Adoptive transfer of EAE-like lesions from rats with coronavirus-induced demyelinating encephalomyelitis

Viruses have been found to induce inflammatory demyelinating lesions in central nervous system (CNS) tissue of both animal and man, either by natural infections or after vaccination. At least two different pathogenic mechanisms have been proposed for these changes, a cytopathic viral infection of oligodendroglia cells with subsequent cell death, and a host immune reaction against virus and brain antigens. We now report the occurrence of cell-mediated immune reactions against basic myelin proteins in the course of coronavirus infections in Lewis rats. Infection of rats with the murine coronavirus JHM leads to demyelinating encephalomyelitis developing several weeks to months postinfection. Lymphocytes from these diseased Lewis rats can be restimulated with basic myelin protein (BMP) and adoptive transfer of these cells leads to lesions resembling those of experimental allergic encephalomyelitis (EAE) in recipients, which can be accompanied by a mild clinical disease. This model demonstrates that a virus infection in CNS tissue is capable of initiating an autoimmune response which may be of pathogenic importance.     

5-HT hyperpolarization of bullforg sympathetic ganglion cell membrane

Zusammenfassung Die Membran der sympathischen Ganglienzelle des Ochsenfrosches (Rana catesbiana) wird durch 5-HT depolarisiert; 5-HT erzeugt jedoch in Gegenwart von Nicotin eine Hyperpolarisation. Es scheint, dass sowohl die Depolarisation als auch die Hyperpolarisation von 5-HT durch direkte Wirkung auf die Zell-Membran zustande kommt. Die durch 5-HT erzeugte Hyperpolarisation zeigte ähnliche Eigenschaften wie des «slow IPSP» welches jedoch während der Entwicklung der 5-HT Hyperpolarisation stark zunimmt. Es wird vermutet, dass 5-HT wahrscheinlich nicht als Überträgerstoff für das «slow IPSP» in Frage kommt.     

Collagen synthesis of cultured fibroblast from Werner's syndromes of premature aging

Summary The difference of collagen producibility between 2 groups of skin fibroblasts from patients with Werner's syndrome with skin change and with normal skin, and the difference of collagen accumulation to cell layer between skin fibroblast from Werner's syndrome and controls were studied.Acknowledgments. We are grateful to Dr M. Ohkido and Dr I. Matsuo of the Department of Dermatology of Tokai University for their supply of materials and generous advice and Mr K. Takeichi of the Department of Pathology of Tokai University for his technical assistance.     

Drosophila RNAi screen identifies host genes important for influenza virus replication

All viruses rely on host cell proteins and their associated mechanisms to complete the viral life cycle. Identifying the host molecules that participate in each step of virus replication could provide valuable new targets for antiviral therapy, but this goal may take several decades to achieve with conventional forward genetic screening methods and mammalian cell cultures. Here we describe a novel genome-wide RNA interference (RNAi) screen in Drosophila that can be used to identify host genes important for influenza virus replication. After modifying influenza virus to allow infection of Drosophila cells and detection of influenza virus gene expression, we tested an RNAi library against 13,071 genes (90% of the Drosophila genome), identifying over 100 for which suppression in Drosophila cells significantly inhibited or stimulated reporter gene (Renilla luciferase) expression from an influenza-virus-derived vector. The relevance of these findings to influenza virus infection of mammalian cells is illustrated for a subset of the Drosophila genes identified; that is, for three implicated Drosophila genes, the corresponding human homologues ATP6V0D1, COX6A1 and NXF1 are shown to have key functions in the replication of H5N1 and H1N1 influenza A viruses, but not vesicular stomatitis virus or vaccinia virus, in human HEK 293 cells. Thus, we have demonstrated the feasibility of using genome-wide RNAi screens in Drosophila to identify previously unrecognized host proteins that are required for influenza virus replication. This could accelerate the development of new classes of antiviral drugs for chemoprophylaxis and treatment, which are urgently needed given the obstacles to rapid development of an effective vaccine against pandemic influenza and the probable emergence of strains resistant to available drugs.     

Chenguodaite （Ag9FeTe2S4）： a new tellurosulfide mineral from the gold district of East Shandong Peninsula,China

Chenguodaite, approved by IMA-CNMMN （2004-042a）, was discovered in the Bunan quartz vein-type gold deposit in the gold district of East Shandong Peninsula. The mineral occurs in high grade Au-Ag-Cu ores, coexisting with galena, chalcopyrite, hessite, electrum, unnamed Ag6TeS2 and AglsFeBiTe3Se, enclosed and replaced by native silver and acanthite. In the reflected light microscope, the mineral has light gray color, indistinguishable anistropism and hardness around 2-3. The color indices of chenguodaite relative to ICE C illuminator are： x=0.3027, y=0.3076, Y=25.78%,λd=474 nm, Pe=3.68%, similar to those of canfieldite. The average chemical composition from 16 microprobe analyses is Ag8.97Fe1.00Te1.99S4.04, idealized to AggFeTe2S4. The polycrystalline X-ray diffraction of chenguodaite by Gandolfi camera and synchrotron oscillation photography results in 67 reflections with the 12 strongest being （relative intensity in bracket）： 6.742（69）, 6.416（39）, 5.951（33）, 3.265（100）, 2.981（24）, 2.649（22）, 2.25（24）, 2.188（71）, 2.142（22）, 2.123（31）, 2.044（23）, 1.949（33）, which are indexed to a primitive orthorhombic cell with a=12.769 （2） A, b= 14.814（2） A, c= 16.233 （1） A, V= 3070.6 A^3, Z= 9, Dcal.=6.85 g/cm^3. The name is for the late Prof. Chen Guoda, a famous Chinese geologist and the founder of Diwa-Geodepression theory of tectonics.     

Northern Hemisphere forcing of climatic cycles in Antarctica over the past 360,000 years

The Milankovitch theory of climate change proposes that glacial-interglacial cycles are driven by changes in summer insolation at high northern latitudes. The timing of climate change in the Southern Hemisphere at glacial-interglacial transitions (which are known as terminations) relative to variations in summer insolation in the Northern Hemisphere is an important test of this hypothesis. So far, it has only been possible to apply this test to the most recent termination, because the dating uncertainty associated with older terminations is too large to allow phase relationships to be determined. Here we present a new chronology of Antarctic climate change over the past 360,000 years that is based on the ratio of oxygen to nitrogen molecules in air trapped in the Dome Fuji and Vostok ice cores. This ratio is a proxy for local summer insolation, and thus allows the chronology to be constructed by orbital tuning without the need to assume a lag between a climate record and an orbital parameter. The accuracy of the chronology allows us to examine the phase relationships between climate records from the ice cores and changes in insolation. Our results indicate that orbital-scale Antarctic climate change lags Northern Hemisphere insolation by a few millennia, and that the increases in Antarctic temperature and atmospheric carbon dioxide concentration during the last four terminations occurred within the rising phase of Northern Hemisphere summer insolation. These results support the Milankovitch theory that Northern Hemisphere summer insolation triggered the last four deglaciations.     

Protein-based peptide-bond formation by aminoacyl-tRNA protein transferase

Eubacterial leucyl/phenylalanyl-tRNA protein transferase (LF-transferase) catalyses peptide-bond formation by using Leu-tRNA(Leu) (or Phe-tRNA(Phe)) and an amino-terminal Arg (or Lys) of a protein, as donor and acceptor substrates, respectively. However, the catalytic mechanism of peptide-bond formation by LF-transferase remained obscure. Here we determine the structures of complexes of LF-transferase and phenylalanyl adenosine, with and without a short peptide bearing an N-terminal Arg. Combining the two separate structures into one structure as well as mutation studies reveal the mechanism for peptide-bond formation by LF-transferase. The electron relay from Asp 186 to Gln 188 helps Gln 188 to attract a proton from the alpha-amino group of the N-terminal Arg of the acceptor peptide. This generates the attacking nucleophile for the carbonyl carbon of the aminoacyl bond of the aminoacyl-tRNA, thus facilitating peptide-bond formation. The protein-based mechanism for peptide-bond formation by LF-transferase is similar to the reverse reaction of the acylation step observed in the peptide hydrolysis reaction by serine proteases.     

Infinite-layer iron oxide with a square-planar coordination

Conventional high-temperature reactions limit the control of coordination polyhedra in transition-metal oxides to those obtainable within the bounds of known coordination geometries for a given transition metal. For example, iron atoms are almost exclusively coordinated by three-dimensional polyhedra such as tetrahedra and octahedra. However, recent works have shown that binary metal hydrides act as reducing agents at low temperatures, allowing access to unprecedented structures. Here we show the reaction of a perovskite SrFeO3 with CaH2 to yield SrFeO2, a new compound bearing a square-planar oxygen coordination around Fe2+. SrFeO2 is isostructural with 'infinite layer' cupric oxides, and exhibits a magnetic order far above room temperature in spite of the two-dimensional structure, indicating strong in-layer magnetic interactions due to strong Fe d to O p hybridization. Surprisingly, SrFeO2 remains free from the structural instability that might well be expected at low temperatures owing to twofold orbital degeneracy in the Fe2+ ground state with D(4h) point symmetry. The reduction and the oxidation between SrFeO2 and SrFeO3 proceed via the brownmillerite-type intermediate SrFeO2.5, and start at the relatively low temperature of approximately 400 K, making the material appealing for a variety of applications, including oxygen ion conduction, oxygen gas absorption and catalysis.     

BluB cannibalizes flavin to form the lower ligand of vitamin B12

Vitamin B12 (cobalamin) is among the largest known non-polymeric natural products, and the only vitamin synthesized exclusively by microorganisms. The biosynthesis of the lower ligand of vitamin B(12), 5,6-dimethylbenzimidazole (DMB), is poorly understood. Recently, we discovered that a Sinorhizobium meliloti gene, bluB, is necessary for DMB biosynthesis. Here we show that BluB triggers the unprecedented fragmentation and contraction of the bound flavin mononucleotide cofactor and cleavage of the ribityl tail to form DMB and D-erythrose 4-phosphate. Our structural analysis shows that BluB resembles an NAD(P)H-flavin oxidoreductase, except that its unusually tight binding pocket accommodates flavin mononucleotide but not NAD(P)H. We characterize crystallographically an early intermediate along the reaction coordinate, revealing molecular oxygen poised over reduced flavin. Thus, BluB isolates and directs reduced flavin to activate molecular oxygen for its own cannibalization. This investigation of the biosynthesis of DMB provides clarification of an aspect of vitamin B12 that was otherwise incomplete, and may contribute to a better understanding of vitamin B12-related disease.