MEATabolomics: Muscle and Meat Metabolomics in Domestic Animals

In the past decades, metabolomics has been used to comprehensively understand a variety of food materials for improvement and assessment of food quality. Farm animal skeletal muscles and meat are one of the major targets of metabolomics for the characterization of meat and the exploration of biomarkers in the production system. For identification of potential biomarkers to control meat quality, studies of animal muscles and meat with metabolomics (MEATabolomics) has been conducted in combination with analyses of meat quality traits, focusing on specific factors associated with animal genetic background and sensory scores, or conditions in feeding system and treatments of meat in the processes such as postmortem storage, processing, and hygiene control. Currently, most of MEATabolomics approaches combine separation techniques (gas or liquid chromatography, and capillary electrophoresis)–mass spectrometry (MS) or nuclear magnetic resonance (NMR) approaches with the downstream multivariate analyses, depending on the polarity and/or hydrophobicity of the targeted metabolites. Studies employing these approaches provide useful information to monitor meat quality traits efficiently and to understand the genetic background and production system of animals behind the meat quality. MEATabolomics is expected to improve the knowledge and methodologies in animal breeding and feeding, meat storage and processing, and prediction of meat quality

MEATabolomics: Muscle and Meat Metabolomics in Domestic Animals

In the past decades, metabolomics has been used to comprehensively understand a variety of food materials for improvement and assessment of food quality. Farm animal skeletal muscles and meat are one of the major targets of metabolomics for the characterization of meat and the exploration of biomarkers in the production system. For identification of potential biomarkers to control meat quality, studies of animal muscles and meat with metabolomics (MEATabolomics) has been conducted in combination with analyses of meat quality traits, focusing on specific factors associated with animal genetic background and sensory scores, or conditions in feeding system and treatments of meat in the processes such as postmortem storage, processing, and hygiene control. Currently, most of MEATabolomics approaches combine separation techniques (gas or liquid chromatography, and capillary electrophoresis)–mass spectrometry (MS) or nuclear magnetic resonance (NMR) approaches with the downstream multivariate analyses, depending on the polarity and/or hydrophobicity of the targeted metabolites. Studies employing these approaches provide useful information to monitor meat quality traits efficiently and to understand the genetic background and production system of animals behind the meat quality. MEATabolomics is expected to improve the knowledge and methodologies in animal breeding and feeding, meat storage and processing, and prediction of meat quality

Crystallization and preliminary X-ray analysis of ginkbilobin-2 from Ginkgo biloba seeds: a novel antifungal protein with homology to the extracellular domain of plant cysteine-rich receptor-like kinases. Erratum

An erratum to the paper by Miyakawa et al. [(2007), Acta Cryst. F63, 737–739]

Crystal structure of a Ca2+-dependent regulator of flagellar motility reveals the open-closed structural transition

Sperm chemotaxis toward a chemoattractant is very important for the success of fertilization. Calaxin, a member of the neuronal calcium sensor protein family, directly acts on outer-arm dynein and regulates specific flagellar movement during sperm chemotaxis of ascidian, Ciona intestinalis. Here, we present the crystal structures of calaxin both in the open and closed states upon Ca2+ and Mg2+ binding. The crystal structures revealed that three of the four EF-hands of a calaxin molecule bound Ca2+ ions and that EF2 and EF3 played a critical role in the conformational transition between the open and closed states. The rotation of α7 and α8 helices induces a significant conformational change of a part of the α10 helix into the loop. The structural differences between the Ca2+- and Mg2+-bound forms indicates that EF3 in the closed state has a lower affinity for Mg2+, suggesting that calaxin tends to adopt the open state in Mg2+-bound form. SAXS data supports that Ca2+-binding causes the structural transition toward the closed state. The changes in the structural transition of the C-terminal domain may be required to bind outer-arm dynein. These results provide a novel mechanism for recognizing a target protein using a calcium sensor protein

A new target region for changing the substrate specificity of amine transaminases

(R)-stereospecific amine transaminases (R-ATAs) are important biocatalysts for the production of (R)-amine compounds in a strict stereospecific manner. An improved R-ATA, ATA-117-Rd11, was successfully engineered for the manufacture of sitagliptin, a widely used therapeutic agent for type-2 diabetes. The effects of the individual mutations, however, have not yet been demonstrated due to the lack of experimentally determined structural information. Here we describe three crystal structures of the first isolated R-ATA, its G136F mutant and engineered ATA-117-Rd11, which indicated that the mutation introduced into the 136th residue altered the conformation of a loop next to the active site, resulting in a substrate-binding site with drastically modified volume, shape, and surface properties, to accommodate the large pro-sitagliptin ketone. Our findings provide a detailed explanation of the previously reported molecular engineering of ATA-117-Rd11 and propose that the loop near the active site is a new target for the rational design to change the substrate specificity of ATAs.UTokyo Research掲載「さまざまな薬の合成に重要な酵素が作用する相手を認識する仕組み」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/how-an-important-enzyme-used-in-drug-production-recognizes-its-substrate.htmlUTokyo Research "How an important enzyme used in drug production recognizes its substrate" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/how-an-important-enzyme-used-in-drug-production-recognizes-its-substrate.htm

Mitochondrial DNA Mutations Induce Mitochondrial Dysfunction, Apoptosis and Sarcopenia in Skeletal Muscle of Mitochondrial DNA Mutator Mice

Background: Aging results in a progressive loss of skeletal muscle, a condition known as sarcopenia. Mitochondrial DNA (mtDNA) mutations accumulate with aging in skeletal muscle and correlate with muscle loss, although no causal relationship has been established. Methodology/Principal Findings: We investigated the relationship between mtDNA mutations and sarcopenia at the gene expression and biochemical levels using a mouse model that expresses a proofreading-deficient version (D257A) of the mitochondrial DNA Polymerase c, resulting in increased spontaneous mtDNA mutation rates. Gene expression profiling of D257A mice followed by Parametric Analysis of Gene Set Enrichment (PAGE) indicates that the D257A mutation is associated with a profound downregulation of gene sets associated with mitochondrial function. At the biochemical level, sarcopenia in D257A mice is associated with a marked reduction (35–50%) in the content of electron transport chain (ETC) complexes I, III and IV, all of which are partly encoded by mtDNA. D257A mice display impaired mitochondrial bioenergetics associated with compromised state-3 respiration, lower ATP content and a resulting decrease in mitochondrial membrane potential (Dym). Surprisingly, mitochondrial dysfunction was not accompanied by an increase in mitochondrial reactive oxygen species (ROS) production or oxidative damage. Conclusions/Significance: These findings demonstrate that mutations in mtDNA can be causal in sarcopenia by affecting the assembly of functional ETC complexes, the lack of which provokes a decrease in oxidative phosphorylation, without an increase in oxidative stress, and ultimately, skeletal muscle apoptosis and sarcopenia

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects