New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS.

The genetics of resistance to infection by HIV-1 cohort consists of 200 slow and 75 rapid progressors to AIDS corresponding to the extremes of HIV disease outcome of 20,000 Caucasians of European descent. A comprehensive analysis of HLA class I and class II genes in this highly informative cohort has identified HLA alleles associated with fast or slow progression, including several not described previously. A quantitative analysis shows an overall HLA influence independent of and equal in magnitude (for the protective effect) to the effect of the CCR5-Delta32 mutation. Among HLA class I genes, A29 (p = 0.001) and B22 (p < 0.0001) are significantly associated with rapid progression, whereas B14 (p = 0.001) and C8 (p = 0.004) are significantly associated with nonprogression. The class I alleles B27, B57, C14 (protective), and C16, as well as B35 (susceptible), are also influential, but their effects are less robust. Influence of class II alleles was only observed for DR11. These results confirm the influence of the immune system on disease progression and may have implications on peptide-based vaccine development.     

THE INFLUENCE OF THE MATING SYSTEM ON SEED SIZE VARIATION IN CRINUM ERUBESCENS (AMARYLLIDACEAE)

We present evidence that extreme seed size variation in fruits of Crinum erubescens (range: 0.1 to 66.5 g per seed) occurs when mating pairs are inbred, either from selfing or biparental inbreeding. Several relatively uniform seeds of intermediate size are produced when pollen from several pollen donors is applied simultaneously to a flower. Selfed fruits and some fruits pollinated with a single pollen donor produce both large and small seeds, although selfed fruits produce fewer seeds than outcrossed fruit. These results are contrary to the hypothesis that variation in seed size is attributable to either pollen competition or differential allocation of maternal resource to seeds of different genotypes.     

Phytochrome Regulation of the Response to Exogenous Gibberellins by Epicotyls of Vigna sinensis

The elongation rate of cowpea epicotyls from whole cowpea (Vigna sinensis) seedlings and derooted and debladed plants (explants) increased after the main light period (8-hour duration) was extended with either continuous low intensity tungsten light or brief (5 minutes) far-red (FR) irradiation. This end-of-day FR effect was reversed by red (R) irradiation suggesting the involvement of phytochrome. These results confirm and extend those obtained previously with other species. Localization studies indicate the epicotyl to be the site of the photoreceptor. Treatment of cowpea seedlings with paclobutrazol, a gibberellin (GA) biosynthetic inhibitor, abolished the FR promoted epicotyl elongation, indicating a role for GAs in this process. There was no significant difference in epicotyl elongation rates of R plus FR irradiated explants treated with GA₁ or GA₂₀ and R irradiated explants treated with GA₁. However, R irradiation inhibited subsequent epicotyl elongation of GA₂₀ treated explants. Moreover, the observation, using GC-MS, that GA₁ and GA₂₀ are native GAs in cowpea lends support to the concept that phytochrome may control the conversion of endogenous GA₂₀ to GA₁ in cowpea.     

Structure-function analysis with tissue-type plasminogen activator. Effect of deletion of NH2-terminal domains on its biochemical and biological properties

Tissue-type plasminogen activator (t-PA) is a mosaic protein containing several distinct structural domains attached to the serine protease catalytic unit present at its COOH terminus. To investigate structure-function relationships in t-PA, we deleted the NH2-terminal domains, finger and epidermal growth factor, by genetic engineering. The genes for the parent and mutant t-PA were expressed in a bovine papilloma virus-dependent mammalian cell system. The secreted proteins were purified to homogeneity. The mutant protein was processed to the expected size of about 60 kDa compared to approximately 68 kDa for the parent t-PA, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fibrin autography. While the mutant t-PA had amidolytic activity comparable to native t-PA, it did not bind appreciably to fibrin. Consequently, fibrin-dependent enzymic activity, i.e. plasminogen activation in the presence of soluble fibrin and fibrinolysis were lower than with native recombinant t-PA. The effect of deletion of NH2-terminal domains on the plasma half-life (t1/2) was investigated by injecting native and mutant t-PA into mice. While the majority of the t-PA disappeared initially with a t1/2 of about 2 min, mutant t-PA cleared at a much slower rate with t1/2 of about 50 min. These findings suggest that the NH2-terminal domains of t-PA not only determine its specificity for binding to fibrin but also mediate its clearance from plasma in vivo. Furthermore, the catalytic unit in t-PA seems to function autonomously.     

A minority of 46,XX true hermaphrodites are positive for the Y-DNA sequence including SRY

Summary A total of 30 cases of 46,XX true hermaphroditism was analysed for Y-DNA sequences including the recently cloned gene for male testis-determination SRY. In 3 cases, a portion of the Y chromosome including SRY was present and, in 2 cases, was localised, to Xp22 by in situ hybridisation. Since previous studies have shown that the majority of XX males are generated by an X-Y chromosomal interchange, the Xp22 position of the Yp material suggests that certain cases of hermaphroditism can arise by the same meiotic event. The phenotype in the 3 SRY-positive cases may be caused by X-inactivation resulting in somatic mosaicism of testis-determining factor expression giving rise to both testicular and ovarian tissues. Autosomal or X-linked mutation(s) elsewhere in the sex-determining pathway may explain the phenotype observed in the remaining 27 SRY-negative cases.     

ECOLOGICAL CONSEQUENCES AND PHENOTYPIC CORRELATES OF PETAL SIZE VARIATION IN WILD RADISH,RAPHANUS SATIVUS (BRASSICACEAE)

In this paper we examine some ecological consequences and phenotypic correlates of flower size variation in wild radish, Raphanus sativus. Mean corolla diameter varied significantly among individuals within natural populations of R. sativus in California. On the average, almost 40% of flower biomass was allocated to corolla tissue. In field experiments, pollinator visitation increased significantly with corolla size. Large flowers also accumulated more nectar when pollinators were excluded from plants. In three populations, corolla size was positively correlated with allocation to pollen per flower (either anther weight or pollen grain number), but there was usually no phenotypic relationship between corolla size and several measures of female allocation (ovule number per flower, proportion fruit set, and total seed mass per fruit). Plants growing in the field produced fewer large flowers per unit of stem, and stem biomass was negatively related to corolla size for plants grown under controlled greenhouse conditions. Male and female fitness may covary differently with allocation to attractive floral features in species such as R. sativus, where seed production is often limited by resources rather than by pollen.     

Transport of gibberellin a(1) in cowpea membrane vesicles

The permeability properties of gibberellin A₁ (GA₁) were examined in membrane vesicles isolated from cowpea hypocotyls. The rate of GA₁ uptake was progressively greater as pH decreased, indicating that the neutral molecule is more permeable than anionic GA₁. Membrane vesicles used in this study possessed a tonoplast-type H⁺-translocating ATPase as assayed by MgATP-dependent quenching of acridine orange fluorescence and methylamine uptake. However, GA₁ uptake was not stimulated by MgATP. At concentrations in excess of 1 micromolar, GA₁, GA₅, and GA, collapsed both MgATP-generated and artifically imposed pH gradients, apparently by shuttling H⁺ across the membrane as neutral GA. The relatively high permeability of neutral GA and the potentially detrimental effects of GA in uncoupling pH gradients across intracellular membranes supports the view that GA₁ accumulation and compartmentation must occur by conversion of GA₁ to more polar metabolites.