18 results on '"Roulston C"'
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2. Fine Particle Emissions From Tropical Peat Fires Decrease Rapidly With Time Since Ignition
- Author
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Roulston, C., primary, Paton‐Walsh, C., additional, Smith, T. E. L., additional, Guérette, É.‐A., additional, Evers, S., additional, Yule, C. M., additional, Rein, G., additional, and Van der Werf, G. R., additional
- Published
- 2018
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3. Characterisation of vasopressin V1A, angiotensin AT1 and AT2 receptor distribution and density in normotensive and hypertensive rat brain stem and kidney: effects of restraint stress
- Author
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McDougall, S. J., Roulston, C. A., Widdop, R. E., and Lawrence, A. J.
- Published
- 2000
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4. Fine particle emissions from tropical peat fires decrease rapidly with time since ignition
- Author
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Roulston, C., Paton-Walsh, C., Smith, T. E. L., Guérette, É. A., Evers, S., Yule, C. M., Rein, G., van der Werf, G. R., Roulston, C., Paton-Walsh, C., Smith, T. E. L., Guérette, É. A., Evers, S., Yule, C. M., Rein, G., and van der Werf, G. R.
- Abstract
Southeast Asia experiences frequent fires in fuel‐rich tropical peatlands, leading to extreme episodes of regional haze with high concentrations of fine particulate matter (PM2.5) impacting human health. In a study published recently, the first field measurements of PM2.5 emission factors for tropical peat fires showed larger emissions than from other fuel types. Here we report even higher PM2.5 emissions factors, measured at newly ignited peat fires in Malaysia, suggesting current estimates of fine particulate emissions from peat fires, may be underestimated by a factor of three or more. In addition, we use both field and laboratory measurements of burning peat to provide the first mechanistic explanation for the high variability in PM2.5 emission factors, demonstrating that build‐up of a surface ash layer causes the emissions of PM2.5 to decrease as the peat fire progresses. This finding implies that peat fires are more hazardous (in terms of aerosol emissions) when first ignited than when still burning many days later. Varying emission factors for PM2.5 also has implications for our ability to correctly model the climate and air quality impacts downwind of the peat fires. For modelers able to implement a time varying emission factor, we recommend an emission factor for PM2.5 from newly ignited tropical peat fires of 58 grams of PM2.5 per kilogram of dry fuel consumed (g.kg‐1), reducing exponentially at a rate of 9% per day. If the age of the fire is unknown or only a single value may be used, we recommend an average value of 28 g.kg‐1. Plain Language Summary This paper provides evidence that peat fire emissions of fine particulates are much larger than for other fires when the peat is newly ignited but decrease rapid as the fire progresses. This is important because it means that newly ignited fires are particularly detrimental to ambient air quality in impacted regions.
5. Structural Correlates of Mental Health Support Access among Sexual Minority Youth of Color during COVID-19.
- Author
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Roulston C, McKetta S, Price M, Fox KR, and Schleider JL
- Subjects
- Humans, United States epidemiology, Adolescent, Mental Health, Pandemics, Health Personnel, COVID-19, Sexual and Gender Minorities
- Abstract
Many youth with mental health needs cannot access treatment, with multiply-marginalized youth, such as sexual minority youth of Color (SMYoC), experiencing both structural and identity-related barriers to care. The COVID-19 pandemic threatens to exacerbate multi-level treatment access barriers facing SMYoC youth nationwide. However, little large-scale research has examined access to mental health care among SMYoC across the United States, either during or prior to the pandemic. Such work is critical to understanding and ameliorating barriers in this domain. Using data from adolescents who self-identified as SMYoC and who endorsed a desire for mental health support during the COVID-19 pandemic ( N = 470, ages 13-16, from 43 U.S. states), we examined associations between state-level, structural factors (income inequality; mental health-care provider shortage; anti-Black racism; homophobia; and the interaction between anti-Black racism and homophobia) and SMYoC mental health treatment access. Multinomial logistic regressions revealed state-level mental health-care provider shortage as the only significant predictor of SMYoC reporting they never (versus always ) accessed mental health support during the COVID-19 pandemic. SMYoC living in areas with both lower homophobia and lower anti-Black racism were more likely to report always (versus sometimes ) accessing mental health treatment. Results highlight the critical importance of considering diverse structural factors and applying an intersectional lens when exploring barriers to mental health treatment among multiply-marginalized youth. In locations where provider shortages are less severe, cultural stigma - including anti-Black racism and homophobia - may still pose challenges for SMYoC in need of mental health care.
- Published
- 2023
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6. Ecological-Systems Contributors to Internalizing Symptoms in a US Sample of Adolescents During the COVID-19 Pandemic.
- Author
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Thorpe D, Mirhashem R, Shen J, Roulston C, Fox K, and Schleider J
- Abstract
Objective: Internalizing problems are common in adolescence and increased substantially during the COVID-19 pandemic. Although rates of anxiety and depression have since improved, the general increase in the prevalence of mental health problems and disruptions to mental health services during the COVID-19 pandemic has resulted in huge gaps in care. Although research has primarily focused on proximal correlates of internalizing problems, a growing literature suggests that factors outside youths' immediate microsystems are equally crucial for their mental well-being. Thus, it is important to investigate multisystemic correlates of internalizing problems to inform individual and community-based interventions to address the current mental health burden., Method: Leveraging secondary data from a nationally diverse U.S. sample of 2,954 adolescents (ages 13-16), we examined the associations between factors at multiple levels of youths' ecologies - spanning indicators of threat and deprivation - and their depression and anxiety symptoms during the COVID-19 pandemic. Furthermore, in follow-up exploratory analyses, we examined if these associations differed by adolescents' racial/ethnic groups., Results: Consistent with socioecological models, we found that indicators of threat and deprivation in the adolescents' immediate home and more distal neighborhood environments were associated with depression and anxiety symptoms. The patterns of associations were similar across racial/ethnic groups in multigroup structural equation models. Additionally, we found that mean levels of internalizing symptoms and socioecological predictors significantly differed across racial/ethnic groups., Conclusion: These findings have important implications for understanding multi-level contributors to adolescent mental health, which may inform research, practice, and policy.
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- 2023
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7. A Digital Single-Session Intervention Platform for Youth Mental Health: Cultural Adaptation, Evaluation, and Dissemination.
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Shroff A, Roulston C, Fassler J, Dierschke NA, Todd JSP, Ríos-Herrera Á, Plastino KA, and Schleider JL
- Abstract
Background: Despite the proliferation of evidence-based digital mental health programs for young people, their low uptake and inconsistent implementation preclude them from benefiting youths at scale. Identifying effective implementation strategies for evidence-based supports is especially critical in regions where treatment access is lowest owing to mental health provider shortages., Objective: The goal of this academic-community partnership, funded by the City of San Antonio Metropolitan Health District, was to culturally adapt, disseminate, and gauge the acceptability and utility of an evidence-based digital mental health platform-Project Youth Empowerment and Support (YES)-among English- and Spanish-speaking youths living in south Texas., Methods: Project YES is an open-access, anonymous platform containing 3 evidence-based, self-guided interventions for youth mental health. Project YES was culturally adapted via focus groups and co-design sessions with San Antonio youths with lived experience of depression and anxiety; translated into Spanish; and disseminated throughout San Antonio, Texas, via community and school partnerships., Results: During the project period (April 2021 to December 2021), 1801 San Antonio youths began and 894 (49.64%) of them completed a 30-minute, single-session intervention within Project YES (aged 11-17 years; n=718, 39.87% male; n=961, 53.36% female; and n=3, 0.17% intersex; n=1477, 82.01% Hispanic; n=77, 4.28% non-Hispanic White; n=113, 6.27% Black; n=28, 1.55% Asian; and n=93, 5.16% other). This completion rate (49.64%) surpassed those previously observed for Project YES (eg, 34% when disseminated via social media). San Antonio youths rated Project YES as highly acceptable across all metrics, both in English and Spanish. In addition, the youths who completed Project YES-ENGLISH reported significant improvements in hopelessness (Cohen d=0.33; P<001), self-hate (Cohen d=0.27; P<001), and perceived agency (Cohen d=0.25; P<001) from before to after the intervention, and the youths who completed Project YES-SPANISH reported significant improvements in self-hate (Cohen d=0.37; P=.049) from before to after the intervention., Conclusions: The results indicate that Project YES-an open-access, free, and anonymous web-based single-session intervention platform-is an acceptable, accessible, and applicable mental health support for English- and Spanish-speaking San Antonio youths., (©Akash Shroff, Chantelle Roulston, Julia Fassler, Nicole A Dierschke, Jennifer San Pedro Todd, Ámbar Ríos-Herrera, Kristen A Plastino, Jessica Lee Schleider. Originally published in JMIR Mental Health (https://mental.jmir.org), 14.02.2023.)
- Published
- 2023
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8. From text to screen: Gentleman Jack then and now.
- Author
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Roulston C
- Subjects
- Female, Humans, Television, Sexual Behavior, Homosexuality, Female, Drama, Sexual and Gender Minorities
- Abstract
As part of the growing genre of post-heritage quality drama for television, Sally Wainwright's BBC-HBO production of Gentleman Jack stands out in terms of its close adherence to the original Lister diaries. While in many ways season one of Gentleman Jack follows the conventional narrative of courtship and marriage that defines much historical costume drama-as in, for example, the adaptations of Jane Austen novels-it also continually subverts the form through its unique queer content, closely based on the Lister diaries. While Gentleman Jack is not the BBC's first queer lesbian historical series, the uniqueness of the source text, which includes explicit descriptions of Lister's sexual practices in code, positions the series as ground-breaking in terms of prime-time television. This essay considers the ways in which the series adapts, mediates and reconfigures the original diaries for a contemporary audience. It will analyze how these transcriptions are supplemented through the performative and the visual and how to read the ideological coding of episodes that move away from the diaries into the realm of the fictional, such as the Lister-Walker marriage proposal at the end of the series. It also asks what the responsibility of the series is to the historical archive on the one hand, and to its contemporary audience on the other.
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- 2022
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9. Performance and Deployment of Low-Cost Particle Sensor Units to Monitor Biomass Burning Events and Their Application in an Educational Initiative.
- Author
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Reisen F, Cooper J, Powell JC, Roulston C, and Wheeler AJ
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- Biomass, Environmental Monitoring, Particulate Matter analysis, Air Pollutants analysis, Air Pollution analysis
- Abstract
Biomass burning smoke is often a significant source of airborne fine particles in regional areas where air quality monitoring is scarce. Emerging sensor technology provides opportunities to monitor air quality on a much larger geographical scale with much finer spatial resolution. It can also engage communities in the conversation around local pollution sources. The SMoke Observation Gadget (SMOG), a unit with a Plantower dust sensor PMS3003, was designed as part of a school-based Science, Technology, Engineering and Mathematics (STEM) project looking at smoke impacts in regional areas of Victoria, Australia. A smoke-specific calibration curve between the SMOG units and a standard regulatory instrument was developed using an hourly data set collected during a peat fire. The calibration curve was applied to the SMOG units during all field-based validation measurements at several locations and during different seasons. The results showed strong associations between individual SMOG units for PM
2.5 concentrations (r2 = 0.93-0.99) and good accuracy (mean absolute error (MAE) < 2 μg m-3 ). Correlations of the SMOG units to reference instruments also demonstrated strong associations (r2 = 0.87-95) and good accuracy (MAE of 2.5-3.0 μg m-3 ). The PM2.5 concentrations tracked by the SMOG units had a similar response time as those measured by collocated reference instruments. Overall, the study has shown that the SMOG units provide relevant information about ambient PM2.5 concentrations in an airshed impacted predominantly by biomass burning, provided that an adequate adjustment factor is applied.- Published
- 2021
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10. Development and delivery of the trainee nursing associate pilot curriculum.
- Author
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Roulston C and Davies M
- Subjects
- Humans, Pilot Projects, State Medicine, United Kingdom, Curriculum, Education, Nursing, Baccalaureate, Training Support
- Abstract
This article discusses the recently launched curriculum for nursing associates and the authors' involvement in the development of a medicine management module. This required recognition of the challenges in an ever-changing healthcare environment with, in this instance, limited guidance from the Nursing and Midwifery Council and associated professional organisations and with multiple stakeholders to satisfy. Curriculum development therefore required consideration of the concerns of service users and providers regarding the integration of this new, poorly understood role, its potential effect on skill mix and lack of knowledge regarding proposed regulation.
- Published
- 2019
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11. '2A-Like' Signal Sequences Mediating Translational Recoding: A Novel Form of Dual Protein Targeting.
- Author
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Roulston C, Luke GA, de Felipe P, Ruan L, Cope J, Nicholson J, Sukhodub A, Tilsner J, and Ryan MD
- Subjects
- Humans, Oligopeptides metabolism, Plant Cells metabolism, Protein Biosynthesis physiology, Protein Sorting Signals physiology, Protein Transport physiology, Ribosomes metabolism
- Abstract
We report the initial characterization of an N-terminal oligopeptide '2A-like' sequence that is able to function both as a signal sequence and as a translational recoding element. Owing to this translational recoding activity, two forms of nascent polypeptide are synthesized: (i) when 2A-mediated translational recoding has not occurred: the nascent polypeptide is fused to the 2A-like N-terminal signal sequence and the fusion translation product is targeted to the exocytic pathway, and, (ii) a translation product where 2A-mediated translational recoding has occurred: the 2A-like signal sequence is synthesized as a separate translation product and, therefore, the nascent (downstream) polypeptide lacks the 2A-like signal sequence and is localized to the cytoplasm. This type of dual-functional signal sequence results, therefore, in the partitioning of the translation products between the two sub-cellular sites and represents a newly described form of dual protein targeting., (© 2016 The Authors. Traffic published by John Wiley & Sons Ltd.)
- Published
- 2016
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12. A beacon of hope in stroke therapy-Blockade of pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies.
- Author
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Hoque A, Hossain MI, Ameen SS, Ang CS, Williamson N, Ng DC, Chueh AC, Roulston C, and Cheng HC
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- Animals, Humans, Memantine pharmacology, Memantine therapeutic use, Peptides pharmacology, Peptides therapeutic use, Signal Transduction drug effects, Cell Death drug effects, Neurons drug effects, Neuroprotective Agents pharmacology, Neuroprotective Agents therapeutic use, Stroke drug therapy
- Abstract
Excitotoxicity, a pathological process caused by over-stimulation of ionotropic glutamate receptors, is a major cause of neuronal loss in acute and chronic neurological conditions such as ischaemic stroke, Alzheimer's and Huntington's diseases. Effective neuroprotective drugs to reduce excitotoxic neuronal loss in patients suffering from these neurological conditions are urgently needed. One avenue to achieve this goal is to clearly define the intracellular events mediating the neurotoxic signals originating from the over-stimulated glutamate receptors in neurons. In this review, we first focus on the key cellular events directing neuronal death but not involved in normal physiological processes in the neurotoxic signalling pathways. These events, referred to as pathologically activated events, are potential targets for the development of neuroprotectant therapeutics. Inhibitors blocking some of the known pathologically activated cellular events have been proven to be effective in reducing stroke-induced brain damage in animal models. Notable examples are inhibitors suppressing the ion channel activity of neurotoxic glutamate receptors and those disrupting interactions of specific cellular proteins occurring only in neurons undergoing excitotoxic cell death. Among them, Tat-NR2B9c and memantine are clinically effective in reducing brain damage caused by some acute and chronic neurological conditions. Our second focus is evaluation of the suitability of the other inhibitors for use as neuroprotective therapeutics. We also discuss the experimental approaches suitable for bridging our knowledge gap in our current understanding of the excitotoxic signalling mechanism in neurons and discovery of new pathologically activated cellular events as potential targets for neuroprotection., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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13. Lost in translation: The biogenesis of non-LTR retrotransposon proteins.
- Author
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Luke GA, Roulston C, Odon V, de Felipe P, Sukhodub A, and Ryan MD
- Abstract
"Young" APE-type non-LTR retrotransposons (non-LTRs) typically encode two open reading frames (ORFs 1 and 2). The shorter ORF1 translation product (ORF1p) comprises an RNA binding activity, thought to bind to non-LTR transcript RNA, protect against nuclease degradation and specify nuclear import of the ribonuclear protein complex (RNP). ORF2 encodes a multifunctional protein (ORF2p) comprising apurinic/apyrimidinic endonuclease (APE) and reverse-transcriptase (RT) activities, responsible for genome replication and re-integration into chromosomal DNA. However, some clades of APE-type non-LTRs only encode a single ORF-corresponding to the multifunctional ORF2p outlined above (and for simplicity referred-to as ORF2 below). The absence of an ORF1 correlates with the acquisition of a 2A oligopeptide translational recoding element (some 18-30 amino acids) into the N-terminal region of ORF2p. In the case of non-LTRs encoding two ORFs, the presence of ORF1 would necessarily downregulate the translation of ORF2. We argue that in the absence of an ORF1, 2A could provide the corresponding translational downregulation of ORF2. While multiple molecules of ORF1p are required to decorate the non-LTR transcript RNA in the cytoplasm, conceivably only a single molecule of ORF2p is required for target-primed reverse transcription/integration in the nucleus. Why would the translation of ORF2 need to be controlled by such mechanisms? An "excess" of ORF2p could result in disadvantageous levels of genome instability by, for example, enhancing short, interspersed, element (SINE) retrotransposition and the generation of processed pseudogenes. If so, the acquisition of mechanisms-such as 2A-to control ORF2p biogenesis would be advantageous.
- Published
- 2013
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14. APE-type non-LTR retrotransposons of multicellular organisms encode virus-like 2A oligopeptide sequences, which mediate translational recoding during protein synthesis.
- Author
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Odon V, Luke GA, Roulston C, de Felipe P, Ruan L, Escuin-Ordinas H, Brown JD, Ryan MD, and Sukhodub A
- Subjects
- Amino Acid Sequence, Genome, Protozoan, Molecular Sequence Data, Oligopeptides chemistry, Open Reading Frames, Phylogeny, Sequence Alignment, Trypanosoma classification, Oligopeptides genetics, Protein Biosynthesis physiology, Retroelements genetics, Trypanosoma genetics, Trypanosoma metabolism
- Abstract
2A oligopeptide sequences ("2As") mediate a cotranslational recoding event termed "ribosome skipping." Previously we demonstrated the activity of 2As (and "2A-like sequences") within a wide range of animal RNA virus genomes and non-long terminal repeat retrotransposons (non-LTRs) in the genomes of the unicellular organisms Trypanosoma brucei (Ingi) and T. cruzi (L1Tc). Here, we report the presence of 2A-like sequences in the genomes of a wide range of multicellular organisms and, as in the trypanosome genomes, within non-LTR retrotransposons (non-LTRs)-clustering in the Rex1, Crack, L2, L2A, and CR1 clades, in addition to Ingi. These 2A-like sequences were tested for translational recoding activity, and highly active sequences were found within the Rex1, L2, CR1, and Ingi clades. The presence of 2A-like sequences within non-LTRs may not only represent a method of controlling protein biogenesis but also shows some correlation with such apurinic/apyrimidinic DNA endonuclease-type non-LTRs encoding one, rather than two, open reading frames (ORFs). Interestingly, such non-LTRs cluster with closely related elements lacking 2A-like recoding elements but retaining ORF1. Taken together, these observations suggest that acquisition of 2A-like translational recoding sequences may have played a role in the evolution of these elements.
- Published
- 2013
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15. The revolting Anne Lister: the U.K.'s first modern lesbian.
- Author
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Roulston C
- Subjects
- Female, History, 20th Century, Humans, United Kingdom, Homosexuality, Female history, Sexual Behavior history, Shame
- Abstract
Anne Lister has recently been turned from a relatively obscure figure of scholarly interest into a modern-day icon of lesbian sexuality. This article asks what gesture we perform when we celebrate Lister's life through the lens of modernity. Why do we need Lister to be modern, and what does it mean to be so? If Lister is recognizable to us as an active and unashamed lesbian subject, is it that modernity itself has managed to erase queer shame? Arguably, rather than claiming Lister for modernity, perhaps it is Lister who is putting our modernity into question.
- Published
- 2013
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16. Isolation and in vitro characterisation of prohaemocytes from the spider crab, Hyas araneus (L.).
- Author
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Roulston C and Smith VJ
- Subjects
- Animals, Cell Proliferation, Centrifugation, Density Gradient, Hemocytes immunology, Hemolymph cytology, Brachyura cytology, Brachyura immunology, Hemocytes cytology
- Abstract
A population of small, mostly undifferentiated, haemocytes were identified and enriched from the circulation of the spider crab, H. araneus, using a two-step density gradient separation procedure. Typically, these cells are spherical, ca. 8-12 μm diameter and have a high nucleus:cytoplasm ratio. Their number in the circulation increases significantly 24 h after a state of haemocytopenia has been created by withdrawal of 2 mL of haemolymph. The rise in the number of these cells at this time is consistent with a left shift phenomenon. A two-step separation procedure was developed to generate enriched populations of these small cells from the haemolymph and in vitro assays revealed that ca. 47% are BrdU-positive in vitro. By contrast BrdU uptake was not observed in the hyaline, semigranular or granular cells. The proliferative ability of the small cells, coupled with their close morphological resemblance to immature haemocytes reported from the haematopoietic tissue of other decapod species, leads us to conclude that these cells are prohaemocytes., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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17. Minocycline treatment attenuates microglia activation and non-angiotensin II [125I] CGP42112 binding in brainstem following nodose ganglionectomy.
- Author
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Roulston CL, Lawrence AJ, Widdop RE, and Jarrott B
- Subjects
- Animals, Antineoplastic Agents pharmacology, Autoradiography, Brain Stem metabolism, Ganglionectomy, Immunohistochemistry, Isoquinolines pharmacology, Male, Microglia metabolism, Oligopeptides metabolism, Rats, Rats, Wistar, Receptor, Angiotensin, Type 2 metabolism, Anti-Bacterial Agents pharmacology, Brain Stem drug effects, Microglia drug effects, Minocycline pharmacology, Nodose Ganglion surgery, Oligopeptides drug effects
- Abstract
We have previously shown that following unilateral nodose ganglionectomy, [125I] CGP42112 binds to a non-angiotensin II (Ang II) related binding site in rat dorsal motor nucleus of the vagus nerve, ambiguus nucleus and nucleus of the solitary tract. Furthermore, this up-regulated binding site localizes with activated microglia. Given that some tetracyclines may inhibit microglia activation in brain, we examined the effect of minocycline treatment on the binding of [125I] CGP42112 and [3H] PK11195 (an established radioligand for microglia), as well as OX-42 immunoreactivity (an immunomarker for activated microglia), following nodose ganglionectomy. Male Wistar Kyoto rats underwent unilateral nodose ganglionectomy or sham operation and were treated with saline or minocycline (50 mg/kg i.p.) 12 h before surgery and twice daily after surgery (each 50mg/kg i.p.) for 3 days. Subsequent to nodose ganglionectomy, [125I] CGP42112 binding (insensitive to PD123319 or Ang II) was increased approximately two-fold in the ipsilateral nucleus of the solitary tract and was also induced in the ipsilateral dorsal motor nucleus of the vagus nerve and ambiguus nucleus of saline-treated rats. Treatment with minocycline reduced this non-angiotensin II [125I] CGP42112 binding (40-50% reduction) in the nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve and ambiguus nucleus. Analogous experiments using [3H] PK11195 also revealed up-regulated binding in the ipsilateral nucleus of the solitary tract ( approximately 205%), dorsal motor nucleus of the vagus nerve (approximately 80%) and ambiguus nucleus (approximately 210%) of saline-treated rats following nodose ganglionectomy, which was reduced by 40-100% with minocycline treatment. Immunoreactivity to OX-42 confirmed an increase in microglia activation and accumulation of macrophages in these brain stem nuclei following nodose ganglionectomy, which was also attenuated following treatment with minocycline. These data demonstrate that non-Ang II [125I] CGP42112 binding following nodose ganglionectomy is attenuated by minocycline treatment. This minocycline-induced effect was associated with reduced activation of microglia and an apparent reduction in the number of macrophages in the abovementioned nuclei. This evidence suggests that a non-Ang II [125I] CGP42112 binding site is located on, or associated with, activated microglia and macrophages, providing a useful tool with which to quantitate the neuroprotective effects of centrally acting anti-inflammatory compounds.
- Published
- 2005
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18. Non-angiotensin II [(125)I] CGP42112 binding is a sensitive marker of neuronal injury in brainstem following unilateral nodose ganglionectomy: comparison with markers for activated microglia.
- Author
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Roulston CL, Lawrence AJ, Jarrott B, and Widdop RE
- Subjects
- Angiotensin II analogs & derivatives, Angiotensin II metabolism, Animals, Autoradiography, Biomarkers, Brain Stem pathology, Ganglionectomy, Glial Fibrillary Acidic Protein metabolism, Gliosis pathology, Gliosis physiopathology, Iodine Radioisotopes, Isoquinolines metabolism, Isoquinolines pharmacology, Male, Microglia physiology, Nodose Ganglion surgery, Oligopeptides metabolism, Rats, Rats, Inbred WKY, Tritium, Vasoconstrictor Agents metabolism, Angiotensin II pharmacology, Brain Stem physiopathology, Nodose Ganglion physiology, Oligopeptides pharmacology, Vasoconstrictor Agents pharmacology
- Abstract
Previously we reported that a non-angiotensin II [(125)I] CGP42112 binding site is up-regulated in rat brainstem nuclei as a result of unilateral nodose ganglionectomy. In the present study, we compared non-angiotensin II [(125)I] CGP42112 binding with microglia/macrophage activation following nodose ganglionectomy, using both in vitro autoradiography and immunohistochemistry. Specific [(125)I] CGP42112 binding was observed in the nucleus of the solitary tract (NTS) and revealed an AT(2) receptor component as well as a non-angiotensin II receptor component. Subsequent to unilateral nodose ganglionectomy, [(125)I] CGP42112 binding in the ipsilateral NTS was increased approximately two-fold and was also induced in the ipsilateral dorsal motor nucleus (DMX) and the nucleus ambiguus (n.amb). This non-angiotensin II [(125)I] CGP42112 binding site was displaced by CGP42112 but not other ligands. Increased [(3)H] PK11195 binding (a known marker of reactive gliosis) was also observed in the same brainstem nuclei as non-angiotensin II [(125)I] CGP42112 binding after nodose ganglionectomy. The similarity in binding patterns between [(125)I] CGP42112 and [(3)H] PK11195 was shown to be primarily due to retrograde degeneration in the ipsilateral NTS, DMX and n.amb, as both radioligands were localized to similar cellular targets within the interstial space and over cellular debris. Immunohistochemical data confirmed reactive gliosis within the ipsilateral NTS, DMX and n.amb, following nodose ganglionectomy, which was predominantly characterized by an increase in OX-42 immunoreactivity (a marker for activated microglia/macrophages), with only a small increase in glial fibrillary acidic protein immunoreactivity (a marker of astrogliosis) detected. These data demonstrate for the first time that non-angiotensin II [(125)I] CGP42112 binding is associated with activated microglia, as well as macrophages, following unilateral nodose ganglionectomy. Furthermore, these studies also demonstrate the potential use of non-angiotensin II [(125)I] CGP42112 binding as a marker for quantitating inflammatory events which occur as a result of damage to the CNS.
- Published
- 2004
- Full Text
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