An eicosanoid-centric view of atherothrombotic risk factors

Cardiovascular disease is the foremost cause of morbidity and mortality in the Western world. Atherosclerosis followed by thrombosis (atherothrombosis) is the pathological process underlying most myocardial, cerebral, and peripheral vascular events. Atherothrombosis is a complex and heterogeneous inflammatory process that involves interactions between many cell types (including vascular smooth muscle cells, endothelial cells, macrophages, and platelets) and processes (including migration, proliferation, and activation). Despite a wealth of knowledge from many recent studies using knockout mouse and human genetic studies (GWAS and candidate approach) identifying genes and proteins directly involved in these processes, traditional cardiovascular risk factors (hyperlipidemia, hypertension, smoking, diabetes mellitus, sex, and age) remain the most useful predictor of disease. Eicosanoids (20 carbon polyunsaturated fatty acid derivatives of arachidonic acid and other essential fatty acids) are emerging as important regulators of cardiovascular disease processes. Drugs indirectly modulating these signals, including COX-1/COX-2 inhibitors, have proven to play major roles in the atherothrombotic process. However, the complexity of their roles and regulation by opposing eicosanoid signaling, have contributed to the lack of therapies directed at the eicosanoid receptors themselves. This is likely to change, as our understanding of the structure, signaling, and function of the eicosanoid receptors improves. Indeed, a major advance is emerging from the characterization of dysfunctional naturally occurring mutations of the eicosanoid receptors. In light of the proven and continuing importance of risk factors, we have elected to focus on the relationship between eicosanoids and cardiovascular risk factors.     

HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains

HAb18G/CD147 is a heavily glycosylated protein containing two immunoglobulin superfamily domains. Our previous studies have indicated that overexpression of HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca²⁺ entry by nitric oxide (NO)/cGMP. In the present study, we investigated the structure-function of HAb18G/CD147 by transfecting truncated HAb18G/CD147 fragments into human 7721 hepatoma cells. The inhibitory effect of HAb18G/CD147 on 8-bromo-cGMP-regulated thapsigargin-induced Ca²⁺ entry was reversed by the expression of either C or N terminus truncated HAb18G/CD147 in T7721C and T7721N cells, respectively. The potential effect of HAb18G/CD147 on metastatic potentials, both adhesion and invasion capacities, of hepatoma cells was abolished in T7721C cells, but not affected in T7721N cells. Release and activation of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were found to be enhanced by the expression of HAb18G/CD147, and this effect was abolished by both truncations. Thapsigargin significantly enhanced release and activation of MMPs (MMP-2 and MMP-9) in non-transfected 7721 cells, and this effect was negatively regulated by SNAP. However, no effects of thapsigargin or SNAP were observed in T7721 cells, and expression of HAb18G/CD147 enhanced secretion and activation of MMPs at a stable and high level. Taken together, these results suggest that both ectodomain and intracellular domains of HAb18G/CD147 are required to mediate the effect of HAb18G/CD147 on the secretion and activation of MMPs and metastasis-related processes in human hepatoma cells by disrupting the regulation of NO/cGMP-sensitive intracellular Ca²⁺ mobilization although each domain may play different roles.Received 1 April 2004; received after revision 15 June 2004; accepted 22 June 2004     

The NOX toolbox: validating the role of NADPH oxidases in physiology and disease

Reactive oxygen species (ROS) are cellular signals but also disease triggers; their relative excess (oxidative stress) or shortage (reductive stress) compared to reducing equivalents are potentially deleterious. This may explain why antioxidants fail to combat diseases that correlate with oxidative stress. Instead, targeting of disease-relevant enzymatic ROS sources that leaves physiological ROS signaling unaffected may be more beneficial. NADPH oxidases are the only known enzyme family with the sole function to produce ROS. Of the catalytic NADPH oxidase subunits (NOX), NOX4 is the most widely distributed isoform. We provide here a critical review of the currently available experimental tools to assess the role of NOX and especially NOX4, i.e. knock-out mice, siRNAs, antibodies, and pharmacological inhibitors. We then focus on the characterization of the small molecule NADPH oxidase inhibitor, VAS2870, in vitro and in vivo, its specificity, selectivity, and possible mechanism of action. Finally, we discuss the validation of NOX4 as a potential therapeutic target for indications including stroke, heart failure, and fibrosis.     

宣钢竖炉球团适宜膨润土配比试验研究

为了探求宣钢球团矿适宜膨润土的配比,进行了一系列的实验室研究。结果表明:膨润土配比控制在2.1%时,球团矿性能满足生产要求且经济合理。     

Morphological variability and genetic diversity in five species of Skeletonema （Bacillariophyta）

Twelve strains of Skeletonema from Chinese coastal waters and another strain from the West Sea of Korea were examined using light microscopy （LM）, scanning and transmission electron microscopy （SEM, TEM）, and small subunit （SSU） rDNA sequence analysis. We identified four species of Skeletonema： S. marinoi Sarno et Zingone, S. subsalsum （A.Cleve） Bethge, S. dohrnii Sarno et Kooistra, S. trop- icum Cleve, as well as a Skeletonerna-like species. These are the first records of S. rnarinoi, S. dohrnii and S. subsalsurn in China. The Skeletonema-like species, MMDLS067, was isolated from the estuary of the Changjiang River. The morphologic and phylogenetic characteristics of this species are not correspond to those of any previously published Skeletonerna species. The intercalary fultoportula pro- cesses （IFPPs） has long open tubes, and the intercalary rimoportula process （IRP） is short and located inside the rim of the IFPPs. Phylogenetic analysis revealed that MMDL5630 clustered with S. tropicurn in the NJ and MP trees, but its IRPs differed from those of previously described specimens of S. tropicum. The IRP is partially open, with an elongated opening at the base of the tube, and is longer than the IFPPs. Some specimens of S. marinoi and S. dohrnii also have longer tubular IRPs than the IFPPs. Compared to pre- viously described specimens of S. rnar＆oi and S. dohrnii, these two specimens we identified have shorter IRPs. Our results reflect the ambiguity and diversity of Skeletonema taxonomy. They are also significant for the future identification and management of red tides caused by Skeletonerna in the seas around China.     

一种围数为八的低密度校验码校验矩阵设计

提出了一种低密度校验（IDPC）码的规则校验矩阵设计算法．首先设计3个不同的子矩阵,每个子矩阵通过对单位矩阵进行不同的移位运算后组合生成,然后将这3个子矩阵组合生成所需要的低密度校验矩阵,最后利用文中提到的短环检验算法搜索出使得生成的校验矩阵四环数、六环数均为零的移位算子．用该校验矩阵所对应的生成矩阵对随机信息进行编码,AWGN信道下的仿真结果表明,具有逼近MacKay随机码的误码率性能．     

Genome sequencing in microfabricated high-density picolitre reactors

The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The apparatus uses a novel fibre-optic slide of individual wells and is able to sequence 25 million bases, at 99% or better accuracy, in one four-hour run. To achieve an approximately 100-fold increase in throughput over current Sanger sequencing technology, we have developed an emulsion method for DNA amplification and an instrument for sequencing by synthesis using a pyrosequencing protocol optimized for solid support and picolitre-scale volumes. Here we show the utility, throughput, accuracy and robustness of this system by shotgun sequencing and de novo assembly of the Mycoplasma genitalium genome with 96% coverage at 99.96% accuracy in one run of the machine.     

Analysis of carbon isotopes in airborne carbonate and implications for aeolian sources

Methods were developed to determine the mass ratios of carbon isotopes in trace amounts of aerosol carbonate. A Finnigan MAT 252 mass spectrometer fitted with an on-line Kiel device was to determine the ^13C/^12C ratio in CO2 produced from the carbonate. A study using these methods was conducted to characterize the carbonate carbon isotopes in aerosol samples collected in Xi‘an on dusty and normal days during March and April 2002. Results of the study demonstrate that insights into the origin of the dust can be deduced from its isotopic composition. That is, the δ^13C ofcarbonate for dust storm samples ranged from -1.4‰ to -4.2‰, and this is consistent with sandy materials in dust source regions upwind. In contrast, for non-dusty days δ^13C ranged from -7.5% to -9.3‰, which is more similar to fine particles emitted from local surface soils. Comparisons of dust storm aerosols with surface soils from source regions and with aerosol samples collected downwind indicate that the δ^13C values did not change appreciably during longrange transport. Therefore, carbon isotopes have the potential for distinguishing among source materials, and this approach provides a powerful new tool for identifying dust provenance.     

长白山区次生林恢复过程中天然更新的动态

以长白山区天然次生林为研究对象,采用空间代替时间的方法,分别对不同年度进行择代后形成的天然次生林进行群落学调查,分析择伐后28年恢复期间高度小于3m的幼苗幼树的天然更新过程及特点。结果表明,恢复初期更新幼苗幼树的树种出现比率较低,随着次生林恢复时间的增加,更新幼苗幼树的树种出现比率超过75％,且15年后变化相对较小;次生林内更新幼苗幼树的分布密度随着恢复时间的增加呈增加的趋势,恢复15年时分布密度达7500株／hm^2,此后分布密度的变化相对较小;在次生林内幼苗幼树主要是集中分布在距最近立木1．5～3．5m的范围内,随着次生林恢复时间的增加,幼树的分布范围相对靠近立木,幼苗的分布范围则相对远离立木。