Lysosome-related organelles promote stress and immune responses in C. elegans.

Lysosome-related organelles (LROs) play diverse roles and their dysfunction causes immunodeficiency. However, their primordial functions remain unclear. Here, we report that C. elegans LROs (gut granules) promote organismal defenses against various stresses. We find that toxic benzaldehyde exposure induces LRO autofluorescence, stimulates the expression of LRO-specific genes and enhances LRO transport capacity as well as increases tolerance to benzaldehyde, heat and oxidative stresses, while these responses are impaired in glo-1/Rab32 and pgp-2 ABC transporter LRO biogenesis mutants. Benzaldehyde upregulates glo-1- and pgp-2-dependent expression of heat shock, detoxification and antimicrobial effector genes, which requires daf-16/FOXO and/or pmk-1/p38MAPK. Finally, benzaldehyde preconditioning increases resistance against Pseudomonas aeruginosa PA14 in a glo-1- and pgp-2-dependent manner, and PA14 infection leads to the deposition of fluorescent metabolites in LROs and induction of LRO genes. Our study suggests that LROs may play a role in systemic responses to stresses and in pathogen resistance.

The long-term impact of restricted access to abortion on children's socioeconomic outcomes.

We examine the long-term consequences of restricted access to abortion following a change in the Hungarian abortion law in 1974. Due to a change that restricted access to legal abortions, the number of induced abortions decreased from 169,650 to 102,022 between 1973 and 1974, whereas the number of live births increased from 156,224 to 186,288. We analyze the effects on the adult outcomes of the affected cohort of newborns (educational attainment, labor market participation, teen fertility). We use matched large-scale, individual-level administrative datasets of the Hungarian Central Statistical Office (population census 2011; live birth register), and we estimate the effects by comparing children born within a short timespan around the time the law change came into effect. We apply a difference-in-differences approach, building on the special rules of the new law that, despite the severe restriction, still made abortion permissible for selected groups of women. We control for the compositional change in the population of parents, rule out the effect of (unobserved) time trends and other potential behavioral responses to the law change, and draw causal inferences. We find that restricted access to abortion had, on average, a negative impact on the socioeconomic outcomes of the affected cohort of children. Children born after the law change have had worse educational outcomes, a greater likelihood of being unemployed at age 37, and a higher probability of being a teen parent.

Toxic stress-specific cytoprotective responses regulate learned behavioral decisions in C. elegans.

BACKGROUND: Recognition of stress and mobilization of adequate "fight-or-flight" responses is key for survival and health. Previous studies have shown that exposure of Caenorhabditis elegans to pathogens or toxins simultaneously stimulates cellular stress and detoxification responses and aversive behavior. However, whether a coordinated regulation exists between cytoprotective stress responses and behavioral defenses remains unclear. RESULTS: Here, we show that exposure of C. elegans to high concentrations of naturally attractive food-derived odors, benzaldehyde and diacetyl, induces toxicity and food avoidance behavior. Benzaldehyde preconditioning activates systemic cytoprotective stress responses involving DAF-16/FOXO, SKN-1/Nrf2, and Hsp90 in non-neuronal cells, which confer both physiological (increased survival) and behavioral tolerance (reduced food avoidance) to benzaldehyde exposure. Benzaldehyde preconditioning also elicits behavioral cross-tolerance to the structurally similar methyl-salicylate, but not to the structurally unrelated diacetyl. In contrast, diacetyl preconditioning augments diacetyl avoidance, weakens physiological diacetyl tolerance, and does not induce apparent molecular defenses. The inter-tissue connection between cellular and behavioral defenses is mediated by JNK-like stress-activated protein kinases and the neuropeptide Y receptor NPR-1. Reinforcement of the stressful experiences using spaced training forms stable stress-specific memories. Memory retrieval by the olfactory cues leads to avoidance of food contaminated by diacetyl and context-dependent behavioral decision to avoid benzaldehyde only if there is an alternative, food-indicative odor. CONCLUSIONS: Our study reveals a regulatory link between conserved cytoprotective stress responses and behavioral avoidance, which underlies "fight-or-flight" responses and facilitates self-protection in real and anticipated stresses. These findings imply that variations in the efficiency of physiological protection during past episodes of stress might shape current behavioral decisions.

Post-conception heat exposure increases clinically unobserved pregnancy losses.

Evidence of the relationship between temperature during pregnancy and human embryo mortality is limited. Most importantly, the literature lacks causal estimations and studies on early pregnancy losses. Here, we estimate the impact of early pregnancy temperature exposure on the clinically unobserved pregnancy loss rate. We use administrative data of clinically observed pregnancies from more than three decades for Hungary. We apply an empirical approach that allows us to infer the impact of temperature on the clinically unobserved pregnancy loss rate from the estimated effects on the clinically observed conception rate. The results show that exposure to hot temperatures during the first few weeks after the conception week increases the clinically unobserved pregnancy loss rate, whereas exposure to colder temperatures seems to decrease it. Importantly, the temperature-induced changes represent changes in the total number of pregnancy losses rather than a compositional change between clinically observed and clinically unobserved pregnancy losses.

A cellular defense memory imprinted by early life toxic stress.

Stress exposure early in life is implicated in various behavioural and somatic diseases. Experiences during the critical perinatal period form permanent, imprinted memories promoting adult survival. Although imprinting is widely recognized to dictate behaviour, whether it actuates specific transcriptional responses at the cellular level is unknown. Here we report that in response to early life stresses, Caenorhabditis elegans nematodes form an imprinted cellular defense memory. We show that exposing newly-born worms to toxic antimycin A and paraquat, respectively, stimulates the expression of toxin-specific cytoprotective reporters. Toxin exposure also induces avoidance of the toxin-containing bacterial lawn. In contrast, adult worms do not exhibit aversive behaviour towards stress-associated bacterial sensory cues. However, the mere re-encounter with the same cues reactivates the previously induced cytoprotective reporters. Learned adult defenses require memory formation during the L1 larval stage and do not appear to confer increased protection against the toxin. Thus, exposure of C. elegans to toxic stresses in the critical period elicits adaptive behavioural and cytoprotective responses, which do not form imprinted aversive behaviour, but imprint a cytoprotective memory. Our findings identify a novel form of imprinting and suggest that imprinted molecular defenses might underlie various pathophysiological alterations related to early life stress.

Smoking ban and health at birth: Evidence from Hungary.

In 2012, smoking restrictions were extended to hospitality venues in Hungary. Women working in bars and restaurants were primarily affected by the intervention. In this research, we analyze the effect of this smoking ban on the outcomes of their pregnancies. Using individual live birth, fetal loss, and infant mortality registry data, we examine the probability of live birth, indicators of health at birth, and the probability of death in the first year of life. We apply a difference-in-differences framework and show that the smoking ban has improved health at birth. We observed birth weight to increase by 56 g (95% CI: 4.2 to 106.8) and gestation length by 0.19 weeks (95% CI: 0.02 to 0.36). Due to the ban, the probability of being born with very low and low birth weight has decreased by 1.2 and 2.2 percentage points, respectively (95% CI: -0.2 to -2.2 and 0.06 to -4.4), and we see a 0.9 percentage points reduction in the chance of being born very preterm (95% CI: -0.03 to -1.9). We also observe a decrease in the probability of being born with a low Ponderal index (decrease of 4.1 percentage points, 95% CI: -0.7 to -7.5). Performing a series of robustness and placebo tests, we provide evidence that supports the causal interpretation of our results. We also show that the ban was more beneficial for newborns of parents with low educational attainment and at the bottom of the fetal health endowment distribution.

[Primary retroperitoneal enteric cyst in an adult]. / Primaer retroperitonealis enteralis ciszta egy felnottben.

The posterior mediastinum is the usual location of enteric cysts. They can be located at any part of the posterior mediastinum adjacent to the oesophagus, but communication with that structure is rare. Approximately 60 percent of the cysts occur in infants less than one year of age, and symptoms of tracheal or oesophageal obstruction are common. The cysts usually contain clear, colorless mucoid fluid. The authors describe here a successfully treated enteric cyst with an unusual, retroperitoneal location, which presented in an adult.