Prosection-based human anatomy teaching during the COVID-19 pandemic

Peer reviewe

Renal pathology in a mouse model of severe Spinal Muscular Atrophy is associated with downregulation of Glial Cell-Line Derived Neurotrophic Factor (GDNF)

Acknowledgements: We would like to acknowledge the Microscopy and Histology Core Facility members; Kevin Mackenzie, Debbie Wilkinson, Gillian Milne and Lucy Wight at the University of Aberdeen, and Margaret Mullin at the Glasgow Imaging Facility, University of Glasgow, for their support, assistance and use of the facilities. Funding: SMA Europe and an Anatomical Society PhD Studentship to S.H.P. and H.A.; the Deutsche Muskelstiftung (E-2019-01 to P.C.)Peer reviewedPostprin

Lamin A/C dysregulation contributes to cardiac pathology in a mouse model of severe spinal muscular atrophy

Cardiac pathology is emerging as a prominent systemic feature of spinal muscular atrophy (SMA), but little is known about the underlying molecular pathways. Using quantitative proteomics analysis, we demonstrate widespread molecular defects in heart tissue from the Taiwanese mouse model of severe SMA. We identify increased levels of lamin A/C as a robust molecular phenotype in the heart of SMA mice and show that lamin A/C dysregulation is also apparent in SMA patient fibroblast cells and other tissues from SMA mice. Lamin A/C expression was regulated in vitro by knockdown of the E1 ubiquitination factor ubiquitin-like modifier activating enzyme 1, a key downstream mediator of SMN-dependent disease pathways, converging on β-catenin signaling. Increased levels of lamin A are known to increase the rigidity of nuclei, inevitably disrupting contractile activity in cardiomyocytes. The increased lamin A/C levels in the hearts of SMA mice therefore provide a likely mechanism explaining morphological and functional cardiac defects, leading to blood pooling. Therapeutic strategies directed at lamin A/C may therefore offer a new approach to target cardiac pathology in SMA

Anatomical variation of the aorta in the west of Scotland – a population with high cardiovascular disease burden. Implications for stent design and deployment

The prevalence and complexity of cardiovascular disease (CVD) in the West of Scotland are high with the aortic arch and abdominal aorta, particularly at increased risk of cardiovascular pathology. Stent deployment can be key in preventing further cardiovascular events, however, current stent design does not account for complex advanced CVD in these areas. This cadaveric study aimed to provide anatomical measurements requested by manufacturers to improve stent design and deployment in this target population. Nine cadavers (six females and three males; age range = 82.7 ± 10.4 years) from the West of Scotland were dissected to expose the aortic arch and abdominal aorta. Digital callipers and protractors were used to collect data on vessel diameters (including taper), branch spacing, angles and presence of collaterals. CVD was present in all cadavers and ranged from mild plaque presence to aortic dissections. One possessed a bovine aortic arch variation. Supra-aortic vessels were approximately equally spaced, but the left common carotid had the most acute branching angle. Angulation of the arch from the coronal plane positively correlated with a deviation of the left subclavian artery (LSA) from the sternal midline (Spearman's coefficient r = 0.82, p = 0.01) which may impact surgical access. The origin of the vertebral artery on the LSA was also highly variable. The diameter of the descending aorta decreased along its length from the aortic hiatus to superior mesenteric by 21 ± 10% indicating a high degree of taper. The artery of Adamkiewicz was present in 33% and additional renal collaterals were present in 22%. 66% had tortuous vessels in the abdominal region. These results highlight the need for more data to aid the refinement of stent-graft design and deployment methods to ensure successful surgical intervention in this population

Lamin A/C dysregulation contributes to cardiac pathology in a mouse model of severe spinal muscular atrophy"

Cardiac pathology is emerging as a prominent systemic feature of spinal muscular atrophy (SMA), but little is known about the underlying molecular pathways. Using quantitative proteomics analysis, we demonstrate widespread molecular defects in heart tissue from the Taiwanese mouse model of severe SMA. We identify increased levels of lamin A/C as a robust molecular phenotype in the heart of SMA mice, and show that lamin A/C dysregulation is also apparent in SMA patient fibroblast cells and other tissues from SMA mice. Lamin A/C expression was regulated in-vitro by knockdown of the E1 ubiquitination factor UBA1, a key downstream mediator of SMN-dependent disease pathways, converging on β-catenin signalling. Increased levels of lamin A are known to increase the rigidity of nuclei, inevitably disrupting contractile activity in cardiomyocytes. The increased lamin A/C levels in the hearts of SMA mice therefore provide a likely mechanism explaining morphological and functional cardiac defects, leading to blood pooling. Therapeutic strategies directed at lamin A/C may therefore offer a new approach to target cardiac pathology in SMA