Paternal mitochondria are eliminated following fertilization by selective autophagy, but the mechanisms that restrict this process to sperm-derived organelles are not well understood. FUNDC1 (FUN14 ...domain containing 1) is a mammalian mitophagy receptor expressed on the mitochondrial outer membrane that contributes to mitochondrial quality control following hypoxic stress. Like FUNDC1, the C. elegans ortholog FNDC-1 is widely expressed in somatic tissues and mediates hypoxic mitophagy. Here, we report that FNDC-1 is strongly expressed in sperm but not oocytes and contributes to paternal mitochondria elimination. Paternal mitochondrial DNA is normally undetectable in wildtype larva, but can be detected in the cross-progeny of fndc-1 mutant males. Moreover, loss of fndc-1 retards the rate of paternal mitochondria degradation, but not that of membranous organelles, a nematode specific membrane compartment whose fusion is required for sperm motility. This is the first example of a ubiquitin-independent mitophagy receptor playing a role in the selective degradation of sperm mitochondria.
•C. elegans selectively express the mitophagy receptor FNDC-1 on sperm mitochondria.•Loss of fndc-1 results in delayed paternal mitochondria elimination.•Loss of fndc-1 does not impact the removal of nematode-specific membranous organelles.
Elimination of paternal mitochondria after fertilization occurs in many species using the process of selective autophagy. The mechanism for targeting paternal mitochondria, but not maternal ...mitochondria, for elimination in the early embryo is not well understood. The results in this paper suggest that there are at least two different mechanisms for targeting paternal mitochondria for elimination: the first involving ubiquitination and a second involving a mitochondrial associated autophagy receptor, fndc-1. Elimination of paternal mitochondria can be visualized in embryos of the nematode, C. elegans. Paternal mitochondria enter the zygote at fertilization. Initially, they are closely associated with another sperm organelle, the membraneous organelle (MO). The MOs become ubiquitinated within minutes after fertilization. Simultaneous RNAi knockdown of two ubiquitin conjugating enzymes, ubc-18 and ubc-16, reduces MO ubiquitination. Loss of function of ubc-18 alone leads to loss of K48-linked polyubiquitin chains and halts the recruitment of proteasome to MOs. Interestingly, knockdown of ubc-18 or ubc-16 or the combination does not reduce the localization of K63-linked ubiquitin chains to MOs suggesting that some ubiquitin structure other than K63 chains is responsible for recruiting the autophagy machinery to MOs. Double knockdown (ubc-18/ubc-16) inhibits the recruitment of the autophagy protein, LGG-1 (homolog of LC3/GABARAP), to paternal organelles and causes the persistence of paternal mitochondria into the two cell stage. If paternal mitochondria are not eliminated via this early process, they are eventually removed from the embryo in a process that depends on the mitophagy adaptor protein, fndc-1. Thus, there are two redundant, but temporally distinct mechanisms that target paternal mitochondria for elimination in C. elegans. In addition to the involvement of ubiquitination in the elimination of paternal mitochondria, two subunits of the proteasome, rpn-10 and rad-23, are required for elimination of paternal mitochondria. These subunits are known to function as ubiquitin receptors and knockdown of either inhibits the recruitment of proteasome to ubiquitinated MOs. Their knockdown does not affect the localization of LGG-1 to paternal structures indicating that the proteasome is not required for autophagy membrane recruitment but might be involved in autophagosome maturation or its fusion with the lysosome.
•In C. elegans, ubc-18 and ubc-16 are E2 enzymes required for ubiquitination of paternal membranous organelles (MOs).•Ubiquitination of MOs is required for autophagosomes recruitment to the MOs after fertilization.•Ubiquitination of the MOs is required for the elimination of paternal mitochondria that occurs during the first cell cycle.•ubc-18 is required for K48 polyubiquitin chains on MOs.•Proteasome recruitment to MOs depends on both K48 ubiquitination and the ubiquitin receptors, rpn-10 and rad-23.•When proteasome localization to MOs is disrupted, autophagosomes still surround the MOs but paternal mitochondria persist.•Elimination paternal mitochondria after the 2 cell stage occurs via a ubiquitin-independent mechanism involving fndc-1.
This study investigated the development of emotion regulation strategies as reflected in the narratives of children between the ages of 3 and 6 years. An experimental procedure based on story ...completion tasks was devised to elicit the emotion‐related narratives of 69 preschool children. Coding of the narratives led to the observation of different emotion regulation strategies: Behavioural strategies, social support, and cognitive reappraisal. Several significant gender and age differences were identified in the use of these strategies. In addition, verbal skills, non‐verbal intelligence, and emotion comprehension were found to be associated with use of the observed emotion regulation strategies, although only at specific ages.
Social cognition is the way in which people process, remember, and use information in social contexts to explain and predict their own behavior and that of others. Children's social cognition may be ...influenced by multiple factors, both external and internal to the child. In the current study, two aspects of social cognition were examined: Theory of Mind and Emotion Understanding. The aim of this study was to analyze the effects of type of early care (0-3 years of age), maternal education, parents' country of birth, and child's language on the social cognition of 118 Italian preschoolers. To our knowledge, the joint effect of these variables on social cognition has not previously been investigated in the literature. The measures used to collect social cognition and linguistic data were not parent- or teacher-reports, but based on direct assessment of the children through two standardized tests, the Test of Emotion Comprehension and the ToM Storybooks. Relationships among the variables showed a complex pattern. Overall, maternal education and linguistic competence showed a systematic effect on social cognition; the linguistic competence mediated the effect of maternal education. In children who had experienced centre-base care in the first 3 years of life, the effect of maternal education disappeared, supporting the protective role of centre-base care for children with less educated mothers. The children with native and foreign parents did not significantly differ on the social cognition tasks. Limits of the study, possible educational outcomes and future research lines were discussed.
Play is a right for every child and has a key role in child development. Play can be analyzed according to the construct of playfulness, which is the child's disposition to play. Children with ...cerebral palsy (CP) show difficulties in play and can also experience lower playfulness scores when compared to matched typically developing children. This paper analyses play and playfulness in children with CP using mainstream robotic toys with supporting adult play partners.
Five mainstream robotic toys were selected and used in play situations with six children with CP interacting with two adult partners. The play situations were coded through the Test of Playfulness (ToP) and the Test of Environmental Supportiveness (ToES), to analyze the role of robotic toys, adult partners and environment in supporting play and playfulness in children with CP.
The children obtained high ToP scores, showing that they were intrinsically motivated to be engaged in the play situations. The ToP scores weakly correlated with the ToES scores. To discuss this result, different features of each robot, the role of adults as scaffolder, and the space characteristics in supporting play are presented and discussed.
This research field is new: to our knowledge, in the literature only one study focused on the use of one type of mainstream robotic toy to support the playfulness of children with CP. The parallel use of the ToP and the ToES was crucial to observe the complexity of the play situations and the role of playmates and toys during the play process. The role of the adult as play scaffolder has been important to mediate between the child with CP and the environment, toys included: the adult should be strongly aware of this role to better support the child in being in charge of the play situation. Further research is needed.
•A simheuristic method for multi-objective stochastic flow shop is proposed.•The simheuristic allows to obtain robust solutions by minimizing standard deviation.•We find Pareto fronts of expected ...tardiness and standard deviation of tardiness.•Two different probability distributions of processing times are tested.•Three different coefficients of variation of processing times are tested.
The aim of this paper is to present a simheuristic approach that obtains robust schedules for a multi-objective permutation flow shop problem with stochastic processing times. In fact, this approach minimizes the expected tardiness and standard deviation of tardiness, as a efficiency and a robustness measure for the stated problem. The simheuristic algorithm hybridize the Tabu Search metaheuristic and the Pareto Archived Evolution Strategy algorithm with a Monte Carlo Simulation process. At first, this approach is tested in 540 benchmarked instances for the deterministic case. It uses a zero-standard-deviation strategy to show the competitiveness compared with other implemented tabu search algorithms. Afterwards, two experimental designs are carried out, with the same 540 instances, where two factors of interest are considered, such as the probability distribution and coefficient of variation of processing times. The probability distributions used were the lognormal and uniform distributions, and three coefficients of variation (0.3, 0.4, and 0.5). Results show that both probability distributions and coefficients of variation have a significant effect in the objective functions, showing the importance of an accurate fitting of probability distributions of the parameter under uncertainty. In addition, these results evidence that the usage of deterministic methods in presence of random events are not desirable or recommended. Finally, the simheuristic was implemented to solve the scheduling problem in an optical laboratory showing better results for expected tardiness and standard deviation of tardiness in comparison with company schedules.
Different strategies have been developed to help parents with introducing new or disliked vegetables. Nonetheless, many parents of preschoolers struggle against children's refusal to eat vegetables. ...In this study, we aimed to evaluate the effectiveness of e-books in promoting positive attitudes toward vegetables through repeated visual exposures. A total of 61 families with preschoolers joined the See & Eat study and received an e-book about one of two vegetables chosen from a list of 24. Parents provided ratings of children's willingness to taste, intake, and liking of the chosen vegetables before and after reading the e-book; parents also evaluated their children's food fussiness and their agreement with respect to three mealtime goals of the family. Using a 2 (vegetable: target or non-target) × 2 (time: pre-test or post-test) within-subjects analysis, results from 53 families revealed a significant increase in children's willingness to taste, intake, and liking at post-test of both target and non-target vegetables. Following a two-week parent-child e-book reading intervention, children's food fussiness and parents' endorsement of positive mealtime goals slightly but significantly increased. Results suggest that e-books are effective in encouraging healthy eating among preschoolers and that the positive effect of e-book reading can generalize to other vegetables.
Bacteria belonging to Anaplasma, Ehrlichia, Rickettsia and Coxiella genera are considered emerging pathogens and livestock is one of the contexts where the transmission of these microorganisms can ...occur. The goal of this study was to determine serological evidence for the exposure to these bacteria in cattle and humans with occupational exposure to livestock in the subregions North and Magdalena Medio, Antioquia, Colombia, and to explore related factors. A cross-sectional study was conducted in 48 livestock farms distributed in six municipalities from both subregions: Belmira, Entrerríos and San Pedro de los Milagros (North), and Puerto Berrío, Puerto Nare and Puerto Triunfo (Magdalena Medio). Blood samples from 332 people and 384 bovines were evaluated by serology (IgM and IgG) screening for bacteria from the Anaplasma, Ehrlichia, Rickettsia, and Coxiella genera. Seropositivity in humans from both regions was 42.4% (95%CI: 31.2-55.1) for Anaplasma, 74.2% (95%CI: 66.0-84.4) for Ehrlichia, 72.5% (95%CI: 62.1-82.0) for Rickettsia, and 60.7% (95%CI: 59.7-69.1) for Coxiella burnetii. In cattle, seropositivity was 31.6% (95%CI: 19.9-44.2), 66.8% (95%CI: 55.2-78.1), 64.6% (95%CI: 53.8-74.5), and 61.6% (95%CI: 51.9-69.2), respectively. History of biting by ticks, milking, vaccination, having dogs and hens in the residence, as well as the consumption of raw milk derivatives were some factors associated with the infection by the bacteria studied. The results suggest a previous and recent exposure to these zoonotic bacteria genera in people with occupational exposure to livestock, as well as in cattle in the two studied subregions.