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Sander Amstrup posted an update 1 day, 21 hours ago
The target of rapamycin (TOR) protein kinase is at the core of growth factor- and nutrient-dependent signaling pathways that are well-known for their regulation of metabolism, growth, and proliferation. However, TOR is also involved in the regulation of gene expression, genomic and epigenomic stability. TOR affects nuclear functions indirectly through its activity in the cytoplasm, but also directly through active nuclear TOR pools. The mechanisms by which TOR regulates its nuclear functions are less well-understood compared with its cytoplasmic activities. TOR is an important pharmacological target for several diseases, including cancer, metabolic and neurological disorders. Thus, studies of the nuclear functions of TOR are important for our understanding of basic biological processes, as well as for clinical implications.Molecular imprinting technology is a promising method for detecting chloramphenicol (CAP), a broad-spectrum antibiotic with potential toxicity to humans, in animal-derived foods. This work aimed to investigate the interactions between the CAP as a template and functional monomers required for synthesizing efficient molecularly imprinted polymers for recognition and isolation of CAP based on density functional theory. The most suitable monomer, methacrylic acid (MAA), was determined based on interaction energies and Gibbs free energy changes. Further, the reaction sites of CAP and MAA was predicted through the frontier molecular orbitals and molecular electrostatic potentials. Atoms in molecules topology analysis and non-covalent interactions reduced density gradient were applied to investigate different types of non-covalent and inter-atomic interactions. The simulation results showed that CAP was the main electron donor, while MAA was the main electron acceptor. Moreover, the CAP-MAA complex simultaneously involved N-H···O and C=O···H double hydrogen bonds, where the strength of the latter was greater than that of the former. The existence of hydrogen bonds was also confirmed by theoretical and experimental hydrogen nuclear magnetic resonance and Fourier transform infrared spectroscopic analyses. This research can act as an important reference for intermolecular interactions and provide strong theoretical guidance regarding CAP in the synthesis of molecularly imprinted polymers.Fatty liver occurs from simple steatosis with accumulated hepatic lipids and hepatic insulin resistance to severe steatohepatitis, with aggravated lipid accumulation and systemic insulin resistance, but this progression is still poorly understood. Analyses of hepatic gene expression patterns from alb-SREBP-1c mice with moderate, or aP2-SREBP-1c mice with aggravated, hepatic lipid accumulation revealed IGFBP2 as key nodal molecule differing between moderate and aggravated fatty liver. SB431542 Reduced IGFBP2 expression in aggravated fatty liver was paralleled with promoter hypermethylation, reduced hepatic IGFBP2 secretion and IGFBP2 circulating in plasma. Physiologically, the decrease of IGFBP2 was accompanied with reduced fatty acid oxidation and increased de novo lipogenesis potentially mediated by IGF1 in primary hepatocytes. Furthermore, methyltransferase and sirtuin activities were enhanced. In humans, IGFBP2 serum concentration was lower in obese men with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) compared to non-obese controls, and liver fat reduction by weight-loss intervention correlated with an increase of IGFBP2 serum levels. In conclusion, hepatic IGFBP2 abundance correlates to its circulating level and is related to hepatic energy metabolism and de novo lipogenesis. This designates IGFBP2 as non-invasive biomarker for fatty liver disease progression and might further provide an additional variable for risk prediction for pathogenesis of fatty liver in diabetes subtype clusters.The link between eating rate and energy intake has long been a matter of extensive research. A better understanding of the effect of food intake speed on body weight and glycemia in the long term could serve as a means to prevent weight gain and/or dysglycemia. Whether a fast eating rate plays an important role in increased energy intake and body weight depends on various factors related to the studied food such as texture, viscosity and taste, but seems to be also influenced by the habitual characteristics of the studied subjects as well. Hunger and satiety quantified via test meals in acute experiments with subsequent energy intake measurements and their association with anorexigenic and orexigenic regulating peptides provide further insight to the complicated pathogenesis of obesity. The present review examines data from the abundant literature on the subject of eating rate, and highlights the main findings in people with normal weight, obesity, and type 2 diabetes, with the aim of clarifying the association between rate of food intake and hunger, satiety, glycemia, and energy intake in the short and long term.Insect desaturases are known to play an important role in chemical communication between individuals. However, their roles in insect growth, development and fecundity, and in regulating interactions of insects with plants, remain largely unknown. In this study, we explored the functions of Nlug-desatA2, a desaturase gene of the brown planthopper (BPH), Nilaparvata lugens (Stål). The RNA interference-based knockdown of Nlug-desatA2 decreased the ratio of monounsaturated fatty acids to saturated fatty acids, and the level of fatty acids and triglycerides in BPH. Nlug-desatA2-knockdown also reduced the food intake, body mass and fecundity of female BPH adults, and led to abdomen atrophy and ovarian agenesis. Nlug-desatA2-knockdown suppressed the transcription of TOR (target of rapamycin), Lpp (Lipophorin) and AKHR (adipokinetic hormone receptor) in female adults. Moreover, the corrected survival rate of BPH with Nlug-desatA2-knockdown fed an artificial diet was higher than the survival rate of those fed on rice plants. Higher levels of salicylic acid in rice infested by Nlug-desatA2-knockdown female BPH adults than in rice infested by control BPH may be the reason. These findings demonstrate that Nlug-desatA2 has an essential role in lipid metabolism and is involved in the food intake, survival, development and fecundity of BPH. In addition, this gene is likely involved in regulating the responses of rice to BPH infestation.