GNE Is Involved in the Early Development of Skeletal and Cardiac Muscle

UDP-N-acetylglucosamine 2 epimerase/N-acetylmannosamime kinase (GNE) is a bifunctional enzyme which catalyzes the two key sequential steps in the biosynthetic pathway of sialic acid, the most abundant terminal monosaccharide on glycoconjugates of eukaryotic cells. GNE knock out (GNE KO) mice are embryonically lethal at day E8.5. Although the role of GNE in the sialic pathway has been well established as well as the importance of sialylation in many diverse biological pathways, less is known about the involvement of GNE in muscle development. To address this issue we have studied the role of GNE during in vitro embryogenesis by comparing the developmental profile in culture of embryonic stem cells (ES) from wild type and from GNE KO E3.5 mice embryos, during 45 days. Neuronal cells appeared rarely in GNE KO ES cultures and did not reach an advanced differentiated stage. Although primary cardiac cells appeared at the same time in both normal and GNE KO ES cultures, GNE KO cardiac cells degraded very soon and their beating capacity decayed rapidly. Furthermore very rare skeletal muscle committed cells were detected in the GNE KO ES cultures at any stage of differentiation, as assessed by analysis of the expression of either Pax7, MyoD and MyHC markers. Beyond the supporting evidence that GNE plays an important role in neuronal cell and brain development, these results show that GNE is strongly involved in cardiac tissue and skeletal muscle early survival and organization. These findings could open new avenues in the understanding of muscle function mechanisms in health and in disease

UDP-N-Acetylglucosamine 2-Epimerase/N-Acetylmannosamine Kinase (GNE) Binds to Alpha-Actinin 1: Novel Pathways in Skeletal Muscle?

Hereditary inclusion body myopathy (HIBM) is a rare neuromuscular disorder caused by mutations in GNE, the key enzyme in the biosynthetic pathway of sialic acid. While the mechanism leading from GNE mutations to the HIBM phenotype is not yet understood, we searched for proteins potentially interacting with GNE, which could give some insights about novel putative biological functions of GNE in muscle. We used a Surface Plasmon Resonance (SPR)-Biosensor based assay to search for potential GNE interactors in anion exchanged fractions of human skeletal muscle primary culture cell lysate. Analysis of the positive fractions by in vitro binding assay revealed alpha-actinin 1 as a potential interactor of GNE. The direct interaction of the two proteins was assessed in vitro by SPR-Biosensor based kinetics analysis and in a cellular environment by a co-immunoprecipitation assay in GNE overexpressing 293T cells. Furthermore, immunohistochemistry on stretched mouse muscle suggest that both GNE and alpha-actinin 1 localize to an overlapping but not identical region of the myofibrillar apparatus centered on the Z line. The interaction of GNE with alpha-actinin 1 might point to its involvement in alpha-actinin mediated processes. In addition these studies illustrate for the first time the expression of the non-muscle form of alpha-actinin, alpha-actinin 1, in mature skeletal muscle tissue, opening novel avenues for its specific function in the sarcomere. Although no significant difference could be detected in the binding kinetics of alpha-actinin 1 with either wild type or mutant GNE in our SPR biosensor based analysis, further investigation is needed to determine whether and how the interaction of GNE with alpha-actinin 1 in skeletal muscle is relevant to the putative muscle-specific function of alpha-actinin 1, and to the muscle-restricted pathology of HIBM

Modeling the Dynamic Effects of Discourse: Principles and Frameworks

International audienceWhen studying the meaning of natural language expressions, sentence level provides a natural entry point. Its relevance of course depends on the focus we want to put on the meaning: as related to thought, to communication, to truth, etc. In this paper, we concentrate on the model theoretic view on meaning, in particular via first order logic representation. More specifically, we present phenomena that illustrate the challenges raised by discourse to truth-conditional semantics and compositionality. We show that proposals to address theses challenges rely on the additional device of contexts and on the way sentences can access and modify these contexts. This capability is usually referred to as the context change potential of a sentence. Depending on the phenomenon, the contexts need to represent different kinds of information: propositions, discourse referents, and variations on these elements. We also show that taking into account the rhetorical structure of discourse leads to even richer structuring of the context. Parallel to the presentation of the phenomena, we concentrate on formalisms giving an account of the dynamics of discourse. We introduce the well established formalisms of Discourse Representation Theory (DRT) Dynamic Predicate Logic (DPL) , and the more recently developed approach based on continuation semantics. Finally, we introduce Segmented Discourse Representation Theory (SDRT) that combines the effects of dynamics and discourse structure.La phrase représente un niveau d'entrée naturel dans l'étude du sens des expressions de la langue naturelle. Sa pertinence dépend bien sûr de la perspective que l'on souhaite mettre en avant sur le sens : celle relative à la pensée, celle relative à la communication, celle relative à la valeur de vérité... Dans cet article, nous nous concentrons sur la perspective donnée au sens par la théorie des modèles, en particulier par la représentation avec la logique du premier ordre. Plus spécifiquement, nous présentons des phénomènes illustrant les difficultés posées par le discours à la sémantique vériconditionnelle et à la compositionalité. Nous montrons que les propositions pour répondre à ces difficultés reposent sur l'utilisation de contextes et de la manière dons les phrases peuvent accéder à ce contexte et le modifier. Ce mécanisme est généralement appelé potentiel de changement du contexte d'une phrase. Suivant le phénomène considéré, le contexte doit représenter différents types d'informations : des propositions, des référents de discours, et des variations de ces éléments. Nous montrons également que la prise en compte de la structure rhétorique du discours conduit à une représentation encore plus riche du contexte. Parallèlement à l'exposé de ces phénomènes, nous présentons différents formalismes qui en rendent compte. Nous présentons la théorie des représentations discursives (DRT), de la logique des prédicats dynamique (DPL), ainsi que l'approche fondée sur les continuations proposée plus récemment. Enfin nous présentons la théorie des représentations discursives segmentées (SDRT) qui combine les effets de la dynamique et de la structure discursive

Anthropogenic and Inherent Effects on Soil Organic Carbon across the U.S

Soil organic carbon (SOC) influences several soil functions, making it one of the most important soil health indicators. Its quantity is determined by anthropogenic and inherent factors that must be understood to improve SOC management and interpretation. Topsoil (≤15 cm) SOC response to tillage depth and intensity, cover crops, stover removal, manure addition, and various cropping systems was assessed using 7610 observations from eight U.S. regions. Overall, including cover crops, reducing tillage depth and intensity increased SOC. The positive effects of cover crops were more noticeable in South Central, Northwest, and Midwest regions. Removing high rates (>65%) of crop residue decreased SOC in Midwestern and Southeastern soils. Depending on region, applying manure increased SOC by 21 to 41%, compared to non-manured soils. Diversified cropping systems (e.g., those utilizing small mixed vegetables, perennials, or dairy-based systems) had the highest topsoil SOC content, while more intensive annual row crops and large-scale single vegetable production systems, had the lowest. Among inherent factors, SOC increased as precipitation increased, but decreased as mean annual temperature increased. Texture influenced SOC, showing higher values in fine-texture than coarse-texture soils. Finally, this assessment confirmed that SOC can be a sensitive soil health indicator for evaluating conservation practices

Anthropogenic and Inherent Effects on Soil Organic Carbon across the U.S

Soil organic carbon (SOC) influences several soil functions, making it one of the most important soil health indicators. Its quantity is determined by anthropogenic and inherent factors that must be understood to improve SOC management and interpretation. Topsoil (≤15 cm) SOC response to tillage depth and intensity, cover crops, stover removal, manure addition, and various cropping systems was assessed using 7610 observations from eight U.S. regions. Overall, including cover crops, reducing tillage depth and intensity increased SOC. The positive effects of cover crops were more noticeable in South Central, Northwest, and Midwest regions. Removing high rates (&gt;65%) of crop residue decreased SOC in Midwestern and Southeastern soils. Depending on region, applying manure increased SOC by 21 to 41%, compared to non-manured soils. Diversified cropping systems (e.g., those utilizing small mixed vegetables, perennials, or dairy-based systems) had the highest topsoil SOC content, while more intensive annual row crops and large-scale single vegetable production systems, had the lowest. Among inherent factors, SOC increased as precipitation increased, but decreased as mean annual temperature increased. Texture influenced SOC, showing higher values in fine-texture than coarse-texture soils. Finally, this assessment confirmed that SOC can be a sensitive soil health indicator for evaluating conservation practices.</jats:p

Ecological insights into soil health according to the genomic traits and environment-wide associations of bacteria in agricultural soils

Abstract Soil microbiomes are sensitive to current and previous soil conditions, and bacterial ‘bioindicators’ of biological, physical, and chemical soil properties have considerable potential for soil health assessment. However, the lack of ecological or physiological information for most soil microorganisms limits our ability to interpret the associations of bioindicators and, thus, their utility for guiding management. We identified bioindicators of tillage intensity and twelve soil properties used to rate soil health using a 16S rRNA gene-based survey of farmland across North America. We then inferred the genomic traits of bioindicators and evaluated their environment-wide associations (EWAS) with respect to agricultural management practice, disturbance, and plant associations with 89 studies from agroecosystems. Most bioindicators were either positively correlated with biological properties (e.g., organic matter) or negatively correlated with physical and chemical properties. Higher soil health ratings corresponded with smaller genome size and higher coding density, while lower ratings corresponded with larger genomes and higher rrn copy number. Community-weighted genome size explained most variation in health ratings. EWAS linked prominent bioindicators with the impacts of environmental disturbances. Our findings provide ecological insights into bioindicators of soil properties relevant to soil health management, illustrating the tight coupling of microbiome and soil function

Ecological insights into soil health according to the genomic traits and environment-wide associations of bacteria in agricultural soils

AbstractSoil microbiomes are sensitive to current and previous soil conditions, and bacterial ‘bioindicators’ of biological, physical, and chemical soil properties have considerable potential for soil health assessment. However, the lack of ecological or physiological information for most soil microorganisms limits our ability to interpret the associations of bioindicators and, thus, their utility for guiding management. We identified bioindicators of tillage intensity and twelve soil properties used to rate soil health using a 16S rRNA gene-based survey of farmland across North America. We then inferred the genomic traits of bioindicators and evaluated their environment-wide associations (EWAS) with respect to agricultural management practice, disturbance, and plant associations with 89 studies from agroecosystems. Most bioindicators were either positively correlated with biological properties (e.g., organic matter) or negatively correlated with physical and chemical properties. Higher soil health ratings corresponded with smaller genome size and higher coding density, while lower ratings corresponded with larger genomes and higher rrn copy number. Community-weighted genome size explained most variation in health ratings. EWAS linked prominent bioindicators with the impacts of environmental disturbances. Our findings provide ecological insights into bioindicators of soil properties relevant to soil health management, illustrating the tight coupling of microbiome and soil function.</jats:p