Mapping the adult human esophagus in vivo and in vitro.

Many esophageal diseases can arise during development or throughout life. Therefore, well-characterized in vitro models and detailed methods are essential for studying human esophageal development, homeostasis and disease. Here, we (1) create an atlas of the cell types observed in the normal adult human esophagus; (2) establish an ancestrally diverse biobank of in vitro esophagus tissue to interrogate homeostasis and injury; and (3) benchmark in vitro models using the adult human esophagus atlas. We created a single-cell RNA sequencing reference atlas using fresh adult esophagus biopsies and a continuously expanding biobank of patient-derived in vitro cultures (n=55 lines). We identify and validate several transcriptionally distinct cell classes in the native human adult esophagus, with four populations belonging to the epithelial layer, including basal, epibasal, early differentiating and terminally differentiated luminal cells. Benchmarking in vitro esophagus cultures to the in vivo reference using single-cell RNA sequencing shows that the basal stem cells are robustly maintained in vitro, and the diversity of epithelial cell types in culture is dependent on cell density. We also demonstrate that cultures can be grown in 2D or as 3D organoids, and these methods can be employed for modeling the complete epithelial layers, thereby enabling in vitro modeling of the human adult esophagus.

Straddling "the line" as a Health Communication Scholar: Reflexive Privilege and Positionality in International Contexts.

In this essay, I offer an equatorial metaphor as a lens for reflexivity about positionality and privilege in field-based research. I draw on my experiences traveling and working with an international research team to reflect on my varying roles as a participant and observer. The lens of an equatorial metaphor reveals the blurred, sometimes collapsed, and ever-shifting line between insider and outsider. Reflexivity is vital, particularly in international contexts where work across differences is informed by embodied identities like race, gender, and sexuality.

In Vitro and In Vivo Development of the Human Airway at Single-Cell Resolution.

Bud tip progenitor cells give rise to all murine lung epithelial lineages and have been described in the developing human lung; however, the mechanisms controlling human bud tip differentiation into specific lineages are unclear. Here, we used homogeneous human bud tip organoid cultures and identified SMAD signaling as a key regulator of the bud tip-to-airway transition. SMAD induction led to the differentiation of airway-like organoids possessing functional basal cells capable of clonal expansion and multilineage differentiation. To benchmark in vitro-derived organoids, we developed a single-cell mRNA sequencing atlas of the human lung from 11.5 to 21 weeks of development, which revealed high degrees of similarity between the in vitro-derived and in vivo airway. Together, this work sheds light on human airway differentiation in vitro and provides a single-cell atlas of the developing human lung.

Cultivating Passion through Collaborative Art: A Dialogic Exploration of Disability, Storytelling, and Social Change.

This essay explores the role of art and storytelling in organizing expressive and vocational opportunities for individuals with developmental disabilities. Passion Works is a non-profit organization that fosters collaborative art-making among people with differing abilities. Guided by an asset-based approach titled the Creative Abundance Model, the studio challenges deficit-based narratives that guide traditional programming in sheltered workshops for individuals with developmental disabilities. The studio functions as an incubator of discovery, a process central to fostering individual well-being and social change.

Defining Moments Telling Stories to Foster Well-being, Humanize Healthcare, and Advocate for Change.

Health Communication launched the "Defining Moments" forum in 2009 to showcase the social and material power of storytelling. On its 10-year anniversary, we take stock of how authors have enacted "Defining Moments" including what was narrated, by whom, and why. In eight loosely coupled thematic clusters, we revisit the more than 75 published essays to date, finding value in ways that speak to the emerging and enduring issues of concern for health communication scholars. Across the essays, the maturation of health narrative theorizing is revealed by the sheer scope of topics addressed, coupled with the expanded voices and ways of voicing experience. Collectively, these essays have enlarged academic conventions and offered diverse entry points for refiguring the experience of illness and well-being.

Computational Studies of Relative Stabilities of Low-Spin d6 cis- and trans-[M(en)2X2]+ Complexes (M = Co, Rh, Ir): Steric and Electronic Effects in the Context of the Structural Trans Influence.

Computational studies of low spin d6 cis- and trans-[M(en)2X2]+ complexes (M = Co, Rh, Ir) employing multiple model chemistries find that isomer preferences fall into three categories. Complexes where X is largely a σ-donor (H-, CH3-, CF3-) prefer cis geometries, in keeping with predictions associated with the trans influence series. Complexes where this donor characteristic is augmented by π acceptor behavior (B(CF3)2-, BCl2-, SiCl3-) evince even greater preference for cis geometries. QTAIM charge data suggest this is marked by lower positive charge on the metal in cis complexes. In contrast, complexes where X is a π donor and low in the trans influence series (X = OH-, F-, Cl-, I-) prefer trans geometries to varying degrees. QTAIM calculations indicate that this arises because the cis complexes are destabilized by distortions of the electron density in the M-X bonds. This can be viewed conceptually as resulting from repulsions between lone pair electrons on the ligands. Complexes where the X ligands are moderately trans-influencing and can interact conjugatively (CN-, NC-, NO2-, C≡CH-) prefer trans geometries because they combine destabilization of cis geometries with enhanced stabilization of trans geometries resulting from conjugation.

Pilot Intervention Addressing Social Support and Functioning of Low Socioeconomic Status Older Adults With ESRD: The Seniors Optimizing Community Integration to Advance Better Living with ESRD (SOCIABLE) Study.

RATIONALE & OBJECTIVE: Older adults with end-stage kidney disease have increased morbidity, fatigue, and decreased physical function, which can inhibit self-care and social engagement. We pilot tested a home-based program to improve physical and social functioning of low socioeconomic status older adults treated with hemodialysis (HD). STUDY DESIGN: Qualitative study and randomized waitlist control intervention. SETTING & PARTICIPANTS: Older adult HD patients in Baltimore, MD. INTERVENTIONS: We identified functional needs and home environmental barriers to social engagement through focus groups; mapped findings onto aspects of an established program, which includes home visits with an occupational therapist, nurse, and handyman to provide ≤$1,300 worth of repairs, modifications, and devices; and piloted the program (Seniors Optimizing Community Integration to Advance Better Living with ESRD [SOCIABLE]) among 12 older adult HD patients. We delivered the services over 5 months in a staggered fashion. OUTCOMES: Feasibility and acceptability of the intervention and change in disability scores. RESULTS: Focus group themes included fatigue, lack of social support, and desire to live independently. SOCIABLE pilot participants were recruited from 2 dialysis units and all were African American (50% men); mean age was 69 years. At baseline, the mean disability score for activities of daily living (ADLs) was 4.4 and for instrumental ADLs (IADLs) was 6.3 (both out of a possible 16). Among the 9 participants alive at follow-up, there was 100% intervention completion and outcomes assessment. All treated participants improved a mean score of 2.3 for ADL and 2.6 for IADL disability, and social support and social network scores improved by 4.8 and 4.6, respectively. LIMITATIONS: Small sample size; all participants were African American. CONCLUSIONS: A home-based intervention addressing physical and social functioning of low socioeconomic status older adults on HD therapy was feasible and acceptable.

Using citizen science to bridge taxonomic discovery with education and outreach.

PREMISE OF THE STUDY: Biological collections are uniquely poised to inform the stewardship of life on Earth in a time of cataclysmic biodiversity loss. Efforts to fully leverage collections are impeded by a lack of trained taxonomists and a lack of interest and engagement by the public. We provide a model of a crowd-sourced data collection project that produces quality taxonomic data sets and empowers citizen scientists through real contributions to science. Entitled MicroPlants, the project is a collaboration between taxonomists, citizen science experts, and teachers and students from universities and K-12. METHODS: We developed an online tool that allows citizen scientists to measure photographs of specimens of a hyper-diverse group of liverworts from a biodiversity hotspot. RESULTS: Using the MicroPlants online tool, citizen scientists are generating high-quality data, with preliminary analysis indicating non-expert data can be comparable to expert data. DISCUSSION: More than 11,000 users from both the website and kiosk versions have contributed to the data set, which is demonstrably aiding taxonomists working toward establishing conservation priorities within this group. MicroPlants provides opportunities for public participation in authentic science research. The project's educational component helps move youth toward engaging in scientific thinking and has been adopted by several universities into curriculum for both biology and non-biology majors.

Pain, Racial Discrimination, and Depressive Symptoms among African American Women.

African American women with osteoarthritis (OA) are at high risk of experiencing pain. They report more pain than non-Hispanic White women and men of other racial/ethnic groups. This pain can limit independence and diminish their quality of life. Despite the detrimental effects that pain can have on older African American women with OA, there is a dearth of literature examining factors beyond the OA pathology that are associated with pain outcomes within this population. The purpose of this study was to examine the relationships between racial discrimination and depressive symptoms with pain intensity in African American women with OA. The sample comprised of 120 African American women, aged 50-80 years, with OA, from Texas and New Mexico. The women completed survey booklets to answer study questionnaires. We used multiple linear regression to test associations between racial discrimination, depressive symptoms, and pain intensity. We tested whether depressive symptoms mediated the relationship between racial discrimination and pain intensity by using bootstrapping. Results indicated that racial discrimination was significantly associated with pain intensity and that this relationship was mediated by depressive symptoms, even after controlling for body mass index, years of education, and length of time with OA. Both depressive symptoms and racial discrimination may be modifiable. If these modifiable factors are addressed in this population, there may be decreased pain in middle-aged and older African American women.

Docking protein domains in contact space.

BACKGROUND: Many biological processes involve the physical interaction between protein domains. Understanding these functional associations requires knowledge of the molecular structure. Experimental investigations though present considerable difficulties and there is therefore a need for accurate and reliable computational methods. In this paper we present a novel method that seeks to dock protein domains using a contact map representation. Rather than providing a full three dimensional model of the complex, the method predicts contacting residues across the interface. We use a scoring function that combines structural, physicochemical and evolutionary information, where each potential residue contact is assigned a value according to the scoring function and the hypothesis is that the real configuration of contacts is the one that maximizes the score. The search is performed with a simulated annealing algorithm directly in contact space. RESULTS: We have tested the method on interacting domain pairs that are part of the same protein (intra-molecular domains). We show that it correctly predicts some contacts and that predicted residues tend to be significantly closer to each other than other pairs of residues in the same domains. Moreover we find that predicted contacts can often discriminate the best model (or the native structure, if present) among a set of optimal solutions generated by a standard docking procedure. CONCLUSION: Contact docking appears feasible and able to complement other computational methods for the prediction of protein-protein interactions. With respect to more standard docking algorithms it might be more suitable to handle protein conformational changes and to predict complexes starting from protein models.