CLINICAL, GENETICS AND MOLECULAR RISK FACTORS OF DENGUE SEVERITY

Ph.DDOCTOR OF PHILOSOPH

FRMD4A regulates the entry of West Nile virus into glioblastoma cells

Master'sJOINT M.SC. IN INFECTIOUS DISEASES, VACCINOLOGY AND DRUG DISCOVER

The impact of the COVID-19 pandemic on irritable bowel syndrome

Background: Gastrointestinal manifestations of the COVID-19 pandemic may mimic Irritable Bowel Syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID-19 on respondents with IBS. Methods: We conducted an anonymised survey using MySurvey platform from May to June 2020 in 35 countries. The general public's knowledge, attitudes and practices regarding personal hygiene and social distancing during this COVID-19 pandemic and the psychological impact of COVID-19 were assessed. Statistical analysis was performed to determine the differences in well-being and compliance to social distancing measures between IBS and non-IBS respondents. Factors associated with worsening of IBS symptoms were evaluated. For newly developed IBS-like symptoms, subjects must fulfill ROME IV criteria. Results: Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had IBS and 374 (13.8%) did not know what IBS was. Respondents with IBS reported significantly worse emotional, social and psychological well-being compared to non-IBS respondents and were less compliant to social distancing (28.2% vs 35.3%, p=0.029, table 1). Of the non-IBS respondents, 96 (4.7%) developed new IBS-like symptoms. Among IBS respondents, the majority reported no change in symptom severity (61.6%), while 26.6% reported improvement and 11.8% reported worsening in IBS symptoms. A higher proportion of respondents with no change in the severity of IBS symptoms was willing to practice social distancing indefinitely compared to those who deteriorated (74.9% vs 51.4%, p=0.016, table 2). In multivariate analysis (table 3), willingness to continue social distancing for only another 2–3 weeks was significantly associated with higher odds of worsening IBS while better emotional well-being was associated with lower odds. Conclusions: Our study showed differences in well-being and compliance to social distancing between IBS and non-IBS respondents, and these factors influence the worsening in severity of IBS. Further research will focus on how occupational stress and dietary changes may influence IBS symptoms

Multiple Conserved Domains of the Nucleoporin Nup124p and Its Orthologs Nup1p and Nup153 Are Critical for Nuclear Import and Activity of the Fission Yeast Tf1 Retrotransposon

The nucleoporin Nup124p is a host protein required for the nuclear import of both, retrotransposon Tf1-Gag as well as the retroviral HIV-1 Vpr in fission yeast. The human nucleoporin Nup153 and the Saccharomyces cerevisiae Nup1p were identified as orthologs of Nup124p. In this study, we show that all three nucleoporins share a large FG/FXFG-repeat domain and a C-terminal peptide sequence, GRKIxxxxxRRKx, that are absolutely essential for Tf1 retrotransposition. Though the FXFG domain was essential, the FXFG repeats themselves could be eliminated without loss of retrotransposon activity, suggesting the existence of a common element unrelated to FG/FXFG motifs. The Nup124p C-terminal peptide, GRKIAVPRSRRKR, was extremely sensitive to certain single amino acid changes within stretches of the basic residues. On the basis of our comparative study of Nup124p, Nup1p, and Nup153 domains, we have developed peptides that specifically knockdown retrotransposon activity by disengaging the Tf1-Gag from its host nuclear transport machinery without any harmful consequence to the host itself. Our results imply that those domains challenged a specific pathway affecting Tf1 transposition. Although full-length Nup1p or Nup153 does not complement Nup124p, the functionality of their conserved domains with reference to Tf1 activity suggests that these three proteins evolved from a common ancestor