Mycn regulates intestinal development through ribosomal biogenesis in a zebrafish model of Feingold syndrome 1.

Feingold syndrome type 1, caused by loss-of-function of MYCN, is characterized by varied phenotypes including esophageal and duodenal atresia. However, no adequate model exists for studying the syndrome's pathological or molecular mechanisms, nor is there a treatment strategy. Here, we developed a zebrafish Feingold syndrome type 1 model with nonfunctional mycn, which had severe intestinal atresia. Single-cell RNA-seq identified a subcluster of intestinal cells that were highly sensitive to Mycn, and impaired cell proliferation decreased the overall number of intestinal cells in the mycn mutant fish. Bulk RNA-seq and metabolomic analysis showed that expression of ribosomal genes was down-regulated and that amino acid metabolism was abnormal. Northern blot and ribosomal profiling analysis showed abnormal rRNA processing and decreases in free 40S, 60S, and 80S ribosome particles, which led to impaired translation in the mutant. Besides, both Ribo-seq and western blot analysis showed that mTOR pathway was impaired in mycn mutant, and blocking mTOR pathway by rapamycin treatment can mimic the intestinal defect, and both L-leucine and Rheb, which can elevate translation via activating TOR pathway, could rescue the intestinal phenotype of mycn mutant. In summary, by this zebrafish Feingold syndrome type 1 model, we found that disturbance of ribosomal biogenesis and blockage of protein synthesis during development are primary causes of the intestinal defect in Feingold syndrome type 1. Importantly, our work suggests that leucine supplementation may be a feasible and easy treatment option for this disease.

[Effects of Different Water Stratification on the Vertical Distribution of Nitrogen in Sediment Interstitial Waters: A Case Study of the Three Gorges Reservoir and Xiaowan Reservoir].

To determine the reasons for the variation in the vertical distribution of nitrogen in sediment interstitial waters between different stratified reservoirs, the characteristics of overlying water-interstitial water in Xiangxi Bay, Yangtze River mainstream, and Xiaowan Reservoir were monitored. The vertical distribution of nitrogen in sediment interstitial waters in these different stratified waters were then analyzed, and the reasons for the variation in this distribution were assessed. The results showed:① the ρ(TN) in the sediment interstitial waters of the Yangtze River mainstream and Xiangxi Bay gradually increased with depth, while that of Xiaowan Reservoir reached its maximum at 12 cm and the bottom layer presented a "C" distribution. The ρ(NH4+) in the sediment interstitial waters of the Yangtze River mainstream and Xiangxi Bay exhibited an increasing trend with depth, while that of Xiaowan Reservoir was slightly higher in the bottom layer than in the surface layer, although the change with depth was not significant. Overall, the ρ(NH4+) in the sediment interstitial waters of the Yangtze River mainstream and Xiangxi Bay was higher than that of Xiaowan Reservoir, and the concentration ranges were as follows:0.512-8.289 mg·L-1, 0.968-9.307 mg·L-1, and 0.950-1.450 mg·L-1. The vertical distribution of the ρ(NO3-) in the sediment interstitial waters of all three waterbodies were opposite to that of ρ(NH4+). Moreover, the ρ(NO3-) in the sediment interstitial waters of Xiangxi Bay and the Yangtze River mainstream was higher than that of Xiaowan Reservoir. The concentration ranges were as follows:0.143-0.674 mg·L-1, 0.107-0.647 mg·L-1, and 0.050-0.051 mg·L-1. ② There were also significant differences in the vertical distribution of physical and chemical indices in the three water bodies. There was no significant change in the vertical distribution of the water temperature in the Yangtze River mainstream and the N2 value was <5×10-5 s-2; hence, the water was well mixed, and the vertical range of the dissolved oxygen content was 6.180-6.318 mg·L-1. The water temperature in the upper and middle reaches of Xiangxi Bay decreased vertically, while the water temperature in the lower reach presented a ladder-like distribution and the N2 values were all>5×10-5 s-2; thus, the water was in a stable stratified state and the dissolved oxygen content presented a "C" distribution. There was obvious stratification at the depths of 5-15 m and 54-70 m in Xiaowan Reservoir. The dissolved oxygen content decreased significantly at higher water temperature gradients, and there was no significant change along the water depth below 80 m. ③ The main reasons for the variation in the vertical distribution of nitrogen in the sediment interstitial waters of the three waterbodies were the differences in the overlying water hydrodynamics, dissolved oxygen distribution, and sediment environment. The ρ(NH4+) and ρ(NO3-) were higher in Xiangxi Bay, which may have increased the denitrification rate and subsequently have helped to remove nitrogen and reduce the nitrogen load in these waters.

[Spatial and Temporal Distribution Characteristics and the Retention Effects of Nutrients in Xiangjiaba Reservoir].

After the construction of the Xiangjiaba Dam, the hydrodynamic conditions, nutrient distributions, and transport conditions of the Jinsha River were changed. Here, the nutrient distribution characteristics and retention effects of Xiangjiaba Reservoir were investigated according to the results of water quality monitoring from 2015 to 2016. Spatial and temporal variations in TN, TP, SiO32-Si, and other nutrients, and retention flux and retention rate were analyzed. The results showed that the nutrient mass concentration of TN, TP, and SiO32--Si was 0.905 mg·L-1, 0.034 mg·L-1, and 7.98 mg·L-1, respectively. The distribution of TN was affected by point sources and the concentration of TN was large in urban areas. This distribution of TP was mainly granular and the mass concentrations decreased along the river path. The mass concentration of SiO32--Si did not significantly vary over time and space. Furthermore, Xiangjiaba Reservoir had a persistent effect on nutrient salts; the average annual retention of TN, TP, and SiO32--Si was 2.30×104 t·a-1, 0.146×104 t·a-1, and -2.4×104 t·a-1, respectively. During different seasons, the retention of TN and SiO32--Si varied between positive or negative; however, TP appeared to be consistent. The average monthly retention efficiency of TN, TP, and SiO32--Si was 17.5%, 32.8%, and -2.14%, respectively. Overall, retention efficiencies were higher during the dry season than that wet season, and phosphorus retention was most pronounced. The retention of TN in the reservoir may be related to denitrification and the input of external load; the flux of SiO32--Si was mainly affected by runoff; and the particle morphology of phosphorus, as well as reservoir period, were the main factors affecting TP retention. There were no clear correlations between nutrient retention and the mass concentrations of TN and SiO32--Si, but the nutrient retention effect of Xiangjiaba Reservoir reduced TP concentrations along the river path and increased TP concentration with vertical depth.