Abstract
Background
There are concerns about the representation of vulnerable and underrepresented racial-ethnic minorities in biomedical and public health research, particularly when the research ...requires the collection of biospecimens. The current paper reports on the acceptability, feasibility, and ethics of saliva collection in a study examining the relationship between chronic stressors among mostly mixed-status, Latinx families (
N
= 30) during high immigration enforcement.
Methods
Data for this study included anthropometric measures and salivary biospecimens from each family member (
N
= 110) and a household survey. Data for this analysis are from ethnographic field notes, which were analyzed using a bricolage of critical ethnography and case study analysis techniques.
Results
We discuss the feasibility, aversions, acceptability, and ethical implications of integrating salivary biomarkers with Mexican-origin mixed-status families living in an area with restrictive immigration enforcement policies. We present the recruitment and data collection strategies used by the research team to gain participants’ trust, retain families, and maintain confidentiality.
Conclusion
We recommend that researchers who obtain biospecimens from Latinx, Mexican-origin, and/or immigrant populations answer the participants’ questions honestly and without fear that they will not understand the science to obtain voluntary assent and consent. We recommend that researchers be knowledgeable of the sociopolitical context that the Latinx, immigrant, and in particular, mixed-status families inhabit so that they are prepared to provide informational resources. Finally, we think it is imperative that the study team in the field be bilingual, multicultural Latinx persons who identify with the community.
Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination ...with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results provide evidence that AT1 cells have both structural and signaling roles in alveolar maturation and can exit their terminally differentiated non-proliferative state. Our findings suggest that AT1 cells might be a new target in the pathogenesis and treatment of lung diseases associated with premature birth.
Mammalian organs, including the lung and kidney, often adopt a branched structure to achieve high efficiency and capacity of their physiological functions. Formation of a functional lung requires two ...developmental processes: branching morphogenesis, which builds a tree-like tubular network, and alveolar differentiation, which generates specialized epithelial cells for gas exchange. Much progress has been made to understand each of the two processes individually; however, it is not clear whether the two processes are coordinated and how they are deployed at the correct time and location. Here we show that an epithelial branching morphogenesis program antagonizes alveolar differentiation in the mouse lung. We find a negative correlation between branching morphogenesis and alveolar differentiation temporally, spatially, and evolutionarily. Gain-of-function experiments show that hyperactive small GTPase Kras expands the branching program and also suppresses molecular and cellular differentiation of alveolar cells. Loss-of-function experiments show that SRY-box containing gene 9 (Sox9) functions downstream of Fibroblast growth factor (Fgf) / Kras to promote branching and also suppresses premature initiation of alveolar differentiation. We thus propose that lung epithelial progenitors continuously balance between branching morphogenesis and alveolar differentiation, and such a balance is mediated by dual-function regulators, including Kras and Sox9 . The resulting temporal delay of differentiation by the branching program may provide new insights to lung immaturity in preterm neonates and the increase in organ complexity during evolution.
The University of Iowa Mobile Clinic (UIMC) is an interdisciplinary student-run free medical clinic founded in 2002. UIMC provides free health screenings, education, and basic services to underserved ...populations in Iowa: immigrants, refugees, migrant farmworkers, individuals experiencing homelessness, low-income individuals, and people who live in rural communities. Forty-four percent of patients surveyed use UIMC as their only source of care. Ninety-seven percent of patients surveyed rate care as excellent or good. UIMC is a crucial safety net health care resource in Iowa to improve health equity.
Leptospirosis is a widespread zoonotic infection that primarily affects residents of tropical regions, but causes infections in animals and humans in temperate regions as well. The agents of ...leptospirosis comprise several members of the genus Leptospira, which also includes non-pathogenic, saprophytic species. Leptospirosis can vary in severity from a mild, non-specific illness to severe disease that includes multi-organ failure and widespread endothelial damage and hemorrhage. To begin to investigate how pathogenic leptospires affect endothelial cells, we compared the responses of two endothelial cell lines to infection by pathogenic versus non-pathogenic leptospires. Microarray analyses suggested that pathogenic L. interrogans and non-pathogenic L. biflexa triggered changes in expression of genes whose products are involved in cellular architecture and interactions with the matrix, but that the changes were in opposite directions, with infection by L. biflexa primarily predicted to increase or maintain cell layer integrity, while L. interrogans lead primarily to changes predicted to disrupt cell layer integrity. Neither bacterial strain caused necrosis or apoptosis of the cells even after prolonged incubation. The pathogenic L. interrogans, however, did result in significant disruption of endothelial cell layers as assessed by microscopy and the ability of the bacteria to cross the cell layers. This disruption of endothelial layer integrity was abrogated by addition of the endothelial protective drug lisinopril at physiologically relevant concentrations. These results suggest that, through adhesion of L. interrogans to endothelial cells, the bacteria may disrupt endothelial barrier function, promoting dissemination of the bacteria and contributing to severe disease manifestations. In addition, supplementing antibiotic therapy with lisinopril or derivatives with endothelial protective activities may decrease the severity of leptospirosis.
Methane is an important component of the gases released from lakes. Understanding the factors influencing the release is important for mitigating this greenhouse gas. The volume of methane (CH4) and ...other gases in sediments, and the rate of CH4 ebullition, were determined for an artificially aerated, shallow, eutrophic freshwater lake in Southern California. Gas volume was measured at 28 sites in July 2010, followed by monthly sampling at 7 sites through December 2011. Gas volumes measured in July 2010 at the 28 sites exhibited a complex dependence on sediment properties; the volume of CH4 and other gases was negligible in very coarse-textured sediment with low water and organic carbon contents. Gas volumes increased strongly with increased silt content, and were highest in sediments with intermediate water contents (60 to 70%), organic carbon contents (2 to 3%) and depths (approximately 4m). Methane was the dominant gas collected from sediment (80 to 90%), while carbon dioxide comprised roughly 2 to 3% of sediment gas in the lake. Gas sampling during cool winter months revealed very low or undetectable volumes of gas present, while sediment gas volumes increased markedly during the spring and early summer months, and then declined in late summer and fall. The rate of CH4 ebullition, quantified with an echosounder, also varied markedly across the lake and seasonally. High rates of ebullition were measured at all 7 sites in July 2011 (up to 96mmolCH4m−2d−1), while the rates were >50% lower in September and negligible in December 2010. Ebullition rates were inversely correlated with depth and most other sediment properties, but strongly positively correlated with sand content. No simple relationship between ebullition rate and sediment gas volume across the set of sites was found, although ebullition rates at individual sites were strongly related to gas volume.
•Volume of gas in sediments and rate of ebullition determined for a shallow lake•Gas storage within sediments dependent upon sediment properties and season•Factors favoring storage of gas were associated with lower rates of ebullition.•Ratio of ebullition rate to gas volume suggested as index of impedance to flux
The flexibility of the ATP synthase's β subunit promotes its role in the ATP synthase rotational mechanism, but its domains stability remains unknown. A reversible thermal unfolding of the isolated β ...subunit (Tβ) of the ATP synthase from Bacillus thermophilus PS3, tracked through circular dichroism and molecular dynamics, indicated that Tβ shape transits from an ellipsoid to a molten globule through an ordered unfolding of its domains, preserving the β‐sheet residual structure at high temperature. We determined that part of the stability origin of Tβ is due to a transversal hydrophobic array that crosses the β‐barrel formed at the N‐terminal domain and the Rossman fold of the nucleotide‐binding domain (NBD), while the helix bundle of the C‐terminal domain is the less stable due to the lack of hydrophobic residues, and thus the more flexible to trigger the rotational mechanism of the ATP synthase.
The p53 pro-apoptotic tumour suppressor is mutated or functionally altered in most cancers. In epithelial tumours induced by 'high-risk' mucosal human papilloma viruses, including human cervical ...carcinoma and a growing number of head-and-neck cancers, p53 is degraded by the viral oncoprotein E6 (ref. 2). In this process, E6 binds to a short leucine (L)-rich LxxLL consensus sequence within the cellular ubiquitin ligase E6AP. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 (ref. 4). Neither E6 nor E6AP are separately able to recruit p53 (refs 3, 5), and the precise mode of assembly of E6, E6AP and p53 is unknown. Here we solve the crystal structure of a ternary complex comprising full-length human papilloma virus type 16 (HPV-16) E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumour suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against oncogenesis mediated by human papilloma virus.
Radiology is among the medical specialties that have made the fewest gains in closing the gap in underrepresented minorities and women. Diversity, equity, and inclusion (DEI) initiatives are ...important for promoting healthy learning environments for trainees, health equity for patients, and equitable career development opportunities for employees, all of which contribute to innovation in today's competitive health care environment. DEI committees can self-organize or form from institutional directives. These committees can implement impactful projects in multiple domains in education, recruitment and retention, department culture, and health equity research. This article describes the formation of a grassroots DEI committee, key initiatives and strategies, and structures for accountability.
RSNA, 2023 Quiz questions for this article are available in the supplemental material.
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