Modulation of apoplast proteome by downy mildew in susceptible and tolerant grapevine cultivars

info:eu-repo/semantics/publishedVersio

Proteomic signatures uncover the early key players on Vitis vinifera cv. “Regent - Plasmopara viticola crosstalk

info:eu-repo/semantics/publishedVersio

Selective Inhibition of Bruton's Tyrosine Kinase by a Designed Covalent Ligand Leads to Potent Therapeutic Efficacy in Blood Cancers Relative to Clinically Used Inhibitors.

Bruton's tyrosine kinase (BTK) is a member of the TEC-family kinases and crucial for the proliferation and differentiation of B-cells. We evaluated the therapeutic potential of a covalent inhibitor (JS25) with nanomolar potency against BTK and with a more desirable selectivity and inhibitory profile compared to the FDA-approved BTK inhibitors ibrutinib and acalabrutinib. Structural prediction of the BTK/JS25 complex revealed sequestration of Tyr551 that leads to BTK's inactivation. JS25 also inhibited the proliferation of myeloid and lymphoid B-cell cancer cell lines. Its therapeutic potential was further tested against ibrutinib in preclinical models of B-cell cancers. JS25 treatment induced a more pronounced cell death in a murine xenograft model of Burkitt's lymphoma, causing a 30-40% reduction of the subcutaneous tumor and an overall reduction in the percentage of metastasis and secondary tumor formation. In a patient model of diffuse large B-cell lymphoma, the drug response of JS25 was higher than that of ibrutinib, leading to a 64% "on-target" efficacy. Finally, in zebrafish patient-derived xenografts of chronic lymphocytic leukemia, JS25 was faster and more effective in decreasing tumor burden, producing superior therapeutic effects compared to ibrutinib. We expect JS25 to become therapeutically relevant as a BTK inhibitor and to find applications in the treatment of hematological cancers and other pathologies with unmet clinical treatment

Trajetória docente em educação física: percursos formativos e profissionais Teacher's trajectory in physical education: formative and professional routes

O presente estudo teve como objetivo analisar a trajetória docente em Educação Física. Os percursos formativos e profissionais de quatro professores de Educação Física, com mais de 25 anos de intervenção profissional em escolas estaduais da cidade de Florianópolis foram investigados. Para analisar a trajetória docente foram utilizadas três fontes de coletas de informações: a) entrevistas semi-estruturadas com os professores de Educação Física; b) entrevistas semi-estruturadas com três colegas de trabalho; c) análise documental. A técnica da análise de conteúdo foi utilizada na análise das informações. Os resultados revelaram que os professores, ao mesmo tempo em que tiveram experiências positivas diversificadas durante suas formações iniciais, vivenciaram experiências negativas muito similares, destacando-se a distância entre suas experiências formativas e a realidade das escolas públicas. Como estratégia de continuidade do percurso formativo, os docentes realizaram cursos de pós-graduação em nível de especialização e de capacitação profissional. A entrada na carreira possibilitou sentimentos tanto de sobrevivência quanto de descoberta, sobressaindo-se o choque com a realidade. No decorrer de seus percursos profissionais, assumiram cargos comissionados e de confiança nas escolas em que atuavam. O desinvestimento amargo predomina no percurso profissional de apenas um professor, enquanto os demais demonstram aguardar a aposentadoria de forma mais serena. Como expectativas relacionadas à aposentadoria, pretendem desenvolver atividades profissionais diversificadas, não retornando à docência escolar.<br>This study aimed to analyze the professional trajectory of Physical Education (PE) teachers. The formative and professional routes of four PE teachers, with more than twenty-five years of professional activity in state schools in the city of Florianopolis were investigated. To analyze the teaching trajectory it was used three sources of information: a) semi-structured interviews with the PE teachers; b) semi-structured interviews with three workmates; c) documental analysis. The technique of content analysis was used for information analysis. The results revealed that the teachers, by the same time they had different positive experiences during their initial training, they had very similar negative experiences, emphasizing the distance between University's experiences and the reality of public schools. As a strategy to continue in the formative course, teachers made post-graduation courses, for expertise and professional improvement. The start in the career made possible feelings of survive and discovery, emphasizing the contrast to the reality. During professional journey, they received activities of reliance at schools they worked. The hard disinvestment predominates in the professional journey of only one teacher, but the other demonstrated to wait for retirement in a soft way. Concerning expectations related to the retirement, they intend to develop different professional activities, but not returning to teaching activities