Spontaneous mutations in FgSAD1 suppress the growth defect of the Fgprp4 mutant by affecting tri-snRNP stability and its docking in Fusarium graminearum

FgPrp4, the only kinase in the spliceosome, is not essential for viability, but is important for splicing efficiency in Fusarium graminearum. The Fgprp4 deletion mutant had severe growth defects but often produced spontaneous suppressors with faster growth rate. To better understand the suppression mechanism, we identified and characterized spontaneous mutations in the tri-snRNP-specific protein, FgSad1, which suppressed the growth defects of Fgprp4. The L512P mutation was verified for its suppressive effects on Fgprp4, suggesting that mutations in FgSad1 may have effects involving FgPrp4 phosphorylation on FgSad1. Phosphoproteomics analysis showed that FgSad1 may not be the direct substrate of FgPrp4 kinase. Furthermore, truncation analysis showed that the N-terminal, extra RS-rich region of FgSad1 is critical for its function and is post-translationally modified. The P258S or S269P mutations in FgSad1 increased its interactions with the U5 protein FgPrp8 and the U4/U6 protein FgPrp31, which may result in tri-snRNP stabilization. Additionally, the D76N mutation increased the association of FgSad1 with the U2 snRNP. These data indicate that suppressor mutations in FgSad1 increase the stability of the tri-snRNP and/or the affinity of FgSad1 with U2 snRNP and therefore potentially facilitate the docking of tri-snRNP into the spliceosome.     

Role of Chitosan in the Regulation of the Growth,Antioxidant System and Photosynthetic Characteristics of Maize Seedlings under Cadmium Stress

Russian Journal of Plant Physiology - Cadmium (Cd) pollution was becoming more and more serious; there is an urgent need for an effective solution to inhibit the harm of cadmium stress. Chitosan...     

Pharmacokinetic,metabolic stability,plasma protein binding and CYP450s inhibition/induction assessment studies of N-(2-pyridylmethyl)-2-hydroxiymethyl-1-pyrrolidinyl-4-(3-chloro-4-methoxy-benzylamino)-5-pyrimidine-carboxamide as potential type 5 phosphodiesterase inhibitors

N-(2-pyridylmethyl)-2-hydroxiymethyl-1-pyrrolidinyl-4-(3-chloro-4-methoxy-benzylamino)-5-pyrimidine-carboxamide (NHPPC) is a new potential of type 5 phosphodiesterase (PDE5) inhibitors, synthesized from the avanafil analogue for the treatment of erectile dysfunction. The targets of this article were to assess plasma protein binding, liver microsomal metabolic stability, inhibition and induction on cytochrome P450 isozymes and the pharmacokinetics of NHPPC. Equilibrium dialysis technique was applied to determine Plasma protein binding (PPB) and NHPPC was evaluated in male Sprague–Dawley rats and Beagle dogs in vivo pharmacokinetic. The NHPPC was highly bound to plasma proteins in rats, dogs and human tested and the mean values for PPB rate were 96.2%, 99.6% and 99.4%, respectively. After in vitro liver microsomes incubated for 60?min, the percent remaining of NHPPC was 42.8%, 0.8% and 42.0% in rats, dogs and human, respectively. In vitro intrinsic clearance was found to be 0.0233, 0.1204 and 0.0214 mL/min/mg protein in rat, dog and human liver microsomes of NHPPC, respectively. NHPPC showed no significant inhibitory effects on major CYP450 enzymes, and had no significant induction potential on CYP1A2 and CYP3A4. Following oral administration in rats and dogs, t_max was 6 and 0.5?h, respectively. The clearance for NHPPC was 1.19 and 1.46?L/h/kg in rats and dogs, respectively. And absolute bioavailability in rat and dog were approximately 34.5% and 53.1%, respectively. These results showed that NHPPC has a good development prospect.     

PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress

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Fitness costs associated with acetyl‐coenzyme A carboxylase mutations endowing herbicide resistance in American sloughgrass (Beckmannia syzigachne Steud.)

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人中鼻甲来源嗅鞘细胞培养与鉴定的初步研究

目的探索一种从人中鼻甲分离培养嗅鞘细胞的方法并鉴定所获得的细胞。 方法通过手术获取人中鼻甲黏膜组织,随后进行两步消化并剥离黏膜上皮组织,得到体积较小的组织块,再进行组织块原代（传代）培养并加压筛选,最终得到双极或多极样细胞并对获得的细胞进行免疫荧光鉴定。上皮样细胞比例、S100β和p75阳性细胞比例用 ±s表示,组间比较采用独立样本t检验。 结果将不剥离上皮层与剥离上皮层培养的原代细胞中上皮样细胞的比例进行对比,发现上皮层组上皮样细胞比例为（92.23±3.93）%高于剥离上皮层组上皮样细胞的比例（77.63±2.97）%,差异具有统计学意义（t = 5.129,P = 0.007）。采用剥离上皮层法培养原代细胞,经过加压筛选的细胞呈现双极或多极样,符合嗅鞘细胞形态学特点。免疫荧光染色发现,S100β阳性细胞占总细胞量的（8.1±1.7）%,而p75阳性细胞占总细胞量的5%以下,达到国内外研究同等水平。 结论通过使用两步消化法和加压筛选联合的方法从人中鼻甲粘膜组织中成功获得了人中鼻甲嗅鞘细胞,相比较传统方法,细胞分离培养周期明显缩短。     

OsRLCK160 contributes to flavonoid accumulation and UV-B tolerance by regulating OsbZIP48 in rice

Science China Life Sciences - Plants produce specialized metabolites to adapt to the ever-changing environments. Flavonoids are antioxidants essential for growth, development, and breeding with...     

Spectroscopic and molecular modeling studies of the interaction between cytidine and human serum albumin and its analytical application

In this study, the interaction between cytidine and human serum albumin (HSA) was investigated for the first time by fluorescence spectroscopy in combination with UV absorption spectrum and molecular modeling under simulative physiological conditions. Experimental results indicated that cytidine had a strong ability to quench the intrinsic fluorescence of human serum albumin. The binding constants (K) at different temperatures, thermodynamic parameter enthalpy changes (DeltaH) and entropy changes (DeltaS) of HSA-cytidine had been calculated according to the relevant fluorescence data, which indicated that the hydrophobic and electrostatic interactions played a major role, which was in agreement with the results of molecular modeling study. In addition, the effects of other ions on the binding constants were also studied. Furthermore, synchronous fluorescence technology was successfully applied to the determination of human serum albumin added into the cytidine solution.     

Nitric oxide destabilizes Pias3 and regulates sumoylation

Small ubiquitin-related protein modifiers (SUMO) modification is an important mechanism for posttranslational regulation of protein function. However, it is largely unknown how the sumoylation pathway is regulated. Here, we report that nitric oxide (NO) causes global hyposumoylation in mammalian cells. Both SUMO E2 conjugating enzyme Ubc9 and E3 ligase protein inhibitor of activated STAT3 (Pias3) were targets for S-nitrosation. S-nitrosation did not interfere with the SUMO conjugating activity of Ubc9, but promoted Pias3 degradation by facilitating its interaction with tripartite motif-containing 32 (Trim32), a ubiquitin E3 ligase. On the one hand, NO promoted Trim32-mediated Pias3 ubiquitination. On the other hand, NO enhanced the stimulatory effect of Pias3 on Trim32 autoubiquitination. The residue Cys459 of Pias3 was identified as a target site for S-nitrosation. Mutation of Cys459 abolished the stimulatory effect of NO on the Pias3-Trim32 interaction, indicating a requirement of S-nitrosation at Cys459 for positive regulation of the Pias3-Trim32 interplay. This study reveals a novel crosstalk between S-nitrosation, ubiquitination, and sumoylation, which may be crucial for NO-related physiological and pathological processes.