DNA methylation 6 mA and histone methylation involved in multi-/trans-generational reproductive effects in Caenorhabditis elegans induced by Atrazine

Atrazine (ATR), a widely used triazine herbicide, is an environmental endocrine disruptor that can cause health problems. However, whether there are multi/trans-generational reproductive impacts of ATR have not been studied. Therefore, in this study, Caenorhabditis elegans was used as a preferable model organism to identify the multi/trans-generational reproductive toxicity of ATR. Only parental C.elegans (P0) were exposed to different concentrations (0.0004–40 mg/L) for 48 h and the subsequent offspring (F1–F5) were grown under ATR-free conditions and ATR conditions.The results showed that ATR exposure during P0 decreased fecundity, including a reduction in fertilized eggs, oocytes, and ovulation rate, delayed gonadal development, and decreased the relative area of gonad arm and germ cell number. Furthermore, continuous ATR exposure (P0–F5) causes a significant increase in reproductive toxicity in subsequent generations, although no significant toxicity occurred in the P0 generation after exposure to environmental-related concentrations, suggesting that ATR exposure might have cumulative effects. Likewise, parental exposure to ATR caused transgenerational toxicity impairments. Interestingly, only reproductive toxicity, not development toxicity, was transmitted to several generations (F1–F4), and the F2 generation showed the most notable changes. QRT-PCR results showed that genes expression related to DNA methylation 6 mA (damt-1, nmad-1) and histone H3 methylation (mes-4, met-2, set-25, set-2, and utx-1) can also be passed on to offspring. The function of H3K4 and H3K9 methylation were explored by using loss-of-function mutants for set-2, set-25, and met-2. Transmissible reproductive toxicity was absent in met-2(n4256), set-2(ok952), and set-25(n5021) mutants, which suggests that the histone methyltransferases H3K4 and H3K9 activity are indispensable for the transgenerational effect of ATR. Finally, the downstream genes of DNA methylation and histone H3 methylation were determined. ATR upregulated the expression of ZC317.7, hsp-6, and hsp-60. Mitochondrial stress in parental generation dependent transcription 6 mA modifiers may establish these epigenetic marks in progeny

Farpls:A Feature-Augmented Robot Trajectory Preference Labeling System to Assist Human Labelers' Preference Elicitation

Preference-based learning aims to align robot task objectives with human values. One of the most common methods to infer human preferences is by pairwise comparisons of robot task trajectories. Traditional comparison-based preference labeling systems seldom support labelers to digest and identify critical differences between complex trajectories recorded in videos. Our formative study (N = 12) suggests that individuals may overlook non-salient task features and establish biased preference criteria during their preference elicitation process because of partial observations. In addition, they may experience mental fatigue when given many pairs to compare, causing their label quality to deteriorate. To mitigate these issues, we propose FARPLS, a Feature-Augmented Robot trajectory Preference Labeling System. FARPLS highlights potential outliers in a wide variety of task features that matter to humans and extracts the corresponding video keyframes for easy review and comparison. It also dynamically adjusts the labeling order according to users' familiarities, difficulties of the trajectory pair, and level of disagreements. At the same time, the system monitors labelers' consistency and provides feedback on labeling progress to keep labelers engaged. A between-subjects study (N = 42, 105 pairs of robot pick-and-place trajectories per person) shows that FARPLS can help users establish preference criteria more easily and notice more relevant details in the presented trajectories than the conventional interface. FARPLS also improves labeling consistency and engagement, mitigating challenges in preference elicitation without raising cognitive loads significantl