Aurora A kinase (AURKA) in normal and pathological cell division

Temporally and spatially controlled activation of the Aurora A kinase (AURKA) regulates centrosome maturation, entry into mitosis, formation and function of the bipolar spindle, and cytokinesis. Genetic amplification and mRNA and protein overexpression of Aurora A are common in many types of solid tumor, and associated with aneuploidy, supernumerary centrosomes, defective mitotic spindles, and resistance to apoptosis. These properties have led Aurora A to be considered a high-value target for development of cancer therapeutics, with multiple agents currently in early-phase clinical trials. More recently, identification of additional, non-mitotic functions and means of activation of Aurora A during interphase neurite elongation and ciliary resorption have significantly expanded our understanding of its function, and may offer insights into the clinical performance of Aurora A inhibitors. Here we review the mitotic and non-mitotic functions of Aurora A, discuss Aurora A regulation in the context of protein structural information, and evaluate progress in understanding and inhibiting Aurora A in cancer.     

Determination of trace elements in peripheral lymphocytes from tumor-bearing rats.

Neutron activation analysis of peripheral lymphocytes from healthy and Walker 256 carcinosarcoma-bearing rats resulted in the quantitative determination of Co, Cu, K, Mn, Rb, Se and Zn, and a qualitative determination of Au and Sb. From corresponding plasma samples, Co, Zn, Rb, Se and Cs were analyzed. Differences in trace element concentrations could only be detected in plasma of tumor-bearing animals which showed a decreased Zn and Co content of 50% and 30%, respectively, and a rise of Rb when compared to plasma of control animals.     

功能树枝聚合物的应用

树枝聚合物是一类新型聚合物材料。树枝聚合物由芯、支化单元和表面组成，包含大量的空穴，具有高支化的3维结构和纳米尺寸以及独特的电、光、热、力学和流变性能。通过对树枝聚合物结构的功能化设计即在树枝聚合物的芯、支化单元和表面引入确定功能的基团，可使之具有催化、分子识别、能量和电子转移、氧化还原、吸热或放热受体等功能，具有可控制的溶液、热等性能和液晶态，并能广泛应用于电活性和电致发光器件，光化学分子器件(能量和电子转移，非线性光学)，太阳能电池，化学传感器，液晶显示，催化剂，超薄膜(层)，胶束与胶囊，生物医用和药用，分析和分离等领域。     

Into the ‘regions of physical and metaphysical chaos’: Maxwell’s scientific metaphysics and natural philosophy of action (agency,determinacy and necessity from theology,moral philosophy and history to mathematics,theory and experiment)

Maxwell’s writings exhibit an enduring preoccupation with the role of metaphysics in the advancement of science, especially the progress of physics. I examine the question of the distinction and the proper relation between physics and metaphysics and the way in which the question relies on key notions that bring together much of Maxwell’s natural philosophy, theoretical and experimental. Previous discussions of his attention to metaphysics have been confined to specific issues and polemics such as conceptions of matter and the problem of free will. I suggest a unifying pattern based on a generalized philosophical perspective and varying expressions, although never a systematic or articulated philosophical doctrine, but at least a theme of action and active powers, natural and human, intellectual and material, with sources and grounds in theology, moral philosophy and historical argument. While science was developing in the direction of professional specialization and alongside the rise of materialism, Maxwell held on to conservative intellectual outlook, but one that included a rich scientific life and held science as part of a rich intellectual, cultural and material life. His philosophical outlook integrated his science with and captured the new Victorian culture of construction and work, political, economic, artistic and engineering.     

信息几何理论与应用研究进展

信息几何是在Riemann流形上采用现代微分几何方法来研究统计学问题的基础性、前沿性学科,被誉为是继Shannon开辟现代信息理论之后的又一新的理论变革,在信息科学与系统理论研究领域展现出了巨大的发展潜力．本文首先从参数化概率分布族的内蕴几何结构特征与信息的几何性质出发,精炼了信息几何的科学内涵,指出信息几何相比于经典统计学与信息论的理论优势与方法的革新．然后简要阐述了信息几何与微分几何的联系,综述了信息几何理论的发展历史与近20年来信息几何在神经网络、统计推断、通信编码、系统理论、物理学和医学成像等各领域应用的研究现状,归纳和总结了其中所体现的信息几何的基本原理和基本方法,并对信息几何的发展给予注记．特别地,对信息几何在信号处理领域中的应用成果进行了较全面的总结和概括,阐述了信息几何在信号检测、参数估计与滤波等方面的最新研究成果．最后,展望信息几何的发展前景,提出了信息几何在信号处理领域中的若干开放性问题．     

History of science and its utopian reconstructions

In recent years explicitly utopian visions have reappeared across the political spectrum. To a surprising degree these visions have drawn on histories and science and technology. What should scholars of Science and Technology Studies (STS) and History and Philosophy of Science (HPS) make of these developments? The concept of utopia has often been treated with considerable distrust in these fields, as an indication of closed end-directed blueprints, or as an indication of fantasies of limitless technological improvement and purification of categories. Alongside this uneasiness, however, HPS and STS scholars have also projected transformative ambitions, seeking to recover from the past different ways of knowing and relating to the human and non-human world. By engaging with critiques of utopia from thinkers including Karl Popper, Otto Neurath, Bruno Latour, Isabelle Stengers and Donna Haraway, and exploring some of the utopian strands which have recurred in studies of science and technology—including the longing for integration, the association of science with planning, and the ways in which feminist scholars have envisaged alternative forms of science—we can understand the ongoing, and often unrecognised, utopian dimensions of HPS and STS.     

Structure of the gap junction channel and its implications for its biological functions

Gap junctions consist of arrays of intercellular channels composed of integral membrane proteins called connexin in vertebrates. Gap junction channels regulate the passage of ions and biological molecules between adjacent cells and, therefore, are critically important in many biological activities, including development, differentiation, neural activity, and immune response. Mutations in connexin genes are associated with several human diseases, such as neurodegenerative disease, skin disease, deafness, and developmental abnormalities. The activity of gap junction channels is regulated by the membrane voltage, intracellular microenvironment, interaction with other proteins, and phosphorylation. Each connexin channel has its own property for conductance and molecular permeability. A number of studies have tried to reveal the molecular architecture of the channel pore that should confer the connexin-specific permeability/selectivity properties and molecular basis for the gating and regulation. In this review, we give an overview of structural studies and describe the structural and functional relationship of gap junction channels.     

Effects of CO2 exposure on distribution of various forms of iron and copper in guinea-pig tissues

The effects on iron and copper distribution and metabolism of exposure to high levels of CO2 were studied in the guinea-pig. Mature, male animals were placed in an atmosphere of 15% CO2, 21% O2 (balance N2), and sacrificed from 1 h to 1 week thereafter. Total iron and copper concentrations of blood, liver, spleen and bone, as well as concentrations of heme and ferritin iron, were measured together with blood hematocrit, reticulocytes, plasma hemoglobin, plasma ceruloplasmin and copper concentrations. The results show clearly that rapid and sustained red cell damage or hemolysis ensued several h from the start of CO2 treatment. This resulted in loss of iron and copper from the blood, an influx of both elements into liver, spleen and bone, and a rise in plasma ceruloplasmin. Influx of iron into liver and spleen caused an accumulation of ferritin, the main site for iron storage in cells. Following the effect on red cells, there was an accumulation of heme iron, and a decreased hematocrit, best explained by a depressed activity of the reticuloendothelial and erythropoietic systems. A period of adaptation succeeded these events, in which all blood parameters and most tissue values returned to normal, despite the continuing presence of high CO2. The only changes not reversed were the elevations in liver, spleen and bone iron stores. These remained high, with a net accumulation of greater than 2 mg iron, or 3-4 times more than originally present. The results indicate that at least in the guinea-pig, high CO2 exposure results in red cell damage and other events leading to an accumulation of additional iron in the body; also, that iron accumulated as ferritin and hemosiderin in liver and spleen may not be readily available to restore blood hemoglobin concentrations on an acute basis.     

复杂软件系统的成长性构造与适应性演化

随着信息网络技术的渗透性发展,复杂软件系统正在成为一种泛在的新型软件形态.此类软件系统通常由相当数量的局部自治的软件系统相互耦合关联而成,具有"系统之系统"、"信息—物理"融合系统和"社会—技术"交融系统的特点,表现出成员异质、边界开放、行为涌现、持续演化等一系列新的性质.这些特征打破了传统基于"还原论"思想的软件工程理论和技术所基于的基本假设,使其难以适用于复杂软件系统的构建.本文分析复杂软件系统的内涵、形成特征和基本性质,深入讨论复杂软件系统在构造和演化环节所面临的挑战,借鉴互联网以及生命系统、社会系统和经济系统等复杂系统的形成和演进模式,提出复杂软件系统的"成长性构造"和"适应性演化"法则,阐述这两条法则所涉及的主要科学问题和关键支撑技术.本文试图为复杂软件系统的构建和发展提供新的方法学和架构层面的支持.     

药用植物羌活现状及其民族植物学调查

羌活为重要的传统中药和藏药常用药材，大量的汉藏药方和成药均作为重要的配伍药材加以使用。羌活传统产区主要是藏族、羌族和其它少数民族的聚居的高寒山区，经济较为落后，交通不便。由于难以驯化栽培，药材来源主要依赖野生资源采挖，但由于受到种子发育不完全、后熟期长等本身繁殖特性的限制，羌活繁殖和种群恢复主要是通过无性繁殖实现，野生资源恢复受到严重制约。道地产区的调查发现，羌活野生生境正受到前所未有的破坏，包括生境丧失、破碎化、土壤退化、土地利用模式改变和环境变化等；调查还发现近年来羌活药材价格与采挖量之间的关系，以及当地民族植物学方面的状况。羌活野生资源的破坏受到利益驱使、致使采挖时间和方式等利用模式发生改变，极不利于羌活野生资源的保存和种群恢复，若不规范羌活野生资源的利用和引种驯化，进行人工栽培，羌活野生资源不但难以实现可持续利用，而且还将遭到毁灭性破坏，并有灭绝的危险。本文最后提出了药用羌活属植物的保护性开发和可持续利用可能途径。     

Bioinformatics and molecular modeling in glycobiology

The field of glycobiology is concerned with the study of the structure, properties, and biological functions of the family of biomolecules called carbohydrates. Bioinformatics for glycobiology is a particularly challenging field, because carbohydrates exhibit a high structural diversity and their chains are often branched. Significant improvements in experimental analytical methods over recent years have led to a tremendous increase in the amount of carbohydrate structure data generated. Consequently, the availability of databases and tools to store, retrieve and analyze these data in an efficient way is of fundamental importance to progress in glycobiology. In this review, the various graphical representations and sequence formats of carbohydrates are introduced, and an overview of newly developed databases, the latest developments in sequence alignment and data mining, and tools to support experimental glycan analysis are presented. Finally, the field of structural glycoinformatics and molecular modeling of carbohydrates, glycoproteins, and protein–carbohydrate interaction are reviewed.     

Microbial dissolution and stabilization of toxic metals and radionuclides in mixed wastes

Summary Microbial activity in mixed wastes can have an appreciable effect on the dissolution or precipitation of toxic metals and radionuclides. Fundamental information on microbial dissolution and stabilization (immobilization) of toxic metals and radionuclides, in particular actinides and fission products, in nuclear wastes under various microbial process conditions, e.g., aerobic, denitrifying, iron-reducing, fermentative, sulfate-reducing, and methanogenic conditions is very limited. Microbial transformations of typical waste components such as metal oxides, metal coprecipitates, naturally occurring minerals, and metal organic complexes are reviewed. Such information can be useful in the development of 1) predictive models on the fate and long-term transport of toxic metals and radionuclides from waste disposal sites, and 2) biotechnological applications of waste treatment leading to volume reduction and stabilization as wall as recovery and recycling of radionuclides and toxic metals.     

The emerging roles for the chromatin structure regulators CTCF and cohesin in neurodevelopment and behavior

Recent genetic and technological advances have determined a role for chromatin structure in neurodevelopment. In particular, compounding evidence has established roles for CTCF and cohesin, two elements that are central in the establishment of chromatin structure, in proper neurodevelopment and in regulation of behavior. Genetic aberrations in CTCF, and in subunits of the cohesin complex, have been associated with neurodevelopmental disorders in human genetic studies, and subsequent animal studies have established definitive, although sometime opposing roles, for these factors in neurodevelopment and behavior. Considering the centrality of these factors in cellular processes in general, the mechanisms through which dysregulation of CTCF and cohesin leads specifically to neurological phenotypes is intriguing, although poorly understood. The connection between CTCF, cohesin, chromatin structure, and behavior is likely to be one of the next frontiers in our understanding of the development of behavior in general, and neurodevelopmental disorders in particular.     

新西兰政府科技投资现状概述

近年来新西兰政府大力调整其科技政策，在建设知识社会的蓝图下，建构了科技投资的基本框架，凸显了知识、经济、环境、社会四大目标，另外通过对投资决策、运行和监督的改革，使政府科技投资的机制更为科学有效，本文还给出了新西兰政府近年来科技投资的分配比例状况，阐明了其投资的重点领域。     

The metabolism and function of sphingolipids and glycosphingolipids

Sphingolipids and glycosphingolipids are emerging as major players in many facets of cell physiology and pathophysiology. We now present an overview of sphingolipid biochemistry and physiology, followed by a brief presentation of recent advances in translational research related to sphingolipids. In discussing sphingolipid biochemistry, we focus on the structure of sphingolipids, and their biosynthetic pathways – the recent identification of most of the enzymes in this pathway has led to significant advances and better characterization of a number of the biosynthetic steps, and the relationship between them. We then discuss some roles of sphingolipids in cell physiology, particularly those of ceramide and sphingosine-1-phosphate, and mention current views about how these lipids act in signal transduction pathways. We end with a discussion of sphingolipids and glycosphingolipids in the etiology and pathology of a number of diseases, such as cancer, immunity, cystic fibrosis, emphysema, diabetes, and sepsis, areas in which sphingolipids are beginning to take a central position, even though many of the details remain to be elucidated. Received 13 February 2007; received after revision 19 April 2007; accepted 26 April 2007     

PTEN proteoforms in biology and disease

Proteoforms are specific molecular forms of protein products arising from a single gene that possess different structures and different functions. Therefore, a single gene can produce a large repertoire of proteoforms by means of allelic variations (mutations, indels, SNPs), alternative splicing and other pre-translational mechanisms, post-translational modifications (PTMs), conformational dynamics, and functioning. Resulting proteoforms that have different sizes, alternative splicing patterns, sets of post-translational modifications, protein–protein interactions, and protein–ligand interactions, might dramatically increase the functionality of the encoded protein. Herein, we have interrogated the tumor suppressor PTEN for its proteoforms and find that this protein exists in multiple forms with distinct functions and sub-cellular localizations. Furthermore, the levels of each PTEN proteoform in a given cell may affect its biological function. Indeed, the paradigm of the continuum model of tumor suppression by PTEN can be better explained by the presence of a continuum of PTEN proteoforms, diversity, and levels of which are associated with pathological outcomes than simply by the different roles of mutations in the PTEN gene. Consequently, understanding the mechanisms underlying the dysregulation of PTEN proteoforms by several genomic and non-genomic mechanisms in cancer and other diseases is imperative. We have identified different PTEN proteoforms, which control various aspects of cellular function and grouped them into three categories of intrinsic, function-induced, and inducible proteoforms. A special emphasis is given to the inducible PTEN proteoforms that are produced due to alternative translational initiation. The novel finding that PTEN forms dimers with biological implications supports the notion that PTEN proteoform–proteoform interactions may play hitherto unknown roles in cellular homeostasis and in pathogenic settings, including cancer. These PTEN proteoforms with unique properties and functionalities offer potential novel therapeutic opportunities in the treatment of various cancers and other diseases.     

Pursuing frequency standards and control: the invention of quartz clock technologies

The quartz clock, the first to replace the pendulum as the time standard and later a ubiquitous and highly influential technology, originated in research on means for determining frequency for the needs of telecommunication and the interests of its users. This article shows that a few groups in the US, Britain, Italy and the Netherlands developed technologies that enabled the construction of the new clock in 1927–28. To coordinate complex and large communication networks, the monopolistic American Telephone and Telegraph Company, and national laboratories needed to determine and maintain a common ‘standard’ frequency measurement unit. Exploiting novel piezoelectric quartz methods and valve electronics techniques, researchers in these organizations constructed a new crystal-based frequency standard. To ensure its accuracy they compared it to an accepted absolute standard - an astronomical clock, constructing thereby the first quartz clock. Other groups, however, had different, though connected, technological aims, which originated from the diverse interests of the industrial, governmental and academic institutes to which they belonged, and for which they needed to measure, control and manipulate with frequencies of electric oscillations. The present article suggests a comparative examination of the research and development paths of these groups on their incentives, the technological and scientific resources they utilized, and the kind of research carried out in the various institutional settings.     

Melatonin,clock genes and mitochondria in sepsis

After the characterization of the central pacemaker in the suprachiasmatic nucleus, the expression of clock genes was identified in several peripheral tissues including the immune system. The hierarchical control from the central clock to peripheral clocks extends to other functions including endocrine, metabolic, immune, and mitochondrial responses. Increasing evidence links the disruption of the clock genes expression with multiple diseases and aging. Chronodisruption is associated with alterations of the immune system, immunosenescence, impairment of energy metabolism, and reduction of pineal and extrapineal melatonin production. Regarding sepsis, a condition coursing with an exaggerated response of innate immunity, experimental and clinical data showed an alteration of circadian rhythms that reflects the loss of the normal oscillation of the clock. Moreover, recent data point to that some mediators of the immune system affects the normal function of the clock. Under specific conditions, this control disappears reactivating the immune response. So, it seems that clock gene disruption favors the innate immune response, which in turn induces the expression of proinflammatory mediators, causing a further alteration of the clock. Here, the clock control of the mitochondrial function turns off, leading to a bioenergetic decay and formation of reactive oxygen species that, in turn, activate the inflammasome. This arm of the innate immunity is responsible for the huge increase of interleukin-1β and entrance into a vicious cycle that could lead to the death of the patient. The broken clock is recovered by melatonin administration, that is accompanied by the normalization of the innate immunity and mitochondrial homeostasis. Thus, this review emphasizes the connection between clock genes, innate immunity and mitochondria in health and sepsis, and the role of melatonin to maintain clock homeostasis.