Biology subjects

Nguyen, E.

Publications and source records attributed to Nguyen, E..

3 recordsLinked to original sources

bioRxiv2018

Local Contractions Test Rigidity of E-Cadherin Adhesions

E-cadherin is a major cell-cell adhesion molecule involved in mechanotransduction at cell-cell contacts in tissues. Since epithelial cells respond to rigidity and tension in the tissue through E-cadherin, there must be active processes that test and respond to the mechanical properties of these adhesive contacts. Using sub-micrometer, E-cadherin-coated PDMS pillars, we find that cells generate local contractions between E-cadherin adhesions and pull to a constant distance for a constant duration, irrespective of pillar rigidity. These cadherin contractions require non-muscle myosin IIB, tropomyosin 2.1, -catenin and binding of vinculin to -catenin; plus, they are correlated with rigidity-dependent cell spreading. Without contractions, cells fail to spread to different areas on soft and rigid surfaces and to maintain monolayer integrity. We further observe that cadherin contractions enable cells to test myosin IIA-mediated tension of neighboring cells, and sort out myosin IIA-depleted cells. Thus, we suggest that epithelial cells test and respond to the mechanical characteristics of neighboring cells through cadherin contractions.

cell biology↗

bioRxiv2017

Structure and misfolding of the flexible tripartite coiled coil domain of glaucoma-associated myocilin

Glaucoma-associated myocilin is a member of the olfactomedins, a protein family broadly involved in neuronal development and human disease. Molecular studies of the myocilin N-terminal coiled coil demonstrate a unique tripartite architecture: a disulfide-linked, parallel dimer-of-dimers Y-shaped molecule, with distinct tetramer and dimer regions. The structure of the C-terminal 7-heptad dimer elucidates an unexpected repeat pattern involving electrostatic inter-strand stabilization. Molecular dynamics simulations reveal an alternate conformation in which the terminal inter-strand disulfide bond limits the extent of unfolding and results in a kinked configuration. Taken together, full-length myocilin is also branched, with two pairs of C-terminal olfactomedin domains. Selected variants within the N-terminal region alter the apparent quaternary structure of myocilin but do so without compromising stability or causing aggregation. In addition to increasing our structural knowledge of extracellular coiled coils for protein design and biomedically important olfactomedins, this work broadens the scope of protein misfolding in the pathogenesis of myocilin-associated glaucoma.\n\nHighlightsO_LIGlaucoma-causing extracellular protein associated with amyloid forming propensity\nC_LIO_LIStructural studies confirm tripartite parallel dimer-of-dimers coiled coil\nC_LIO_LILeucine zipper exhibits non-canonical heptad repeat pattern with disulfide cap\nC_LIO_LIGlaucoma-associated variants in tetramer alter structure but not stability\nC_LI\n\neTOC blurbHill et al describe the structure of the coiled-coil region of myocilin, the extracellular olfactomedin family member closely associated with the ocular disorder glaucoma. Myocilins coiled coil adopts a unique Y-shaped parallel dimer-of-timers employing an unusual heptad repeat pattern. Selected disease variants alter quaternary structure.

biochemistry↗

bioRxiv2017

Exposure to Wood Smoke is Associated with Increased Risk of Asthma and Respiratory Symptoms in a Honduran Population

BackgroundExposure to environmental pollutants has been shown to be associated with asthma, but few studies have evaluated the effect of wood smoke on asthma and disease severity in a developing country, where use of stoves powered by solid fuels is a common practice.\n\nObjectiveIn a population in Olancho, Honduras, we evaluated the association between cooking fuel, stove type and asthma. We also evaluated the effects of these factors on asthma symptoms, lung function, and atopy.\n\nMethodsParticipants with physician-diagnosed asthma (n = 597) and controls without asthma (n = 429) were recruited from the Olancho province in Honduras. Participants were interviewed using a questionnaire and their baseline pulmonary function was measured using spirometry.\n\nResultsThe prevalence of use of wood as a cooking fuel was 66.9% in the study population, of which 42.1% of participants used wood as their only fuel. Use of wood as a cooking fuel was more prevalent among households with lower income, lower maternal education, and less urbanization. The prevalence of use of an open wood stove as the primary cooking stove among participants with asthma was 6.2% higher (95% CI 0.8 - 11.7%, p = .02) than among healthy controls. In a multiple logistic regression model, we identified a significant association between use of an open wood stove and asthma (OR = 1.80, 95% CI = 1.17 - 2.78, p = 0.007), compared to the referent (electric) stove category. Among participants with asthma, we identified a significant association between use of wood as cooking fuel and increased daytime respiratory symptoms (OR = 1.46, CI: 1.01 - 2.58, p = 0.046) and nocturnal symptoms (OR = 2.51, CI: 1.04 - 2.62, p = 0.04), though not with pulmonary function. Among control participants without asthma, use of wood as cooking fuel was associated with atopy (OR = 1.94, CI = 1.14 - 3.33, p = 0.015) and cough (OR = 2.22, CI = 1.09 - 4.88, p = 0.04).\n\nConclusionsUse of an open wood stove for cooking in a developing country appears to be a significant risk factor for asthma and respiratory symptoms. Exposure to wood smoke may play a role in atopic sensitization and respiratory symptoms, leading to the development of obstructive lung disease in susceptible individuals.

epidemiology↗