231 results on '"M. A. Gordon"'
Search Results
2. Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure
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Roy Oelen, Dylan H. de Vries, Harm Brugge, M. Grace Gordon, Martijn Vochteloo, single-cell eQTLGen consortium, BIOS Consortium, Chun J. Ye, Harm-Jan Westra, Lude Franke, and Monique G. P. van der Wijst
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Science - Abstract
Not just differential gene expression but also differential gene regulation in immune cells account for individual differences in the immune response. Authors show here by single-cell RNA-sequencing of peripheral blood mononuclear cells from a large cohort of genetically diverse individuals that gene expression and regulatory changes in these cells depend on the context of and interactions between cell types, genetics, type of pathogen and time after exposure.
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- 2022
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3. Increased retention of tau PET ligand [18F]-AV1451 in Alzheimer’s Disease Psychosis
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J. J. Gomar, G. Tan, J. Halpern, M. L. Gordon, B. Greenwald, and J. Koppel
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Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract Psychosis in Alzheimer’s disease (AD) represents a distinct disease subtype with a more rapid progression of illness evidenced by an increased velocity of cognitive decline and a hastened mortality. Previous biomarker and post-mortem studies have implicated tau neuropathology as a possible mediator of the accelerated decline in AD psychosis. Tau positron emission tomography (PET) neuroimaging provides the opportunity to evaluate tau pathology in-vivo, so that clinical symptomatology can be correlated with disease pathology. [18F]-AV1451 (Flortaucipir) is a PET ligand with high affinity for insoluble paired-helical filaments (PHFs) of hyperphosphorylated tau. In order to determine whether the development of psychosis and worsened prognosis in AD is associated with an increased burden of tau pathology that can be identified with tau imaging, we identified subjects within the Alzheimer’s disease neuroimaging initiative (ADNI) who had [18F]-AV1451 imaging at baseline and became psychotic over the course of the study (N = 17) and matched them 1:3 for gender, age, and education to subjects who had [18F]-AV1451 imaging at baseline and did not become psychotic (N = 50). We compared baseline [18F]-AV1451 retention, in addition to cognitive and functional baseline and longitudinal change, in those who became psychotic over the course of participation in ADNI with those who did not. Results suggest that increases in tau pathology in frontal, medial temporal, and occipital cortices, visualized with [18F]-AV1451 binding, are associated with psychosis and a more rapid cognitive and functional decline.
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- 2022
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4. Evaluating COVID-19 reporting data in the context of testing strategies across 31 low- and middle-income countries
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Mollie M. Van Gordon, Kevin A. McCarthy, Joshua L. Proctor, and Brittany L. Hagedorn
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COVID-19 ,Change detection ,Disease surveillance ,Infectious and parasitic diseases ,RC109-216 - Abstract
ABSTRACT: Background: The case count for coronavirus disease 2019 (COVID-19) is the predominant measure used to track epidemiological dynamics and inform policy decision-making. Case counts, however, are influenced by testing rates and strategies, which have varied over time and space. A method to interpret COVID-19 case counts consistently in the context of other surveillance data is needed, especially for data-limited settings in low- and middle-income countries (LMICs). Methods: Statistical analyses were used to detect changes in COVID-19 surveillance data. The pruned exact linear time change detection method was applied for COVID-19 case counts, number of tests, and test positivity rate over time. With this information, change points were categorized as likely driven by epidemiological dynamics or non-epidemiological influences, such as noise. Findings: Higher rates of epidemiological change detection are more associated with open testing policies than with higher testing rates. This study quantified alignment of non-pharmaceutical interventions with epidemiological changes. LMICs have the testing capacity to measure prevalence with precision if they use randomized testing. Rwanda stands out as a country with an efficient COVID-19 surveillance system. Subnational data reveal heterogeneity in epidemiological dynamics and surveillance. Interpretation: Relying solely on case counts to interpret pandemic dynamics has important limitations. Normalizing counts by testing rate mitigates some of these limitations, and an open testing policy is key to efficient surveillance. The study findings can be leveraged by public health officials to strengthen COVID-19 surveillance and support programmatic decision-making.
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- 2021
- Full Text
- View/download PDF
5. Characterization of microglial transcriptomes in the brain and spinal cord of mice in early and late experimental autoimmune encephalomyelitis using a RiboTag strategy
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Shaona Acharjee, Paul M. K. Gordon, Benjamin H. Lee, Justin Read, Matthew L. Workentine, Keith A. Sharkey, and Quentin J. Pittman
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Medicine ,Science - Abstract
Abstract Microglia play an important role in the pathogenesis of multiple sclerosis and the mouse model of MS, experimental autoimmune encephalomyelitis (EAE). To more fully understand the role of microglia in EAE we characterized microglial transcriptomes before the onset of motor symptoms (pre-onset) and during symptomatic EAE. We compared the transcriptome in brain, where behavioral changes are initiated, and spinal cord, where damage is revealed as motor and sensory deficits. We used a RiboTag strategy to characterize ribosome-bound mRNA only in microglia without incurring possible transcriptional changes after cell isolation. Brain and spinal cord samples clustered separately at both stages of EAE, indicating regional heterogeneity. Differences in gene expression were observed in the brain and spinal cord of pre-onset and symptomatic animals with most profound effects in the spinal cord of symptomatic animals. Canonical pathway analysis revealed changes in neuroinflammatory pathways, immune functions and enhanced cell division in both pre-onset and symptomatic brain and spinal cord. We also observed a continuum of many pathways at pre-onset stage that continue into the symptomatic stage of EAE. Our results provide additional evidence of regional and temporal heterogeneity in microglial gene expression patterns that may help in understanding mechanisms underlying various symptomology in MS.
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- 2021
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6. Can the Unemployed Borrow? Implications for Public Insurance.
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Braxton, J. Carter, Herkenhoff, Kyle, and M. Phillips, Gordon
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LINES of credit ,INCOME ,INTEREST rates ,DEFAULT (Finance) ,LAYOFFS - Abstract
We empirically establish that unemployed individuals maintain significant access to credit and that upon a layoff, the unconstrained borrow while the constrained default and delever. Motivated by these findings, we develop a theory of credit lines and labor income risk to analyze optimal transfers to the unemployed. Since credit lines offer fixed interest rates and limits, credit lines are unresponsive to layoffs and provide greater consumption insurance relative to when debt is repriced period by period. At US levels of credit lines, the government can optimally reduce transfers to the unemployed, whereas this is not true when debt is counterfactually repriced period by period. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Evaluating the effectiveness of ensemble voting in improving the accuracy of consensus signals produced by various DTWA algorithms from step-current signals generated during nanopore sequencing.
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Michael Smith, Rachel Chan, Maaz Khurram, and Paul M K Gordon
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Biology (General) ,QH301-705.5 - Abstract
Nanopore sequencing device analysis systems simultaneously generate multiple picoamperage current signals representing the passage of DNA or RNA nucleotides ratcheted through a biomolecule nanopore array by motor proteins. Squiggles are a noisy and time-distorted representation of an underlying nucleotide sequence, "gold standard model", due to experimental and algorithmic artefacts. Other research fields use dynamic time warped-space averaging (DTWA) algorithms to produce a consensus signal from multiple time-warped sources while preserving key features distorted by standard, linear-averaging approaches. We compared the ability of DTW Barycentre averaging (DBA), minimize mean (MM) and stochastic sub-gradient descent (SSG) DTWA algorithms to generate a consensus signal from squiggle-space ensembles of RNA molecules Enolase, Sequin R1-71-1 and Sequin R2-55-3 without knowledge of their associated gold standard model. We propose techniques to identify the leader and distorted squiggle features prior to DTWA consensus generation. New visualization and warping-path metrics are introduced to compare consensus signals and the best estimate of the "true" consensus, the study's gold standard model. The DBA consensus was the best match to the gold standard for both Sequin studies but was outperformed in the Enolase study. Given an underlying common characteristic across a squiggle ensemble, we objectively evaluate a novel "voting scheme" that improves the local similarity between the consensus signal and a given fraction of the squiggle ensemble. While the gold standard is not used during voting, the increase in the match of the final voted-on consensus to the underlying Enolase and Sequin gold standard sequences provides an indirect success measure for the proposed voting procedure in two ways: First is the decreased least squares warped distance between the final consensus and the gold model, and second, the voting generates a final consensus length closer to the known underlying RNA biomolecule length. The results suggest considerable potential in marrying squiggle analysis and voted-on DTWA consensus signals to provide low-noise, low-distortion signals. This will lead to improved accuracy in detecting nucleotides and their deviation model due to chemical modifications (a.k.a. epigenetic information). The proposed combination of ensemble voting and DTWA has application in other research fields involving time-distorted, high entropy signals.
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- 2021
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8. A shared core microbiome in soda lakes separated by large distances
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Jackie K. Zorz, Christine Sharp, Manuel Kleiner, Paul M. K. Gordon, Richard T. Pon, Xiaoli Dong, and Marc Strous
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Science - Abstract
Alkaline lakes have some of the highest productivity rates in freshwater ecosystems. Here the authors report amplicon, metagenome, and proteome sequencing from microbial mat communities of four alkaline lakes in Canada, and compare these lakes to central Asian soda lakes, revealing a shared core microbiome despite the geographical distance.
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- 2019
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9. Regional differences in NPI efficacy and recommendations for Africa
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Mollie M. Van Gordon
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Infectious and parasitic diseases ,RC109-216 - Published
- 2021
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10. Reconstructing SARS-CoV-2 infection dynamics through the phylogenetic inference of unsampled sources of infection.
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Deshan Perera, Ben Perks, Michael Potemkin, Andy Liu, Paul M K Gordon, M John Gill, Quan Long, and Guido van Marle
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Medicine ,Science - Abstract
The COVID-19 pandemic has illustrated the importance of infection tracking. The role of asymptomatic, undiagnosed individuals in driving infections within this pandemic has become increasingly evident. Modern phylogenetic tools that take into account asymptomatic or undiagnosed individuals can help guide public health responses. We finetuned established phylogenetic pipelines using published SARS-CoV-2 genomic data to examine reasonable estimate transmission networks with the inference of unsampled infection sources. The system utilised Bayesian phylogenetics and TransPhylo to capture the evolutionary and infection dynamics of SARS-CoV-2. Our analyses gave insight into the transmissions within a population including unsampled sources of infection and the results aligned with epidemiological observations. We were able to observe the effects of preventive measures in Canada's "Atlantic bubble" and in populations such as New York State. The tools also inferred the cross-species disease transmission of SARS-CoV-2 transmission from humans to lions and tigers in New York City's Bronx Zoo. These phylogenetic tools offer a powerful approach in response to both the COVID-19 and other emerging infectious disease outbreaks.
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- 2021
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11. Rapid deployment of SARS-CoV-2 testing: The CLIAHUB.
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Emily D Crawford, Irene Acosta, Vida Ahyong, Erika C Anderson, Shaun Arevalo, Daniel Asarnow, Shannon Axelrod, Patrick Ayscue, Camillia S Azimi, Caleigh M Azumaya, Stefanie Bachl, Iris Bachmutsky, Aparna Bhaduri, Jeremy Bancroft Brown, Joshua Batson, Astrid Behnert, Ryan M Boileau, Saumya R Bollam, Alain R Bonny, David Booth, Michael Jerico B Borja, David Brown, Bryan Buie, Cassandra E Burnett, Lauren E Byrnes, Katelyn A Cabral, Joana P Cabrera, Saharai Caldera, Gabriela Canales, Gloria R Castañeda, Agnes Protacio Chan, Christopher R Chang, Arthur Charles-Orszag, Carly Cheung, Unseng Chio, Eric D Chow, Y Rose Citron, Allison Cohen, Lillian B Cohn, Charles Chiu, Mitchel A Cole, Daniel N Conrad, Angela Constantino, Andrew Cote, Tre'Jon Crayton-Hall, Spyros Darmanis, Angela M Detweiler, Rebekah L Dial, Shen Dong, Elias M Duarte, David Dynerman, Rebecca Egger, Alison Fanton, Stacey M Frumm, Becky Xu Hua Fu, Valentina E Garcia, Julie Garcia, Christina Gladkova, Miriam Goldman, Rafael Gomez-Sjoberg, M Grace Gordon, James C R Grove, Shweta Gupta, Alexis Haddjeri-Hopkins, Pierce Hadley, John Haliburton, Samantha L Hao, George Hartoularos, Nadia Herrera, Melissa Hilberg, Kit Ying E Ho, Nicholas Hoppe, Shayan Hosseinzadeh, Conor J Howard, Jeffrey A Hussmann, Elizabeth Hwang, Danielle Ingebrigtsen, Julia R Jackson, Ziad M Jowhar, Danielle Kain, James Y S Kim, Amy Kistler, Oriana Kreutzfeld, Jessie Kulsuptrakul, Andrew F Kung, Charles Langelier, Matthew T Laurie, Lena Lee, Kun Leng, Kristoffer E Leon, Manuel D Leonetti, Sophia R Levan, Sam Li, Aileen W Li, Jamin Liu, Heidi S Lubin, Amy Lyden, Jennifer Mann, Sabrina Mann, Gorica Margulis, Diana M Marquez, Bryan P Marsh, Calla Martyn, Elizabeth E McCarthy, Aaron McGeever, Alexander F Merriman, Lauren K Meyer, Steve Miller, Megan K Moore, Cody T Mowery, Tanzila Mukhtar, Lusajo L Mwakibete, Noelle Narez, Norma F Neff, Lindsay A Osso, Diter Oviedo, Suping Peng, Maira Phelps, Kiet Phong, Peter Picard, Lindsey M Pieper, Neha Pincha, Angela Oliveira Pisco, Angela Pogson, Sergei Pourmal, Robert R Puccinelli, Andreas S Puschnik, Elze Rackaityte, Preethi Raghavan, Madhura Raghavan, James Reese, Joseph M Replogle, Hanna Retallack, Helen Reyes, Donald Rose, Marci F Rosenberg, Estella Sanchez-Guerrero, Sydney M Sattler, Laura Savy, Stephanie K See, Kristin K Sellers, Paula Hayakawa Serpa, Maureen Sheehy, Jonathan Sheu, Sukrit Silas, Jessica A Streithorst, Jack Strickland, Doug Stryke, Sara Sunshine, Peter Suslow, Renaldo Sutanto, Serena Tamura, Michelle Tan, Jiongyi Tan, Alice Tang, Cristina M Tato, Jack C Taylor, Iliana Tenvooren, Erin M Thompson, Edward C Thornborrow, Eric Tse, Tony Tung, Marc L Turner, Victoria S Turner, Rigney E Turnham, Mary J Turocy, Trisha V Vaidyanathan, Ilia D Vainchtein, Manu Vanaerschot, Sara E Vazquez, Anica M Wandler, Anne Wapniarski, James T Webber, Zara Y Weinberg, Alexandra Westbrook, Allison W Wong, Emily Wong, Gajus Worthington, Fang Xie, Albert Xu, Terrina Yamamoto, Ying Yang, Fauna Yarza, Yefim Zaltsman, Tina Zheng, and Joseph L DeRisi
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Published
- 2020
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12. Glucocorticoid-driven transcriptomes in human airway epithelial cells: commonalities, differences and functional insight from cell lines and primary cells
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Mahmoud M. Mostafa, Christopher F. Rider, Suharsh Shah, Suzanne L. Traves, Paul M. K. Gordon, Anna Miller-Larsson, Richard Leigh, and Robert Newton
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Glucocorticoid ,Inhaled corticosteroid (ICS) ,Airway epithelium ,Transactivation ,Transrepression ,Asthma ,Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Glucocorticoids act on the glucocorticoid receptor (GR; NR3C1) to resolve inflammation and, as inhaled corticosteroids (ICS), are the cornerstone of treatment for asthma. However, reduced efficacy in severe disease or exacerbations indicates a need to improve ICS actions. Methods Glucocorticoid-driven transcriptomes were compared using PrimeView microarrays between primary human bronchial epithelial (HBE) cells and the model cell lines, pulmonary type II A549 and bronchial epithelial BEAS-2B cells. Results In BEAS-2B cells, budesonide induced (≥2-fold, P ≤ 0.05) or, in a more delayed fashion, repressed (≤0.5-fold, P ≤ 0.05) the expression of 63, 133, 240, and 257 or 15, 56, 236, and 344 mRNAs at 1, 2, 6, and 18 h, respectively. Within the early-induced mRNAs were multiple transcriptional activators and repressors, thereby providing mechanisms for the subsequent modulation of gene expression. Using the above criteria, 17 (BCL6, BIRC3, CEBPD, ERRFI1, FBXL16, FKBP5, GADD45B, IRS2, KLF9, PDK4, PER1, RGCC, RGS2, SEC14L2, SLC16A12, TFCP2L1, TSC22D3) induced and 8 (ARL4C, FLRT2, IER3, IL11, PLAUR, SEMA3A, SLC4A7, SOX9) repressed mRNAs were common between A549, BEAS-2B and HBE cells at 6 h. As absolute gene expression change showed greater commonality, lowering the cut-off (≥1.25 or ≤ 0.8-fold) within these groups produced 93 induced and 82 repressed genes in common. Since large changes in few mRNAs and/or small changes in many mRNAs may drive function, gene ontology (GO)/pathway analyses were performed using both stringency criteria. Budesonide-induced genes showed GO term enrichment for positive and negative regulation of transcription, signaling, proliferation, apoptosis, and movement, as well as FOXO and PI3K-Akt signaling pathways. Repressed genes were enriched for inflammatory signaling pathways (TNF, NF-κB) and GO terms for cytokine activity, chemotaxis and cell signaling. Reduced growth factor expression and effects on proliferation and apoptosis were highlighted. Conclusions While glucocorticoids repress mRNAs associated with inflammation, prior induction of transcriptional activators and repressors may explain longer-term responses to these agents. Furthermore, positive and negative effects on signaling, proliferation, migration and apoptosis were revealed. Since many such gene expression changes occurred in human airways post-ICS inhalation, the effects observed in cell lines and primary HBE cells in vitro may be relevant to ICS in vivo.
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- 2019
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13. Design of sub-Angstrom compact free-electron laser source
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Bonifacio, Rodolfo, Fares, Hesham, Ferrario, Massimo, W. J. McNeil, Brian, and R. M. Robb, Gordon
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- 2017
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14. The oncogene BCL6 is up-regulated in glioblastoma in response to DNA damage, and drives survival after therapy.
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Marie-Sophie Fabre, Nicole M Stanton, Tania L Slatter, Samuel Lee, Dinindu Senanayake, Rosemary M A Gordon, M Leticia Castro, Matthew R Rowe, Ahmad Taha, Janice A Royds, Noelyn Hung, Ari M Melnick, and Melanie J McConnell
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Medicine ,Science - Abstract
The prognosis for people with the high-grade brain tumor glioblastoma is very poor, due largely to low cell death in response to genotoxic therapy. The transcription factor BCL6, a protein that normally suppresses the DNA damage response during immune cell maturation, and a known driver of B-cell lymphoma, was shown to mediate the survival of glioblastoma cells. Expression was observed in glioblastoma tumor specimens and cell lines. When BCL6 expression or activity was reduced in these lines, increased apoptosis and a profound loss of proliferation was observed, consistent with gene expression signatures suggestive of anti-apoptotic and pro-survival signaling role for BCL6 in glioblastoma. Further, treatment with the standard therapies for glioblastoma-ionizing radiation and temozolomide-both induced BCL6 expression in vitro, and an in vivo orthotopic animal model of glioblastoma. Importantly, inhibition of BCL6 in combination with genotoxic therapies enhanced the therapeutic effect. Together these data demonstrate that BCL6 is an active transcription factor in glioblastoma, that it drives survival of cells, and that it increased with DNA damage, which increased the survival rate of therapy-treated cells. This makes BCL6 an excellent therapeutic target in glioblastoma-by increasing sensitivity to standard DNA damaging therapy, BCL6 inhibitors have real potential to improve the outcome for people with this disease.
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- 2020
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15. Evaluating COVID-19 reporting data in the context of testing strategies across 31 low- and middle-income countries
- Author
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Joshua L. Proctor, Mollie M. Van Gordon, Kevin A. McCarthy, and Brittany Hagedorn
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Microbiology (medical) ,medicine.medical_specialty ,Disease surveillance ,Public health ,Psychological intervention ,Developing country ,COVID-19 ,Context (language use) ,General Medicine ,Infectious and parasitic diseases ,RC109-216 ,Test (assessment) ,Infectious Diseases ,Geography ,Environmental health ,Epidemiology ,medicine ,Change detection - Abstract
Background: The case count for coronavirus disease 2019 (COVID-19) is the predominant measure used to track epidemiological dynamics and inform policy decision-making. Case counts, however, are influenced by testing rates and strategies, which have varied over time and space. A method to interpret COVID-19 case counts consistently in the context of other surveillance data is needed, especially for data-limited settings in low- and middle-income countries (LMICs). Methods: Statistical analyses were used to detect changes in COVID-19 surveillance data. The pruned exact linear time change detection method was applied for COVID-19 case counts, number of tests, and test positivity rate over time. With this information, change points were categorized as likely driven by epidemiological dynamics or non-epidemiological influences, such as noise. Findings: Higher rates of epidemiological change detection are more associated with open testing policies than with higher testing rates. This study quantified alignment of non-pharmaceutical interventions with epidemiological changes. LMICs have the testing capacity to measure prevalence with precision if they use randomized testing. Rwanda stands out as a country with an efficient COVID-19 surveillance system. Subnational data reveal heterogeneity in epidemiological dynamics and surveillance. Interpretation: Relying solely on case counts to interpret pandemic dynamics has important limitations. Normalizing counts by testing rate mitigates some of these limitations, and an open testing policy is key to efficient surveillance. The study findings can be leveraged by public health officials to strengthen COVID-19 surveillance and support programmatic decision-making.
- Published
- 2021
16. Epidemiology, diversity, and management of bacterial spot of tomato caused by Xanthomonas perforans
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Gary E. Vallad, Jeannie M. Klein-Gordon, Peter Abrahamian, and Jeffrey B. Jones
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Germplasm ,Genetic diversity ,Bacterial disease ,Resistance (ecology) ,Xanthomonas perforans ,fungi ,food and beverages ,Virulence ,General Medicine ,Biology ,Applied Microbiology and Biotechnology ,Crop ,Agronomy ,Pathogen ,Biotechnology - Abstract
Tomato is an important crop grown worldwide. Various plant diseases cause massive losses in tomato plants due to diverse biotic agents. Bacterial spot of tomato (BST) is a worldwide disease that results in high losses in processed and fresh tomato. Xanthomonas perforans, an aerobic, single-flagellated, rod-shaped, Gram-negative plant pathogenic bacterium, is one of the leading causes of BST. Over the past three decades, X. perforans has increasingly been reported from tomato-growing regions and became a major bacterial disease. X. perforans thrives under high humidity and high temperature, which is commonplace in tropical and subtropical climates. Distinguishing symptoms of BST are necrotic lesions that can coalesce and cause a shot-hole appearance. X. perforans can occasionally cause fruit symptoms depending on disease pressure during fruit development. Short-distance movement in the field is mainly dependent on wind-driven rain, whereas long distance movement occurs through contaminated seed or plant material. X. perforans harbors a suite of effectors that increase pathogen virulence, fitness, and dissemination. BST management mainly relies on copper-based compounds; however, resistance is widespread. Alternative compounds, such as nanomaterials, are currently being evaluated and show high potential for BST management. Resistance breeding remains difficult to attain due to limited resistant germplasm. While the increased genetic diversity and gain and loss of effectors in X. perforans limits the success of single-gene resistance, the adoption of effector-specific transgenes and quantitative resistance may lead to durable host resistance. However, further research that aims to more effectively implement novel management tools is required to curb disease spread. KEY POINTS: • Xanthomonas perforans causes bacterial spot on tomato epidemics through infected seedlings and movement of plant material. • Genetic diversity plays a major role in shaping populations which is evident in loss and gain of effectors. • Management relies on copper sprays, but nanoparticles are a promising alternative to reduce copper toxicity.
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- 2021
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17. Transgenic mice overexpressing desmocollin-2 (DSC2) develop cardiomyopathy associated with myocardial inflammation and fibrotic remodeling.
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Andreas Brodehl, Darrell D Belke, Lauren Garnett, Kristina Martens, Nelly Abdelfatah, Marcela Rodriguez, Catherine Diao, Yong-Xiang Chen, Paul M K Gordon, Anders Nygren, and Brenda Gerull
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Medicine ,Science - Abstract
BACKGROUND:Arrhythmogenic cardiomyopathy is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure, mainly as a result of mutations in cardiac desmosomal genes. Desmosomes are cell-cell junctions mediating adhesion of cardiomyocytes; however, the molecular and cellular mechanisms underlying the disease remain widely unknown. Desmocollin-2 is a desmosomal cadherin serving as an anchor molecule required to reconstitute homeostatic intercellular adhesion with desmoglein-2. Cardiac specific lack of desmoglein-2 leads to severe cardiomyopathy, whereas overexpression does not. In contrast, the corresponding data for desmocollin-2 are incomplete, in particular from the view of protein overexpression. Therefore, we developed a mouse model overexpressing desmocollin-2 to determine its potential contribution to cardiomyopathy and intercellular adhesion pathology. METHODS AND RESULTS:We generated transgenic mice overexpressing DSC2 in cardiac myocytes. Transgenic mice developed a severe cardiac dysfunction over 5 to 13 weeks as indicated by 2D-echocardiography measurements. Corresponding histology and immunohistochemistry demonstrated fibrosis, necrosis and calcification which were mainly localized in patches near the epi- and endocardium of both ventricles. Expressions of endogenous desmosomal proteins were markedly reduced in fibrotic areas but appear to be unchanged in non-fibrotic areas. Furthermore, gene expression data indicate an early up-regulation of inflammatory and fibrotic remodeling pathways between 2 to 3.5 weeks of age. CONCLUSION:Cardiac specific overexpression of desmocollin-2 induces necrosis, acute inflammation and patchy cardiac fibrotic remodeling leading to fulminant biventricular cardiomyopathy.
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- 2017
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18. Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease
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Seyhan Yazar, Jose Alquicira-Hernandez, Kristof Wing, Anne Senabouth, M. Grace Gordon, Stacey Andersen, Qinyi Lu, Antonia Rowson, Thomas R. P. Taylor, Linda Clarke, Katia Maccora, Christine Chen, Anthony L. Cook, Chun Jimmie Ye, Kirsten A. Fairfax, Alex W. Hewitt, and Joseph E. Powell
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Multidisciplinary ,Gene Expression Regulation ,Sequence Analysis, RNA ,Precursor Cells, B-Lymphoid ,Quantitative Trait Loci ,Leukocytes, Mononuclear ,Humans ,Genetic Predisposition to Disease ,Polymorphism, Single Nucleotide ,Alleles ,Autoimmune Diseases ,Genome-Wide Association Study - Abstract
The human immune system displays substantial variation between individuals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type–specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interindividual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interindividual variation in the immune system.
- Published
- 2022
19. Jabiru: Harnessing Java 3D Behaviors for Device and Display Portability.
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Julie N. Stromer, Gerald T. Quon, Paul M. K. Gordon, Andrei L. Turinsky, and Christoph W. Sensen
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- 2005
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20. Antibodies to the Vi capsule of Salmonella Typhi in the serum of typhoid patients and healthy control subjects from a typhoid endemic region
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Deborah House1,2, Vo A. Ho4,To S. Diep5, Nguyen T. Chinh6, Phan V. Bay4, Ha Vinh5, Minh Duc4, Christopher M. Parry2,3, Gordon Dougan1, Nicholas J. White2,3, Jeremy J. Farrar2,3, Tran Tinh Hien5, John Wain2
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capsule ,Salmonella Typhi ,typhoid fever ,antibodies ,Viet Nam ,Vietnam ,Internal medicine ,RC31-1245 ,Microbiology ,QR1-502 - Abstract
Background: There is very little published data on the antibody response to the Vi capsular polysaccharide (Vi-CPS) of S. Typhi during naturally acquired typhoid fever in an endemic area.Methodology: An indirect ELISA, using tyraminated, purified Vi-CPS, was used to assay anti-Vi-CPS antibodies from typhoid fever cases and controls living in the Ho Chi Minh City and Mekong Delta region of Viet Nam.Results: Antibody response to Vi-CPS is significantly higher in typhoid patients who have been ill for more than two weeks than those who are in the first two weeks of illness. The anti-Vi-CPS response is similar for adults and children. Anti-Vi-CPS antibodies can be detected in the sera of non-typhoid patients. The frequency with which this occurs increases with age, probably reflecting increased exposure to S. Typhi.Conclusions: Anti-Vi_CPS is elicited in persons infected with S. Typhi but only after a prolonged duration of illness. Vaccine trials have shown anti-Vi-CPS antibodies to be protective; thus early treatment of typhoid patients, i.e. in the first two week of illness before the Vi-CPS response is elicited, may inhibit the development of this protective immune response.
- Published
- 2008
21. Pyrroloquinoline derivatives from a Tongan specimen of the marine sponge Strongylodesma tongaensis
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Rose M. A. Gordon, Robert A. Keyzers, John H. Miller, Peter T. Northcote, Kainat Hira, Taitusi Taufa, Muhammad Ali Hashmi, Matthias Lein, and Jane Fromont
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biology ,010405 organic chemistry ,Stereochemistry ,Chemistry ,Organic Chemistry ,010402 general chemistry ,biology.organism_classification ,01 natural sciences ,Biochemistry ,Leukemia cell line ,0104 chemical sciences ,Sponge ,chemistry.chemical_compound ,Drug Discovery ,Moiety ,Large group ,Cytotoxicity ,Oxazole - Abstract
Pyrroloquinoline alkaloids are well known bioactive metabolites commonly found from latrunculiid sponges. Two new pyrroloquinoline alkaloids, 6-bromodamirone B (1) and makaluvamine W (2), were isolated from the Tongan sponge Strongylodesma tongaensis. Makaluvamine W (2) contains an oxazole moiety, which is rare in this large group of natural products, and is the first example of a pyrroloquinoline with nitrogen substitution at C-8. Both 1 and 2 lacked activity against a human promyelocytic leukemia cell line (HL-60), supporting the premise that an intact iminoquinone moiety plays a key role in the cytotoxicity of this compound class. The chemotaxonomic impact of these makaluvamine-type compounds is also discussed.
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- 2019
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22. Epidemiology, diversity, and management of bacterial spot of tomato caused by Xanthomonas perforans
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Peter, Abrahamian, Jeannie M, Klein-Gordon, Jeffrey B, Jones, and Gary E, Vallad
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Xanthomonas ,Solanum lycopersicum ,Copper ,Plant Diseases - Abstract
Tomato is an important crop grown worldwide. Various plant diseases cause massive losses in tomato plants due to diverse biotic agents. Bacterial spot of tomato (BST) is a worldwide disease that results in high losses in processed and fresh tomato. Xanthomonas perforans, an aerobic, single-flagellated, rod-shaped, Gram-negative plant pathogenic bacterium, is one of the leading causes of BST. Over the past three decades, X. perforans has increasingly been reported from tomato-growing regions and became a major bacterial disease. X. perforans thrives under high humidity and high temperature, which is commonplace in tropical and subtropical climates. Distinguishing symptoms of BST are necrotic lesions that can coalesce and cause a shot-hole appearance. X. perforans can occasionally cause fruit symptoms depending on disease pressure during fruit development. Short-distance movement in the field is mainly dependent on wind-driven rain, whereas long distance movement occurs through contaminated seed or plant material. X. perforans harbors a suite of effectors that increase pathogen virulence, fitness, and dissemination. BST management mainly relies on copper-based compounds; however, resistance is widespread. Alternative compounds, such as nanomaterials, are currently being evaluated and show high potential for BST management. Resistance breeding remains difficult to attain due to limited resistant germplasm. While the increased genetic diversity and gain and loss of effectors in X. perforans limits the success of single-gene resistance, the adoption of effector-specific transgenes and quantitative resistance may lead to durable host resistance. However, further research that aims to more effectively implement novel management tools is required to curb disease spread. KEY POINTS: • Xanthomonas perforans causes bacterial spot on tomato epidemics through infected seedlings and movement of plant material. • Genetic diversity plays a major role in shaping populations which is evident in loss and gain of effectors. • Management relies on copper sprays, but nanoparticles are a promising alternative to reduce copper toxicity.
- Published
- 2021
23. Uptake of long chain fatty acids by human placental choriocarcinoma (BeWo) cells: role of plasma membrane fatty acid-binding protein
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F M Campbell, A M Clohessy, M J Gordon, K R Page, and A K Dutta-Roy
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Biochemistry ,QD415-436 - Abstract
In order to understand the mechanisms by which fatty acids are taken up by the placenta, the uptake of oleic, linoleic, arachidonic, and docosahexaenoic acids by cultured human placental choriocarcinoma (BeWo) cells was examined. Fatty acid uptake by BeWo cells was temperature-dependent and exhibited saturable kinetics. Oleic acid was taken up least and docosahexaenoic acid most by these cells. Moreover, competitive studies of fatty acid uptake by BeWo cells also indicated preferential uptake compared with oleic acid in the order of docosahexaenoic acid, arachidonic acid, and linoleic acid. Western blot analysis demonstrated that BeWo cells express a protein immunoreactive with antibodies to the human placental plasma membrane fatty acid-binding protein (p-FABPpm). Furthermore, pre-treatment of BeWo cells with these antibodies inhibited most of the uptake of docosahexaenoic (64%) and arachidonic acids (68%) whereas oleic acid uptake was inhibited only 32% compared with the controls treated with preimmune serum. These results clearly demonstrate that the pFABPpm may be involved in the preferential uptake of essential fatty acids (EFA) and their long chain polyunsaturated fatty acids (LCPUFA) by these cells. Studies on the distribution of radiolabeled fatty acids in the cellular lipids of BeWo cells showed that docosahexaenoic acid was incorporated mainly in the triacylglycerol fraction, followed by the phospholipid fraction, whereas for arachidonic acid the reverse was true. The preferential incorporation of docosahexaenoic acid into triacylglycerol suggests that triacylglycerol may play an important role in the placental transport of docosahexaenoic acid to the fetal circulation. Together these results demonstrate the preferential uptake of EFA/LCPUFA by BeWo cells that is most probably mediated via the pFABPpm. We thus propose that the p-FABPpm may be involved in the sequestration of maternal plasma LCPUFA by the placenta.
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- 1997
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24. A suite of automated sequence analyses reduces the number of candidate deleterious variants and reveals a difference between probands and unaffected siblings
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Anchi Wu, Fangning Gu, Elizabeth A. Burke, Shane Macnamara, M. Grace Gordon, Lukas Vlahos, Cynthia J. Tifft, Thomas C. Markello, Camilo Toro, May Christine V. Malicdan, William A. Gahl, and David R. Adams
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Proband ,Male ,DNA Copy Number Variations ,Genotype ,diagnosis ,Population ,agnostic exome analysis ,Biology ,Compound heterozygosity ,Polymorphism, Single Nucleotide ,Article ,symbols.namesake ,SNP ,Humans ,Exome ,education ,Nuclear family ,Genetics (clinical) ,Sequence Deletion ,Genetics ,education.field_of_study ,Electronic Data Processing ,Siblings ,Genetic Diseases, Inborn ,rare diseases ,High-Throughput Nucleotide Sequencing ,Undiagnosed Diseases Network ,Exons ,Sequence Analysis, DNA ,Pedigree ,Phenotype ,Mendelian inheritance ,symbols ,Female - Abstract
Develop an automated exome analysis workflow that can produce a very small number of candidate variants yet still detect different numbers of deleterious variants between probands and unaffected siblings. Ninety-seven outbred nuclear families from the Undiagnosed Diseases Program/Network included single probands and the corresponding unaffected sibling(s). Single-nucleotide polymorphism (SNP) chip and exome analyses were performed on all, with proband and unaffected sibling considered independently as the target. The total burden of candidate genetic variants was summed for probands and siblings over all considered disease models. Exome analysis workflow include automated programs for ethnicity-matched genotype calling, salvage pathway for Mendelian inconsistency, compound heterozygous recessive detection, BAM file regional curation, population frequency filtering, pedigree-aware BAM file noise evaluation, and exon deletion filtration. This workflow relied heavily on BAM file analysis. A greater average pathogenic variant number was found compared with unaffected siblings. This was significant (p
- Published
- 2019
25. SimPEL: Simulation-based power estimation for sequencing studies of low-prevalence conditions
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Paul M. K. Gordon, Pei Wang, Chen Cao, Lauren Mak, Minghao Li, Quan Long, Chad A. Bousman, and Maja Tarailo-Graovac
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0301 basic medicine ,Epidemiology ,Computer science ,Penetrance ,computer.software_genre ,Statistical power ,03 medical and health sciences ,Annotation ,Prevalence ,Humans ,Leverage (statistics) ,Computer Simulation ,Simulation based ,Alleles ,Genetic Association Studies ,Genetics (clinical) ,Models, Genetic ,Clinical study design ,Sequence Analysis, DNA ,Gene Annotation ,computer.file_format ,030104 developmental biology ,Sample size determination ,Sample Size ,Data mining ,Executable ,computer ,Genome-Wide Association Study - Abstract
Power estimations are important for optimizing genotype-phenotype association study designs. However, existing frameworks are designed for common disorders, and thus ill-suited for the inherent challenges of studies for low-prevalence conditions such as rare diseases and infrequent adverse drug reactions. These challenges include small sample sizes and the need to leverage genetic annotation resources in association analyses for the purpose of ranking potential causal genes. We present SimPEL, a simulation-based program providing power estimations for the design of low-prevalence condition studies. SimPEL integrates the usage of gene annotation resources for association analyses. Customizable parameters, including the penetrance of the putative causal allele and the employed pathogenic scoring system, allow SimPEL to realistically model a large range of study designs. To demonstrate the effects of various parameters on power, we estimated the power of several simulated designs using SimPEL and captured power trends in agreement with observations from current literature on low-frequency condition studies. SimPEL, as a tool, provides researchers studying low-frequency conditions with an intuitive and highly flexible avenue for statistical power estimation. The platform-independent "batteries included" executable and default input files are available at https://github.com/precisionomics/SimPEL.
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- 2018
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26. 'Everything Is About Balance': Graduate Education Faculty and the Navigation of Difficult Discourses on Race
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Jovita M. Ross-Gordon and Kayon Murray-Johnson
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Semi-structured interview ,Balance (metaphysics) ,Teaching method ,Discourse analysis ,05 social sciences ,Ethnic group ,Self-concept ,050301 education ,050109 social psychology ,Education ,Race (biology) ,Pedagogy ,ComputingMilieux_COMPUTERSANDEDUCATION ,0501 psychology and cognitive sciences ,Sociology ,0503 education ,Qualitative research - Abstract
The purpose of this multiple case study was to describe the experiences of graduate education faculty of varying racial/ethnic backgrounds, learning to navigate difficult discourses on race effectively over time. The study employed positionality as a theoretical framework. Findings indicate that faculty balance what we refer to as strategies of self in a bid to work through difficult race talk. In turn, their practice may hold strong potential for influencing a fresh and more holistic approach to engaging in classroom race talk.
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- 2018
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27. Exercise training, Glut-4 protein abundance and glutamine in skeletal muscle of mature and very old horses
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M. E. Gordon, H. C. Manso Filho, Kenneth H. McKeever, C. L. Betros, Helena Emília Cavalcanti da Costa Cordeiro Manso, and Malcolm Watford
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medicine.medical_specialty ,040301 veterinary sciences ,Physiology ,Veterinary (miscellaneous) ,Endocrinology, Diabetes and Metabolism ,Biophysics ,Biochemistry ,Incremental exercise ,0403 veterinary science ,Physiology (medical) ,Internal medicine ,Heart rate ,Blood plasma ,medicine ,Orthopedics and Sports Medicine ,Dry matter ,business.industry ,0402 animal and dairy science ,Horse ,Skeletal muscle ,04 agricultural and veterinary sciences ,040201 dairy & animal science ,Glutamine ,Endocrinology ,medicine.anatomical_structure ,Hay ,business - Abstract
Two groups of unfit Standardbred mares (adult: 9-14 years, 540 kg, n=7) and old (20-25 years, 530 kg, n=5) were used to test two hypotheses, first, that aging and training would alter plasma and muscle glutamine [Gln] and glutamate [Glu] and second, that aging and training would alter Glut-4 expression in skeletal muscle. All animals were housed on pasture with free access to grass and all received hay and supplementation with a commercially prepared supplement (15% crude protein and 3.00 Mcal/kg dry matter) in individual stalls. Mares were fed to meet or exceed NRC (2007) nutrient recommendations for moderate to heavy exercise. The mares were exercise trained in a free-stall motorised circular exercise machine for 30 min/d, 5 d/week, for 8 weeks. Work intensity during training was set at a relative intensity of ~60% of the maximum heart rate, previously determined during an incremental exercise test (GXT). Blood samples and muscle biopsies (gluteus) obtained before and after 8 weeks of training were used for measurement of [Gln], [Glu] and Glut-4 abundance. Samples were collected before the initiation of training and at 24 h after cessation of last bout of exercise in the training period. All samples were immediately frozen in liquid nitrogen and stored at -80 °C until enzymatic analysis for [Gln], [Glu] and Western Blot analysis for Glut-4 protein abundance. Data were analysed by one-way or two-way ANOVA for repeated measures and the Pearson correlation method. Post-hoc differences were identified with the Tukey test. Significance was set at P0.05) in muscle [Glu] due to aging. Training decreased (P0.05) due to training. Glut-4 abundance analysis did not differ (P>0.05) between the young adult and old horses; however, there was a trend (P=0.063) towards an effect of training when samples from both groups were pooled. It was concluded that training and aging produce changes in plasma and muscle [Gln], which may affect immune function in athletic horses, but not in Glut-4.
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- 2017
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28. Structure of the Sac3 RNA-binding M-region in the Saccharomyces cerevisiae TREX-2 complex
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James M. B. Gordon, Murray Stewart, and Shintaro Aibara
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Models, Molecular ,0301 basic medicine ,Saccharomyces cerevisiae Proteins ,Protein domain ,Saccharomyces cerevisiae ,Active Transport, Cell Nucleus ,Biology ,Crystallography, X-Ray ,Protein Structure, Secondary ,03 medical and health sciences ,Protein structure ,Protein Domains ,Structural Biology ,Gene expression ,Genetics ,medicine ,RNA, Messenger ,Gene ,Cell Nucleus ,Messenger RNA ,RNA ,RNA, Fungal ,biology.organism_classification ,Cell biology ,Cell nucleus ,030104 developmental biology ,medicine.anatomical_structure ,Multiprotein Complexes - Abstract
Transcription-export complex 2 (TREX-2, or THSC) facilitates localization of actively transcribing genes such as GAL1 to the nuclear periphery, contributes to the generation of export-competent mRNPs and influences gene expression through interactions with Mediator. TREX-2 is based on a Sac3 scaffold to which Thp1, Sem1, Cdc31 and Sus1 bind and consists of three modules: the N-region (Sac3∼1-100), which binds mRNA export factor Mex67:Mtr2; the M-region, in which Thp1 and Sem1 bind to Sac3∼100-550; and the CID region in which Cdc31 and two Sus1 chains bind to Sac3∼720-805. Although the M-region of Sac3 was originally thought to encompass residues ∼250-550, we report here the 2.3Å resolution crystal structure of a complex containing Sac3 residues 60–550 that indicates that the TPR-like repeats of the M-region extend to residue 137 and that residues 90–125 form a novel loop that links Sac3 to Thp1. These new structural elements are important for growth and mRNA export in vivo. Although deleting Sac3 residues 1–90 produced a wild-type phenotype, deletion of the loop as well generated growth defects at 37°C, whereas the deletion of residues 1–250 impaired mRNA export and also generated longer lag times when glucose or raffinose was replaced by galactose as the carbon source.
- Published
- 2017
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29. Subdiffraction-limited chemical imaging of patterned phthalocyanine films using tip-enhanced near-field optical microscopy
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M. J. Gordon and R. Hermann
- Subjects
Chemical imaging ,Materials science ,business.industry ,Near-field optics ,Physics::Optics ,Near and far field ,02 engineering and technology ,Inelastic scattering ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,law.invention ,symbols.namesake ,Optics ,Optical microscope ,law ,symbols ,General Materials Science ,Thin film ,0210 nano-technology ,business ,Raman spectroscopy ,Spectroscopy ,Plasmon - Abstract
A tip-enhanced near-field optical microscope, based on a shear-force atomic force microscope with plasmonic tip coupled to an inverted, confocal optical microscope, has been constructed for nanoscale chemical (Raman) imaging of surfaces. The design and validation of the instrument, along with its application to near-field Raman mapping of patterned organic thin films (coumarin-6 and Cu(II) phthalocyanine), are described. Lateral resolution of the instrument is estimated at 50 nm (better than λ/10), which is roughly dictated by the size of the plasmonic tip apex. Additional observations, such as the distance scaling of Raman enhancement and the inelastic scattering background generated by the plasmonic tip, are presented. Copyright © 2016 John Wiley & Sons, Ltd.
- Published
- 2016
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30. An assessment of the factor structure and factorial invariance of scores from the Readiness to Learn scale
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Jovita M. Ross-Gordon, M Cecil Smith, Amy D. Rose, and Thomas J. Smith
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Factorial invariance ,Social Psychology ,Scale (ratio) ,05 social sciences ,Statistics ,Developmental and Educational Psychology ,050301 education ,050109 social psychology ,0501 psychology and cognitive sciences ,Psychology ,Factor structure ,0503 education ,Education - Published
- 2016
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31. Hematopoietic Commitment of ES Cells in Culture
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Kennedy, Marion and M. Keller, Gordon
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- 2003
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32. Novel tape termination method for automated fibre placement: Cutting characteristics and delamination suppression
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Tharan M G Gordon, Michael R Wisnom, Xiaodong Xu, and Byung-Chul Kim
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Materials science ,Composite number ,Tapering ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Discontinuity (geotechnical engineering) ,Critical parameter ,Mechanics of Materials ,Cutting force ,Ultimate tensile strength ,Ceramics and Composites ,Composite material ,0210 nano-technology - Abstract
A novel tape termination method for tapering the ply end and removing the fibre discontinuity owing to a dropped ply in a tapered composite was demonstrated. The forces required for this process – referred to as tape scarfing – were experimentally investigated with respect to blade speed, scarfing ratio, tape thickness and width. Tensile tests were conducted on unidirectional laminate specimens with a scarfed ply at two different aspect ratios to examine the effect of scarfing ratio on the delamination behaviour of the specimens. The results showed that the ply scarfing ratio is a critical parameter controlling the cutting force and delamination behaviour in a tapered specimen, and upon reaching a certain threshold delamination can be completely suppressed. The method demonstrated has potential for implementation in commercial AFP machines, theoretically realising a more compact cutting mechanism, with the capability of preventing delamination in the ply drop regions.
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- 2020
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33. Evaluation of simulation models to mimic the distortions introduced into squiggles by nanopore sequencers and segmentation algorithms
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Michael Smith, Paul M. K. Gordon, and Rachel Chan
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Computer science ,02 engineering and technology ,Signal-To-Noise Ratio ,Biochemistry ,chemistry.chemical_compound ,Nanopores ,Black box ,0202 electrical engineering, electronic engineering, information engineering ,Feature (machine learning) ,Biochemical Simulations ,Preprocessor ,Nanotechnology ,Nucleotide ,Segmentation ,Sequence Deletion ,chemistry.chemical_classification ,0303 health sciences ,Multidisciplinary ,Artificial neural network ,Simulation and Modeling ,Nucleic acid sequence ,Nanopore ,Physical Sciences ,Engineering and Technology ,Medicine ,020201 artificial intelligence & image processing ,Algorithm ,Algorithms ,Research Article ,Biotechnology ,Science ,Enolase ,Motor Proteins ,Nucleotide sequencing ,Nucleotide Sequencing ,Bioengineering ,Research and Analysis Methods ,DNA sequencing ,03 medical and health sciences ,Molecular Motors ,Computer Simulation ,Molecular Biology Techniques ,Sequencing Techniques ,Signal to Noise Ratio ,Molecular Biology ,030304 developmental biology ,Probability ,Messenger RNA ,RNA ,Biology and Life Sciences ,Computational Biology ,Proteins ,Cell Biology ,Models, Theoretical ,Probability Theory ,Probability Distribution ,Probability Density ,Nanopore Sequencing ,chemistry ,Minion ,Bionanotechnology ,Signal Processing ,DNA ,Mathematics - Abstract
Nucleotides ratcheted through the biomolecular pores of nanopore sequencers generate raw picoamperage currents, which are segmented into step-current level signals representing the nucleotide sequence. These ‘squiggles’ are a noisy, distorted representation of the underlying true stepped current levels due to experimental and algorithmic factors. We were interested in developing a simulation model to support a white-box approach to identify common distortions, rather than relying on commonly used black box neural network techniques for basecalling nanopore signals. Dynamic time warped-space averaging (DTWA) techniques can generate a consensus from multiple noisy signals without introducing key feature distortions that occur with standard averaging. As a preprocessing tool, DTWA could provide cleaner and more accurate current signals for direct RNA or DNA analysis tools. However, DTWA approaches need modification to take advantage of the a-priori knowledge regarding a common, underlying gold-standard RNA / DNA sequence. Using experimental data, we derive a simulation model to provide known squiggle distortion signals to assist in validating the performance of analysis tools such as DTWA. Simulation models were evaluated by comparing mocked and experimental squiggle characteristics from one Enolase mRNA squiggle group produced by an Oxford MinION nanopore sequencer, and cross-validated using other Enolase, Sequin R1_71_1 and Sequin R2_55_3 mRNA studies. New techniques identified high inserted but low deleted base rates, generating consistent x1.7 squiggle event to base called ratios. Similar probability density and cumulative distribution functions, PDF and CDF, were found across all studies. Experimental PDFs were not the normal distributions expected if squiggle distortion arose from segmentation algorithm artefacts, or through individual nucleotides randomly interacting with individual nanopores. Matching experimental and mocked CDFs required the assumption that there are unique features associated with individual raw-current data streams. Z-normalized signal-to-noise ratios suggest intrinsic sensor limitations being responsible for half the gold standard and noisy squiggle DTW differences.
- Published
- 2019
34. Effects of exogenous ghrelin infusion on feed intake and metabolic parameters of energy homeostasis in Standardbred mares
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Donald L. Thompson, Kenneth H. McKeever, and M. E. Gordon
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medicine.medical_specialty ,Physiology ,Veterinary (miscellaneous) ,Endocrinology, Diabetes and Metabolism ,Leptin ,Insulin ,medicine.medical_treatment ,digestive, oral, and skin physiology ,Biophysics ,Horse ,Biology ,Growth hormone ,Biochemistry ,Energy homeostasis ,Endocrinology ,Physiology (medical) ,Internal medicine ,Hay ,medicine ,Orthopedics and Sports Medicine ,Ghrelin ,Active Ghrelin ,hormones, hormone substitutes, and hormone antagonists - Abstract
Six Standardbred mares (age 12±2 years, body weight 502±63 kg; mean ± standard deviation) were given 1.6 µg/kg acylated human ghrelin or vehicle treatment as an intravenous bolus in a randomised, cross-over design to test the hypothesis that exogenous ghrelin infusion would increase feed intake and alter metabolic parameters of energy homeostasis, leptin, glucose, insulin and cortisol. After the horses had initial access to hay cubes for 1.5 h, doses were given and hay cubes were available once again. Leftover feed was weighed 6 times over each of the 24 h testing periods. Blood samples for measurement of active ghrelin, growth hormone, leptin, glucose, insulin and cortisol were taken at time 0 (immediately before infusion) and 20, 40, 60, 80, 100, 120, 240, 480, and 720 min post-infusion. Every 10 min, the horses’ behaviour was recorded for eating, drinking, resting, and other behaviours. Ghrelin infusion did not increase (P≯0.05) feed intake in the mares as a group, but did increase feed intake (P
- Published
- 2014
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35. Effects of added chelated trace minerals, organic selenium, yeast culture, direct-fed microbials, and Yucca schidigera extract in horses: II. Nutrient excretion and potential environmental impact1
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M. E. Gordon, C. R. Sweeney, M. L. Jerina, and M. S. Edwards
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Selenium yeast ,Chemistry ,chemistry.chemical_element ,General Medicine ,Urine ,Phosphate ,Phosphorus metabolism ,Excretion ,chemistry.chemical_compound ,Nutrient ,Animal science ,Environmental chemistry ,Genetics ,Animal Science and Zoology ,Feces ,Selenium ,Food Science - Abstract
The objective of this study was to test the hypothesis that an equine diet formulated with chelated trace minerals, organic selenium, yeast culture, direct-fed microbials (DFM) and Yucca schidigera extract would decrease excretion of nutrients that have potential for environmental impact. Horses were acclimated to 100% pelleted diets formulated with (ADD) and without (CTRL) the aforementioned additives. Chelated sources of Cu, Zn, Mn, and Co were included in the ADD diet at a 100% replacement rate of sulfate forms used in the CTRL diet. Additionally, the ADD diet included organic selenium yeast, DFM, and Yucca schidigera extract. Ten horses were fed the 2 experimental diets during two 42-d periods in a crossover design. Total fecal and urine collection occurred during the last 14 d of each period. Results indicate no significant differences between Cu, Zn, Mn, and Co concentrations excreted via urine (P > 0.05) due to dietary treatment. There was no difference between fecal Cu and Mn concentrations (P > 0.05) based on diet consumed. Mean fecal Zn and Co concentrations excreted by horses consuming ADD were greater than CTRL (P 0.05). In feces stockpiled to simulate a crude composting method, no differences (P > 0.05) due to diet were detected for particle size, temperature, moisture, OM, total N, P, phosphate, K, moisture, potash, or ammonia N (P > 0.05). Although no difference (P = 0.2737) in feces stockpile temperature due to diet was found, temperature differences over time were documented (P < 0.0001). In conclusion, the addition of certain chelated mineral sources, organic Se yeast, DFM, and Yucca schidigera extract did not decrease most nutrient concentrations excreted. Horses consuming organic selenium as part of the additive diet had lower fecal and urine Se concentrations, as well as greater fecal K concentrations.
- Published
- 2013
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36. Genomic compartmentalization of gene families encoding core components of metazoan signaling systems
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Jung Soh, Edward J. Parr, Christoph Wilhelm Sensen, Howard Wong, Tom Yu, Paul M. K. Gordon, and Randal N. Johnston
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Mammals ,Genetics ,Protein family ,Genetic Linkage ,Wnt signaling pathway ,General Medicine ,Biology ,Genome ,Receptor tyrosine kinase ,Birds ,Genetic Loci ,Multigene Family ,biology.protein ,Animals ,Humans ,Gene family ,Janus kinase ,Molecular Biology ,Gene ,Signal Transduction ,Biotechnology ,Genomic organization - Abstract
To investigate the role of gene localization and genome organization in cell–cell signalling and regulation, we mapped the distribution pattern of gene families that comprise core components of intercellular communication networks. Our study is centered on the distinct evolutionarily conserved metazoan signalling pathways that employ proteins in the receptor tyrosine kinase, WNT, hedgehog, NOTCH, Janus kinase/STAT, transforming growth factor beta, and nuclear hormone receptor protein families. Aberrant activity of these signalling pathways is closely associated with the promotion and maintenance of human cancers. The cataloguing and mapping of genes encoding these signalling proteins and comparisons across species has led us to propose that the genome can be subdivided into six genome-wide primary linkage groups (PLGs). PLGs are composed of assemblages of gene families that are often mutually exclusive, raising the possibility of unique functional identities for each group. Examination of the localization patterns of genes with distinct functions in signal transduction demonstrates dichotomous segregation patterns. For example, gene families of cell-surface receptors localize to genomic compartments that are distinct from the locations of their cognate ligand gene families. Additionally, genes encoding negative-acting components of signalling pathways (inhibitors and antagonists) are topologically separated from their positive regulators and other signal transducer genes. We, therefore, propose the existence of conserved genomic territories that encode key proteins required for the proper activity of metazoan signaling and regulatory systems. Disruption in this pattern of topologic genomic organization may contribute to aberrant regulation in hereditary or acquired diseases such as cancer. We further propose that long-range looping genomic regulatory interactions may provide a mechanism favouring the remarkable retention of these conserved gene clusters during chordate evolution.
- Published
- 2013
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37. Muscle disorders * 111. The impact of fatigue in patients with idiopathic inflammatory myopathy: a mixed method study
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R. Campbell, D. Hofmann, S. Hatch, P. Gordon, H. Lempp, L. Das, P. Blumbergs, V. Limaye, E. Vermaak, N. McHugh, M. H. Edwards, K. Jameson, A. A. Sayer, E. Dennison, C. Cooper, F. B. Salvador, C. Huertas, D. Isenberg, E. J. Jackson, A. Middleton, D. Churchill, K. Walker-Bone, P. R. Worsley, S. Mottram, M. Warner, D. Morrissey, S. Gadola, A. Carr, M. Stokes, R. N. Srivastava, D. Sanghi, A. Elbaz, A. Mor, G. Segal, M. Drexler, D. Norman, E. Peled, N. Rozen, Y. Goryachev, E. M. Debbi, A. Haim, A. Wolf, R. Debi, M. S. Cohen, I. Igolnikov, Y. Bar Ziv, V. Benkovich, B. Bernfeld, J. Collins, R. J. Moots, P. D. Clegg, P. I. Milner, H. D. Ejtehadi, P. N. Nelson, C. Wenham, S. Balamoody, R. Hodgson, P. Conaghan, R. Wilkie, M. Blagojevic, K. P. Jordan, J. Mcbeth, M. J. Peffers, R. J. Beynon, D. J. Thornton, R. Chapman, V. Chapman, D. Walsh, S. Kelly, M. Hui, W. Zhang, S. Doherty, F. Rees, K. Muir, R. Maciewicz, M. Doherty, S. Snelling, R. K. Davidson, T. Swingler, A. Price, I. Clark, E. Stockley, G. Hathway, H. Faas, D. Auer, G. Hirsch, E. Hale, G. Kitas, R. Klocke, A. Abraham, M. S. Pearce, K. D. Mann, R. M. Francis, F. Birrell, M. Tucker, S. J. Mellon, L. Jones, A. J. Price, P. A. Dieppe, H. S. Gill, S. Ashraf, D. A. Walsh, D. McCollum, C. McCabe, S. Grieve, J. Shipley, R. Gorodkin, A. G. Oldroyd, B. Evans, C. Greenbank, M. Bukhari, R. Rajak, C. Bennett, A. Williams, J. C. Martin, R. Abdulkader, C. MacNicol, K. Brixey, S. Stephenson, G. Clunie, R. N. Andrews, E. M. Clark, V. C. Gould, L. Carter, L. Morrison, J. H. Tobias, S. R. Pye, D. Vanderschueren, T. W. O'Neill, D. M. Lee, I. Jans, J. Billen, E. Gielen, M. Laurent, F. Claessens, J. E. Adams, K. A. Ward, G. Bartfai, F. Casanueva, J. D. Finn, G. Forti, A. Giwercman, T. S. Han, I. Huhtaniemi, K. Kula, M. E. Lean, N. Pendleton, M. Punab, F. C. Wu, S. Boonen, C. Mercieca, J. Webb, A. Bhalla, S. Fairbanks, K. E. Moss, C. Collins, P. Sedgwick, J. Parker, N. C. Harvey, Z. A. Cole, S. R. Crozier, G. Ntani, P. A. Mahon, S. M. Robinson, H. M. Inskip, K. M. Godfrey, E. M. Dennison, M. Bridges, S. Ruddick, C. R. Holroyd, P. Mahon, K. Godfrey, T. McNeilly, C. McNally, T. Beringer, M. Finch, A. Coda, J. Davidson, J. Walsh, P. Fowlie, T. Carline, D. Santos, P. Patil, C. Rawcliffe, A. Olaleye, S. Moore, A. Fox, D. Sen, Y. Ioannou, S. Nisar, K. Rankin, M. Birch, S. Finnegan, M. Rooney, D. S. Gibson, A. Malviya, C. M. Ferris, S. P. Rushton, H. E. Foster, H. Hanson, K. Muthumayandi, D. J. Deehan, L. Birt, F. Poland, A. MacGregor, K. Armon, M. Pfeil, F. McErlane, M. W. Beresford, E. M. Baildam, W. Thomson, K. Hyrich, A. Chieng, J. Gardner-Medwin, M. Lunt, L. Wedderburn, K. Newell, A. Evans, G. Manning, C. Scaife, C. McAllister, S. R. Pennington, M. Duncan, T. Moore, C. Pericleous, S. C. Croca, I. Giles, K. Alber, H. Yong, A. Midgely, A. Rahman, M. Rzewuska, C. Mallen, V. Y. Strauss, J. Belcher, G. Peat, R. Byng-Maddick, M. Wijendra, H. Penn, E. Roddy, S. Muller, R. Hayward, F. Kamlow, A. Pakozdi, A. Jawad, D. J. Green, S. L. Hider, S. Singh Bawa, S. Bawa, A. Turton, M. Palmer, J. Lewis, T. Moss, C. E. Goodchild, N. Tang, D. Scott, P. Salkovskis, S. Selvan, L. Williamson, N. Thalayasingam, M. Higgins, V. Saravanan, M. Rynne, J. D. Hamilton, C. Heycock, C. Kelly, S. Norton, A. Sacker, J. Done, A. Young, J. S. Smolen, R. M. Fleischmann, P. Emery, R. F. van Vollenhoven, B. Guerette, S. Santra, H. Kupper, L. Redden, A. Kavanaugh, E. C. Keystone, D. van der Heijde, M. E. Weinblatt, N. Mozaffarian, S. Liu, N. Zhang, S. Wilkinson, M. Riaz, A. J. Ostor, M. K. Nisar, G. Burmester, X. Mariette, F. Navarro-Blasco, U. Oezer, S. Kary, K. Unnebrink, P. Jobanputra, F. Maggs, A. Deeming, D. Carruthers, E. Rankin, A. Jordan, A. Faizal, C. Goddard, M. Pugh, S. Bowman, S. Brailsford, P. Nightingale, N. Tugnet, S. C. Cooper, K. M. Douglas, C. S. Edwin Lim, S. Bee Lian Low, C. Joy, L. Hill, P. Davies, S. Mukherjee, P. Cornell, S. L. Westlake, S. Richards, F. Rahmeh, P. W. Thompson, F. Breedveld, E. Keystone, R. Landewe, M. McIlraith, C. Dharmapalaiah, L. Shand, G. Rose, R. Watts, A. Eldashan, B. Dasgupta, F. A. Borg, G. M. Bell, A. E. Anderson, R. A. Harry, J. N. Stoop, C. M. Hilkens, J. Isaacs, A. Dickinson, E. McColl, S. Banik, L. Smith, J. France, A. Rutherford, A. Scott Russell, J. Smith, I. Jassim, R. Withrington, P. Bacon, D. De Lord, L. McGregor, I. Morrison, A. Stirling, D. R. Porter, S. A. Saunders, S. Else, O. Semenova, H. Thompson, O. Ogunbambi, S. Kallankara, E. Baguley, Y. Patel, S. Alzabin, S. Abraham, T. E. Taher, A. Palfeeman, D. Hull, K. McNamee, E. Pathan, A. Kinderlerer, P. Taylor, R. O. Williams, R. A. Mageed, O. Iaremenko, G. Mikitenko, M. Ferrari, T. Kamalati, C. Pitzalis, F. Pearce, S. Tosounidou, K. Obrenovic, N. Erb, J. Packham, R. Sandhu, C. White, C. M. Cardy, E. Justice, M. Frank, L. Li, M. Lloyd, A. Ahmed, S. Readhead, A. Ala, M. Fittall, J. Manson, J. Sibilia, R. Marc Flipo, B. Combe, C. Gaillez, M. Le Bars, C. Poncet, A. Elegbe, R. Westhovens, R. Hassanzadeh, C. Mangan, R. Fleischmann, R. van Vollenhoven, T. W. J. Huizinga, R. Goldermann, B. Duncan, J. Timoshanko, K. Luijtens, O. Davies, M. Dougados, J. Hewitt, M. Owlia, M. Schiff, R. Alten, J. L. Kaine, P. T. Nash, I. Delaet, K. Qi, M. C. Genovese, J. Clark, S. Kardash, E. Wong, R. Hull, F. McCrae, R. Shaban, L. Thomas, S. Young-Min, J. Ledingham, A. Covarrubias Cobos, G. Leon, E. F. Mysler, M. W. Keiserman, R. M. Valente, J. Abraham Simon Campos, W. Porawska, J. H. Box, C. W. Legerton, E. L. Nasonov, P. Durez, R. Pappu, J. Teng, C. J. Edwards, N. Arden, J. Campbell, T. van Staa, C. Housden, I. Sargeant, E. Choy, S. McAuliffe, K. Roberts, P. Sarzi-Puttini, A. Andrianakos, T. P. Sheeran, D. Choquette, A. Finckh, M.-L. Desjuzeur, E. K. Gemmen, C. Mpofu, J.-E. Gottenberg, P. Shah, M. Cox, A. Nye, A. O'Brien, P. Jones, G. T. Jones, P. Paudyal, H. MacPherson, J. Sim, E. Ernst, M. Fisken, G. Lewith, J. Tadman, G. J. Macfarlane, P. Bertin, C. Arendt, I. Terpstra, B. VanLunen, M. de Longueville, H. Zhou, A. Cai, E. Lacy, J. Kay, E. Matteson, C. Hu, E. Hsia, M. Doyle, M. Rahman, D. Shealy, D. L. Scott, F. Ibrahim, H. Abozaid, A. Hassell, M. Plant, D. Walker, G. Simpson, A. Kowalczyk, P. Prouse, A. Brown, M. George, N. Kumar, K. Mackay, S. Marshall, C. L. Ludivico, B. Murthy, M. Corbo, W. Samborski, F. Berenbaum, J. Ambrugeat, B. Bennett, H. Burkhardt, V. Bykerk, J. Roman Ivorra, J. Wollenhaupt, A. Stancati, C. Bernasconi, D. G. I. Scott, P. Claydon, C. Ellis, S. Buchan, J. Pope, C. O. Bingham, E. M. Massarotti, G. Coteur, M. Weinblatt, C. Ball, T. Ainsworth, J. Kermik, J. Woodham, I. Haq, E. Quesada-Masachs, A. Carolina Diaz, G. Avila, I. Acosta, X. Sans, C. Alegre, S. Marsal, D. McWilliams, P. D. Kiely, R. Bolce, J. Wang, M. Ingham, R. Dehoratius, D. Decktor, V. Rao, A. Pavlov, M. Klearman, D. Musselman, J. Giles, J. Bathon, N. Sattar, J. Lee, D. Baxter, J. S. McLaren, M.-M. Gordon, K. Z. Thant, E. L. Williams, S. Earl, P. White, J. Williams, A. K. Jan, A. I. Bhatti, C. Stafford, M. Carolan, and S. A. Ramakrishnan
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medicine.medical_specialty ,Comorbid anxiety ,business.industry ,Osteoarthritis ,Primary care ,medicine.disease ,Rheumatology ,Internal medicine ,General practice ,medicine ,Anxiety ,Pharmacology (medical) ,In patient ,medicine.symptom ,business ,Depression (differential diagnoses) - Published
- 2012
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38. Revisiting debates on learning disabilities in adult education
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Jovita M. Ross-Gordon and Alisa Belzer
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Educational research ,Adult education ,Adult basic education ,Adult development ,education ,Pedagogy ,Learning disability ,Learning theory ,medicine ,medicine.symptom ,Psychology ,Special education ,Intellectual history - Abstract
Since the 1980s, educators in adult basic education and special education have speculated that a substantial if unknown percentage of adults have specific learning disabilities and have sought to identify and address effectively the needs of these learners.
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- 2011
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39. Faculty Perceptions of Adult Learners in College Classrooms
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Beverly Woodson Day, Jovita M. Ross-Gordon, Candace Tull, and Stella Lovato
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Higher education ,business.industry ,media_common.quotation_subject ,Teacher education ,Education ,Perception ,Pedagogy ,ComputingMilieux_COMPUTERSANDEDUCATION ,Public university ,College instruction ,Community college ,Psychology ,business ,Adult Learning ,College classroom ,media_common - Abstract
The number of nontraditional students on college and university campuses continues to increase. Therefore, faculty members need to become aware of issues regarding adult learners in the college classroom. Interviews were conducted with faculty at a large community college and a four-year public university in south central Texas. This study focused on faculty members’ perceptions of adult learners in the college classroom, their preparation for teaching in higher education and for teaching adult students in particular, and the strategies they found to be effective for teaching adults. Three themes were identified, including conceptions of adult learners, faculty preparation for college teaching, and teaching adults.
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- 2011
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40. Sputtering behavior and evolution of depth resolution upon low energy ion irradiation of GaAs
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Teya Topuria, Christian Gerl, Devendra K. Sadana, Philip M. Rice, Chiara Marchiori, M. Richter, M. J. P. Hopstaken, Dirk Pfeiffer, and M. S. Gordon
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Materials science ,Ion beam mixing ,Ion beam ,Process Chemistry and Technology ,Analytical chemistry ,Condensed Matter::Mesoscopic Systems and Quantum Hall Effect ,Focused ion beam ,Molecular physics ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Ion ,Secondary ion mass spectrometry ,Condensed Matter::Materials Science ,Ion beam deposition ,Physics::Plasma Physics ,Sputtering ,Materials Chemistry ,Irradiation ,Electrical and Electronic Engineering ,Instrumentation - Abstract
The authors have investigated the sputtering behavior and evolution of depth resolution upon low energy ion irradiation during secondary ion mass spectrometry (SIMS) depth profiling of GaAs. They presented a systematic and quantitative study of the impact of ion species, primary ion impact energy, and incident angle on (evolution of) depth resolution using a well-characterized dedicated InGaAs/GaAs multilayer structure with nearly atomically abrupt heterointerfaces. They demonstrated that for low energy O2+ ion beam irradiation, the SIMS depth resolution is severely degraded by (transient) incorporation of high surface O-concentration into the altered layer, leading to detrimental ion beam induced formation of topography. They provided evidence that topography formation is primarily invoked by the strong angular dependence of the sputter yield on (local) incident angle. In the case of low energy, oblique Cs+ ion beam irradiation, the sputtering behavior of GaAs is well-behaved with no significant transien...
- Published
- 2010
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41. Persistence of hormonal and metabolic rhythms during fasting in 7- to 9-day-old rabbits entrained by nursing during the night
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Enrique Meza, Claudia Juárez, M. Kathleen Gordon, Mario Caba, Elvira Morgado, and Francis K.-Y. Pau
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Blood Glucose ,Leptin ,Litter (animal) ,medicine.medical_specialty ,Fatty Acids, Nonesterified ,Motor Activity ,Biology ,Article ,Behavioral Neuroscience ,chemistry.chemical_compound ,Endocrinology ,Nursing ,Corticosterone ,Internal medicine ,Lactation ,medicine ,Zeitgeber ,Animals ,Circadian rhythm ,Glycogen ,Endocrine and Autonomic Systems ,Fasting ,Ghrelin ,Animals, Suckling ,Circadian Rhythm ,medicine.anatomical_structure ,Animals, Newborn ,Liver ,chemistry ,Female ,Rabbits - Abstract
Rabbit does nurse their litter once every 24 h during the night. We hypothesized that corticosterone, ghrelin, leptin, and metabolites such as glucose, liver glycogen, and free fatty acids could be affected in the pups by the time at which does nurse them. Therefore, we measured these parameters in pups nursed at 02:00 h (nighttime for the doe) to compare them with results from a previous study where does nursed at 10:00 h, during daytime. From postnatal day 7, pups were sacrificed either just before their scheduled time of nursing or at 4, 8, 12, 16, or 20 h after nursing ( n = 6 at each time point); additional pups were sacrificed at 4 h intervals between 48 and 72 h after nursing to study the persistence of oscillations during fasting. All pups developed locomotor anticipatory activity to nursing. Corticosterone, ghrelin, and free fatty acids exhibited a rhythm that persisted in fasted pups. Glucose concentrations were lower in fasted than in nursed pups, and glycogen was only detected in nursed subjects. Leptin values were stable and low in nursed subjects but increased significantly in fasted subjects up to 72 h after the expected nursing time. The rhythm of ghrelin persisted during fasting, contrary to our previous findings in pups nursed during daytime (i.e., outside the natural time of nursing for this species). Therefore, in 7-day-old rabbit pups, night nursing is a strong zeitgeber for corticosterone, ghrelin, free fatty acids, and energy metabolites but not for leptin.
- Published
- 2010
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42. Hispanic Adults at a Southwestern University: Reasons They Come, Reasons They Stay
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Jovita M. Ross-Gordon, Elizabeth Speight, Christopher J. Russian, and Linda Muñoz
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Gerontology ,Psychology ,Education - Published
- 2008
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43. Novel findings regarding Glut-4 expression in adipose tissue and muscle in horses – A preliminary report
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M. E. Gordon, Kenneth H. McKeever, Hélio Cordeiro Manso Filho, Malcolm Watford, and H.E.C. Costa
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endocrine system ,medicine.medical_specialty ,Adipose tissue ,White adipose tissue ,Carbohydrate metabolism ,Insulin resistance ,Western blot ,Internal medicine ,medicine ,Animals ,Horses ,Muscle, Skeletal ,Glucose Transporter Type 4 ,General Veterinary ,biology ,medicine.diagnostic_test ,Skeletal muscle ,biology.organism_classification ,medicine.disease ,Medius ,Endocrinology ,medicine.anatomical_structure ,Adipose Tissue ,Gene Expression Regulation ,Female ,Animal Science and Zoology ,Densitometry ,hormones, hormone substitutes, and hormone antagonists - Abstract
One of the hallmarks of insulin resistance is a reduction in glucose transporter-4 (Glut-4) expression in adipose tissue but not in skeletal muscle. However, while Glut-4 has been demonstrated in skeletal and cardiac muscles in horses it has not been demonstrated in adipose tissue. The initial objectives of the present study were: (1) to test the hypothesis that Glut-4 expression would vary between selected key skeletal muscles; (2) to test the hypothesis that it would also vary between representative adipose tissue depots, and (3) to see whether expression would be greater in adipose tissue compared to muscle. Glut-4 expression was determined by Western blot using samples obtained from post mortem biopsies obtained from four muscles (gluteus medius, semitendinosus, heart, and diaphragm), and four adipose tissues (subcutaneous, retroperitoneal, mesenteric, and omental) in three horses. There were no differences (P>0.05) in Glut-4 protein expression between the muscles sampled. Likewise there were no differences (P>0.05) in Glut-4 protein expression between fat depots. There was a significant difference (P=0.03) when pooled means for Glut-4 expression in muscle (58.8+/-2.5 densitometry units) were compared with adipose tissue (115.8+/-15.7). This difference in Glut-4 expression in these two tissues with distinctly different metabolic reasons for taking up glucose may warrant further investigation to see if there are more pronounced differences in Glut-4 expression in muscle and adipose tissue in various populations of horses.
- Published
- 2007
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44. Interactions between subunits of Saccharomyces cerevisiae RNase MRP support a conserved eukaryotic RNase P/MRP architecture
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Panagiotis Karahalios, Tanya V. Aspinall, James M B Gordon, John Paul Bukowski, Johanna M. Avis, Hayley J. Bennett, Scott C. Walker, and David R. Engelke
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Saccharomyces cerevisiae Proteins ,RNase P ,Protein subunit ,Saccharomyces cerevisiae ,RNase PH ,Ribonuclease P ,03 medical and health sciences ,stomatognathic system ,Endoribonucleases ,Protein Interaction Mapping ,Genetics ,RNA Precursors ,Humans ,030304 developmental biology ,Ribonucleoprotein ,0303 health sciences ,biology ,030302 biochemistry & molecular biology ,RNA ,RNA, Fungal ,Ribosomal RNA ,biology.organism_classification ,Molecular biology ,RNase MRP ,Protein Subunits ,Biochemistry ,Ribonucleoproteins ,RNA, Ribosomal - Abstract
Ribonuclease MRP is an endonuclease, related to RNase P, which functions in eukaryotic pre-rRNA processing. In Saccharomyces cerevisiae, RNase MRP comprises an RNA subunit and ten proteins. To improve our understanding of subunit roles and enzyme architecture, we have examined protein-protein and protein-RNA interactions in vitro, complementing existing yeast two-hybrid data. In total, 31 direct protein-protein interactions were identified, each protein interacting with at least three others. Furthermore, seven proteins self-interact, four strongly, pointing to subunit multiplicity in the holoenzyme. Six protein subunits interact directly with MRP RNA and four with pre-rRNA. A comparative analysis with existing data for the yeast and human RNase P/MRP systems enables confident identification of Pop1p, Pop4p and Rpp1p as subunits that lie at the enzyme core, with probable addition of Pop5p and Pop3p. Rmp1p is confirmed as an integral subunit, presumably associating preferentially with RNase MRP, rather than RNase P, via interactions with Snm1p and MRP RNA. Snm1p and Rmp1p may act together to assist enzyme specificity, though roles in substrate binding are also indicated for Pop4p and Pop6p. The results provide further evidence of a conserved eukaryotic RNase P/MRP architecture and provide a strong basis for studies of enzyme assembly and subunit function.
- Published
- 2007
45. Exercise-induced alterations in plasma concentrations of ghrelin, adiponectin, leptin, glucose, insulin, and cortisol in horses
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C. L. Betros, Hélio Cordeiro Manso Filho, Kenneth H. McKeever, and M. E. Gordon
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Leptin ,medicine.medical_specialty ,Time Factors ,Hydrocortisone ,Peptide Hormones ,medicine.medical_treatment ,Incremental exercise ,Oxygen Consumption ,Physical Conditioning, Animal ,Internal medicine ,medicine ,Animals ,Insulin ,Horses ,Analysis of Variance ,Meal ,Cross-Over Studies ,General Veterinary ,Adiponectin ,business.industry ,digestive, oral, and skin physiology ,Repeated measures design ,Ghrelin ,Glucose ,Endocrinology ,Exercise Test ,Female ,Animal Science and Zoology ,Analysis of variance ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Six Standardbred (STB) mares (11+/-2 years, 521+/-77 kg; means+/-SD) performed an exercise trial (EX) where they underwent an incremental exercise test (GXT) as well as a parallel control trial (CON) to test the hypothesis that short-term, high intensity exercise would alter plasma concentrations of glucose, leptin, adiponectin, ghrelin, insulin and cortisol. Plasma samples were taken before (0 min), during (last 10s at 6, 8m/s, and the velocity eliciting VO(2max)), and after exercise (2, 10, 30, 60 min; 12 and 24h post-GXT). A second set of blood samples was collected before and after an afternoon meal given at 1515 h (at 1500, 1514, 1530, and 1545 h). Data were analyzed using ANOVA for repeated measures and Tukey's test. During the GXT, there were no changes (P0.05) in the plasma concentrations of glucose, leptin, adiponectin or ghrelin. However, there was a 29% increase (P0.05) in mean plasma cortisol concentration and a 35% decrease (P0.05) in mean plasma insulin concentration. Substantial increases (P0.05) in the mean plasma concentrations of glucose and cortisol of 36% and 102%, respectively, were seen in the EX trial during the first 60 min post-GXT. Plasma leptin concentration, measured at the 24h post-GXT time point, was 20% lower (P0.05) during the EX trial compared with the parallel time point in the standing control (CON) trial. Plasma ghrelin concentration was 37% lower (P0.05) in the EX trial compared with CON before and after the afternoon meal, but was 43% higher (P0.05) 12h post-GXT. There were no differences between EX and CON for plasma concentrations of insulin or adiponectin during recovery. It was concluded that short-term high intensity exercise alters plasma leptin and ghrelin concentrations in STB mares post-exercise, which may signal the exercised animals to alter energy intake.
- Published
- 2007
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46. Developing Evidence-Based Interventions for Foster Children: An Example of a Randomized Clinical Trial with Infants and Toddlers
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Mary Dozier, Oliver Lindhiem, M. Kathleen Gordon, Melissa Manni, Seymour Levine, John P. Ackerman, Elizabeth Peloso, Annie Bernier, and Sandra Sepulveda
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business.industry ,education ,Psychological intervention ,General Social Sciences ,law.invention ,Foster care ,Relationship formation ,Randomized controlled trial ,Welfare system ,law ,Evidence based interventions ,Intervention (counseling) ,Medicine ,business ,Foster parents ,Clinical psychology - Abstract
Children who enter foster care have usually experienced maltreatment as well as disruptions in relationships with primary caregivers. These children are at risk for a host of problematic outcomes. However, there are few evidence-based interventions that target foster children. This article presents preliminary data testing the effectiveness of an intervention, Attachment and Biobehavioral Catch-up, to target relationship formation in young children in the foster care system. Children were randomly assigned to the experimental intervention that was designed to enhance regulatory capabilities or to a control intervention. In both conditions, the foster parents received in-home training for 10 weekly sessions. Post-intervention measures were collected 1 month following the completion of the training. Outcome measures included children's diurnal production of cortisol (a stress hormone), and parent report of children's problem behaviors. Children in the experimental intervention group had lower cortisol values than children in the control intervention. Also, the experimental intervention parents reported fewer behavior problems for older versus younger foster children. Results provide preliminary evidence of the effectiveness of an intervention that targets children's regulatory capabilities and serve as an example of how interventions can effectively target foster children in the child welfare system.
- Published
- 2006
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47. Effect of orange peel and black tea extracts on markers of performance and cytokine markers of inflammation in horses
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Jennifer Streltsova, N.R. Liburt, Kenneth H. McKeever, Hélio Cordeiro Manso Filho, Robert T. Rosen, William C. Franke, David W. Horohov, and M. E. Gordon
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medicine.medical_specialty ,Pathology ,biology ,business.industry ,Horse ,Orange (colour) ,Placebo ,Crossover study ,Endocrinology ,Internal medicine ,medicine ,biology.protein ,Ventricular pressure ,Creatine kinase ,Treadmill ,business ,Respiratory exchange ratio - Abstract
This study tested the hypothesis that orange peel (O) and decaffeinated black tea (T) extracts would alter markers of exercise performance as well as exercise-induced mRNA expression for the inflammatory cytokines IL-6, TNF-alpha and IFN-gamma. Nine healthy, unfit Standardbred mares (age: 10±4years, ∼450kg) were assigned to three treatment groups in a randomized crossover design where each horse was administered one of the following; placebo (O; 21 water), black tea extract in water (T; 21) or orange peel extract in water (W; 21), via a nasogastric tube. One hour later the horses completed an incremental graded exercise test (GXT) on a treadmill at a fixed 6% grade with measurements and blood samples obtained at rest, at the end of each 1min step of the GXT and at 2 and 5min post-GXT. An additional set of blood samples for Polymerase Chain Reaction (PCR) measurements of mRNA was obtained before exercise and at 5 and 30min and 1, 2, 4 and 24h post-GXT. The GXTs were conducted between 0700 and 1200h not less than 7days apart. There were no differences (P>0.05) in VO2max, respiratory exchange ratio, run time, velocity at VO2max, core body temperature, haematocrit, creatine kinase (CK), plasma lactate concentrations, HR, right ventricular pressure (RVP) or pulmonary artery pressure (PAP) across treatments. A major finding was that orange peel extract significantly reduced post-exercise VO2 recovery time (W = 112±7, O = 86±6, and T = 120±11s). There was a significant difference in plasma total protein concentration (TP) in the O runs compared with water and T. TNF-alpha mRNA expression was lower in the T runs compared with water and O trials. IFN-gamma mRNA expression levels appeared to be lower in both the T and O extract runs compared with the water trials. The mRNA expression of IL-6 was unaltered across treatment groups. These data suggest that orange peel and black tea extracts may modulate the cytokine responses to intense exercise. Orange peel extract reduced post-exercise recovery time and may potentially enhance the ability of horses to perform subsequent bouts of high-intensity exercise.
- Published
- 2006
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48. Oral and intravenous carbohydrate challenges decrease active ghrelin concentrations and alter hormones related to control of energy metabolism in horses1
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M. E. Gordon and Kenneth H. McKeever
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medicine.medical_specialty ,Adiponectin ,Chemistry ,Leptin ,Insulin ,medicine.medical_treatment ,Energy metabolism ,Horse ,General Medicine ,Carbohydrate ,Endocrinology ,Internal medicine ,Genetics ,medicine ,Animal Science and Zoology ,Ghrelin ,hormones, hormone substitutes, and hormone antagonists ,Food Science ,Hormone - Abstract
This study tested the hypothesis that grain and intravenous dextrose challenges would alter plasma concentrations of active ghrelin, adiponectin, leptin, glucose, insulin, and cortisol in Standardbred mares. To deliver 0.5 g of glucose (dextrose solution for the intravenous test)/kg of BW, mares received intravenous dextrose (50% solution) or oral grain administration in 2 trials. In response to the oral grain challenge, plasma glucose and insulin concentrations increased (P < 0.001) by 56 and 802%, respectively. Plasma ghrelin concentration initially decreased (P < 0.001) by 40%, then subsequently increased (P < 0.05) from its nadir by 259%. Plasma leptin concentration decreased (P = 0.002) 17% compared with baseline. There was no change (P = 0.34) in plasma adiponectin concentration in response to oral grain challenge; however, plasma cortisol concentrations decreased (P < 0.001) by 24%. In response to the intravenous dextrose challenge, plasma glucose and insulin concentrations increased (P < 0.001) by 432 and 395%, respectively. Plasma active ghrelin concentration initially decreased (P < 0.001) by 56%, then subsequently increased (P < 0.001) from its nadir by 314%. Plasma leptin concentration also increased (P < 0.001) by 33% compared with baseline. There was no change (P = 0.18) in plasma adiponectin concentration throughout the dextrose challenge. Plasma cortisol concentration increased (P = 0.027) by 20%. Hence, oral grain and intravenous nutrient challenges have the ability to alter variables potentially related to energy metabolism in mares, with acute changes in glucose and insulin possibly modulating changes in ghrelin and leptin.
- Published
- 2006
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49. Training-induced energy balance mismatch in Standardbred mares
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HC Manso-Filho, Kenneth H. McKeever, S. Bokman, Jennifer Streltsova, M. E. Gordon, C. L. Betros, and N.R. Liburt
- Subjects
Animal science ,business.industry ,Leptin ,Insulin ,medicine.medical_treatment ,Heart rate ,Hay ,Medicine ,VO2 max ,Ghrelin ,Total mixed ration ,business ,Incremental exercise - Abstract
This study tested the hypothesis that exercise training would alter feed intake (FI), body composition (BC) and plasma concentrations of active ghrelin, leptin, cortisol, insulin and glucose. Eight Standardbred mares (12±2 years, 509±36 kg body weight (BW), mean±SD) were trained (EX) in an equine Equi-ciser (initially 3 days per week at 60% maximal heart rate (HRmax) for 20 min and gradually increased to 5 days per week at 70% HRmax for 30 min, with a 10-min warm-up and 10-min cool-down period at the walk). Six mares (12±2 years, 537±45 kg) served as non-exercise controls (CON). All mares were unfit and had not been subjected to conditioning for 3 years before the experiment. Pre- and post-training incremental exercise tests (GXT) were run to determine HRmax and maximal oxygen uptake (VO2max). A total mixed ration (TMR) of hay cubes was fed free choice for 16 h day-1 with the primary experiment following a 6-week diet adaptation period. Mares' FI was measured daily and reported in grams per kilogram BW of feed eaten per week. Changes in BC were assessed using BW (electronic scale) and percentage fat calculated using rump fat thickness and the Westervelt equation. Blood samples were taken every 2 weeks at 15:25, before mares were given their allotment of hay cubes on a day when they did not exercise, to measure plasma hormone and glucose concentrations. Gastroscopy for gastric ulcers was performed before, during and after the trial. VO2max increased by 7.0% (PP>0.05) in CON. FI decreased (PP-1) was initially higher (PPPPPPP>0.05) in active ghrelin, glucose, insulin or cortisol between the groups and over time. Five out of seven EX mares developed gastric ulcers. No CON mares developed gastric ulcers. Training was associated with changes in plasma leptin concentration, an increased incidence of gastric ulcers and a disruption of the balance between required DE and actual intake.
- Published
- 2006
- Full Text
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50. Foster Children’s Diurnal Production of Cortisol: An Exploratory Study
- Author
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Diana Eldreth, Mary Dozier, K. Chase Stovall-McClough, Elizabeth Peloso, M. Kathleen Gordon, Melissa Manni, Megan R. Gunnar, and Seymour Levine
- Subjects
Male ,Hypothalamo-Hypophyseal System ,Hydrocortisone ,Pituitary-Adrenal System ,Bedtime ,Foster Home Care ,Developmental psychology ,Child Development ,Developmental and Educational Psychology ,medicine ,Humans ,0501 psychology and cognitive sciences ,Saliva ,Morning ,05 social sciences ,Infant ,Child development ,Social relation ,Circadian Rhythm ,Foster care ,Caregivers ,El Niño ,050902 family studies ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Female ,0509 other social sciences ,Psychology ,050104 developmental & child psychology ,medicine.drug ,Clinical psychology - Abstract
Young children in foster care have often experienced inadequate early care and separations from caregivers. Preclinical studies suggest that early inadequate care and separations are associated with long-term changes in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the daytime pattern of cortisol production was examined among 55 young children who had been placed into foster care and 104 children who had not. Saliva samples were taken at wake-up, in the afternoon, and bedtime for 2 days. Average salivary cortisol values for each time of day were computed. A group (foster vs. comparison) time (morning, afternoon, night) interaction emerged, reflecting less decline in levels across the day for foster than comparison children. Daytime patterns were categorized as typical, low, or high. Children who had been in foster care had higher incidences of atypical patterns of cortisol production than children who had not. These differences suggest that conditions associated with foster care interfere with children’s ability to regulate neuroendocrine functioning.
- Published
- 2006
- Full Text
- View/download PDF
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