C2-phytoceramide perturbs lipid rafts and cell integrity in Saccharomyces cerevisiae in a sterol-dependent manner

Specific ceramides are key regulators of cell fate, and extensive studies aimed to develop therapies based on ceramide-induced cell death. However, the mechanisms regulating ceramide cytotoxicity are not yet fully elucidated. Since ceramides also regulate growth and stress responses in yeast, we studied how different exogenous ceramides affect yeast cells. C2-phytoceramide, a soluble form of phytoceramides, the yeast counterparts of mammalian ceramides, greatly reduced clonogenic survival, particularly in the G2/M phase, but did not induce autophagy nor increase apoptotic markers. Rather, the loss of clonogenic survival was associated with PI positive staining, disorganization of lipid rafts and cell wall weakening. Sensitivity to C2-phytoceramide was exacerbated in mutants lacking Hog1p, the MAP kinase homolog of human p38 kinase. Decreasing sterol membrane content reduced sensitivity to C2-phytoceramide, suggesting sterols are the targets of this compound. This study identified a new function of C2-phytoceramide through disorganization of lipid rafts and induction of a necrotic cell death under hypo-osmotic conditions. Since lipid rafts are important in mammalian cell signaling and adhesion, our findings further support pursuing the exploitation of yeast to understand the basis of synthetic ceramides' cytotoxicity to provide novel strategies for therapeutic intervention in cancer and other diseases.This work was supported by Fundacao para a Ciencia e Tecnologia through projects PTDC/BIA-BCM/69448/2006 and PEst-C/BIA/UI4050/2011, and fellowships to A. P. (SFRH/BPD/65003) and F. A. (SFRH/BD/80934/2011), as well as by FEDER through POFC - COMPETE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Cork oak vulnerability to fire: the role of bark harvesting, tree characteristics and abiotic factors

Forest ecosystems where periodical tree bark harvesting is a major economic activity may be particularly vulnerable to disturbances such as fire, since debarking usually reduces tree vigour and protection against external agents. In this paper we asked how cork oak Quercus suber trees respond after wildfires and, in particular, how bark harvesting affects post-fire tree survival and resprouting. We gathered data from 22 wildfires (4585 trees) that occurred in three southern European countries (Portugal, Spain and France), covering a wide range of conditions characteristic of Q. suber ecosystems. Post-fire tree responses (tree mortality, stem mortality and crown resprouting) were examined in relation to management and ecological factors using generalized linear mixed-effects models. Results showed that bark thickness and bark harvesting are major factors affecting resistance of Q. suber to fire. Fire vulnerability was higher for trees with thin bark (young or recently debarked individuals) and decreased with increasing bark thickness until cork was 3–4 cm thick. This bark thickness corresponds to the moment when exploited trees are debarked again, meaning that exploited trees are vulnerable to fire during a longer period. Exploited trees were also more likely to be top-killed than unexploited trees, even for the same bark thickness. Additionally, vulnerability to fire increased with burn severity and with tree diameter, and was higher in trees burned in early summer or located in drier south-facing aspects. We provided tree response models useful to help estimating the impact of fire and to support management decisions. The results suggested that an appropriate management of surface fuels and changes in the bark harvesting regime (e.g. debarking coexisting trees in different years or increasing the harvesting cycle) would decrease vulnerability to fire and contribute to the conservation of cork oak ecosystemsinfo:eu-repo/semantics/publishedVersio

Efeitos da fadiga muscular induzida por exercícios no tempo de reação muscular dos fibulares em indivíduos sadios Efectos de la fatiga muscular inducida por ejercicios sobre el tiempo de reacción muscular peronea en individuos sanos Effects of the exercise-induced muscular fatigue on the time of muscular reaction of the fibularis in healthy individuals

A fadiga muscular (FM) é um fenômeno comum nas atividades esportivas e diárias, resultando numa piora da performance motora. Ela é considerada um dos fatores causadores de lesões músculo-esqueléticas. A entorse de tornozelo é um exemplo: a FM afetaria tanto o sistema aferente quanto o eferente. Vários estudos têm analisado a influência da FM no controle neuromuscular (CNM); entretanto, existe pouca pesquisa sobre essa influência na velocidade de reação dos músculos. O objetivo deste estudo foi verificar os efeitos da FM no tempo de reação muscular (TRM) dos músculos fibulares, que são os primeiros a responder a um estresse em inversão do tornozelo. Foram estudados 14 indivíduos saudáveis masculinos (idade: 20-35 anos), que tiveram seus TRM avaliados por meio de eletromiografia (EMG) de superfície. O início da atividade muscular foi definido como a média de repouso + 3x o desvio-padrão (DP). O TRM dos fibulares foi mensurado após uma inversão súbita de 20º realizada numa plataforma. A inversão súbita foi realizada antes e depois da fadiga muscular, que foi induzida por exercícios localizados dos fibulares até a exaustão. Os resultados mostraram que houve um aumento significativo do tempo de reação muscular após a fadiga (p < 0,01). Durante atividades esportivas prolongadas e durante o processo de reabilitação, deve-se ter cautela na realização de tarefas que requeiram respostas musculares extremamente rápidas sob condições de fadiga muscular.<br>La fatiga muscular (FM) es un fenómeno común en las actividades diarias, produciendo un empeoramiento de la actuación. Se la considera una de las causas de factores lesionantes musculares de esqueleto. El esguince del tobillo es un ejemplo: La FM afectaría tanto el sistema aferente cuanto el eferente. Varios estudios han estado analizando la influencia de FM en el comando neuromuscular (CNM), sin embargo, la existen pocas investigaciones sobre la influencia en la velocidad de reacción de los músculos. El objetivo de ese estudio era verificar los efectos de FM en el tiempo de reacción muscular (TRM) de los músculos peroneos, que son los primeros en responder a una tensión en la inversión del tobillo. Se estudiaron 14 individuos saludables masculinos (con edad: entre 20-35 años), que tenían su TRM estimado a través de la eletromiografia (EMG) de superficie. El principio de la actividad muscular se definió como el promedio del resto + 3x la desviación normal (DP). TRM de músculos peroneos estava moderado después de una inversión súbita de 20º cumplida en una plataforma. La inversión súbita se realizaba antes y después de la fatiga muscular, que era inducido por los ejercicios localizados en los músculos peróneos hasta agotamiento. Los resultados mostraron que había un aumento significante del tiempo de reacción muscular después de la fatiga (p < 0.01). Durante las actividades deportivas y durante el proceso de la rehabilitación, debe tenerse cautela en la realización de las tareas que se solicitan como respuestas musculares sumamente rápidas bajo las condiciones de fatiga muscular.<br>The muscular fatigue (MF) is a common phenomenon in the daily sports activities that results in a worsening of the motor performance. It is considered one of the major factors for muscle-skeletal damages, such as the ankle sprain, when the MF would affect both the afferent and the efferent systems. Several studies have been analyzing the influence of the MF on the neuromuscular control (NMC). Nevertheless, there are few researches comprising that influence on the velocity of the muscular reaction. The purpose of this study was to check the effects of the MF on the time of the muscular reaction (TMR) in the fibularis muscles, which are the first to respond to an inversion stress of the ankle. Fourteen healthy male individuals (age: 20-35 years) were studied, who had their TMR assessed by means of the surface electromyography (EMG). The beginning of the muscular activity was defined as the mean resting value +3x the standard deviation (SD). The TMR of the fibularis was measured after a sudden 20º inversion performed on a platform. The sudden inversion was performed before and after the muscular fatigue, which was induced through localized exercises of the fibularis up to the exhaustion. The results have shown a significant increase in the time of the muscular reaction after the fatigue (p < 0.01). While performing prolonged sportive activities and during the rehabilitation process, there must be caution to perform tasks that require extremely fast muscular responses