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The structure−activity relationship (SAR) of a novel hydrophobic binding interaction within a subsite of the influenza neuraminidase (NA) active site was characterized and optimized for a series of trisubstituted pyrrolidine inhibitors modified at the 4-position. Previously, potent inhibitors have targeted this subsite with hydrophilic substituents such as amines and guanidines. Inhibitor-bound crystal structures revealed that hydrophobic substituents with sp² hybridization could achieve optimal interactions by virtue of a low-energy binding conformation and favorable π-stacking interactions with the residue Glu119. From a lead methyl ester, investigation of five-membered heteroaromatic substituents at C-4 produced a 3-pyrazolyl analogue that improved activity by making a targeted hydrogen bond with Trp178. The SAR of substituted vinyl substituents at C-4 produced a Z-propenyl analogue with improved activity over the lead methyl ester. The C-1 ethyl ester prodrugs of the substituted C-4 vinyl analogues gave compounds with excellent oral bioavailability (F > 60%) when dosed in rat.

Dispersal of Larus novaehollandiae Stephens, from 10 colonies in South Australia, was studied during 1968-8 1 by means of bands designed for identification of free-living, uncaptured individuals. Dispersal patterns were characteristic of each colony, even for three colonies which were, at most, 10 km apart. Almost all dispersal records came from the area between Adelaide and Melbourne, and within 30 km of the coast. After breeding, the majority of gulls disperse eastwards; however, dispersal from each colony was correlated with a shift of gull population into areas where food was available from human sources such as rubbish dumps. From colonies 80 km south-east of Adelaide, a major human population, the predominant winter dispersal of these gulls was north-west, into the city and suburbs. The maximum direct-line dispersal distances recorded for 95% of the 3133 resighted gulls were <458 km. The greatest direct-line distance recorded was 1430 km. Overall, there was no significant difference in the mean dispersal distances of juveniles and adults, although at distances >480 km significantly more juveniles (<2y) were seen than adults (>2y). This involved only 2.5% of the total number of birds resighted. It is suggested that older, dominant birds maintain high status at preferred feeding places, and juveniles are possibly more erratic in their movements, as they search for food. This would account for the difference in the dispersal ofjuveniles and adults from a particular colony, and also for the significantly higher proportion of juveniles found at extreme distances from their natal colonies.

Aspects of the reproductive ecology of silver gulls, Larus novaehollandiae Stephens, were studied in South Australia during 1968-78. Some 15 950 pulli and 597 breeding adults were banded on 15 colonies, using numbered and coloured leg bands designed for identification of free-living individuals without the necessity of recapture. Nine colonies were on marine islands, four were on lacustrine islands, one was on a port breakwater, and one was on causeways in a saltworks complex. Fidelity to colony, mate and nest-site, and timing of breeding are considered in detail. The spatial relationship of adult and immature gulls, on the colony studied in greatest detail, and reproductive longevity of the gulls are also discussed. The gulls nested from June to December inclusive, although the commencement and length of breeding seasons varied between colonies and between years. There was a marked absence of 1-year-old gulls on breeding colonies. Of 3530 pulli banded on the major study colony, Penguin Island (3730''S., 14001''E.) at Beachport, in 1968, 950 were known to be alive in the 1970 breeding season. Almost 40% of these 2-year-olds were seen on breeding colonies, and mostly on the natal colony; however, only 0.3% were known to raise pulli, and a further 0.7% to produce eggs. Significant breeding activity therefore did not commence until the end of the third year, or later. The older, previously established breeders on Penguin Island were significantly more successful, and had significantly earlier laying dates, than younger birds. Potential reproductive longevity appears to be at least 11 breeding seasons. In this study, silver gulls showed considerably less fidelity to nest-sites and colonies than has been suggested previously. Significant shifts of nest-site, or change of colony, with or without the previous mate, were not uncommon. Of gulls banded on nests as established breeding aduls, 7-44% of gulls found breeding in subsequent years were at colonies other than the one where banded. In 1970, over 80% of 2-year-old gulls recorded present on any colony were only recorded on the natal one. Of the pulli banded on Penguin Island in 1968 and 1969 and later found actually nesting or breeding, 18% were recorded on other colonies. A small percentage of gulls were seen to have high fidelity to nest-site and to mate over 3 or 4 seasons, but it is suggested that, for some colonies, over 50% of silver gulls which eventually breed may do so at colonies other than natal. Significant spatial separation was found on Penguin Island between areas generally occupied by established breeders, which were known to be at least 4-year-olds, and by the 2-year-olds. The older birds may select and hold the territories most suitable for nesting, where vegetation or topography minimise intraspecific aggression which often leads to high mortality rates of eggs and pulli, and assist protection of eggs and pulli from extreme weather. Non-breeding gulls associating with the colonies occasionally move into the nesting areas, but are aggressively forced away and tend to congregate on the periphery of the colony or on exposed areas not suitable for successful breeding.

Black-backed Magpies in Australia feed mainly in open grasslands on arthropods found from just below ground level to about 45 cm above ground. In a 10-year period stomachs of 1319 magpies of known age, sex and social status were examined. The numbers of food organisms and the number and percentage of birds taking each food are tabulated. Weevils, the largest coleopteran family in Australia, were eaten by the largest numbers of birds, and weevils were preferred in feeding experiments when weevils were presented to caged magpies with several other arthropods. The insects taken in largest numbers were ants, all the identified genera being producers of formic acid, and members of the genus Myrmecia which sting. Organisms found in a large proportion of birds (percentage of stomachs in parenthesis) were earthworms (37.7), spiders (38.1), crickets (20.8), Acrididae (39.9), weevils 73.1), caterpillars (41.4), ants (70.3); occasional remains of frogs, avian egg shell and other chordates were present, also plant remains thought to have been eaten accidentally except that some samples taken in winter had rather more plant remains of grass and clover. There were other seasonal variations and effects of dry and wet spells on food taken. There were also some differences in diets of flock and territorial birds but little difference between immature and mature birds.

Exchange experiments carried out between nestlings of the crested tern, Sterna bergii, on Montagu I., N.S.W., indicate that while parents do not recognize their own eggs or newly hatched chicks individually, they have learnt to recognize their own chicks by the time they are 2 days old. Comparison of these results with those obtained in other Laridae suggests that the ability of the parents to distinguish their own chick appears shortly before the latter begins to wander from the nest. A sound spectrograph study of the calls of the chicks showed some inter-individual variation, but also much intra-individual variation. The value of the chick's voice as a recognition character therefore remains uncertain.

Witschi and Miller1have shown experimentally that the yellow bill colour of the starling in the breeding season is induced by male sex hormone. This yellow colour does not develop after the removal of the ovary or the testes, but in such castrated animals it may be induced in either sex by injections of androgenic substances. œstrogenic substances have no effect on bill colour. It is concluded that the ovary produces male sex hormone, and that the most prominent secondary sexual character of the female starling is in fact a male character.