Adverse Childhood Experiences and Use of Cigarettes and Smokeless Tobacco Products

Adverse childhood experiences (ACEs) have been linked to increased use of tobacco products later in life. However, studies to date have ignored smokeless tobacco products. To address this, data from the 2011 Behavioral Risk Factor Surveillance System, which interviewed adults 18 years and over (N = 102,716) were analyzed. Logistic regression models were fit to estimate odds ratios of ever smoking, current smoking and current smokeless tobacco use in relation to ACEs. Results showed that less than 4 % of respondents currently used smokeless tobacco products, while 44.95 and 18.57 % reported ever and current smoking, respectively. Physical abuse (OR 1.40; 95 % CI 1.14, 1.72), emotional abuse (OR 1.41; 95 % CI 1.19, 1.67), sexual abuse (OR 0.70; 95 % CI 0.51, 0.95), living with a drug user (OR 1.50; 95 % CI 1.17, 1.93), living with someone who was jailed (OR 1.50; 95 % CI 1.11, 2.02) and having parents who were separated or divorced (OR 1.31; 95 % CI 1.09, 1.57) were associated with smokeless tobacco use in unadjusted models. After accounting for confounders, physical abuse (OR 1.43; 95 % CI 1.16, 1.78), emotional abuse (OR 1.32; 95 % CI 1.10, 1.57), living with a problem drinker (OR 1.30; 95 % CI 1.08, 1.58), living with a drug user (OR 1.31; 95 % CI 1.00, 1.72) and living with adults who treated each other violently (OR 1.30; 95 % CI 1.05, 1.62) were associated with smokeless tobacco use. Living with someone who was mentally ill (OR 0.70; 95 % CI 0.53, 0.92) was associated with smokeless tobacco use after accounting for confounders and all ACEs. Results indicated that some childhood adversities are associated with use of smokeless tobacco products. Special attention is needed to prevent tobacco use of different types among those experiencing ACEs

Affinity and competition for TBP are molecular determinants of gene expression noise

Cell-to-cell variation in gene expression levels (noise) generates phenotypic diversity and is an important phenomenon in evolution, development and disease. TATA-box binding protein (TBP) is an essential factor that is required at virtually every eukaryotic promoter to initiate transcription. While the presence of a TATA-box motif in the promoter has been strongly linked with noise, the molecular mechanism driving this relationship is less well understood. Through an integrated analysis of multiple large-scale data sets, computer simulation and experimental validation in yeast, we provide molecular insights into how noise arises as an emergent property of variable binding affinity of TBP for different promoter sequences, competition between interaction partners to bind the same surface on TBP (to either promote or disrupt transcription initiation) and variable residence times of TBP complexes at a promoter. These determinants may be fine-tuned under different conditions and during evolution to modulate eukaryotic gene expression noise

SAGA mediates transcription from the TATA-like element independently of Taf1p/TFIID but dependent on core promoter structures in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, core promoters of class II genes contain a TATA element, either a TATA box (TATA[A/T]A[A/T][A/G]) or TATA-like element (1 or 2 bp mismatched version of the TATA box). The TATA element directs the assembly of the preinitiation complex (PIC) to ensure accurate transcriptional initiation. It has been proposed the PIC is assembled by two distinct pathways in which TBP is delivered by TFIID or SAGA, leading to the widely accepted model that these complexes mediate transcription mainly from TATA-like element- or TATA box-containing promoters, respectively. Although both complexes are involved in transcription of nearly all class II genes, it remains unclear how efficiently SAGA mediates transcription from TATA-like element-containing promoters independently of TFIID. We found that transcription from the TATA box-containing AGP1 promoter was greatly stimulated in a Spt3p-dependent manner after inactivation of Taf1p/TFIID. Thus, this promoter provides a novel experimental system in which to evaluate SAGA-mediated transcription from TATA-like element(s). We quantitatively measured transcription from various TATA-like elements in the Taf1p-dependent CYC1 promoter and Taf1p-independent AGP1 promoter. The results revealed that SAGA could mediate transcription from at least some TATA-like elements independently of Taf1p/TFIID, and that Taf1p-dependence or -independence is highly robust with respect to variation of the TATA sequence. Furthermore, chimeric promoter mapping revealed that Taf1p-dependence or independence was conferred by the upstream activating sequence (UAS), whereas Spt3p-dependent transcriptional stimulation after inactivation of Taf1p/TFIID was specific to the AGP1 promoter and dependent on core promoter regions other than the TATA box. These results suggest that TFIID and/or SAGA are regulated in two steps: the UAS first specifies TFIID or SAGA as the predominant factor on a given promoter, and then the core promoter structure guides the pertinent factor to conduct transcription in an appropriate manner

Computable Banach spaces via domain theory

AbstractThis paper extends the order-theoretic approach to computable analysis via continuous domains to complete metric spaces and Banach spaces. We employ the domain of formal balls to define a computability theory for complete metric spaces. For Banach spaces, the domain specialises to the domain of closed balls, ordered by reversed inclusion. We characterise computable linear operators as those which map computable sequences to computable sequences and are effectively bounded. We show that the domain-theoretic computability theory is equivalent to the well-established approach by Pour-El and Richards