The poly(C)-binding protein Pcbp2 is essential for CD4+ T cell activation and proliferation.

The RNA-binding protein Pcbp2 is widely expressed in the innate and adaptive immune systems and is essential for mouse development. To determine whether Pcbp2 is required for CD4+ T cell development and function, we derived mice with conditional Pcbp2 deletion in CD4+ T cells and assessed their overall phenotype and proliferative responses to activating stimuli. We found that Pcbp2 is essential for T conventional cell (Tconv) proliferation, working through regulation of co-stimulatory signaling. Pcbp2 deficiency in the CD4+ lineage did not impact Treg abundance in vivo or function in vitro. In addition, our data demonstrate a clear association between Pcbp2 control of Runx1 exon 6 splicing in CD4+ T cells and a specific role for Pcbp2 in the maintenance of peripheral CD4+ lymphocyte population size. Last, we show that Pcbp2 function is required for optimal in vivo Tconv cell activation in a T cell adoptive transfer colitis model system.

Survey of Heteronormative Attitudes and Tolerance Toward Gender Non-conformity in Mountain West Undergraduate Students.

INTRODUCTION: Heteronormative attitudes are prevalent in the United States and may contribute to discrimination against individuals who do not conform to traditional gender roles. Understanding the attitudes of undergraduate students is of particular interest as they may represent emergent societal views toward gender non-conformity. MATERIALS AND METHODS: We conducted an online survey of Mountain West college students between the ages of 18-24 years to assess perceptions of personal gender conformity using the Traditional Masculinity-Femininity Scale (TMF), endorsement of heteronormative beliefs using the Heteronormative Attitudes and Beliefs Scale (HABS), and explicit tolerance of gender non-conformity on a seven-point Likert Scale. RESULTS: The sample (n = 502) was 84% female and 78% white. Approximately 21% of respondents identified as a sexual minority and 36% identified as liberal or somewhat liberal (27% were conservative). The mean score on the TMF was 5.23 (95% CI: 5.15-5.32), indicating moderate levels of personal gender conformity. The mean HABS score was 3.31 (95% CI: 3.19-3.43), indicating relatively low endorsement of heteronormative attitudes. TMF and HABS scores were both highest in heterosexual males. Most respondents (73%) were taught traditional gender roles in their childhood home, and 89% had heard negative opinions about non-conformity. The majority (80.6%) of respondents reported that they know someone who displays non-conforming characteristics and 61% said that they associate gender non-conformity with homosexuality. Approximately, 7% reported they had bullied others for not conforming to their gender. Among heterosexuals, 13.6% reported they had been bullied for gender non-conformity as did 42.7% of LGBTQ-identified individuals. Nearly 1-in-4 (23.6%) believed that male cross-dressing is wrong. Nearly 1-in-5 (17.2%) agreed with the statement that those who dress or act like the opposite sex were more likely to be abused or neglected during their development. CONCLUSION: Students reported relatively low endorsement of heteronormative attitudes and moderate levels of acceptance toward gender non-conforming persons. The sample may reflect shifting attitudes when compared with outside data sets.

Poly(C)-Binding Protein Pcbp2 Enables Differentiation of Definitive Erythropoiesis by Directing Functional Splicing of the Runx1 Transcript.

Formation of the mammalian hematopoietic system is under a complex set of developmental controls. Here, we report that mouse embryos lacking the KH domain poly(C) binding protein, Pcbp2, are selectively deficient in the definitive erythroid lineage. Compared to wild-type controls, transcript splicing analysis of the Pcbp2-/- embryonic liver reveals accentuated exclusion of an exon (exon 6) that encodes a highly conserved transcriptional control segment of the hematopoietic master regulator, Runx1. Embryos rendered homozygous for a Runx1 locus lacking this cassette exon (Runx1ΔE6) effectively phenocopy the loss of the definitive erythroid lineage in Pcbp2-/- embryos. These data support a model in which enhancement of Runx1 cassette exon 6 inclusion by Pcbp2 serves a critical role in development of hematopoietic progenitors and constitutes a critical step in the developmental pathway of the definitive erythropoietic lineage.