Em Suplicantes, uma das mais políticas tragédias de Eurípides, é produzida uma aproximação surpreendente entre o mundo do mito e o do espectador. Embora Teseu, seu protagonista, seja representado ...como um “rei democrático”, nela não está presente uma cena que possa ser equiparada à experiência da mais típica instituição da democracia ateniense, a deliberação coletiva definidora da assembleia aberta a todos os cidadãos. Todavia, em diferentes momentos do primeiro episódio, chega-se bastante perto. Assim, o objetivo deste texto é discutir como essa tragédia representa formas de deliberação e consenso, para o que se investiga os meandros de dois cenários que levam a uma política de guerra de ataque desenvolvidos no drama, um em Argos, outro, em Atenas.
Abstract
Aims
It is unknown whether different training modalities exert differential cellular effects. Telomeres and telomere-associated proteins play a major role in cellular aging with implications ...for global health. This prospective training study examines the effects of endurance training, interval training (IT), and resistance training (RT) on telomerase activity and telomere length (TL).
Methods and results
One hundred and twenty-four healthy previously inactive individuals completed the 6 months study. Participants were randomized to three different interventions or the control condition (no change in lifestyle): aerobic endurance training (AET, continuous running), high-intensive IT (4 × 4 method), or RT (circle training on 8 devices), each intervention consisting of three 45 min training sessions per week. Maximum oxygen uptake (VO2max) was increased by all three training modalities. Telomerase activity in blood mononuclear cells was up-regulated by two- to three-fold in both endurance exercise groups (AET, IT), but not with RT. In parallel, lymphocyte, granulocyte, and leucocyte TL increased in the endurance-trained groups but not in the RT group. Magnet-activated cell sorting with telomerase repeat-ampliflication protocol (MACS-TRAP) assays revealed that a single bout of endurance training—but not RT—acutely increased telomerase activity in CD14+ and in CD34+ leucocytes.
Conclusion
This randomized controlled trial shows that endurance training, IT, and RT protocols induce specific cellular pathways in circulating leucocytes. Endurance training and IT, but not RT, increased telomerase activity and TL which are important for cellular senescence, regenerative capacity, and thus, healthy aging.
Haloacetonitriles (HANs) are a group of disinfection byproducts with high toxicity and frequent occurrence. Past studies have focused on the free amine groups, especially those in amino acids, as HAN ...precursors. This study reports, for the first time, that the indole moiety such as that in the tryptophan side chain is also a potent precursor for the most common HANs dichloroacetonitrile, bromochloroacetonitrile, and dibromoacetonitrile. 3-Indolepropionic acid, differing from tryptophan only in the absence of the free amine group, formed HANs at levels 57–76% of those by tryptophan at a halogen/nitrogen molar ratio of 10. Experiments with tryptophan-(amino-15N) showed that the indole contributed to 28–51% of the HANs formed by tryptophan. At low oxidant excess (e.g., halogen/precursor = 5), 3-indolepropionic acid even formed more HANs than Trp by 3.5-, 2.5-, and 1.8-fold during free chlorination, free bromination, and chlorination in the presence of bromide (0.6 mg/L), respectively. Indole’s HAN formation pathway was investigated by exploring the chlorination/bromination products of 3-indolepropionic acid using liquid chromatography–orbitrap high-resolution mass spectrometry. A total of 22 intermediates were detected, including pyrrole ring-opening products with an N-formyl group, 2-substituted anilines with different hydroxyl/halogen substitutions, and an intermediate with a postulated non-aromatic ring structure.
H3K27M diffuse intrinsic pontine gliomas (DIPGs) are fatal and lack treatments. They mainly harbor H3.3K27M mutations resulting in H3K27me3 reduction. Integrated analysis in H3.3K27M cells, tumors, ...and in vivo imaging in patients showed enhanced glycolysis, glutaminolysis, and tricarboxylic acid cycle metabolism with high alpha-ketoglutarate (α-KG) production. Glucose and/or glutamine-derived α-KG maintained low H3K27me3 in H3.3K27M cells, and inhibition of key enzymes in glycolysis or glutaminolysis increased H3K27me3, altered chromatin accessibility, and prolonged survival in animal models. Previous studies have shown that mutant isocitrate-dehydrogenase (mIDH)1/2 glioma cells convert α-KG to D-2-hydroxyglutarate (D-2HG) to increase H3K27me3. Here, we show that H3K27M and IDH1 mutations are mutually exclusive and experimentally synthetic lethal. Overall, we demonstrate that H3.3K27M and mIDH1 hijack a conserved and critical metabolic pathway in opposing ways to maintain their preferred epigenetic state. Consequently, interruption of this metabolic/epigenetic pathway showed potent efficacy in preclinical models, suggesting key therapeutic targets for much needed treatments.
Display omitted
•H3.3K27M mutations enhance glucose, glutamine, and TCA cycle metabolism•TCA cycle intermediate α-KG enables maintenance of H3K27 hypomethylation•Targeting enzymes related to α-KG synthesis including WT-IDH1 and/or GDH is therapeutic•H3.3K27M and mutant-IDH1 in gliomas are mutually exclusive and are synthetic lethal
Chung et al. show that H3.3K27M mutation in DIPGs enhances glycolysis and TCA cycle metabolism to produce α-KG that is required to maintain a preferred epigenetic state of low H3K27me3. Inhibiting enzymes related to α-KG production increases H3K27me3 and results in anti-tumor activity in mouse models of DIPG.
There is a rich repertoire of methods for stress detection using various physiological signals and algorithms. However, there is still a gap in research efforts moving from laboratory studies to ...real-world settings. A small number of research has verified when a physiological response is a reaction to an extrinsic stimulus of the participant's environment in real-world settings. Typically, physiological signals are correlated with the spatial characteristics of the physical environment, supported by video records or interviews. The present research aims to bridge the gap between laboratory settings and real-world field studies by introducing a new algorithm that leverages the capabilities of wearable physiological sensors to detect moments of stress (MOS). We propose a rule-based algorithm based on galvanic skin response and skin temperature, combing empirical findings with expert knowledge to ensure transferability between laboratory settings and real-world field studies. To verify our algorithm, we carried out a laboratory experiment to create a "gold standard" of physiological responses to stressors. We validated the algorithm in real-world field studies using a mixed-method approach by spatially correlating the participant's perceived stress, geo-located questionnaires, and the corresponding real-world situation from the video. Results show that the algorithm detects MOS with 84% accuracy, showing high correlations between measured (by wearable sensors), reported (by questionnaires and eDiary entries), and recorded (by video) stress events. The urban stressors that were identified in the real-world studies originate from traffic congestion, dangerous driving situations, and crowded areas such as tourist attractions. The presented research can enhance stress detection in real life and may thus foster a better understanding of circumstances that bring about physiological stress in humans.
Essential polyunsaturated fatty acids (PUFAs) have been recognized as a crucial factor that determines the trophic transfer efficiency in plankton communities. As many animals cannot synthesize the ...classes of ω3- and ω6-PUFAs, the dietary availability of these PUFAs can constrain the fitness of freshwater zooplankton such as Daphnia spp. In particular, eicosapentaenoic acid (EPA, 20:5ω3) is considered to be a crucial determinant of the transfer of biomass at the freshwater plant-herbivore interface. In contrast to ω3-PUFAs, the group of ω6-PUFAs has previously been considered to be of less ecological relevance, although the potential role of the ω6-PUFA arachidonic acid (ARA, 20:4ω6) remains controversial. To investigate its potential role, we conducted dose-response growth experiments with two Daphnia species, D. pulex and D. magna, supplemented with EPA or ARA, which allowed us to calculate EPA and ARA saturation thresholds for growth and reproduction of both Daphnia species. Our results provide evidence that not only the availability of ω3-PUFAs, but also the availability of a ω6-PUFA, namely ARA, can limit both the growth and reproduction of Daphnia spp. to an equal extent. The saturation thresholds for growth and reproduction were consistently, but not significantly, higher for EPA than for ARA in both Daphnia species. As shifts in phytoplankton community composition might result in environmental fluctuations in the dietary availability of ω3- and ω6-PUFAs, our findings present a significant step in understanding the consequences of the ongoing global biodiversity loss for trophic transfer efficiency at the phytoplankton-zooplankton interface.
PDF
