Health Profile of Afghan Pediatric Refugees Resettled to Philadelphia in 2021-2022.

To elucidate the physical and psychosocial health needs of newly arrived Afghan children, we conducted a retrospective chart review of patients 0 to 19 years re-settled to Philadelphia with ≥1 outpatient visit during August 2021 to August 2022. Findings on 121 patients include dental caries (74%), elevated lead (32%), eosinophilia (29%), malnutrition (25%), schistosomiasis (6%), strongyloidiasis (8%), latent tuberculosis (7%), and two cases of cutaneous leishmaniasis. Mental health symptoms include poor sleep in 16%, low energy in 10%, and behavioral concerns in 13%. Families with low English proficiency were more often met with delayed medical care (26.7% vs 11.5% P = .12). Parents with less than a high school education were more likely to experience delayed care (38.5% vs 9.1%; P = .001). We conclude that recently arrived Afghan children have unique physical and mental health needs that need to be addressed.

A TET1-PSPC1-Neat1 molecular axis modulates PRC2 functions in controlling stem cell bivalency.

TET1 maintains hypomethylation at bivalent promoters through its catalytic activity in embryonic stem cells (ESCs). However, TET1 catalytic activity-independent function in regulating bivalent genes is not well understood. Using a proteomics approach, we map the TET1 interactome in ESCs and identify PSPC1 as a TET1 partner. Genome-wide location analysis reveals that PSPC1 functionally associates with TET1 and Polycomb repressive complex-2 (PRC2). We establish that PSPC1 and TET1 repress, and the lncRNA Neat1 activates, bivalent gene expression. In ESCs, Neat1 is preferentially bound to PSPC1 alongside its PRC2 association at bivalent promoters. During the ESC-to-epiblast-like stem cell (EpiLC) transition, PSPC1 and TET1 maintain PRC2 chromatin occupancy at bivalent gene promoters, while Neat1 facilitates the activation of certain bivalent genes by promoting PRC2 binding to their mRNAs. Our study demonstrates a TET1-PSPC1-Neat1 molecular axis that modulates PRC2-binding affinity to chromatin and bivalent gene transcripts in controlling stem cell bivalency.

The roles of TET family proteins in development and stem cells.

Ten-eleven translocation (TET) methylcytosine dioxygenases are enzymes that catalyze the demethylation of 5-methylcytosine on DNA. Through global and site-specific demethylation, they regulate cell fate decisions during development and in embryonic stem cells by maintaining pluripotency or by regulating differentiation. In this Primer, we provide an updated overview of TET functions in development and stem cells. We discuss the catalytic and non-catalytic activities of TETs, and their roles as epigenetic regulators of both DNA and RNA hydroxymethylation, highlighting how TET proteins function in regulating gene expression at both the transcriptional and post-transcriptional levels.

Analysis of JC virus DNA replication using a quantitative and high-throughput assay.

Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication.