These findings demonstrate that exposure to famine during early life including prenatal period and early childhood facilitates aging-associated cognitive deficits.

BackgroundAlcohol is detrimental to early development. Fetal alcohol spectrum disorders (FASD) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. Previous studies have been shown that ethanol exposure causes neural crest (NC) apoptosis and perturbation of neural crest migration. However, the underlying mechanism remains elusive. In this report we investigated the fetal effect of alcohol on the process of neural crest development in the Xenopus leavis.ResultsPre-gastrulation exposure of 2-4% alcohol induces apoptosis in Xenopus embryo whereas 1% alcohol specifically impairs neural crest migration without observing discernible apoptosis. Additionally, 1% alcohol treatment considerably increased the phenotype of small head (43.4% ± 4.4%, total embryo n = 234), and 1.5% and 2.0% dramatically augment the deformation to 81.2% ± 6.5% (n = 205) and 91.6% ± 3.0% (n = 235), respectively (P < 0.05). Significant accumulation of Homocysteine was caused by alcohol treatment in embryos and 5-mehtyltetrahydrofolate restores neural crest migration and alleviates homocysteine accumulation, resulting in inhibition of the alcohol-induced neurocristopathies.ConclusionsOur study demonstrates that prenatal alcohol exposure causes neural crest cell migration abnormality and 5-mehtyltetrahydrofolate could be beneficial for treating FASD.

Purpose Employing multi-type laborers (MLs) is common in multinational and cross-culture projects (MPCs). Different attributes of MLs can lead to uncertain and dynamic laborer behaviors (i.e. behavioral diversities), which may cause project deviations. Previous studies do not consider the uncertainties or dynamics of behaviors adequately or they only provide general suggestions. The purpose of this paper is to combine system dynamics (SD) and agent-based modeling (ABM) to build an integrated model. The proposed ABM-SD can gain better understanding of MLs’ behavioral diversities, reveal the associated impacts and improve project management. Design/methodology/approach Based on extensively review in construction labor management and computer simulation, architecture is built to depict the relationships between the affecting factors of MLs’ behaviors, MLs’ behavioral diversities and project performance. Second, conceptual structures of the ABM-SD model are developed. Third, methods to implement the model in practice are introduced, focusing on data collection and model structure adjustment. Finally, the model is tested in a case study. Findings Different ML groups have distinctive behaviors which constantly change through interactions between MLs, engineers and external environment. Inadequate consideration of the diversities can result in inaccurate estimation of productivity, work quality and absenteeism, causing severe project deviations such as schedule delay, cost overrun and high absenteeism. On the other hand, using the ABM-SD model, the root causes of project deviations are analyzed from the perspective of MLs’ behavioral diversities and the optimization of labor management can significantly improve project performance. Research limitations/implications This paper supplements previous studies because the ABM-SD model takes fully use of the strength of simulation of solving uncertain and dynamic problems and combines both qualitative and quantitative findings in existing studies of labor management. Besides, the ABM-SD model is also a practical management tool to better monitor laborer behaviors and forecast the impacts. The limitation is mainly about the small scale of the case study. However, the ABM-SD model already demonstrates the mechanism about how MLs’ different behaviors affect a project, which fulfill the aim of the study. Practical implications The ABM-SD model can simulate MLs’ behavioral diversities and produce reliable estimations of project performance. It also allows to optimize management plans. Furthermore, The ABM-SD model is adjustable based on specific project conditions, which make it applicable for different tasks, different laborer compositions and even different projects. Thus, the ABM-SD model can be a practical tool for engineers in MCPs. Originality/value SD and ABM are applied to study behaviors with well-known benefits in both separated and integrated manner. However, few studies use the approach to investigate MLs’ behaviors in MCPs. Hence, the proposed ABM-SD model is an original attempt to improve the laborer management level in MCPs.

Apolipoprotein E (ApoE) plays a vital role in cholesterol metabolism and its allele polymorphisms have been associated with several diseases including Alzheimer's disease (AD). There are few systematic studies on ApoE polymorphism and its association with AD in Chinese population. To examine this issue, participants included 4251 subjects and 404 AD patients with 390 healthy elderly residing in Chongqing city were genotyped. The results showed that the ε3 allele presented the highest frequency (82%), followed by ε4 (6.25%) and ε2 (11.75%) in general population. ε3/ε3 genotype carriers are the most common ones (64.19%) and the ε4/ε4 had the lowest frequency (0.59%). The frequency of ApoEε4 allele frequency in AD (15.35%) was significantly higher than control (10.00%). Those carriers of two ε4 allele have five time higher risk to develop AD. Our study demonstrate that ApoEε4 allele is a risk factor of AD for Chinese population.

Ketamine is a potent dissociative anesthetic and the most commonly used illicit drug. Many addicts are women at childbearing age. Although ketamine has been extensively studied as a clinical anesthetic, its effects on embryonic development are poorly understood. Here, we applied the Xenopus model to study the effects of ketamine on development. We found that exposure to ketamine from pre-gastrulation (stage 7) to early neural plate (stage 13.5) resulted in disruption of neural crest (NC) derivatives. Ketamine exposure did not affect mesoderm development as indicated by the normal expression of Chordin, Xbra, Wnt8, and Fgf8. However, ketamine treatment significantly inhibited Zic5 and Slug expression at early neural plate stage. Overexpression of Zic5 rescued ketamine-induced Slug inhibition, suggesting the blockage of NC induction was mediated by Zic5. Furthermore, we found Notch signaling was altered by ketamine. Ketamine inhibited the expression of Notch targeted genes including Hes5.2a, Hes5.2b, and ESR1 and ketamine-treated embryos exhibited Notch-deficient somite phenotypes. A 15 bp core binding element upstream of Zic5 was induced by Notch signaling and caused transcriptional activation. These results demonstrated that Zic5 works as a downstream target gene of Notch signaling in Xenopus NC induction. Our study provides a novel teratogenic mechanism whereby ketamine disrupts NC induction via targeting a Notch-Zic5 signaling pathway.