Structural and biochemical insights into small RNA 3' end trimming by Arabidopsis SDN1.

A family of DEDDh 3'→5' exonucleases known as Small RNA Degrading Nucleases (SDNs) initiates the turnover of ARGONAUTE1 (AGO1)-bound microRNAs in Arabidopsis by trimming their 3' ends. Here, we report the crystal structure of Arabidopsis SDN1 (residues 2-300) in complex with a 9 nucleotide single-stranded RNA substrate, revealing that the DEDDh domain forms rigid interactions with the N-terminal domain and binds 4 nucleotides from the 3' end of the RNA via its catalytic pocket. Structural and biochemical results suggest that the SDN1 C-terminal domain adopts an RNA Recognition Motif (RRM) fold and is critical for substrate binding and enzymatic processivity of SDN1. In addition, SDN1 interacts with the AGO1 PAZ domain in an RNA-independent manner in vitro, enabling it to act on AGO1-bound microRNAs. These extensive structural and biochemical studies may shed light on a common 3' end trimming mechanism for 3'→5' exonucleases in the metabolism of small non-coding RNAs

Comparative Study on Trace Element Excretions between Nonanuric and Anuric Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Few studies have been reported on alterations of trace elements (TE) in peritoneal dialysis patients. Our objective was to investigate and assess the characteristics of daily TE excretions in continuous ambulatory peritoneal dialysis (CAPD) patients. This cross-sectional study included 61 CAPD patients (nonanuric/anuric: 45/16) and 11 healthy subjects in Wuhan, China between 2013 and 2014. The dialysate and urine of patients and urine of healthy subjects were collected. The concentrations of copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo), and arsenic (As) in dialysate and urine were determined using inductively coupled plasma mass spectrometer (ICP-MS). Various clinical variables were obtained from automatic biochemical analyzer. Daily Cu, Zn, Se, and Mo excretions in nonanuric patients were higher than healthy subjects, while arsenic excretion in anuric patients was lower. A strong and positive correlation was observed between Se and Mo excretion in both dialysate (β = 0.869, p < 0.010) and urine (β = 0.968, p < 0.010). Furthermore, the clinical variables associated with Se excretion were found to be correlated with Mo excretion. Our findings indicated that nonanuric CAPD patients may suffer from deficiency of some essential TEs, while anuric patients are at risk of arsenic accumulation. A close association between Se and Mo excretion was also found

Resveratrol ameliorates diet-induced dysregulation of lipid metabolism in zebrafish (<i>Danio rerio</i>)

<div><p>Defective lipid metabolism is associated with increased risk of various chronic diseases, such as obesity, cardiovascular diseases, and diabetes. Resveratrol (RSV), a natural polyphenol, has been shown the potential of ameliorating disregulations of lipid metabolism. The objective of this study was to investigate the effects of feed intake and RSV on lipid metabolism in zebrafish (<i>Danio rerio</i>). The adult males were randomly allocated to 6 groups: control (Con, 8 mg cysts/fish/day), control with 20 μmol/L RSV (Con+RSV), calorie restriction (CR, 5 mg cysts/fish/day), calorie restriction with RSV (CR+RSV), overfeed (OF, 60 mg cysts/fish/day), and overfeed with RSV (OF+RSV) groups. The treatment period was 8 weeks. Results showed that CR reduced body length, body weight, and condition factor of zebrafish. CR reduced levels of plasma triglyceride (TG) and induced protein expression of phosphorylated AMP-activated protein kinase-α (pAMPKα), silent information regulator 2 homolog 1 (Sirt1), and peroxisome proliferator activated receptor gamma coactivator-1α (PGC1α). RSV attenuated CR-induced pAMPKα/AMPKαincreases. RSV increased levels of Sirt1 protein in the OF zebrafish, and decreased OF-induced increase in peroxisome proliferator-activated receptor-γ (PPARγ) protein level. Additionally, RSV down-regulated caveolin-1 and up-regulated microtubule-associated protein 1 light chain 3 -II (LC3-II) protein levels in OF zebrafish. In conclusion, these results suggest that 1) CR reduces plasma TG level through activation of the AMPKα-Sirt1- PGC1α pathway; 2) under different dietary stress conditions RSV might regulate AMPK phosphorylation bi-directionally; 3) RSV might regulate lipid metabolism through the AMPKα-Sirt1-PPARγ pathway in OF zebrafish.</p></div

Does preconception paternal exposure to a physiologically relevant level of bisphenol A alter spatial memory in an adult rat?

Bisphenol A (BPA) is a ubiquitous environmental endocrine disrupting compound (EDC); public health concerns have been fueled by findings that maternal BPA exposure can change sex differences in the brain and in some behaviors. We investigated whether a physiologically relevant dose of BPA ingested by male rats before conception would affect spatial memory and hippocampal acetylcholinesterase (AchE) in their adult offspring. Twenty-two 60-day-old male rats (F0) received either a BPA diet (50 μg/kg/day) or vehicle alone for 10 weeks before being mated with non-exposed females. The paternal rats and their forty adult offspring's (F1) behaviors were then examined in the Morris Water Maze (MWM) and their AchE activities in the hippocampus were evaluated. BPA exposure led to spatial memory deficits along with decreased AchE activities in the hippocampus (p = 0.01) in adult F0 rats. This paternal exposure also induced impairment in spatial memory acquisition in both sexes while retention only in females in F1 rats, as well as abolished sex differences in the hippocampus AchE. Overall, these data provide new evidence that paternal BPA exposure, at a "safe" dose, may induce transgenerational alterations in spatial memory in a sex-specific manner

Histopathological observation of liver tissue in zebrafish (×400 magnification, HE staining).

<p>A. Con, B. Con+RSV, C. CR, D. CR+RSV, E. OF, F. OF+RSV.</p

Effects of resveratrol on blood glucose, plasma total cholesterol and triglyceride in different diet zebrafish.

<p>Effects of resveratrol on blood glucose, plasma total cholesterol and triglyceride in different diet zebrafish.</p

Effects of resveratrol on body length, body weight and condition factor in different diet zebrafish.

<p>Effects of resveratrol on body length, body weight and condition factor in different diet zebrafish.</p

Effects of feed intake and RSV on AMPKα and pAMPKα levels in zebrafish muscle.

<p>A. AMPK<b>α</b> mRNA levels, B. AMPK<b>α</b> protein levels, C. pAMPK<b>α</b> protein levels, D. Ratio of AMPK<b>α</b> protein level to pAMPK<b>α</b> protein level, E. Immunoblots of AMPK<b>α</b> and pAMPK<b>α</b>. The data were presented as Mean ± SD. Letters (a, b, c) indicated the multiple comparison results among various feed intake groups without RSV. Capital letters (A, B, C) indicated the multiple comparison results among various feed intake groups with RSV. Same letters indicated no significant difference, different letters indicated significant differences in statistics. * indicated the significant difference between groups without RSV and with RSV. For those there was no statistically significant difference between groups, the letters were not shown. Significance level was 0.05.</p

Effects of feed intake and RSV on Cav-1 and LC3 in zebrafish muscle.

<p>A. Cav-1 protein level. B. Ratio of LC3-II protein level to LC3-I protein level. C. Co-immunoprecipitation (IP) and immunoblots (IB) of Cav-1 and LC3. The data were presented as Mean ± SD. Letters (a, b, c) indicated the multiple comparison results among various feed intake groups without RSV. Capital letters (A, B, C) indicated the multiple comparison results among various feed intake groups with RSV. Same letters indicated no significant difference, different letters indicated significant differences in statistics. * indicated the significant difference between groups without RSV and with RSV. For those there was no statistically significant difference between groups, the letters were not shown. Significance level was 0.05.</p