Large-scale modeling of plant metabolism provides the possibility to compare and contrast different cellular and environmental scenarios with the ultimate aim of identifying the components underlying ...the respective plant behavior. The existing models of Arabidopsis (Arabidopsis thaliana) are top-down assembled, whereby the starting point is the annotated genome, in particular, metabolic genes. Hence, dead-end metabolites and blocked reactions can arise that are subsequently addressed by using gapfilling algorithms in combination with species-unspecific genes. Here, we present a bottom-up-assembled, large-scale model that relies solely on Arabidopsis-specific annotations and results in the inclusion of only manually curated reactions. While the existing models are largely condition unspecific by employing a single biomass reaction, we provide three biomass compositions that pertain to realistic and frequently examined scenarios: carbon-limiting, nitrogen-limiting, and optimal growth conditions. The comparative analysis indicates that the proposed Arabidopsis core model exhibits comparable efficiency in carbon utilization and flexibility to the existing network alternatives. Moreover, the model is utilized to quantify the energy demand of amino acid and enzyme de novo synthesis in photoautotrophic growth conditions. Illustrated by the case of the most abundant protein in the world, Rubisco, we determine its synthesis cost in terms of ATP requirements. This, in turn, allows us to explore the tradeoff between protein synthesis and growth in Arabidopsis. Altogether, the model provides a solid basis for completely species-specific integration of high-throughput data, such as gene expression levels, and for condition-specific investigations of in silico metabolic engineering strategies.
Synthetic, resorbable scaffolds for bone regeneration have potential to transform the clinical standard of care. Here, we demonstrate that functional graphenic materials (FGMs) could serve as an ...osteoinductive scaffold: recruiting native cells to the site of injury and promoting differentiation into bone cells. By invoking a Lewis acid-catalyzed Arbuzov reaction, we are able to functionalize graphene oxide (GO) to produce phosphate graphenes (PGs) with unprecedented control of functional group density, mechanical properties, and counterion identity. In aqueous environments, PGs release inducerons, including Ca2+ and PO₄3−. Calcium phosphate graphene (CaPG) intrinsically induces osteogenesis in vitro and in the presence of bone marrow stromal cells (BMSCs), can induce ectopic bone formation in vivo. Additionally, an FGM can be made by noncovalently loading GO with the growth factor recombinant human bone morphogenetic protein 2 (rhBMP-2), producing a scaffold that induces ectopic bone formation with or without BMSCs. The FGMs reported here are intrinsically inductive scaffolds with significant potential to revolutionize the regeneration of bone.
Abstract
Behavioural disorders are a major reason for euthanasia and sheltering of pet dogs. The prevention and treatment of behavioural disorders requires a better understanding of the underlying ...causes. Early life experiences, such as maternal care, attachment and socialisation, have long lasting and serious consequences for the behavioural and physiological development of an individual. The complex interplay between these factors is likely to have consequences for the future dog-owner bond and the vulnerability to develop behavioural disorders. Here, we summarise the current literature on the interactions between maternal care, attachment formation, and the sensitive socialisation period and their potential consequences on adult dog behaviour. Based on the findings we highlight gaps in knowledge and provide suggestions for future research which are necessary to formulate recommendations for pet dog breeding and socialisation.
Forest insects are among the most important factors of disturbance in European forests. The increase in and duration of drought stress events due to climate change not only increase the vulnerability ...of rural and urban forests but also predispose weakened stands to insect pest calamities. In this context, many German and European forest research institutes and environmental institutions report an increase in the densities and calamity developments of the oak processionary moth (Thaumetopoea processionea L.) not only in oak and mixed-oak forests but also in smaller areas where oak trees regularly occur, e.g., parklands, urban areas, copses, avenues, recreational forests, etc. It is expected that the oak processionary moth (OPM) will benefit from the overall weakened vitality of both individual oaks and oak stands in the future and that mass outbreaks will occur at an increased frequency. This paper reports on the effects that the OPM can have on tree performance for rural forest and urban oak trees by applying the chlorophyll fluorescence non-destructive diagnostic method for the identification and quantification of damage to oak leaves. The aim of the study was to investigate the effects of OPM frass activity on tree leaf health using chlorophyll fluorescence measurements, comparing infested host oaks with non-infested oaks in urban and forest environs. The study assessed: 1. the quantum efficiency of photosystem II (PS II), which counts as an indicator for leaf conditions, 2. the performance index, which indicates the efficiency of the photosynthetic light reaction, 3. the energy loss of the photosynthetic reaction, which is an indicator for cell damage, and 4. the degree of open reaction centers in PS II, which indicates how well light energy can be absorbed for photosynthesis. Infested urban and rural oaks showed a significantly reduced quantum yield of PS II by up to 10% compared to non-infested oak leaves. The leaf performance was significantly reduced by up to 35% for infested urban oaks and by up to 60% for infested forest oaks, respectively. The energy losses were two times higher for infested urban and forest oaks. However, OPM infestation led to a higher reduction in the photosynthetic performance in the leaves of forest oaks compared to that of urban oaks. In order to avoid permanent damage, suitable countermeasures must be taken quickly, as, immediately after pest infestation, the performance decreases significantly. A lower performance means a significant loss in biomass production as well as in tree vitality.
The application of functional graphenic materials (FGMs) in medicine has been limited due to insufficient knowledge of long–term degradation and cytocompatibility. Degradation studies that match the ...timeframe of clinical treatments are difficult to perform due to the limited timeframe in which in vitro studies can be conducted and the short lifespan of in vivo animal models. Here, we have designed an ex vivo experimental approach, where the degradation of FGMs can be monitored indefinitely and sampled at any point during the degradation process. We used this approach to study the aqueous and enzymatic degradation of phosphate graphenes (PGs), which are promising materials for biodegradable bone implants. We found that PGs chemically degrade through cation elution and basal plane scission of polyphosphates, and degradation timeframes are dependent on cation identity. Further, PGs also undergo physical degradation indicated by reduction of particle size. The pathways and timeframes of physical degradation of PGs are different for aqueous and enzymatic conditions. PG degradation was related to structure, which according to kinetic studies of the synthesis, could be manipulated to tune degradation. Nevertheless, all PGs and the resulting degradation byproducts are cytocompatible, opening the door for long–term biomedical applications, such as synthetic bone graft implants.
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Bone regenerative engineering could replace autografts; however, no synthetic material fulfills all design criteria. Nanocarbons incorporated into three-dimensional printed (3DP) matrices can improve ...properties, but incorporation is constrained to low wt%. Further, unmodified nanocarbons have limited osteogenic potential. Functionalization to calcium phosphate graphene (CaPG) imparts osteoinductivity and osteoconductivity, but loading into matrices remained limited. This work presents ultra-high content (90%), 3DP-CaPG matrices. 3DP-CaPG matrices are highly porous (95%), moderately stiff (3 MPa), and mechanically robust. In vitro, they are cytocompatible and induce osteogenic differentiation of human mesenchymal stem cells (hMSCs), indicated by alkaline phosphatase, mineralization, and COL1α1 expression. In vivo, bone regeneration was studied using a transgenic fluorescent-reporter mouse non-union calvarial defect model. 3DP-CaPG stimulates cellular ingrowth, retains donor cells, and induces osteogenic differentiation. Histology shows TRAP staining around struts, suggesting potential osteoclast activity. Apparent resorption of 3DP-CaPG was observed and presented no toxicity. 3DP-CaPG represents an advancement towards a synthetic bone regeneration matrix.
Plants as sessile organisms cannot escape their environment and have to adapt to any changes in the availability of sunlight and nutrients. The quantification of synthesis costs of metabolites, in ...terms of consumed energy, is a prerequisite to understand trade-offs arising from energetic limitations. Here, we examine the energy consumption of amino acid synthesis in Arabidopsis thaliana. To quantify these costs in terms of the energy equivalent ATP, we introduce an improved cost measure based on flux balance analysis and apply it to three state-of-the-art metabolic reconstructions to ensure robust results. We present the first systematic in silico analysis of the effect of nitrogen supply (nitrate/ammonium) on individual amino acid synthesis costs as well as of the effect of photoautotrophic and heterotrophic growth conditions, integrating day/night-specific regulation. Our results identify nitrogen supply as a key determinant of amino acid costs, in agreement with experimental evidence. In addition, the association of the determined costs with experimentally observed growth patterns suggests that metabolite synthesis costs are involved in shaping regulation of plant growth. Finally, we find that simultaneous uptake of both nitrogen sources can lead to efficient utilization of energy source, which may be the result of evolutionary optimization.
Aging is associated with far-reaching changes in physiological functions resulting in morbidity and ultimately death. Age-related frailty, insecurity and reduced physical activity contribute to a ...progressive loss of muscle mass and function, commonly referred to as sarcopenia. Due to the increase in life expectancy in many countries, loss of muscle mass and its consequences gain in relevance for public health. At the same time, the molecular mechanisms that underlie sarcopenia are poorly understood and therefore, therapeutic approaches are limited. Interestingly though, endurance, strength and stretching exercise is significantly superior to all known pharmacological, nutritional and hormonal interventions for stabilizing, alleviating and reversing sarcopenia. Thus, increased knowledge about the plastic changes of skeletal muscle after physical activity and the signaling factors that mediate the beneficial effects of exercise on other organs might yield a better understanding of the disease and open new avenues for treatment. Here, we discuss how current discoveries about the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a key exercise factor in muscle, and myokines, factors produced and secreted by active muscle fibers, expand our view of the pathological changes and the therapeutic options for sarcopenia.
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