Adherens junctions and desmosomes are critical for embryogenesis and the integrity of adult tissues. To form these junctions, classical cadherins interact via α- and β-catenin with the actin cytoskeleton, whereas desmosomal cadherins interact with the intermediate filament system. Here, we used a hormone-activated mutant N-cadherin expressed in fibroblasts to show the existence of a novel classical cadherin adhesion system. N-cadherin was fused at its C-terminus to a modified estrogen receptor ligand-binding domain (NcadER) that binds 4-hydroxytamoxifen (4OHT) and expressed in L cells, which lack an endogenous cadherin. Cells with the mutant cadherin (LNER cells) aggregated in the absence of 4OHT, but only in its presence formed tightly compacted aggregates like those formed by L cells expressing wild-type N-cadherin (LN cells). Compaction of LNER cells treated with 4OHT was accompanied by elevated levels of p120ctn in NcadER immunoprecipitates, compared to immunoprecipitates of non-treated cells, but without changes in α- and β-catenin, or actin. Compaction induced by 4OHT was also accompanied by increased interaction of the NcadER with the cytoskeleton and increased vimentin organization. Vimentin co-immunoprecipitated with the NcadER/catenin complex, suggesting an interaction between cadherin and vimentin. The mechanism by which vimentin interacts with the cadherin appears to involve p120ctn as it co-immunoprecipitates and colocalizes with vimentin in the parent L cells, which lack a cadherin and α- and β-catenins. Disrupting the actin cytoskeleton with cytochalasin B inhibited aggregation, whereas knocking down vimentin with specific siRNAs inhibited compaction. Based on our results we propose that a vimentin-based classical cadherin complex functions together with the actin-based complex to promote strong cell-cell adhesion in fibroblasts.
Objectives. We conducted a qualitative study of primary care providers to assess the challenges and opportunities in implementing a universal screening program for Hepatitis C Virus (HCV) at an urban community-based health center serving a largely disadvantaged population. Methods. Qualitative semi-structured interviews of prescribing providers took place pre-and posteducational intervention, at a single federally qualified health center in Wilmington, Delaware, between September 2018 and July 2019. The intervention included a two-day didactic session and shadowing specialist providers. Data captured provider perspectives on universal screening and treatment. The interviews were transcribed verbatim, then grouped into codes, then finally, themes. Results. Emergent themes included hesitancy in managing universal screening programs in the primary care environment, positive attitudes surrounding treatment, fewer HCV cases than expected, and concern with both patient-level barriers and practice-level barriers. Preintervention and post-intervention themes were similar. Conclusions. Implementation programs exploring universal HCV screening in the primary care environment should include educational opportunities that are available to all individuals in the practice, sustained organizational support, and available patient literature targeted to patients with varying health literacy and in languages other than English. In short, universal HCV screening and treatment is feasible in the primary medical environment but requires ongoing support and education for providers to ensure success.
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