高原人体左心室舒张功能和顺应性的改变

应用同步描记心电图、心音图、颈动脉搏动图和心尖搏动图以测定高原人体的左心室舒张功能和顺应性。在4个不同海拔高度进行实验,即76m(海平对照)、2161m、3270m和4179m,每一高度40名健康男性青年,高原3组世居、移居各20名。结果显示:随着海拔增高,主动舒张时间指数(TRTI)有减小趋势,RF波相对振幅(F/H)逐渐降低,A波相对振幅(A/D)则渐趋增大,3270m以上增大明显(p<0.05),舒张振幅时间指数(DATI)逐渐降低,3270m以上差异极显著(p<0.001)。高原世居与移居者相比,在海拔4179m出现明显差别,移居组TRTI、DATI、F/H较低而A/D较高(D<0.05)。测定射血前期与左室射血时间比值(PEP/LVET)、射血分数(EF)及左室周径纤维平均缩短速度(mVcf)3项指标作对照,显示在此高度左室收缩功能仍能保持。高原慢性心肌缺氧可能是导致左室舒张功能和顺应性轻度降低的原因。     

Climatic and technological ceilings for Chinese rice stagnation based on yield gaps and yield trend pattern analysis

Climatic or technological ceilings could cause yield stagnation. Thus, identifying the principal reasons for yield stagnation within the context of the local climate and socio‐economic conditions are essential for informing regional agricultural policies. In this study, we identified the climatic and technological ceilings for seven rice‐production regions in China based on yield gaps and on a yield trend pattern analysis for the period 1980–2010. The results indicate that 54.9% of the counties sampled experienced yield stagnation since the 1980. The potential yield ceilings in northern and eastern China decreased to a greater extent than in other regions due to the accompanying climate effects of increases in temperature and decreases in radiation. This may be associated with yield stagnation and halt occurring in approximately 49.8–57.0% of the sampled counties in these areas. South‐western China exhibited a promising scope for yield improvement, showing the greatest yield gap (30.6%), whereas the yields were stagnant in 58.4% of the sampled counties. This finding suggests that efforts to overcome the technological ceiling must be given priority so that the available exploitable yield gap can be achieved. North‐eastern China, however, represents a noteworthy exception. In the north‐central area of this region, climate change has increased the yield potential ceiling, and this increase has been accompanied by the most rapid increase in actual yield: 1.02 ton ha^?1 per decade. Therefore, north‐eastern China shows a great potential for rice production, which is favoured by the current climate conditions and available technology level. Additional environmentally friendly economic incentives might be considered in this region.     

BMP2/7 heterodimer enhances osteogenic differentiation of rat BMSCs via ERK signaling compared with respective homodimers

Bone morphogenetic protein (BMP)2/7 heterodimer shows greater efficacy in enhancing bone regeneration. However, the precise mechanism and the role of mitogen-activated protein kinase (MAPK) signaling network in BMP2/7-driven osteogenesis remain ambiguous. In this study, we evaluated the effects of BMP2/7 heterodimers on osteoblastic differentiation in rat bone marrow mesenchymal stem cells (BMSCs), with the aim to elaborate how MAPKs might be involved in this cellular process by treatment of rat BMSCs with BMP2/-7 with a special signal-pathway inhibitor. We found that BMP2/7 heterodimer induced a much stronger osteogenic response in rat BMSCs compared with either homodimer. Most interestingly, extracellular signal-regulated kinase (ERK) demonstrated a highly sustained phosphorylation and activation in the BMP2/7 heterodimer treatment groups, and inhibition of ERK cascades using U0126 special inhibitor that significantly reduced the activity of ALP and calcium mineralization to a substantial degree in rat BMSCs treated with BMP2/7 heterodimers. Collectively, we demonstrate that BMP2/7 heterodimer shows a potent ability to stimulate osteogenesis in rat BMSCs. The activated ERK signaling pathway involved in this process may contribute partially to an increased osteogenic potency of heterodimeric BMP2/7 growth factors.     

The Investigation on Polyion Complex Micelles Composed of Diammonium Glycyrrhizinate/Poly(Ethylene Glycol)–Glycidyltrimethylammonium Chloride-Grafted Polyasparthydrazide

To prepare stable polyion complex (PIC) micelles, polyasparthydrazide (PAHy) modified with glycidyltrimethylammonium groups and methoxy poly(ethylene glycol) (mPEG) (mPEG-g-PAHy-GTA) was synthesized. The cytotoxicity of the polymer was evaluated by the methyl tetrazolium assay. The polymer entrapped the diammonium glycyrrhizinate (DG) and formed polyion complexes. The effect of pH value, grafting degree of mPEG, copolymer and drug concentration on the micelle formation was investigated by means of measuring entrapment efficiency and micelle size. In vitro DG release from the PIC micelles was detected by dialysis in various media of different ionic strengths. To examine the pharmacokinetic behavior of micelles in vivo, the time course of the drug in plasma was evaluated. The cytotoxicity of the polymer was very low. The results showed that entrapment efficiency can reach about 93%, and the mean particle size was almost 50 nm. The drug release rate decreased with a decrease in ionic strength of the release medium or an increase in the PEG grafting degree. Compared with DG solution, the AUC of DG micelles had a twofold increase. The smaller clearance and longer mean residence time of the DG micelles group compared with DG solution group showed that the DG loaded in PIC micelles can reduce drug elimination and prolong the drug residence time in the blood circulation. The results indicated that PIC micelles composed of mPEG-g-PAHy-GTA would be prospective as a drug carrier to the drugs which can be ionized in solution.KEY WORDS: diammonium glycyrrhizinate, drug delivery systems, poly(ethylene glycol)–glycidyltrimethylammonium chloride-grafted polyasparthydrazide, polyion complex micelles     

大豆膨胀素基因GmEXPB5和GmEXPB7生物信息学及表达分析

膨胀素(expansin,EXP)通过调控细胞壁的松弛在植物应对环境胁迫过程中起着重要作用。为研究EXP基因在大豆应对非生物胁迫过程中的作用,该文对大豆中的两个EXP基因(GmEXPB5和GmEXPB7)及其蛋白序列进行生物信息学分析,通过实时荧光定量PCR(qRT-PCR)检测基因表达量。结果表明:(1)GmEXPB5和GmEXPB7分别位于大豆第10号和第12号染色体上,编码的蛋白序列长度分别为272和267个氨基酸。GmEXPB5蛋白分子量为29.07 kD,理论等电点为7.51; GmEXPB7蛋白分子量为29.09 kD,理论等电点为8.66。GmEXPB5和GmEXPB7均为稳定的亲水蛋白且定位于细胞壁中。GmEXPB5和GmEXPB7蛋白均含有一段信号肽序列和一个保守的DPBB_1结构域。(2)GmEXPB5蛋白与鹰嘴豆CaEXPB15蛋白亲缘关系最近,GmEXPB7蛋白与密花豆、赤豆和豇豆的EXPB3蛋白有着较近的亲缘关系。(3)GmEXPB5和GmEXPB7在大豆根、茎和叶中均有表达且它们在根和叶中的表达量均显著高于茎中的表达量。(4)GmEXPB5和GmEXPB7在大豆幼苗中可以响应盐、干旱和低温胁迫。(5)GmEXPB5启动子区域含有2种与逆境相关的顺式作用元件(ABRE和ARE); GmEXPB7启动子区域含有5种与逆境相关的顺式作用元件(ABRE、ARE、CGTCA-motif、TC-rich repeats和MBS)。综上所述,GmEXPB5和GmEXPB7能够参与大豆对非生物胁迫的应答。     

摇蚊幼虫对底泥中氮、磷释放作用的研究

本文研究了摇蚊幼虫对底泥中氮、磷释放的影响,初步探讨了摇蚊在湖泊富营养化过程中的生态作用。结果表明,摇蚊幼虫能明显促进底泥中氮、磷的释放,而释放到水层中的氮、磷又容易被藻类吸收利用,从而促进藻类生长。这种生态效应与水体营养循环和富营养化的发生及发展过程间存在着重要的关系。     

Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome

Two groups of tau, 3R- and 4R-tau, are generated by alternative splicing of tau exon 10. Normal adult human brain expresses equal levels of them. Disruption of the physiological balance is a common feature of several tauopathies. Very early in their life, individuals with Down syndrome (DS) develop Alzheimer-type tau pathology, the molecular basis for which is not fully understood. Here, we demonstrate that Dyrk1A, a kinase encoded by a gene in the DS critical region, phosphorylates alternative splicing factor (ASF) at Ser-227, Ser-234, and Ser-238, driving it into nuclear speckles and preventing it from facilitating tau exon 10 inclusion. The increased dosage of Dyrk1A in DS brain due to trisomy of chromosome 21 correlates to an increase in 3R-tau level, which on abnormal hyperphosphorylation and aggregation of tau results in neurofibrillary degeneration. Imbalance of 3R- and 4R-tau in DS brain by Dyrk1A-induced dysregulation of alternative splicing factor-mediated alternative splicing of tau exon 10 represents a novel mechanism of neurofibrillary degeneration and may help explain early onset tauopathy in individuals with DS.     

Activation of the bitter taste sensor TRPM5 prevents high salt-induced cardiovascular dysfunction

Science China Life Sciences - High salt intake is a known risk factor of cardiovascular diseases. Our recent study demonstrated that long-term high salt intake impairs transient receptor potential...     

A Fast Workflow for Identification and Quantification of Proteomes

The current in-depth proteomics makes use of long chromatography gradient to get access to more peptides for protein identification, resulting in covering of as many as 8000 mammalian gene products in 3 days of mass spectrometer running time. Here we report a fast sequencing (Fast-seq) workflow of the use of dual reverse phase high performance liquid chromatography - mass spectrometry (HPLC-MS) with a short gradient to achieve the same proteome coverage in 0.5 day. We adapted this workflow to a quantitative version (Fast quantification, Fast-quan) that was compatible to large-scale protein quantification. We subjected two identical samples to the Fast-quan workflow, which allowed us to systematically evaluate different parameters that impact the sensitivity and accuracy of the workflow. Using the statistics of significant test, we unraveled the existence of substantial falsely quantified differential proteins and estimated correlation of false quantification rate and parameters that are applied in label-free quantification. We optimized the setting of parameters that may substantially minimize the rate of falsely quantified differential proteins, and further applied them on a real biological process. With improved efficiency and throughput, we expect that the Fast-seq/Fast-quan workflow, allowing pair wise comparison of two proteomes in 1 day may make MS available to the masses and impact biomedical research in a positive way.The performance of mass spectrometry has been improved tremendously over the last few years (1–3), making mass spectrometry-based proteomics a viable approach for large-scale protein analysis in biological research. Scientists around the world are striving to fulfill the promise of identifying and quantifying almost all gene products expressed in a cell line or tissue. This would make mass spectrometry-based protein analysis an approach that is compatible to the second-generation mRNA deep-seq technique (4, 5).Two liquid chromatography (LC)-MS strategies have been employed to achieve deep proteome coverage. One is a single run with a long chromatography column and gradient to take advantage of the resolving power of HPLC to reduce the complexity of peptide mixtures; the other is a sequential run with two-dimensional separation (typically ion-exchange and reverse phase) to reduce peptide complexity. It was reported by two laboratories that 2761 and 4500 proteins were identified with a 10 h chromatography gradient on a dual pressure linear ion-trap orbitrap mass spectrometer (LTQ Orbitrap Velos)(6–8). Similarly, 3734 proteins were identified using a 8 h gradient on a 2 m long column with a hybrid triple quadrupole - time of flight (Q-TOF, AB sciex 5600 Q-TOF)(9) mass spectrometer. The two-dimensional approach has yielded more identification with longer time. For example, 10,006 proteins (representing over 9000 gene products, GPs)¹ were identified in U2OS cell (10), and 10,255 proteins (representing 9207 GPs) from HeLa cells (11). It took weeks (for example, 2–3 weeks) of machine running time to achieve such proteome coverage, pushing proteome analysis to the level that is comparable to mRNA-seq. With the introduction of faster machines, human proteome coverage now has reached the level of 7000–8500 proteins (representing 7000–8000 GPs) in 3 days (12). Notwithstanding the impressive improvement, the current approach using long column and long gradient suffers from inherent limitations: it takes long machine running time and it is challenging to keep reproducibility among repeated runs. Thus, current throughput and reproducibility have hindered the application of in-depth proteomics to traditional biological researches. A timesaving approach is in urgent need.In this study, we used the first-dimension (1D) short pH 10 RP prefractionation to reduce the complexity of the proteome (13), followed by sequential 30 min second-dimension (2D) short pH 3 reverse phase-(RP)-LC-MS/MS runs for protein identification (14). The results demonstrated that it is possible to identify 8000 gene products from mammalian cells within 12 h of total MS measurement time by applying this dual-short 2D-RPLC-MS/MS strategy (Fast sequencing, Fast-seq). The robustness of the strategy was revealed by parallel testing on different MS systems including quadrupole orbitrap mass spectrometer (Q-Exactive), hybrid Q-TOF (Triple-TOF 5600), and dual pressure linear ion-trap orbitrap mass spectrometer (LTQ-Orbitrap Velos), indicating the inherent strength of the approach as to merely taking advantage of the better MS instruments. This strategy increases the efficiency of MS sequencing in unit time for the identification of proteins. We achieved identification of 2200 proteins/30 mins on LTQ-Orbitrap Velos, 2800 proteins/30 mins on Q-Exactive and Triple-TOF 5600 respectively. We further optimized Fast-seq and worked out a quantitative-version of the Fast-seq workflow: Fast-quantification (Fast-quan) and applied it for protein abundance quantification in HUVEC cell that was treated with a drug candidate MLN4924 (a drug in phase III clinical trial). We were able to quantify > 6700 GPs in 1 day of MS running time and found 99 proteins were up-regulated with high confidence. We expect this efficient alternative approach for in-depth proteome analysis will make the application of MS-based proteomics more accessible to biological applications.