Vaccine hesitancy in prenatal women and mothers of newborns: Results of an interventional study.

INTRODUCTION: The purpose of this study was to determine the effectiveness of a web-based, vaccine resource-directed, interactive communication intervention for vaccine-hesitant prenatal women and mothers of newborns/infants to make informed decisions based on scientific evidence about vaccinating themselves and their newborns/infants, respectively. METHODS: A prospective quasi-experimental design was used to determine the effectiveness of the intervention for vaccine-hesitant prenatal women (stage 1) and for mothers of newborns (stage 2). A survey was administered to prenatal women to determine attitudes about vaccines for themselves during pregnancy. A survey on parental attitudes about vaccination for their children was administered to mothers of newborns. The surveys were administered to determine levels of vaccine acceptance. Vaccine acceptors and vaccine-hesitant individuals were included in the study as control and intervention group participants, respectively; vaccine refusers were eliminated from the study. RESULTS: Among prenatal vaccine-hesitant women, 82% had full prenatal vaccination coverage after receiving the intervention (χ2 = 7.2, P = .02). The majority of mothers of newborns/infants (74%) fully immunized their infants. DISCUSSION: The interventions for prenatal vaccine-hesitant women were effective in changing their status from hesitant to acceptors. The mothers of newborns/infants who were initially hesitant had vaccination rates that exceeded the comparison group comprised of vaccine acceptors.

Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells.

The transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into the functions of Ebf1 at distinct stages of differentiation, we conditionally inactivated Ebf1. We found that Ebf1 is required for the proliferation, survival, and signaling of pro-B cells and peripheral B-cell subsets, including B1 cells and marginal zone B cells. The proliferation defect of Ebf1-deficient pro-B cells and the impaired expression of multiple cell cycle regulators are overcome by transformation with v-Abl. The survival defect of transformed Ebf1(fl/fl) pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-x(L). In mature B cells, Ebf1 deficiency interferes with signaling via the B-cell-activating factor receptor (BAFF-R)- and B-cell receptor (BCR)-dependent Akt pathways. Moreover, Ebf1 is required for germinal center formation and class switch recombination. Genome-wide analyses of Ebf1-mediated gene expression and chromatin binding indicate that Ebf1 regulates both common and distinct sets of genes in early and late stage B cells. By regulating important components of transcription factor and signaling networks, Ebf1 appears to be involved in the coordination of cell proliferation, survival, and differentiation at multiple stages of B lymphopoiesis.

Early B cell factor 1 regulates B cell gene networks by activation, repression, and transcription- independent poising of chromatin.

The transcription factor early B cell factor-1 (Ebf1) is a key determinant of B lineage specification and differentiation. To gain insight into the molecular basis of Ebf1 function in early-stage B cells, we combined a genome-wide ChIP sequencing analysis with gain- and loss-of-function transcriptome analyses. Among 565 genes that are occupied and transcriptionally regulated by Ebf1, we identified large sets involved in (pre)-B cell receptor and Akt signaling, cell adhesion, and migration. Interestingly, a third of previously described Pax5 targets was found to be occupied by Ebf1. In addition to Ebf1-activated and -repressed genes, we identified targets at which Ebf1 induces chromatin changes that poise the genes for expression at subsequent stages of differentiation. Poised chromatin states on specific targets could also be established by Ebf1 expression in T cells but not in NIH 3T3 cells, suggesting that Ebf1 acts as a "pioneer" factor in a hematopoietic chromatin context.

The BMP pathway acts to directly regulate Tbx20 in the developing heart.

TBX20 has been shown to be essential for vertebrate heart development. Mutations within the TBX20 coding region are associated with human congenital heart disease, and the loss of Tbx20 in a wide variety of model systems leads to cardiac defects and eventually heart failure. Despite the crucial role of TBX20 in a range of cardiac cellular processes, the signal transduction pathways that act upstream of Tbx20 remain unknown. Here, we have identified and characterized a conserved 334 bp Tbx20 cardiac regulatory element that is directly activated by the BMP/SMAD1 signaling pathway. We demonstrate that this element is both necessary and sufficient to drive cardiac-specific expression of Tbx20 in Xenopus, and that blocking SMAD1 signaling in vivo specifically abolishes transcription of Tbx20, but not that of other cardiac factors, such as Tbx5 and MHC, in the developing heart. We further demonstrate that activation of Tbx20 by SMAD1 is mediated by a set of novel, non-canonical, high-affinity SMAD-binding sites located within this regulatory element and that phospho-SMAD1 directly binds a non-canonical SMAD1 site in vivo. Finally, we show that these non-canonical sites are necessary and sufficient for Tbx20 expression in Xenopus, and that reporter constructs containing these sites are expressed in a cardiac-specific manner in zebrafish and mouse. Collectively, our findings define Tbx20 as a direct transcriptional target of the BMP/SMAD1 signaling pathway during cardiac maturation.

Transcription control of early B cell differentiation.

Differentiation of B lymphocytes involves the step-wise acquisition of a specialized phenotype that depends on the expression of lineage-specific genes and the repression of genes characteristic of multipotent progenitors and alternate lineages. The early steps of B lineage specification and commitment are, partly, controlled by the well-characterized transcription factors Ikaros, Pu.1, E2A, early B cell factor-1, and Pax5 that act in a complex regulatory network. However, our understanding of B cell differentiation is far from complete. Recent work has shed light on the mechanisms by which transcription factors implement cell type-specific gene expression patterns and epigenetic changes in chromatin that allow for B lineage specification and commitment.

Developmental expression patterns of Tbx1, Tbx2, Tbx5, and Tbx20 in Xenopus tropicalis.

T-box genes have diverse functions during embryogenesis and are implicated in several human congenital disorders. Here, we report the identification, sequence analysis, and developmental expression patterns of four members of the T-box gene family in the diploid frog Xenopus tropicalis. These four genes-Tbx1, Tbx2, Tbx5, and Tbx20-have been shown to influence cardiac development in a variety of organisms, in addition to their individual roles in regulating other aspects of embryonic development. Our results highlight the high degree of evolutionary conservation between orthologs of these genes in X. tropicalis and other vertebrates, both at the molecular level and in their developmental expression patterns, and also identify novel features of their expression. Thus, X. tropicalis represents a potentially valuable vertebrate model in which to further investigate the functions of these genes through genetic approaches.

The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation.

Understanding the molecular mechanisms that regulate cellular proliferation and differentiation is a central theme of developmental biology. MicroRNAs (miRNAs) are a class of regulatory RNAs of approximately 22 nucleotides that post-transcriptionally regulate gene expression. Increasing evidence points to the potential role of miRNAs in various biological processes. Here we show that miRNA-1 (miR-1) and miRNA-133 (miR-133), which are clustered on the same chromosomal loci, are transcribed together in a tissue-specific manner during development. miR-1 and miR-133 have distinct roles in modulating skeletal muscle proliferation and differentiation in cultured myoblasts in vitro and in Xenopus laevis embryos in vivo. miR-1 promotes myogenesis by targeting histone deacetylase 4 (HDAC4), a transcriptional repressor of muscle gene expression. By contrast, miR-133 enhances myoblast proliferation by repressing serum response factor (SRF). Our results show that two mature miRNAs, derived from the same miRNA polycistron and transcribed together, can carry out distinct biological functions. Together, our studies suggest a molecular mechanism in which miRNAs participate in transcriptional circuits that control skeletal muscle gene expression and embryonic development.