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Biology subjects

Shepherd, E.

Publications and source records attributed to Shepherd, E..

2 recordsLinked to original sources

Phenotypic variation in divergent mitochondrial haplotypes in migratory three-spined stickleback

Mitochondria are essential components in life-sustaining organismal processes. The mitochondrial genome can be influenced by selection, and divergent mitochondrial haplotypes have substantial potential to affect interspecies variation in life-history and physiology, yet little is known about whole organism phenotypic changes that might accompany mitochondrial genomic divergence. Three-spined stickleback on the Scottish island of North Uist provide a model to study this as their populations exhibit a well-mixed nuclear genome, yet two highly diverged mitochondrial haplotypes ( trans-Atlantic and European). Three-spined stickleback were sampled from six lochs to investigate associations between mitochondrial haplotype and phenotypic traits including organ size, body size, and ovule volume/clutch size, as well as citrate synthase enzyme activity. Results showed that mitochondrial haplotype has an influence on male gonadosomatic index (GSI) and potentially citrate synthase (CS) enzyme activity. Differences in male GSI may be explained by the timing of male spermatogenesis or potentially a need for larger testes in European haplotype fish. While no other phenotypic trait showed differences between mitochondrial haplotypes, there were many differences between sexes and populations e.g. in body size and organ/muscle size.

ecology↗

Evaluation of Gremlin-1 as a therapeutic target in metabolic dysfunction-associated steatohepatitis

Gremlin-1 has been implicated in liver fibrosis in metabolic dysfunction-associated steatohepatitis (MASH) via inhibition of bone-morphogenetic protein (BMP) signalling and has thereby been identified as a potential therapeutic target. Using rat in vivo and human in vitro and ex vivo model systems of MASH fibrosis, we show that neutralisation of Gremlin-1 activity with monoclonal therapeutic antibodies does not reduce liver inflammation or liver fibrosis. Still, Gremlin-1 was upregulated in human and rat MASH fibrosis, but expression was restricted to a small subpopulation of COL3A1/THY1+ myofibroblasts. Lentiviral overexpression of Gremlin-1 in LX-2 cells and primary hepatic stellate cells led to changes in BMP-related gene expression, which did not translate to increased fibrogenesis. Furthermore, we show that Gremlin-1 binds to heparin with high affinity, which prevents Gremlin-1 from entering systemic circulation, prohibiting Gremlin-1-mediated organ crosstalk. Overall, our findings suggest a redundant role for Gremlin-1 in the pathogenesis of liver fibrosis, which is unamenable to therapeutic targeting.

pathology↗