Williams, A. M. — Page 2 | bioRxiv Science

bioRxiv2020

Cardio-centric hemodynamic management improves spinal cord oxygenation and mitigates hemorrhage in acute spinal cord injury

Chronic high-thoracic and cervical spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, including impaired left-ventricular contractility. Here, we sought to determine whether such dysfunction manifests immediately post-injury, and if so, whether correcting impaired contractility can improve spinal cord oxygenation (SCO2), blood flow (SCBF) and metabolism. Using a porcine model of SCI, we demonstrate that high-thoracic SCI acutely impairs cardiac contractility and causes substantial reductions in intraparenchymal SCO2 and SCBF within the first hours post-injury. Utilizing the same model, we next show that treating the reduced contractile function with the {beta}-agonist dobutamine is more efficacious at increasing SCO2 and SCBF than the current clinical standard of vasopressor therapy, whilst also mitigating increased anaerobic metabolism and hemorrhage in the injured cord. Our data provide compelling evidence that cardio-centric hemodynamic management represents a novel and advantageous alternative to the current clinical standard of vasopressor therapy for acute traumatic SCI.

neuroscience↗

bioRxiv2018

Extreme variation in rates of evolution in the plastid Clp protease complex

Eukaryotic cells represent an intricate collaboration between multiple genomes, even down to the level of multisubunit complexes in mitochondria and plastids. One such complex in plants is the caseinolytic protease (Clp), which plays an essential role in plastid protein turnover. The proteolytic core of Clp comprises subunits from one plastid-encoded gene (clpP1) and multiple nuclear genes. The clpP1 gene is highly conserved across most green plants, but it is by far the fastest evolving plastid-encoded gene in some angiosperms. To better understand these extreme and mysterious patterns of divergence, we investigated the history of clpP1 molecular evolution across green plants by extracting sequences from 988 published plastid genomes. We find that clpP1 has undergone remarkably frequent bouts of accelerated sequence evolution and architectural changes (e.g., loss of introns and RNA-editing sites) within seed plants. Although clpP1 is often assumed to be a pseudogene in such cases, multiple lines of evidence suggest that this is rarely the case. We applied comparative native gel electrophoresis of chloroplast protein complexes followed by protein mass spectrometry in two species within the angiosperm genus Silene, which has highly elevated and heterogeneous rates of clpP1 evolution. We confirmed that clpP1 is expressed as a stable protein and forms oligomeric complexes with the nuclear-encoded Clp subunits, even in one of the most divergent Silene species. Additionally, there is a tight correlation between amino-acid substitution rates in clpP1 and the nuclear-encoded Clp subunits across a broad sampling of angiosperms, suggesting ongoing selection on interactions within this complex.

evolutionary biology↗