Targeting of SMN to Cajal bodies is mediated by self-association

The childhood autosomal recessive disorder spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron (SMN) gene. SMN localizes diffusely in the cytoplasm and in distinct nuclear structures called Cajal bodies. Cajal bodies are believed to be the storage and processing sites of several ribonucleoproteins. Here, using a novel panel of SMN exon deletion constructs, we report a systematic analysis of internal targeting domains in the SMN protein. We demonstrate that the peptides encoded by exons 2b, 3 and 6 perform an integral role in the cellular targeting of SMN. In addition, we identify a nine amino acid motif within the highly conserved sequences of the exon 2b encoded domain that mediates Cajal body targeting and self-association. Deletion of this domain dramatically affects SMN activity and results in a dominant-negative clone. These results identify critical domains within the SMN protein and have an impact on our understanding of the SMN protein with regards to SMA as well as cellular biology.     

Food spending behaviors and perceptions are associated with fruit and vegetable intake among parents and their preadolescent children

OBJECTIVE: Examine the role of food spending behaviors and perceptions on fruit and vegetable intake among preadolescent children and their parents. DESIGN: Cross-sectional study. SETTING: Metropolitan city. PARTICIPANTS: Five hundred fifty-five parent/child dyads participating in the PARADE study. More than 50% of participants were African American and nearly 40% of households were low income. VARIABLES MEASURED: Body mass index calculated from child anthropometric data and parents' self-reported height and weight. Adult and child fruit and vegetable intake, annual household income, and food purchase behavior and perceptions obtained from parent questionnaire. ANALYSIS: Analysis of variance used to identify differences in means at P<.05 level. RESULTS: No statistically significant differences in fruit and vegetable intake by income status were observed. Children in households spending the least per week on groceries consumed fewer daily fruits and vegetables. Perceptions of cost of fruits and vegetables were also found to be significantly associated with fruit and vegetable intake among children and parents. CONCLUSIONS AND IMPLICATIONS: Public health efforts to raise awareness of the relatively low cost of fruits and vegetables should be continued. These efforts may be complemented with policy strategies that make fruits and vegetables more viable options for low-income households.     

Bladder cancer and exposure to water disinfection by-products through ingestion, bathing, showering, and swimming in pools

Bladder cancer has been associated with exposure to chlorination by-products in drinking water, and experimental evidence suggests that exposure also occurs through inhalation and dermal absorption. The authors examined whether bladder cancer risk was associated with exposure to trihalomethanes (THMs) through ingestion of water and through inhalation and dermal absorption during showering, bathing, and swimming in pools. Lifetime personal information on water consumption and water-related habits was collected for 1,219 cases and 1,271 controls in a 1998-2001 case-control study in Spain and was linked with THM levels in geographic study areas. Long-term THM exposure was associated with a twofold bladder cancer risk, with an odds ratio of 2.10 (95% confidence interval: 1.09, 4.02) for average household THM levels of >49 versus < or =8 micro g/liter. Compared with subjects not drinking chlorinated water, subjects with THM exposure of >35 micro g/day through ingestion had an odds ratio of 1.35 (95% confidence interval: 0.92, 1.99). The odds ratio for duration of shower or bath weighted by residential THM level was 1.83 (95% confidence interval: 1.17, 2.87) for the highest compared with the lowest quartile. Swimming in pools was associated with an odds ratio of 1.57 (95% confidence interval: 1.18, 2.09). Bladder cancer risk was associated with long-term exposure to THMs in chlorinated water at levels regularly occurring in industrialized countries.     

Cigarette smoking and cancer risk: modeling total exposure and intensity

A recent analysis showed that the excess odds ratio (EOR) for lung cancer due to smoking can be modeled by a function which is linear in total pack-years and exponential in the logarithm of smoking intensity and its square. Below 15-20 cigarettes per day, the EOR/pack-year increased with intensity (direct exposure rate or enhanced potency effect), suggesting greater risk for a total exposure delivered at higher intensity (for a shorter duration) than for an equivalent exposure delivered at lower intensity. Above 20 cigarettes per day, the EOR/pack-year decreased with increasing intensity (inverse exposure rate or reduced potency effect), suggesting greater risk for a total exposure delivered at lower intensity (for a longer duration) than for an equivalent exposure delivered at higher intensity. The authors applied this model to data from 10 case-control studies of cancer, including cancers of the lung, bladder, oral cavity, pancreas, and esophagus. At lower intensities, there was enhanced potency for several cancer sites, but narrow ranges for pack-years increased uncertainty, precluding definitive conclusions. At higher intensities, there was a consistent reduced potency effect across studies. The intensity effects were statistically homogeneous, indicating that after accounting for risk from total pack-years, intensity patterns were comparable across the diverse cancer sites.     

Biological,Familial, and Peer Influences on Dating in Early Adolescence

The current study examined the joint contributions of pubertal maturation, parental monitoring, involvement in older peer groups, peer dating, and peer delinquency on dating in a sample of early adolescent boys and girls. The sample consisted of 784 adolescents (394 boys, 390 girls) enrolled in grades 5, 6, and 7 who were followed for one year. In addition to measures of pubertal maturation and parental monitoring, adolescents and their peer group members completed indices of dating and delinquency. Average dating and delinquency scores for each participant's peer group network were computed. Results indicated that it was the combination of pubertal maturation, peer delinquency, and peer dating that explained increases in early dating. For boys only, parental monitoring was a significant predictor. The more knowledgeable parents were about their boys' activities, the lower the number of dating activities reported. These results highlight the importance of considering the joint effects of these biological and social predictors in understanding early dating. When rapid changes occur in all three domains, early dating is most likely to ensue. The findings of this study have practical importance. Parents and professionals who work closely with youth should attend to the special vulnerability of early maturing adolescents in the face of peer pressure and to the important role of parental monitoring in regulating dating activities.     

Fourteen-day safety and acceptability study of the universal placebo gel

OBJECTIVE: This study evaluated the effect of the so-called universal placebo compared to the polystyrene sulfonate (PSS) placebo on genital irritation. DESIGN: A single-center, Phase I, randomized, closed-label study was performed to evaluate the genital irritation of microbicide placebo gels. Thirty healthy, sexually abstinent women were randomly assigned to apply 3.5 mL of either the universal placebo or the PSS placebo gel intravaginally twice daily for 14 days. METHODS: Genital irritation was assessed by signs as seen on pelvic examination and colposcopy and reports of symptoms. Vaginal health was assessed by wet mounts, Gram stains for Nugent score and polymorphonuclear leukocytes, and semiquantitative vaginal cultures. Acceptability was assessed as reported on the follow-up questionnaire. RESULTS: The universal placebo was less irritating than the PSS placebo with a lower proportion of women experiencing signs and/or symptoms of genital irritation throughout follow-up (36% compared to 80%, p=.0253). The universal placebo was associated with few and mild genital symptoms, few and minor colposcopic findings and good vaginal health with no clinically significant changes in genital flora. Most participants found the feel of the universal placebo gel neutral or pleasant, and all participants found it odorless. CONCLUSIONS: The universal placebo appeared safe and acceptable when used twice daily for 14 days. The strategy of creating a de novo inert universal placebo is a successful approach. The universal placebo is appropriate for use as a placebo gel in HIV prevention trials with microbicide candidates.