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https://www.readbyqxmd.com/read/28644920/genome-scale-metabolic-models-applied-to-human-health-and-disease
#1
REVIEW
Daniel J Cook, Jens Nielsen
Advances in genome sequencing, high throughput measurement of gene and protein expression levels, data accessibility, and computational power have allowed genome-scale metabolic models (GEMs) to become a useful tool for understanding metabolic alterations associated with many different diseases. Despite the proven utility of GEMs, researchers confront multiple challenges in the use of GEMs, their application to human health and disease, and their construction and simulation in an organ-specific and disease-specific manner...
June 23, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28643936/phenotypic-analysis-of-organoids-by-proteomics
#2
REVIEW
Alexis Gonneaud, Claude Asselin, François Boudreau, François-Michel Boisvert
The development of 3D cell cultures into self-organizing organ-like structures named organoids provides a model that better reflects in vivo organ physiology and their functional properties. Organoids have been established from several organs, such as the intestine, prostate, brain, liver, kidney and pancreas. With recent advances in high-throughput and -omics profiling technologies, it is now possible to study the mechanisms of cellular organisation at the systems level. It is therefore not surprising that these methods are now used to characterize organoids at the transcriptomic, proteomic, chromatin state and transcription factor DNA-binding levels...
June 23, 2017: Proteomics
https://www.readbyqxmd.com/read/28642462/metabolic-changes-in-medaka-fish-induced-by-cyanobacterial-exposures-in-mesocosms-an-integrative-approach-combining-proteomic-and-metabolomic-analyses
#3
Benoît Sotton, Alain Paris, Séverine Le Manach, Alain Blond, Gérard Lacroix, Alexis Millot, Charlotte Duval, Hélène Huet, Qin Qiao, Sophie Labrut, Giovanni Chiapetta, Joelle Vinh, Arnaud Catherine, Benjamin Marie
Cyanobacterial blooms pose serious threats to aquatic organisms and strongly impact the functioning of aquatic ecosystems. Due to their ability to produce a wide range of potentially bioactive secondary metabolites, so called cyanotoxins, cyanobacteria have been extensively studied in the past decades. Proteomic and metabolomic analyses provide a unique opportunity to evaluate the global response of hundreds of proteins and metabolites at a glance. In this study, we provide the first combined utilization of these methods targeted to identify the response of fish to bloom-forming cyanobacteria...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642329/experimental-and-computational-insight-into-human-mesenchymal-stem-cell-paracrine-signaling-and-heterocellular-coupling-effects-on-cardiac-contractility-and-arrhythmogenicity
#4
Joshua Mayourian, Timothy J Cashman, Delaine K Ceholski, Bryce V Johnson, David Sachs, Deepak A Kaji, Susmita Sahoo, Joshua M Hare, Roger J Hajjar, Eric A Sobie, Kevin D Costa
Rationale: Myocardial delivery of human mesenchymal stem cells (hMSCs) is an emerging therapy for treating the failing heart. However, the relative effects of hMSC-mediated heterocellular coupling (HC) and paracrine signaling (PS) on human cardiac contractility and arrhythmogenicity remain unresolved. Objective: To better understand hMSC PS and HC effects on human cardiac contractility and arrhythmogenicity by integrating experimental and computational approaches. Methods and Results: : Extending our previous hMSC-cardiomyocyte HC computational model, we incorporated experimentally calibrated hMSC PS effects on cardiomyocyte L-type calcium channel/SERCA activity and cardiac tissue fibrosis...
June 22, 2017: Circulation Research
https://www.readbyqxmd.com/read/28641528/drug-design-synthesis-and-in-vitro-evaluation-of-substituted-benzofurans-as-hsp90-inhibitors
#5
Sundeep Kadasi, Thadeu E M M Costa, Neha Arukala, Mallika Toshakani, Chaitanya Duggineti, Sreekanth Thota, Sayan Dutta Gupta, Shiva Raj, Carmen Penido, Maria G Henriques, Nulgumnalli Manjunathaiah Raghavendra
BACKGROUND: Heat shock protein 90 is a molecular chaperone required for the stability and function of several client proteins that promote cancer cell growth and/or survival. Discovery of Hsp90 inhibitors has emerged as an attractive target of research in cancer therapeutics. Natural products like geldanamycin and radicicol are established Hsp90 inhibitors, but face limitations with toxicity and inactivity, by in vivo studies respectively. However, they lay the logical starting point for the design of novel synthetic or semi-synthetic congeners as Hsp90 inhibitors...
June 22, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28636309/quantitative-chemical-proteomic-profiling-of-the-in-vivo-targets-of-reactive-drug-metabolites
#6
Landon R Whitby, R Scott Obach, Gabriel M Simon, Matthew M Hayward, Benjamin F Cravatt
Idiosyncratic liver toxicity represents an important problem in drug research and pharmacotherapy. Reactive drug metabolites that modify proteins are thought to be a principal factor in drug-induced liver injury. Here, we describe a quantitative chemical proteomic method to identify the targets of reactive drug metabolites in vivo. Treating mice with clickable analogues of four representative hepatotoxic drugs, we demonstrate extensive covalent binding that is confined primarily to the liver. Each drug exhibited a distinct target profile that, in certain cases, showed strong enrichment for specific metabolic pathways (e...
June 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28635333/molecular-biomarkers-to-guide-precision-medicine-in-localized-prostate-cancer
#7
Minke Smits, Niven Mehra, Michiel Sedelaar, Winald Gerritsen, Jack A Schalken
Major advances through tumor profiling technologies, that include next-generation sequencing, epigenetic, proteomic and transcriptomic methods, have been made in primary prostate cancer, providing novel biomarkers that may guide precision medicine in the near future. Areas covered: The authors provided an overview of novel molecular biomarkers in tissue, blood and urine that may be used as clinical tools to assess prognosis, improve selection criteria for active surveillance programs, and detect disease relapse early in localized prostate cancer...
June 21, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28632398/the-mitochondrial-protein-atlas-a-database-of-experimentally-verified-information-on-the-human-mitochondrial-proteome
#8
Noa Godin, Jerry Eichler
Given its central role in various biological systems, as well as its involvement in numerous pathologies, the mitochondrion is one of the best-studied organelles. However, although the mitochondrial genome has been extensively investigated, protein-level information remains partial, and in many cases, hypothetical. The Mitochondrial Protein Atlas (MPA; URL: lifeserv.bgu.ac.il/wb/jeichler/MPA ) is a database that provides a complete, manually curated inventory of only experimentally validated human mitochondrial proteins...
June 20, 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/28631009/methods-of-probing-the-interactions-between-small-molecules-and-disordered-proteins
#9
REVIEW
Gabriella T Heller, Francesco A Aprile, Michele Vendruscolo
It is generally recognized that a large fraction of the human proteome is made up of proteins that remain disordered in their native states. Despite the fact that such proteins play key biological roles and are involved in many major human diseases, they still represent challenging targets for drug discovery. A major bottleneck for the identification of compounds capable of interacting with these proteins and modulating their disease-promoting behaviour is the development of effective techniques to probe such interactions...
June 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28630587/the-most-common-technologies-and-tools-for-functional-genome-analysis
#10
Evelina Gasperskaja, Vaidutis Kučinskas
Since the sequence of the human genome is complete, the main issue is how to understand the information written in the DNA sequence. Despite numerous genome-wide studies that have already been performed, the challenge to determine the function of genes, gene products, and also their interaction is still open. As changes in the human genome are highly likely to cause pathological conditions, functional analysis is vitally important for human health. For many years there have been a variety of technologies and tools used in functional genome analysis...
2017: Acta medica Lituanica
https://www.readbyqxmd.com/read/28627464/analysis-of-protein-complexes-in-arabidopsis-leaves-using-size-exclusion-chromatography-and-label-free-protein-correlation-profiling
#11
Uma K Aryal, Zachary McBride, Donglai Chen, Jun Xie, Daniel B Szymanski
Protein complexes are fundamentally important for diverse cellular functions, and create functionalities that could never be achieved by a single polypeptide. Knowledge of the protein complex assemblies that exist in plant cells are limited. To close this gap, we applied an integrative proteomic approach that combines cell fractionation, protein chromatography and quantitative mass spectrometry (MS) to analyze the oligomerization state of thousands of proteins in a single experiment. Soluble extracts from intact Arabidopsis leaves were fractionated using size exclusion chromatography (SEC), and abundance profiles across the column fractions were quantified using label-free precursor ion (MS1) intensity...
June 13, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28626931/insecticide-resistance-and-intracellular-proteases
#12
REVIEW
Richard M Wilkins
Pesticide resistance is an example of evolution in action with mechanisms of resistance arising from mutations or increased expression of intrinsic genes. Intracellular proteases have a key role in maintaining healthy cells and in responding to stressors such as pesticides. Insecticide resistant insects have constitutively elevated intracellular protease activity when compared to corresponding susceptible strains. This increase was shown for some cases originally through biochemical enzyme studies and subsequently putatively by transcriptomics and proteomics methods...
June 19, 2017: Pest Management Science
https://www.readbyqxmd.com/read/28624540/cross-%C3%AE-polymerization-and-hydrogel-formation-by-low-complexity-sequence-proteins
#13
Masato Kato, Yi Lin, Steven L McKnight
Low-complexity (LC) sequences, typically believed to be incapable of assuming structural order, are abundant constituents of the proteomes of all eukaryotic organisms. These sequences have emerged as critical components for formation of meso-scaled, sub-cellular organelles not invested by surrounding membranes, exemplified by RNA granules. We have observed that LC domains of many RNA binding proteins known to be constituents of RNA granules readily form labile cross-β polymers under physiological conditions...
June 14, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28623316/revealing-protein-networks-and-gene-drug-connectivity-in-cancer-from-direct-information
#14
Xian-Li Jiang, Emmanuel Martinez-Ledesma, Faruck Morcos
The connection between genetic variation and drug response has long been explored to facilitate the optimization and personalization of cancer therapy. Crucial to the identification of drug response related genetic features is the ability to separate indirect correlations from direct correlations across abundant datasets with large number of variables. Here we analyzed proteomic and pharmacogenomic data in cancer tissues and cell lines using a global statistical model connecting protein pairs, genes and anti-cancer drugs...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622336/a-knowledge-based-t2-statistic-to-perform-pathway-analysis-for-quantitative-proteomic-data
#15
En-Yu Lai, Yi-Hau Chen, Kun-Pin Wu
Approaches to identify significant pathways from high-throughput quantitative data have been developed in recent years. Still, the analysis of proteomic data stays difficult because of limited sample size. This limitation also leads to the practice of using a competitive null as common approach; which fundamentally implies genes or proteins as independent units. The independent assumption ignores the associations among biomolecules with similar functions or cellular localization, as well as the interactions among them manifested as changes in expression ratios...
June 16, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28619636/isolation-and-characterization-of-a-non-specific-lipid-transfer-protein-from-chelidonium-majus-l-latex
#16
Robert Nawrot, Damian Jozefiak, Anna Sip, Dorota Kuzma, Oskar Musidlak, Anna Gozdzicka-Jozefiak, Jakub Barylski
Plant non-specific lipid transfer proteins (nsLTPs) are small basic proteins, which mostly play a role in intracellular lipid transport and antimicrobial defense. Recently it was shown using shotgun proteomic approach that the whole plant extract of Chelidonium majus L. (Papaveraceae) contains relatively abundant nsLTPs. Therefore the aim of the work was to isolate and characterize nsLTP from C. majus latex. RESULTS: obtained using PCR approach with degenerate primers showed nsLTP protein from C...
June 12, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28617227/in-silico-re-identification-of-properties-of-drug-target-proteins
#17
Baeksoo Kim, Jihoon Jo, Jonghyun Han, Chungoo Park, Hyunju Lee
BACKGROUND: Computational approaches in the identification of drug targets are expected to reduce time and effort in drug development. Advances in genomics and proteomics provide the opportunity to uncover properties of druggable genomes. Although several studies have been conducted for distinguishing drug targets from non-drug targets, they mainly focus on the sequences and functional roles of proteins. Many other properties of proteins have not been fully investigated. METHODS: Using the DrugBank (version 3...
May 31, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28617221/identification-of-cancer-specific-motifs-in-mimotope-profiles-of-serum-antibody-repertoire
#18
Ekaterina Gerasimov, Alex Zelikovsky, Ion Măndoiu, Yurij Ionov
BACKGROUND: For fighting cancer, earlier detection is crucial. Circulating auto-antibodies produced by the patient's own immune system after exposure to cancer proteins are promising bio-markers for the early detection of cancer. Since an antibody recognizes not the whole antigen but 4-7 critical amino acids within the antigenic determinant (epitope), the whole proteome can be represented by a random peptide phage display library. This opens the possibility to develop an early cancer detection test based on a set of peptide sequences identified by comparing cancer patients' and healthy donors' global peptide profiles of antibody specificities...
June 7, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28616130/quantitative-investigation-of-human-cell-surface-n-glycoprotein-dynamics
#19
Haopeng Xiao, Ronghu Wu
Surface glycoproteins regulate nearly every extracellular event and they are dynamic for cells to adapt to the ever-changing extracellular environment. These glycoproteins contain a wealth of information on cellular development and disease states, and have significant biomedical implications. Systematic investigation of surface glycoproteins will result in a better understanding of surface protein functions, cellular activities and the molecular mechanisms of disease. However, it is extraordinarily challenging to specifically and globally analyze surface glycoproteins...
January 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28615669/differential-effects-of-a-post-anthesis-heat-stress-on-wheat-triticum-aestivum-l-grain-proteome-determined-by-itraq
#20
Yufeng Zhang, Jiajia Pan, Xiuwen Huang, Dandan Guo, Hongyao Lou, Zhenghong Hou, Meng Su, Rongqi Liang, Chaojie Xie, Mingshan You, Baoyun Li
Heat stress, a major abiotic stressor of wheat (Triticum aestivum L.), often results in reduced yield and decreased quality. In this study, a proteomic method, Tags for Relative and Absolute Quantitation Isobaric (iTRAQ), was adopted to analyze the protein expression profile changes among wheat cultivar Jing411 under heat stress. Results indicated that there were 256 different proteins expressed in Jing411 under heat stress. According to the result of gene annotation and functional classification, 239 proteins were annotated by 856 GO function entries, including growth and metabolism proteins, energy metabolism proteins, processing and storage proteins, defense-related proteins, signal transduction, unknown function proteins and hypothetical proteins...
June 14, 2017: Scientific Reports
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