Personalized Genome-Scale Modeling Reveals Metabolic Perturbations in Fibroblasts of Methylmalonic Aciduria Patients.

Cobalamin (vitamin B12) is an essential cofactor for two human enzymes, methionine synthase and methylmalonyl-CoA mutase. Inborn errors of cobalamin metabolism (IECMs) are inherited genetic defects resulting in improper transport, modification, or utilization of cobalamin and include inherited methylmalonic acidurias, a group of IECMs most frequently caused by a defect in the methylmalonyl-CoA mutase enzyme. Here, we performed genome-scale modeling of IECMs to gain insight into their metabolic perturbations.

Generation of iPSC Lines with Tagged α-Synuclein for Visualization of Endogenous Protein in Human Cellular Models of Neurodegenerative Disorders.

α-Synuclein is a synaptic protein that accumulates primarily in synucleinopathies and secondarily in certain lysosomal storage disorders. However, its physiological roles in health and disease are not fully understood. In part, this has been hampered by the inability to visualize α-synuclein and its cellular localization, due to the lack of specific antibodies and faithful reporters.

A Multi-Omics Framework for Decoding Disease Mechanisms: Insights From Methylmalonic Aciduria.

The diverse perspectives offered by multi-omics data analysis can aid in identifying the most relevant molecular pathways involved in disease processes, and findings in one layer can substantiate findings in other layers of information. Integrating data from multiple omics sources is becoming increasingly important to improve disease diagnosis and treatment, especially for conditions with complex and poorly understood underlying pathomechanisms. Methylmalonic aciduria (MMA), an inherited metabolic disorder, serves as an illustrative example of such a disease with poorly understood pathogenesis for which published multi-omics data are readily available.

Sustainability insights from Late Pleistocene climate change and horse migration patterns.

Climate affects habitat, food availability, and the movement and sustainability of all life. In this work, we apply Indigenous and Western scientific methods, including genomics and isotope profiling, on fossils from across Beringia to explore the effect of climate change on horses. We find that Late Pleistocene horses from Alaska and northern Yukon are related to populations from Eurasia and crossed the Bering land bridge multiple times during the last glacial interval.

Mitochondrial dysfunction drives a neuronal exhaustion phenotype in methylmalonic aciduria.

Methylmalonic aciduria (MMA) is an inborn error of metabolism resulting in loss of function of the enzyme methylmalonyl-CoA mutase (MMUT). Despite acute and persistent neurological symptoms, the pathogenesis of MMA in the central nervous system is poorly understood, which has contributed to a dearth of effective brain specific treatments. Here we utilised patient-derived induced pluripotent stem cells and in vitro differentiation to generate a human neuronal model of MMA.