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Article ; Online: An insight into new glycotherapeutics in glial inflammation: Understanding the role of glycosylation in mitochondrial function and acute to the chronic phases of inflammation.

Patil, Vaibhav / Bohara, Raghvendra / Winter, Carla / Kilcoyne, Michelle / McMahon, Siobhan / Pandit, Abhay

2022 Volume 29, Issue 1, Page(s) 429–444

Abstract: Introduction: Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodeling ... ...

Abstract	Introduction: Glycosylation plays a critical role during inflammation and glial scar formation upon spinal cord injury (SCI) disease progression. Astrocytes and microglia are involved in this cascade to modulate the inflammation and tissue remodeling from acute to chronic phases. Therefore, understating the glycan changes in these glial cells is paramount. Method and results: A lectin microarray was undertaken using a cytokine-driven inflammatory mixed glial culture model, revealing considerable differential glycosylation from the acute to the chronic phase in a cytokine-combination generated inflamed MGC model. It was found that several N- and O-linked glycans associated with glia during SCI were differentially regulated. Pearson's correlation hierarchical clustering showed that groups were separated into several clusters, illustrating the heterogenicity among the control, cytokine combination, and LPS treated groups and the day on which treatment was given. Control and LPS treatments were observed to be in dense clusters. This was further confirmed with lectin immunostaining in which GalNAc, GlcNAc, mannose, fucose and sialic acid-binding residues were detected in astrocytes and microglia. However, the sialyltransferase inhibitor inhibited this modification (upregulation of the sialic acid expression), which indeed modulates the mitochondrial functions. Conclusions: The present study is the first functional investigation of glycosylation modulation in a mixed glial culture model, which elucidates the role of the glycome in neuroinflammation in progression and identified potential therapeutic targets for future glyco therapeutics in neuroinflammation.
MeSH term(s)	Humans ; Lipopolysaccharides/toxicity ; Glycosylation ; Neuroinflammatory Diseases ; N-Acetylneuraminic Acid ; Neuroglia/physiology ; Inflammation/drug therapy ; Inflammation/metabolism ; Spinal Cord Injuries/metabolism ; Cytokines/metabolism ; Lectins/metabolism
Chemical Substances	Lipopolysaccharides ; N-Acetylneuraminic Acid (GZP2782OP0) ; Cytokines ; Lectins
Language	English
Publishing date	2022-11-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2423461-8
ISSN	1755-5949 ; 1755-5930
ISSN (online)	1755-5949
ISSN	1755-5930
DOI	10.1111/cns.14016
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Zs.A 4537: Show issues

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Article ; Online: Toward Clinical Adoption of Standardized mHealth Solutions: The Feasibility of Using MyStrengths+MyHealth Consumer-Generated Health Data for Knowledge Discovery.

Austin, Robin R / Mathiason, Michelle A / Lu, Sheng-Chieh / Lindquist, Ruth A / McMahon, Siobhan K / Pieczkiewicz, David S / Monsen, Karen A

Computers, informatics, nursing : CIN

2022 Volume 40, Issue 2, Page(s) 71–79

MeSH term(s)	Feasibility Studies ; Humans ; Knowledge Discovery ; Telemedicine
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078463-6
ISSN	1538-9774 ; 1538-2931
ISSN (online)	1538-9774
ISSN	1538-2931
DOI	10.1097/CIN.0000000000000862
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Article ; Online: Postintervention and follow-up changes in caregiving behavior and representations after individually or group delivered hybrid Circle of Security-intensive intervention with New Zealand caregiver-child dyads.

Huber, Anna / Hicks, Anne-Marie / Ball, Michelle / McMahon, Catherine

Attachment & human development

2020 Volume 23, Issue 6, Page(s) 931–952

Abstract: The Circle of Security Intensive intervention (COS-I) aims to improve child attachment security and reduce disorganisation by improving caregiver capacities, including caregiving behavior and representations. Research on COS-I effectiveness with these ... ...

Abstract	The Circle of Security Intensive intervention (COS-I) aims to improve child attachment security and reduce disorganisation by improving caregiver capacities, including caregiving behavior and representations. Research on COS-I effectiveness with these goals is limited and none examines if positive changes are sustained. A recently revised hybrid COS-I protocol (COS-I-RH) incorporates Circle of Security-Parenting (COS-P) material and individual or group delivery options. We examined (1) post intervention and follow-up changes in caregiving behavior and representations after COS-I-RH and (2) if individual or group delivery moderated changes. New Zealand parent-child dyads with relationship concerns (n=36; child age M =35 months) referred to a community-based program completed COS-I-RH. Four caregiver capacities (supportive and unsupportive parenting (CTNES), parenting self-efficacy and satisfaction (PSOC)) were measured pre- and post-treatment, and one year later. Regardless of delivery mode, after COS-I-RH, parents showed large improvements on all 4 indices of caregiving behavior and representations, maintained at one-year follow-up.
MeSH term(s)	Caregivers ; Child, Preschool ; Follow-Up Studies ; Humans ; New Zealand ; Object Attachment ; Parent-Child Relations ; Parenting ; Parents
Language	English
Publishing date	2020-08-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1497969-x
ISSN	1469-2988 ; 1461-6734
ISSN (online)	1469-2988
ISSN	1461-6734
DOI	10.1080/14616734.2020.1809057
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Article ; Online: Origin and Diversification of the Saguaro Cactus (Carnegiea gigantea): A Within-Species Phylogenomic Analysis.

Sanderson, Michael J / Búrquez, Alberto / Copetti, Dario / McMahon, Michelle M / Zeng, Yichao / Wojciechowski, Martin F

Systematic biology

2022 Volume 71, Issue 5, Page(s) 1178–1194

Abstract: Reconstructing accurate historical relationships within a species poses numerous challenges, not least in many plant groups in which gene flow is high enough to extend well beyond species boundaries. Nonetheless, the extent of tree-like history within a ... ...

Abstract	Reconstructing accurate historical relationships within a species poses numerous challenges, not least in many plant groups in which gene flow is high enough to extend well beyond species boundaries. Nonetheless, the extent of tree-like history within a species is an empirical question on which it is now possible to bring large amounts of genome sequence to bear. We assess phylogenetic structure across the geographic range of the saguaro cactus, an emblematic member of Cactaceae, a clade known for extensive hybridization and porous species boundaries. Using 200 Gb of whole genome resequencing data from 20 individuals sampled from 10 localities, we assembled two data sets comprising 150,000 biallelic single nucleotide polymorphisms (SNPs) from protein coding sequences. From these, we inferred within-species trees and evaluated their significance and robustness using five qualitatively different inference methods. Despite the low sequence diversity, large census population sizes, and presence of wide-ranging pollen and seed dispersal agents, phylogenetic trees were well resolved and highly consistent across both data sets and all methods. We inferred that the most likely root, based on marginal likelihood comparisons, is to the east and south of the region of highest genetic diversity, which lies along the coast of the Gulf of California in Sonora, Mexico. Together with striking decreases in marginal likelihood found to the north, this supports hypotheses that saguaro's current range reflects postglacial expansion from the refugia in the south of its range. We conclude with observations about practical and theoretical issues raised by phylogenomic data sets within species, in which SNP-based methods must be used rather than gene tree methods that are widely used when sequence divergence is higher. These include computational scalability, inference of gene flow, and proper assessment of statistical support in the presence of linkage effects. [Phylogenomics; phylogeography; rooting; Sonoran Desert.].
MeSH term(s)	Cactaceae/genetics ; Hybridization, Genetic ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA
Language	English
Publishing date	2022-03-04
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1482572-7
ISSN	1076-836X ; 1063-5157
ISSN (online)	1076-836X
ISSN	1063-5157
DOI	10.1093/sysbio/syac017
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Article ; Online: OregonFluor enables quantitative intracellular paired agent imaging to assess drug target availability in live cells and tissues.

Wang, Lei G / Montaño, Antonio R / Combs, Jason R / McMahon, Nathan P / Solanki, Allison / Gomes, Michelle M / Tao, Kai / Bisson, William H / Szafran, Dani A / Samkoe, Kimberley S / Tichauer, Kenneth M / Gibbs, Summer L

Nature chemistry

2023 Volume 15, Issue 5, Page(s) 729–739

Abstract: Non-destructive fluorophore diffusion across cell membranes to provide an unbiased fluorescence intensity readout is critical for quantitative imaging applications in live cells and tissues. Commercially available small-molecule fluorophores have been ... ...

Abstract	Non-destructive fluorophore diffusion across cell membranes to provide an unbiased fluorescence intensity readout is critical for quantitative imaging applications in live cells and tissues. Commercially available small-molecule fluorophores have been engineered for biological compatibility, imparting high water solubility by modifying rhodamine and cyanine dye scaffolds with multiple sulfonate groups. The resulting net negative charge, however, often renders these fluorophores cell-membrane-impermeant. Here we report the design and development of our biologically compatible, water-soluble and cell-membrane-permeable fluorophores, termed OregonFluor (ORFluor). By adapting previously established ratiometric imaging methodology using bio-affinity agents, it is now possible to use small-molecule ORFluor-labelled therapeutic inhibitors to quantitatively visualize their intracellular distribution and protein target-specific binding, providing a chemical toolkit for quantifying drug target availability in live cells and tissues.
MeSH term(s)	Fluorescent Dyes/chemistry ; Rhodamines/chemistry ; Water
Chemical Substances	Fluorescent Dyes ; Rhodamines ; Water (059QF0KO0R)
Language	English
Publishing date	2023-03-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2464596-5
ISSN	1755-4349 ; 1755-4330
ISSN (online)	1755-4349
ISSN	1755-4330
DOI	10.1038/s41557-023-01173-6
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Article ; Online: Comparative Pharmacokinetics of Commercially Available Cannabidiol Isolate, Broad-Spectrum, and Full-Spectrum Products.

Berthold, Erin C / Kamble, Shyam H / Kanumuri, Siva Rama Raju / Kuntz, Michelle A / Senetra, Alexandria S / Chiang, Yi-Hua / McMahon, Lance R / McCurdy, Christopher R / Sharma, Abhisheak

European journal of drug metabolism and pharmacokinetics

2023 Volume 48, Issue 4, Page(s) 427–435

Abstract: Background and objectives: A wide variety of products containing cannabidiol (CBD) are available on the commercial market. One of the most common products, CBD oil, is administered to self-treat a variety of conditions. These oils are available as CBD ... ...

Abstract	Background and objectives: A wide variety of products containing cannabidiol (CBD) are available on the commercial market. One of the most common products, CBD oil, is administered to self-treat a variety of conditions. These oils are available as CBD isolate, broad-spectrum [all terpenes and minor cannabinoids except Δ-9-tetrahydrocannabinol (THC)], or full-spectrum (all terpenes and minor cannabinoids with THC < 0.3% dried weight) products. A systematic pharmacokinetic study was performed to determine whether there are differences in the pharmacokinetic parameters and systemic exposure of CBD after oral dosing as an isolate, broad-spectrum, or full-spectrum product. Methods: Male and female Sprague Dawley rats were treated with a single, equivalent oral dose of CBD delivered as isolate, broad-spectrum, or full-spectrum product. An additional study using an in-house preparation of CBD isolate plus 0.2% THC was performed. A permeability assay was also conducted to investigate whether the presence of THC alters the intestinal permeability of CBD. Results: There was an increase in the oral bioavailability of CBD (12% and 21% in male and female rats, respectively) when administered as a full-spectrum product compared with the isolate and broad-spectrum products. There was no difference in the bioavailability of CBD between the commercially available full-spectrum formulation (3.1% CBD; containing 0.2% THC plus terpenes and other minor cannabinoids) versus the in-house preparation of CBD full-spectrum (CBD isolate 3.2% plus 0.2% THC isolate). In vitro permeability assays demonstrated that the presence of THC increases permeability of CBD while also decreasing efflux through the gut wall. Conclusions: The presence of 0.2% THC increased the oral bioavailability of CBD in male and female rats, indicating that full-spectrum products may produce increased effectiveness of CBD due to a greater exposure available systemically.
MeSH term(s)	Male ; Female ; Rats ; Animals ; Cannabidiol ; Dronabinol ; Rats, Sprague-Dawley ; Cannabinoids ; Biological Availability
Chemical Substances	Cannabidiol (19GBJ60SN5) ; Dronabinol (7J8897W37S) ; Cannabinoids
Language	English
Publishing date	2023-06-19
Publishing country	France
Document type	Journal Article
ZDB-ID	196729-0
ISSN	2107-0180 ; 0398-7639 ; 0378-7966
ISSN (online)	2107-0180
ISSN	0398-7639 ; 0378-7966
DOI	10.1007/s13318-023-00839-3
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Article ; Online: Publisher Correction: OregonFluor enables quantitative intracellular paired agent imaging to assess drug target availability in live cells and tissues.

Nature chemistry

2022 Volume 15, Issue 5, Page(s) 740

Language	English
Publishing date	2022-03-24
Publishing country	England
Document type	Published Erratum
ZDB-ID	2464596-5
ISSN	1755-4349 ; 1755-4330
ISSN (online)	1755-4349
ISSN	1755-4330
DOI	10.1038/s41557-023-01213-1
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Article ; Online: The Risk of Multiple Anthropogenic and Climate Change Threats Must Be Considered for Continental Scale Conservation and Management of Seagrass Habitat

Kathryn McMahon / Kieryn Kilminster / Robert Canto / Chris Roelfsema / Mitchell Lyons / Gary A. Kendrick / Michelle Waycott / James Udy

Frontiers in Marine Science, Vol

2022 Volume 9

Abstract: Globally marine-terrestrial interfaces are highly impacted due to a range of human pressures. Seagrass habitats exist in the shallow marine waters of this interface, have significant values and are impacted by a range of pressures. Cumulative risk ... ...

Abstract	Globally marine-terrestrial interfaces are highly impacted due to a range of human pressures. Seagrass habitats exist in the shallow marine waters of this interface, have significant values and are impacted by a range of pressures. Cumulative risk analysis is widely used to identify risk from multiple threats and assist in prioritizing management actions. This study conducted a cumulative risk analysis of seagrass habitat associated with the Australian continent to support management actions. We developed a spatially explicit risk model based on a database of threats to coastal aquatic habitat in Australia, spanning 35,000 km of coastline. Risk hotspots were identified using the model and reducing the risk of nutrient and sediment pollution for seagrass habitat was assessed. Incorporating future threats greatly altered the spatial-distribution of risk. High risk from multiple current threats was identified throughout all bioregions, but high risk from climate change alone manifested in only two. Improving management of nutrient and sediment loads, a common approach to conserve seagrass habitat did reduce risk, but only in temperate regions, highlighting the danger of focusing management on a single strategy. Monitoring, management and conservation actions from a national and regional perspective can be guided by these outputs.
Keywords	coastal habitat ; seagrass ; risk assessment ; climate change ; management ; Science ; Q ; General. Including nature conservation ; geographical distribution ; QH1-199.5
Subject code	333
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Soluble immune checkpoints as correlates for HIV persistence and T cell function in people with HIV on antiretroviral therapy.

Chiu, Chris Y / Schou, Maya D / McMahon, James H / Deeks, Steven G / Fromentin, Rémi / Chomont, Nicolas / Wykes, Michelle N / Rasmussen, Thomas A / Lewin, Sharon R

Frontiers in immunology

2023 Volume 14, Page(s) 1123342

Abstract: Introduction: In people with HIV (PWH) both off and on antiretroviral therapy (ART), the expression of immune checkpoint (IC) proteins is elevated on the surface of total and HIV-specific T-cells, indicating T-cell exhaustion. Soluble IC proteins and ... ...

Abstract	Introduction: In people with HIV (PWH) both off and on antiretroviral therapy (ART), the expression of immune checkpoint (IC) proteins is elevated on the surface of total and HIV-specific T-cells, indicating T-cell exhaustion. Soluble IC proteins and their ligands can also be detected in plasma, but have not been systematically examined in PWH. Since T-cell exhaustion is associated with HIV persistence on ART, we aimed to determine if soluble IC proteins and their ligands also correlated with the size of the HIV reservoir and HIV-specific T-cell function. Methods: We used multiplex bead-based immunoassay to quantify soluble programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin domain and mucin domain 3 (TIM-3), PD-1 Ligand 1 (PD-L1) and PD-1 Ligand 2 (PD-L2) in plasma from PWH off ART (n=20), on suppressive ART (n=75) and uninfected controls (n=20). We also quantified expression of membrane-bound IC and frequencies of functional T-cells to Gag and Nef peptide stimulation on CD4+ and CD8+ T-cells using flow cytometry. The HIV reservoir was quantified in circulating CD4+ T-cells using qPCR for total and integrated HIV DNA, cell-associated unspliced HIV RNA and 2LTR circles. Results: Soluble (s) PD-L2 level was higher in PWH off and on ART compared to uninfected controls. Higher levels of sPD-L2 correlated with lower levels of HIV total DNA and higher frequencies of gag-specific CD8+ T-cells expressing CD107a, IFNγ or TNFα. In contrast, the concentration of sLAG-3 was similar in uninfected individuals and PWH on ART, but was significantly elevated in PWH off ART. Higher levels of sLAG-3 correlated with higher levels of HIV total and integrated DNA, and lower frequency of gag-specific CD4+ T cells expressing CD107a. Similar to sLAG-3, levels of sPD-1 were elevated in PWH off ART and normalized in PWH on ART. sPD-1 was positively correlated with the frequency of gag-specific CD4+ T cells expressing TNF-a and the expression of membrane-bound PD-1 on total CD8+ T-cells in PWH on ART. Discussion: Plasma soluble IC proteins and their ligands correlate with markers of the HIV reservoir and HIV-specific T-cell function and should be investigated further in in large population-based studies of the HIV reservoir or cure interventions in PWH on ART.
MeSH term(s)	Humans ; Programmed Cell Death 1 Receptor/metabolism ; Ligands ; Lymphocyte Activation ; CD4-Positive T-Lymphocytes ; HIV Infections
Chemical Substances	Programmed Cell Death 1 Receptor ; Ligands
Language	English
Publishing date	2023-03-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1123342
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Article ; Online: Distinct Glycosylation Responses to Spinal Cord Injury in Regenerative and Nonregenerative Models.

Ronan, Rachel / Kshirsagar, Aniket / Rebelo, Ana Lúcia / Sunny, Abbah / Kilcoyne, Michelle / Flaherty, Roisin O' / Rudd, Pauline M / Schlosser, Gerhard / Saldova, Radka / Pandit, Abhay / McMahon, Siobhan S

Journal of proteome research

2022 Volume 21, Issue 6, Page(s) 1449–1466

Abstract: Traumatic spinal cord injury (SCI) results in disruption of tissue integrity and loss of function. We hypothesize that glycosylation has a role in determining the occurrence of regeneration and that biomaterial treatment can influence this glycosylation ... ...

Abstract	Traumatic spinal cord injury (SCI) results in disruption of tissue integrity and loss of function. We hypothesize that glycosylation has a role in determining the occurrence of regeneration and that biomaterial treatment can influence this glycosylation response. We investigated the glycosylation response to spinal cord transection in
MeSH term(s)	Animals ; Glycosylation ; Hydrogels ; Mammals ; N-Acetylneuraminic Acid ; Rats ; Spinal Cord ; Spinal Cord Injuries ; Xenopus laevis
Chemical Substances	Hydrogels ; N-Acetylneuraminic Acid (GZP2782OP0)
Language	English
Publishing date	2022-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.2c00043
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