Subcomplex Iλ Specifically Controls Integrated Mitochondrial Functions in Caenorhabditis elegans

Complex I dysfunction is a common, heterogeneous cause of human mitochondrial disease having poorly understood pathogenesis. The extensive conservation of complex I composition between humans and Caenorhabditis elegans permits analysis of individual subunit contribution to mitochondrial functions at both the whole animal and mitochondrial levels. We provide the first experimentally-verified compilation of complex I composition in C. elegans, demonstrating 84% conservation with human complex I. Individual subunit contribution to mitochondrial respiratory capacity, holocomplex I assembly, and animal anesthetic behavior was studied in C. elegans by RNA interference-generated knockdown of nuclear genes encoding 28 complex I structural subunits and 2 assembly factors. Not all complex I subunits directly impact respiratory capacity. Subcomplex Iλ subunits along the electron transfer pathway specifically control whole animal anesthetic sensitivity and complex II upregulation, proportionate to their relative impairment of complex I-dependent oxidative capacity. Translational analysis of complex I dysfunction facilitates mechanistic understanding of individual gene contribution to mitochondrial disease. We demonstrate that functional consequences of complex I deficiency vary with the particular subunit that is defective

Gene Expression in a Drosophila Model of Mitochondrial Disease

Background A point mutation in the Drosophila gene technical knockout (tko), encoding mitoribosomal protein S12, was previously shown to cause a phenotype of respiratory chain deficiency, developmental delay, and neurological abnormalities similar to those presented in many human mitochondrial disorders, as well as defective courtship behavior. Methodology/Principal Findings Here, we describe a transcriptome-wide analysis of gene expression in tko25t mutant flies that revealed systematic and compensatory changes in the expression of genes connected with metabolism, including up-regulation of lactate dehydrogenase and of many genes involved in the catabolism of fats and proteins, and various anaplerotic pathways. Gut-specific enzymes involved in the primary mobilization of dietary fats and proteins, as well as a number of transport functions, were also strongly up-regulated, consistent with the idea that oxidative phosphorylation OXPHOS dysfunction is perceived physiologically as a starvation for particular biomolecules. In addition, many stress-response genes were induced. Other changes may reflect a signature of developmental delay, notably a down-regulation of genes connected with reproduction, including gametogenesis, as well as courtship behavior in males; logically this represents a programmed response to a mitochondrially generated starvation signal. The underlying signalling pathway, if conserved, could influence many physiological processes in response to nutritional stress, although any such pathway involved remains unidentified. Conclusions/Significance These studies indicate that general and organ-specific metabolism is transformed in response to mitochondrial dysfunction, including digestive and absorptive functions, and give important clues as to how novel therapeutic strategies for mitochondrial disorders might be developed.Public Library of Scienc

Detection and explanation of anomalies in real-time gross settlement systems by lossy data compression

In this paper, we discuss how to apply an autoencoder to detect anomalies in payment data derived from an Real-Time Gross Settlement system. Moreover, we introduce a drill-down procedure to measure the extent to which the inflow or outflow of a particular bank explains an anomaly. Experimental results on real-world payment data show that our method can detect the liquidity problems of a bank when it was subject to a bank run with reasonable accuracy

Anomaly detection in real-time gross payment data

We discuss how an autoencoder can detect system-level anomalies in a real-time gross settlement system by reconstructing a set of liquidity vectors. A liquidity vector is an aggregated representation of the underlying payment network of a settlement system for a particular time interval. Furthermore, we evaluate the performance of two autoencoders on real-world payment data extracted from the TARGET2 settlement system. We do this by generating different types of artificial bank runs in the data and determining how the autoencoders respond. Our experimental results show that the autoencoders are able to detect unexpected changes in the liquidity flows between banks

Anomaly detection in real-time gross payment data

We discuss how an autoencoder can detect system-level anomalies in a real-time gross settlement system by reconstructing a set of liquidity vectors. A liquidity vector is an aggregated representation of the underlying payment network of a settlement system for a particular time interval. Furthermore, we evaluate the performance of two autoencoders on real-world payment data extracted from the TARGET2 settlement system. We do this by generating different types of artificial bank runs in the data and determining how the autoencoders respond. Our experimental results show that the autoencoders are able to detect unexpected changes in the liquidity flows between banks

Anomaly Detection in Real-Time Gross Payment Data

We discuss how an autoencoder can detect system-level anomalies in a real-time gross settlement system by reconstructing a set of liquidity vectors. A liquidity vector is an aggregated representation of the underlying payment network of a settlement system for a particular time interval. Furthermore, we evaluate the performance of two autoencoders on real-world payment data extracted from the TARGET2 settlement system. We do this by generating different types of artificial bank runs in the data and determining how the autoencoders respond. Our experimental results show that the autoencoders are able to detect unexpected changes in the liquidity flows between banks