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https://www.readbyqxmd.com/read/28806774/fibroblast-growth-factor-receptor-1-mediates-internalization-of-pathogenic-spotted-fever-rickettsiae-into-host-endothelium
#1
Abha Sahni, Jignesh Patel, Hema P Narra, Casey L C Schroeder, David H Walker, Sanjeev K Sahni
Rickettsial infections continue to cause serious morbidity and mortality in severe human cases around the world. Host cell adhesion and invasion is an essential requisite for intracellular growth, replication, and subsequent dissemination of pathogenic rickettsiae. Heparan sulfate proteoglycans [HSPGs] facilitate the interactions between fibroblast growth factor(s) and their tyrosine kinase receptors resulting in receptor dimerization/activation and have been implicated in bacterial adhesion to target host cells...
2017: PloS One
https://www.readbyqxmd.com/read/28805808/constraints-and-consequences-of-the-emergence-of-amino-acid-repeats-in-eukaryotic-proteins
#2
Sreenivas Chavali, Pavithra L Chavali, Guilhem Chalancon, Natalia Sanchez de Groot, Rita Gemayel, Natasha S Latysheva, Elizabeth Ing-Simmons, Kevin J Verstrepen, Santhanam Balaji, M Madan Babu
Proteins with amino acid homorepeats have the potential to be detrimental to cells and are often associated with human diseases. Why, then, are homorepeats prevalent in eukaryotic proteomes? In yeast, homorepeats are enriched in proteins that are essential and pleiotropic and that buffer environmental insults. The presence of homorepeats increases the functional versatility of proteins by mediating protein interactions and facilitating spatial organization in a repeat-dependent manner. During evolution, homorepeats are preferentially retained in proteins with stringent proteostasis, which might minimize repeat-associated detrimental effects such as unregulated phase separation and protein aggregation...
August 14, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28804598/a-rigorous-method-to-enrich-for-exosomes-from-brain-tissue
#3
Laura J Vella, Benjamin J Scicluna, Lesley Cheng, Emma G Bawden, Colin L Masters, Ching-Seng Ang, Nicholas Willamson, Catriona McLean, Kevin J Barnham, Andrew F Hill
Extracellular vesicles, including exosomes, are released by all cells, including those of the nervous system. Capable of delivering lipid, protein and nucleic acids to both nearby and distal cells, exosomes have been hypothesized to play a role in progression of many diseases of the nervous system. To date, most analyses on the role of these vesicles in the healthy and diseased state have relied on studying vesicles from in vitro sources, such as conditioned cell culture media, or body fluids. Here we have taken a critical approach to the enrichment and characterization of exosomes from human frontal cortex...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28803608/identification-of-simvastatin-regulated-targets-associated-with-jnk-activation-in-du145-human-prostate-cancer-cell-death-signaling
#4
Eun Joo Jung, Ky Hyun Chung, Choong Won Kim
In this study, our results showed that the c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1) and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways...
August 11, 2017: BMB Reports
https://www.readbyqxmd.com/read/28802824/highly-accurate-prediction-of-protein-self-interactions-by-incorporating-the-average-block-and-pssm-information-into-the-general-pseaac
#5
Jing-Xuan Zhai, Tian-Jie Cao, Ji-Yong An, Yong-Tao Bian
It is a challenging task for fundamental research whether proteins can interact with their partners. Protein self-interaction (SIP) is a special case of PPIs, which plays a key role in the regulation of cellular functions. Due to the limitations of experimental self-interaction identification, it is very important to develop an effective biological tool for predicting SIPs based on protein sequences. In the study, we developed a novel computational method called RVM-AB that combines the Relevance Vector Machine (RVM) model and Average Blocks (AB) for detecting SIPs from protein sequences...
August 9, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28802714/in-silico-structure-based-approaches-to-discover-protein-protein-interaction-targeting-drugs
#6
REVIEW
Woong-Hee Shin, Charles W Christoffer, Daisuke Kihara
A core concept behind modern drug discovery is finding a small molecule that modulates a function of a target protein. This concept has been successfully applied since the mid-1970s. However, the efficiency of drug discovery is decreasing because the druggable target space in the human proteome is limited. Recently, protein-protein interaction (PPI) has been identified as an emerging target space for drug discovery. PPI plays a pivotal role in biological pathways including diseases. Current human interactome research suggests that the number of PPIs ranges from 130,000 to 650,000, and only a small number of them have been targeted as drug targets...
August 9, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28801789/multimodal-laser-ablation-desorption-imaging-analysis-of-zn-and-mmp-11-in-breast-tissues
#7
Raquel González de Vega, María Luisa Fernández Sanchez, Noemí Eiro, Francisco J Vizoso, Michael Sperling, Uwe Karst, Alfredo Sanz Medel
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases. The main functions of these metalloproteinases are the degradation of the stromal connective tissue and basement membrane components. Recent data from model systems suggest that MMPs are involved in breast cancer (BC) initiation, invasion, and metastasis. Particularly, MMP-11 (stromelysin-3) is expressed in stromal fibroblasts adjacent to epithelial tumor cells, and high levels of this metalloproteinase were associated with tumor progression and poor prognosis of BC...
August 12, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28801230/a-mitochondrial-proteomics-view-of-complex-i-deficiency-in-candida-albicans
#8
Xiaodong She, Pengyi Zhang, Ying Gao, Lulu Zhang, Qiong Wang, Hui Chen, Richard Calderone, Weida Liu, Dongmei Li
Proteomic analyses were carried out on isolated mitochondrial samples of C. albicans from gene-deleted mutants (nuo1Δ, nuo2Δ and goa1Δ) as well as the parental strain in order to better understand the contribution of these three fungal-specific mitochondrial ETC complex I (CI) subunits to cellular activities. Herein, we identify 2333 putative proteins from four strains, in which a total of 663 proteins (28.5%) are putatively located in mitochondria. Comparison of protein abundances between mutants and the parental strain reveal 146 differentially-expressed proteins, of which 78 are decreased and 68 are increased in at least one mutant...
August 8, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28800539/development-of-a-rapid-and-sensitive-multiple-reaction-monitoring-proteomic-approach-for-quantification-of-transporters-in-human-liver-tissue
#9
Li Wang, Kasi J Rubadue, Jeffrey Alberts, David W Bedwell, Kenneth J Ruterbories
With increasing knowledge on the role of hepatic transporters in drug disposition, numerous efforts have been described to quantify the expression of human hepatic transporters. However, reported quantitative proteomic approaches often require long analysis times. Additionally, greater assay sensitivity is still necessary for less abundant transporters or limited quantity of samples (e.g. hepatocytes and liver tissue). In the present study, an LC-MS/MS method for rapid and simultaneous quantification of 12 hepatic transporters (BCRP, BSEP, MATE1, MRP2, MRP3, MRP4, NTCP, OATP1B1, 1B3, 2B1, OCT1, and P-gp) was developed...
August 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28798330/metabolic-networks-for-nitrogen-utilization-in-prevotella-ruminicola-23
#10
Jong Nam Kim, Celia Méndez-García, Renae R Geier, Michael Iakiviak, Jongsoo Chang, Isaac Cann, Roderick I Mackie
Nitrogen metabolism in gut systems remains poorly studied in spite of its importance for microbial growth and its implications for the metabolism of the host. Prevotella spp. are the most predominant bacteria detected in the rumen, but their presence has also been related to health and disease states in the human gut and oral cavity. To explore the metabolic networks for nitrogen assimilation in this bacterium, changes in gene expression profiles in response to variations in the available nitrogen source and to different concentrations of ammonium were analyzed by microarray and reverse transcription quantitative PCR, and linked with function by further proteomic analysis...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28798251/lungmap-the-molecular-atlas-of-lung-development-program
#11
Maryanne E Ardini-Poleske, Robert Fred Clark, Charles Ansong, James P Carson, Richard A Corley, Gail H Deutsch, James S Hagood, Naftali Kaminski, Thomas J Mariani, Steven S Potter, Gloria S Pryhuber, David Warburton, Jeffrey A Whitsett, Scott M Palmer, Namasivayam Ambalavanan, The LungMAP Consortium
The National Heart Lung and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic crosstalk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28797096/prediction-of-n-linked-glycosylation-sites-using-position-relative-features-and-statistical-moments
#12
Muhammad Aizaz Akmal, Nouman Rasool, Yaser Daanial Khan
Glycosylation is one of the most complex post translation modification in eukaryotic cells. Almost 50% of the human proteome is glycosylated as glycosylation plays a vital role in various biological functions such as antigen's recognition, cell-cell communication, expression of genes and protein folding. It is a significant challenge to identify glycosylation sites in protein sequences as experimental methods are time taking and expensive. A reliable computational method is desirable for the identification of glycosylation sites...
2017: PloS One
https://www.readbyqxmd.com/read/28796813/a-novel-organotypic-3d-sweat-gland-model-with-physiological-functionality
#13
Patricia Klaka, Sabine Grüdl, Bernhard Banowski, Melanie Giesen, Andrea Sättler, Peter Proksch, Thomas Welss, Thomas Förster
Dysregulated human eccrine sweat glands can negatively impact the quality-of-life of people suffering from disorders like hyperhidrosis. Inability of sweating can even result in serious health effects in humans affected by anhidrosis. The underlying mechanisms must be elucidated and a reliable in vitro test system for drug screening must be developed. Here we describe a novel organotypic three-dimensional (3D) sweat gland model made of primary human eccrine sweat gland cells. Initial experiments revealed that eccrine sweat gland cells in a two-dimensional (2D) culture lose typical physiological markers...
2017: PloS One
https://www.readbyqxmd.com/read/28795660/systems-and-synthetic-biology-perspective-of-the-versatile-plant-pathogenic-and-polysaccharide-producing-bacterium-xanthomonas-campestris
#14
Sarah Schatschneider, Jessica Schneider, Jochen Blom, Fabien Létisse, Karsten Niehaus, Alexander Goesmann, Frank-Jörg Vorhölter
Bacteria of the genus Xanthomonas are a major group of plant pathogens. They are hazardous to important crops and closely related to human pathogens. Being collectively a major focus of molecular phytopathology, an increasing number of diverse and intricate mechanisms are emerging by which they communicate, interfere with host signalling and keep competition at bay. Interestingly, they are also biotechnologically relevant polysaccharide producers. Systems biotechnology techniques have revealed their central metabolism and a growing number of remarkable features...
August 10, 2017: Microbiology
https://www.readbyqxmd.com/read/28795044/n-glycoproteomic-analysis-of-human-follicular-fluid-during-natural-and-stimulated-cycles-in-patients-undergoing-in-vitro-fertilization
#15
Hee-Joung Lim, Ae Eun Seok, Jiyou Han, Jiyeong Lee, Sungeun Lee, Hee-Gyoo Kang, Byung Heun Cha, Yunseok Yang
OBJECTIVE: Hyperstimulation methods are broadly used for in vitro fertilization (IVF) in patients with infertility; however, the side effects associated with these therapies, such as ovarian hyperstimulation syndrome (OHSS), have not been well studied. N-glycoproteomes are subproteomes used for the remote sensing of ovarian stimulation in follicular growth. Glycoproteomic variation in human follicular fluid (hFF) has not been evaluated. In this study, we aimed to identify and quantify the glycoproteomes and N-glycoproteins (N-GPs) in natural and stimulated hFF using label-free nano-liquid chromatography/electrospray ionization-quad time-of-flight mass spectrometry...
June 2017: Clinical and Experimental Reproductive Medicine
https://www.readbyqxmd.com/read/28792503/multi-scale-encoding-of-amino-acid-sequences-for-predicting-protein-interactions-using-gradient-boosting-decision-tree
#16
Chang Zhou, Hua Yu, Yijie Ding, Fei Guo, Xiu-Jun Gong
Nowadays a number of computational approaches have been developed to effectively and accurately predict protein interactions. However, most of these methods typically perform worse when other biological data sources (e.g., protein structure information, protein domains, or gene neighborhoods information) are not available. In the present work, we propose a method for predicting protein interactions making full use of physicochemical characteristics of amino acids. A protein sequence is encoded at multi-scale by seven properties, including their qualitative and quantitative descriptions, of amino acids...
2017: PloS One
https://www.readbyqxmd.com/read/28791745/a-novel-pathway-of-protein-haptenation-by-%C3%A3-lactams
#17
M Consuelo Jiménez, Raúl Pérez-Ruiz, Emilio Lence, Inmaculada Andreu, Concepción González-Bello, Miguel A Miranda, Daniel Limones-Herrero
The covalent binding of β-lactams to proteins upon photochemical activation has been demonstrated using an integrated approach that combines photochemical, proteomic and computational studies, selecting human serum albumin (HSA) as target protein and ezetimibe (1) as probe. The results have revealed a novel protein haptenation pathway by this family of drugs that is alternative to the known nucleophilic ring opening of β-lactams by the free amino group of lysine residues. Thus, photochemical ring splitting of the β-lactam ring following a formal retro-Staudinger reaction gives a highly reactive ketene intermediate that is trapped by the neighboring lysine residues, leading to an amide adduct...
August 9, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28790197/breast-tumors-educate-the-proteome-of-stromal-tissue-in-an-individualized-but-coordinated-manner
#18
Xuya Wang, Arshag D Mooradian, Petra Erdmann-Gilmore, Qiang Zhang, Rosa Viner, Sherri R Davies, Kuan-Lin Huang, Ryan Bomgarden, Brian A Van Tine, Jieya Shao, Li Ding, Shunqiang Li, Matthew J Ellis, John C Rogers, R Reid Townsend, David Fenyö, Jason M Held
Cancer forms specialized microenvironmental niches that promote local invasion and colonization. Engrafted patient-derived xenografts (PDXs) locally invade and colonize naïve stroma in mice while enabling unambiguous molecular discrimination of human proteins in the tumor from mouse proteins in the microenvironment. To characterize how patient breast tumors form a niche and educate naïve stroma, subcutaneous breast cancer PDXs were globally profiled by species-specific quantitative proteomics. Regulation of PDX stromal proteins by breast tumors was extensive, with 35% of the stromal proteome altered by tumors consistently across different animals and passages...
August 8, 2017: Science Signaling
https://www.readbyqxmd.com/read/28789634/screening-of-nucleotide-variations-in-genomic-sequences-encoding-charged-protein-regions-in-the-human-genome
#19
Sabrine Belmabrouk, Najla Kharrat, Rania Abdelhedi, Amine Ben Ayed, Riadh Benmarzoug, Ahmed Rebai
BACKGROUND: Studying genetic variation distribution in proteins containing charged regions, called charge clusters (CCs), is of great interest to unravel their functional role. Charge clusters are 20 to 75 residue segments with high net positive charge, high net negative charge, or high total charge relative to the overall charge composition of the protein. We previously developed a bioinformatics tool (FCCP) to detect charge clusters in proteomes and scanned the human proteome for the occurrence of CCs...
August 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28783398/biologics-structural-heterogeneity-and-immunogenicity
#20
Roy Jefferis
In principle the whole human proteome is available for the generation of recombinant proteins and glycoproteins that may serve as drugs (biologics). Endogenous human proteins and glycoproteins are structurally heterogeneous but are recognized as self by the immune system; however, recombinant protein and glycoprotein molecules are necessarily produced in heterologous systems and may include structural variants that are non-self and potentially immunogenic. The addition of human type oligosaccharides may be critical to function while the addition of non-human sugar residues can render biologics immunogenic...
August 2, 2017: British Journal of Hospital Medicine
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