Genetic variability of muscle biological characteristics of young Limousin bulls

Genetic parameters of 4 muscle biological characteristics (protein to DNA ratio (Pro/DNA), lactate dehydrogenase (LDH) activity, isocitrate dehydrogenase (ICDH) activity and the proportion of type I myosin heavy chains (MHC I)), in the Semitendinosus and the Longissimus thoracis, were estimated simultaneously with average daily gain (ADG), 480-d final weight (FW), carcass lean and fat contents (CL% and CF% respectively) in a sample of young Limousin bulls tested in station. The data came from 144 animals, the progeny of 15 sires. Sire and residual variances and covariances were estimated u using an expectation maximization restricted maximum likelihood (EM-REML) procedure applied to a multitrait mixed model. Heritability coefficients of production traits, ADG, FW, CL% and CF%, were 0.19, 0.49, 0.39 and 0.43, respectively, while heritability coefficients of muscle characteristics, Pro/DNA, LDH, ICDH and MHC I, were 0.11, 0.26, 1.03 and 0.35 respectively, in the Semitendinosus muscle and 0.29, 0.31, 0.28 and 0.41, respectively, in the Longissimus thoracis muscle. In both muscles, the oxidative activity of the ICDH appeared to be genetically associated with the proportion of type I myosin heavy chains and opposed to the glycolytic activity of the LDH. The LDH activity was clearly associated with higher muscle-to-fat ratio, while the opposite relationship was observed between that ratio and the ICDH activity or the MHC I proportion.Les paramètres génétiques de 4 caractéristiques biologiques - le rapport protéines /ADN (Pro/DNA), les activités de la lactate déshydrogénase (LDH) et de l’isocitrate déshydrogénase (ICDH) et la proportion en chaînes lourdes de myosine lente (MHC I) - des muscles Semitendinosus et Longissimus thoracis, et ceux du gain moyen quotidien (ADG), du poids vif finaL à 480 j (FW) et des teneurs de la carcasse en muscles et en dépôts adipeux (CL% and CF% respectivement), ont été estimés simultanément à partir d’un échantillon de taurillons Limousins contrôlés en station. Le fichier comprenait 144 veaux issus de 15 pères testés sur descendance. Les variances et covariances paternelles et résiduelles ont été estimées par la méthode du maximum de vraisemblance restreinte, avec l’algorithme d’espérance-maximisation, appliquée à un modèle mixte multicaractère (EM-REML). Les coefficients d’héritabilité des variables de production, ADG, FW, CL% et CF%, s’élevaient respectivement à 0,19, 0,49, 0,39 et 0,43, tandis que les coefficients d’héritabilité des caractéristiques musculaires, Pro/DNA, LDH, ICDH et MHC I, valaient respectivement 0,11, 0,26, 1,03 et 0,35 dans le muscle Semitendinosus et 0,29, 0,31, 0,28 et 0,41 dans le muscle Longissimus thoracis. Dans les 2 muscles, l’activité oxidative de l’ICDH était génétiquement associée à la proportion de myosine lente et opposée à l’activité glycolytique du LDH. Cette activité du LDH était positivement corrélée avec le rapport muscles / dépôts adipeux, alors qu’une relation inverse était observée avec l’activité de l’ICDH et la proportion de MHC I

On the Representability of Complete Genomes by Multiple Competing Finite-Context (Markov) Models

A finite-context (Markov) model of order yields the probability distribution of the next symbol in a sequence of symbols, given the recent past up to depth . Markov modeling has long been applied to DNA sequences, for example to find gene-coding regions. With the first studies came the discovery that DNA sequences are non-stationary: distinct regions require distinct model orders. Since then, Markov and hidden Markov models have been extensively used to describe the gene structure of prokaryotes and eukaryotes. However, to our knowledge, a comprehensive study about the potential of Markov models to describe complete genomes is still lacking. We address this gap in this paper. Our approach relies on (i) multiple competing Markov models of different orders (ii) careful programming techniques that allow orders as large as sixteen (iii) adequate inverted repeat handling (iv) probability estimates suited to the wide range of context depths used. To measure how well a model fits the data at a particular position in the sequence we use the negative logarithm of the probability estimate at that position. The measure yields information profiles of the sequence, which are of independent interest. The average over the entire sequence, which amounts to the average number of bits per base needed to describe the sequence, is used as a global performance measure. Our main conclusion is that, from the probabilistic or information theoretic point of view and according to this performance measure, multiple competing Markov models explain entire genomes almost as well or even better than state-of-the-art DNA compression methods, such as XM, which rely on very different statistical models. This is surprising, because Markov models are local (short-range), contrasting with the statistical models underlying other methods, where the extensive data repetitions in DNA sequences is explored, and therefore have a non-local character

FactSage thermochemical software and databases, 2010–2016

The FactSage computer package consists of a series of information, calculation and manipulation modules that enable one to access and manipulate compound and solution databases. With the various modules running under Microsoft Windows® one can perform a wide variety of thermochemical calculations and generate tables, graphs and figures of interest to chemical and physical metallurgists, chemical engineers, corrosion engineers, inorganic chemists, geochemists, ceramists, electrochemists, environmentalists, etc. This paper presents a summary of the developments in the FactSage thermochemical software and databases during the last six years. Particular emphasis is placed on the new databases and developments in calculating and manipulating phase diagrams

Muscle cells of sporadic amyotrophic lateral sclerosis patients secrete neurotoxic vesicles

Background: The cause of the motor neuron (MN) death that drives terminal pathology in amyotrophic lateral sclerosis (ALS) remains unknown, and it is thought that the cellular environment of the MN may play a key role in MN survival. Several lines of evidence implicate vesicles in ALS, including that extracellular vesicles may carry toxic elements from astrocytes towards MNs, and that pathological proteins have been identified in circulating extracellular vesicles of sporadic ALS patients. Because MN degeneration at the neuromuscular junction is a feature of ALS, and muscle is a vesicle-secretory tissue, we hypothesized that muscle vesicles may be involved in ALS pathology. Methods: Sporadic ALS patients were confirmed to be ALS according to El Escorial criteria and were genotyped to test for classic gene mutations associated with ALS, and physical function was assessed using the ALSFRS-R score. Muscle biopsies of either mildly affected deltoids of ALS patients (n = 27) or deltoids of aged-matched healthy subjects (n = 30) were used for extraction of muscle stem cells, to perform immunohistology, or for electron microscopy. Muscle stem cells were characterized by immunostaining, RT-qPCR, and transcriptomic analysis. Secreted muscle vesicles were characterized by proteomic analysis, Western blot, NanoSight, and electron microscopy. The effects of muscle vesicles isolated from the culture medium of ALS and healthy myotubes were tested on healthy human-derived iPSC MNs and on healthy human myotubes, with untreated cells used as controls. Results: An accumulation of multivesicular bodies was observed in muscle biopsies of sporadic ALS patients by immunostaining and electron microscopy. Study of muscle biopsies and biopsy-derived denervation-naïve differentiated muscle stem cells (myotubes) revealed a consistent disease signature in ALS myotubes, including intracellular accumulation of exosome-like vesicles and disruption of RNA-processing. Compared with vesicles from healthy control myotubes, when administered to healthy MNs the vesicles of ALS myotubes induced shortened, less branched neurites, cell death, and disrupted localization of RNA and RNA-processing proteins. The RNA-processing protein FUS and a majority of its binding partners were present in ALS muscle vesicles, and toxicity was dependent on the expression level of FUS in recipient cells. Toxicity to recipient MNs was abolished by anti-CD63 immuno-blocking of vesicle uptake. Conclusions: ALS muscle vesicles are shown to be toxic to MNs, which establishes the skeletal muscle as a potential source of vesicle-mediated toxicity in ALS