The Cdc25 and Ras1 Proteins of Candida albicans Influence Epithelial Toxicity in a Niche-Specific Way

The PKA pathway is a signaling pathway involved in virulence in Candida albicans. This mechanism can be activated via addition of glucose and activation involves at least two proteins, namely Cdc25 and Ras1. Both proteins are involved in specific virulence traits. However, it is not clear if Cdc25 and Ras1 also affect virulence independently of PKA. C. albicans holds a second, atypical, Ras protein, Ras2, but its function in PKA activation is still unclear. We investigated the role of Cdc25, Ras1, and Ras2 for different in vitro and ex vivo virulence characteristics. We show that deletion of CDC25 and RAS1 result in less toxicity towards oral epithelial cells, while deletion of RAS2 has no effect. However, toxicity towards cervical cells increases in both the ras2 and the cdc25 mutants while it decreases in a ras1 mutant compared to the WT. Toxicity assays using mutants of the transcription factors downstream of the PKA pathway (Efg1) or the MAPK pathway (Cph1) show that the ras1 mutant shows similar phenotypes as the efg1 mutant, whereas the ras2 mutant shows similar phenotypes as the cph1 mutant. These data show niche-specific roles for different upstream components in regulating virulence through both signal transduction pathways

Veldonderzoek fusionerende gemeenten Vlaanderen 2018: Discoursen en motieven in vrijwillige gemeentefusie en motieven bij gemeenten die besluiten toch niet te fusioneren

status: publishe

Testosterone restores body composition, bone mass, and bone strength following early puberty suppression in a mouse model mimicking the clinical strategy in trans boys

Transgender youth increasingly present at pediatric gender services. Some of them receive long-term puberty suppression with gonadotropin-releasing hormone analogues (GnRHa) before starting gender-affirming hormones (GAH). The impact of GnRHa use started in early puberty on bone composition and bone mass accrual is unexplored. It is furthermore unclear whether subsequent GAH fully restore GnRHa effects and whether the timing of GAH introduction matters. To answer these questions, we developed a mouse model mimicking the clinical strategy applied in trans boys. Prepubertal 4-week-old female mice were treated with GnRHa alone or with GnRHa supplemented with testosterone (T) from 6 weeks (early puberty) or 8 weeks (late puberty) onward. Outcomes were analyzed at 16 weeks and compared with untreated mice of both sexes. GnRHa markedly increased total body fat mass, decreased lean body mass, and had a modest negative impact on grip strength. Both early and late T administration shaped body composition to adult male levels, whereas grip strength was restored to female values. GnRHa-treated animals showed lower trabecular bone volume and reduced cortical bone mass and strength. These changes were reversed by T to female levels (cortical bone mass and strength) irrespective of the time of administration or even fully up to adult male control values (trabecular parameters) in case of earlier T start. The lower bone mass in GnRHa-treated mice was associated with increased bone marrow adiposity, also reversed by T. In conclusion, prolonged GnRHa use started in prepubertal female mice modifies body composition toward more fat and less lean mass and impairs bone mass acquisition and strength. Subsequent T administration counteracts GnRHa impact on these parameters, shaping body composition and trabecular parameters to male values while restoring cortical bone architecture and strength up to female but not male control levels. These findings could help guide clinical strategies in transgender care. (c) 2023 American Society for Bone and Mineral Research (ASBMR)

Atividades de controle do dengue na visão de seus agentes e da população atendida, São José do Rio Preto, São Paulo, Brasil Dengue control as viewed by agents and the target population in São José do Rio Preto, São Paulo, Brazil

O objetivo foi identificar, no contexto da atuação dos agentes responsáveis pelo controle do dengue e na sua relação com moradores, situações vivenciadas no dia-a-dia de suas funções. Realizou-se estudo transversal com aplicação de questionários à população dos agentes de controle de vetores (ACV), à dos agentes comunitários de saúde (ACS) e a uma amostra de mulheres. As respostas dadas pelos agentes foram agrupadas nos âmbitos do trabalho, particular e coletivo. As mulheres foram abordadas sobre a relação mantida com os agentes. As dificuldades citadas nos âmbitos particular e trabalho pelos ACV diferiram das citadas pelos ACS. No coletivo foram coincidentes e mostraram que ambos não estão preparados para lidar com estas questões. Das mulheres entrevistadas, 87,0% afirmaram estar bem ou muito bem informadas sobre dengue, 84,0% afirmaram que os trabalhos dos agentes ajudam sempre e 54,0% apontaram como dificuldade o horário impróprio da visita realizada pelo agente. Identificou-se a necessidade de um novo profissional que reconheça e respeite as particularidades dos locais onde atua e desenvolva suas atividades de forma integrada às questões sócio-ambientais da comunidade.<br>The aim of this article was to identify daily situations experienced by dengue control agents in their relationship to local residents. A cross-sectional study applied questionnaires among vector control agents, community health workers, and a sample of local women. The answers by the dengue control agents and community health workers were grouped in the categories of work, private life, and community. The women were asked about the relationship with the vector control and community health workers. The difficulties cited in the private and work areas by the vector control agents were different from those reported by community health workers. At the community level they coincided and showed that neither group is adequately prepared to deal with these issues. Of the local women interviewed, 87.0% reported that they were well-informed or very well-informed about dengue, 84.0% stated that the work by the vector control agents and community health workers was always helpful, and 54.0% identified inappropriate visiting hours by vector control agents and community health workers as a difficulty. The study identified the need for a new job profile that would recognize and respect the specificities of the areas where their activities are conducted, integrating the community's socio-environmental issues