Neuronenaktivität hypothalamischer Kerngebiete von Kaninchen nach intraventrikulärer Applikation von Vasopressin und Oxytocin

Summary Intraventricularly applied vasopressin ncreased, and oxytocin decreased, the impulse activity of neurones in the paraventricular and supraoptic nuclei. We found a shorter reaction time for the paraventricular nucleus in comparison with the supraoptic nucleus.

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Diese Arbeit wurde mit Mitteln des Ministeriums für Wissenschaft und Technik der DDR durchgeführt.

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Die Autoren danken FrauE. Müller und Frl.H. Papajewski für gewissenhafte technische Assistenz.     

<Emphasis Type="Italic">O</Emphasis>-GlcNAc transferase associates with the MCM2–7 complex and its silencing destabilizes MCM–MCM interactions

O-GlcNAcylation of proteins is governed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). The homeostasis of O-GlcNAc cycling is regulated during cell cycle progression and is essential for proper cellular division. We previously reported the O-GlcNAcylation of the minichromosome maintenance proteins MCM2, MCM3, MCM6 and MCM7. These proteins belong to the MCM2–7 complex which is crucial for the initiation of DNA replication through its DNA helicase activity. Here we show that the six subunits of MCM2–7 are O-GlcNAcylated and that O-GlcNAcylation of MCM proteins mainly occurs in the chromatin-bound fraction of synchronized human cells. Moreover, we identify stable interaction between OGT and several MCM subunits. We also show that down-regulation of OGT decreases the chromatin binding of MCM2, MCM6 and MCM7 without affecting their steady-state level. Finally, OGT silencing or OGA inhibition destabilizes MCM2/6 and MCM4/7 interactions in the chromatin-enriched fraction. In conclusion, OGT is a new partner of the MCM2–7 complex and O-GlcNAcylation homeostasis might regulate MCM2–7 complex by regulating the chromatin loading of MCM6 and MCM7 and stabilizing MCM/MCM interactions.     

Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease

Integration of genome-wide expression profiling with linkage analysis is a new approach to identifying genes underlying complex traits. We applied this approach to the regulation of gene expression in the BXH/HXB panel of rat recombinant inbred strains, one of the largest available rodent recombinant inbred panels and a leading resource for genetic analysis of the highly prevalent metabolic syndrome. In two tissues important to the pathogenesis of the metabolic syndrome, we mapped cis- and trans-regulatory control elements for expression of thousands of genes across the genome. Many of the most highly linked expression quantitative trait loci are regulated in cis, are inherited essentially as monogenic traits and are good candidate genes for previously mapped physiological quantitative trait loci in the rat. By comparative mapping we generated a data set of 73 candidate genes for hypertension that merit testing in human populations. Mining of this publicly available data set is expected to lead to new insights into the genes and regulatory pathways underlying the extensive range of metabolic and cardiovascular disease phenotypes that segregate in these recombinant inbred strains.     

Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2

Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.     

Ursachen der geschlechtsunterschiedlichen MilchdrÜsengewebsentwickiung bei Ratten

Summary Under the same hormonal conditions, mammary gland growth in adult female rats is more pronounced than in males. Since there are no differences in the glandular development of both sexes, either at birth or at 30 days of life, it is assumed that male rats react less sensitively than female rats in response to a hormonal stimulus with regard to mammary gland growth. It is presumed that androgen influence during the differentiation stage is responsible for the fixation of a decreased sensitivity of the positive feedback-mechanism between estrogens and prolactin secretion in males. Thus changes in sensitivity would be the reason for mammary gland growth in males being smaller than in females under the same hormonal conditions.

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Dieser Arbeit liegen zum Teil die Untersuchungsergebnisse einer SchÜler-Facharbeit von U.Rieser zugrunde.     

一种简单的溶胶-凝胶法制备二氧化锆介质层

在电子产业中,能够进行低压操作以及能够在非常薄的薄层上进行器件设计的材料备受关注.并且,这些材料需要使用方法简单、快速、可靠.作者提出一种简单且快速可靠的沉积高k二氧化锆介电层的方法.整个过程从原来常规过程的140分钟缩短到10分钟.这种改进的方法在操作流程方面有显著的提升.这种溶胶凝胶法制备的样品介电层厚度远小于与之前报道的样品,其厚度约为原方法制备样品的25%.在优化操作过程与降低介电层厚度的同时,二氧化锆的介电性质并没有被影响.作者进一步研究了样品的介电特性,在90K到300K之间介电性质的变化小于10%.     

Relating ligand binding to activation gating in CNGA2 channels

Cyclic nucleotide-gated (CNG) ion channels mediate sensory signal transduction in photoreceptors and olfactory cells. Structurally, CNG channels are heterotetramers composed of either two or three homologue subunits. Although it is well established that activation is a cooperative process of these subunits, it remains unknown whether the cooperativity is generated by the ligand binding, the gating, or both, and how the subunits interact. In this study, the action of homotetrameric olfactory-type CNGA2 channels was studied in inside-out membrane patches by simultaneously determining channel activation and ligand binding, using the fluorescent cGMP analogue 8-DY547-cGMP as the ligand. At concentrations of 8-DY547-cGMP < 1 microM, steady-state binding was larger than steady-state activation, whereas at higher concentrations it was smaller, generating a crossover of the steady-state relationships. Global analysis of these relationships together with multiple activation time courses following cGMP jumps showed that four ligands bind to the channels and that there is significant interaction between the binding sites. Among the binding steps, the second is most critical for channel opening: its association constant is three orders of magnitude smaller than the others and it triggers a switch from a mostly closed to a maximally open state. These results contribute to unravelling the role of the subunits in the cooperative mechanism of CNGA2 channel activation and could be of general relevance for the action of other ion channels and receptors.