AMP-activated protein kinase (AMPK) is an evolutionarily conserved master regulator of metabolism and a therapeutic target in type 2 diabetes. As an energy sensor, AMPK activity is responsive to both metabolic inputs, for instance the ratio of AMP to ATP, and numerous hormonal cues. As in mammals, each of two genes, aak-1 and aak-2, encode for the catalytic subunit of AMPK in C. elegans. Here we show that in C. elegans loss of aak-2 mimics the effects of elevated serotonin signaling on fat reduction, slowed movement, and promoting exit from dauer arrest. Reconstitution of aak-2 in only the nervous system restored wild type fat levels and movement rate to aak-2 mutants and reconstitution in only the ASI neurons was sufficient to significantly restore dauer maintenance to the mutant animals. As in elevated serotonin signaling, inactivation of AAK-2 in the ASI neurons caused enhanced secretion of dense core vesicles from these neurons. The ASI neurons are the site of production of the DAF-7 TGF-β ligand and the DAF-28 insulin, both of which are secreted by dense core vesicles and play critical roles in whether animals stay in dauer or undergo reproductive development. These findings show that elevated levels of serotonin promote enhanced secretions of systemic regulators of pro-growth and differentiation pathways through inactivation of AAK-2. As such, AMPK is not only a recipient of hormonal signals but can also be an upstream regulator. Our data suggest that some of the physiological phenotypes previously attributed to peripheral AAK-2 activity on metabolic targets may instead be due to the role of this kinase in neural serotonin signaling.
BackgroundThe early postoperative period is critical for surgical patients. SOFA, SAPS 3 and APACHE II are prognostic scores widely used to predict mortality in ICU patients. This study aimed to evaluate these index tests for their prognostic accuracy for intra-ICU and in-hospital mortalities as target conditions in patients admitted to ICU after urgent or elective surgeries and to test whether they aid in decision-making. The process comprised the assessment of discrimination through analysis of the areas under the receiver operating characteristic curves and calibration of the prognostic models for the target conditions. After, the clinical relevance of applying them was evaluated through the measurement of the net benefit of their use in the clinical decision.ResultsIndex tests were found to discriminate regular for both target conditions with a poor calibration (C statistics—intra-ICU mortality AUROCs: APACHE II 0.808, SAPS 3 0.821 and SOFA 0.797/in-hospital mortality AUROCs: APACHE II 0.772, SAPS 3 0.790 and SOFA 0.742). Calibration assessment revealed a weak correlation between the observed and expected number of cases in several thresholds of risk, calculated by each model, for both tested outcomes. The net benefit analysis showed that all score’s aggregate value in the clinical decision when the calculated probabilities of death ranged between 10 and 40%.ConclusionsIn this study, we observed that the tested ICU prognostic scores are fair tools for intra-ICU and in-hospital mortality prediction in a cohort of postoperative surgical patients. Also, they may have some potential to be used as ancillary data to support decision-making by physicians and families regarding the level of therapeutic investment and palliative care.Electronic supplementary materialThe online version of this article (10.1186/s13613-019-0488-9) contains supplementary material, which is available to authorized users.
Caffeine is a widely used psychoactive substance. Studies have shown that caffeine may play a protective role in aging-associated disorders. However, the mechanisms by which caffeine modulates aging are not yet clear. In this study, we have shown that caffeine increases Caenorhabditis elegans lifespan, delays its larval development, reduces reproduction and body length. These phenotypes were partly reversed by worm’s exposure to adenosine, which suggest a putative common target. Moreover, they were dependent on a functional insulin/IGF-1-like pathway. Our results may shed light on new genetic determinants of aging.
Asian soybean rust (ASR), caused by Phakopsora pachyrhizi, is one of the most important foliar diseases affecting soybean production worldwide. This study aimed to investigate the photosynthetic performance (leaf gas exchange, chlorophyll (Chl) a fluorescence images and photosynthetic pigment pools) of soybean plants sprayed with Acibenzolar‐S‐Methyl (ASM) and the fungicide epoxiconazole + pyraclostrobin (Epo+Pyr) and further inoculated with P. pachyrhizi. The ASR symptoms progressed much faster on the leaves of plants from the control treatment (water spray) in comparison with the ASM and Epo+Pyr treatments. In general, the values for the leaf gas exchange parameters net carbon assimilation rate (A), stomatal conductance to water vapour (gs), internal CO2 concentration (Ci) and transpiration rate (E) increased for the infected plants sprayed with ASM or Epo+Pyr in comparison with plants from the control treatment. The values for the initial fluorescence (Fo), maximal fluorescence (Fm), maximal photosystem II quantum efficiency (Fv/Fm), effective photosystem II quantum yield (Y(II)) and quantum yield of regulated energy dissipation (Y(NPQ)) were consistently higher for the ASM and Epo+Pyr treatments in comparison with the control treatment at advanced stages of fungal infection. By contrast, the values for quantum yield of non‐regulated energy dissipation (Y(NO) were significantly lower for the ASM and Epo+Pyr treatments. The concentrations of total Chl a+b and carotenoids significantly increased for infected plants sprayed with ASM and Epo+Pyr in comparison with plants from the control treatment. The results of this study demonstrated that the spray of soybean plants with either ASM or Epo+Pyr contributed to reduce the negative effect of ASR on the photosynthesis of soybean plants.
The regulation of energy balance involves an intricate interplay between neural mechanisms that respond to internal and external cues of energy demand and food availability. Compelling data have implicated the neurotransmitter dopamine as an important part of body weight regulation. However, the precise mechanisms through which dopamine regulates energy homeostasis remain poorly understood. Here, we investigate mechanisms through which dopamine modulates energy storage. We showed that dopamine signaling regulates fat reservoirs in Caenorhabditis elegans. We found that the fat reducing effects of dopamine were dependent on dopaminergic receptors and a set of fat oxidation enzymes. Our findings reveal an ancient role for dopaminergic regulation of fat and suggest that dopamine signaling elicits this outcome through cascades that ultimately mobilize peripheral fat depots.
Deoxynivalenol-3-glucoside (D3G) is a modified mycotoxin formed by the metabolism of plants through the conjugation of deoxynivalenol (DON) with glucose. Toxicology studies of D3G for human and animal health are still under investigation, and the development of practical and reliable methods for its direct determination, especially in cereal matrices, is of great importance. In the present study, a methodology for simultaneous determination of D3G, DON, and nivalenol (NIV) in wheat grains, using immunoaffinity column (IAC) cleanup, separation by C18 column and detection by ultraviolet (UV) absorption, was optimized and inhouse validated. The results demonstrated adequate values of D3G recovery from IAC and spiked samples. Intraday precision, linearity, limit of detection and limit of quantification (LOQ) were also adequate for the determination of these mycotoxins. Range of applicability varied from 47.1 to 1000 μg/ kg for D3G and from 31.3 to 1000 μg/kg for DON and NIV, with recovery ranging from 84.7 ± 7.2 % to 112.3 ± 8.1 %. A high incidence of D3G (41.2 %, all samples
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