Zebrafish Trap230/Med12 is required for Sox9 activity and limb induction

This thesis deals with the mapping and cloning of trapped (tpd), a novel zebrafish mutant found to disrupt an ortholog of Trap230, a member of the Mediator complex. Mediator is a coactivator complex transducing the interaction of DNA-binding transcription factors with RNA polymerase II. The vertebrate Sox9 transcription factor directs the development of neural crest, otic placodes, cartilage, and bone. In zebrafish, there are two Sox9 orthologs, Sox9a and Sox9b, which together perform the functions of the single-copy tetrapod Sox9. The mutant phenotypes of tpd and the Sox9a/Sox9b double mutant are remarkably similar. The results of this thesis show that Trap230 is required for Sox9 activity. In addition, I show that Trap230 is required for an early step in pectoral fin induction, indicating that it also participates in Sox9-independent signaling events. Moreover, additional phenotypes in brain, eye, heart, muscle and gut development as well as axon guidance and a general downregulation phenotype of fibroblast growth factor expression in tpd mutants are described. These phenotypes may or may not be Sox9- dependent. This is the first characterisation of a vertebrate Trap230 mutant, and reveals a surprisingly specific requirement for Trap230 in mediating Sox9 activity

Unc5B Interacts with FLRT3 and Rnd1 to Modulate Cell Adhesion in Xenopus Embryos

The FLRT family of transmembrane proteins has been implicated in the regulation of FGF signalling, neurite outgrowth, homotypic cell sorting and cadherin-mediated adhesion. In an expression screen we identified the Netrin receptors Unc5B and Unc5D as high-affinity FLRT3 interactors. Upon overexpression, Unc5B phenocopies FLRT3 and both proteins synergize in inducing cell deadhesion in Xenopus embryos. Morpholino knock-downs of Unc5B and FLRT3 synergistically affect Xenopus development and induce morphogenetic defects. The small GTPase Rnd1, which transmits FLRT3 deadhesion activity, physically and functionally interacts with Unc5B, and mediates its effect on cell adhesion. The results suggest that FLRT3, Unc5B and Rnd1 proteins interact to modulate cell adhesion in early Xenopus development

Expression patterns of protein C inhibitor in mouse development

Proteolysis of extracellular matrix is an important requirement for embryonic development and is instrumental in processes such as morphogenesis, angiogenesis, and cell migration. Efficient remodeling requires controlled spatio-temporal expression of both the proteases and their inhibitors. Protein C inhibitor (PCI) effectively blocks a range of serine proteases, and recently has been suggested to play a role in cell differentiation and angiogenesis. In this study, we mapped the expression pattern of PCI throughout mouse development using in situ hybridization and immunohistochemistry. We detected a wide-spread, yet distinct expression pattern with prominent PCI levels in skin including vibrissae, and in fore- and hindgut. Further sites of PCI expression were choroid plexus of brain ventricles, heart, skeletal muscles, urogenital tract, and cartilages. A strong and stage-dependent PCI expression was observed in the developing lung. In the pseudoglandular stage, PCI expression was present in distal branching tubules whereas proximal tubules did not express PCI. Later in development, in the saccular stage, PCI expression was restricted to distal bronchioli whereas sacculi did not express PCI. PCI expression declined in postnatal stages and was not detected in adult lungs. In general, embryonic PCI expression indicates multifunctional roles of PCI during mouse development. The expression pattern of PCI during lung development suggests its possible involvement in lung morphogenesis and angiogenesis

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Zebrafish Trap230/Med12 is required for Sox9 activity and limb induction

This thesis deals with the mapping and cloning of trapped (tpd), a novel zebrafish mutant found to disrupt an ortholog of Trap230, a member of the Mediator complex. Mediator is a coactivator complex transducing the interaction of DNA-binding transcription factors with RNA polymerase II. The vertebrate Sox9 transcription factor directs the development of neural crest, otic placodes, cartilage, and bone. In zebrafish, there are two Sox9 orthologs, Sox9a and Sox9b, which together perform the functions of the single-copy tetrapod Sox9. The mutant phenotypes of tpd and the Sox9a/Sox9b double mutant are remarkably similar. The results of this thesis show that Trap230 is required for Sox9 activity. In addition, I show that Trap230 is required for an early step in pectoral fin induction, indicating that it also participates in Sox9-independent signaling events. Moreover, additional phenotypes in brain, eye, heart, muscle and gut development as well as axon guidance and a general downregulation phenotype of fibroblast growth factor expression in tpd mutants are described. These phenotypes may or may not be Sox9- dependent. This is the first characterisation of a vertebrate Trap230 mutant, and reveals a surprisingly specific requirement for Trap230 in mediating Sox9 activity

Um estudo de caso sobre a qualidade de vida no trabalho de bancários de Porto Alegre

O tema Qualidade de Vida no Trabalho expressa uma preocupação com a busca da satisfação das necessidades do trabalhador, englobando diversos aspectos da relação entre o trabalhador e a organização, tais como a remuneração, o relacionamento com colegas e com superiores hierárquicos, as condições e o ambiente de trabalho, o tempo destinado ao lazer e as oportunidades de crescimento. Este estudo objetivou analisar a percepção dos funcionários de uma agência de Porto Alegre, sobre as práticas de QVT adotadas na instituição pesquisada. Para tanto, procurou descrever as práticas adotadas no que se refere à QVT na instituição e levantar os fatores considerados de satisfação ou insatisfação em relação à QVT dos bancários pesquisados. Os dados da pesquisa foram obtidos pela aplicação de questionários a dezenove funcionários, gerando resultados de natureza quantitativa. Através da análise dos dados constatou-se que os fatores críticos para a QVT da Agência MS são a compensação justa e adequada e as condições de trabalho, enquanto os fatores que denotam maior satisfação por parte dos bancários são o uso e o desenvolvimento de capacidades, a oportunidade de crescimento e segurança a integração social na organização, o constitucionalismo, o trabalho e o espaço total de vida, e a relevância total do trabalho na vida

Um estudo de caso sobre a qualidade de vida no trabalho de bancários de Porto Alegre

O tema Qualidade de Vida no Trabalho expressa uma preocupação com a busca da satisfação das necessidades do trabalhador, englobando diversos aspectos da relação entre o trabalhador e a organização, tais como a remuneração, o relacionamento com colegas e com superiores hierárquicos, as condições e o ambiente de trabalho, o tempo destinado ao lazer e as oportunidades de crescimento. Este estudo objetivou analisar a percepção dos funcionários de uma agência de Porto Alegre, sobre as práticas de QVT adotadas na instituição pesquisada. Para tanto, procurou descrever as práticas adotadas no que se refere à QVT na instituição e levantar os fatores considerados de satisfação ou insatisfação em relação à QVT dos bancários pesquisados. Os dados da pesquisa foram obtidos pela aplicação de questionários a dezenove funcionários, gerando resultados de natureza quantitativa. Através da análise dos dados constatou-se que os fatores críticos para a QVT da Agência MS são a compensação justa e adequada e as condições de trabalho, enquanto os fatores que denotam maior satisfação por parte dos bancários são o uso e o desenvolvimento de capacidades, a oportunidade de crescimento e segurança a integração social na organização, o constitucionalismo, o trabalho e o espaço total de vida, e a relevância total do trabalho na vida

Zebrafish Trap230/Med12 is required as a coactivator for Sox9-dependent neural crest, cartilage and ear development

AbstractThe vertebrate Sox9 transcription factor directs the development of neural crest, otic placodes, cartilage and bone. In zebrafish, there are two Sox9 orthologs, Sox9a and Sox9b, which together perform the functions of the single-copy tetrapod Sox9. In a large-scale genetic screen, we have identified a novel zebrafish mutant that strongly resembles the Sox9a/Sox9b double mutant phenotype. We show that this mutation disrupts the zebrafish Trap230/Med12 ortholog, a member of the Mediator complex. Mediator is a coactivator complex transducing the interaction of DNA-binding transcription factors with RNA polymerase II, and our results reveal a critical function of the Trap230 subunit as a coactivator for Sox9