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ERA is a digital repository of original research produced at The University of Edinburgh. The archive contains documents written by, or affiliated with, academic authors, or units, based at Edinburgh that have sufficient quality to be collected and preserved by the Library, but which are not controlled by commercial publishers. Holdings include full-text digital doctoral theses, masters dissertations, project reports, briefing papers and out-of-print materials.

Information on current research activity including staff, projects and publications is available via the Edinburgh Research Explorer.

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Postnatal development of the somatosensory cortex in a rat model of Fragile X Syndrome
(2026-05-05) Sumera, Anna; Booker, Sam; Kind, Peter; Sibley, Chris; Abbott, Cathy
Fragile X Syndrome (FXS) is a common single-gene cause of autism and intellectual disability. Prevalent symptoms such as seizures and sensory hypersensitivity arise from cortical dysfunction, which could be underpinned by cortical hyperexcitability. Despite extensive research, currently there are no effective therapies targeting the underlying mechanisms, which could be due to species differences and limited understanding of how cortical dysfunction arises during development. In this thesis, I examined the first 4 weeks of postnatal development of the somatosensory cortex (S1) in a rat model of FXS, by characterizing the electrophysiological properties and morphology of S1 neurons, combined with an investigation of interneuron density. Using whole-cell patch clamp recordings from layer 4 of S1, I found that Fmr1-/y stellate cells (SCs) are hyperexcitable during early development, in agreement with previous research. Thanks to the high temporal resolution of these recordings, I have identified multiple phases of development in Fmr1-/y SCs, with distinct periods of intrinsic hyperexcitability flanked by typical excitability, which were not previously described. The different phases could arise due to different mechanisms, as SCs have a reduced dendritic complexity during the second postnatal week that is normalized before hyperexcitability arises for the second time. Changes in excitability are accompanied by an increase in the density of somatostatin-expressing interneurons. Early pharmacological treatment with BPN14770 was able to normalize the action potential output and morphology of the SCs during the second postnatal week, but did not provide a long-term rescue of excitability. Additionally, I have identified cell type-specific transcriptomic differences in the developing somatosensory cortex of Fmr1-/y rats, which support the physiological changes. Together, these data suggest that the developmental trajectory taken by the Fmr1-/y cortex is significantly altered, but partially amenable to therapeutic intervention albeit without long-term effects.
Reactivation of developmental genes to promote neovascularisation and cardiac regeneration after myocardial infarction
(2026-05-05) Tang, Michelle Nga Huen; Brittan, Mairi; Baker, Andrew; Medical Research Scotland; N2 pharmaceuticals
Myocardial infarction (MI) remains a leading cause of heart failure (HF), compounded by the limited regenerative capacity of the adult heart. Despite advances in MI treatments, HF remains common, highlighting the urgent need for novel strategies to prevent HF progression and promote cardiac regeneration. Effective cardiac repair requires rapid reconstruction of a functional vascular network, yet the mechanisms driving neovascularisation remain poorly understood. Increasing evidence suggests that genes deployed during embryonic development can be reactivated in the adult heart to support regeneration pathways. Owing to its exceptional regenerative ability, the zebrafish represents a powerful model to investigate myocardial-vascular regeneration pathways. I hypothesised that reactivation of foetal genes in adult coronary endothelial cells (ECs) promotes neovascularisation and cardiac repair post- MI. Multimodal omics analyses identified Annexin A2 (ANXA2) and Poly(A) binding protein cytoplasmic 1 (PABPC1) as endothelial genes expressed during development and reactivated in the adult coronary vasculature post-MI. Protein level upregulation of both targets was confirmed in cardiac ECs from MI patients versus healthy controls (n = 7; %ANXA2⁺CD31⁺ ECs = 77.1± 12.1 versus. 56.9 ± 9.2, P = 0.002; %PABPC1⁺CD31⁺ ECs = 68.0 ± 15.6 versus. 37.9 ± 18.6, P = 0.013). The ANXA2 fibrinolytic co-regulator, Serpin Family E Member 1 (SERPINE1), was also significantly increased in MI (%SERPINE1⁺CD31⁺ ECs = 32.7 ± 11.7 versus. 16.1 ± 7.3, P = 0.001). These findings suggest that a balanced interplay between ANXA2 and SERPINE1 may influence coronary neovasculogenic responses post-MI, in addition to their known roles in fibrinolysis. ANXA2 was prioritised as a lead candidate for functional analysis. CRISPR/Cas9- mediated knockdown of orthologues anxa2a/b was generated in Tg(fli1:eGFP)y1tg / Tg(myl7:DsRed2-NLS)f2) zebrafish to investigate the role of ANXA2 in cardiovascular development and regeneration. At 3 days post-fertilisation (dpf), crispants (CRISPR- Cas9 engineered animals) exhibited developmental abnormalities, including smaller eyes (n = 45 – 80; eye diameter in mm = 0.68 ± 0.16 versus. 0.91 ± 0.07, P < 0.0001), shorter body length (body length in mm = 9.75 ± 0.99 versus. 10.82 ± 0.41, P < 0.0001), and disrupted intersegmental vessels (n = 25-48; number of complete intersegmental vessels = 23.31 ± 3.05 versus. 27.83 ± 1.36, P < 0.0001). By 5 dpf, 45.3% of crispants displayed mild phenotypes, and 45.0% showed moderate or severe developmental defects, such as curled tails, pericardial oedema, failure to hatch, and full body malformations. I developed and optimised a cardiac laser injury and regeneration model in <5 dpf larvae. Laser injury significantly reduced heart rate, EC number, and ventricular volume at 2 hours post-injury (hpi) (n = 20-38; heart rate in bpm = 142.63 ± 67.44 versus. 200.74 ± 66.15, P = 0.0012; GFP+ EC counts = 62.00 ± 28.27 versus. 107.09 ± 29.46, P=0.0018; diastolic endocardial volume of ventricle (µm3) = 3.02e6 ± 2.37e6 versus. 7.29e6 ± 5.22e6, P = 0.0014), all of which had shown complete recovery by 48 hpi in wild type (WT) siblings. Compared with injured WT siblings, mild anxa2ab crispants showed partial regeneration at 48 hpi, characterised by reduced EC repopulation (n = 24; GFP+ EC counts = 61.70 ± 21.25 vs 89.00 ± 20.11, P < 0.0001), diminished cardiomyocytes numbers (mCherry+ cardiomyocyte counts = 56.61 ± 17.03 vs 83.25 ± 14.06, P < 0.0001), and smaller ventricular volume (diastolic endocardial volume of ventricle (µm3) = 6.19e6 ± 2.00e6 vs 1.03e7 ± 2.62e6; P < 0.0001). Moderate anxa2ab crispants exhibited severely impaired regeneration, with persistently low EC and cardiomyocyte counts, reduced ventricular volume, and distorted ventricular morphology (n = 21; GFP+ EC counts = 34.71 ± 19.21 vs 76.79 ± 13.01; mCherry+ cardiomyocyte count = 25.29 ± 17.01 vs 72.47 ± 13.34; diastolic endocardial volume of ventricle (µm3) = 4.14e6 ± 2.49e6 vs 8.88e6 ± 2.00e6; P < 0.0001). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) at 48 hpi revealed transcriptional alterations in targets associated with ANXA2 function in crispants, including S100 calcium binding protein A10ab (s100a10ab), vascular endothelial growth factor Ab (vegfab), C-X-C motif chemokine ligand 12b (cxcl12b), Notch receptor 1a/3 (notch1a/3), and pabpc1ab, but not serpine1. This suggests ANXA2 may act upstream of a network of endothelial and regenerative signalling genes, and that its loss compromises repair responses. Overall, this study identifies PABPC1 and ANXA2 as developmental genes reactivated upon cardiac injury, with ANXA2 deficiency leading to impaired cardiac regeneration. The phenotypic defects observed in anxa2ab knockdown zebrafish highlight the essential role of ANXA2 in embryonic development, neovascularisation, and cardiac repair. ANXA2 and SERPINE1 act antagonistically to regulate plasmin generation and fibrin turnover; an imbalance between ANXA2 and SERPINE1 may contribute to the impaired neovascularisation, pathological cardiac remodelling and fibrosis that drives the progression of heart failure. Therefore, elucidating ANXA2/SERPINE1-mediated pathways may provide strategies to enhance neovascularisation and heart regeneration. Future work should focus on understanding the mechanisms by which ANXA2, PABPC1 or other related genes regulate endothelial responses to injury, to inform the development of novel regenerative therapies for cardiovascular disease and the prevention of heart failure, for which there is currently no cure.
Peace Agreements in 2025: Insights from the PA-X Peace Agreements Database
(PeaceRep: The Peace and Conflict Resolution Evidence Platform, 2026) Badanjak, Sanja; Beaujouan; Epple; Farquhar; Henry; Wilson, Robert; Wise, Laura
Mediation in 2025: Mediation across overlapping conflict systems
(PeaceRep: The Peace and Conflict Resolution Evidence Platform, 2026) Peter, Mateja; Badanjak, Sanja; D’Amico, Elisa; Houghton, Kasia
Mediation in 2025 reached an inflection point, with interstate mediation increasingly embedded within internationalised intrastate conflicts rather than operating as a standalone diplomatic tool. Such mediation activity increasingly reflected not discrete wars, but overlapping conflict systems characterised by escalation of risks, regional spillover, and multi-actor entanglement.
A low-carbon hydrogen deployment model for Scotland
(Ramboll, 2026-05-05) Mouelhi, Ben; Nieto, Carlos Martin; Lüth, Alexandra; Raheli, Enrica; Bush , Ruth
The report describes the development of a hydrogen deployment model for Scotland and its use in testing potential deployment scenarios. The model provides a quantitative, user friendly tool for translating a variety of assumptions in to hydrogen demand projections and infrastructure requirements. The report describes the model’s use to test two scenarios, broadly aligned with International Energy Agency projections. The model proved to be most sensitive to two particular parameters: electricity prices and the availability of export infrastructure, highlighting these as priorities for policy and investment.