Social networking between mobile introns and their host genes.
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ABSTRACT:
SUBMITTER: Stoddard B
PROVIDER: S-EPMC2943980 | biostudies-literature | 2010 Oct
REPOSITORIES: biostudies-literature
Publications
Social networking between mobile introns and their host genes.
Stoddard Barry B Belfort Marlene M
Molecular microbiology 20101001 1
Homing endonucleases have long been known as the orchestrators of intron mobility. However, the extent of their influence on the intron and its genetic and cellular environment is still being elucidated. The accompanying paper emphasizes the importance of temporal control of endonuclease expression on splicing, expression of the host gene and cellular metabolism, while it raises questions to guide future inquiry. ...[more]
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Project description:Self-splicing introns populate several highly conserved protein-coding genes in fungal and plant mitochondria. In fungi, many of these introns have retained their ability to spread to intron-free target sites, often assisted by intron-encoded endonucleases that initiate the homing process. Here, leveraging population genomic data from Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Lachancea kluyveri, we expose nonrandom patterns of genetic diversity in exons that border self-splicing introns. In particular, we show that, in all three species, the density of single nucleotide polymorphisms increases as one approaches a mobile intron. Through multiple lines of evidence, we rule out relaxed purifying selection as the cause of uneven nucleotide diversity. Instead, our findings implicate intron mobility as a direct driver of host gene diversity. We discuss two mechanistic scenarios that are consistent with the data: either endonuclease activity and subsequent error-prone repair have left a mutational footprint on the insertion environment of mobile introns or nonrandom patterns of genetic diversity are caused by exonic coconversion, which occurs when introns spread to empty target sites via homologous recombination. Importantly, however, we show that exonic coconversion can only explain diversity gradients near intron-exon boundaries if the conversion template comes from outside the population. In other words, there must be pervasive and ongoing horizontal gene transfer of self-splicing introns into extant fungal populations.
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Project description:BACKGROUND:Technological interventions such as mobile apps, Web-based social networks, and wearable trackers have the potential to influence physical activity; yet, only a few studies have examined the efficacy of an intervention bundle combining these different technologies. OBJECTIVE:This study aimed to pilot test an intervention composed of a social networking mobile app, connected with a wearable tracker, and investigate its efficacy in improving physical activity, as well as explore participant engagement and the usability of the app. METHODS:This was a pre-post quasi-experimental study with 1 arm, where participants were subjected to the intervention for a 6-month period. The primary outcome measure was the difference in daily step count between baseline and 6 months. Secondary outcome measures included engagement with the intervention and system usability. Descriptive and inferential statistical tests were conducted; posthoc subgroup analyses were carried out for participants with different levels of steps at baseline, app usage, and social features usage. RESULTS:A total of 55 participants were enrolled in the study; the mean age was 23.6 years and 28 (51%) were female. There was a nonstatistically significant increase in the average daily step count between baseline and 6 months (mean change=14.5 steps/day, P=.98, 95% CI -1136.5 to 1107.5). Subgroup analysis comparing the higher and lower physical activity groups at baseline showed that the latter had a statistically significantly higher increase in their daily step count (group difference in mean change from baseline to 6 months=3025 steps per day, P=.008, 95% CI 837.9-5211.8). At 6 months, the retention rate was 82% (45/55); app usage decreased over time. The mean system usability score was 60.1 (SD 19.2). CONCLUSIONS:This study showed the preliminary efficacy of a mobile social networking intervention, integrated with a wearable tracker to promote physical activity, particularly for less physically active subgroups of the population. Future research should explore how to address challenges faced by physically inactive people to provide tailored advices. In addition, users' perspectives should be explored to shed light on factors that might influence their engagement with the intervention.
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Project description:BackgroundMobile group I introns encode homing endonucleases that confer intron mobility initiated by a double-strand break in the intron-lacking allele at the site of insertion. Nuclear ribosomal DNA of some fungi and protists contain mobile group I introns harboring His-Cys homing endonuclease genes (HEGs). An intriguing question is how protein-coding genes embedded in nuclear ribosomal DNA become expressed. To address this gap of knowledge we analyzed nuclear L2066 group I introns from myxomycetes and ascomycetes.ResultsA total of 34 introns were investigated, including two identified mobile-type introns in myxomycetes with HEGs oriented in sense or antisense directions. Intriguingly, both HEGs are interrupted by spliceosomal introns. The intron in Didymium squamulosum, which harbors an antisense oriented HEG, was investigated in more detail. The group I intron RNA self-splices in vitro, thus generating ligated exons and full-length intron circles. The intron HEG is expressed in vivo in Didymium cells, which involves removal of a 47-nt spliceosomal intron (I-47) and 3' polyadenylation of the mRNA. The D. squamulosum HEG (lacking the I-47 intron) was over-expressed in E. coli, and the corresponding protein was purified and shown to confer endonuclease activity. The homing endonuclease was shown to cleave an intron-lacking DNA and to produce a pentanucleotide 3' overhang at the intron insertion site.ConclusionsThe L2066 family of nuclear group I introns all belong to the group IE subclass. The D. squamulosum L2066 intron contains major hallmarks of a true mobile group I intron by encoding a His-Cys homing endonuclease that generates a double-strand break at the DNA insertion site. We propose a potential model to explain how an antisense HEG becomes expressed from a nuclear ribosomal DNA locus.
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Project description:BackgroundDespite many health benefits of physical activity, nearly a third of the world's adult population is insufficiently active. Technological interventions, such as mobile apps, wearable trackers, and Web-based social networks, offer great promise in promoting physical activity, but little is known about users' acceptability and long-term engagement with these interventions.ObjectiveThe aim of this study was to understand users' perspectives regarding a mobile social networking intervention to promote physical activity.MethodsParticipants, mostly university students and staff, were recruited using purposive sampling techniques. Participants were enrolled in a 6-month feasibility study where they were provided with a wearable physical activity tracker (Fitbit Flex 2) and a wireless scale (Fitbit Aria) integrated with a social networking mobile app (named "fit.healthy.me"). We conducted semistructured, in-depth qualitative interviews and focus groups pre- and postintervention, which were recorded and transcribed verbatim. The data were analyzed in Nvivo 11 using thematic analysis techniques.ResultsIn this study, 55 participants were enrolled; 51% (28/55) were females, and the mean age was 23.6 (SD 4.6) years. The following 3 types of factors emerged from the data as influencing engagement with the intervention and physical activity: individual (self-monitoring of behavior, goal setting, and feedback on behavior), social (social comparison, similarity and familiarity between users, and participation from other users in the network), and technological. In addition, automation and personalization were observed as enhancing the delivery of both individual and social aspects. Technological limitations were mentioned as potential barriers to long-term usage.ConclusionsSelf-regulatory techniques and social factors are important to consider when designing a physical activity intervention, but a one-size-fits-all approach is unlikely to satisfy different users' preferences. Future research should adopt innovative research designs to test interventions that can adapt and respond to users' needs and preferences throughout time.
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Project description:The duality of group II introns, capable of carrying out both self-splicing and retromobility reactions, is hypothesized to have played a profound role in the evolution of eukaryotes. These introns likely provided the framework for the emergence of eukaryotic retroelements, spliceosomal introns and other key components of the spliceosome. Group II introns are found in all three domains of life and are therefore considered to be exceptionally successful mobile genetic elements. Initially identified in organellar genomes, group II introns are found in bacteria, chloroplasts, and mitochondria of plants and fungi, but not in nuclear genomes. Although there is no doubt that prokaryotic and organellar group II introns are evolutionary related, there are remarkable differences in survival strategies between them. Furthermore, an evolutionary relationship of group II introns to eukaryotic retroelements, including telomeres, and spliceosomes is unmistakable.
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Project description:BackgroundSmartphone apps, fitness trackers, and online social networks have shown promise in weight management and physical activity interventions. However, there are knowledge gaps in identifying the most effective and engaging interventions and intervention features preferred by their users.ObjectiveThis 6-month pilot study on a social networking mobile app connected to wireless weight and activity tracking devices has 2 main aims: to evaluate changes in BMI, weight, and physical activity levels in users from different BMI categories and to assess user perspectives on the intervention, particularly on social comparison and automated self-monitoring and feedback features.MethodsThis was a mixed methods study involving a one-arm, pre-post quasi-experimental pilot with postintervention interviews and focus groups. Healthy young adults used a social networking mobile app intervention integrated with wireless tracking devices (a weight scale and a physical activity tracker) for 6 months. Quantitative results were analyzed separately for 2 groups-underweight-normal and overweight-obese BMI-using t tests and Wilcoxon sum rank, Wilcoxon signed rank, and chi-square tests. Weekly BMI change in participants was explored using linear mixed effects analysis. Interviews and focus groups were analyzed inductively using thematic analysis.ResultsIn total, 55 participants were recruited (mean age of 23.6, SD 4.6 years; 28 women) and 45 returned for the final session (n=45, 82% retention rate). There were no differences in BMI from baseline to postintervention (6 months) and between the 2 BMI groups. However, at 4 weeks, participants' BMI decreased by 0.34 kg/m2 (P<.001), with a loss of 0.86 kg/m2 in the overweight-obese group (P=.01). Participants in the overweight-obese group used the app significantly less compared with individuals in the underweight-normal BMI group, as they mentioned negative feelings and demotivation from social comparison, particularly from upward comparison with fitter people. Participants in the underweight-normal BMI group were avid users of the app's self-monitoring and feedback (P=.02) and social (P=.04) features compared with those in the overweight-obese group, and they significantly increased their daily step count over the 6-month study duration by an average of 2292 steps (95% CI 898-3370; P<.001). Most participants mentioned a desire for a more personalized intervention.ConclusionsThis study shows the effects of different interventions on participants from higher and lower BMI groups and different perspectives regarding the intervention, particularly with respect to its social features. Participants in the overweight-obese group did not sustain a short-term decrease in their BMI and mentioned negative emotions from app use, while participants in the underweight-normal BMI group used the app more frequently and significantly increased their daily step count. These differences highlight the importance of intervention personalization. Future research should explore the role of personalized features to help overcome personal barriers and better match individual preferences and needs.
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