No abstract

In two swordtail species of the genus Xiphophorus, the onset of puberty has been shown to be modulated at the P locus by sequence polymorphism and gene copy-number variation affecting the type 4 melanocortin hormone receptor Mc4r. The system works through the interaction of two allelic types, one encoding wild type and the other dominant-negative receptors. We have analyzed the structure and evolution of the P locus in the platyfish Xiphophorus maculatus, where as many as nine alleles of P determining the onset of sexual maturity in males and females, fecundity in females, and adult size in males are located on both the X and Y chromosomes in a region linked to the master sex-determining locus. In this species, mc4r has been amplified to up to 10 copies on both the X and Y chromosomes through recent large serial duplications. Subsequently, mc4r paralogues have diverged considerably into many different subtypes. Certain copies have acquired new untranslated regions through genomic rearrangements, and transposable element insertions and other mutations have accumulated in promoter regions, possibly explaining observed deviations from the classical mc4r transcriptional pattern. In the mc4r-coding sequence, in-frame insertions and deletions as well as nonsense and missense mutations have generated a high diversity of Mc4r-predicted proteins. Most of these variants are expressed in embryos, adults, and/or tumors. Functional receptor characterization demonstrated major divergence in pharmacological behavior for Mc4r receptors encoded by different copies of platyfish mc4r, with differences in constitutive activity as well as binding and stimulation by hormones. The high degree of allelic and copy-number variation observed between individuals can explain the high level of polymorphism for sexual maturation, fecundity, and body size in the platyfish: multiple combinations of Mc4r variants with different biochemical properties might interact to modulate the melanocortin signaling that regulates the hypothalamus-pituitary-gonadal axis.T ELEOST fish of the genus Xiphophorus, which comprise two major and morphologically quite divergent groups, the platyfish and swordtails, are prominent models for the study of polymorphic traits such as sexual development, reproduction, pigmentation, and cancer (Kallman

Der reaktive Cluster RuCo,(CO),, wurde mit zahlreichen anorganischen, elementorganischen und organischen Reagenzien umgesetzt, die potentielle Vorlaufer von p3-verbriickenden Vierelektronenliganden sind. uberdachung konnte erzielt werden rnit Co(C0) 7 zu RuCo3(CO)& mit RPH2 (R = Me, Ph, Tol) zu RuCo2(CObPR (3a-c), rnit MeAsH, zu RuCo2(CO)9AsMe (4), rnit H2S, HSEt und S8 zu RuCO~(CO)~S (S), rnit Ph2Se2 zu RuCo2(CO)gSc (6), rnit TOICE WCp(CO), Capping Reactions of RUCO~(CO),~ with Main Group and Transition Element ReagentsThe reactive cluster RUCO~(CO)~~ was treated with numerous inorganic, organo-element, and organic reagents which are potential precursors of p3-bridging four electron ligands. Capping could be achieved with Co(C0)z forming RuCo3(CO)~, with RPH, (R = Me, Ph, Tol) forming RuCo2 (C0bPR (3a -c), with MeAsH, forming RuCo2(CO)9AsMe (4), with H2S, HSEt, or S8 forming RuCO,(CO)~S (9, with Ph2Se2 leading to RuCo$2O)gSe Unter den Reaktionen der Organometall-Cluster kommt denjenigen eine besondere Bedeutung zu, die Material zur Cluster-Oberflachen-Analogie liefern. Denn wahrend die Identifizierung der agierenden Spezies bei Oberflachenreaktionen betrachtlichen Aufwand erfordert, gelingt sie fur Substrate, die rnit mehreren Metallatomen eines Clusters verkniipft sind, rnit den iiblichen Methoden der Strukturanalyse. Da gleichzeitig fur eine Reihe von Fallen Analogie zwischen Cluster-und Oberflachen-gebundenen Spezies festgestellt wurde I), konnen Bindungsart und Reaktionen von Substraten, die iiber Mehrzentren-Verkniipfung an Cluster gebunden sind, Indizien zur Chemie auf Oberflachen liefern.Der erste Schritt einer chemischen Realisierung dieses Konzepts ist die MehrzentrenAnbindung der Substrate, die als chemische Reaktion eine aerdachungsreaktion (engl.

The excretion of N tau-methylhistidine and creatinine was determined in a totally paralysed patient wih neither macroscopic nor microscopic detectable skeletal-muscle tissue. In this subject, it was possible for the first time to measure the basal non-skeletal-muscle-dependent excretion of N tau-methylhistidine and creatinine per 24 h and per kg of non-muscular body weight, 1.15 mumol (N tau-methylhistidine) and 35 mumol (creatinine) respectively. For the calculation of myofibrillar protein breakdown and skeletal-muscle mass on the basis of N tau-methylhistidine and creatinine excretion, the values have to be corrected for non-muscular sources. Our data show that skeletal-muscle tissue is the major contributor of N tau-methylhistidine in urine, since it contributes as much as 75% to the urinary excretion.

Melanoma formation in certain interspecific hybrids of the genus Xiphophorus (Teleostei: Poeciliidae) is associated with the overexpression of the Xmrk receptor tyrosine kinase oncogene. The Xmrk oncogene arose by duplication of the pre-existing Xmrk protooncogene in a highly unstable subtelomeric region of the X and Y sex chromosomes undergoing frequent rearrangements including duplications, deletions, amplifications, and transpositions. Some of these rearrangements are likely to be responsible for the overexpression of the Xmrk oncogene in melanoma. The oncogene itself is very unstable in Xiphophorus and is frequently removed by deletion or disrupted by transposable elements. The Xmrk oncogene region displays a high concentration of retroelements not observed in the corresponding Xmrk protooncogene region. Particularly, a retrovirus long terminal repeat-like sequence was amplified in the proximity of the Xmrk oncogene. Additional genes, some of them also duplicated copies, were detected in this region and might be involved in modulating the melanoma's phenotype.