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Chromatin-based epigenetic memory relies on the accurate distribution of parental histone H3-H4 tetramers to newly replicated DNA strands. Mcm2, a subunit of the replicative helicase, and Dpb3/4, subunits of DNA polymerase ε, govern parental histone H3-H4 deposition to the lagging and leading strands, respectively. However, their contribution to epigenetic inheritance remains controversial. Here, using fission yeast heterochromatin inheritance systems that eliminate interference from initiation pathways, we show that a Mcm2 histone binding mutation severely disrupts heterochromatin inheritance, while mutations in Dpb3/4 cause only moderate defects. Surprisingly, simultaneous mutations of Mcm2 and Dpb3/4 stabilize heterochromatin inheritance. eSPAN (enrichment and sequencing of protein-associated nascent DNA) analyses confirmed the conservation of Mcm2 and Dpb3/4 functions in parental histone H3-H4 segregation, with their combined absence showing a more symmetric distribution of parental histone H3-H4 than either single mutation alone. Furthermore, the FACT histone chaperone regulates parental histone transfer to both strands and collaborates with Mcm2 and Dpb3/4 to maintain parental histone H3-H4 density and faithful heterochromatin inheritance. These results underscore the importance of both symmetric distribution of parental histones and their density at daughter strands for epigenetic inheritance and unveil distinctive properties of parental histone chaperones during DNA replication.

BackgroundEvidence of an association between maternal use of anti-seizure medication (ASM) during pregnancy and the risk of autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children is conflicting. This systematic review and meta-analysis aimed to summarize the relationship between fetal exposure to ASM and the development of ASD or ADHD in offspring.MethodsA comprehensive literature search was conducted in PubMed and other databases to identify relevant epidemiological studies published from inception until 1 March 2024.ResultsSeven cohort studies were included in the meta-analysis. The results showed that maternal exposure to ASMs during pregnancy was associated with an increased risk of ASD [odds ratio (OR): 2.1, 95% confidence interval (CI): 1.63–2.71; p

Genetic targeting (e.g., gene knockout and tagging) based on polymerase chain reaction (PCR) is a simple yet powerful approach for studying gene functions. Although originally developed in classic budding and fission yeast models, the same principle applies to other eukaryotic systems with efficient homologous recombination. One‐step PCR‐based genetic targeting is conventionally used but the sizes of the homologous arms that it generates for recombination‐mediated genetic targeting are usually limited. Alternatively, gene targeting can also be performed via fusion PCR, which can create homologous arms that are orders of magnitude larger, therefore substantially increasing the efficiency of recombination‐mediated genetic targeting. Here, we present GetPrimers (https://www.evomicslab.org/app/getprimers/), a generalized computational framework and web tool to assist automatic targeting and verification primer design for both one‐step PCR‐based and fusion PCR‐based genetic targeting experiments. Moreover, GetPrimers by design runs for any given genetic background of any species with full genome scalability. Therefore, GetPrimers is capable of empowering high‐throughput functional genomic assays at multipopulation and multispecies levels. Comprehensive experimental validations have been performed for targeting and verification primers designed by GetPrimers across multiple organism systems and experimental setups. We anticipate GetPrimers to become a highly useful and popular tool to facilitate easy and standardized gene modification across multiple systems. Take‐away: Developed GetPrimers for generalized primer design of PCR‐based genetic targeting.GetPrimers shines with its high versatility and genome‐wide scalability.GetPrimers was validated across multiple organisms and experimental setups. [ABSTRACT FROM AUTHOR]

The phthalic acid esters (PAEs) are one class of the most abundant and frequently studied pseudo-persistent organic pollutants. Noninvasive urine is an effective substrate for evaluating PAE exposure, but repeated sampling is needed to overcome this bias. This adds much work to on-site collection and the cost of detection increases exponentially. Therefore, the aim of this study was to conduct a scope review to describe the detection methods and validity of the use of other noninvasive matrices, such as nails and hair, for assessing long-term exposure to PAEs. The PubMed, Web of Science and China National Knowledge Infrastructure (CNKI), electronic databases were searched from 1 January 2000 to 3 April 2024, and 12 studies were included. Nine and three studies used hair and nails, respectively, as noninvasive matrices for detecting PAE exposure. Five articles compared the results of nail or hair and urine tests for validity of the assessment of PAE exposure. The preprocessing and detection methods for these noninvasive samples are also described. The results of this review suggest that, compared with nails, hair may be more suitable as a noninvasive alternative matrix for assessing long-term exposure to PAEs. However, sample handling procedures such as the extraction and purification of compounds from hair are not uniform in various studies; therefore, further exploration and optimization of this process, and additional research evidence to evaluate its effectiveness, are needed to provide a scientific basis for the promotion and application of hair detection methods for assessing long-term PAE exposure levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Chen, Mo, Shan, Zhu, Gao and Tao.)

Chromatin-based epigenetic memory relies on the symmetric distribution of parental histones to newly synthesized daughter DNA strands, aided by histone chaperones within the DNA replication machinery. However, the mechanism of parental histone transfer remains elusive. Here, we reveal that in fission yeast, the replisome protein Mrc1 plays a crucial role in promoting the transfer of parental histone H3-H4 to the lagging strand, ensuring proper heterochromatin inheritance. In addition, Mrc1 facilitates the interaction between Mcm2 and DNA polymerase alpha, two histone-binding proteins critical for parental histone transfer. Furthermore, Mrc1's involvement in parental histone transfer and epigenetic inheritance is independent of its known functions in DNA replication checkpoint activation and replisome speed control. Instead, Mrc1 interacts with Mcm2 outside of its histone-binding region, creating a physical barrier to separate parental histone transfer pathways. These findings unveil Mrc1 as a key player within the replisome, coordinating parental histone segregation to regulate epigenetic inheritance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Evidence of an association between maternal use of anti-seizure medication (ASM) during pregnancy and the risk of autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children is conflicting. This systematic review and meta-analysis aimed to summarize the relationship between fetal exposure to ASM and the development of ASD or ADHD in offspring., Methods: A comprehensive literature search was conducted in PubMed and other databases to identify relevant epidemiological studies published from inception until 1 March 2024., Results: Seven cohort studies were included in the meta-analysis. The results showed that maternal exposure to ASMs during pregnancy was associated with an increased risk of ASD [odds ratio (OR): 2.1, 95% confidence interval (CI): 1.63-2.71; p  < 0.001] in the general population. This association became weaker (ASD: OR: 1.38, 95% CI: 1.11-1.73; p  = 0.004) when the reference group was mothers with a psychiatric disorder or epilepsy not treated during pregnancy. Furthermore, an increased risk of ADHD was observed when the study data adjusted for drug indications were pooled (OR: 1.43, 95% CI: 1.07-1.92; p  = 0.015). In subgroup analyses based on individual ASM use, only exposure to valproate preconception was significantly associated with an increased risk of ASD or ADHD., Conclusion: The significant association between maternal ASM use during pregnancy and ASD or ADHD in offspring may be partially explained by the drug indication or driven by valproate., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Zhong, Jiang and Tang.)

Background: This study was designed to assess stress levels and related factors during the coronavirus disease 2019 (COVID-19) epidemic among individuals in centralized quarantine camps in Wenzhou, China., Methods: The survey was conducted using a questionnaire. The questionnaire included questions on sociodemographic characteristics, life events related to the COVID-19 and stressful situations, as well as Perceived Stress Scale-14. Participants included close contacts of patients with COVID-19 or at-risk individuals in quarantine camps. Multivariate logistic regression was used to analyze different factors affecting perceived stress., Results: The prevalence of high stress among quarantine camp participants was 37.45%. Of the 881 respondents, 51.99% were concerned about the difficulty of controlling the epidemic, 46.20% were concerned about the health of themselves and their family members and 39.61% were concerned about not being able to leave their homes. Multivariate logistic regression analysis revealed statistically significant differences in the prevalence of stress among different groups for certain variables, including occupation, education level and knowledge of COVID-19 (all P < 0.05). Our study found that at-risk individuals and close contacts experienced high levels of stress in quarantine camps during the COVID-19 pandemic., Conclusions: These findings suggest that centralized quarantine policies should be adapted and optimized to minimize negative psychological effects on quarantined individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)