P2X1 receptors for ATP are ligand-gated cation channels, present on many excitable cells including vas deferens smooth muscle cells. A substantial component of the contractile response of the vas deferens to sympathetic nerve stimulation, which propels sperm into the ejaculate, is mediated through P2X receptors. Here we show that male fertility is reduced by approximately 90% in mice with a targeted deletion of the P2X1 receptor gene. Male mice copulate normally--reduced fertility results from a reduction of sperm in the ejaculate and not from sperm dysfunction. Female mice and heterozygote mice are unaffected. In P2X1-receptor-deficient mice, contraction of the vas deferens to sympathetic nerve stimulation is reduced by up to 60% and responses to P2X receptor agonists are abolished. These results show that P2X1 receptors are essential for normal male reproductive function and suggest that the development of selective P2X1 receptor antagonists may provide an effective non-hormonal male contraceptive pill. Also, agents that potentiate the actions of ATP at P2X1 receptors may be useful in the treatment of male infertility.

This paper reports the results of two parallel 1996 surveys, one of economists, one of the public. It finds that the public has a bleaker picture of what has happened economically to the average family and is more pessimistic than most economists about the intermediate future. The public cites different reasons than economists do for why the economy is not doing better. Also, individuals' perceptions of their own economic experiences yield a different set of beliefs about economic conditions than that described in official statistics. The authors offer possible explanations of the perception gap between the public and economists. Coauthors are John M. Benson, Mollyann Brodie, Richard Morin, Drew E. Altman, Daniel Gitterman, Mario Brossard, and Matt James.

Background: Isocitrate dehydrogenase (IDH) mutations occur in diverse tumor types, leading to production of the oncometabolite 2-hydroxyglutarate (2-HG). Results: High 2-HG levels lead to a reversible epithelial-mesenchymal transition (EMT) phenotype, which is dependent on ZEB1/miR-200. Conclusion: Mutant IDH reversibly disrupts normal epithelial morphology through EMT induction, a possible tumorigenic mechanism. Significance: This is the first report of a reversible mutant IDH-dependent signaling phenotype.

1 Contractile responses to short trains of nerve stimulation have been characterized in small, medium and large arteries from the rat mesenteric circulation (5th ± 6th, 2nd ± 3rd and 1st order, respectively). In addition, sources of calcium for smooth muscle contraction have been investigated. 2 Nerve stimulation (10 pulses at 10 Hz) evoked reproducible contractions. The P2 receptor antagonist suramin (100 mM) reduced constrictions by 65.3+7.4, 82.7+3.3 and 3.1+6.1% in small, medium and large arteries respectively. The a-adrenoceptor antagonist prazosin (0.1 mM) reduced responses by 32.6+2.6, 27.0+1.5 and 97.0+1.9% respectively. 3 The L-type calcium channel antagonist nifedipine (1 mM) reduced nerve-evoked contractions by 2.8+3.3, 10.0+3.7 and 13.5+2.7% in small, medium and large arteries respectively. When the adrenergic component of contraction was blocked by prazosin (0.1 mM) nifedipine reduced responses by 4.6+7.9, 14.3+2.0 and 3.0+1.9% respectively. 4 Contractile responses to exogenous a,b-meATP were una ected by the depletion of calcium stores with cyclopiazonic acid (30 mM). This indicates that mobilization of calcium from internal stores is not required for P2X receptor mediated smooth muscle contraction. 5 We conclude that for neurogenic responses, the P2X receptor mediated component of constriction dominates in small mesenteric arteries (3rd ± 6th order) while in large arteries (1st order) noradrenaline mediates contraction. For P2X receptor mediated responses all the calcium required for smooth muscle contraction enters the cell directly through P2X receptor channels.