Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1

Background: AML1/RUNX1 is the most frequently mutated gene in leukaemia and is central to the normal biology of hematopoietic stem and progenitor cells. However, the role of different AML1 isoforms within these primitive compartments is unclear. Here we investigate whether altering relative expression of AML1 isoforms impacts the balance between cell self-renewal and differentiation in vitro and in vivo. Methods and Findings: The human AML1a isoform encodes a truncated molecule with DNA-binding but no transactivation capacity. We used a retrovirus-based approach to transduce AML1a into primitive haematopoietic cells isolated from the mouse. We observed that enforced AML1a expression increased the competitive engraftment potential of murine long-term reconstituting stem cells with the proportion of AML1a-expressing cells increasing over time in both primary and secondary recipients. Furthermore, AML1a expression dramatically increased primitive and committed progenitor activity in engrafted animals as assessed by long-term culture, cobblestone formation, and colony assays. In contrast, expression of the full-length isoform AML1b abrogated engraftment potential. In vitro, AML1b promoted differentiation while AML1a promoted proliferation of progenitors capable of short-term lymphomyeloid engraftment. Consistent with these findings, the relative abundance of AML1a was highest in the primitive stem/progenitor compartment of human cord blood, and forced expression of AML1a in these cells enhanced maintenance of primitive potential both in vitro and in vivo. Conclusions: These data demonstrate that the "a" isoform of AML1 has the capacity to potentiate stem and progenitor cell engraftment, both of which are required for successful clinical transplantation. This activity is consistent with its expression pattern in both normal and leukaemic cells. Manipulating the balance of AML1 isoform expression may offer novel therapeutic strategies, exploitable in the contexts of leukaemia and also in cord blood transplantation in adults, in whom stem and progenitor cell numbers are often limiting. © 2007 Tsuzuki et al

Traceless Cross-Linker for Photocleavable Bioconjugation

Photoresponsive bioconjugation empowers the development of novel methods for drug discovery, disease diagnosis, and high-throughput screening, among others. In this paper, we report on the characteristics of a traceless photocleavable cross-linker, di-6-(3-succinimidyl carbonyloxymethyl-4-nitro-phenoxy)-hexanoic acid disulfide diethanol ester (SCNE). The traceless feature and the biocompatibility of this photocleavable cross-linking reagent were corroborated. Consequently, we demonstrated its application in reversible phage particle immobilization that could provide a platform for direct single-phage screening. We also applied it in protein-photoprinting, where SCNE acts as a “photo-eraser” to remove the cross-linked protein molecules at a desired region in a simple, clean, and light-controllable fashion. We further demonstrated the two-tier atomic force microscopic (AFM) method that uses SCNE to carry out two subsequent AFM tasks <i>in situ</i>. The approach allows guided protein delivery and subsequent high-resolution imaging at the same local area, thus opening up the possibility of monitoring protein functions in live cells. The results imply that SCNE is a versatile cross-linker that can be used for a wide range of applications where photocleavage ensures clean and remote-controllable release of biological molecules from a substrate

Maternal cooking during pregnancy may increase hyperactive behaviors among children aged at around 3 years old

Cooking is one of the main sources of indoor air pollution in China. Given emerging evidence of a link between air pollutants and neurodevelopmental delays, we examined whether maternal experiences with cooking during gestation might increase their child's hyperactivity at 3 years of age. The participants involved 45 518 mothers of children who were newly enrolled at kindergarten in the Longhua District of Shenzhen from 2015 to 2017. The results show that maternal exposure to cooking fumes during pregnancy was related to an increased risk of their offspring having hyperactivity behaviors at the age of 3 years. Compared with pregnant mothers who never cooked, pregnant mothers who cooked sometimes, often, or always had children who showed a significantly higher hyperactivity risk. Households using cooking fuels such as coal, gas during the mothers’ pregnancy, exhibited more hyperactivity behaviors in the young child when compared to those using electricity for cooking. In addition, poor ventilation during cooking, while mothers were pregnant, was found to be a significant risk factor for clinical levels of the offspring's hyperactive behaviors. Furthermore, the positive association with maternal cooking during pregnancy and their offsprings’ hyperactivity was relatively consistent across strata defined by social class, education, and other covariates

Prenatal exposure to environmental tobacco smoke and hyperactivity behavior in Chinese young children

This study aimed to examine the association between prenatal environmental tobacco smoke (ETS) exposure and hyperactivity behaviors in young children. A cross-sectional study was undertaken among 21,243 participants from all of the kindergartens in Longhua District of Shenzhen, China. Multivariate logistic regression models and hierarchical linear models were employed to assess the associations. After adjusting for potential confounders of gender, preterm birth, birth asphyxiation, etc., prenatal ETS exposure was significantly associated with an increased risk of hyperactivity behaviors in young children (OR (95% CI) = 1.51 (1.28–1.77); β (95% CI) = 0.017 (0.013–0.020)). Along with increases in children’s prenatal ETS exposure dose (measured by daily ETS exposure duration, daily cigarette consumption by household members, and overall score of prenatal ETS exposure), the children were also increasingly more likely to exhibit hyperactivity behaviors. Furthermore, children whose mothers had prenatal ETS exposure in any one or more of the pregnancy trimesters were more likely to exhibit hyperactivity behaviors as compared with those born to non-exposure mothers (all p < 0.05). Overall, prenatal ETS exposure could be associated with a detrimental impact on offspring’s hyperactivity behaviors, and public health efforts are needed to reduce prenatal ETS exposure

Family childcare types and conduct problem behaviors in young children: The mediation role of caregiver-child interaction

Background: Previous studies have demonstrated the impacts of genetic, family, and community factors on child conduct problems (CPs). However, little is understood regarding the association between family childcare types and child conduct problem behaviors, as well as whether and to what extent caregiver-child interaction mediates the above association. Methods: 9,289 children first entering kindergartens in the Longhua New District of Shenzhen, China were enrolled in this cross-sectional study. Primary caregivers were invited to fulfill a self-administered structured questionnaire containing data regarding socio-demographics, family childcare types, caregiver-child interaction, and child conduct problem behaviors (measured by the Conners' Conduct Problem Subscale). A series of multiple logistic and linear regression models were employed to assess the associations among family childcare, caregiver-child interaction, and child conduct problem behaviors. Results: Family childcare types other than by parents together (i.e., mother alone, mother with others, grandparents, or changing caregivers) were all significantly associated with higher risks of conduct problem behaviors in young children (adjusted ORs ranged from 2.18 to 2.55, and adjusted βs ranged from 0.043 to 0.073; all p < 0.05), after adjusting for confounders including child age, gender, parental education level, parental age at pregnancy, marital status, and family income. The following family childcare types (mother alone, or grandparents, or changing caregivers) vs. the childcare by parents together showed significant relative indirect effects on conduct problem behaviors through caregiver-child interaction, indicating the significant mediation effect of caregiver-child interaction on the above associations. Mediation of caregiver-child interaction on the effect of being cared by mother with others relative to care by parents together on child conduct problem behaviors was yet non-significant. Conclusions: Family childcare types other than by parents together are associated with increased risks for conduct problem behaviors in young children. Caregiver-child interaction may function as a potential mediator for the above association

Association between prenatal exposure to household inhalants exposure and ADHD-like behaviors at around 3 years of age: Findings from Shenzhen Longhua Child Cohort Study

Background Prenatal exposure to air pollutants has been suggested as a possible etiologic factor for the occurrence of ADHD or ADHD-like behaviors. But we still lack a comprehensive assessment of household air pollutants exposure on the development of ADHD-like behaviors during childhood. Object We aimed to assess whether prenatal household inhalants exposure is associated with preschoolers’ ADHD-like behaviors in a nonclinical population. Methods This study used the baseline data of the Longhua Child Cohort Study. During 2015–2017, we recruited 42,983 mothers and their kindergarten-aged children who enrolled at kindergarten in the Longhua district of Shenzhen, to obtain the demographic data and relevant exposure information through self-administrated questionnaire survey. The source of prenatal household inhalants exposure include cooking fumes, environmental tobacco smoke, mosqutio coils, home renovated and indoor burning incense. Logistic and censored least absolute deviations (CLAD) models were used to reveal the association between prenatal exposure to household air pollutants and hyperactive behaviors in child. Results We found that exposure to five types of household inhalants during pregnancy were independently associated with an increased risk of child hyperactive behaviors. Moreover, we observed a significant interaction between exposure to environmental tobacco smoke and cooking fumes during gestation on child hyperactive behaviors in CLAD models. We also found a significant joint effect between burning mosquito coils and incense during gestation for child hyperactive behaviors risk both in CLAD and Logistic models. Furthermore, a household inhalants exposure index was used to demonstrate a dose-response relationship between the cumulative effect of exposure to the five household air pollutants and child hyperactivity. Conclusions Our results suggest that prenatal exposure to different household inhalants might increase the risk of children's hyperactive behaviors at around 3 years of age with the presence of interaction effects between some inhalants

Teacher's type D personality and Chinese children's hyperactive behaviors: Moderation effect of parental type D personality and mediation effect of teacher-student relationship

This study aimed to explore the association between teacher’s type D personality (TDP) and children’s hyperactive behaviors, along with the moderation effect of parental TDP and the mediation effect of the teacher–student relationship. In this prospective study, a total of 25,852 children were surveyed from 2014 to 2016 in Longhua District of Shenzhen, China, and followed up 1 year later. At baseline, parents provided data on parental TDP and children’s hyperactive behaviors, while teachers reported on their TDP. At follow-up, parents provided data on children’s hyperactive behaviors again, and teachers described their relationship with each student. Two-level multilevel logistic models were conducted to assess the influence of a teacher’s TDP, parental TDP, and their interaction on children’s hyperactive behaviors. Mediation analysis was used to examine the mediating role of the teacher–student relationship. Results indicated that teachers’ TDP was not a significant predictor of children’s hyperactive behaviors after 1 year in kindergarten. Conversely, maternal and paternal TDP were prospectively and positively associated with children’s subsequent hyperactive behaviors. However, the children with a TDP teacher, a TDP mother, and/or a TDP father had higher risk of hyperactive behaviors than those with either a TDP teacher or a TDP mother or a TDP father. In addition, the teacher–student relationship was not a significant mediator between teacher’s TDP and children’s hyperactive behaviors. Further, researchers may consider the effect of the combination of teacher’s TDP, maternal TDP, and paternal TDP on hyperactive behaviors in children in further studies.</p