BackgroundMicrosatellite loci are frequently used in genomic studies of DNA sequence repeats and in population studies of genetic variability. To investigate the effect of sequence properties of microsatellites on their level of variability we have analyzed genotypes at 627 microsatellite loci in 1,048 worldwide individuals from the HGDP-CEPH cell line panel together with the DNA sequences of these microsatellites in the human RefSeq database.ResultsCalibrating PCR fragment lengths in individual genotypes by using the RefSeq sequence enabled us to infer repeat number in the HGDP-CEPH dataset and to calculate the mean number of repeats (as opposed to the mean PCR fragment length), under the assumption that differences in PCR fragment length reflect differences in the numbers of repeats in the embedded repeat sequences. We find the mean and maximum numbers of repeats across individuals to be positively correlated with heterozygosity. The size and composition of the repeat unit of a microsatellite are also important factors in predicting heterozygosity, with tetra-nucleotide repeat units high in G/C content leading to higher heterozygosity. Finally, we find that microsatellites containing more separate sets of repeated motifs generally have higher heterozygosity.ConclusionsThese results suggest that sequence properties of microsatellites have a significant impact in determining the features of human microsatellite variability.

Mucociliary clearance is composed of three components (i.e., mucin secretion, airway surface hydration, and ciliary-activity) which function coordinately to clear inhaled microbes and other foreign particles from airway surfaces. Airway surface hydration is maintained by water fluxes driven predominantly by active chloride and sodium ion transport. The ion channels that mediate electrogenic ion transport are regulated by extracellular purinergic signals that signal through G protein-coupled receptors. These purinoreceptors and the signaling pathways they activate have been identified as possible therapeutic targets for treating lung disease. A systems-level description of airway surface liquid (ASL) homeostasis could accelerate development of such therapies. Accordingly, we developed a mathematical model to describe the dynamic coupling of ion and water transport to extracellular purinergic signaling. We trained our model from steady-state and time-dependent experimental measurements made using normal and cystic fibrosis (CF) cultured human airway epithelium. To reproduce CF conditions, reduced chloride secretion, increased potassium secretion, and increased sodium absorption were required. The model accurately predicted ASL height under basal normal and CF conditions and the collapse of surface hydration due to the accelerated nucleotide metabolism associated with CF exacerbations. Finally, the model predicted a therapeutic strategy to deliver nucleotide receptor agonists to effectively rehydrate the ASL of CF airways.airway surface liquid | cystic fibrosis | mathematical modeling | purinergic signaling

Active learning improves student performance in STEM courses. Exposure to active learning environments generally occurs through traditional laboratory courses and independent research, both of which require access to resources that are limited at many universities. A previously reported active learning-based undergraduate journal club improved student achievement in communicating science. Here, we expanded on this previous journal club to improve student performance in the process of science. We developed and implemented a series of workshops and seminars referred to as “CASL Club,” an undergraduate journal club targeted at improving student development in applying the scientific process. Students were surveyed before and after CASL club about their confidence in accessing, analyzing, and reporting scientific research. Post-CASL club, the students reported increases in confidence in their abilities to access and present scientific articles and write scientific abstracts. Additionally, the students reported improved confidence and performance in their courses. Compared to the previous journal club study, the majority of sampled journal club participants were not exposed to primary literature as part of their general coursework. Our results illustrate active-learning based undergraduate journal clubs as a way to expose students to primary literature and improve students’ ability to apply scientific process in an active-learning environment at resource-limited universities.