Coupled transcription-splicing regulation of mutually exclusive splicing events at the 5' exons of protein 4.1R gene.

The tightly regulated production of distinct erythrocyte protein 4.1R isoforms involves differential splicing of 3 mutually exclusive first exons (1A, 1B, 1C) to the alternative 3' splice sites (ss) of exon 2'/2. Here, we demonstrate that exon 1 and 2'/2 splicing diversity is regulated by a transcription-coupled splicing mechanism. We also implicate distinctive regulatory elements that promote the splicing of exon 1A to the distal 3' ss and exon 1B to the proximal 3' ss in murine erythroleukemia cells. A hybrid minigene driven by cytomegalovirus promoter mimicked 1B-promoter-driven splicing patterns but differed from 1A-promoter-driven splicing patterns, suggesting that promoter identity affects exon 2'/2 splicing. Furthermore, splicing factor SF2/ASF ultraviolet (UV) cross-linked to the exon 2'/2 junction CAGAGAA, a sequence that overlaps the distal U2AF(35)-binding 3' ss. Consequently, depletion of SF2/ASF allowed exon 1B to splice to the distal 3' ss but had no effect on exon 1A splicing. These findings identify for the first time that an SF2/ASF binding site also can serve as a 3' ss in a transcript-dependent manner. Taken together, our results suggest that 4.1R gene expression involves transcriptional regulation coupled with a complex splicing regulatory network.

Long-term follow-up of a randomized controlled trial comparing acceptance and commitment therapy and standard cognitive behavior therapy for anxiety and depression.

The present study represents one of the first comparisons of the long-term effectiveness of traditional cognitive behavior therapy (i.e., Beckian cognitive therapy; CT) and acceptance and commitment therapy (ACT). One hundred thirty-two anxious or depressed outpatients were randomly assigned to receive either CT or ACT, and were assessed at posttreatment (n=90) and at 1.5-year (n=91) follow-up. As previously reported, the two treatments were equivalently effective at posttreatment according to measures of depression, anxiety, overall (social/occupational/symptom-related) functioning, and quality of life. However, current results suggest that treatment gains were better maintained at follow-up in the CT condition. Clinical significance analyses revealed that, at follow-up, one-third more CT patients were in the clinically normative range in terms of depressive symptoms and more than twice as many CT patients were in the normative range in terms of functioning levels. The possible long-term advantage of CT relative to ACT in this population is discussed.

RBFOX2 promotes protein 4.1R exon 16 selection via U1 snRNP recruitment.

The erythroid differentiation-specific splicing switch of protein 4.1R exon 16, which encodes a spectrin/actin-binding peptide critical for erythrocyte membrane stability, is modulated by the differentiation-induced splicing factor RBFOX2. We have now characterized the mechanism by which RBFOX2 regulates exon 16 splicing through the downstream intronic element UGCAUG. Exon 16 possesses a weak 5' splice site (GAG/GTTTGT), which when strengthened to a consensus sequence (GAG/GTAAGT) leads to near-total exon 16 inclusion. Impaired RBFOX2 binding reduces exon 16 inclusion in the context of the native weak 5' splice site, but not the engineered strong 5' splice site, implying that RBFOX2 achieves its effect by promoting utilization of the weak 5' splice site. We further demonstrate that RBFOX2 increases U1 snRNP recruitment to the weak 5' splice site through direct interaction between its C-terminal domain (CTD) and the zinc finger region of U1C and that the CTD is required for the effect of RBFOX2 on exon 16 splicing. Our data suggest a novel mechanism for exon 16 5' splice site activation in which the binding of RBFOX2 to downstream intronic splicing enhancers stabilizes the pre-mRNA-U1 snRNP complex through interactions with U1C.

Prevalence of baby bottle versus breastfeeding graphics on products in national chain stores.

OBJECTIVE: This study surveyed the prevalence of bottle versus breastfeeding graphic images on products marketed for pregnant mothers and young children available for purchase in national chain stores. STUDY DESIGN AND METHODS: This was a product survey/content analysis. Eighteen national chain stores located in a 10-mile radius of Charlottesville, VA were visited. In total, 2,670 individual items in 11 categories of baby shower and baby gift merchandise (shower invitations, greeting cards, gift wrap, shower decorations, baby dolls, baby books, infant clothing, bibs, nursery decorations, baby blankets, and disposable diapers) were assessed. The main outcome measures were prevalences of baby bottle and breastfeeding graphic images. RESULTS: Baby bottle images were found on products in eight of the 11 categories of items surveyed. Thirty-five percent of baby dolls were marketed with a baby bottle. The prevalence of bottle images on items in all other categories, however, was low. Of the 2,670 items surveyed, none contained a breastfeeding image. CONCLUSIONS: The low prevalence of baby bottle images on commonly purchased baby gift and baby shower items is encouraging. However, the absence of breastfeeding images and the relatively high prevalence of baby dolls marketed with a baby bottle demonstrate that breastfeeding is not portrayed as the physiologic norm on these products. Product designers should explore ways to promote breastfeeding, consumers should make informed choices in product selection, and advocacy groups should promote guidelines for these products.