Defining "Ethical Mathematical Practice" Through Engagement with Discipline-Adjacent Practice Standards and the Mathematical Community.

This project explored what constitutes "ethical practice of mathematics". Thematic analysis of ethical practice standards from mathematics-adjacent disciplines (statistics and computing), were combined with two organizational codes of conduct and community input resulting in over 100 items. These analyses identified 29 of the 52 items in the 2018 American Statistical Association Ethical Guidelines for Statistical Practice, and 15 of the 24 additional (unique) items from the 2018 Association of Computing Machinery Code of Ethics for inclusion. Three of the 29 items synthesized from the 2019 American Mathematical Society Code of Ethics, and zero of the Mathematical Association of America Code of Ethics, were identified as reflective of "ethical mathematical practice" beyond items already identified from the other two codes. The community contributed six unique items. Item stems were standardized to, "The ethical mathematics practitioner…". Invitations to complete the 30-min online survey were shared nationally (US) via Mathematics organization listservs and other widespread emails and announcements. We received 142 individual responses to the national survey, 75% of whom endorsed 41/52 items, with 90-100% endorsing 20/52 items on the survey. Items from different sources were endorsed at both high and low rates. A final thematic analysis yielded 44 items, grouped into "General" (12 items), "Profession" (10 items) and "Scholarship" (11 items). Moreover, for the practitioner in a leader/mentor/supervisor/instructor role, there are an additional 11 items (4 General/7 Professional). These results suggest that the community perceives a much wider range of behaviors by mathematicians to be subject to ethical practice standards than had been previously included in professional organization codes. The results provide evidence against the argument that mathematics practitioners engaged in "pure" or "theoretical" work have minimal, small, or no ethical obligations.

Matrix metalloproteinase-7 coordinates airway epithelial injury response and differentiation of ciliated cells.

Matrix metalloproteinase-7 (MMP7) expression is quickly up-regulated after injury, and functions to regulate wound repair and various mucosal immune processes. We evaluated the global transcriptional response of airway epithelial cells from wild-type and Mmp7-null mice cultured at an air-liquid interface. The analysis of differentially expressed genes between genotypes after injury revealed an enrichment of functional categories associated with inflammation, cilia, and differentiation. Because these analyses suggested that MMP7 regulated ciliated cell formation, we evaluated the recovery of the airway epithelium in wild-type and Mmp7-null mice in vivo after naphthalene injury, which revealed augmented ciliated cell formation in the absence of MMP7. Moreover, in vitro studies evaluating cell differentiation in air-liquid interface cultures also showed faster ciliated cell production under Mmp7-null conditions compared with wild-type conditions. These studies identified a new role for MMP7 in attenuating ciliated cell differentiation during wound repair.

Transmembrane and extracellular domains of syndecan-1 have distinct functions in regulating lung epithelial migration and adhesion.

Syndecan-1 is a cell surface proteoglycan that can organize co-receptors into a multimeric complex to transduce intracellular signals. The syndecan-1 core protein has multiple domains that confer distinct cell- and tissue-specific functions. Indeed, the extracellular, transmembrane, and cytoplasmic domains have all been found to regulate specific cellular processes. Our previous work demonstrated that syndecan-1 controls lung epithelial migration and adhesion. Here, we identified the necessary domains of the syndecan-1 core protein that modulate its function in lung epithelial repair. We found that the syndecan-1 transmembrane domain has a regulatory function in controlling focal adhesion disassembly, which in turn controls cell migration speed. In contrast, the extracellular domain facilitates cell adhesion through affinity modulation of α(2)ß(1) integrin. These findings highlight the fact that syndecan-1 is a multidimensional cell surface receptor that has several regulatory domains to control various biological processes. In particular, the lung epithelium requires the syndecan-1 transmembrane domain to govern cell migration and is independent from its ability to control cell adhesion via the extracellular domain.

Syndecan-1 controls cell migration by activating Rap1 to regulate focal adhesion disassembly.

After injury, residual epithelial cells coordinate contextual clues from cell-cell and cell-matrix interactions to polarize and migrate over the wound bed. Protrusion formation, cell body translocation and rear retraction is a repetitive process that allows the cell to move across the substratum. Fundamental to this process is the assembly and disassembly of focal adhesions that facilitate cell adhesion and protrusion formation. Here, we identified syndecan-1 as a regulator of focal adhesion disassembly in migrating lung epithelial cells. Syndecan-1 altered the dynamic exchange of adhesion complex proteins, which in turn regulates migration speed. Moreover, we provide evidence that syndecan-1 controls this entire process through Rap1. Thus, syndecan-1 restrains migration in lung epithelium by activating Rap1 to slow focal adhesion disassembly.