S100A1 enhances the L-type Ca2+ current in embryonic mouse and neonatal rat ventricular cardiomyocytes

S100A1 is an EF-hand type Ca2+-binding protein with a muscle-specific expression pattern. The highest S100A1 protein levels are found in cardiomyocytes, and it is expressed already at day 8 in the heart during embryonic development. Since S100A1 is known to be involved in the regulation of Ca2+ homeostasis, we tested whether extracellular S100A1 plays a role in regulating the L-type Ca2+ current (I(Ca)) in ventricular cardiomyocytes. Murine embryonic (day 16.5 postcoitum) ventricular cardiomyocytes were incubated with S100A1 (0.001-10 microM) for different time periods (20 min to 48 h). I(Ca) density was found to be significantly increased as early as 20 min (from -10.8 +/- 1 pA/pF, n = 18, to -22.9 +/- 1.4 pA/pF; +112.5 +/- 13%, n = 9, p < 0.001) after the addition of S100A1 (1 microM). S100A1 also enhanced I(Ca) current density in neonatal rat cardiomyocytes. Fluorescence and capacitance measurements evidenced a fast translocation of rhodamine-coupled S100A1 from the extracellular space into cardiomyocytes. S100A1 treatment did not affect cAMP levels. However, protein kinase inhibitor, a blocker of cAMP-dependent protein kinase A (PKA), abolished the S100A1-induced enhancement of I(Ca). Accordingly, measurements of PKA activity yielded a significant increase in S100A1-treated cardiomyocytes. In vitro reconstitution assays further demonstrated that S100A1 enhanced PKA activity. We conclude that the Ca2+-binding protein S100A1 augments transsarcolemmal Ca2+ influx via an increase of PKA activity in ventricular cardiomyocytes and hence represents an important regulator of cardiac function.     

beta-cyclodextrin-immobilized (4S)-phenoxy-(S)-proline as a catalyst for direct asymmetric aldol reactions

beta-Cyclodextrin-immobilized (4S)-phenoxy-(S)-proline was prepared conveniently by simply heating the amino acid and beta-cyclodextrin in ethanol-water (1/1, v/v) and removal of the solvent. This proved to be an efficient catalyst for direct asymmetric aldol reactions, and the catalyst could be recycled four times without loss of enantioselectivity.     

AtNAP1 represents an atypical SufB protein in Arabidopsis plastids

The assembly of iron-sulfur (Fe-S) clusters involves several pathways and in prokaryotes the mobilization of the sulfur (SUF) system is paramount for Fe-S biogenesis and repair during oxidative stress. The prokaryotic SUF system consists of six proteins: SufC is an ABC/ATPase that forms a complex with SufB and SufD, SufA acts as a scaffold protein, and SufE and SufS are involved in sulfur mobilization from cysteine. Despite the importance of Fe-S proteins in higher plant plastids, little is known regarding plastidic Fe-S cluster assembly. We have recently shown that Arabidopsis harbors an evolutionary conserved plastidic SufC protein (AtNAP7) capable of hydrolyzing ATP and interacting with the SufD homolog AtNAP6. Based on this and the prokaryotic SUF system we speculated that a SufB-like protein may exist in plastids. Here we demonstrate that the Arabidopsis plastid-localized SufB homolog AtNAP1 can complement SufB deficiency in Escherichia coli during oxidative stress. Furthermore, we demonstrate that AtNAP1 can interact with AtNAP7 inside living chloroplasts suggesting the presence of a plastidic AtNAP1.AtNAP6.AtNAP7 complex and remarkable evolutionary conservation of the SUF system. However, in contrast to prokaryotic SufB proteins with no associated ATPase activity we show that AtNAP1 is an iron-stimulated ATPase and that AtNAP1 is capable of forming homodimers. Our results suggest that AtNAP1 represents an atypical plastidic SufB-like protein important for Fe-S cluster assembly and for regulating iron homeostasis in Arabidopsis.     

毛乌素沙地优势克隆半灌木生物量配置对小尺度植被盖度变异的响应

克隆植物根据其构型可以分为游击型和密集型。游击型克隆植物的间隔子长,分株在水平空间的扩展范围大,可以利用更大空间范围内的资源,其通过克隆生理整合作用发生的非局部反应的能力强。由此可以得出的推论之一是,小生境斑块的环境发生变化,生长于其中的密集型克隆植物的反应可能会更灵敏。这种反应可能会体现在生物量以及配置格局的变化上。以毛乌素地区沙生半灌木群落中两种优势克隆植物羊柴(H edy sarum laeve)和油蒿(A rtem isia ord osica)为研究对象,前者是典型的游击型克隆植物,后者是密集型克隆植物。采取野外调查的方式,观测在不同植被盖度的小生境斑块内二者地上生物量分配格局的变化情况,并结合二者的克隆构型和生活史特征试图探讨产生这种格局的原因。结果表明:羊柴的地上各部分生物量对植被盖度变化的响应不如油蒿敏感。这或者是因为羊柴的游击型克隆构型决定其可以跨越小尺度斑块实现克隆生理整合,可以利用不同小生境斑块的资源导致的。油蒿只能利用小生境斑块内的资源,当小生境斑块的条件改变,其生物量以及配置方式也随之发生相应的变化。在繁殖方式上,羊柴的有性繁殖结构以及有性繁殖投资显著小于油蒿。在资源有限的条件下,对一种繁殖方式的投资常常会削弱另一种繁殖方式。羊柴主要依靠克隆繁殖,这或者符合并支持配置理论的观点。     

Blood substitutes based on nanobiotechnology

Stimulated by concerns of potential infective agents in donated blood, commercial enterprises have attempted to develop blood substitutes since the 1900s. After several years of development, a few of the many leads are showing promise. In this article, nanobiotechnological approaches that are now in phase III clinical trials are reviewed, followed by a discussion of how important basic knowledge gained is being used to develop new generations of blood substitutes based on nanobiotechnology.     

The rational designed antagonist derived from the complex structure of interleukin-6 and its receptor affectively blocking interleukin-6 might be a promising treatment in multiple myeloma

Human interleukin-6 is involved in the maintenance and progression of several diseases such as multiple myeloma (MM), rheumatoid arthritis, or osteoporosis. Our previous work demonstrated that an interleukin-6 antagonist peptide (named PT) possessed potential bioactivity to antagonize the function of hIL-6 and could efficiently induce the growth arrest and apoptosis of XG-7 and M1 cells in a dose-dependent manner. In this study, the theoretical interaction of the peptide PT with its receptor was analyzed further more with molecular docking and molecular dynamics methods. The theoretical studies showed that PT possessed very high affinity to interleukin-6R and offered a practical means of imposing long-term blockade of interleukin-6 activity in vivo. According to the theoretical results, the biological evaluation of PT was researched on two different cells models with more sensitive approaches: (1) The antagonist activity of PT was studied on the interleukin-6 dependent MM cells (XG-7) cultured with interleukin-6. In the other interleukin-6 dependent MM cells (SKO-007), they survived themselves by auto/paracrine without the exogenous interleukin-6, and also could be antagonized by PT. The therapeutic value of PT only limited on the interleukin-6 dependent category in MM. (2) Myeloid leukemia M1 cells were induced for growth arrest and apoptosis in response to interleukin-6. The results supported our previous findings and showed that PT could be evaluated by protecting the cells from interleukin-6 induced apoptosis. In conclusion, PT could induce interleukin-6-dependent XG-7 and SKO-007 cells to apoptosis while inhibit interleukin-6-stimulated apoptosis in M1 cells.     

PTEN regulates RPA1 and protects DNA replication forks

Tumor suppressor PTEN regulates cellular activities and controls genome stability through multiple mechanisms. In this study, we report that PTEN is necessary for the protection of DNA replication forks against replication stress. We show that deletion of PTEN leads to replication fork collapse and chromosomal instability upon fork stalling following nucleotide depletion induced by hydroxyurea. PTEN is physically associated with replication protein A 1 (RPA1) via the RPA1 C-terminal domain. STORM and iPOND reveal that PTEN is localized at replication sites and promotes RPA1 accumulation on replication forks. PTEN recruits the deubiquitinase OTUB1 to mediate RPA1 deubiquitination. RPA1 deletion confers a phenotype like that observed in PTEN knockout cells with stalling of replication forks. Expression of PTEN and RPA1 shows strong correlation in colorectal cancer. Heterozygous disruption of RPA1 promotes tumorigenesis in mice. These results demonstrate that PTEN is essential for DNA replication fork protection. We propose that RPA1 is a target of PTEN function in fork protection and that PTEN maintains genome stability through regulation of DNA replication.     

农药残留检测用植物酯酶的筛选

基于酶法分析中的酶抑制原理,通过对8种植物种子及2种植物加工材料总酯酶活力及其比活力进行比较,筛选农药残留检测用适宜的植物酯酶。结果显示,花豇豆总酯酶活力和比活力分别达7.325 U和0.617 U/mg,显著高于其它9个实验材料。用花豇豆酯酶对6种有机磷及氨基甲酸酯类农药——敌敌畏、辛硫磷、敌百虫、速灭威、克百威、灭多威进行敏感性分析,最低检测限均比国家规定的最大残留量小,符合检测要求。结果表明,花豇豆的酯酶总活力、比活力及其敏感性最好,是一种农药残留检测的理想酶源植物。