SLC2A9 influences uric acid concentrations with pronounced sex-specific effects

Serum uric acid concentrations are correlated with gout and clinical entities such as cardiovascular disease and diabetes. In the genome-wide association study KORA (Kooperative Gesundheitsforschung in der Region Augsburg) F3 500K (n = 1,644), the most significant SNPs associated with uric acid concentrations mapped within introns 4 and 6 of SLC2A9, a gene encoding a putative hexose transporter (effects: -0.23 to -0.36 mg/dl per copy of the minor allele). We replicated these findings in three independent samples from Germany (KORA S4 and SHIP (Study of Health in Pomerania)) and Austria (SAPHIR; Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk), with P values ranging from 1.2 x 10(-8) to 1.0 x 10(-32). Analysis of whole blood RNA expression profiles from a KORA F3 500K subgroup (n = 117) showed a significant association between the SLC2A9 isoform 2 and urate concentrations. The SLC2A9 genotypes also showed significant association with self-reported gout. The proportion of the variance of serum uric acid concentrations explained by genotypes was about 1.2% in men and 6% in women, and the percentage accounted for by expression levels was 3.5% in men and 15% in women.     

Molecular mechanism for duplication 17p11.2- the homologous recombination reciprocal of the Smith-Magenis microdeletion

Recombination between repeated sequences at various loci of the human genome are known to give rise to DNA rearrangements associated with many genetic disorders. Perhaps the most extensively characterized genomic region prone to rearrangement is 17p12, which is associated with the peripheral neuropathies, hereditary neuropathy with liability to pressure palsies (HNPP) and Charcot-Marie-Tooth disease type 1A (CMT1A;ref. 2). Homologous recombination between 24-kb flanking repeats, termed CMT1A-REPs, results in a 1.5-Mb deletion that is associated with HNPP, and the reciprocal duplication product is associated with CMT1A (ref. 2). Smith-Magenis syndrome (SMS) is a multiple congenital anomalies, mental retardation syndrome associated with a chromosome 17 microdeletion, del(17)(p11.2p11.2) (ref. 3,4). Most patients (>90%) carry deletions of the same genetic markers and define a common deletion. We report seven unrelated patients with de novo duplications of the same region deleted in SMS. A unique junction fragment, of the same apparent size, was identified in each patient by pulsed field gel electrophoresis (PFGE). Further molecular analyses suggest that the de novo17p11.2 duplication is preferentially paternal in origin, arises from unequal crossing over due to homologous recombination between flanking repeat gene clusters and probably represents the reciprocal recombination product of the SMS deletion. The clinical phenotype resulting from duplication [dup(17)(p11.2p11.2)] is milder than that associated with deficiency of this genomic region. This mechanism of reciprocal deletion and duplication via homologous recombination may not only pertain to the 17p11.2 region, but may also be common to other regions of the genome where interstitial microdeletion syndromes have been defined.     

Distinguishing causality principles

We distinguish two sub-types of each of the two causality principles formulated in connection with the Common Cause Principle in Henson (2005) and raise and investigate the problem of logical relations among the resulting four causality principles. Based in part on the analysis of the status of these four principles in algebraic quantum field theory we will argue that the four causal principles are non-equivalent.     

Chromosomal rearrangements induced inDrosophila salivary gland chromosomes by an acridine half mustard

Zusammenfassung Bei Kontrolle der Speicheldrüsen ergibt sich, dass die Acridinbehandlung beiDrosophila Komplexinversionen erzeugt.     

Ontogeny of the sex steroid and prolactin receptors in the male rat adrenal gland

Summary Cytosolic estrogen and androgen receptors and membrane prolactin-binding sites in the male adrenal glands showed a definite pattern during sexual development. The level of sexual steroid receptors paralleled adrenal growth, whereas prolactin binding reached its maximum value in mature rats.Lüthy, I. A., Predoctoral Fellow from the Consejo Nacional de Investigaciones Cientificas y Técnicas and Calandra, R. S., Research Career Awardee from the Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.Acknowledgments. We would like to thank Mrs D. Bas and Mrs D. B. Destéfano for the skillful technical assistance and the secretarial work, respectively. This work was partially supported by the Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina (CONICET), and the Comisión Nacional de Energía Atómica.     

Captivity affects behavioral physiology: Plasticity in signaling sexual identity

Summary Little is known about the link between captivity, physiology, and behavior in wild-caught vertebrates. Anecdotal evidence suggests that hormonal changes are responsible for behavioral changes in wild animals brought into captivity. Studying the effects of captivity on reproduction is hampered because wild animals often fail to exhibit sexual behavior under captive conditions. In weakly discharging electric fish, field studies have reported sex differences in electric organ discharges which are rarely seen in the laboratory. I now report the results of a series of laboratory investigations which show thatGnathonemus petersii exhibits seasonal, hormone-dependent, phasespecific sex differences in electric organ discharges. Captivity dramatically alters and may even reverse these sex differences as a result of rapid changes in endogenous plasma hormone levels. These findings have broad implications for research on animal physiology and behavior performed in laboratory settings.     

Interference of sodium ethylenediaminetetraacetate in the determination of proteins and its elimination

Zusammenfassung Es wird die Interferenz von Natrium Ethylendiaminotetraacetat bei der Eiweissbestimmung nach der Methode vonLowry et al. und deren Verhinderung gezeigt. Die Anwesenheit von Natrium Ethylendiaminotetraacetat interferiert bei der Eiweissbestimmung nach der Methode vonLowry, da sie selbst zur Reduktion des Folin-Reagens führt. Es gelingt, diese Interferenz durch Zusatz von CaCl₂ zu verhindern.