Genetic and structural analysis of a virulence determinant in polyomavirus VP1.

The LID strain of polyomavirus differs from other laboratory strains in causing a rapidly lethal infection of newborn C3H/Bi mice. This virulent behavior of LID was attenuated by dilution, yet at sublethal doses LID was able to induce tumors at a high frequency, like its parent virus PTA. By constructing and assaying LID-PTA recombinant viruses and by DNA sequencing, the determinant of virulence in LID was mapped to the major viral capsid protein, VP1. The VP1s of LID and PTA differed at two positions: at 185, LID has phenylalanine and PTA has tyrosine, and at 296, LID has alanine and PTA has valine. Results obtained with viruses constructed by site-directed mutagenesis showed that alanine at position 296 is sufficient to confer a fully virulent phenotype regardless of which amino acid is at position 185. However, with valine at position 296, an effect of phenylalanine at position 185 is apparent, as this virus possesses an intermediate level of virulence. A crystal structure of polyomavirus complexed with 3'-sialyl lactose previously indicated van der Waals contacts between the side chain of valine 296 and the sialic acid ring (T. Stehle, Y. Yan, T. L. Benjamin, and S. C. Harrison, Nature [London] 369:160-163, 1994). When this interaction was modeled with alanine, these contacts were greatly reduced. Direct confirmation that the substitutions in VP1 affected receptor binding was obtained by studying virus hemagglutination behavior. The ensemble of results are discussed in terms of the idea that a lower affinity of the virus for its receptor can result in more rapid spread and increased pathogenicity.     

High-performance liquid chromatography of p-nitrophenacyl esters of selected prostaglandins on silver ion-loaded microparticulate cation-exchange resin

A silver ion-loaded microparticulate cation-exchange resin column has been used for high-performance liquid chromatographic (HPLC) separation of the p-nitrophenacyl esters of several series of closely related prostaglandins: 8-iso-PGE₂, 11-epi-PGE₂, 5-trans-PGE₂, PGE₂, PGF_1α, PGE₁, and PGF_2α, PGA₂ and PGB₂; 15 (R)-methyl-PGE₂ and 15 (S)-methyl-PGE₂; 5-trans-PGA₂ and PGA₂; and 5-trans-PGF_2α and PGF_2α. The properties of this column are compared with those of silica-gel and reversed-phase columns.     

Seasonal reproduction of a tropical bat, Anoura geoffroyi, in relation to photoperiod.

Anoura geoffroyi (Chiroptera, Phyllostomidae, Glossophaginae), Geoffroy's hairy-legged long-tongued bat, were collected from September 1984 to August 1985, and these bats were found to breed seasonally in the wild on Trinidad, West Indies, at 10 degrees N latitude. Histological examination of these samples indicated that females became pregnant in July or August, and young were born in late November or early December. The testes and epididymides were small from September to mid-April, increased threefold in weight between mid-April and late May, reached a peak weight in July, and decreased in weight in August. Spermatogenesis occurred throughout the testes of males captured from May to August. In 1990, the timing of parturition in females that gave birth in the laboratory to young conceived in the wild was similar to the timing in the field in 1984-1985. Groups of 10-13 males were subjected in the laboratory to (i) a gradually changing, civil twilight photoperiod that mimicked the natural cycle of annual change at 10 degrees N latitude, (ii) the same gradually changing cycle of photoperiod accelerated to a six-month period, or (iii) a constant photoperiod (light 12:54 h: dark 11:06 h). These treatments began in mid-December, four months before the initiation of testicular recrudescence in the wild. In all three groups, testicular volume remained low until April, and then increased two- to threefold between late April and late June, rising to a peak in July, as occurred in the wild.(ABSTRACT TRUNCATED AT 250 WORDS)     

Brain weight-body weight relationships in 12 species of nonhuman primates

Necropsy data from a Primate Center were used in a study of the brain weight-body weight relationships of 12 species of nonhuman primates. The sample sizes ranged from six Cercopithecus aethiops to 163 Macaca mulatta. By plotting mean brain-mean body weight of each species on log-log paper, it was shown that the straight line fitting the plots of all species had a slope of 0.72. Slopes for three species of the genus Macaca, and for six species of the family Cebidae, were 0.61 and 0.81 respectively. Coefficients of determination of the three lines were greater than 0.90. Two species of the family Cebiade, Saimiri sciureus and Aotus trivirgatus, had equivalent body weights, but the former had a 30% larger brain than the latter. The results suggest that brain-body weight scaling characteristics of primate species can be studied effectively using necropsy data. Some statistically significant discrepancies between these and published data, however, show that more data are required to describe these characteristics with greater certainty.     

A New Synthesis of the Potent and Selective Anti-Herpesvirus Agent (S)-1-[3-Hydroxy-2-(Phosphonylmethoxy)Propyl]Cytosine

Abstract

A new synthetic approach to (S)-1-[3-hydroxy-2-(phosphonyl-methoxy)propyl]cytosine (3, (S)-HPMPC) is based on coupling of the heterocyclic moiety with a glycerol-derived side chain, followed by introduction of the phosphonylmethyl ether group.     

Discovery of disubstituted piperidines and homopiperidines as potent dual NK1 receptor antagonists–serotonin reuptake transporter inhibitors for the treatment of depression

This report describes the synthesis, structure–activity relationships and activity of piperidine, homopiperidine, and azocane derivatives combining NK₁ receptor (NK₁R) antagonism and serotonin reuptake transporter (SERT) inhibition. Our studies culminated in the discovery of piperidine 2 and homopiperidine 8 as potent dual NK₁R antagonists-SERT inhibitors. Compound 2 demonstrated significant activity in the gerbil forced swimming test, suggesting that dual NK₁R antagonists-SERT inhibitors may be useful in treating depression disorders.     

Land use and dispersal influence mortality in white-tailed deer

Restoring male age structure in white-tailed deer populations has become an important objective for many state agencies aimed at improving herd dynamics. Limiting mortality in the yearling (1–2 yr old) age class is a primary consideration, and regional differences in climate, habitat characteristics, hunting regulations, and hunter behavior complicate the understanding of how specific factors influence the risk of mortality. We used Cox proportional hazard modeling to determine the effects of body size, mean distance to road, dispersal behaviors, use of forested land, and use of land open to public hunting on the risk of mortality for a population of radio-collared, yearling males (n = 76) in Sussex County, Delaware, USA. Annual survival averaged 0.55 (95% CI = 0.45–0.68), with harvest accounting for 79% (26/33) of all mortalities. Measurements of body size (chest girth, shoulder height, and total length; cm) influenced dispersal probability but not dispersal distance. The best approximating model for mortality risk included a covariate for landownership, whereby mortality risk increased on public land. Among males who dispersed, longer-distance dispersal was associated with reduced mortality, which contradicts previous research describing dispersal as a high-risk behavior. The effect of landownership on mortality risk has not been previously identified, especially when regulations regarding harvest of yearling males are similar between landownership types. We observed annual survival rates of 0.69 (95% CI = 0.57–0.82) for deer apparently using private land exclusively during the hunting season, and 0.20 (95% CI = 0.11–0.48) for deer that used public land during the hunting season. Survival rates on private land were comparable to those of other regions actively managing male age structure. These results suggest survival of yearling males in the region is influenced by hunter harvest and the risks associated with dispersal may be minimal in areas where harvest pressure is low, although hunter harvest on public land may limit male age structure on a localized scale. © The Wildlife Society, 2019