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Background: Over 100 mutations in the SRD5A2 gene have been identified in subjects with 46,XY disorder of sex development (DSD). Exploration of SRD5A2 mutations and elucidation of the molecular mechanisms behind their effects should reveal the functions of the domains of the 5α-reductase 2 enzyme and identify the cause of 46,XY DSD. Previously, we reported a novel compound heterozygous p.Q6X/p.H232R mutation of the SRD5A2 gene in a case with 46,XY DSD. Whether the compound heterozygous p.Q6X/p.H232R mutation in this gene causes 46,XY DSD requires further exploration. Methods: The two 46,XY DSD cases were identified and sequenced. In order to identify the source of the compound heterozygous p.Q6X/p.H232R mutation, the parents, maternal grandparents, and maternal uncle were sequenced. Since p.Q6X mutation is a nonsense mutation, p.H232R mutation was transfected into HEK293 cells and dihydrotestosterone (DHT) production were analyzed by liquid chromatography–mass spectrometry (LC–MS) for 5α-reductase 2 enzyme activities test. Apparent michaelis constant (Km) were measured of p.H232R mutation to analyze the binding ability change of 5α-reductase 2 enzyme with testosterone (T) or NADPH. Results: The sequence results showed that the two 46,XY DSD cases were the compound heterozygous p.Q6X/p.H232R mutation, of which the heterozygous p.Q6X mutation originating from maternal family and heterozygous p.H232R mutation originating from the paternal family. The function analysis confirmed that p.H232R variant decreased the DHT production by LC–MS test. The Km analysis demonstrated that p.H232R mutation affected the binding of SRD5A2 with T or NADPH. Conclusions: Our findings confirmed that the compound heterozygous p.Q6X/p.H232R mutation in the SRD5A2 gene is the cause of 46,XY DSD. p.H232R mutation reduced DHT production while attenuating the catalytic efficiency of the 5α-reductase 2 enzyme. [ABSTRACT FROM AUTHOR]

Rationale: MicroRNAs (miRNAs) regulate neuroplasticity-related proteins and are implicated in methamphetamine (METH) addiction. RhoA is a small Rho GTPase that regulates synaptic plasticity and addictive behaviors. Nevertheless, the functional relationship between RhoA and upstream miRNAs of METH addiction remains unclear. Objective: To explore the molecular biology and epigenetic mechanisms of the miR-31-3p/RhoA pathway in METH addiction. Methods: RhoA protein and its potential upstream regulator, miR-31-3p, were detected. A dual luciferase reporter was employed to determine whether RhoA constituted a specific target of miR-31-3p. Following adeno-associated virus (AAV)-mediated knockdown or overexpression of miR-31-3p or RhoA in the dorsal hippocampus (dHIP), mice were subjected to conditioned place preference (CPP) to investigate the effects of miR-31-3p and RhoA on METH-induced addictive behaviors. Results: RhoA protein was significantly decreased in the dHIP of CPP mice with a concomitant increase in miR-31-3p. RhoA was identified as a direct target of miR-31-3p. Knockdown of miR-31-3p in the dHIP was associated with increased RhoA protein and attenuation of METH-induced CPP. Conversely, overexpression of miR-31-3p was associated with decreased RhoA protein and enhancement of METH effects. Similarly, knockdown of RhoA in the dHIP enhanced METH-induced CPP, whereas RhoA overexpression attenuated the effects of METH. Parallel experiments using sucrose preference revealed that the effects of miR-31-3p/RhoA pathway modulation were specific to METH. Conclusions: Our findings indicate that the miR-31-3p/RhoA pathway in the dHIP modulates METH-induced CPP in mice. Our results highlight the potential role of epigenetics represented by non-coding RNAs in the treatment of METH addiction. [ABSTRACT FROM AUTHOR]

The C-band radar instruments onboard the two-satellite GMES Sentinel-1 constellation provide global measurements with short revisit time (about six days) and medium spatial resolution (5 × 20 m), which are appropriate for watershed scale hydrological applications. This paper aims to explore the potential of Sentinel-1 for estimating surface soil moisture using a multi-temporal approach. To this end, a linear mixed effects (LME) model was developed over Poyang Lake ungauged zone, using time series Sentinel 1A and 1B images and soil moisture ground measurements from 15 automatic observation sites. The model assumed a linear relationship that varied with both time and space between soil moisture and backscattering coefficient (SM-s0). Results showed that three LME models developed with different polarized s0 images all meet the European Space Agency (ESA) accuracy requirement for GMES soil moisture product (≤5% in volume), with the vertical transmit and vertical receive (VV) polarized model achieving the best performance. However, the SM-s0 relationship was found to depend strongly on space, making it difficult to predict absolute soil moisture for each grid. Therefore, a relative soil moisture index was then proposed to correct for site effect. When compared with those of the linear fixed effects model, the soil moisture indices predicted by the LME model captured the temporal dynamics of measured soil moisture better, with the overall R2 and cross-validated R2 being 0.68 and 0.64, respectively. These results indicate that the LME model can be effectively applied to estimate soil moisture from multi-temporal Sentinel-1 images, which is useful for monitoring flood and drought disasters, and for improving stream flow prediction over ungauged zones. [ABSTRACT FROM AUTHOR]

• Low (0.33 mg/kg) dose of LY235959 could increase mice locomotor activity. • High (3.0 mg/kg) dose of LY235959 could induce some symptoms caused by NMDAR inhibition. • Medium (1.0 mg/kg) dose of LY235959 could disrupt development phase of METH-induced behavioral sensitization. Drug addiction can be described as a chronic and relapsing brain disease. Behavioral sensitization is common animal model in the study of addiction and N-Methyl-D-aspartate subtype of glutamate receptor (NMDAR) is believed play key role in this process. LY235959 is a competitive NMDAR antagonist, however, its effect on methamphetamine (METH)-induced behavioral sensitization is not been reported yet. In this study, we choose three doses (0.33 mg/kg, 1.0 mg/kg, and 3.0 mg/kg) of LY235959 to investigate its effect on locomotor activity, METH-induced behavioral sensitization and different phases of it in C57/BL6 mice. We also used western blotting to examine the PP2A/B – AKT cascade which had been proved involved in METH-induced behavioral sensitization in the dorsal striatum (DS). The results showed that only 0.33 mg/kg LY235959 increased locomotor activity dramatically, however, 1.0 mg/kg and 3.0 mg/kg of LY235959 could attenuate METH-induced behavioral sensitization markedly. We also found that LY235959 only disrupted the development phase of METH-induced behavioral sensitization and the following western blotting results further indicated that PP2A/B – AKT cascade might involve in this process. Taken together, these results indicated that LY235959 attenuates development phase of METH-induced behavioral sensitization through the PP2A/B - AKT cascade in the DS. [ABSTRACT FROM AUTHOR]

Organic amendment (OA) has positive effects on rice yield in literature, but few studies have reported positive effects on rice yield trend in a region, which need to be distinguished for the development of sustainable agriculture in terms of management of organic resources available in agroecosystems. The objectives of the present study were to examine the long-term effects of OA on rice yield, yield trends and soil fertility change under the same double rice cropping system at three experimental sites established in 1980s in subtropical China. Organic amendments at the sites covered different strategies in use of locally available green manure, rice straw and farmyard manure to partially substitute inorganic fertilizers at different doses of recommended N, P and K in combination at Jinxian, Jiangxi Province, to partially substitute inorganic N at rates of 30%, 50% and 70% of the recommended rate at Nanchang, Jiangxi Province, and to fully substitute single element of inorganic N, P and K at Qiyang, Hunan Province. The actual rice yield showed no significant time trends at Jinxian and Nanchang and negative trends in the treatments with low N application rates at Qiyang. Analysis of the relative yield trends showed significant positive effects of OA on the yield trends for either first or second rice crop in the treatments except for those without sufficient nutrient supply. The positive effects can be attributed mainly to the increased soil organic carbon and soil nutrient capacity due to the long-term application of OA. The results suggest that the organic amendments strategies should be encouraged as partial substitution of inorganic fertilizers for the consideration long-term yield trends and soil fertility. [Copyright &y& Elsevier]