Alterations in the human lung proteome with lipopolysaccharide

<p>Abstract</p> <p>Background</p> <p>Recombinant human activated protein C (rhAPC) is associated with improved survival in high-risk patients with severe sepsis; however, the effects of both lipopolysaccharide (LPS) and rhAPC on the bronchoalveolar lavage fluid (BALF) proteome are unknown.</p> <p>Methods</p> <p>Using differential in gel electrophoresis (DIGE) we identified changes in the BALF proteome from 10 healthy volunteers given intrapulmonary LPS in one lobe and saline in another lobe. Subjects were randomized to pretreatment with saline or rhAPC.</p> <p>Results</p> <p>An average of 255 protein spots were detected in each proteome. We found 31 spots corresponding to 8 proteins that displayed abundance increased or decreased at least 2-fold after LPS. Proteins that decreased after LPS included surfactant protein A, immunoglobulin J chain, fibrinogen-γ, α₁-antitrypsin, immunoglobulin, and α₂-HS-glycoprotein. Haptoglobin increased after LPS-treatment. Treatment with rhAPC was associated with a larger relative decrease in immunoglobulin J chain, fibrinogen-γ, α₁-antitrypsin, and α₂-HS-glycoprotein.</p> <p>Conclusion</p> <p>Intrapulmonary LPS was associated with specific protein changes suggesting that the lung response to LPS is more than just a loss of integrity in the alveolar epithelial barrier; however, pretreatment with rhAPC resulted in minor changes in relative BALF protein abundance consistent with its lack of affect in ALI and milder forms of sepsis.</p

Storm-induced upwelling of high pCO2 waters onto the continental shelf of the western Arctic Ocean and implications for carbonate mineral saturation states

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 39 (2012): L07606, doi:10.1029/2012GL051574.The carbon system of the western Arctic Ocean is undergoing a rapid transition as sea ice extent and thickness decline. These processes are dynamically forcing the region, with unknown consequences for CO2 fluxes and carbonate mineral saturation states, particularly in the coastal regions where sensitive ecosystems are already under threat from multiple stressors. In October 2011, persistent wind-driven upwelling occurred in open water along the continental shelf of the Beaufort Sea in the western Arctic Ocean. During this time, cold (32.4) halocline water—supersaturated with respect to atmospheric CO2 (pCO2 > 550 μatm) and undersaturated in aragonite (Ωaragonite < 1.0) was transported onto the Beaufort shelf. A single 10-day event led to the outgassing of 0.18–0.54 Tg-C and caused aragonite undersaturations throughout the water column over the shelf. If we assume a conservative estimate of four such upwelling events each year, then the annual flux to the atmosphere would be 0.72–2.16 Tg-C, which is approximately the total annual sink of CO2 in the Beaufort Sea from primary production. Although a natural process, these upwelling events have likely been exacerbated in recent years by declining sea ice cover and changing atmospheric conditions in the region, and could have significant impacts on regional carbon budgets. As sea ice retreat continues and storms increase in frequency and intensity, further outgassing events and the expansion of waters that are undersaturated in carbonate minerals over the shelf are probable.Funding for this work was provided by the National Science Foundation (ARC1041102 – JTM, OPP0856244-RSP, and ARC1040694- LWJ), the National Oceanic and Atmospheric Administration (CIFAR11021- RHB) and the West Coast & Polar Regions Undersea Research Center (POFP00983 – CLM and JM).2012-10-1

Perspective:Dietary Biomarkers of Intake and Exposure - Exploration with Omics Approaches

While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research. The current Perspective summarizes key gaps and challenges identified, as well as the recommendations from the workshop that could serve as a guide for scientists interested in dietary biomarkers research. Topics addressed included study designs for biomarker development, analytical and bioinformatic considerations, and integration of dietary biomarkers with other omics techniques. Several clear needs were identified, including larger controlled feeding studies, testing a variety of foods and dietary patterns across diverse populations, improved reporting standards to support study replication, more chemical standards covering a broader range of food constituents and human metabolites, standardized approaches for biomarker validation, comprehensive and accessible food composition databases, a common ontology for dietary biomarker literature, and methodologic work on statistical procedures for intake biomarker discovery. Multidisciplinary research teams with appropriate expertise are critical to moving forward the field of dietary biomarkers and producing robust, reproducible biomarkers that can be used in public health and clinical research

Perspective: Dietary Biomarkers of Intake and Exposure - Exploration with Omics Approaches

While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research. The current Perspective summarizes key gaps and challenges identified, as well as the recommendations from the workshop that could serve as a guide for scientists interested in dietary biomarkers research. Topics addressed included study designs for biomarker development, analytical and bioinformatic considerations, and integration of dietary biomarkers with other omics techniques. Several clear needs were identified, including larger controlled feeding studies, testing a variety of foods and dietary patterns across diverse populations, improved reporting standards to support study replication, more chemical standards covering a broader range of food constituents and human metabolites, standardized approaches for biomarker validation, comprehensive and accessible food composition databases, a common ontology for dietary biomarker literature, and methodologic work on statistical procedures for intake biomarker discovery. Multidisciplinary research teams with appropriate expertise are critical to moving forward the field of dietary biomarkers and producing robust, reproducible biomarkers that can be used in public health and clinical research

Hands-on Workshops as An Effective Means of Learning Advanced Technologies Including Genomics, Proteomics and Bioinformatics

Genomics and proteomics have emerged as key technologies in biomedical research, resulting in a surge of interest in training by investigators keen to incorporate these technologies into their research. At least two types of training can be envisioned in

Microbiome, metabolism, and immunoregulation of asthma: an American Thoracic Society and National Institute of Allergy and Infectious Diseases workshop report

This report presents the proceedings from a workshop titled "Microbiome, Metabolism and Immunoregulation of Asthma" that was held virtually May 13 and 14, 2021. The workshop was jointly sponsored by the American Thoracic Society (Assembly on Allergy, Immunology, and Inflammation) and the National Institute of Allergy and Infectious Diseases. It convened an interdisciplinary group of experts with backgrounds in asthma immunology, microbiome science, metabolomics, computational biology, and translational pulmonary research. The main purpose was to identify key scientific gaps and needs to further advance research on microbial and metabolic mechanisms that may contribute to variable immune responses and disease heterogeneity in asthma. Discussions were structured around several topics, including 1) immune and microbial mechanisms of asthma pathogenesis in murine models, 2) the role of microbes in pediatric asthma exacerbations, 3) dysregulated metabolic pathways in asthma associated with obesity, 4) metabolism effects on macrophage function in adipose tissue and the lungs, 5) computational approaches to dissect microbiome-metabolite links, and 6) potential confounders of microbiome-disease associations in human studies. This report summarizes the major points of discussion, which included identification of specific knowledge gaps, challenges, and suggested directions for future research. These include questions surrounding mechanisms by which microbiota and metabolites shape host health versus an allergic or asthmatic state; direct and indirect influences of other biological factors, exposures, and comorbidities on these interactions; and ongoing technical and analytical gaps for clinical translation

Storm-induced Upwelling of High \u3cem\u3ep\u3c/em\u3eCO\u3csub\u3e2\u3c/sub\u3e Waters Onto the Continental Shelf of the Western Arctic Ocean and Implications for Carbonate Mineral Saturation States

The carbon system of the western Arctic Ocean is undergoing a rapid transition as sea ice extent and thickness decline. These processes are dynamically forcing the region, with unknown consequences for CO2 fluxes and carbonate mineral saturation states, particularly in the coastal regions where sensitive ecosystems are already under threat from multiple stressors. In October 2011, persistent wind-driven upwelling occurred in open water along the continental shelf of the Beaufort Sea in the western Arctic Ocean. During this time, cold (\u3c−1.2°C), salty (\u3e32.4) halocline water—supersaturated with respect to atmospheric CO2 (pCO2 \u3e 550 μatm) and undersaturated in aragonite (Ωaragonite \u3c 1.0) was transported onto the Beaufort shelf. A single 10-day event led to the outgassing of 0.18–0.54 Tg-C and caused aragonite undersaturations throughout the water column over the shelf. If we assume a conservative estimate of four such upwelling events each year, then the annual flux to the atmosphere would be 0.72–2.16 Tg-C, which is approximately the total annual sink of CO2 in the Beaufort Sea from primary production. Although a natural process, these upwelling events have likely been exacerbated in recent years by declining sea ice cover and changing atmospheric conditions in the region, and could have significant impacts on regional carbon budgets. As sea ice retreat continues and storms increase in frequency and intensity, further outgassing events and the expansion of waters that are undersaturated in carbonate minerals over the shelf are probable