26 research outputs found

    Higher Energy Collisional Dissociation Mass Spectrometry of Sulfated O‑Linked Oligosaccharides

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    Sulfation is the final decoration of mucin-type O-linked oligosaccharides before mucins are released into the lumen of the gastrointestinal, respiratory, and genital tracts. Because only a fraction of oligosaccharides undergo this type of modifications in the Golgi apparatus, sometimes also only by dedicated cells, the glycobiology of these low abundant sulfated oligosaccharides is often overlooked. At the same time, the technology to consistently identify and characterize them has been lagging. We adopted higher energy collisional dissociation to characterize sulfated oligosaccharides from porcine gastric and human salivary MUC5B mucins. With this approach we could generate conclusive spectra up to nonasaccharides. Both singly and doubly sulfated oligosaccharides were characterized. By comparing the fragmentation of low-mass fragments of m/z 100–320 with standards for six-linked and three-linked sulfate, it could be shown that characteristic fragmentation exists, verifying that porcine gastric mucin contains mostly six-linked sulfate to GlcNAc, whereas human MUC5B contains mostly three-linked Gal. When performing ion-trap MS2 fragmentation, these low-molecular-mass fragments are usually not detected. Hence it can be concluded that to be able to address biological questions of sulfation low-mass fragments are important for the assignment of sulfate position

    Higher Energy Collisional Dissociation Mass Spectrometry of Sulfated O-Linked Oligosaccharides

    No full text
    Sulfation is the final decoration of mucin-type O-linked oligosaccharides before mucins are released into the lumen of the gastrointestinal, respiratory, and genital tracts. Because only a fraction of oligosaccharides undergo this type of modifications in the Golgi apparatus, sometimes also only by dedicated cells, the glycobiology of these low abundant sulfated oligosaccharides is often overlooked. At the same time, the technology to consistently identify and characterize them has been lagging. We adopted higher energy collisional dissociation to characterize sulfated oligosaccharides from porcine gastric and human salivary MUC5B mucins. With this approach we could generate conclusive spectra up to nonasaccharides. Both singly and doubly sulfated oligosaccharides were characterized. By comparing the fragmentation of low-mass fragments of m/z 100-320 with standards for six-linked and three linked sulfate, it could be shown that characteristic fragmentation exists, verifying that porcine gastric mucin contains mostly six linked sulfate to GlcNAc, whereas human MUC5B contains mostly three-linked Gal. When performing ion-trap MS2 fragmentation, these low-molecular-mass fragments are usually not detected. Hence it can be concluded that to be able to address biological questions of sulfation low-mass fragments are important for the assignment of sulfate position

    Time-dependent therapeutic roles of nitazoxanide on high-fat diet/streptozotocin-induced diabetes in rats: Effects on hepatic PPAR-γ receptors.

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    Targeting Peroxisome Proliferator-Activated Receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for the diabetes mellitus (DM)-type 2. The PPAR-γ modulators display improvements in the insulin sensitizing and adverse effects of the traditional thiazolidinediones (TZDs). Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand, with agonistic post-transcriptional effects. Currently, NTZ-antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozotocin (HFD/STZ) rat model of type-2 diabetes was explored. Diabetic adult male Wistar rats were treated orally by either PIO (2.7 mg/kg/day) or NTZ (200 mg/kg/day) for 14, 21, and 28 days. Body weights, fasting blood glucose, insulin resistance, lipid profiles, and liver and kidney functions of rats were assayed. The hepatic glucose metabolism, and PPAR-γ protein expressional levels, as well as the hepatic, pancreatic, muscular, and renal histopathology, were evaluated. Significant time-dependent euglycemic, and insulin sensitizing effects, with preservation of liver and kidney functions were offered by NTZ. Higher hepatic levels of glucose-6-phosphatase (G-6-P) and glucose-6-phosphate dehydrogenase (G-6-PD) enzymes, and PPAR-γ proteins expressions were acquired by NTZ and PIO, respectively. NTZ could be considered an oral therapeutic strategy for DM-type-2. Further systematic NTZ/PPAR-γ receptor subtypes molecular activations are recommended. Simultaneous use of NTZ with other approved antidiabetics should be explored.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

    Analysis of mucosal mucins separated by SDS-urea agarose polyacrylamide composite gel electrophoresis

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    Efficient separation of mucins (200?kDa2?MDa) was demonstrated using gradient SDS agarose/polyacrylamide composite gel electrophoresis (SDS-AgPAGE). Inclusion of urea (SDS-UAgPAGE) in the gels casting were shown to have no effect on the migration of mucins in the gel and allowed casting of gel at room temperature. This simplified the procedure for multiple casting of agarose polyacrylamide gradients and increased reproducibility of these gels. Hence, the implementation of urea makes the technique applicable for high throughput isolation and screening of mucin oligosaccharides by LC-MS after releasing the oligosaccharides from isolated, blotted mucin subpopulations. It was also shown that the urea addition had no effect on other supporting applications such as western and lectin blotting. In addition, identification of the mucin protein after tryptic digestion and LC-MS was possible and no protein carbamylation due to the presence of urea in the gel was detected. LC-MS software developed for metabolomic analysis was used for O-linked oligosaccharide detection and differential display of various mucin samples. Using this method, heterogeneous glycosylation of mucins and mucin-type molecules isolated by SDS-AgPAGE and SDS-UAgPAGE was shown to consist of more than 80 different components in a single band, and in the extreme cases, up to 300500 components (MUC5B/AC from saliva and sputum and). Metabolomic software was also used to show that the migration of mucin isoforms within the gel is due to heterogeneous size distribution of the oligosaccharides, with the slower migrating bands enriched in high-molecular-weight oligosaccharides

    Lagrangian tracking in stochastic fields with application to an ensemble of velocity fields in the Red Sea

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    Lagrangian tracking of passive tracers in a stochastic velocity field within a sequential ensemble data assimilation framework is challenging due to the exponential growth in the number of particles. This growth arises from describing the behavior of velocity over time as a set of possible combinations of the different realizations, before and after each assimilation cycle. This paper addresses the problem of efficiently advecting particles in stochastic flow fields, whose statistics are prescribed by an underlying ensemble, in a parallel computational framework (openMP). To this end, an efficient algorithm for forward and backward tracking of passive particles in stochastic flow-fields is presented. The algorithm, which employs higher order particle advection schemes, presents a mechanism for controlling the growth in the number of particles. The mechanism uses an adaptive binning procedure, while conserving the zeroth, first and second moments of probability (total probability, mean position, and variance). The adaptive binning process offers a tradeoff between speed and accuracy by limiting the number of particles to a desired maximum. To validate our method, we conducted various forward and backward particles tracking experiments within a realistic high-resolution ensemble assimilation setting of the Red Sea, focusing on the effect of the maximum number of particles, the time step, the variance of the ensemble, the travel time, the source location, and history of transport. © 2018 Elsevier Lt

    Outdoor air pollution and respiratory health: a bibliometric analysis of publications in peer-reviewed journals (1900 – 2017)

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    Abstract Background Outdoor air pollution is a major threat to global public health that needs responsible participation of researchers at all levels. Assessing research output is an important step in highlighting national and international contribution and collaboration in a certain field. Therefore, the aim of this study was to analyze globally-published literature in outdoor air pollution – related respiratory health. Method Outdoor air pollution documents related to respiratory health were retrieved from Scopus database. The study period was up to 2017. Mapping of author keywords was carried out using VOSviewer 1.6.6. Results Search query yielded 3635 documents with an h-index of 137. There was a dramatic increase in the number of publications in the last decade of the study period. The most frequently encountered author keywords were: air pollution (835 occurrences), asthma (502 occurrences), particulate matter (198 occurrences), and children (203 occurrences). The United States of America ranked first (1082; 29.8%) followed by the United Kingdom (279; 7.7%) and Italy (198; 5.4%). Annual research productivity stratified by income and population size indicated that China ranked first (22.2) followed by the USA (18.8). Analysis of regional distribution of publications indicated that the Mediterranean, African, and South-East Asia regions had the least contribution. Harvard University (92; 2.5%) was the most active institution/organization followed the US Environmental Protection Agency (89; 2.4%). International collaboration was restricted to three regions: Northern America, Europe, and Asia. The top ten preferred journals were in the field of environmental health and respiratory health. Environmental Health Perspective was the most preferred journal for publishing documents in outdoor pollution in relation to respiratory health. Conclusion Research on the impact of outdoor air pollution on respiratory health had accelerated lately and is receiving a lot of interest. Global research networks that include countries with high level of pollution and limited resources are highly needed to create public opinion in favor of minimizing outdoor air pollution and investing in green technologies

    O-linked oligosaccharides from salivary agglutinin: helicobacter pylori binding sialyl-lewis x and lewis b are terminating moieties on hyperfucosylated oligo-n-acetyllactosamine

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    Salivary agglutinin plays a vital biological role modulating the protective effect in the oral cavity by interacting with a broad range of oral pathogens. Here, we describe the first characterization of the O-linked oligosaccharides of salivary agglutinin identified by negative ion liquid chromatography-mass spectrometry. The dominating structures were neutral or monosialylated core 1 (Gal beta 1-3GalNAc alpha 1-Ser/Thr) and core 2 (Gal beta 1-3(GlcNAc beta 1-6)GalNAc alpha 1-Ser/Thr) structures extended by fucosylated oligo-N-acetyllactosamine units. Oligosaccharides detected as [M-H](-) or [M-2H](2-) ions ranged from the disaccharide Gal beta 1-3GalNAcol up to structures of almost 4000 Da, corresponding to core 1/2 structures with five N-acetyllactosamine units and 11 fucoses. Fucose was found either as terminal or internal blood group H structures in type 1 (Gal beta 1-3GlcNAc beta 1-R), type 2 (Gal beta 1-4GlcNAc beta 1-R) and type 3 (Gal beta 1-3GalNAc alpha 1-Ser/Thr) units, where the chains also could be fucosylated on GlcNAc yielding repeated Lewis a/b or Lewis x/y structures. Sialylation was located either at the non-reducing end of the N-acetyllactosamine chains as sialyl-Lewis x or as sialyl-T (NeuAc alpha 2-3Gal beta 1-3GalNAc alpha 1-Ser/Thr) type structures with or without further extension of the C-6 branch of GalNAc with neutral fucosylated N-acetyllactosamine chains. The data indicated that sialylation, fucosylation and type 1 N-acetyllactosamine termination are important regulatory elements for controlling the oligosaccharide chain length. Furthermore, it was shown that these regulatory oligosaccharide elements could be utilized by the pathogen Helicobacter pylori to colonize the oral cavity, reside in dental plaque and serve as a reservoir for reinfection after successful clearance of H. pylori gastric infection

    O-linked oligosaccharides from salivary agglutinin: helicobacter pylori binding sialyl-lewis x and lewis b are terminating moieties on hyperfucosylated oligo-n-acetyllactosamine

    No full text
    Salivary agglutinin plays a vital biological role modulating the protective effect in the oral cavity by interacting with a broad range of oral pathogens. Here, we describe the first characterization of the O-linked oligosaccharides of salivary agglutinin identified by negative ion liquid chromatography-mass spectrometry. The dominating structures were neutral or monosialylated core 1 (Gal beta 1-3GalNAc alpha 1-Ser/Thr) and core 2 (Gal beta 1-3(GlcNAc beta 1-6)GalNAc alpha 1-Ser/Thr) structures extended by fucosylated oligo-N-acetyllactosamine units. Oligosaccharides detected as [M-H](-) or [M-2H](2-) ions ranged from the disaccharide Gal beta 1-3GalNAcol up to structures of almost 4000 Da, corresponding to core 1/2 structures with five N-acetyllactosamine units and 11 fucoses. Fucose was found either as terminal or internal blood group H structures in type 1 (Gal beta 1-3GlcNAc beta 1-R), type 2 (Gal beta 1-4GlcNAc beta 1-R) and type 3 (Gal beta 1-3GalNAc alpha 1-Ser/Thr) units, where the chains also could be fucosylated on GlcNAc yielding repeated Lewis a/b or Lewis x/y structures. Sialylation was located either at the non-reducing end of the N-acetyllactosamine chains as sialyl-Lewis x or as sialyl-T (NeuAc alpha 2-3Gal beta 1-3GalNAc alpha 1-Ser/Thr) type structures with or without further extension of the C-6 branch of GalNAc with neutral fucosylated N-acetyllactosamine chains. The data indicated that sialylation, fucosylation and type 1 N-acetyllactosamine termination are important regulatory elements for controlling the oligosaccharide chain length. Furthermore, it was shown that these regulatory oligosaccharide elements could be utilized by the pathogen Helicobacter pylori to colonize the oral cavity, reside in dental plaque and serve as a reservoir for reinfection after successful clearance of H. pylori gastric infection.peer-reviewe

    Global research trends of literature in sugar-sweetened beverages: 2000–2016

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    BACKGROUND: Sugar-sweetened beverages (SSBs) are commonly used. The objective of this study was to analyze the quantity and quality of published literature on SSBs and present the results in a bibliometric format. METHODOLOGY: Scopus database was used to retrieve documents from 2000 to 2015. Annual growth of publications, collaborations, geographic distribution, visualization and mapping of collaboration, author analysis, and top-cited articles will be presented and discussed. RESULTS: The total number of worldwide publications on SSBs was 3345, published in 27 subject areas. More than half (58.30%) of the SSB publications were within the area of medicine. The number of publications gradually increased until 2013 followed by a steady state. The median of number of citations was 3 (0–14) per document. The annual growth rate of publications on SSBs dropped from 15.22 in 2001 to 1.00 in 2016. The total number of authors was 13,813, with a mean of 3.72 ± 0.72 authors per document. Most documents (2942, 87.95%) were multi-authored publications. The USA was the most productive country (1062; 31.75%) followed by the United Kingdom (234; 7%) and Brazil (171, 5.11%). Harvard University was the leading institution with 112 publications. The most commonly preferred journal for publishing was “Public Health Nutrition” with 81 publications. Half of the top ten preferred journals were in the field of nutrition. CONCLUSION: Bibliometric analysis of literature on SSBs is one method to enrich literature and encourage health policymakers and nutrition specialists to take the case of SSBs one step further to limit the consumption of SSBs
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