Members of the Ras subfamily of small guanine-nucleotide-binding proteins are essential for controlling normal and malignant cell proliferation as well as cell differentiation. The neuronal-specific guanine-nucleotide-exchange factor, Ras-GRF/CDC25Mm, induces Ras signalling in response to Ca2+ influx and activation of G-protein-coupled receptors in vitro, suggesting that it plays a role in neurotransmission and plasticity in vivo. Here we report that mice lacking Ras-GRF are impaired in the process of memory consolidation, as revealed by emotional conditioning tasks that require the function of the amygdala; learning and short-term memory are intact. Electrophysiological measurements in the basolateral amygdala reveal that long-term plasticity is abnormal in mutant mice. In contrast, Ras-GRF mutants do not reveal major deficits in spatial learning tasks such as the Morris water maze, a test that requires hippocampal function. Consistent with apparently normal hippocampal functions, Ras-GRF mutants show normal NMDA (N-methyl-D-aspartate) receptor-dependent long-term potentiation in this structure. These results implicate Ras-GRF signalling via the Ras/MAP kinase pathway in synaptic events leading to formation of long-term memories.

Background-Elevated plasma homocysteine is a risk factor for arteriosclerosis, but a cause-and-effect relationship remains to be fully established. Endothelial dysfunction, an early event in the atherogenic process, has been shown to be associated with hyperhomocysteinemia in experimental and human studies. To further establish a direct relationship between changes in plasma homocysteine and endothelial dysfunction, we investigated whether moderate hyperhomocysteinemia induced by an oral methionine load would acutely impair flow-mediated endothelium-dependent vasodilatation in healthy adults. Methods and Results-Twenty-four healthy volunteers completed a randomized crossover study in which an oral methionine load (0.1 g/kg) was administered on 1 of 2 study days, 7 days apart. At each visit, plasma homocysteine and brachial artery endothelium-dependent and -independent dilatation were measured at baseline and at 4 hours. To further elucidate the temporal relationship between methionine, homocysteine, and endothelial function, an oral methionine load was administered in 10 subjects on a separate visit, and the time courses of plasma methionine, homocysteine, and flow-mediated brachial artery dilatation were measured at baseline and after 1, 2, 3, 4, and 8 hours.

These data indicate that conduit artery distensibility is increased by acetylcholine and increased blood flow in healthy subjects but not in CHF patients, whereas the effects of adenosine and GTN on distensibility are preserved in CHF patients. This implies that EDRF-mediated increases in distensibility are impaired in CHF patients, thus adding to cardiac work.

Marine omega-3 fatty acids improve large artery endothelium-dependent dilation in subjects with hypercholesterolemia without affecting endothelium-independent dilation.

Floral traits that increase attractiveness to pollinators are predicted to evolve through selection on male function rather than on female function. To determine the importance of male-biased selection in dioecious Wurmbea dioica, we examined sexual dimorphism in flower size and number and the effects of these traits on pollinator visitation and reproductive success of male and female plants. Males produced more and larger flowers than did females. Bees and butterflies responded to this dimorphism and visited males more frequently than females, although flies did not differentiate between the sexes. Within sexes, insect pollinators made more visits to and visited more flowers on plants with many flowers. However, visits per flower did not vary with flower number, indicating that visitation was proportional to the number of flowers per plant. When flower number was experimentally held constant, visitation increased with flower size under sunny but not overcast conditions. Flower size but not number affected pollen removal per flower in males and deposition in females. In males, pollen removal increased with flower size 3 days after flowers opened, but not after 6 days when 98% of pollen was removed. Males with larger flowers therefore, may have higher fitness not because pollen removal is more complete, but because pollen is removed more rapidly providing opportunities to pre-empt ovules. In females, pollen deposition increased with flower size 3 days but not 6 days after flowers opened. At both times, deposition exceeded ovule production by four-fold or more, and for 2 years seed production was not limited by pollen. Flower size had no effect on seed production per plant and was negatively related to percent seed set, implying a tradeoff between allocation to attraction and reproductive success. This indicates that larger flower size in females is unlikely to increase fitness. In both sexes, gamete production was positively correlated with flower size. In males, greater pollen production would increase the advantage of large flowers, but in females more ovules may represent a resource cost. Selection to increase flower size and number in W. dioica has probably occurred through male rather than female function.

Summary 0We examined the sources and consequences of seed mass variation in Banksia marginata occurring in _re!prone heath on nutrient!poor soils to determine factors in~uencing seed size and possible _tness bene_ts of large seeds[ 1 Individual seed mass varied _vefold[ Variation occurred among populations "18) of total#\ among years "09)# and among plants "plants\ 5)^year × plants\ 02)#\ but was most pronounced within plants "31)#[ Within plants\ seed mass variation was greater within infructescences "24)# than among infructescences "6)#[ 2 Seed mass variation within infructescences was not related to whether follicles contained one or two seeds[ Seed mass was also una}ected by ovule position within follicles and follicle position within infructescences[ 3 Seed mass variation among infructescences and plants was related to the limited availability of nutrient resources during seed provisioning[ Mean seed mass was negatively related to seed number per infructescence and per plant[ When resources decreased late in the~owering season and after defoliation\ seed mass declined by 6Ð 09) and seed number by 20Ð34)[ When resources increased after in~orescence removal\ seed mass increased by 7) but seed number was una}ected[ Plants thus had only a limited capacity to maintain seed mass by adjusting seed number when resources varied[ 4 The N and P contents of seeds "mg seed −0 # increased linearly with seed mass\ indicating costs of producing larger seeds in terms of limited environmental nutrients[ 5 Seedling size increased with seed mass\ implying _tness bene_ts of larger seeds in terms of increased seedling establishment on nutrient!poor soils[ Seed mass had little or no e}ect on seed germination\ relative growth rates and root]shoot ratios[ 6 Although stabilizing selection should eliminate seed mass variation occurring within plants\ such variation persists because resource constraints limit the ability of plants to control individual seed size[ Keywords] nutrient allocation patterns\ nutrient!poor soils\ seed nutrient content\ seed size and number\ seedlings Journal of Ecology "0887# 75\ 452Ð462

The findings suggest that endothelial dysfunction is a consequence of foetal malnutrition, consistent with contributing to the clinical features of the 'Small Baby Syndrome' in later adult life.

High dose folic acid supplementation enhances endothelium-dependent vascular function and lowers plasma Hcy. This provides preliminary evidence that folate may have beneficial cardiovascular effects in adults with mild hyperhomocysteinaemia.