SAGA is a 1.8-MDa yeast protein complex that is composed of several distinct classes of transcriptionrelated factors, including the adaptor/acetyltransferase Gcn5, Spt proteins, and a subset of TBP-associated factors. Our results indicate that mutations that completely disrupt SAGA (deletions of SPT7 or SPT20) strongly reduce transcriptional activation at the HIS3 and TRP3 genes and that Gcn5 is required for normal HIS3 transcriptional start site selection. Surprisingly, mutations in Spt proteins involved in the SAGA-TBP interaction (Spt3 and Spt8) cause derepression of HIS3 and TRP3 transcription in the uninduced state. Consistent with this finding, wild-type SAGA inhibits TBP binding to the HIS3 promoter in vitro, while SAGA lacking Spt3 or Spt8 is not inhibitory. We detected two distinct forms of SAGA in cell extracts and, strikingly, one lacks Spt8. Conditions that induce HIS3 and TRP3 transcription result in an altered balance between these complexes strongly in favor of the form without Spt8. These results suggest that the composition of SAGA may be dynamic in vivo and may be regulated through dissociable inhibitory subunits.

This study examined the relations among parenting behaviors of 97 coresident mothers and fathers of infants during a dyadic free-play setting. The authors examined the extent to which observed sensitive and intrusive parenting behaviors in mother-child and father-child dyads were related and how perceived marital quality may be associated with the similarity between maternal and paternal parenting behaviors. The authors found support for interdependence of parenting by mothers and fathers. High perceived marital quality was associated with interdependence of sensitive parenting behaviors in mother-infant and father-infant interactions. Negative parenting behaviors by mothers and fathers were interrelated regardless of marital quality. The findings highlight the importance of studying parenting by mothers and fathers as embedded within particular family systems.

Rapid changes in language skills and social competence, both of which are linked to sensitive parenting, characterize early childhood. The present study examines bidirectional associations among mothers’ sensitive parenting and children’s language skills and social competence from 24 to 36 months in a community sample of 174 families. In addition, this study examines how these developmental pathways vary by child sex. Findings indicate stability across time in sensitive parenting, expressive language skills, and social competence, as well as positive main effects of sensitive parenting on expressive and receptive language skills for girls and boys. We find mixed evidence over time of reciprocal links between social competence and sensitive parenting. Further, boys’ receptive language skills at 24 months uniquely contribute to increases in mothers’ observed sensitive parenting from 24 to 36 months. These findings highlight the utility of applying transactional frameworks to the study of sex-based differences in early developmental processes.

The current study examined the individual and joint effects of self-reported adult attachment style, psychological distress, and parenting stress on maternal caregiving behaviors at 6 and 12 months of child age. We proposed a diathesis-stress model to examine the potential deleterious effects of stress for mothers with insecure adult attachment styles. Data from 137 mothers were gathered by the longitudinal Durham Child Health and Development Study. Mothers provided self-reports using Hazan and Shaver’s (1987) Adult Attachment Style measure, the Brief Symptom Inventory, and the Parent Stress Inventory; observations of parenting data were made from 10-minute free play interactions. Consistently avoidant mothers were less sensitive with their infants than consistently secure mothers; however, this effect was limited to avoidant mothers who experienced elevated levels of psychological distress. Results suggest that the association between insecure adult attachment style and insensitive parenting behavior is moderated by concurrent psychosocial stress. Clinical implications for these findings are discussed.

Toll-like receptor 3 (TLR3), a member of the pathogen recognition receptors, is widely expressed in various cells and has been shown to activate immune signaling pathways by recognizing viral double-stranded RNA. Recently, it was reported that the activation of TLR3 induced apoptosis in some cells, but the detailed molecular mechanism is not fully understood. In this study, we found that in endothelial cells polyinosinic-polycytidylic acid (poly(I-C)) induced dose-and time-dependent cell apoptosis, which was elicited by TLR3 activation, as TLR3 neutralization and down-regulation repressed the apoptosis. Poly(I-C) induced the activation of both caspases 8 and 9, indicating that TLR3 triggered the signaling of both the extrinsic and intrinsic apoptotic pathways. Poly(I-C) up-regulated tumor necrosis factor-related apoptosis-inducing ligand and its receptors, death receptors 4/5, resulting in initiating the extrinsic pathway. Furthermore, poly(I-C) down-regulated anti-apoptotic protein, B cell lymphoma 2 (Bcl-2), and up-regulated Noxa, a key Bcl-2 homology 3-only antagonist of Bcl-2, leading to the priming of the intrinsic pathway. A p53-related protein, the transactivating p63 isoform ␣ (TAp63␣), was induced by TLR3 activation and contributed to the activation of both the intrinsic and extrinsic apoptotic pathways. Both the cells deficient in p63 gene expression by RNA interference and cells that overexpressed the N-terminally truncated p63 isoform ␣ (⌬Np63␣), a dominant-negative variant of TAp63␣, by gene transfection, survived TLR3 activation. Taken together, TAp63␣ is a crucial regulator downstream of TLR3 to induce cell death via death receptors and mitochondria.