MTO1 mediates tissue-specificity of OXPHOS defects via tRNA modification and translation optimization, which can be bypassed by dietary intervention.

Mitochondrial diseases often exhibit tissue-specific pathologies, but this phenomenon is poorly understood. Here we present regulation of mitochondrial translation by the Mitochondrial Translation Optimization Factor 1, MTO1, as a novel player in this scenario. We demonstrate that MTO1 mediates tRNA modification and controls mitochondrial translation rate in a highly tissue specific manner associated with tissue-specific OXPHOS defects. Activation of mitochondrial proteases, aberrant translation products, as well as defects in OXPHOS complex assembly observed in MTO1 KO mice further imply that MTO1 impacts translation fidelity. In our mouse model, MTO1-related OXPHOS deficiency can be bypassed by feeding a ketogenic diet. This therapeutic intervention is independent of the MTO1-mediated tRNA modification and involves balancing of mitochondrial and cellular secondary stress responses. Our results thereby establish mammalian MTO1 as a novel factor in the tissue-specific regulation of OXPHOS and fine-tuning of mitochondrial translation accuracy

A review of Australia’s Mesozoic fishes

© 2020 Geological Society of Australia Inc., Australasian Palaeontologists. The Australian Mesozoic fish fauna is considered to be depauperate in comparison with fish faunas in the Northern Hemisphere. However, due to its geographical location as a potential radiation center in the Southern Hemisphere, Australia’s Mesozoic fish fauna is important for understanding fish radiations. Most of the modern fish groups originated during the Mesozoic, but the first records of a modern fish fauna (freshwater and marine) in Australia does not occur until the lower Paleogene. Here, we review all known fossil fish-bearing localities from the Mesozoic of Australia, to improve the understanding of the record. The apparent low Australian Mesozoic fish diversity is likely due to its understudied status of the constituent fossils rather than to a depauperate record. In addition, we review recent work with the aim of placing the Australian Mesozoic fish fauna in a global context. We review the taxonomy of Australian fossil fishes and conclude that the assignments of many actinopterygians need major revision within a modern phylogenetic context. The vast majority of chondrichthyans are yet to be formally described; to the contrary all of the known lungfish specimens have been described. This study considers the microscopic and fragmented remains of Mesozoic fish already found in Australia, allowing a more complete view of the diversity of the fishes that once inhabited this continent

The XENON1T data acquisition system

The XENON1T liquid xenon time projection chamber is the most sensitive detector built to date for the measurement of direct interactions of weakly interacting massive particles with normal matter. The data acquisition system (DAQ) is constructed from commercial, open source, and custom components to digitize signals from the detector and store them for later analysis. The system achieves an extremely low signal threshold by triggering each channel independently, achieving a single photoelectron acceptance of (93 \ub1 3)%, and deferring the global trigger to a later, software stage. The event identification is based on MongoDB database queries and has over 98% efficiency at recognizing interactions at the analysis threshold in the center of the target. A readout bandwidth over 300 MB/s is reached in calibration modes and is further expandable via parallelization. This DAQ system was successfully used during three years of operation of XENON1T

A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.Diabetes mellitus: pathophysiological changes and therap