Novel inhibitors of influenza sialidases related to GG167 structure-activity, crystallographic and Molecular dynamics studies with 4H-pyran-2-carboxylic acid 6-carboxamides

The structure-activity relationships of a series of 4-amino and guanidino-4H-pyran-2-carboxylic acid 6-carboxamides are described. These compounds represent a new class of inhibitor of influenza sialidases and are particularly active against influenza A sialidase. The binding of the N-phenethyl-N-propylamide 41 to influenza A and B sialidases has been investigated using X-ray crystallography and molecular dynamics simulations. Our results suggest that formation of a hitherto unobserved intramolecular salt bridge within the enzymes may account for the observed activity and selectivity of the series.     

A 12 000-year record of environmental change in the Lomond Hills, Fife, Scotland: Vegetational and climatic variability

The Lomond Hills of Fife, an isolated upland area rising to over 500 m, provide an opportunity to investigate the effect of altitude on vegetation and climate in an area otherwise dominated by lower-lying land. The West Lomond site contains sediments of the Devensian Late-glacial period; they reveal a well-defined sequence of Bolling-Older Dryas-Allerod-Younger Dryas events, commencing ca. 12 190 radiocarbon years B.P. and a probable Amphi-Atlantic Oscillation between ca. 11 040 and 10 800 B.P. The Holocene record is constrained by low sediment input but does reveal a woodland presence at this altitude, dominated byBetula andCorylus. Size statistics forBetula pollen are presented and the implications of the vegetational and climatic record are discussed. The traditional view of a smooth progress towards more temperate conditions following the Younger Dryas is not supported; between 10 180 and 9120 B.P., three cooler periods are inferred, the earliest of which may belong to a terminal phase of the Younger Dryas. Comparative pollen ‘influx’ data strongly suggest thatQuercus,Ulmus andAlnus were not present locally. As a working hypothesis, it is suggested that the demise of woodland, from ca. 5950 B.P., was a result of exposure. Pollen indicative of human impact was probably derived from areas of lowland agricultural activity from ca. 5330 B.P. onwards.     

Differentiation of HL-60 cells: cell volume and cell cycle changes

HL-60 promyelocytic leukemic cells can differentiate into more mature myeloid cells with the addition of dimethylsulfoxide, butyric acid or retinoic acid and can differentiate into macrophages with the addition of phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA). After the addition of an inducer, the HL-60 cell volume shows a daily decrease while the cell number increases at a rate similar to the untreated control cells. Flow cytometry measurements show an increase in G1 cells and a decrease in S cells after day 1. Since the generation time is constant, the data suggest that the length of time spent in the different cell cycle stages has changed during differentiation. Within 3 hours after the addition of TPA to HL-60 cells, selective adhesion of G1 cells occurs. Smaller sized cells are recovered from the flask bottom and larger sized cells are recovered from the supernate. Flow cytometric analysis reveals a G1 and S block in cells obtained from both the supernatant and from the flask bottom. After 1 day of TPA incubation, there is preferential adhesion of G1 and G2 cells with the nonadherent cells being primarily in the S and G2 cell cycle stages and undergoing a cell cycle traverse.     

Nitrate reductase activity (in vivo and in vitro) of ditelosomic stocks of wheat (Triticum aestivum L.)

The nitrate reductase activities (NRA) of 31 ditelosomic stocks were compared with that of the control plant [Chinese Spring (CS) euploid], using in vivo and in vitro assay procedures that had been optimized with respect to the euploid. Fourteen stocks exhibited significant differences in in vivo NRA from that of the euploid; the effect of removal of a chromosome arm was always to increase NRA. Eight of these stocks showed similar effects in vitro, although in three, a casein-sensitive factor had to be eliminated before the difference was expressed. Homoeologous group effects were evident among ditelosomics of groups 2, 4, and 7, while for three chromosomes (2D, 7A, and 7B), removal of either arm resulted in a similar increase in NRA in vivo and probably in vitro.P. W. Jones was supported by a Science Research Council C.A.S.E. award with the Plant Breeding Institute, Cambridge, U.K.     

Effect of DMSO on the dielectric properties of canine kidney tissue

The dielectric permittivity and conductivity of canine kidney tissue samples were measured at R_f frequencies between ?20 °C and +20 °C. Some of the kidneys had been perfused with DMSO (10%) in canine plasma, others with physiological saline alone. The DMSO greatly increases the conductivity of frozen tissue above that of tissue not treated with this cryoprotectant. Apparently, the chief reason for nonuniform heating of a partially frozen organ in a microwave field is the great change in tissue conductivity as it thaws. We suggest that the effect on the conductivity of tissue should be considered in the choice of a cryoprotectant for tissues which are to be thawed by microwave or radiofrequency irradiation.