Social stress can affect the ability of fish to respond to various stressors, such as pathogens or environmental variations. In this paper, the effects of social stress on gilt-head bream (Sparus aurata) were investigated. To study the effects of physiological stress, we evaluated biochemical and cellular parameters, such as cortisol, glucose, lactate, osmolarity, and phagocytosis, 24 h after the establishment of social hierarchy in a group of three fish. Social hierarchy was determined and characterized by behavioral observation (aggressive acts and feeding order) of the specimens (dominant: “α”; subordinate: “β” and “γ”). After the establishment of social hierarchy, we observed that, overall, levels of plasma cortisol and other biochemical plasmatic stress markers (glucose and lactate) were higher in subordinate individuals than in dominant individuals. In addition, the modulation of phagocytic activity of the peritoneal exudate cells (PECs) demonstrated that social stress appeared to affect immune response. Finally, principal component analysis clearly separated the subordinate fish groups from the dominant groups, based on stress markers and the phagocytic activity of peritoneal exudate cells. This study contributes to current knowledge on gilt-head sea bream, helping to understand the link between social stress, behavior, and physiology of this species, relevant in the aquaculture sector, where fish are subjected to several kinds of stress.

Fertility rates in the developing world have dramatically dropped in the last decades. This drop is likely due to a decline in sperm quality and women having children at older ages. Loss of function mutations in DJ-1 , a Parkinson’s associated gene, are linked to alterations in multiple cellular processes such as mitochondrial activity, ROS production or sperm motility and lead to an early onset of Parkinson’s disease and male infertility in humans and other species. Glycolate (GA) and D-lactate (DL), products of DJ-1 glyoxalase activity, sustain mitochondrial function and protect against environmental aggressions. We, therefore, tested whether these substances could also have a rescue effect on these phenotypes. Here, we show that DJ-1 loss of function not only affects sperm motility but also leads to defects in mitosis and an age-dependent increase in the abortion rate. Remarkably, whereas DL was only able to rescue embryonic lethality in C. elegans , GA rescued these phenotypes in all model systems tested and even increased sperm motility in wild-type sperm. These positive effects seem to be mediated through an increase in NAD(P)H production and the regulation of intracellular calcium. These findings not only strongly suggest GA as a new therapeutic candidate to improve male and female fertility but also show its potential to treat diseases associated with a decline in mitochondrial function or to improve mitochondrial function in aging.

Competitive interactions between tumor cells and surrounding healthy cells are constantly present during the progression of a solid tumor, and their outcome has been proposed to affect the clinical behavior. Previous studies have described various mechanistic and molecular aspects that characterize this process, overall indicating that cancer cells behave as supercompetitors, which eliminate neighboring healthy cells to gain vital space for growth and infiltration of the tissue. Nevertheless, there is a lack of systematic characterization of these competitive interactions, particularly in the context of cancer in mammals. Furthermore, previous studies in the field of cell competition have primarily focused on homotypic cell competition, involving different clones of the same cell or cells deriving from the same tissue. Data are scarce regarding heterotypic cell competition between two unrelated cell types, which is particularly critical for the understanding of metastatic tumors. In this research, we study cell competition in the context of liver metastases, providing a broad characterization of this process in different relevant scenarios, including cells growing in vitro in 2D and 3D, and in vivo . Results show that in vitro , only a subset of cancer cell lines are coherently strong or moderate competitors against hepatocytes, while the remaining demonstrate poor competitiveness. The competitive proficiency can vary depending on the experimental growth system that is employed, and often predicts the phenotype of liver metastases in terms of aggressiveness and morphology. Finally, our data point towards an involvement of mechanical competition in determining the supercompetitor trait of cancer cells. Altogether, our research provides the first comprehensive characterization of heterotypic cell competition, and indicates that cancer cells possess heterogeneous competitive proficiency towards hepatocytes which can be affected by the growth conditions.