Phosphatidate phosphatase-1 is functionally conserved in lipid synthesis and storage from human to yeast.

Phosphatidate phosphatase-1 (PAP1) enzymes (yeast Pah1p/Smp2p, mammalian lipin1-3) have a key role in lipid homeostasis by controlling the relative proportions of its substrate phosphatidate (PA) and its product diacylglycerol (DAG). Recent investigation shows that mammalian lipin-1 complements phenotypes exhibited by yeast pah1Δ mutant cells, which indicates the functions of PAP1 enzymes are evolutionarily conserved. The observation was confirmed after transformation of human LPIN1 into PAH1-defective yeast, which resulted in human LPIN1-induced accumulation of triacylglycerol (TAG )and lipid droplet formation. In double mutants lacking Tgl3p and Tgl4p, overexpression of PAH1 or LPIN1 induced TAG accumulation and excessive obesity. Furthermore, the obese yeast was used as a model to study the anti-obesity effects of PAP1 activity inhibitors, including propranolol and clenbuterol. The data showed that the inhibitors significantly suppressed TAG accumulation and lipid droplets formation. These findings demonstrate that LPIN1 plays a functional role in lipid synthesis and storage, a role which is highly conserved from human to yeast. Inhibition of TAG synthesis will become an efficacious treatment strategy for obesity and our excessive obesity model will provide a very useful tool for discovery of new anti-obesity drugs in the future.

A long lifetime ratiometrically luminescent tetracycline nanoprobe based on Ir(III) complex-doped and Eu3+-functionalized silicon nanoparticles.

Different from fluorescent dyes-doped or carbon materials-based ratiometric tetracycline nanoprobes, herein, a new Ir(III) complex-doped and europium(III) ion (Eu3+)-functionalized silicon nanoparticles (Ir(III)@SiNPs-Eu3+) with long luminescent lifetimes was firstly fabricated for selective detection of tetracycline (TC) in complex systems through time-resolved emission spectra (TRES) measurement. In the presence of TC, the red phosphorescence of Eu3+ is greatly enhanced by adsorption energy transfer emission (AETE) of TC, while the strong green luminescence of Ir(III)@SiNPs is quenched by the inner filtration effect (IFE) of TC. Based on these striking emission changes, Ir(III)@SiNPs-Eu3+ can sensitively detect TC in the linear range of 0.01-20 µM with a detection limit of 4.9 × 10-3 µM. Benefitting from the long lifetime of Ir(III)@SiNPs-Eu3+, the nanoprobe demonstrates excellent TC detection performance through TRES in high background system of 5 % human serum. Furthermore, the formed Ir(III)@SiNPs-Eu3+/TC complex can be used to sensitively recognize Hg2+ via a ratiometric luminescence mode. Notably, the cytotoxicity of Ir(III)@SiNPs-Eu3+ is very low and thus the sensitive monitoring the detection of Ir(III)@SiNPs-Eu3+ to TC and Hg2+ also works well in porcine renal cells, demonstrating high application potential in real samples.

Harsh parenting and academic achievement in Chinese adolescents: Potential mediating roles of effortful control and classroom engagement.

This study examined (a) the potential mediating roles of effortful control and classroom engagement in the association between harsh parenting and adolescent academic achievement, and (b) the potential moderating role of gender. Sixth through eighth graders in rural China (n=815, mean age=12.55years) reported on harsh parenting, effortful control, and classroom engagement. Parents also reported on each other's harsh parenting. Academic achievement was assessed by students' test scores and teacher-rated academic performance. Results of structural equation modeling revealed gender differences in patterns of association among the model variables. Harsh parenting was negatively and directly associated with academic achievement for both boys and girls. It was also negatively and indirectly associated with academic achievement via effortful control and classroom engagement sequentially, forming a common indirect "path" for boys and girls. The indirect negative effect of harsh parenting on boys' academic achievement was mainly realized through the mediator of effortful control, whereas this same indirect effect for girls was mainly realized through the mediator of classroom engagement. Jointly, effortful control and classroom engagement precipitates more indirect effects for boys than for girls in the association between harsh parenting and academic achievement. The discussion analyzes the potential "paths" from harsh parenting to adolescent academic achievement, as well as gender differences in these "paths." The current study has implications for teachers and parents eager to improve students' classroom engagement and academic achievement.

A critical role for very long-chain fatty acid elongases in oleic acid-mediated Saccharomyces cerevisiae cytotoxicity.

Elongases FEN1/ELO2 and SUR4/ELO3 are important enzymes involved in the elongation of long-chain fatty acids (LCFAs) to very long-chain fatty acids (VLCFAs) in Saccharomyces cerevisiae. The molecular mechanism of the involvement of these elongases in lipotoxicity is unclear. In the present study, we investigated the role of VLCFA elongases in oleic acid-mediated yeast cytotoxicity. The spot test showed that yeast strains with the deletion of ELO2 or ELO3 were strikingly sensitive to oleic acid, while there was no change on the growth of strain with deleted ELO1 which was involved in the elongation of C14 fatty acid (FA) to C16 FA. By using GC-MS, the unsaturation index was increased in elo2△ and elo3△ mutants after treatment with oleic acid (OLA). However, the proportion of VLCFAs was increased in response to OLA in the wild-type strain. The growth inhibition of elo2△ and elo3△ could be partially rescued by two commonly used antioxidant agents N-acetyl cysteine (NAC) and Ascorbic acid (VC). The further study showed that exposure to excess OLA led to an increase in the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS), and a decline in the quantity of reduced glutathione (GSH) in both the wild type and mutant strains. However, the antioxidant enzyme activities of superoxide dismutase (SOD) and catalase (CAT) were increased in the wild type and elo1△ strains, while they were significantly decreased in the mutants of elo2△ and elo3△ after treated with excess OLA. Thus, oxidative damage mainly contributed to the cell death induced by OLA in ole2△ and ole3△. Taken together, although disruption of ELO2 or ELO3 did not affect the cellular lipid unsaturation, they altered the distribution and propotion of cellular VLCFAs, leading to the cell membrane impairment, which augmented the ability of OLA to permeabilize the plasma membrane. The data suggest that the very long-chain fatty acids elongases ELO2 and ELO3 play important roles in lipotoxic cell death induced by OLA through maintaining a balanced FA composition in plasma membrane.