No abstract

Trauma or neurodegenerative diseases trigger the retrograde death of retinal ganglion cells (RGCs), causing an irreversible functional loss. AT-rich interaction domain 1A (ARID1A), a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex, has been shown to play crucial roles in cell homeostasis and tissue regeneration. However, its function in adult RGC regeneration remains elusive. Here, we show that optic nerve injury induces dynamic changes of Arid1a expression. Importantly, deleting Arid1a in mice dramatically promotes RGC survival, but insignificantly impacts axon regeneration after optic nerve injury. Next, joint profiling of transcripts and accessible chromatin in mature RGCs reveals that Arid1a regulates several genes involved in apoptosis and JAK/STAT signaling pathway. Thus, our findings suggest modulation of Arid1a as a potential therapeutic strategy to promote RGC neuroprotection after damage.

Abstract. Objective: To understand the association between exposure in pregnant women to phthalic acid esters (PAEs) and birth outcomes. Method: The study was conducted from April to June 2013 in Xiamen, China. A total 1020 pregnant women (gestational age ≤16 weeks) met the inclusion criteria and were included in the cohort. Finally, 25 women with premature delivery and 15 with low birth weight were defined as case groups. According to the study criteria, we selected 100 healthy participants as a control group. Participant information was collected by questionnaires and urine samples were collected, and detect five PAEs (MMP, MEP, MBP, MBzP, and MEHP) levels in urine samples. Single and multi-factor logistic analyses were used to analyze the association between PAE concentration and birth outcomes. Results: Medians of the five PAEs above in the premature delivery group were 36.13 ng/ml, 19.02 ng/ml, 13.64 ng/ml, 2.11 ng/ml, 43.47 ng/ml, respectively. In the control group, these were 35.48 ng/ml, 17.62 ng/ml, 10.15 ng/ml, 2.34 ng/ml, 35.62 ng/ml, respectively. The result of multi-factor logistic analysis indicated that MBP and MEHP were associated with premature delivery: OR 1.629, 95% CI (1.067, 2.488), OR 1.675, 95% CI (1.028, 2.729), respectively. Medians of the five PAEs in the low birth weight group were 37.28 ng/ml, 21.36 ng/ml, 14.60 ng/ml, 2.63 ng/ml, 45.72 ng/ml, respectively. In the control group, these were 35.48 ng/ml, 17.62 ng/ml, 10.15 ng/ml, 2.34 ng/ml, 35.62 ng/ml respectively. MEP, MBP, and MEHP were associated with low birth weight: OR 1.699, 95% CI (1.074, 2.688), OR 1.621, 95% CI (1.061, 2.475), and OR 1.817, 95% CI (1.005, 3.284), respectively. Conclusion: MBP and MEHP exposure in pregnant women were risk factors of premature delivery and MEP, MBP, MEHP exposure were risk factors of low birth weight. Preventing or reducing environmental exposure of pregnant women to these PAEs is of utmost importance.