Abstract. E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent, homotypic cell-cell adhesion and plays an important role in maintaining the normal phenotype of epithelial cells. Disruption of E-cadherin activity in epithelial cells correlates with formation of metastatic tumors. Decreased adhesive function may be implemented in a number of ways including: (a) decreased expression of E-cadherin; (b) mutations in the gene encoding E-cadherin; or (c) mutations in the genes that encode the catenins, proteins that link the cadherins to the cytoskeleton and are essential for cadherin mediated cell-cell adhesion. In this study, we explored the possibility that inappropriate expression of a nonepithelial cadherin by an epithelial cell might also result in disruption of cell-cell adhesion. We showed that a squamous cell carcinoma--derived cell line expressed N-cadherin and displayed a scattered fibroblastic phenotype along with decreased expression of E-and P-cadherin. Transfection of this cell line with antisense N-cadherin resulted in reversion to a normalappearing squamous epithelial cell with increased E-and P-cadherin expression. In addition, transfection of a normal-appearing squamous epithelial cell line with N-cadherin resulted in downregulation of both E-and P-cadherin and a scattered fibroblastic phenotype. In all cases, the levels of expression of N-cadherin and E-cadherin were inversely related to one another. In addition, we showed that some squamous cell carcinomas expressed N-cadherin in situ and those tumors expressing N-cadherin were invasive. These studies led us to propose a novel mechanism for tumorigenesis in squamous epithelial ceils; i.e., inadvertent expression of a nonepithelial cadherin. THE cadherins are members of a large family of transmembrane glycoproteins that mediate calciumdependent, homotypic cell-cell adhesion and play an important role in the maintenance of normal tissue architecture (reviewed in Takeichi, 1990). As the transmembrane component of the adherens junction, they are composed of three segments: (a) an extracellular domain responsible for cadherin-cadherin interaction; (b) a singlepass transmembrane domain; and (c) a highly conserved cytoplasmic domain that associates with actin filaments and thus serves to connect the outside of the cell to the cytoskeleton. Cadherins are not bound directly to the actin cytoskeleton, but rather, are connected indirectly via a group of proteins known as the catenins.The catenins were identified as proteins coimmunoprecipitating with the classic cadherins, and were named ~-catenin, 13-catenin, and ~/-catenin according to their mobility on SDS-PAGE (Nagafuchi and Takeichi, 1988;Ozawa

Axon guidance proteins are critical for the correct wiring of the nervous system during development. Several axon guidance cues and their family members have been well characterized. More unidentified axon guidance cues are assumed to participate in the formation of the extremely complex nervous system. We identified a secreted protein, draxin, that shares no homology with known guidance cues. Draxin inhibited or repelled neurite outgrowth from dorsal spinal cord and cortical explants in vitro. Ectopically expressed draxin inhibited growth or caused misrouting of chick spinal cord commissural axons in vivo. draxin knockout mice showed defasciculation of spinal cord commissural axons and absence of all forebrain commissures. Thus, draxin is a previously unknown chemorepulsive axon guidance molecule required for the development of spinal cord and forebrain commissures.

Background Post-coronavirus disease (COVID-19) syndrome includes persistence of symptoms beyond viral clearance and fresh development of symptoms or exaggeration of chronic diseases within a month after initial clinical and virological cure of the disease with a viral etiology. We aimed to determine the incidence, association, and risk factors associated with development of the post-COVID-19 syndrome. Methods We conducted a prospective cohort study at Dhaka Medical College Hospital between June 01, 2020 and August 10, 2020. All the enrolled patients were followed up for a month after clinical improvement, which was defined according the World Health Organization and Bangladesh guidelines as normal body temperature for successive 3 days, significant improvement in respiratory symptoms (respiratory rate <25/breath/minute with no dyspnea), and oxygen saturation >93% without assisted oxygen inhalation. Findings Among the 400 recruited patients, 355 patients were analyzed. In total, 46% patients developed post-COVID-19 symptoms, with post-viral fatigue being the most prevalent symptom in 70% cases. The post-COVID-19 syndrome was associated with female gender (relative risk [RR]: 1.2, 95% confidence interval [CI]: 1.02–1.48, p = 0.03), those who required a prolonged time for clinical improvement (p<0.001), and those showing COVID-19 positivity after 14 days (RR: 1.09, 95% CI: 1.00–1.19, p<0.001) of initial positivity. Patients with severe COVID-19 at presentation developed post-COVID-19 syndrome (p = 0.02). Patients with fever (RR: 1.5, 95% CI: 1.05–2.27, p = 0.03), cough (RR: 1.36, 95% CI: 1.02–1.81, p = 0.04), respiratory distress (RR: 1.3, 95% CI: 1.4–1.56, p = 0.001), and lethargy (RR: 1.2, 95% CI: 1.06–1.35, p = 0.003) as the presenting features were associated with the development of the more susceptible to develop post COVID-19 syndrome than the others. Logistic regression analysis revealed female sex, respiratory distress, lethargy, and long duration of the disease as risk factors. Conclusion Female sex, respiratory distress, lethargy, and long disease duration are critical risk factors for the development of post-COVID-19 syndrome.

Abstract. E-and N-cadherin are members of the classical cadherin family of proteins. E-cadherin plays an important role in maintaining the normal phenotype of epithelial cells. Previous studies from our laboratory and other laboratories have shown that inappropriate expression of N-cadherin by tumor cells derived from epithelial tissue results in conversion of the cell to a more fibroblast-like cell, with increased motility and invasion. Our present study was designed to determine which domains of N-cadherin make it different from E-cadherin, with respect to altering cellular behavior, such as which domains are responsible for the epithelial to mesenchymal transition and increased cell motility and invasion. To address this question, we constructed chimeric cadherins comprised of selected domains of E-and N-cadherin. The chimeras were transfected into epithelial cells to determine their effect on cell morphology and cellular behavior. We found that a 69-amino acid portion of EC-4 of N-cadherin was necessary and sufficient to promote both an epithelial to mesenchymal transition in squamous epithelial cells and increased cell motility. Here, we show that different cadherin family members promote different cellular behaviors. In addition, we identify a novel activity that can be ascribed to the extracellular domain of N-cadherin.

Objective We evaluated whether ivermectin combined with doxycycline reduced the clinical recovery time in adults with COVID-19 infection. Methods This was a randomized, blinded, placebo-controlled trial in patients with mild-to-moderate COVID-19 symptoms randomly assigned to treatment (n = 200) and placebo (n = 200) groups. The primary outcome was duration from treatment to clinical recovery. Secondary outcomes were disease progression and persistent COVID-19 positivity by RT-PCR. Results Among 556 screened patients, 400 were enrolled and 363 completed follow-up. The mean patient age was 40 years, and 59% were men. The median recovery time was 7 (4–10, treatment group) and 9 (5–12, placebo group) days (hazard ratio, 0.73; 95% confidence interval, 0.60–0.90). The number of patients with a ≤7-day recovery was 61% (treatment group) and 44% (placebo groups) (hazard ratio, 0.06; 95% confidence interval, 0.04–0.09). The proportion of patients who remained RT-PCR positive on day 14 and whose disease did not progress was significantly lower in the treatment group than in the placebo group. Conclusions Patients with mild-to-moderate COVID-19 infection treated with ivermectin plus doxycycline recovered earlier, were less likely to progress to more serious disease, and were more likely to be COVID-19 negative by RT-PCR on day 14. Trial Registration ClinicalTrials.gov Identifier: NCT04523831. Data Repository ID Dryad. doi:10.5061/dryad.qjq2bvqf6