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Article ; Online: A Murine Kitl Allele Regulates Skin Mast Cell Density across 58 Collaborative Mouse Cross Strains.

Walker, Graeme J / Galbraith, Jack A / Baz, Betoul / Ferguson, Blake / Handoko, Herlina Y / Khosrotehrani, Kiarash

The Journal of investigative dermatology

2022 Volume 142, Issue 8, Page(s) 2275–2280.e4

MeSH term(s)	Alleles ; Animals ; Cell Count ; Mast Cells ; Mice ; Skin
Language	English
Publishing date	2022-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2021.12.032
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Article ; Online: Evidence of the Storegga Tsunami 8200 BP? An Archaeological Review of Impact After a Large-Scale Marine Event in Mesolithic Northern Europe

Astrid J. Nyland / James Walker / Graeme Warren

Frontiers in Earth Science, Vol

2021 Volume 9

Abstract: Around 8,200 years ago, the Storegga tsunami hit the coasts of the Norwegian and North Seas. This event is well known from wide ranging geological and palaeobotanical work undertaken over the last 30 years. Outside of attempts at palaeodemographic models, ...

Abstract	Around 8,200 years ago, the Storegga tsunami hit the coasts of the Norwegian and North Seas. This event is well known from wide ranging geological and palaeobotanical work undertaken over the last 30 years. Outside of attempts at palaeodemographic models, however, exploration of the social impact of the wave on Mesolithic hunter-gatherer societies living on the coasts of west Norway, the north and east British Isles, and around the southern North Sea basin have been less common. It has been widely assumed that the tsunami was a disaster–but what constituted a disaster for the Mesolithic peoples who lived through this event? What can we learn about life after natural hazards by considering the archaeological material from regions with distinct Mesolithic histories? This paper presents a review of evidence of the Storegga tsunami at Mesolithic sites from western Norway, the Northeast UK, and elsewhere around the southern North Sea basin. We consider the ways in which the social impact of the Storegga tsunami has been studied up till now and suggest an alternative way forward.
Keywords	Storegga tsunami ; mesolithic ; Norway ; Scotland ; Doggerland ; disaster ; Science ; Q
Subject code	930
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: trans

Alzahrani, Seraj O / McRobbie, Graeme / Khan, Abid / D'huys, Thomas / Van Loy, Tom / Walker, Ashlie N / Renard, Isaline / Hubin, Timothy J / Schols, Dominique / Burke, Benjamin P / Archibald, Stephen J

Dalton transactions (Cambridge, England : 2003)

2024 Volume 53, Issue 12, Page(s) 5616–5623

Abstract: The chemokine receptor CXCR4 is implicated in multiple diseases including inflammatory disorders, cancer growth and metastasis, and HIV/AIDS. CXCR4 targeting has been evaluated in treating cancer metastasis and therapy resistance. Cyclam derivatives, ... ...

Abstract	The chemokine receptor CXCR4 is implicated in multiple diseases including inflammatory disorders, cancer growth and metastasis, and HIV/AIDS. CXCR4 targeting has been evaluated in treating cancer metastasis and therapy resistance. Cyclam derivatives, most notably AMD3100 (Plerixafor™), are a common motif in small molecule CXCR4 antagonists. However, AMD3100 has not been shown to be effective in cancer treatment as an individual agent. Configurational restriction and transition metal complex formation increases receptor binding affinity and residence time. In the present study, we have synthesized novel
MeSH term(s)	Benzylamines ; Coordination Complexes/pharmacology ; Cyclams ; Heterocyclic Compounds/pharmacology ; Heterocyclic Compounds/chemistry ; Receptors, CXCR4/antagonists & inhibitors
Chemical Substances	Benzylamines ; Coordination Complexes ; cyclam (295-37-4) ; Cyclams ; Heterocyclic Compounds ; plerixafor (S915P5499N) ; Receptors, CXCR4
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	1472887-4
ISSN	1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
ISSN (online)	1477-9234 ; 1364-5447
ISSN	0300-9246 ; 1477-9226
DOI	10.1039/d3dt01729j
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Article ; Online: Does fetal growth restriction induce neuropathology within the developing brainstem?

Ahmadzadeh, Elham / Polglase, Graeme R / Stojanovska, Vanesa / Herlenius, Eric / Walker, David W / Miller, Suzanne L / Allison, Beth J

The Journal of physiology

2023 Volume 601, Issue 21, Page(s) 4667–4689

Abstract: Fetal growth restriction (FGR) is a complex obstetric issue describing a fetus that does not reach its genetic growth potential. The primary cause of FGR is placental dysfunction resulting in chronic fetal hypoxaemia, which in turn causes altered ... ...

Abstract	Fetal growth restriction (FGR) is a complex obstetric issue describing a fetus that does not reach its genetic growth potential. The primary cause of FGR is placental dysfunction resulting in chronic fetal hypoxaemia, which in turn causes altered neurological, cardiovascular and respiratory development, some of which may be pathophysiological, particularly for neonatal life. The brainstem is the critical site of cardiovascular, respiratory and autonomic control, but there is little information describing how chronic hypoxaemia and the resulting FGR may affect brainstem neurodevelopment. This review provides an overview of the brainstem-specific consequences of acute and chronic hypoxia, and what is known in FGR. In addition, we discuss how brainstem structural alterations may impair functional control of the cardiovascular and respiratory systems. Finally, we highlight the clinical and translational findings of the potential roles of the brainstem in maintaining cardiorespiratory adaptation in the transition from fetal to neonatal life under normal conditions and in response to the pathological environment that arises during development in growth-restricted infants. This review emphasises the crucial role that the brainstem plays in mediating cardiovascular and respiratory responses during fetal and neonatal life. We assess whether chronic fetal hypoxaemia might alter structure and function of the brainstem, but this also serves to highlight knowledge gaps regarding FGR and brainstem development.
MeSH term(s)	Infant, Newborn ; Pregnancy ; Female ; Humans ; Fetal Growth Retardation ; Placenta ; Brain Stem ; Lung ; Hypoxia
Language	English
Publishing date	2023-08-17
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP284191
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Article ; Online: Structure of smectic-A liquid crystals in nonuniform domains: Modeling the impact of imperfect boundaries.

Al Sallo, Ayad S / Walker, Alan J / Boswell, Graeme P

Physical review. E

2020 Volume 101, Issue 3-1, Page(s) 32703

Abstract: This paper describes the construction of equilibrium configurations for smectic-A liquid crystals subjected to nonuniform physical boundary conditions, with two-dimensional dependence on the director and layer normal, and a nonlinear layer function. ... ...

Abstract	This paper describes the construction of equilibrium configurations for smectic-A liquid crystals subjected to nonuniform physical boundary conditions, with two-dimensional dependence on the director and layer normal, and a nonlinear layer function. Euler-Lagrange equations are constructed that describe key properties of liquid crystals confined between two boundaries exhibiting spatial imperfections. The results of the model are shown to be consistent with previous published findings in simple domains while results are obtained on how the structure of the liquid crystals changes in response to boundary perturbations. Domain sizes are considered representing those currently used in applications while predictions in smaller domains at the limit of current technologies are also made. In particular, it is shown that the curvature along a boundary impacts on the liquid crystal's structure distant from the boundary feature and therefore previously developed mathematical models, that essentially reduced the problem to a single spatial dimension, cannot be used in such circumstances. Consequences for practical applications are briefly discussed.
Language	English
Publishing date	2020-04-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.101.032703
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Article: Folic Acid Supplementation in Early Pregnancy, Homocysteine Concentration, and Risk of Gestational Diabetes Mellitus.

Guo, Yanfang / Luo, Rong / Corsi, Daniel J / White, Ruth Rennicks / Smith, Graeme / Rodger, Marc / Retnakaran, Ravi / Walker, Mark / Wen, Shi Wu

Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC

2022 Volume 44, Issue 2, Page(s) 196–199

Abstract: We used a prospective cohort of pregnant women at 12 to 20 weeks gestation between 2002 and 2008 in Ottawa and Kingston to evaluate the impact of early pregnancy folic acid supplementation on the risk of gestational diabetes mellitus. Among 7552 eligible ...

Abstract	We used a prospective cohort of pregnant women at 12 to 20 weeks gestation between 2002 and 2008 in Ottawa and Kingston to evaluate the impact of early pregnancy folic acid supplementation on the risk of gestational diabetes mellitus. Among 7552 eligible women, 84 (1.11%) were diagnosed of gestational diabetes mellitus. Non-significant associations were observed between gestational diabetes mellitus and folate supplementation, homocysteine levels, and methylenetetrahydrofolate reductase 677 TT genotype. Although we found no significant associations between folic acid supplementation and the risk of gestational diabetes mellitus, genetic associations were not confounded by lifestyle or socioeconomic factors, which may have biased previous studies.
MeSH term(s)	Diabetes, Gestational/epidemiology ; Dietary Supplements ; Female ; Folic Acid/therapeutic use ; Homocysteine ; Humans ; Pregnancy ; Prospective Studies
Chemical Substances	Homocysteine (0LVT1QZ0BA) ; Folic Acid (935E97BOY8)
Language	English
Publishing date	2022-02-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2171082-X
ISSN	1701-2163
ISSN	1701-2163
DOI	10.1016/j.jogc.2021.06.005
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Article ; Online: The influence of maternal and paternal education on birth outcomes: an analysis of the Ottawa and Kingston (OaK) birth cohort.

Swaminathan, Akshay / Lahaie Luna, Marianne / Rennicks White, Ruth / Smith, Graeme / Rodger, Marc / Wen, Shi Wu / Walker, Mark / Corsi, Daniel J

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians

2022 Volume 35, Issue 25, Page(s) 9631–9638

Abstract: Background: Education is considered one of the most robust determinants of health. However, it is unclear whether maternal education and paternal education have differential impacts on perinatal health outcomes. We assess maternal and paternal education ...

Abstract	Background: Education is considered one of the most robust determinants of health. However, it is unclear whether maternal education and paternal education have differential impacts on perinatal health outcomes. We assess maternal and paternal education differences and their association with adverse birth outcomes in a large birth cohort from Ontario, Canada. Methods: The OaK Birth Cohort recruited patients from Ontario, Canada, between October 2002 and April 2009. We recruited mothers were recruited between 12 and 20 weeks' gestation and collected both mother and infant data. The final sample size of the cohort was 8,085 participants. We use logistic regression to model the probability of preterm birth (less than 34 and 37 weeks' gestation), small-for-gestational-age (SGA), or stillbirth as a function of maternal and paternal educational attainment. We adjust for household-level income, maternal and paternal race and ethnicity, and compare the strength of the association between maternal and paternal education on outcomes using Wald tests. Results: 7,928 mother-father-offspring triads were available for the current analysis. 75% of mothers and fathers had college or university level education, and 8.7% of mothers experienced preterm delivery. Compared to mothers with college or university education, mothers with a high school education had an odds ratio of 1.37 (95% CI: 1.01-1.87) for SGA. Paternal education was not associated with infant outcomes. Comparing the odds ratios for maternal education and paternal education showed a stronger association than paternal education at the high school level for SGA birth (difference in odds ratio: 1.95, 95% CI: 1.13-3.36, Conclusion: Maternal education was associated with SGA, and this effect was more robust than paternal education, but both associations were weaker than previously reported.
MeSH term(s)	Pregnancy ; Infant ; Male ; Infant, Newborn ; Humans ; Female ; Adult ; Premature Birth/epidemiology ; Quercus ; Pregnancy Outcome/epidemiology ; Birth Cohort ; Fathers ; Fetal Growth Retardation
Language	English
Publishing date	2022-03-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2077261-0
ISSN	1476-4954 ; 1057-0802 ; 1476-7058
ISSN (online)	1476-4954
ISSN	1057-0802 ; 1476-7058
DOI	10.1080/14767058.2022.2049751
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Article ; Online: The medullary serotonergic centres involved in cardiorespiratory control are disrupted by fetal growth restriction.

Ahmadzadeh, Elham / Dudink, Ingrid / Walker, David W / Sutherland, Amy E / Pham, Yen / Stojanovska, Vanesa / Polglase, Graeme R / Miller, Suzanne L / Allison, Beth J

The Journal of physiology

2023

Abstract: Fetal growth restriction (FGR) is associated with cardiovascular and respiratory complications after birth and beyond. Despite research showing a range of neurological changes following FGR, little is known about how FGR affects the brainstem ... ...

Abstract	Fetal growth restriction (FGR) is associated with cardiovascular and respiratory complications after birth and beyond. Despite research showing a range of neurological changes following FGR, little is known about how FGR affects the brainstem cardiorespiratory control centres. The primary neurons that release serotonin reside in the brainstem cardiorespiratory control centres and may be affected by FGR. At two time points in the last trimester of sheep brain development, 110 and 127 days of gestation (0.74 and 0.86 of gestation), we assessed histopathological alterations in the brainstem cardiorespiratory control centres of the pons and medulla in early-onset FGR versus control fetal sheep. The FGR cohort were hypoxaemic and asymmetrically growth restricted. Compared to the controls, the brainstem of FGR fetuses exhibited signs of neuropathology, including elevated cell death and reduced cell proliferation, grey and white matter deficits, and evidence of oxidative stress and neuroinflammation. FGR brainstem pathology was predominantly observed in the medullary raphé nuclei, hypoglossal nucleus, nucleus ambiguous, solitary tract and nucleus of the solitary tract. The FGR groups showed imbalanced brainstem serotonin and serotonin 1A receptor abundance in the medullary raphé nuclei, despite evidence of increased serotonin staining within vascular regions of placentomes collected from FGR fetuses. Our findings demonstrate both early and adaptive brainstem neuropathology in response to placental insufficiency. KEY POINTS: Early-onset fetal growth restriction (FGR) was induced in fetal sheep, resulting in chronic fetal hypoxaemia. Growth-restricted fetuses exhibit persistent neuropathology in brainstem nuclei, characterised by disrupted cell proliferation and reduced neuronal cell number within critical centres responsible for the regulation of cardiovascular and respiratory functions. Elevated brainstem inflammation and oxidative stress suggest potential mechanisms contributing to the observed neuropathological changes. Both placental and brainstem levels of 5-HT were found to be impaired following FGR.
Language	English
Publishing date	2023-08-28
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP284971
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Article ; Online: NMR Molecular Replacement Provides New Insights into Binding Modes to Bromodomains of BRD4 and TRIM24.

Torres, Felix / Walser, Reto / Kaderli, Janina / Rossi, Emanuele / Bobby, Romel / Packer, Martin J / Sarda, Sunil / Walker, Graeme / Hitchin, James R / Milbradt, Alexander G / Orts, Julien

Journal of medicinal chemistry

2022 Volume 65, Issue 7, Page(s) 5565–5574

Abstract: Structure-based drug discovery (SBDD) largely relies on structural information from X-ray crystallography because traditional NMR structure calculation methods are too time consuming to be aligned with typical drug discovery timelines. The recently ... ...

Abstract	Structure-based drug discovery (SBDD) largely relies on structural information from X-ray crystallography because traditional NMR structure calculation methods are too time consuming to be aligned with typical drug discovery timelines. The recently developed NMR molecular replacement (
MeSH term(s)	Crystallography, X-Ray ; Magnetic Resonance Spectroscopy ; Nuclear Proteins/metabolism ; Protein Binding ; Protein Domains ; Transcription Factors/metabolism
Chemical Substances	Nuclear Proteins ; Transcription Factors
Language	English
Publishing date	2022-03-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218133-2
ISSN	1520-4804 ; 0022-2623
ISSN (online)	1520-4804
ISSN	0022-2623
DOI	10.1021/acs.jmedchem.1c01703
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Article: Augmented Intelligence for Clinical Discovery in Hypertensive Disorders of Pregnancy Using Outlier Analysis.

Janoudi, Ghayath / Fell, Deshayne B / Ray, Joel G / Foster, Angel M / Giffen, Randy / Clifford, Tammy J / Rodger, Marc A / Smith, Graeme N / Walker, Mark C

Cureus

2023 Volume 15, Issue 3, Page(s) e36909

Abstract: Objectives Clinical discoveries are heralded by observing unique and unusual clinical cases. The effort of identifying such cases rests on the shoulders of busy clinicians. We assess the feasibility and applicability of an augmented intelligence ... ...

Abstract	Objectives Clinical discoveries are heralded by observing unique and unusual clinical cases. The effort of identifying such cases rests on the shoulders of busy clinicians. We assess the feasibility and applicability of an augmented intelligence framework to accelerate the rate of clinical discovery in preeclampsia and hypertensive disorders of pregnancy-an area that has seen little change in its clinical management. Methods We conducted a retrospective exploratory outlier analysis of participants enrolled in the folic acid clinical trial (FACT, N=2,301) and the Ottawa and Kingston birth cohort (OaK, N=8,085). We applied two outlier analysis methods: extreme misclassification contextual outlier and isolation forest point outlier. The extreme misclassification contextual outlier is based on a random forest predictive model for the outcome of preeclampsia in FACT and hypertensive disorder of pregnancy in OaK. We defined outliers in the extreme misclassification approach as mislabelled observations with a confidence level of more than 90%. Within the isolation forest approach, we defined outliers as observations with an average path length z score less or equal to -3, or more or equal to 3. Content experts reviewed the identified outliers and determined if they represented a potential novelty that could conceivably lead to a clinical discovery. Results In the FACT study, we identified 19 outliers using the isolation forest algorithm and 13 outliers using the random forest extreme misclassification approach. We determined that three (15.8%) and 10 (76.9%) were potential novelties, respectively. Out of 8,085 participants in the OaK study, we identified 172 outliers using the isolation forest algorithm and 98 outliers using the random forest extreme misclassification approach; four (2.3%) and 32 (32.7%), respectively, were potential novelties. Overall, the outlier analysis part of the augmented intelligence framework identified a total of 302 outliers. These were subsequently reviewed by content experts, representing the human part of the augmented intelligence framework. The clinical review determined that 49 of the 302 outliers represented potential novelties. Conclusions Augmented intelligence using extreme misclassification outlier analysis is a feasible and applicable approach for accelerating the rate of clinical discoveries. The use of an extreme misclassification contextual outlier analysis approach has resulted in a higher proportion of potential novelties than using the more traditional point outlier isolation forest approach. This finding was consistent in both the clinical trial and real-world cohort study data. Using augmented intelligence through outlier analysis has the potential to speed up the process of identifying potential clinical discoveries. This approach can be replicated across clinical disciplines and could exist within electronic medical records systems to automatically identify outliers within clinical notes to clinical experts.
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.36909
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