A novel MET-interacting protein shares high sequence similarity with RanBPM, but fails to stimulate MET-induced Ras/Erk signaling

MET is a receptor protein tyrosine kinase for hepatocyte growth factor, a multifunctional cytokine controlling cell growth, morphogenesis, and motility. In our previous study, RanBPM/RanBP9, whose name originated from its ability to interact with Ran, was identified as a MET-interacting protein. RanBPM/RanBP9 activates the Ras/Erk signaling pathway by serving as an adaptor protein of MET to recruit Sos. In this study, we identify a protein sharing a high amino acid sequence identity with RanBPM/RanBP9, especially in its SPRY domain, the region responsible for MET binding. This protein lacks the N-terminal poly-proline and poly-glutamine (Poly-PQ) stretch present in RanBPM/RanBP9 and has less homology with RanBPM/RanBP9 in its mid-region. We subsequently named this protein RanBP10 after demonstrating its interaction with Ran. We show that, like RanBPM/RanBP9, RanBP10 interacts with the tyrosine kinase domain of MET via its SPRY domain and these two proteins can compete with each other to bind to MET. Interestingly, unlike RanBPM/RanBP9, overexpression of RanBP10 cannot induce Erk1/2 phosphorylation and serum response element-luciferase (SRE-LUC) reporter gene expression. More importantly, co-transfection of RanBPM/RanBP9 and RanBP10 significantly represses SRE-LUC reporter gene expression induced by overexpression of RanBPM/RanBP9. Additional binding assays demonstrate that RanBP10 fails to interact with Sos, which explains its inability to activate the Ras/Erk pathway. Furthermore, we show that the N-terminus of RanBPM/RanBP9 with the Poly-PQ stretch is required for recruiting Sos and a truncated RanBPM/RanBP9 lacking this region fails to recruit Sos, indicating that the functional difference between RanBP10 and RanBPM/RanBP9 lies in their sequence difference in their N-termini.     

Orexin 受体拮抗剂：治疗失眠的新途径

Orexin 受体有2 种亚型,即orexin-1 受体和oerxin-2 受体,为下丘脑外侧神经元中的2 个G 蛋白偶联受体,其内源性配体分别为orexin-A 和-B。研究发现,动物或人的orexin 神经元损伤后会引起嗜睡症,且orexin 受体在调节睡眠- 觉醒周期方面发挥重要作用。因此,开发orexin 受体拮抗剂,成为改善睡眠和治疗失眠的一条新途径。简介orexin 及其受体,综述orexin 信号通路对睡眠- 觉醒的调控作用与机制以及orexin 受体拮抗剂的研究与开发。     

Partial Protective Effect of Intranasal Immunization with Recombinant Toxoplasma gondii Rhoptry Protein 17 against Toxoplasmosis in Mice

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects a variety of mammals, including humans. An effective vaccine for this parasite is therefore needed. In this study, RH strain T. gondii rhoptry protein 17 was expressed in bacteria as a fusion with glutathione S-transferase (GST) and the recombinant proteins (rTgROP17) were purified via GST-affinity chromatography. BALB/c mice were nasally immunised with rTgROP17, and induction of immune responses and protection against chronic and lethal T. gondii infections were investigated. The results revealed that mice immunised with rTgROP17 produced high levels of specific anti-rTgROP17 IgGs and a mixed IgG1/IgG2a response of IgG2a predominance. The systemic immune response was associated with increased production of Th1 (IFN-γand IL-2) and Th2 (IL-4) cytokines, and enhanced lymphoproliferation (stimulation index, SI) in the mice immunised with rTgROP17. Strong mucosal immune responses with increased secretion of TgROP17-specific secretory IgA (SIgA) in nasal, vaginal and intestinal washes were also observed in these mice. The vaccinated mice displayed apparent protection against chronic RH strain infection as evidenced by their lower liver and brain parasite burdens (59.17% and 49.08%, respectively) than those of the controls. The vaccinated mice also exhibited significant protection against lethal infection of the virulent RH strain (survival increased by 50%) compared to the controls. Our data demonstrate that rTgROP17 can trigger strong systemic and mucosal immune responses against T. gondii and that ROP17 is a promising candidate vaccine for toxoplasmosis.     

Survival Impact of Delaying Postoperative Radiotherapy in Patients with Esophageal Cancer

The purpose of the current study was to retrospectively assess the effect of postoperative radiotherapy (RT) delay on survival for patients with esophageal cancer. From 2008 to 2011, patients with esophageal cancer who had undergone postoperative RT in five different hospitals in China were reviewed. Clinical data, including time interval between surgery to RT, were prospectively collected. Kaplan-Meier method was conducted to estimate the effect of each variable on progression-free survival (PFS) and overall survival (OS), with differences assessed by log-rank test. Univariate Cox proportional-hazards models were performed for both PFS and OS for all assumed predictor variables. Statistically significant predictor variables (P < .05) on univariate analysis were then included in multivariate Cox proportional-hazards models, which were performed to compare the effects of RT delay on PFS and OS. A total of 316 patients were finally enrolled in this prospectively multicentric study. Time to RT after surgery varied from 12 days to over 60 days (median, 26 days). Multivariate analysis showed that delay to RT longer than the median does not appear to be a survival cost. There was also no statistically difference in PFS (P = .513) or OS (P = .236) between patients stratified by quartiles (≤21 days vs ≧35 days). However, patients with particularly long delays (≧42 days) demonstrated a detrimental impact on OS (P = .021) but not PFS (P = .580). Delaying postoperative RT of esophageal cancer does not impact PFS, but results in a significant reduction on OS if delaying longer than 6 weeks.     

硝尔库勒湖可培养放线菌多样性及其功能酶和抗细菌活性

【目的】认识和了解硝尔库勒湖可培养放线菌的多样性、功能酶和抗细菌活性特点,为今后的开发和利用奠定基础。【方法】应用可培养技术和基于16S r RNA基因序列的系统发育分析硝尔库勒盐湖沉积物中放线菌的多样性。常规方法检测样品成分因子,并筛选了嗜盐放线菌的蛋白酶、淀粉酶和酯酶活性;抑菌圈法检测放线菌新种的抗细菌活性。【结果】分离获得了51个OTUs,分属于24个不同的属,其中15个OTUs代表了放线菌新种;链霉菌属是优势菌属,占全部分离菌株数量的16.25%。硝尔库勒湖放线菌类群数量一定程度上受样品成分因子的协同影响。代表新种的菌株展示了良好的功能酶活性和抗细菌活性,其中代表链霉菌新种的菌株XHU5011不仅具有多种酶活性,而且具有强大的抗金黄葡萄球菌、耻垢分枝杆菌和荧光假单胞菌的能力,具有很好的开发潜能。【结论】硝尔库勒盐湖中存在丰富的可培养放线菌多样性,潜藏着大量的放线菌新资源,并且具有很好的功能酶和天然产物挖掘潜力。     

PAC对谷子花后土壤氮素供应和叶片抗氧化特性的影响

全基施肥方式会造成作物全生育期内营养供应失衡,导致生育后期缺氮早衰。为探究聚天门冬氨酸和壳聚糖复配剂(PAC)保障谷子(Setariaitalica)花后氮素供应和调控叶片抗氧化特性的机制,建立全基施肥背景下东北春谷防衰增产的生产技术,于2020–2021年在中国农业科学院作物科学研究所公主岭试验站开展大田试验,以谷子品种张杂谷13号和华优谷9号为材料,设置常规氮素(CN)和PAC配合氮素(PN) 6个氮素水平(0、75、112.5、150、225和337.5 kg·hm^–2)播种前进行全基施肥处理。结果表明,与常规氮肥处理相比,相同施氮量下,PAC处理后,两品种谷子花期和灌浆中期0–20cm和20–40 cm土层土壤硝态氮和铵态氮含量升高,花后叶面积显著增大,叶面积降幅减小;花后0–40天旗叶超氧化物歧化酶、过氧化物酶及过氧化氢酶活性升高,丙二醛含量降低。因此, PAC有效保障了谷子生育中、后期土壤氮素的供应,提高了叶片抗氧化能力,延缓了叶片衰老进程,进而提高产量。2020年和2021年Z13的增产幅度分别为11.24%–21.55%和8.65%–14.22%,...     

Hyposensitive canopy conductance renders ecosystems vulnerable to meteorological droughts

Increased meteorological drought intensity with rising atmospheric demand for water (hereafter vapor pressure deficit [VPD]) increases the risk of tree mortality and ecosystem dysfunction worldwide. Ecosystem-scale water-use strategy is increasingly recognized as a key factor in regulating drought-related ecosystem responses. However, the link between water-use strategy and ecosystem vulnerability to meteorological droughts is poorly established. Using the global flux observations, historic hydroclimatic data, remote-sensing products, and plant functional-trait archive, we identified potentially vulnerable ecosystems, examining how ecosystem water-use strategy, quantified by the percentage bias (δ) of the empirical canopy conductance sensitivity to VPD relative to the theoretical value, mediated ecosystem responses to droughts. We found that prevailing soil water availability substantially impacted δ in dryland regions where ecosystems with insufficient soil moisture usually showed conservative water-use strategy, while ecosystems in humid regions exhibited more pronounced climatic adaptability. Hyposensitive and hypersensitive ecosystems, classified based on δ falling below or above the theoretical sensitivity, respectively, achieved similar net ecosystem productivity during droughts, employing different structural and functional strategies. However, hyposensitive ecosystems, risking their hydraulic system with a permissive water-use strategy, were unable to recover from droughts as quickly as hypersensitive ones. Our findings highlight that processed-based models predicting current functions and future performance of vegetation should account for the greater vulnerability of hyposensitive ecosystems to intensifying atmospheric and soil droughts.     

High-Resolution Performance of Polycaprolactone Functionalized with Guanidinium Ionic Liquid for Gas Chromatography

This work firstly reported a new polycaprolactone based material functionalized with guanidinium ionic liquid (PCL-GIL) as the stationary phase with high resolution performance for capillary gas chromatography (GC). It is composed of polycaprolactone (PCL) and guanidinium ionic liquid (GIL) with amphiphilic conformation. The PCL-GIL capillary column coated by static method exhibited high column efficiency of 3942 plates/m and moderate polarity. As a result, the PCL-GIL column exhibited high-resolution capability. For a mixture of 27 analytes with a wide ranging polarity and outperformed the PCL-2OH and HP-35 columns, showing its advantageous separation capability for analytes of diverse types. Moreover, the PCL-GIL column showed high resolving capability for various positional isomers and cis-/trans-isomers, including alkylbenzenes, chlorobenzenes, naphthalenes, bromonitrobenzenes, chloronitrobenzenes, benzaldehydes, phenols, alcohols, respectively. In a word, PCL derivatized by GIL units as a new type of stationary phase has a promising future in GC separations.     

Effects of small interfering RNA-mediated hepatic glucagon receptor inhibition on lipid metabolism in db/db mice

Hepatic glucose overproduction is a major characteristic of type 2 diabetes. Because glucagon is a key regulator for glucose homeostasis, antagonizing the glucagon receptor (GCGR) is a possible therapeutic strategy for the treatment of diabetes mellitus. To study the effect of hepatic GCGR inhibition on the regulation of lipid metabolism, we generated siRNA-mediated GCGR knockdown (si-GCGR) in the db/db mouse. The hepatic knockdown of GCGR markedly reduced plasma glucose levels; however, total plasma cholesterol was increased. The detailed lipid analysis showed an increase in the LDL fraction, and no change in VLDL HDL fractions. Further studies showed that the increase in LDL was the result of over-expression of hepatic lipogenic genes and elevated de novo lipid synthesis. Inhibition of hepatic glucagon signaling via siRNA-mediated GCGR knockdown had an effect on both glucose and lipid metabolism in db/db mice.