Fibroblast Memory in Development, Homeostasis and Disease

Fibroblasts are the major cell population in the connective tissue of most organs, where they are essential for their structural integrity. They are best known for their role in remodelling the extracellular matrix, however more recently they have been recognised as a functionally highly diverse cell population that constantly responds and adapts to their environment. Biological memory is the process of a sustained altered cellular state and functions in response to a transient or persistent environmental stimulus. While it is well established that fibroblasts retain a memory of their anatomical location, how other environmental stimuli influence fibroblast behaviour and function is less clear. The ability of fibroblasts to respond and memorise different environmental stimuli is essential for tissue development and homeostasis and may become dysregulated in chronic disease conditions such as fibrosis and cancer. Here we summarise the four emerging key areas of fibroblast adaptation: positional, mechanical, inflammatory, and metabolic memory and highlight the underlying mechanisms and their implications in tissue homeostasis and disease.

Effects of conditioning on the welfare of jaguars (Panthera onca) in captivity

ABSTRACT The jaguar is the largest feline in the Americas and in the face of the threat of extinction and the reduction of natural areas, keeping the species in captivity may be important for its conservation. This condition can lead to a reduction in well-being, especially due to spatial limitation and lack of environmental stimulus. In recent decades, techniques have been sought to minimize the negative impacts of captivity, with an increase in the use of environmental enrichment and operational conditioning in order to facilitate routine procedures for the animal management. In this scenario, this study aimed to evaluate the effects of conditioning on the welfare of jaguars in captivity, analyzing behavioral and physiological effects through salivary cortisol. Seven jaguars were studied in a Scientific Breeder. There was an increase in behaviors associated with welfare and cortisol during conditioning, possibly related to learning. The increase in behaviors associated with welfare suggests that the technique can contribute to improve the quality of life of these animals in captivity.

Crosstalk between Ethylene and ABA during changes in soil water content reveals a role of ACC in coffee anthesis regulation

Coffee (Coffea arabica L.) presents an asynchronous flowering regulated by endogenous and environmental stimulus, and anthesis occurs once plants are rehydrated after a period of water deficit. We evaluated the evolution of Abscisic Acid (ABA), ethylene, 1-aminocyclopropane-1-carboxylate (ACC) content, ACC oxidase (ACO) activity, and expression analysis of the Lysine Histidine Transporter 1 (LHT1) transporter, in roots, leaves and, flower buds from three coffee genotypes (Coffea arabica L. cv Oeiras, Acaua, and Semperflorens) cultivated under field conditions with two experiments. In a third field experiment, the effect of exogenous supply of ACC in coffee anthesis was evaluated. We found an increased ACC level in all tissues from the three coffee genotypes in the re-watering period just before anthesis for all tissues and high expression of the LHT1 gene in flower buds and leaves. Ethylene content and ACO activity decreased from rainy to dry period whereas ABA content increased. Higher number of opened and G6 stage flower buds were observed in the treatment with exogenous ACC. The results showed that the interaction of ABA-ACO-ethylene and intercellular ACC transport among leaves, buds, and roots in coffee favors an increased level of ACC that is most likely, involved as a modulator in coffee anthesis.

Additive Manufacturing for Effective Smart Structures: The Idea of 6D Printing

This paper aims to establish six-dimensional (6D) printing as a new branch of additive manufacturing investigating its benefits, advantages as well as possible limitations concerning the design and manufacturing of effective smart structures. The concept of 6D printing, to the authors’ best knowledge, is introduced for the first time. The new method combines the four-dimensional (4D) and five-dimensional (5D) printing techniques. This means that the printing process is going to use five degrees of freedom for creating the final object while the final produced material component will be a smart/intelligent one (i.e., will be capable of changing its shape or properties due to its interaction with an environmental stimulus). A 6D printed structure can be stronger and more effective than a corresponding 4D printed structure, can be manufactured using less material, can perform movements by being exposed to an external stimulus through an interaction mechanism, and it may learn how to reconfigure itself suitably, based on predictions via mathematical modeling and simulations.

Arabidopsis NF-YCs play dual roles in repressing brassinosteroid biosynthesis and signaling during light-regulated hypocotyl elongation

Light functions as the primary environmental stimulus and brassinosteroids (BRs) as important endogenous growth regulators throughout the plant lifecycle. Photomorphogenesis involves a series of vital developmental processes that require the suppression of BR-mediated seedling growth, but the mechanism underlying the light-controlled regulation of the BR pathway remain unclear. Here, we reveal that nuclear factor YC proteins (NF-YCs) function as essential repressors of the BR pathway during light-controlled hypocotyl growth in Arabidopsis thaliana. In the light, NF-YCs inhibit BR biosynthesis by directly targeting the promoter of the BR biosynthesis gene BR6ox2 and repressing its transcription. NF-YCs also interact with BIN2, a critical repressor of BR signaling, and facilitate its stabilization by promoting its Tyr200 autophosphorylation, thus inhibiting the BR signaling pathway. Consistently, loss-of-function mutants of NF-YCs show etiolated growth and constitutive BR responses, even in the light. Our findings uncover a dual role of NF-YCs in repressing BR biosynthesis and signaling, providing mechanistic insights into how light antagonizes the BR pathway to ensure photomorphogenic growth in Arabidopsis.

The Di2/pet variant in PETALOSA gene underlies a major heat requirement-related QTL for blooming date in peach (P. persica L. Batsch)

Environmental adaptation of deciduous fruit trees largely depends on their ability to synchronize growth and development with seasonal climate change. Winter dormancy of flower buds is a key process to prevent frost damage and ensure reproductive success. Temperature is a crucial environmental stimulus largely influencing the timing of flowering, only occurring after fulfillment of certain temperature requirements. Nevertheless, genetic variation affecting chilling or heat-dependent dormancy release still remains largely unknown. In this study, a major QTL able to delay blooming date in peach by increasing heat-requirement was finely mapped in three segregating progenies, revealing a strict association with a genetic variant (petDEL) in a PETALOSA gene, previously shown to also affect flower morphology. Analysis of segregating genome-edited tobacco plants provided further evidence of the potential ability of PET-variations to delay flowering time. Potential applications of the petDEL variant for improving phenological traits in peach are discussed.

Sources of predictive information in dynamical neural networks

Behavior involves the ongoing interaction between an organism and its environment. One of the prevailing theories of adaptive behavior is that organisms are constantly making predictions about their future environmental stimuli. However, how they acquire that predictive information is still poorly understood. Two complementary mechanisms have been proposed: predictions are generated from an agent’s internal model of the world or predictions are extracted directly from the environmental stimulus. In this work, we demonstrate that predictive information, measured using bivariate mutual information, cannot distinguish between these two kinds of systems. Furthermore, we show that predictive information cannot distinguish between organisms that are adapted to their environments and random dynamical systems exposed to the same environment. To understand the role of predictive information in adaptive behavior, we need to be able to identify where it is generated. To do this, we decompose information transfer across the different components of the organism-environment system and track the flow of information in the system over time. To validate the proposed framework, we examined it on a set of computational models of idealized agent-environment systems. Analysis of the systems revealed three key insights. First, predictive information, when sourced from the environment, can be reflected in any agent irrespective of its ability to perform a task. Second, predictive information, when sourced from the nervous system, requires special dynamics acquired during the process of adapting to the environment. Third, the magnitude of predictive information in a system can be different for the same task if the environmental structure changes.

Hypoxia uncouples HIF gene transcription and metabolic flux in proliferating primary cells

Hypoxia is an important environmental stimulus that causes transcriptional and metabolic reprogramming in cells to facilitate their survival. Here, we performed stable isotope tracing and metabolic flux analyses of proliferating primary cells in hypoxia. Despite activation of the hypoxia-inducible factor (HIF) transcriptional program and up-regulation of glycolytic genes, glycolytic flux was decreased in hypoxic cells in our models. No evidence for increased glutaminolysis or reductive carboxylation was observed. While pharmacologic stabilization of HIF in normoxia with the prolyl hydroxylase inhibitor molidustat did increase glycolytic flux as expected, hypoxia abrogated this effect. Together, these data suggest that primary cell bioenergetic metabolism is closely coupled to cell proliferation rate and that other regulatory factors override the effects of HIF-dependent up-regulation of glycolytic gene expression on glycolytic flux.

Cellular and molecular events of inflammation induced transdifferentiation (EMT) and regeneration (MET) in mesenteric mesothelial cells

In this review we summarize the cellular and molecular events of inflammation induced epithelial-to-mesenchymal (EMT) and mesothelial-to-macrophage transition (MET) during regeneration. Since the receptor transmits the environmental stimulus, downregulating or upregulating the process on an epigenetic level, the intracellular localization of receptors (signaling organelles: early endosomes or lysosomal degradation: late endosomes) plays a crucial role in the signaling events regulating inflammation and regeneration. Therefore, we focused on the internalization of the receptors as well as the intracellular compartmentalization of signaling molecules during EMT and MET. The review draws the reader’s attention to the plasticity of mesothelial cells and supports the idea that during inflammation an ambient macrophage population might derive from mesothelial cells.

C. elegans aversive olfactory learning generates diverse intergenerational effects

ABSTRACTParental experience can modulate the behavior of the progeny through the inheritance of phenotypic traits acquired by the progenitors. While the molecular mechanisms for behavioral inheritance are studied under several environmental conditions, it remains largely unexplored how the nature of the parental experience affects the information transferred to the next generation. To address this question we used C. elegans, a nematode that feeds on bacteria in its habitat. Some of these bacteria are pathogenic and the worm learns to avoid them after a brief exposure. We found, unexpectedly, that a short parental experience increased the preference for the pathogen in the progeny. Furthermore, increasing the time of parental exposure switched the response of the progeny from attraction to avoidance. To characterize the underlying molecular mechanisms, we found that the RNA-dependent RNA Polymerase (RdRP) RRF-3, required for the biogenesis of 26G endo-siRNAs, regulated both types of intergenerational effects. Together, we show that different parental experiences with the same environmental stimulus generate diverse effects on the behavior of the progeny through small RNA-mediated regulation of gene expression.