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Article: Functional expression of L-, N-, P/Q-, and R-type calcium channels in the human NT2-N cell line.

Neelands, T R / King, A P / Macdonald, R L

2000 Volume 84, Issue 6, Page(s) 2933–2944

Abstract: ... reduced further by SNX-482 (7-14% of current remained), consistent with functional expression of L-, N ... and P/Q-calcium channel types and one or more R-type channel. The presence of multiple calcium ... of the regulation, expression and cellular function of human derived calcium channel currents; in particular the R ...

Abstract	The biophysical and pharmacological properties of voltage-gated calcium channel currents in the human teratocarcinoma cell line NT2-N were studied using the whole cell patch-clamp technique. When held at -80 mV, barium currents (I(Ba)s) were evoked by voltage commands to above -35 mV that peaked at +5 mV. When holding potentials were reduced to -20 mV or 5 mM barium was substituted for 5 mM calcium, there was a reduction in peak currents and a right shift in the current-voltage curve. A steady-state inactivation curve for I(Ba) was fit with a Boltzmann curve (V(1/2) = -43.3 mV; slope = -17.7 mV). Maximal current amplitude increased from 1-wk (232 pA) to 9-wk (1025 pA) postdifferentiation. Whole cell I(Ba)s were partially blocked by specific channel blockers to a similar extent in 1- to 3-wk and 7- to 9-wk postdifferentiation NT2-N cells: 10 microM nifedipine (19 vs. 25%), 10 microM conotoxin GVIA (27 vs. 25%), 10 microM conotoxin MVIIC (15 vs. 16%), and 1.75 microM SNX-482 (31 vs. 33%). Currents were completely blocked by 300 microM cadmium. In the presence of nifedipine, GVIA, and MVIIC, approximately 35% of current remained, which was reduced further by SNX-482 (7-14% of current remained), consistent with functional expression of L-, N-, and P/Q-calcium channel types and one or more R-type channel. The presence of multiple calcium currents in this human neuronal-type cell line provides a potentially useful model for study of the regulation, expression and cellular function of human derived calcium channel currents; in particular the R-type current(s).
MeSH term(s)	Calcium Channel Blockers/pharmacology ; Calcium Channels/biosynthesis ; Calcium Channels, L-Type/biosynthesis ; Calcium Channels, N-Type/biosynthesis ; Calcium Channels, P-Type/biosynthesis ; Calcium Channels, Q-Type/biosynthesis ; Calcium Channels, R-Type/biosynthesis ; Cell Differentiation ; Dose-Response Relationship, Drug ; Humans ; Membrane Potentials/drug effects ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; Nifedipine/pharmacology ; Patch-Clamp Techniques ; Spider Venoms/pharmacology ; Teratocarcinoma/metabolism ; Teratocarcinoma/pathology ; Tumor Cells, Cultured ; omega-Conotoxin GVIA/pharmacology ; omega-Conotoxins/pharmacology
Chemical Substances	Calcium Channel Blockers ; Calcium Channels ; Calcium Channels, L-Type ; Calcium Channels, N-Type ; Calcium Channels, P-Type ; Calcium Channels, Q-Type ; Calcium Channels, R-Type ; SNX 482 ; Spider Venoms ; omega-Conotoxins ; omega-conotoxin-MVIIC (147794-23-8) ; omega-Conotoxin GVIA (92078-76-7) ; Nifedipine (I9ZF7L6G2L)
Language	English
Publishing date	2000-12
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
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Article ; Online: Deriving relations at multiple levels of complexity following minimal instruction: A demonstration.

Paranczak, Jessica L / Lambert, Joseph M / Ledford, Jennifer R / Copeland, Bailey A / Macdonald, M Janey

Journal of applied behavior analysis

2024 Volume 57, Issue 2, Page(s) 408–425

Abstract: Recommendations for achieving generalized instructional outcomes often overlook the capacity for generative learning for most verbally competent humans. Four children (ages 5-8) participated in this project. In Study 1, we provided decontextualized ... ...

Abstract	Recommendations for achieving generalized instructional outcomes often overlook the capacity for generative learning for most verbally competent humans. Four children (ages 5-8) participated in this project. In Study 1, we provided decontextualized discrete trial teaching to establish arbitrary relations between colors, pictures of characters, and researcher motor actions. All participants engaged in derivative responding, providing evidence of relational framing. Subsequently, we demonstrated that, with no additional instruction, these derivatives contributed to effective action within a socially valid context (i.e., Candyland gameplay). Study 2 extended the demonstration by teaching frames of opposition. Following teaching, all participants engaged in novel and contextually appropriate responding that entailed the derivation of both coordination and opposition between untrained stimuli. This outcome demonstrates how teaching simple relations can result in learning that manifests at higher levels of complexity (i.e., relational networking), providing some evidence that there can be socially valid benefits to decontextualized discrete trial instruction.
MeSH term(s)	Child ; Humans ; Learning
Language	English
Publishing date	2024-03-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	218065-0
ISSN	1938-3703 ; 0021-8855
ISSN (online)	1938-3703
ISSN	0021-8855
DOI	10.1002/jaba.1067
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Article ; Online: Lower limb blood flow occlusion increases systemic pressor response without increasing brachial arterial blood flow redistribution in women.

Fleming, Abby R / MacDonald, Hayley V / Buckner, Samuel L / Winchester, Lee J

Clinical physiology and functional imaging

2024

Abstract: ... Repeated measures correlations (r ...

Abstract	This study was conducted to investigate the systemic hemodynamic and vascular changes in women during and after two commonly used clinical blood flow restriction (BFR) pressures at rest. There are minimal data regarding the independent effects of BFR on hemodynamic and systemic vascular changes due to pressor response, particularly among women. Therefore, this study investigated BFR-induced alterations in pressor response and systemic flow redistribution at rest during two commonly used pressures (50% and 80% limb occlusion pressure [LOP]). Fifteen women (22.1 ± 4.2 years) completed two randomised sessions involving 8-min of bilateral, lower limb restriction at 50% or 80% LOP followed by 8-min of recovery post-deflation. Changes in vascular (arterial diameter [DIA], time-averaged mean velocity [TAMV], volume flow [VF], and area) and hemodynamic (heart rate [HR] and blood pressure) measures over time (pre-, during, post-occlusion) and by session (50% vs. 80% LOP) were tested using repeated measures analysis of variance. Repeated measures correlations (r
Language	English
Publishing date	2024-02-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2071203-0
ISSN	1475-097X ; 1475-0961
ISSN (online)	1475-097X
ISSN	1475-0961
DOI	10.1111/cpf.12873
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Article ; Online: Impact of built environment change on all-cause and cause-specific mortality: a novel longitudinal method and study.

Macdonald, Laura / Nicholls, Natalie / Brown, Denise / Mitchell, Richard

Journal of epidemiology and community health

2023 Volume 77, Issue 9, Page(s) 594–600

Abstract: Background: Public health research increasingly acknowledges the influence of built environments (BE) on health; however, it is uncertain how BE change is associated with better population health and whether BE change can help narrow health inequalities. ...

Abstract	Background: Public health research increasingly acknowledges the influence of built environments (BE) on health; however, it is uncertain how BE change is associated with better population health and whether BE change can help narrow health inequalities. This knowledge gap is partly due to a lack of suitable longitudinal BE data in most countries. We devised a method to quantify BE change longitudinally and explored associations with mortality. The method is replicable in any nation that captures BE vector map data. Methods: Ordnance Survey data were used to categorise small areas as having no change, loss or gain, in buildings, roads, and woodland between 2015 and 2019. We examined individual mortality records for 2012-2015 and 2016-2019, using negative binomial regression to explore associations between BE change and all-cause and cause-specific mortality, adjusting for income deprivation. Results: BE change varied significantly by deprivation and urbanicity. Change in the BE and change in mortality were not related, however, areas that went on to experience BE change had different baseline mortality rates compared with those that did not. For example, areas that gained infrastructure already had lower mortality rates. Conclusion: We provide new methodology to quantify BE change over time across a nation. Findings provide insight into the health of areas that do/do not experience change, prompting critical perspectives on cross-sectional studies of associations between BE and health. Methods and findings applied internationally could explore the context of BE change and its potential to improve health in areas most in need beyond the UK.
MeSH term(s)	Humans ; Built Environment ; Cause of Death ; Cross-Sectional Studies ; Income ; Mortality ; Public Health
Language	English
Publishing date	2023-06-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	391868-3
ISSN	1470-2738 ; 0142-467X ; 0141-7681 ; 0143-005X
ISSN (online)	1470-2738
ISSN	0142-467X ; 0141-7681 ; 0143-005X
DOI	10.1136/jech-2023-220681
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Zs.A 186: Show issues

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Article: Tolerability of Breast Radiation Therapy in the Setting of Mondor Disease.

Lin, Kevin / MacDonald, Heather R / Tetef, Merry L / Coleman, Colleen L

Advances in radiation oncology

2022 Volume 8, Issue 2, Page(s) 101120

Language	English
Publishing date	2022-11-04
Publishing country	United States
Document type	Case Reports
ISSN	2452-1094
ISSN	2452-1094
DOI	10.1016/j.adro.2022.101120
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Article ; Online: Differential Protease Specificity by Collagenase as a Novel Approach to Serum Proteomics That Includes Identification of Extracellular Matrix Proteins without Enrichment.

Macdonald, Jade K / Clift, Cassandra L / Saunders, Janet / Zambrzycki, Stephen C / Mehta, Anand S / Drake, Richard R / Angel, Peggi M

Journal of the American Society for Mass Spectrometry

2024 Volume 35, Issue 3, Page(s) 487–497

Abstract: Circulating extracellular matrix (ECM) proteins are serological biomarkers of interest due to their association with pathologies involving disease processes such as fibrosis and cancers. In this study, we investigate the potential for serum biomarker ... ...

Abstract	Circulating extracellular matrix (ECM) proteins are serological biomarkers of interest due to their association with pathologies involving disease processes such as fibrosis and cancers. In this study, we investigate the potential for serum biomarker research using differential protease specificity (DPS), leveraging alternate protease specificity as a targeting mechanism to selectively digest circulating ECM protein serum proteins. A proof-of-concept study is presented using serum from patients with cirrhotic liver or hepatocellular carcinoma. The approach uses collagenase DPS for digestion of deglycosylated serum and liquid-chromatography-trapped ion mobility-tandem mass spectrometry (LC-TIMS-MS/MS) to enhance the detection of ECM proteins in serum. It requires no sample enrichment and minimizes the albumin average precursor intensity readout to less than 1.2%. We further demonstrate the capabilities for using the method as a high-throughput matrix-assisted laser/desorption ionization mass spectrometry (MALDI-MS) assay coupled with reference library searching. A goal is to improve the depth and breadth of biofluid proteomics for noninvasive assays.
MeSH term(s)	Humans ; Peptide Hydrolases ; Tandem Mass Spectrometry ; Proteomics/methods ; Chromatography, Liquid/methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Collagenases ; Biomarkers
Chemical Substances	Peptide Hydrolases (EC 3.4.-) ; Collagenases (EC 3.4.24.-) ; Biomarkers
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1073671-2
ISSN	1879-1123 ; 1044-0305
ISSN (online)	1879-1123
ISSN	1044-0305
DOI	10.1021/jasms.3c00366
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Zs.A 4618: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 241: Show issues

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Article ; Online: Saliva sampling method influences oral microbiome composition and taxa distribution associated with oral diseases.

Roca, Cristian / Alkhateeb, Alaa A / Deanhardt, Bryson K / Macdonald, Jade K / Chi, Donald L / Wang, Jeremy R / Wolfgang, Matthew C

PloS one

2024 Volume 19, Issue 3, Page(s) e0301016

Abstract: Saliva is a readily accessible and inexpensive biological specimen that enables investigation of the oral microbiome, which can serve as a biomarker of oral and systemic health. There are two routine approaches to collect saliva, stimulated and ... ...

Abstract	Saliva is a readily accessible and inexpensive biological specimen that enables investigation of the oral microbiome, which can serve as a biomarker of oral and systemic health. There are two routine approaches to collect saliva, stimulated and unstimulated; however, there is no consensus on how sampling method influences oral microbiome metrics. In this study, we analyzed paired saliva samples (unstimulated and stimulated) from 88 individuals, aged 7-18 years. Using 16S rRNA gene sequencing, we investigated the differences in bacterial microbiome composition between sample types and determined how sampling method affects the distribution of taxa associated with untreated dental caries and gingivitis. Our analyses indicated significant differences in microbiome composition between the sample types. Both sampling methods were able to detect significant differences in microbiome composition between healthy subjects and subjects with untreated caries. However, only stimulated saliva revealed a significant association between microbiome diversity and composition in individuals with diagnosed gingivitis. Furthermore, taxa previously associated with dental caries and gingivitis were preferentially enriched in individuals with each respective disease only in stimulated saliva. Our study suggests that stimulated saliva provides a more nuanced readout of microbiome composition and taxa distribution associated with untreated dental caries and gingivitis compared to unstimulated saliva.
MeSH term(s)	Humans ; Saliva/microbiology ; RNA, Ribosomal, 16S/genetics ; Dental Caries ; Microbiota/genetics ; Gingivitis
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0301016
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Article: Fluids or vasopressors for the initial resuscitation of septic shock.

Macdonald, Stephen / Peake, Sandra L / Corfield, Alasdair R / Delaney, Anthony

Frontiers in medicine

2022 Volume 9, Page(s) 1069782

Abstract: Intravenous fluid resuscitation is recommended first-line treatment for sepsis-associated hypotension and/or hypoperfusion. The rationale is to restore circulating volume and optimize cardiac output in the setting of shock. Nonetheless, there is limited ... ...

Abstract	Intravenous fluid resuscitation is recommended first-line treatment for sepsis-associated hypotension and/or hypoperfusion. The rationale is to restore circulating volume and optimize cardiac output in the setting of shock. Nonetheless, there is limited high-level evidence to support this practice. Over the past decade emerging evidence of harm associated with large volume fluid resuscitation among patients with septic shock has led to calls for a more conservative approach. Specifically, clinical trials undertaken in Africa have found harm associated with initial fluid resuscitation in the setting of infection and hypoperfusion. While translating these findings to practice in other settings is problematic, there has been a re-appraisal of current practice with some recommending earlier use of vasopressors rather than repeated fluid boluses as an alternative to restore perfusion in septic shock. There is consequently uncertainty and variation in practice. The question of fluids or vasopressors for initial resuscitation in septic shock is the subject of international multicentre clinical trials.
Language	English
Publishing date	2022-11-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2022.1069782
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Article ; Online: Impact of chemogenetic activation of dorsal vagal complex astrocytes in mice on adaptive glucoregulatory responses.

MacDonald, Alastair J / Pye, Katherine R / Beall, Craig / Ellacott, Kate L J

Journal of neuroendocrinology

2023 Volume 35, Issue 8, Page(s) e13315

Abstract: The dorsal vagal complex (DVC) regulates diverse aspects of physiology including food intake and blood glucose homeostasis. Astrocytes play an active role in regulating DVC function and, by extension, physiological parameters. DVC astrocytes in ex vivo ... ...

Abstract	The dorsal vagal complex (DVC) regulates diverse aspects of physiology including food intake and blood glucose homeostasis. Astrocytes play an active role in regulating DVC function and, by extension, physiological parameters. DVC astrocytes in ex vivo slices respond to low tissue glucose. The response of neurons to low glucose is conditional on intact astrocyte signalling in slice preparations, suggesting astrocytes are primary sensors of glucose deprivation (glucoprivation). Based on these published findings we hypothesised that in vivo DVC astrocyte manipulation with chemogenetics would be sufficient to alter physiological responses that control blood glucose. We found that 2-h after systemic 2-DG-induced glucoprivation there were no observable changes in morphology of glial fibrillary acidic protein (GFAP)-immunoreactive DVC cells, specifically those in the nucleus of the solitary tract (NTS). Chemogenetic activation of DVC astrocytes was sufficient to suppress nocturnal food intake by reducing both meal size and meal number and this manipulation also suppressed 2-DG-induced glucoprivic food intake. Chemogenetic activation of DVC astrocytes did not increase basal blood glucose nor protect against insulin-induced hypoglycaemia. In male mice, chemogenetic DVC astrocyte activation did not alter glucose tolerance. In female mice, the initial glucose excursion was reduced in a glucose tolerance test, suggesting enhanced glucose absorption. Based on our data and published work, we propose that DVC astrocytes may play an indispensable homeostatic role, that is, are necessary to maintain the function of glucoregulatory neuronal circuitry, but alone their bulk activation is not sufficient to result in adaptive glucoregulatory responses. It is possible that there are state-dependent effects and/or DVC astrocyte subsets that have this specialised role, but this was unresolvable using the experimental approaches employed here.
MeSH term(s)	Male ; Female ; Mice ; Animals ; Blood Glucose ; Astrocytes/metabolism ; Vagus Nerve/physiology ; Glucose/metabolism ; Hypoglycemia/metabolism
Chemical Substances	Blood Glucose ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2023-06-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1007517-3
ISSN	1365-2826 ; 0953-8194
ISSN (online)	1365-2826
ISSN	0953-8194
DOI	10.1111/jne.13315
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Zs.A 2634: Show issues

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Article ; Online: Is spatial exposure to heritage associated with visits to heritage and to mental health? A cross-sectional study using data from the UK Household Longitudinal Study (UKHLS).

Macdonald, Laura / Nicholls, Natalie / Gallou, Eirini / Monckton, Linda / Mitchell, Richard

BMJ open

2023 Volume 13, Issue 3, Page(s) e066986

Abstract: Objectives: Existing research highlights the beneficial nature of heritage engagement for mental health, but engagement varies geographically and socially, and few studies explore spatial exposure (ie, geographic availability) to heritage and heritage ... ...

Abstract	Objectives: Existing research highlights the beneficial nature of heritage engagement for mental health, but engagement varies geographically and socially, and few studies explore spatial exposure (ie, geographic availability) to heritage and heritage visits. Our research questions were 'does spatial exposure to heritage vary by area income deprivation?', 'is spatial exposure to heritage linked to visiting heritage?' and 'is spatial exposure to heritage linked to mental health?'. Additionally, we explored whether local heritage is associated with mental health regardless of the presence of green space. Design: Data were collected from January 2014 to June 2015 via the UK Household Longitudinal Study (UKHLS) wave 5. Our study is cross-sectional. Setting: UKHLS data were either collected via face-to-face interview or online questionnaire. Participants: 30 431 adults (16+ years) (13 676 males, 16 755 females). Participants geocoded to Lower Super Output Area (LSOA) 'neighbourhood' and 'English Index of Multiple Deprivation' 2015 income score. Main exposures/outcome measures: LSOA-level heritage exposure and green space exposure (ie, population and area densities); heritage site visit in the past year (outcome, binary: no, yes); mental distress (outcome, General Health Questionnaire-12, binary: less distressed 0-3, more distressed 4+). Results: Heritage varied by deprivation, the most deprived areas (income quintile (Q)1: 1.8) had fewer sites per 1000 population than the least deprived (Q5: 11.1) (p<0.01). Compared with those with no LSOA-level heritage, those with heritage exposure were more likely to have visited a heritage site in the past year (OR: 1.12 (95% CI 1.03 to 1.22)) (p<0.01). Among those with heritage exposure, visitors to heritage had a lower predicted probability of distress (0.171 (95% CI 0.162 to 0.179)) than non-visitors (0.238 (95% CI 0.225 to 0.252)) (p<0.001). Conclusions: Our research contributes to evidence for the well-being benefits of heritage and is highly relevant to the government's levelling-up heritage strategy. Our findings can feed into schemes to tackle inequality in heritage exposure to improve both heritage engagement and mental health.
MeSH term(s)	Adult ; Male ; Female ; Humans ; Mental Health ; Longitudinal Studies ; Cross-Sectional Studies ; Mental Disorders ; United Kingdom/epidemiology
Language	English
Publishing date	2023-03-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-066986
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