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Article: Cannabinoids and endocannabinoids as therapeutics for nervous system disorders: preclinical models and clinical studies.

Duncan, R Scott / Riordan, Sean M / Gernon, Matthew C / Koulen, Peter

2023 Volume 19, Issue 4, Page(s) 788–799

Abstract: Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body. They have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several ... ...

Abstract	Cannabinoids are lipophilic substances derived from Cannabis sativa that can exert a variety of effects in the human body. They have been studied in cellular and animal models as well as in human clinical trials for their therapeutic benefits in several human diseases. Some of these include central nervous system (CNS) diseases and dysfunctions such as forms of epilepsy, multiple sclerosis, Parkinson's disease, pain and neuropsychiatric disorders. In addition, the endogenously produced cannabinoid lipids, endocannabinoids, are critical for normal CNS function, and if controlled or modified, may represent an additional therapeutic avenue for CNS diseases. This review discusses in vitro cellular, ex vivo tissue and in vivo animal model studies on cannabinoids and their utility as therapeutics in multiple CNS pathologies. In addition, the review provides an overview on the use of cannabinoids in human clinical trials for a variety of CNS diseases. Cannabinoids and endocannabinoids hold promise for use as disease modifiers and therapeutic agents for the prevention or treatment of neurodegenerative diseases and neurological disorders.
Language	English
Publishing date	2023-10-16
Publishing country	India
Document type	Journal Article ; Review
ZDB-ID	2388460-5
ISSN	1876-7958 ; 1673-5374
ISSN (online)	1876-7958
ISSN	1673-5374
DOI	10.4103/1673-5374.382220
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Article ; Online: Boom-bust population dynamics drive rapid genetic change.

Stringer, Emily J / Gruber, Bernd / Sarre, Stephen D / Wardle, Glenda M / Edwards, Scott V / Dickman, Christopher R / Greenville, Aaron C / Duncan, Richard P

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 18, Page(s) e2320590121

Abstract: Increasing environmental threats and more extreme environmental perturbations place species at risk of population declines, with associated loss of genetic diversity and evolutionary potential. While theory shows that rapid population declines can cause ... ...

Abstract	Increasing environmental threats and more extreme environmental perturbations place species at risk of population declines, with associated loss of genetic diversity and evolutionary potential. While theory shows that rapid population declines can cause loss of genetic diversity, populations in some environments, like Australia's arid zone, are repeatedly subject to major population fluctuations yet persist and appear able to maintain genetic diversity. Here, we use repeated population sampling over 13 y and genotype-by-sequencing of 1903 individuals to investigate the genetic consequences of repeated population fluctuations in two small mammals in the Australian arid zone. The sandy inland mouse (
MeSH term(s)	Animals ; Mice ; Australia ; Population Dynamics ; Genotype ; Mammals ; Heterozygote ; Marsupialia ; Genetic Variation ; Genetics, Population
Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2320590121
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Article ; Online: Proteome changes in a human retinal pigment epithelial cell line during oxidative stress and following antioxidant treatment.

Duncan, R Scott / Keightley, Andrew / Lopez, Adam A / Hall, Conner W / Koulen, Peter

Frontiers in immunology

2023 Volume 14, Page(s) 1138519

Abstract: Age related macular degeneration (AMD) is the most common cause of blindness in the elderly. Oxidative stress contributes to retinal pigment epithelium (RPE) dysfunction and cell death thereby leading to AMD. Using improved RPE cell model systems, such ... ...

Abstract	Age related macular degeneration (AMD) is the most common cause of blindness in the elderly. Oxidative stress contributes to retinal pigment epithelium (RPE) dysfunction and cell death thereby leading to AMD. Using improved RPE cell model systems, such as human telomerase transcriptase-overexpressing (hTERT) RPE cells (hTERT-RPE), pathophysiological changes in RPE during oxidative stress can be better understood. Using this model system, we identified changes in the expression of proteins involved in the cellular antioxidant responses after induction of oxidative stress. Some antioxidants such as vitamin E (tocopherols and tocotrienols) are powerful antioxidants that can reduce oxidative damage in cells. Alpha-tocopherol (α-Toc or αT) and gamma-tocopherol (γ-Toc or γT) are well-studied tocopherols, but signaling mechanisms underlying their respective cytoprotective properties may be distinct. Here, we determined what effect oxidative stress, induced by extracellularly applied tBHP in the presence and absence of αT and/or γT, has on the expression of antioxidant proteins and related signaling networks. Using proteomics approaches, we identified differential protein expression in cellular antioxidant response pathways during oxidative stress and after tocopherol treatment. We identified three groups of proteins based on biochemical function: glutathione metabolism/transfer, peroxidases and redox-sensitive proteins involved in cytoprotective signaling. We found that oxidative stress and tocopherol treatment resulted in unique changes in these three groups of antioxidant proteins indicate that αT and γT independently and by themselves can induce the expression of antioxidant proteins in RPE cells. These results provide novel rationales for potential therapeutic strategies to protect RPE cells from oxidative stress.
MeSH term(s)	Humans ; Aged ; Antioxidants/pharmacology ; Antioxidants/metabolism ; Proteome/metabolism ; Oxidative Stress/physiology ; Tocopherols/metabolism ; Macular Degeneration/metabolism ; Epithelial Cells/metabolism ; Retinal Pigments/metabolism
Chemical Substances	Antioxidants ; Proteome ; Tocopherols (R0ZB2556P8) ; Retinal Pigments
Language	English
Publishing date	2023-04-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1138519
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Article: Differential Mechanisms of Action and Efficacy of Vitamin E Components in Antioxidant Cytoprotection of Human Retinal Pigment Epithelium.

Duncan, R Scott / Hurtado, Daniel T / Hall, Conner W / Koulen, Peter

Frontiers in pharmacology

2022 Volume 12, Page(s) 798938

Abstract: The purpose of this study was to determine if different vitamin E components exhibit similar efficacy and mechanism of action in protecting Retinal pigment epithelium (RPE) cells from oxidative damage. We hypothesized that α-tocopherol (αT) is unique ... ...

Abstract	The purpose of this study was to determine if different vitamin E components exhibit similar efficacy and mechanism of action in protecting Retinal pigment epithelium (RPE) cells from oxidative damage. We hypothesized that α-tocopherol (αT) is unique among vitamin E components in its cytoprotective mechanism of action against oxidative stress in RPE cells and that it requires protein synthesis for optimal antioxidant effect. We used cell viability assays, fluorescent chemical labeling of DNA and actin and immuno-labeling of the antioxidant proteins Nrf2 and Sod2 and of the tight junction protein, ZO-1, and confocal microscopy to determine the effects of αT and γT against oxidative stress in immortalized human RPE cells (hTERT-RPE). Using the four main vitamin E components, αT, γT, δ-tocopherol (δT) and α-tocotrienol (αTr), we ascertained that they exhibit similar, but not identical, antioxidant activity as αT when used at equimolar concentrations. In addition, we determined that the exposure time of RPE cells to α-tocopherol is critical for its ability to protect against oxidative damage. Lastly, we determined that αT, but not γT, partially requires the synthesis of new proteins within a 24-h period and prior to exposure to tBHP for optimal cytoprotection. We conclude that, unlike γT and δT, αT appears to be unique in its requirement for transport and/or signaling for it to be an effective antioxidant. As a result, more focus should be paid to which vitamin E components are used for antioxidant interventions.
Language	English
Publishing date	2022-01-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2021.798938
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Article: Analysis of Glaucoma Associated Genes in Response to Inflammation, an Examination of a Public Data Set Derived from Peripheral Blood from Patients with Hepatitis C.

Player, Jacob K / Riordan, Sean M / Duncan, R Scott / Koulen, Peter

Clinical ophthalmology (Auckland, N.Z.)

2022 Volume 16, Page(s) 2093–2103

Abstract: Introduction: Glaucoma is the second leading cause of blindness worldwide and despite its prevalence, there are still many unanswered questions related to its pathogenesis. There is evidence that oxidative stress and inflammation play a major role in ... ...

Abstract	Introduction: Glaucoma is the second leading cause of blindness worldwide and despite its prevalence, there are still many unanswered questions related to its pathogenesis. There is evidence that oxidative stress and inflammation play a major role in disease progression. Glaucoma patients from several studies showed altered gene expression in leukocytes, revealing the possibility of using peripheral biomarkers to diagnose or stage glaucoma. The fact that glaucoma is associated with gene expression changes in tissues distant from the retina underscores the possible involvement of systemic oxidative stress and inflammation as potential contributing or compounding factors in glaucoma. Methods: We assembled a list of oxidative stress and inflammatory markers related to glaucoma based on a review of the literature. In addition, we utilized publicly available data sets of gene expression values collected from peripheral blood mononuclear cells and macrophages from two patient groups: those chronically infected by the hepatitis C virus and those who have cleared it. Activation of the innate immune response can render cells or tissues more responsive to a second delayed proinflammatory stimulus. Additional gene expression data from these cells after subsequent polyinosinic:polycytidylic acid treatment, used to elicit an acute inflammatory response, allowed for the investigation of the acute inflammatory response in these groups. We used fold-change comparison values between the two patient groups to identify genes of interest. Results: A comparison analysis identified 17 glaucoma biomarkers that were differentially expressed in response to HCV-mediated inflammation. Of these 17, six had significant p-values in the baseline vs treated values. Expression data of these genes were compared between patients who had cleared the Hepatitis C virus versus those who had not and identified three genes of interest for further study. Discussion: These results support our hypothesis that inflammation secondary to Hepatitis C virus infection affects the expression of glaucoma biomarker genes related to the antioxidant response and inflammation. In addition, they provide several potential targets for further research into understanding the relationship between innate responses to viral infection and inflammatory aspects of glaucoma and for potential use as a predictive biomarker or pharmacological intervention in glaucoma.
Language	English
Publishing date	2022-06-23
Publishing country	New Zealand
Document type	Journal Article
ISSN	1177-5467
ISSN	1177-5467
DOI	10.2147/OPTH.S364739
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Article: The Contribution of Anterior Segment Abnormalities to Changes in Intraocular Pressure in the DBA/2J Mouse Model of Glaucoma: DBA/2J-

Rohowetz, Landon J / Mardelli, Marc E / Duncan, R Scott / Riordan, Sean M / Koulen, Peter

Frontiers in neuroscience

2022 Volume 15, Page(s) 801184

Abstract: The contributions of anterior segment abnormalities to the development of ocular hypertension was determined in the DBA/2J mouse model of glaucoma. Intraocular pressure (IOP) was measured non-invasively. Iris pigment dispersion (IPD) and corneal ... ...

Abstract	The contributions of anterior segment abnormalities to the development of ocular hypertension was determined in the DBA/2J mouse model of glaucoma. Intraocular pressure (IOP) was measured non-invasively. Iris pigment dispersion (IPD) and corneal calcification were measured weekly starting at 20 weeks of age in DBA/2J and DBA/2J-
Language	English
Publishing date	2022-02-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2021.801184
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Article ; Online: slimr: An R package for tailor-made integrations of data in population genomic simulations over space and time.

Dinnage, Russell / Sarre, Stephen D / Duncan, Richard P / Dickman, Christopher R / Edwards, Scott V / Greenville, Aaron C / Wardle, Glenda M / Gruber, Bernd

Molecular ecology resources

2023 Volume 24, Issue 3, Page(s) e13916

Abstract: ... with simulations. However, the integration between standalone simulation software and R is currently not well ... developed. Here, we present slimr, an R package designed to create a seamless link between standalone ... software SLiM >3.0, one of the most powerful population genomic simulation frameworks, and the R ...

Abstract	Software for realistically simulating complex population genomic processes is revolutionizing our understanding of evolutionary processes, and providing novel opportunities for integrating empirical data with simulations. However, the integration between standalone simulation software and R is currently not well developed. Here, we present slimr, an R package designed to create a seamless link between standalone software SLiM >3.0, one of the most powerful population genomic simulation frameworks, and the R development environment, with its powerful data manipulation and analysis tools. We show how slimr facilitates smooth integration between genetic data, ecological data and simulation in a single environment. The package enables pipelines that begin with data reading, cleaning and manipulation, proceed to constructing empirically based parameters and initial conditions for simulations, then to running numerical simulations and finally to retrieving simulation results in a format suitable for comparisons with empirical data - aided by advanced analysis and visualization tools provided by R. We demonstrate the use of slimr with an example from our own work on the landscape population genomics of desert mammals, highlighting the advantage of having a single integrated tool for both data analysis and simulation. slimr makes the powerful simulation ability of SLiM directly accessible to R users, allowing integrated simulation projects that incorporate empirical data without the need to switch between software environments. This should provide more opportunities for evolutionary biologists and ecologists to use realistic simulations to better understand the interplay between ecological and evolutionary processes.
MeSH term(s)	Animals ; Metagenomics ; Software ; Computer Simulation ; Genomics/methods ; Biological Evolution ; Mammals
Language	English
Publishing date	2023-12-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2406833-0
ISSN	1755-0998 ; 1755-098X
ISSN (online)	1755-0998
ISSN	1755-098X
DOI	10.1111/1755-0998.13916
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Article: N

Duncan, R Scott / Riordan, Sean M / Hall, Conner W / Payne, Andrew J / Chapman, Kent D / Koulen, Peter

Frontiers in cellular neuroscience

2022 Volume 16, Page(s) 902278

Abstract: ... ...

Abstract	N
Language	English
Publishing date	2022-08-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2022.902278
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Article ; Online: Increasing Prevalence of Cerebral Palsy Among Two-Year-Old Children Born at <27 Weeks of Gestation: A Cohort Study.

DeMauro, Sara B / McDonald, Scott A / Heyne, Roy J / Vohr, Betty R / Duncan, Andrea F / Newman, Jamie E / Das, Abhik / Hintz, Susan R

The Journal of pediatrics

2024 Volume 268, Page(s) 113944

Abstract: Objective: To evaluate changes in prevalence and severity of cerebral palsy (CP) among surviving children born at <27 weeks of gestation over time and to determine associations between CP and other developmental domains, functional impairment, medical ... ...

Abstract	Objective: To evaluate changes in prevalence and severity of cerebral palsy (CP) among surviving children born at <27 weeks of gestation over time and to determine associations between CP and other developmental domains, functional impairment, medical morbidities, and resource use among 2-year-old children who were born extremely preterm. Study design: Retrospective cohort study using prospective registry data, conducted at 25 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Participants were children born at <27 weeks of gestation and followed at 18 through 26 months of corrected age from 2008 through 2019. Outcomes of interest were changes in prevalence of any CP and severity of CP over time and associations between CP and other neurodevelopmental outcomes, functional impairment, and medical comorbidities. Adjusted logistic, linear, multinomial logistic, and robust Poisson regression evaluated the relationships between child characteristics, CP severity, and outcomes. Results: Among 6927 surviving children with complete follow-up data, 3717 (53.7%) had normal neurologic examinations, 1303 (18.8%) had CP, and the remainder had abnormal neurologic examinations not classified as CP. Adjusted rates of any CP increased each year of the study period (aOR 1.11 per year, 95% CI 1.08-1.14). Cognitive development was significantly associated with severity of CP. Children with CP were more likely to have multiple medical comorbidities, neurosensory problems, and poor growth at follow-up. Conclusions: The rate of CP among surviving children who were born extremely preterm increased from 2008 through 2019. At 18 to 26 months of corrected age, neurodevelopmental and medical comorbidities are strongly associated with all severity levels of CP.
MeSH term(s)	Humans ; Cerebral Palsy/epidemiology ; Female ; Child, Preschool ; Prevalence ; Male ; Retrospective Studies ; Infant, Newborn ; Infant, Extremely Premature ; Gestational Age ; Severity of Illness Index ; United States/epidemiology ; Infant ; Cohort Studies ; Registries
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Multicenter Study
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2024.113944
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Article ; Online: The ATCC genome portal: 3,938 authenticated microbial reference genomes.

Nguyen, Scott V / Puthuveetil, Nikhita P / Petrone, Joseph R / Kirkland, Jade L / Gaffney, Kaitlyn / Tabron, Corina L / Wax, Noah / Duncan, James / King, Stephen / Marlow, Robert / Reese, Amy L / Yarmosh, David A / McConnell, Hannah H / Fernandes, Ana S / Bagnoli, John / Benton, Briana / Jacobs, Jonathan L

Microbiology resource announcements

2024 Volume 13, Issue 2, Page(s) e0104523

Abstract: The ATCC Genome Portal (AGP, https://genomes.atcc.org/) is a database of authenticated genomes for bacteria, fungi, protists, and viruses held in ATCC's biorepository. It now includes 3,938 assemblies (253% increase) produced under ISO 9000 by ATCC. Here, ...

Abstract	The ATCC Genome Portal (AGP, https://genomes.atcc.org/) is a database of authenticated genomes for bacteria, fungi, protists, and viruses held in ATCC's biorepository. It now includes 3,938 assemblies (253% increase) produced under ISO 9000 by ATCC. Here, we present new features and content added to the AGP for the research community.
Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article
ISSN	2576-098X
ISSN (online)	2576-098X
DOI	10.1128/mra.01045-23
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