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.     

Putting CENP-A in its place

The centromere is the chromosomal region that directs kinetochore assembly during mitosis in order to facilitate the faithful segregation of sister chromatids. The location of the human centromere is epigenetically specified. The presence of nucleosomes that contain the histone H3 variant, CENP-A, are thought to be the epigenetic mark that indicates active centromeres. Maintenance of centromeric identity requires the deposition of new CENP-A nucleosomes with each cell cycle. During S-phase, existing CENP-A nucleosomes are divided among the daughter chromosomes, while new CENP-A nucleosomes are deposited during early G1. The specific assembly of CENP-A nucleosomes at centromeres requires the Mis18 complex, which recruits the CENP-A assembly factor, HJURP. We will review the unique features of centromeric chromatin as well as the mechanism of CENP-A nucleosome deposition. We will also highlight a few recent discoveries that begin to elucidate the factors that temporally and spatially control CENP-A deposition.     

Knowledge transfer and its contexts

Knowledge transfer across different contexts has become an increasingly prevalent feature of current science. As such, it is a relevant topic also for historians and philosophers of science. This special issue presents a set of papers that study knowledge transfer in various disciplines. The contributions approach the topic from 1) an integrated history and philosophy of science perspective, 2) a systematic philosophical perspective, or 3) a historical perspective. Taken together, they give a broad introduction into the topic and offer a set of conceptual resources for the study of knowledge transfer in multiple contexts.     

Mycobacterial adjuvant and its carrier

Résumé Une fraction peptidoglycolipidique peut être extraite à partir du BCG par décapage acide dans un mélange de solvants fortement lipophiles. Cette fraction appelée ?LF? peut reproduire l'activité adjuvante du BCG entier dans les réactions immunitaires à médiation cellulaire et humorale. L'activité adjuvante du BCG appara?t comme liée à ce composant actif, LF, car après son extraction, le résidu bacillaire (BB) est dépourvu d'activité adjuvante. Néanmoins lorsque BB est utilisé pour adsorber (?véhiculer?) LF, le complexe BB-LF s'est révélé le meilleur adjuvant.

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This work was performed at the Laboratory of Experimental Hematology, Department of Zoology, the University of Nebraska-Lincoln, Lincoln, Nebraska 68508, USA.     

量子关联及其应用

量子关联是量子系统具有的一种重要的非经典性质,被普遍研究的量子纠缠就是量子信息处理中重要的量子关联.随着研究的深入,最近发现了很多不需要纠缠的非经典现象在量子信息中扮演了关键角色.文章介绍了基于量子失协及其相关的非经典量子关联,讨论了各种量子关联在量子信息模型中各种物理解释与应用.     

The apicomplexan plastid and its evolution

Protistan species belonging to the phylum Apicomplexa have a non-photosynthetic secondary plastid—the apicoplast. Although its tiny genome and even the entire nuclear genome has been sequenced for several organisms bearing the organelle, the reason for its existence remains largely obscure. Some of the functions of the apicoplast, including housekeeping ones, are significantly different from those of other plastids, possibly due to the organelle’s unique symbiotic origin.     

Synthesis of Seselin and its hydroderivatives

Zusammenfassung Die Synthese des Naturstoffes Tetrahydroseselin aus der FruchtSeseli indicum wird beschrieben.

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Part X of a seriesCoumarins and Related Compounds. Part IX, A. K.Das Gupta, R. M.Chatterje and K. R.Das, J. chem. Soc. (C), (1969), 2618.     

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.     

Cholesteryl ester transfer protein and its inhibition

Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that facilitates the transfer of cholesteryl esters from the atheroprotective high density lipoprotein (HDL) to the proatherogenic low density lipoprotein cholesterol (LDL) and very low density lipoprotein cholesterol (VLDL) leading to lower levels of HDL but raising the levels of proatherogenic LDL and VLDL. Inhibition of CETP is considered a potential approach to treat dyslipidemia. However, discussions regarding the role of CETP-mediated lipid transfer in the development of atherosclerosis and CETP inhibition as a potential strategy for prevention of atherosclerosis have been controversial. Although many animal studies support the hypothesis that inhibition of CETP activity may be beneficial, negative phase III studies on clinical endpoints with the CETP inhibitor torcetrapib challenged the future perspectives of CETP inhibitors as potential therapeutic agents. The review provides an update on current understanding of the molecular mechanisms involved in CETP activity and its inhibition.     

Endothelial injury by nicotine and its prevention

Summary Nicotine administered i.v. or p.o. in doses above 0.0125 mg/kg to the rat caused a highly significant increase in circulating anuclear carcasses of endothelial cells estimated by an original method. This effect of nicotine was completely prevented by a prior oral administration of the flavonoids hydroxyethylrutosides (HR) or Mono-7-HR.Acknowledgment. Both flavonoid preparations were kindly supplied by Zyma SA, Nyon Switzerland.     

Square ZnO nano-column and its thermal evolution

Square ZnO nano-columns have been manufactured by molecular beam epitaxy on p-type Si (100) substrate. The morphology and the evolution sequences after thermal annealing were investigated by in-situ scanning tunneling microscopy. We associated the morphology and microstructure evolution with the cubic Si (100) substrate, large lattice mismatching, the coexistence of wurtzite and zincblende phases of ZnO, and the thermal effect.     

Molecular recognition in antibodies and its application

The structure and function of immunoglobulins, and the nature of the antibody — antigen interaction are described. Applications of the molecular recognition properties of antibodies are discussed in the areas of immunotherapy, immunoassay, immunotargeting and catalytic antibodies.     

Aptamer and its applications in neurodegenerative diseases

Aptamers are small single-stranded DNA or RNA oligonucleotide fragments or small peptides, which can bind to targets by high affinity and specificity. Because aptamers are specific, non-immunogenic and non-toxic, they are ideal materials for clinical applications. Neurodegenerative disorders are ravaging the lives of patients. Even though the mechanism of these diseases is still elusive, they are mainly characterized by the accumulation of misfolded proteins in the central nervous system. So it is essential to develop potential measures to slow down or prevent the onset of these diseases. With the advancements of the technologies, aptamers have opened up new areas in this research field. Aptamers could bind with these related target proteins to interrupt their accumulation, subsequently blocking or preventing the process of neurodegenerative diseases. This review presents recent advances in the aptamer generation and its merits and limitations, with emphasis on its applications in neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, transmissible spongiform encephalopathy, Huntington’s disease and multiple sclerosis.     

Matriptase and its putative role in cancer

Tumor progression and metastasis are the pathologic effects of uncontrolled or deregulated invasive growth, a process in which proteases play a fundamental role. They mediate the degradation of extracellular matrix components and intercellular cohesive structures to allow migration of the cells into the extracellular environment and activate growth and angiogenic factors. In addition to metalloproteases and the plasminogen activation system, another protease, matriptase, contributes substantially to these processes. Matriptase is a type II transmembrane trypsin-like serine protease that is expressed by cells of epithelial origin and is overexpressed in a variety of human cancers. It has been suggested that this protease not only facilitates cellular invasiveness but may also activate oncogenic pathways. This review summarizes current knowledge about matriptase, its putative role in tumor initiation and progression, and its potential as a novel target in anti-cancer therapy. Received 29 June 2006; received after revision 1 August 2006; accepted 19 September 2006