Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro

Objective: to determine if sildenafil citrate; a cyclic monophosphate specific type 5 phosphodiesterase inhibitor, influences sperm motility or the acrosome reaction. Design: laboratory analysis of sperm motility after exposure to sildenafil citrate using computer assisted semen analysis (CASA) and acrosome reaction by fluoroscein isothiocyanate labelled peanut agglutinin (FITC-PNA) staining. Setting: An ART unit Patients: 57 male patients Interventions: Sperm were divided into 90% (the best fertilizing potential used in assisted conception) and 45% (the poorer subpopulation) fractions by density centrifugation and incubated with sildenafil citrate ( 0.67uM) at 37ï?°C for up to 180 minutes. Main outcome measures: both the numbers and velocity of progressively motile sperm were significantly increased by sildenafil citrate between 15 and 135 minutes. Further, samples revealed that these effects were consistent in the 90% and 45% subpopulations of sperm. In both subpopulations, sildenafil also caused a significant increase in the proportion of acrosome reacted sperm - 22.1% compared with 11.8% in the control group of the good quality fraction (p

The causes and consequences of Rent-seeking in Northern Ireland, 1945-72

Northern Ireland's economic performance during the 'golden age' was weak. Crafts suggested that rent-seeking was an important determinant of this poor record. This article offers support for such a conclusion. It is suggested that the growth record was shaped by British regulations preventing conflicts of ministerial interest not being made operational until 1963. This institutional divergence tended to promote rent-seeking behaviour, which impeded the pursuit of an industrial policy that could promote economic efficiency. In 1963 the institutional structure and the industrial policy framework changed. These changes stimulated the pursuit of efficiency and contributed to an improved regional economic performance.

Rapid change in energy status in fighting animals: causes and effects of strategic decisions

Energetic costs of fighting, such as high lactate or low glucose, have been shown in a range of species to correlate with the decisions made by each opponent, particularly the decision by one opponent, the 'loser', to end the fight by 'giving up'. Studies based on complete fights of differing duration, however, do not provide information on the changes in the physiological correlates of fighting that may take place during the course of the encounter, or how these changes may influence the capability and decisions of the contestants. We interrupted fights between hermit crabs, Pagurus bernhardus, at specific points, and related energy status to the preceding activities. Costs rose quickly with a rapid accumulation of lactic acid in attackers and declining muscular glycogen in defenders. Changes in physiological status appeared much earlier than the changes in behaviour that they may have caused. Furthermore, some physiological changes might have been an effect, rather than the cause, of fight decisions. (c) 2005 The Association for the Study of Animal Behaviour Published by Elsevier Ltd. All rights reserved.

Rarity and decline in bumblebees - A test of causes and correlates in the Irish fauna

Bees are believed to be in decline across many of the world's ecosystems. Recent studies on British bumblebees proposed alternative theories to explain declines. One study suggested that greater dietary specialization among the rarer bumblebee species makes them more susceptible to decline. A second study disputed this theory and found that declines in British bumblebees were correlated with the size of species' European ranges, leading to the suggestion that climate and habitat specialization may be better indicators of the risk of decline. Here we use a new and independent dataset based on Irish bumblebees to test the generality of these theories. We found that most of the same bumblebee species are declining across the British Isles, but that, within Ireland, a simple food-plant specialization model is inadequate to explain these declines. Furthermore, we found no evidence of a relationship between declines in Irish bumblebees and the size of species' European ranges. However, we demonstrate that the late emerging species have declined in Ireland (and in Britain), and that these species show a statistically significant westward shift to the extremity of their range, probably as a result of changing land use. Irish data support the finding that rare and declining bumblebees are later nesting species, associated with open grassy habitats. We suggest that the widespread replacement of hay with silage in the agricultural landscape, which results in earlier and more frequent mowing and a reduction in late summer wildflowers, has played a major role in bumblebee declines. (C) 2006 Elsevier Ltd. All rights reserved.

Substitution of pseudokinase domain residue Val-617 by large non-polar amino acids causes activation of JAK2

Explaining the uniqueness of the acquired somatic JAK2 V617F mutation, which is present in more than 95% of polycythemia vera patients, has been a challenge. The V617F mutation in the pseudokinase domain of JAK2 renders the unmutated kinase domain constitutively active. We have performed random mutagenesis at position 617 of JAK2 and tested each of the 20 possible amino acids for ability to induce constitutive signaling in Ba/F3 cells expressing the erythropoietin receptor. Four JAK2 mutants, V617W, V617M, V617I, and V617L, were able to induce cytokine independence and constitutive downstream signaling. Only V617W induced a level of constitutive activation comparable with V617F. Also, only V617W stabilized tyrosine-phosphorylated suppressor of cytokine signaling 3 ( SOCS3), a mechanism by which JAK2 V617F overcomes inhibition by SOCS3. The V617W mutant induced a myeloproliferative disease in mice, mainly characterized by erythrocytosis and megakaryocytic proliferation. Although JAK2 V617W would predictably be pathogenic in humans, the substitution of the Val codon, GTC, by TTG, the codon for Trp, would require three base pair changes, and thus it is unlikely to occur. We discuss how the predicted conformations of the activated JAK2 mutants can lead to better screening assays for novel small molecule inhibitors.