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This paper advocates for the inclusion of big questions into the basic course curriculum. It begins by exploring the nature of big questions as those that engage pressing and perennial civic and global issues, and details their effectiveness in encouraging students and faculty to think about interpersonal responsibility and social space as dynamically interfacing and mutually reflexive, thus challenging us to negotiate the civic call of engaging in democratic processes. The basic course, whether public speaking or hybrid, offers a crucial opportunity for big questions to emerge because it brings people together to critically question and produce messages about the social and civic contexts in which we all engage as students, faculty, employees, family, and citizens. Thus, the article includes examples from several basic course instructors and administrators of how big questions can be incorporated into the curriculum to enhance the learning outcomes of students, while at the same time situating the basic course as more deeply embedded into the stated mission and requirements of our departments, colleges, and general education programs.

Riboswitches rely on structured aptamer domains to selectively sense their target ligands and regulate gene expression. However, some riboswitch aptamers in bacteria carry mutations in their otherwise strictly conserved binding pockets that change ligand specificities. The aptamer domain of a riboswitch class originally found to selectively sense guanine forms a three-stem junction that has since been observed to exploit numerous alterations in its ligand-binding pocket. These rare variants have modified their ligand specificities to sense other purines or purine derivatives, including adenine, 2'-deoxyguanosine (three classes), and xanthine. Herein, we report the characteristics of a rare variant that is narrowly distributed in the Paenibacillaceae family of bacteria. Known representatives are always associated with genes encoding 8-oxoguanine deaminase. As predicted from this gene association, these variant riboswitches tightly bind 8-oxoguanine (8-oxoG), strongly discriminate against other purine derivatives, and function as genetic "ON" switches. Following exposure of cells to certain oxidative stresses, a representative 8-oxoG riboswitch activates gene expression, likely caused by the accumulation of 8-oxoG due to oxidative damage to G nucleobases in DNA, RNA, and the nucleotide pool. Furthermore, an engineered version of the variant aptamer was prepared that exhibits specificity for 8-oxoadenine, further demonstrating that RNA aptamers can acquire mutations that expand their ability to detect and respond to oxidative damage. [ABSTRACT FROM AUTHOR]

Fractional exhaled nitric oxide (FeNO) is a well-established measure of allergic airway inflammation and possible useful adjunct disease management tool. We investigated the association of baseline and follow-up FeNO measurements with disease burden in minority children with persistent asthma. A retrospective chart review was conducted on 352 African American and Hispanic children seen at an urban Asthma Center in Bronx, NY. Demographic, clinical characteristics, and pulmonary function tests (PFTs) were compared between children with low, intermediate, and high baseline FeNO levels. Among 95 children with subsequent follow up visits, associations of change in FeNO with demographics, clinical characteristics, and PFTs were examined using mixed effects linear regression models. A higher proportion of children with intermediate (54%) and high FeNO (58%) levels had lower airways obstruction compared to those with low FeNO levels (33%). Children with intermediate FeNO levels had more annual hospitalizations (2.8 ± 6.2) compared to those with low and high FeNO levels (1.3 ± 2.8 and 1.3 ± 2.5). These associations did not differ between ethnicities. An increase in FeNO over time was associated with higher BMI z-scores (β = 6.2, 95% CI: 1.0 to 11.4) and two or more hospitalizations in the past year (β = 16.1, 95% CI: 1.5 to 30.8). Intermediate and high FeNO levels are associated with lower airways obstruction and hospitalizations. Initial and serial FeNO measurements can be a useful adjunctive tool in identifying asthma-related morbidity in urban African American and Hispanic children. [ABSTRACT FROM AUTHOR]