The tektin family of microtubule-stabilizing proteins

Tektins are insoluble a-helical proteins essential for the construction of cilia and flagella and are found throughout the eukaryotes apart from higher plants

Adolescents’ responses to the promotion and flavouring of e-cigarettes

Objectives The purpose of the study is to examine adolescents’ awareness of e-cigarette marketing and investigate the impact of e-cigarette flavour descriptors on perceptions of product harm and user image. Methods Data come from the 2014 Youth Tobacco Policy Survey, a cross-sectional in-home survey conducted with 11–16 year olds across the UK (n = 1205). Adolescents’ awareness of e-cigarette promotion, brands, and flavours was assessed. Perceptions of product harm, and likely user of four examples of e-cigarette flavours was also examined. Results Some participants had tried e-cigarettes (12 %) but regular use was low (2 %) and confined to adolescents who had also smoked tobacco. Most were aware of at least one promotional channel (82 %) and that e-cigarettes came in different flavours (69 %). Brand awareness was low. E-cigarettes were perceived as harmful (M = 3.54, SD = 1.19) but this was moderated by product flavours. Fruit and sweet flavours were perceived as more likely to be tried by young never smokers than adult smokers trying to quit (p < 0.001). Conclusions There is a need to monitor the impact of future market and regulatory change on youth uptake and perceptions of e-cigarettes

Microtubules in Bacteria: Ancient Tubulins Build a Five-Protofilament Homolog of the Eukaryotic Cytoskeleton

Microtubules play crucial roles in cytokinesis, transport, and motility, and are therefore superb targets for anti-cancer drugs. All tubulins evolved from a common ancestor they share with the distantly related bacterial cell division protein FtsZ, but while eukaryotic tubulins evolved into highly conserved microtubule-forming heterodimers, bacterial FtsZ presumably continued to function as single homopolymeric protofilaments as it does today. Microtubules have not previously been found in bacteria, and we lack insight into their evolution from the tubulin/FtsZ ancestor. Using electron cryomicroscopy, here we show that the tubulin homologs BtubA and BtubB form microtubules in bacteria and suggest these be referred to as “bacterial microtubules” (bMTs). bMTs share important features with their eukaryotic counterparts, such as straight protofilaments and similar protofilament interactions. bMTs are composed of only five protofilaments, however, instead of the 13 typical in eukaryotes. These and other results suggest that rather than being derived from modern eukaryotic tubulin, BtubA and BtubB arose from early tubulin intermediates that formed small microtubules. Since we show that bacterial microtubules can be produced in abundance in vitro without chaperones, they should be useful tools for tubulin research and drug screening

Regulated Expression of Chromobox Homolog 5 Revealed in Tumors of ApcMin/+ ROSA11 Gene Trap Mice

The gene-trap lacZ reporter insertion, ROSA11, in the Cbx5 mouse gene illuminates the regulatory complexity of this locus in ApcMin/+ mice. The insertion site of the β-Geo gene-trap element lies in the 24-kb intron proximal to the coding region of Cbx5. Transcript analysis indicates that two promoters for Cbx5 flank this insertion site. Heterozygotes for the insertion express lacZ widely in fetal tissues but show limited expression in adult tissues. In the intestine, strong expression is limited to proliferative zones of crypts and tumors. Homozygotes for ROSA11, found at a lower than Mendelian frequency, express reduced levels of the coding region transcript in normal tissues, using a downstream promoter. Analysis via real-time polymerase chain reaction indicates that the upstream promoter is the dominant promoter in normal epithelium and tumors. Bioinformatic analysis of the Cbx5 locus indicates that WNT and its target transcription factor MYC can establish a feedback loop that may play a role in regulating the self-renewal of the normal intestinal epithelium and its tumors

A qualitative evaluation of a novel intervention using insight into tobacco industry tactics to prevent the uptake of smoking in school-aged children

Background: Evidence from the US Truth campaign suggests that interventions focusing on tobacco industry tactics can be effective in preventing smoking uptake by children. Operation Smoke Storm is the first school-based intervention based on this premise and comprises three classroom sessions in which students act as secret agents uncovering tobacco industry tactics through videos, quizzes, discussions, and presentations. We report a qualitative evaluation of its acceptability. Methods: We conducted eight focus groups with 79 students aged 11-12 who participated in Operation Smoke Storm at two UK schools in Autumn 2013, and 20 interviews with teachers who delivered the intervention. These were digitally audio-recorded, transcribed verbatim and analysed using the framework method. Results: Students enjoyed the secret agent scenario and reported acquiring new knowledge about smoking and the tobacco industry, which seemed to strengthen their aversion to smoking. Teachers felt confident delivering the ‘off the shelf’ resource, although they would have welcomed more background information about the topic and guidance on steering discussions. Teachers highlighted a need for the resource to be flexible and not dependent on lesson length, teacher confidence, or expertise. Students and teachers endorsed the idea of developing a booster component for older students and supported the development of printed information complementing the resource to encourage parents to support their child not to smoke. Conclusions: These findings demonstrate that Operation Smoke Storm can be delivered by teachers to raise awareness about smoking-related issues. The ideas and issues raised are now being used to improve and extend the resource for further evaluation

Effects of MDM2, MDM4 and TP53 Codon 72 Polymorphisms on Cancer Risk in a Cohort Study of Carriers of TP53 Germline Mutations

Previous studies have shown that MDM2 SNP309 and p53 codon 72 have modifier effects on germline P53 mutations, but those studies relied on case-only studies with small sample sizes. The impact of MDM4 polymorphism on tumor onset in germline mutation carriers has not previously been studied.We analyzed 213 p53 germline mutation carriers including 168(78.9%) affected with cancer and 174 who had genotypic data. We analyzed time to first cancer using Kaplan-Meier and Cox proportional hazards methods, comparing risks according to polymorphism genotypes. For MDM2 SNP309, a significant difference of 9.0 years in the average age of cancer diagnosis was observed between GG/GT and TT carriers (18.6 versus 27.6 years, P = 0.0087). The hazards ratio was 1.58 (P = 0.03) comparing risks among individuals with GG/GT to risk among TT, but this effect was only significant in females (HR = 1.60, P = 0.02). Compared to other genotypes, P53 codon 72 PP homozygotes had a 2.24 times (P = 0.03) higher rate for time to develop cancer. We observed a multiplicative joint effect of MDM2 and p53 codon72 polymorphism on risk. The MDM4 polymorphism had no significant effects.Our results suggest that the MDM2 SNP309 G allele is associated with cancer risk in p53 germline mutation carriers and accelerates time to cancer onset with a pronounced effect in females. A multiplicative joint effect exists between the MDM2 SNP309 G allele and the p53 codon 72 G allele in the risk of cancer development. Our results further define cancer risk in carriers of germline p53 mutations

Female Chromosome X Mosaicism is Age-Related and Preferentially Affects the Inactivated X Chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events 4 2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases