615 research outputs found

    THESEUS1 and RALF34 monitor cell wall integrity

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    The cell wall is a rigid network being the first barrier between a plant cell and its environment, but at the same time has to be a dynamic network whose cell growth and shape is given by deposition and remodeling of the cell wall. Maintaining cell wall integrity (CWI) is essential for correct plant development and stress response. Members of the family of Catharanthus roseus receptor-like kinase 1-like (CrRLK1L) proteins have been shown to play a role in cell wall homeostasis, mechanoperception, CWI maintenance and growth control. One of the 17 members in Arabidopsis, THESEUS1 (THE1), was identified in a suppressor screen of a cellulose deficient mutant, revealing that the reduction in growth is part of a THE1-mediated compensatory response to cell wall perturbation (Hématy et al., 2007). Interestingly, several CrRLK1L members have been shown to be receptors for Rapid Alkalinisation Factor (RALF) peptides. RALFs are on average 50 amino acids highly basic, cysteine-rich peptides, most of which are predicted to be cleaved from a highly acidic prodomain by a subtilisin protease. Recently, THE1 has been identified as a receptor for RALF34 (Gonneau et al., 2018). However, this peptide might not be the only THE1 ligand, since ralf34 loss-of-function mutants do not phenocopy all aspects of the1 mutants. RALF24 and RALF31 clustered together with RALF34, based on expression values across different tissues. We generated CRISPR/Cas9 mutants on RALF24, RALF31 and RALF34 with the aim to study which THE1 responses depend on these peptides. Our data suggest that RALF34 could not be the ligand for CWI response of THE1. The presence of RALF34 is acting negatively through THE1, inhibiting its response to cell wall damage.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

    Metabolic consequences of chronic sleep restriction in rats:Changes in body weight regulation and energy expenditure

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    Epidemiological studies have shown an association between short or disrupted sleep and an increased risk to develop obesity. In animal studies, however, sleep restriction leads to an attenuation of weight gain that cannot be explained by changes in energy intake. In the present study, we assessed whether the attenuated weight gain under conditions of restricted sleep is a consequence of an overall increase in energy expenditure. Adult male rats were subjected to a schedule of chronic sleep restriction (SR) for 8 days with a 4 h window of unrestricted rest per day. Electroencephalogram and electromyogram recordings were performed to quantify the effect of the sleep restriction schedule on sleep-wake patterns. In a separate experiment, we measured sleep restriction-induced changes in body weight, food intake, and regulatory hormones such as glucose, insulin, leptin and corticosterone. To investigate whether a change in energy expenditure underlies the attenuation of weight gain, energy expenditure was measured by the doubly labeled water method from day 5 until day 8 of the SR protocol. Results show a clear attenuation of weight gain during sleep restriction but no change in food intake. Baseline plasma glucose, insulin and leptin levels are decreased after sleep restriction which presumably reflects the nutritional status of the rats. The daily energy expenditure during SR was significantly increased compared to control rats. Together, we conclude that the attenuation of body weight gain in sleep restricted rats is explained by an overall increase in energy expenditure together with an unaltered energy intake. Published by Elsevier Inc

    DIET : new developments and recent results

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    Among existing grid middleware approaches, one simple, powerful, and flexibleapproach consists of using servers available in different administrative domainsthrough the classic client-server or Remote Procedure Call (RPC) paradigm.Network Enabled Servers (NES) implement this model also called GridRPC.Clients submit computation requests to a scheduler whose goal is to find aserver available on the grid. The aim of this paper is to give an overview of anNES middleware developed in the GRAAL team called DIET and to describerecent developments. DIET (Distributed Interactive Engineering Toolbox) is ahierarchical set of components used for the development of applications basedon computational servers on the grid.Parmi les intergiciels de grilles existants, une approche simple, flexible et performante consiste a utiliser des serveurs disponibles dans des domaines administratifs différents à travers le paradigme classique de l’appel de procédure àdistance (RPC). Les environnements de ce type, connus sous le terme de Network Enabled Servers, implémentent ce modèle appelé GridRPC. Des clientssoumettent des requêtes de calcul à un ordonnanceur dont le but consiste àtrouver un serveur disponible sur la grille.Le but de cet article est de donner un tour d’horizon d’un intergiciel développédans le projet GRAAL appelé DIET 1. DIET (Distributed Interactive Engineering Toolbox) est un ensemble hiérarchique de composants utilisés pour ledéveloppement d’applications basées sur des serveurs de calcul sur la grille

    Challenges in working towards an internal Threshold of Toxicological Concern (iTTC) for use in the safety assessment of cosmetics: Discussions from the Cosmetics Europe iTTC Working Group workshop

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    The Threshold of Toxicological Concern (TTC) is an important risk assessment tool which establishes acceptable low-level exposure values to be applied to chemicals with limited toxicological data. One of the logical next steps in the continued evolution of TTC is to develop this concept further so that it is representative of internal exposures (TTC based on plasma concentration). An internal TTC (iTTC) would provide threshold values that could be utilized in exposure-based safety assessments. As part of a Cosmetics Europe (CosEu) research program, CosEu has initiated a project that is working towards the development of iTTCs that can be used for the human safety assessment. Knowing that the development of an iTTC is an ambitious and broad-spanning topic, CosEu organized a Working Group comprised a balance of multiple stakeholders (cosmetics and chemical industries, the EPA and JRC and academia) with relevant experience and expertise and workshop to critically evaluate the requirements to establish an iTTC. Outcomes from the workshop included an evaluation on the current state of the science for iTTC, the overall iTTC strategy, selection of chemical databases, capture and curation of chemical information, ADME and repeat dose data, expected challenges, as well as next steps and ongoing work

    A mode-of-action ontology model for safety evaluation of chemicals: outcome of a series of workshops on repeated dose toxicity

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    Repeated dose toxicity evaluation aims at assessing the occurrence of adverse effects following chronic or repeated exposure to chemicals. Non-animal approaches have gained importance in the last decades because of ethical considerations as well as due to scientific reasons calling for more human-based strategies. A critical aspect of this challenge is linked to the capacity to cover a comprehensive set of interdependent mechanisms of action, link them to adverse effects and interpret their probability to be triggered in the light of the exposure at the (sub)cellular level. Inherent to its structured nature, an ontology addressing repeated dose toxicity could be a scientific and transparent way to achieve this goal. Additionally, repeated dose toxicity evaluation through the use of a harmonized ontology should be performed in a reproducible and consistent manner, while mimicking as accurately as possible human physiology and adaptivity. In this paper, the outcome of a series of workshops organized by Cosmetics Europe on this topic is reported. As such, this manuscript shows how experts set critical elements and ways of establishing a mode-of-action ontology model as a support to risk assessors aiming to perform animal-free safety evaluation of chemicals based on repeated dose toxicity data

    Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia

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    In the mammary gland, epithelial cells are embedded in a ‘soft' environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we define the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for β-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of β-casein expression required both laminin signalling and a ‘soft' extracellular matrix, as is the case in normal tissues in vivo, and biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of β-casein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues' unique biochemical milieu and mechanical properties, processes involved in maintenance of tissue integrity and protection against tumorigenesis

    Impacts of climate change on plant diseases – opinions and trends

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    There has been a remarkable scientific output on the topic of how climate change is likely to affect plant diseases in the coming decades. This review addresses the need for review of this burgeoning literature by summarizing opinions of previous reviews and trends in recent studies on the impacts of climate change on plant health. Sudden Oak Death is used as an introductory case study: Californian forests could become even more susceptible to this emerging plant disease, if spring precipitations will be accompanied by warmer temperatures, although climate shifts may also affect the current synchronicity between host cambium activity and pathogen colonization rate. A summary of observed and predicted climate changes, as well as of direct effects of climate change on pathosystems, is provided. Prediction and management of climate change effects on plant health are complicated by indirect effects and the interactions with global change drivers. Uncertainty in models of plant disease development under climate change calls for a diversity of management strategies, from more participatory approaches to interdisciplinary science. Involvement of stakeholders and scientists from outside plant pathology shows the importance of trade-offs, for example in the land-sharing vs. sparing debate. Further research is needed on climate change and plant health in mountain, boreal, Mediterranean and tropical regions, with multiple climate change factors and scenarios (including our responses to it, e.g. the assisted migration of plants), in relation to endophytes, viruses and mycorrhiza, using long-term and large-scale datasets and considering various plant disease control methods
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