10 results on '"Nicole Gorman"'
Search Results
2. Plasma Markers of Disrupted Gut Permeability in Severe COVID-19 Patients
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Leila B. Giron, Harsh Dweep, Xiangfan Yin, Han Wang, Mohammad Damra, Aaron R. Goldman, Nicole Gorman, Clovis S. Palmer, Hsin-Yao Tang, Maliha W. Shaikh, Christopher B. Forsyth, Robert A. Balk, Netanel F. Zilberstein, Qin Liu, Andrew Kossenkov, Ali Keshavarzian, Alan Landay, and Mohamed Abdel-Mohsen
- Subjects
SARS-CoV-2 ,COVID-19 ,microbial translocation ,inflammation ,zonulin ,metabolomics ,Immunologic diseases. Allergy ,RC581-607 - Abstract
A disruption of the crosstalk between the gut and the lung has been implicated as a driver of severity during respiratory-related diseases. Lung injury causes systemic inflammation, which disrupts gut barrier integrity, increasing the permeability to gut microbes and their products. This exacerbates inflammation, resulting in positive feedback. We aimed to test whether severe Coronavirus disease 2019 (COVID-19) is associated with markers of disrupted gut permeability. We applied a multi-omic systems biology approach to analyze plasma samples from COVID-19 patients with varying disease severity and SARS-CoV-2 negative controls. We investigated the potential links between plasma markers of gut barrier integrity, microbial translocation, systemic inflammation, metabolome, lipidome, and glycome, and COVID-19 severity. We found that severe COVID-19 is associated with high levels of markers of tight junction permeability and translocation of bacterial and fungal products into the blood. These markers of disrupted intestinal barrier integrity and microbial translocation correlate strongly with higher levels of markers of systemic inflammation and immune activation, lower levels of markers of intestinal function, disrupted plasma metabolome and glycome, and higher mortality rate. Our study highlights an underappreciated factor with significant clinical implications, disruption in gut functions, as a potential force that may contribute to COVID-19 severity.
- Published
- 2021
- Full Text
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3. Using a novel framework of animal space-use behaviors reveals a gradient of responses to human modification
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Nicole Gorman, Mike Eichholz, Daniel Skinner, Peter Schlichting, and Guillaume Bastille-Rousseau
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Spatial behavior, including home-ranging behaviors, habitat selection, and movement, can be extremely informative in estimating how animals respond to landscape heterogeneity. Responses in these spatial behaviors to factors such as human modification and resources on the landscape can highlight a species’ spatial strategy to maximize fitness and minimize risk. These strategies can vary on spatial, temporal, and individual scales, and the combination of behaviors on these scales can lead to very different strategies among species. Harnessing the variation present at these scales, we developed a framework for predicting how species may respond to changes in their environments on a gradient ranging from generic, where a species exhibits broad-stroke spatial responses to their environment, to nuanced, in which a species uses a combination of temporal and spatial strategies paired with functional responses in selection behaviors. Using 46 GPS-tracked bobcats and coyotes inhabiting a landscape encompassing a range of human modification, we evaluated where each species falls along the generic-to-nuanced gradient. Bobcats and coyotes studied occupied opposite ends of this gradient, using different strategies in response to human modification in their home ranges, with bobcats broadly expanding their home range with increases in human modification and clearly selecting for or avoiding features on the landscape with temporal consistency. Meanwhile, coyotes did not expand their home ranges with human modification, but instead displayed temporal and spatial adjustments in their functional responses to human modification. These differences in response to habitat, resources, and risk between the two species highlighted the variation in spatial behaviors animals can use to exist in anthropogenic environments influenced by interspecific variation in behavioral plasticity. Categorizing animal spatial behavior based on the generic-to-nuanced gradient can help in predicting how a species will respond to future change based on their current spatial behavior.
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- 2023
4. Steric-free bioorthogonal profiling of cellular acetylation and glycosylation via a fluorine-selenol displacement reaction (FSeDR)
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Yue Zhao, Mi Zhao, Zhigang Lyu, Nicole Gorman, Todd R. Lewis, Aaron R. Goldman, Hsin-Yao Tang, and Rongsheng E. Wang
- Abstract
Global detection and identification of protein post-translational modification (PTM) is a major bottleneck due to its dynamic property and rather low abundance. Tremendous efforts have been since made to develop antibody-based immunoaffinity enrichment or bioorthogonal chemistry-based chemical reporter approach but both suffer from inherent limitations. Following our previously reported steric-free tagging strategy, we hereby report the invention of selenol as a new generation of fluorine-displacement probe. The fluorine-selenol based displacement reaction enabled us to efficiently label and image acetylation and glycosylation at cellular level. We further pursued FSeDR in tandem with SILAC based quantitative proteomics to globally profile acetylation substrate proteins in a representative prostate cancer cell line PC3. Our results unraveled the fluorine-based toolbox for powerful chemical biology probing and allow for the future study of PTMs in a systemic manner.
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- 2022
5. Steric-Free Bioorthogonal Labeling of Acetylation Substrates Based on a Fluorine–Thiol Displacement Reaction
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Zakey Yusuf Buuh, Nicole Gorman, Hsin-Yao Tang, Zhigang Lyu, Aaron R. Goldman, Yue Zhao, Rongsheng E. Wang, and Shafiqul Islam
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Steric effects ,Fluorophore ,Biotin ,Alkyne ,Proof of Concept Study ,Biochemistry ,Article ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Acetyl Coenzyme A ,Acetyltransferases ,Humans ,Sulfhydryl Compounds ,Fluorescent Dyes ,chemistry.chemical_classification ,Molecular Structure ,Rhodamines ,Chemistry ,Substrate (chemistry) ,Acetylation ,General Chemistry ,Combinatorial chemistry ,HEK293 Cells ,Biocatalysis ,Molecular Probes ,Azide ,Bioorthogonal chemistry - Abstract
We have developed a novel bioorthogonal reaction that can selectively displace fluorine substitutions alpha to amide bonds. This fluorine–thiol displacement reaction (FTDR) allows for fluorinated cofactors or precursors to be utilized as chemical reporters, hijacking acetyltransferase-mediated acetylation both in vitro and in live cells, which cannot be achieved with azide- or alkyne-based chemical reporters. The fluoroacetamide labels can be further converted to biotin or fluorophore tags using FTDR, enabling the general detection and imaging of acetyl substrates. This strategy may lead to a steric-free labeling platform for substrate proteins, expanding our chemical toolbox for functional annotation of post-translational modifications in a systematic manner.
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- 2021
6. MYC regulates fatty acid metabolism through a multigenic program in claudin-low triple negative breast cancer
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Johan Vande Voorde, Caroline Perry, Ann Hedley, Richard Schlegel, Mairi E. Sandison, David W. Speicher, Tony McBryan, Zachary T. Schug, Susan Chalmers, Peter D. Adams, Adam J. Cohen-Nowak, Qin Liu, Eyal Gottlieb, Andrew V. Kossenkov, Hsin-Yao Tang, Jessica C. Casciano, Katelyn D. Miller, John G. McCarron, Nicole Gorman, Qifeng Zhang, Michael J.O. Wakelam, Xuefeng Liu, and Thomas Beer
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RM ,Cancer Research ,Epithelial-Mesenchymal Transition ,Triple Negative Breast Neoplasms ,PDGFRB ,Biology ,Transfection ,Article ,Proto-Oncogene Proteins c-myc ,RC0254 ,Transcriptome ,03 medical and health sciences ,chemistry.chemical_compound ,Breast cancer ,0302 clinical medicine ,Cell Line, Tumor ,Metabolomics ,Humans ,Beta oxidation ,Triple-negative breast cancer ,Cell Proliferation ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Fatty acid metabolism ,Kinase ,digestive, oral, and skin physiology ,Fatty Acids ,Fatty acid ,Oncogenes ,Claudin-Low ,Cancer metabolism ,3. Good health ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Claudins ,Cancer research ,Female - Abstract
BackgroundRecent studies have suggested that fatty acid oxidation (FAO) is a key metabolic pathway for the growth of triple negative breast cancers (TNBCs), particularly those that have high expression of MYC. However, the underlying mechanism by which MYC promotes FAO remains poorly understood.MethodsWe used a combination of metabolomics, transcriptomics, bioinformatics, and microscopy to elucidate a potential mechanism by which MYC regulates FAO in TNBC.ResultsWe propose that MYC induces a multigenic program that involves changes in intracellular calcium signalling and fatty acid metabolism. We determined key roles for fatty acid transporters (CD36), lipases (LPL), and kinases (PDGFRB, CAMKK2, and AMPK) that each contribute to promoting FAO in human mammary epithelial cells that express oncogenic levels of MYC. Bioinformatic analysis further showed that this multigenic program is highly expressed and predicts poor survival in the claudin-low molecular subtype of TNBC, but not other subtypes of TNBCs, suggesting that efforts to target FAO in the clinic may best serve claudin-low TNBC patients.ConclusionWe identified critical pieces of the FAO machinery that have the potential to be targeted for improved treatment of patients with TNBC, especially the claudin-low molecular subtype.
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- 2020
7. Steric-Free Bioorthogonal Labeling of Acetylation Substrates Based on a Fluorine-Thiol Displacement Reaction (FTDR)
- Author
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Shafiqul Islam, Nicole Gorman, Yue Zhao, Hsin-Yao Tang, Zakey Yusuf Buuh, Zhigang Lyu, Rongsheng E. Wang, and Aaron R. Goldman
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chemistry.chemical_classification ,Steric effects ,chemistry.chemical_compound ,Fluorophore ,Chemistry ,Acetylation ,Acetyltransferase ,Alkyne ,Substrate (chemistry) ,Azide ,Bioorthogonal chemistry ,Combinatorial chemistry - Abstract
We have developed a novel bioorthogonal reaction that can selectively displace fluorine substitutions alpha to amide bonds. This fluorine-thiol displacement reaction (FTDR) allows for fluorinated cofactors or precursors to be utilized as chemical reporters; hijacking acetyltransferase mediated acetylation both in vitro and in live cells, which cannot be achieved with azide- or al- kyne- based chemical reporters. The fluoroacetamide labels can be further converted to biotin or fluorophore tags using FTDR, enabling the general detection and imaging of acetyl substrates. This strategy may lead to a steric-free labeling platform for substrate proteins, expanding our chemical toolbox for functional annotation of post-translational modifications (PTMs) in a systematic manner.
- Published
- 2020
8. Planning Telehealth for Older Adults With Atrial Fibrillation in Rural Communities: Understanding Stakeholder Perspectives
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Louann Janicki, Petr Polasek, Nicole Gorman, Matt Shay, Kathy L. Rush, and Linda Hatt
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Male ,Canada ,Health Personnel ,education ,Specialty ,Professional practice ,Telehealth ,Interviews as Topic ,03 medical and health sciences ,0302 clinical medicine ,Nursing ,Stakeholder Participation ,Atrial Fibrillation ,Humans ,In patient ,030212 general & internal medicine ,Qualitative Research ,health care economics and organizations ,General Nursing ,Aged ,030504 nursing ,Rural health ,Qualitative descriptive ,Stakeholder ,Telemedicine ,Telephone ,Female ,Rural Health Services ,0305 other medical science ,Psychology ,Healthcare providers - Abstract
Older adults with atrial fibrillation (AF) in rural communities have less access to cardiac specialty care. Telehealth offers a viable approach to provide cardiac care, yet little is known about patients’ and providers’ views on telehealth’s potential to support rural patients with AF. This qualitative descriptive study examines patient and health providers’ perspectives, an important first step in planning a telehealth initiative. Eight patients with AF, along with one partner from rural communities, were recruited through an urban-based AF clinic. Five providers were recruited through professional practice leads in the health region. Semistructured telephone interviews were conducted with both stakeholder groups. The overriding theme was variability in patient and provider receptiveness to telehealth. Receptiveness reflected differences in past experience with telehealth, in perceived adequacy of rural health services, and in perceived gaps in AF care. These are important considerations in planning effective and sustainable telehealth in rural communities.
- Published
- 2018
9. The Stressors and Coping Strategies of Older Adults With Persistent Atrial Fibrillation Prior to and Following Direct Current Cardioversion
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Ryan Wilson, Linda Hatt, Kathy L. Rush, R. Colin Reid, Nicole Gorman, Carol G Laberge, and Matt Shay
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Male ,Coping (psychology) ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Electric Countershock ,030204 cardiovascular system & hematology ,Cardioversion ,Interviews as Topic ,03 medical and health sciences ,0302 clinical medicine ,Adaptation, Psychological ,Atrial Fibrillation ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Aged, 80 and over ,business.industry ,Self-Management ,Stressor ,Qualitative descriptive ,Atrial fibrillation ,Middle Aged ,medicine.disease ,Persistent atrial fibrillation ,Direct current cardioversion ,Physical therapy ,Female ,Geriatrics and Gerontology ,business ,Gerontology ,Stress, Psychological - Abstract
Objective:The purpose of this study was to explore the stressors and coping strategies of older adults with persistent atrial fibrillation (AF) before and after direct current cardioversion. Method: The study used a qualitative descriptive design. Sixteen patients were recruited through an AF clinic to participate in individual interviews prior to the cardioversion and at 6 and 12 weeks post procedure. Results: Pre-cardioversion, older adults experienced symptom and health care–related stressors superimposed on existing non-AF stressors. They used a range of emotion and problem-focused coping. Non-AF stressors increased post procedure at the same time that participants perceived less need for coping strategies with a return to regular rhythm. Discussion: There was a shift from AF to non-AF related stressors following the cardioversion but a decrease in coping strategies. Older adults with AF should be encouraged to maintain use of coping strategies to manage ongoing stress and reduce the risk of AF recurrence.
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- 2015
10. N-terminal sequence analysis of proteins and peptides
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Kaye D. Speicher, David W. Speicher, and Nicole Gorman
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Sequence analysis ,Molecular Sequence Data ,Peptide ,Biology ,Biochemistry ,Article ,Protein structure ,Organophosphorus Compounds ,Structural Biology ,Protein methods ,Sequence Analysis, Protein ,Humans ,Amino Acid Sequence ,Amino Acids ,Peptide sequence ,Chromatography, High Pressure Liquid ,chemistry.chemical_classification ,Chromatography ,Edman degradation ,Proteins ,General Medicine ,Reference Standards ,Amino acid ,chemistry ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Polyvinyls ,Glass ,Bottom-up proteomics ,Peptides ,Filtration - Abstract
Amino-terminal (N-terminal) sequence analysis is used to identify the order of amino acids of proteins or peptides, starting at their N-terminal end. This unit describes the sequence analysis of protein or peptide samples in solution or bound to PVDF membranes using a Perkin-Elmer Procise Sequencer. Sequence analysis of protein or peptide samples in solution or bound to PVDF membranes using a Hewlett-Packard Model G1005A sequencer is also described. Methods are provided for optimizing separation of PTH amino acid derivatives on Perkin-Elmer instruments and for increasing the proportion of sample injected onto the PTH analyzer on older Perkin-Elmer instruments by installing a modified sample loop. The amount of data obtained from a single sequencer run is substantial, and careful interpretation of this data by an experienced scientist familiar with the current operation performance of the instrument used for this analysis is critically important. A discussion of data interpretation is therefore provided. Finally, discussion of optimization of sequencer performance as well as possible solutions to frequently encountered problems is included.
- Published
- 2009
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