Effects of sodium, potassium and chloride ions on the membrane potential of Valonia aegagropila

Changes of the resting potential of Valonia cell in sea wateragainst a 10-fold increase of the external concentrations ofK^$, Na^$ and Cl^– were 1±1, 6.2±0.1 and 38.9±4mV, respectively. The potassium conductance was smaller than7 µ/cm², while the Na and Cl conductances were 45 and281 µ/cm², respectively, in normal sea water. The positivevacuolar potential could be explained by these ionic conductances.On the other hand, the membrane became more sensitive to K^$,if the cell was incubated for about 30 min in K-rich (100 mM)sea water. It is worth noting, however, that the membrane conductancewas lower in the K-rich sea water than in the normal sea water. (Received October 7, 1974; )     

Neural induction: Historical views and application to pluripotent stem cells

Embryonic stem (ES) cells are a useful experimental material to recapitulate the differentiation steps of early embryos, which are usually invisible and inaccessible from outside of the body, especially in mammals. ES cells have greatly facilitated the analyses of gene expression profiles and cell characteristics. In addition, understanding the mechanisms during neural differentiation is important for clinical purposes, such as developing new therapeutic methods or regenerative medicine. As neurons have very limited regenerative ability, neurodegenerative diseases are usually intractable, and patients suffer from the disease throughout their lifetimes. The functional cells generated from ES cells in vitro could replace degenerative areas by transplantation. In this review, we will first demonstrate the historical views and widely accepted concepts regarding the molecular mechanisms of neural induction and positional information to produce the specific types of neurons in model animals. Next, we will describe how these concepts have recently been applied to the research in the establishment of the methodology of neural differentiation from mammalian ES cells. Finally, we will focus on examples of the applications of differentiation systems to clinical purposes. Overall, the discussion will focus on how historical developmental studies are applied to state‐of‐the‐art stem cell research.     

Nucleosides and Nucleotides. 140. Synthesis and Antileukemic Activity of 5-Carbon-Substituted 1-β-d-Ribofuflranosylimidazole-4-Carboxamides

Abstract

Synthesis of 5-carbon-substituted 1-β-d-ribofuranosylimidazole-4-carboxamides are described. Treatment of 5-iodo derivative 8 with methyl acrylate in the presence of palladium catalyst gave (E)-5-(2-carbomethoxyvinyl)-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide (9), followed by appropriate manipulations to afford various 5-carbon-substituted imidazole derivatives 1–7. The antileukemic activities of these imidazole nucleosides are also described.

     

Crystal structure of pantoate kinase from Thermococcus kodakarensis

The coenzyme A biosynthesis pathways in most archaea involve two unique enzymes, pantoate kinase and phosphopantothenate synthetase, to convert pantoate to 4′-phosphopantothenate. Here, we report the first crystal structure of pantoate kinase from the hyperthermophilic archaeon, Thermococcus kodakarensis and its complex with ATP and a magnesium ion. The electron density for the adenosine moiety of ATP was very weak, which most likely relates to its broad nucleotide specificity. Based on the structure of the active site that contains a glycerol molecule, the pantoate binding site and the roles of the highly conserved residues are suggested.     

Single Quantum Dot Tracking Reveals that an Individual Multivalent HIV-1 Tat Protein Transduction Domain Can Activate Machinery for Lateral Transport and Endocytosis

The mechanisms underlying the cellular entry of the HIV-1 Tat protein transduction domain (TatP) and the molecular information necessary to improve the transduction efficiency of TatP remain unclear due to the technical limitations for direct visualization of TatP''s behavior in cells. Using confocal microscopy, total internal reflection fluorescence microscopy, and four-dimensional microscopy, we developed a single-molecule tracking assay for TatP labeled with quantum dots (QDs) to examine the kinetics of TatP initially and immediately before, at the beginning of, and immediately after entry into living cells. We report that even when the number of multivalent TatP (mTatP)-QDs bound to a cell was low, each single mTatP-QD first locally induced the cell''s lateral transport machinery to move the mTatP-QD toward the center of the cell body upon cross-linking of heparan sulfate proteoglycans. The centripetal and lateral movements were linked to the integrity and flow of actomyosin and microtubules. Individual mTatP underwent lipid raft-mediated temporal confinement, followed by complete immobilization, which ultimately led to endocytotic internalization. However, bivalent TatP did not sufficiently promote either cell surface movement or internalization. Together, these findings provide clues regarding the mechanisms of TatP cell entry and indicate that increasing the valence of TatP on nanoparticles allows them to behave as cargo delivery nanomachines.