS)...
2017: Theranostics
https://www.readbyqxmd.com/read/29158489/yeast-display-biopanning-identifies-human-antibodies-targeting-glioblastoma-stem-like-cells
#7
Michael Zorniak, Paul A Clark, Benjamin J Umlauf, Yongku Cho, Eric V Shusta, John S Kuo
Glioblastoma stem-like cells (GSC) are hypothesized to evade current therapies and cause tumor recurrence, contributing to poor patient survival. Existing cell surface markers for GSC are developed from embryonic or neural stem cell systems; however, currently available GSC markers are suboptimal in sensitivity and specificity. We hypothesized that the GSC cell surface proteome could be mined with a yeast display antibody library to reveal novel immunophenotypes. We isolated an extensive collection of antibodies that were differentially selective for GSC...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158431/salmonella-typhimurium-alters-the-extracellular-proteome-of-macrophages-and-leads-to-the-production-of-pro-inflammatory-exosomes
#8
Winnie W Hui, Kamil Hercik, Sayali Belsare, Navatha Alugubelly, Beata Clapp, Carlos Rinaldi, Mariola J Edelmann
Salmonella enterica serovar Typhimurium is a Gram-negative bacterium, which can invade and survive within macrophages. Pathogenic Salmonellae induce the secretion of specific cytokines from these phagocytic cells and interfere with the host secretory pathways. In this study, we describe the extracellular proteome of human macrophages infected with S. Typhimurium, followed by analysis of canonical pathways of proteins isolated from the extracellular milieu. We demonstrate that some of the proteins secreted by macrophages upon S...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29158353/blood-pressure-control-by-a-secreted-fgfbp1-fibroblast-growth-factor-binding-protein
#9
Elena Tassi, En Yin Lai, Lingli Li, Glenn Solis, Yifan Chen, William E Kietzman, Patricio E Ray, Anna T Riegel, William J Welch, Christopher S Wilcox, Anton Wellstein
Fibroblast growth factors (FGFs) participate in organ development and tissue maintenance, as well as the control of vascular function. The paracrine-acting FGFs are stored in the extracellular matrix, and their release is controlled by a secreted FGF-binding protein (FGF-BP, FGFBP1, and BP1) that modulates FGF receptor signaling. A genetic polymorphism in the human FGFBP1 gene was associated with higher gene expression and an increased risk of familial hypertension. Here, we report on the effects of inducible BP1 expression in a transgenic mouse model...
November 20, 2017: Hypertension
https://www.readbyqxmd.com/read/29158163/identification-of-tissue-damage-extracellular-matrix-remodeling-and-bacterial-challenge-as-common-mechanisms-associated-with-high-risk-cutaneous-squamous-cell-carcinomas
#10
Melanie C Föll, Matthias Fahrner, Christine Gretzmeier, Käthe Thoma, Martin L Biniossek, Dimitra Kiritsi, Frank Meiss, Oliver Schilling, Alexander Nyström, Johannes S Kern
In this study we used a genetic extracellular matrix (ECM) disease to identify mechanisms associated with aggressive behavior of cutaneous squamous cell carcinoma (cSCC). cSCC is one of the most common malignancies and usually has a good prognosis. However, some cSCCs recur or metastasize and cause significant morbidity and mortality. Known factors that are associated with aggressiveness of cSCCs include tumor grading, size, localization and microinvasive behavior. To investigate molecular mechanisms that influence biologic behavior we used global proteomic and histologic analyses of formalin-fixed paraffin-embedded tissue of primary human cSCCs...
November 17, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29157295/single-cell-multiplexed-cytokine-profiling-of-cd19-car-t-cells-reveals-a-diverse-landscape-of-polyfunctional-antigen-specific-response
#11
Qiong Xue, Emily Bettini, Patrick Paczkowski, Colin Ng, Alaina Kaiser, Timothy McConnell, Olja Kodrasi, Máire F Quigley, James Heath, Rong Fan, Sean Mackay, Mark E Dudley, Sadik H Kassim, Jing Zhou
BACKGROUND: It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. METHODS: We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29157261/role-of-omics-techniques-in-the-toxicity-testing-of-nanoparticles
#12
REVIEW
Eleonore Fröhlich
Nanotechnology is regarded as a key technology of the twenty-first century. Despite the many advantages of nanotechnology it is also known that engineered nanoparticles (NPs) may cause adverse health effects in humans. Reports on toxic effects of NPs relay mainly on conventional (phenotypic) testing but studies of changes in epigenome, transcriptome, proteome, and metabolome induced by NPs have also been performed. NPs most relevant for human exposure in consumer, health and food products are metal, metal oxide and carbon-based NPs...
November 21, 2017: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/29156374/genetic-profiling-and-surface-proteome-analysis-of-human-atrial-stromal-cells-and-rat-ventricular-epicardium-derived-cells-reveals-novel-insights-into-their-cardiogenic-potential
#13
Sebastian Temme, Daniela Friebe, Timo Schmidt, Gereon Poschmann, Julia Hesse, Bodo Steckel, Kai Stühler, Meik Kunz, Thomas Dandekar, Zhaoping Ding, Payam Akhyari, Artur Lichtenberg, Jürgen Schrader
Epicardium-derived cells (EPDC) and atrial stromal cells (ASC) display cardio-regenerative potential, but the molecular details are still unexplored. Signals which induce activation, migration and differentiation of these cells are largely unknown. Here we have isolated rat ventricular EPDC and rat/human ASC and performed genetic and proteomic profiling. EPDC and ASC expressed epicardial/mesenchymal markers (WT-1, Tbx18, CD73, CD90, CD44, CD105), cardiac markers (Gata4, Tbx5, troponin T) and also contained phosphocreatine...
November 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29155757/dissection-of-human-retina-and-rpe-choroid-for-proteomic-analysis
#14
Thiago Cabral, Marcus A Toral, Gabriel Velez, James E DiCarlo, Anuradha M Gore, MaryAnn Mahajan, Stephen H Tsang, Alexander G Bassuk, Vinit B Mahajan
The human retina is composed of the sensory neuroretina and the underlying retinal pigmented epithelium (RPE), which is firmly complexed to the vascular choroid layer. Different regions of the retina are anatomically and molecularly distinct, facilitating unique functions and demonstrating differential susceptibility to disease. Proteomic analysis of each of these regions and layers can provide vital insights into the molecular process of many diseases, including Age-Related Macular Degeneration (AMD), diabetes mellitus, and glaucoma...
November 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155708/enrichment-of-detergent-insoluble-protein-aggregates-from-human-postmortem-brain
#15
Ian Diner, Tram Nguyen, Nicholas T Seyfried
In this study, we describe an abbreviated single-step fractionation protocol for the enrichment of detergent-insoluble protein aggregates from human postmortem brain. The ionic detergent N-lauryl-sarcosine (sarkosyl) effectively solubilizes natively folded proteins in brain tissue allowing the enrichment of detergent-insoluble protein aggregates from a wide range of neurodegenerative proteinopathies, such as Alzheimer's disease (AD), Parkinson's disease and amyotrophic lateral sclerosis, and prion diseases...
October 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155586/deconstructing-lipid-kinase-inhibitors-by-chemical-proteomics
#16
Rebecca L McCloud, Caroline E Franks, Sean T Campbell, Benjamin W Purow, Thurl E Harris, Ku-Lung Hsu
Diacylglycerol kinases (DGKs) regulate lipid metabolism and cell signaling through ATP-dependent phosphorylation of diacylglycerol to biosynthesize phosphatidic acid. Selective chemical probes for studying DGKs are currently lacking and are needed to annotate isoform-specific functions of these elusive lipid kinases. Previously, we explored fragment-based approaches to discover a core fragment of DGK-α (DGKα) inhibitors responsible for selective binding to the DGKα active site. Here, we utilize quantitative chemical proteomics to deconstruct widely used DGKα inhibitors to identify structural regions mediating off-target activity...
November 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/29155091/dynamic-molecular-events-associated-to-plasmodium-berghei-gametogenesis-through-proteomic-approach
#17
Carlos H S Garcia, Delphine Depoix, Rayner M L Queiroz, Jaques M F Souza, Wagner Fontes, Marcelo V de Sousa, Marlon D M Santos, Paulo C Carvalho, Philippe Grellier, Sébastien Charneau
Plasmodium mature sexual cycle occurs in the vector mosquitoes and ensures the transmission to a new host. Gametogenesis takes place within minutes in the vector midgut. Gametocytes have to complete a deep nuclear reorganization, quick differentiation, and in the case of male gametocytes, intracytoplasmic flagellum assembly that results in free-swimming microgametes required for macrogamete fertilization. In efforts to improve our knowledge of molecular mechanisms involved in gamete morphogenesis, we carried out a nanoLC/MSMS based quantitative proteomic analysis throughout the xanthurenic acid-induced gametogenesis of the rodent parasite P...
November 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29154769/extracellular-lipids-accumulate-in-human-carotid-arteries-as-distinct-three-dimensional-structures-and-have-proinflammatory-properties
#18
Satu Lehti, Su D Nguyen, Ilya Belevich, Helena Vihinen, Hanna M Heikkilä, Rabah Soliymani, Reijo Käkelä, Jani Saksi, Matti Jauhiainen, Gregory A Grabowski, Outi Kummu, Sohvi Hörkkö, Marc Baumann, Perttu J Lindsberg, Eija Jokitalo, Petri T Kovanen, Katariina Öörni
Lipid accumulation is a key characteristic of advancing atherosclerotic lesions. Here we analyzed the ultrastructure of the accumulated lipids in endarterectomized human carotid atherosclerotic plaques using three-dimensional (3D) electron microscopy, a method never used in this context before. 3D-electron microscopy revealed intracellular lipid droplets and extracellular lipoprotein particles. The majority of the particles were aggregated and some connected to needle-shaped or sheet-like cholesterol crystals...
November 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29152096/the-non-canonical-ubiquitin-activating-enzyme-uba6-suppresses-epithelial-mesenchymal-transition-of-mammary-epithelial-cells
#19
Xianpeng Liu, Limin Sun, Demirkan B Gursel, Chonghui Cheng, Sui Huang, Alfred W Rademaker, Seema A Khan, Jun Yin, Hiroaki Kiyokawa
Ubiquitination plays critical roles in the regulation of oncoproteins and tumor suppressors during carcinogenesis. The two ubiquitin activating enzymes (E1) in human genome, UBA1 and UBA6, initiate ubiquitination by ATP-dependent activation of ubiquitin. Recent evidence suggests that UBA1 and UBA6 play partially overlapped yet distinct roles in controlling the proteome. Here we demonstrate that ubiquitination pathways initiated specifically by UBA6 set a suppressive barrier against critical steps of mammary carcinogenesis such as loss of polarity, anoikis resistance and epithelial-mesenchymal transition (EMT)...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151691/parallel-mrna-proteomics-and-mirna-expression-analysis-in-cell-line-models-of-the-intestine
#20
Finbarr O'Sullivan, Joanne Keenan, Sinead Aherne, Fiona O'Neill, Colin Clarke, Michael Henry, Paula Meleady, Laura Breen, Niall Barron, Martin Clynes, Karina Horgan, Padraig Doolan, Richard Murphy
AIM: To identify miRNA-regulated proteins differentially expressed between Caco2 and HT-29: two principal cell line models of the intestine. METHODS: Exponentially growing Caco-2 and HT-29 cells were harvested and prepared for mRNA, miRNA and proteomic profiling. mRNA microarray profiling analysis was carried out using the Affymetrix GeneChip Human Gene 1.0 ST array. miRNA microarray profiling analysis was carried out using the Affymetrix Genechip miRNA 3.0 array...
November 7, 2017: World Journal of Gastroenterology: WJG
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