Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase

Notch signalling is a key intercellular communication mechanism that is essential for cell specification and tissue patterning, and which coordinates critical steps of blood vessel growth. Although subtle alterations in Notch activity suffice to elicit profound differences in endothelial behaviour and blood vessel formation, little is known about the regulation and adaptation of endothelial Notch responses. Here we report that the NAD(+)-dependent deacetylase SIRT1 acts as an intrinsic negative modulator of Notch signalling in endothelial cells. We show that acetylation of the Notch1 intracellular domain (NICD) on conserved lysines controls the amplitude and duration of Notch responses by altering NICD protein turnover. SIRT1 associates with NICD and functions as a NICD deacetylase, which opposes the acetylation-induced NICD stabilization. Consequently, endothelial cells lacking SIRT1 activity are sensitized to Notch signalling, resulting in impaired growth, sprout elongation and enhanced Notch target gene expression in response to DLL4 stimulation, thereby promoting a non-sprouting, stalk-cell-like phenotype. In vivo, inactivation of Sirt1 in zebrafish and mice causes reduced vascular branching and density as a consequence of enhanced Notch signalling. Our findings identify reversible acetylation of the NICD as a molecular mechanism to adapt the dynamics of Notch signalling, and indicate that SIRT1 acts as rheostat to fine-tune endothelial Notch responses.     

Conserved requirement for a plant host cell protein in powdery mildew pathogenesis

In the fungal phylum Ascomycota, the ability to cause disease in plants and animals has been gained and lost repeatedly during phylogenesis. In monocotyledonous barley, loss-of-function mlo alleles result in effective immunity against the Ascomycete Blumeria graminis f. sp. hordei, the causal agent of powdery mildew disease. However, mlo-based disease resistance has been considered a barley-specific phenomenon to date. Here, we demonstrate a conserved requirement for MLO proteins in powdery mildew pathogenesis in the dicotyledonous plant species Arabidopsis thaliana. Epistasis analysis showed that mlo resistance in A. thaliana does not involve the signaling molecules ethylene, jasmonic acid or salicylic acid, but requires a syntaxin, glycosyl hydrolase and ABC transporter. These findings imply that a common host cell entry mechanism of powdery mildew fungi evolved once and at least 200 million years ago, suggesting that within the Erysiphales (powdery mildews) the ability to cause disease has been a stable trait throughout phylogenesis.     

Gemini表面活性剂在气/液界面上的微区形貌随表面压的变化

测定了Gemini表面活性剂在pH值为10．86,NaBr浓度为1．0mol／L的溶液气／液界面上的表面压一分子面积的等温线。用自制的Brewster角显微镜(BAM)观察了由Gemini表面活性剂在界面上所形成单分子膜的微区形貌随表面压的变化。结果表明：当pH值为10．86时,Gemini表面活性剂在1．0mol／L NaBr溶液的气／液界面上生成了凝聚态的单分子膜;当表面压较低时,观察到在界面上形成了同心圆结构;随着表面压的增加,这些同心圆可发生聚并而形成多中心结构。     

Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes

Calorie restriction extends lifespan and produces a metabolic profile desirable for treating diseases of ageing such as type 2 diabetes. SIRT1, an NAD+-dependent deacetylase, is a principal modulator of pathways downstream of calorie restriction that produce beneficial effects on glucose homeostasis and insulin sensitivity. Resveratrol, a polyphenolic SIRT1 activator, mimics the anti-ageing effects of calorie restriction in lower organisms and in mice fed a high-fat diet ameliorates insulin resistance, increases mitochondrial content, and prolongs survival. Here we describe the identification and characterization of small molecule activators of SIRT1 that are structurally unrelated to, and 1,000-fold more potent than, resveratrol. These compounds bind to the SIRT1 enzyme-peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates. In diet-induced obese and genetically obese mice, these compounds improve insulin sensitivity, lower plasma glucose, and increase mitochondrial capacity. In Zucker fa/fa rats, hyperinsulinaemic-euglycaemic clamp studies demonstrate that SIRT1 activators improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver. Thus, SIRT1 activation is a promising new therapeutic approach for treating diseases of ageing such as type 2 diabetes.     

BP网络应用于黄河水质的预测研究

利用黄河兰州段水质指标浓度时间序列作为学习样本，选取了DO、COD、氨氮、重金属离子等l0项指标作为输出参数，运用人工神经网络BP模型中的Levenberg—Marguardt优化算法对学习样本优化建模，将优化好的网络的预测结果与实测结果进行了比较，表明BP网络可以很好地用于黄河水质指标值及水质类别的预测。     

Histochemische Untersuchungen zur Natur der Cytoplasma-Einschlüsse des Lungentumors der Maus

Résumé Dans une étude histochimique on a montré que les inclusions cytoplasmiques des tumeurs pulmonaires de la souris (Klärner etGieseking) contenaient une polysaccharide neutre jointe à l'acide ribonucléique. Les résultats ont été discutés au sens d'une hypothèse virale.     

关于加强青年农民工的思想道德建设的思考

青年农民工是我国工业化、城市化进程中的一支重要力量,他们在为我国经济社会发展做出巨大贡献的同时,却遭受着不公正的待遇,不能取得与拥有城镇户口身份的劳动者平等的地位并享受相应权益等等,这些问题在一定程度上造成青年农民工在思想和道德素质上表现出种种不足,给社会和谐稳定带来了隐患。为此,加强青年农民工的思想道德建设,成为和谐社会发展中的一个重要课题。     

磁性隧道结中自旋相关输运的势垒影响

为了研究势垒对铁磁/绝缘层/半导体/绝缘层/铁磁(FM/I/SM/I/FM)双隧道结中自旋相关电子输运特性的影响,提出了在半导体层厚度合适的情况下,非对称势垒对于提高平行结构磁性双隧道结的自旋注入效率SIE(spin injection efficiency)更具优势.数值计算结果表明,当两势垒强度的比率达到合适数值时双结的SIE和隧穿磁电阻TMR(tunneling magnetore resistance)都将达到最大,这给提高从铁磁到半导体的SIE带来新选择.研究还表明,非对称势垒结构磁性隧道结中增大铁磁交换能对提高SIE和TMR都是有益的,而且铁磁交换能的增加对SIE的提高要比对TMR的提高更显著.