The insertion/deletion in the DNA-binding region allows the discrimination and subsequent identification of the glucocorticoid receptor 1 (gr1) and gr2 nucleotide sequences in gilthead sea bream (Sparus aurata): Standardizing the gr nomenclature for a better understanding of the stress response in teleost fish species

Cortisol carries out its physiological mechanism of action through the recognition by the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) 1 (GR1) and GR2. Previous studies reported that the main difference between gr1 and gr2 nucleotide sequences resides in a 27-nucleotide insertion/deletion in the DNA-binding region, respectively. However, in gilthead sea bream (Sparus aurata) the annotation for gr1 and gr2 seems contradictory. The gr2 sequence possesses the characteristic 27-nucleotide insertion that, in fact, is associated with the gr1 nucleotide sequence. Thus, this study aimed to elucidate the nucleotide sequences for the gr1 and gr2 in gilthead sea bream. The Clustal Omega alignment for different fish species corroborated the presence of such 27-nucleotide insertion/deletion in the DNA-binding region for gr1 and gr2, respectively. Then, we design specific primers set for the amplification of the gilthead sea bream gr1 by polymerase chain reaction (PCR). Importantly, the gr1 nucleotide partial sequence has a high similarity with other gr1 sequences already published for other fish species, being present in all of them the 27-nucleotide insertion in the DNA-binding region. We also detected that in European sea bass the gr1 and gr2 sequences had not been named according to the 27-nucleotide insertion/deletion criteria in the DNA-binding region. Thus, our study makes an urgent call to the scientific community to discuss the establishment of an updated agreement that allows homogenizing the criteria for the nomenclature defining the gr1 and gr2 nucleotide sequences for a better understanding of the stress response in teleost fish species.This study thanks to the AGL2016-76069-C2-2- R, PID2020-117557RB-C21, PID2020-117557RB-C22 grants (AEI-MINECO; Spain). EV-V thanks the support of Fondecyt iniciacion grant (project number 11221308; Agencia Nacional de Investigacion y Desarrollo de Chile, Government of Chile). AK was the recipient of a Ministry of Science, Research, and Technology (Iran) fellowship. MT thanks for the support of the post-doctoral fellowship "Ramon y Cajal" (ref. RYC2019-026841-I) (Ministerio de Ciencia e Innovacion, Spanish Government). FER-L thanks the support of Fondecyt regular grant (project number: 1211841; Agencia Nacional de Investigacion y Desarrollo de Chile, Government of Chile)

Comparison of Yarrowia lipolytica and Pichia pastoris cellular response to different agents of oxidative stress

Yeast cells exposed to adverse conditions employ a number of defense mechanisms in order to respond effectively to the stress effects of reactive oxygen species. In this work, the cellular response of Yarrowia lipolytica and Pichia pastoris to the exposure to the ROSinducing agents’ paraquat, hydrogen peroxide, and increased air pressure was analyzed. Yeast cells at exponential phase were exposed for 3 h to 1 mM paraquat, to 50 mM H2O2, or to increased air pressure of 3 or 5 bar. For both strains, the cellular viability loss and lipid peroxidation was lower for the cells exposed to increased air pressure than for those exposed to chemical oxidants. The glutathione induction occurred only in Y. lipolytica strain and reached the highest level as a response to PQ exposure. In general, antioxidant enzymes were more expressed in Y. lipolytica than in P. pastoris. The enzyme superoxide dismutase was induced in both strains under all the oxidant conditions but was dependent on the cellular growth phase, being undetectable in non-growing cells, whereas glutathione reductase was more induced in those conditions. Hydrogen peroxide was the most efficient inducer of catalase. Both yeast cultures underwent no cellular growth inhibition with increased air pressure, indicating that these yeast species were able to adapt to the oxidative stressful environment.The authors acknowledge the financial support provided by "Fundacao para a Ciencia e Tecnologia" (Grant SFRH/BD/47371/2008)

Including Smart Architecture in environments for people with dementia

Environments which aim to promote human well-being must address both functional and psychosocial needs. This paper comprises a description of a framework for a smart home environment, which aims to comprehensively address issues of environmental fit, in particular for a person with cognitive impairment associated with dementia, by means of introducing sensing of user affect as a factor in system management of a smart personal life space, and in generation of environmental response, adapting to changing user need. The introduction of affective computing into an intelligent system managing environmental response and adaptation is seen as a critical component in successfully realizing an interactive personal life-space, where a continuous feedback loop operates between user and environment, in real time. The overall intention is to maximize environmental congruence for the user, both functionally and psychosocially, by factoring in adjustment to changing user status. Design thinking, at all scales, is perceived as being essential to achieving a coherent smart environment, where architecture is reframed as interaction design

ROS release by PPARβ/δ-null fibroblasts reduces tumor load through epithelial antioxidant response.

Tumor stroma has an active role in the initiation, growth, and propagation of many tumor types by secreting growth factors and modulating redox status of the microenvironment. Although PPARβ/δ in fibroblasts was shown to modulate oxidative stress in the wound microenvironment, there has been no evidence of a similar effect in the tumor stroma. Here, we present evidence of oxidative stress modulation by intestinal stromal PPARβ/δ, using a FSPCre-Pparb/d <sup>-/-</sup> mouse model and validated it with immortalized cell lines. The FSPCre-Pparb/d <sup>-/-</sup> mice developed fewer intestinal polyps and survived longer when compared with Pparb/d <sup>fl/fl</sup> mice. The pre-treatment of FSPCre-Pparb/d <sup>-/-</sup> and Pparb/d <sup>fl/fl</sup> with antioxidant N-acetyl-cysteine prior DSS-induced tumorigenesis resulted in lower tumor load. Gene expression analyses implicated an altered oxidative stress processes. Indeed, the FSPCre-Pparb/d <sup>-/-</sup> intestinal tumors have reduced oxidative stress than Pparb/d <sup>fl/fl</sup> tumors. Similarly, the colorectal cancer cells and human colon epithelial cells also experienced lower oxidative stress when co-cultured with fibroblasts depleted of PPARβ/δ expression. Therefore, our results establish a role for fibroblast PPARβ/δ in epithelial-mesenchymal communication for ROS homeostasis

WldS Reduces Paraquat-Induced Cytotoxicity via SIRT1 in Non-Neuronal Cells by Attenuating the Depletion of NAD

WldS is a fusion protein with NAD synthesis activity, and has been reported to protect axonal and synaptic compartments of neurons from various mechanical, genetic and chemical insults. However, whether WldS can protect non-neuronal cells against toxic chemicals is largely unknown. Here we found that WldS significantly reduced the cytotoxicity of bipyridylium herbicides paraquat and diquat in mouse embryonic fibroblasts, but had no effect on the cytotoxicity induced by chromium (VI), hydrogen peroxide, etoposide, tunicamycin or brefeldin A. WldS also slowed down the death of mice induced by intraperitoneal injection of paraquat. Further studies demonstrated that WldS markedly attenuated mitochondrial injury including disruption of mitochondrial membrane potential, structural damage and decline of ATP induced by paraquat. Disruption of the NAD synthesis activity of WldS by an H112A or F116S point mutation resulted in loss of its protective function against paraquat-induced cell death. Furthermore, WldS delayed the decrease of intracellular NAD levels induced by paraquat. Similarly, treatment with NAD or its precursor nicotinamide mononucleotide attenuated paraquat-induced cytotoxicity and decline of ATP and NAD levels. In addition, we showed that SIRT1 was required for both exogenous NAD and WldS-mediated cellular protection against paraquat. These findings suggest that NAD and SIRT1 mediate the protective function of WldS against the cytotoxicity induced by paraquat, which provides new clues for the mechanisms underlying the protective function of WldS in both neuronal and non-neuronal cells, and implies that attenuation of NAD depletion may be effective to alleviate paraquat poisoning

Changing perceptions of hunger on a high nutrient density diet

<p>Abstract</p> <p>Background</p> <p>People overeat because their hunger directs them to consume more calories than they require. The purpose of this study was to analyze the changes in experience and perception of hunger before and after participants shifted from their previous usual diet to a high nutrient density diet.</p> <p>Methods</p> <p>This was a descriptive study conducted with 768 participants primarily living in the United States who had changed their dietary habits from a low micronutrient to a high micronutrient diet. Participants completed a survey rating various dimensions of hunger (physical symptoms, emotional symptoms, and location) when on their previous usual diet versus the high micronutrient density diet. Statistical analysis was conducted using non-parametric tests.</p> <p>Results</p> <p>Highly significant differences were found between the two diets in relation to all physical and emotional symptoms as well as the location of hunger. Hunger was not an unpleasant experience while on the high nutrient density diet, was well tolerated and occurred with less frequency even when meals were skipped. Nearly 80% of respondents reported that their experience of hunger had changed since starting the high nutrient density diet, with 51% reporting a dramatic or complete change in their experience of hunger.</p> <p>Conclusions</p> <p>A high micronutrient density diet mitigates the unpleasant aspects of the experience of hunger even though it is lower in calories. Hunger is one of the major impediments to successful weight loss. Our findings suggest that it is not simply the caloric content, but more importantly, the micronutrient density of a diet that influences the experience of hunger. It appears that a high nutrient density diet, after an initial phase of adjustment during which a person experiences "toxic hunger" due to withdrawal from pro-inflammatory foods, can result in a sustainable eating pattern that leads to weight loss and improved health. A high nutrient density diet provides benefits for long-term health as well as weight loss. Because our findings have important implications in the global effort to control rates of obesity and related chronic diseases, further studies are needed to confirm these preliminary results.</p

Robot Learning with Task-Parameterized Generative Models

Task-parameterized models provide a representation of movement/behavior that can adapt to a set of task parameters describing the current situation encountered by the robot, such as location of objects or landmarks in its workspace. This paper gives an overview of the task-parameterized Gaussian mixture model (TP-GMM) introduced in previous publications, and introduces a number of extensions and ongoing challenges required to move the approach toward unconstrained environments. In particular, it discusses its generalization capability and the handling of movements with a high number of degrees of freedom. It then shows that the method is not restricted to movements in task space, but that it can also be exploited to handle constraints in joint space, including priority constraints