Über die Fettsäuren aus Spinatchloroplasten

Summary The fatty acids of two samples of chloroplasts fromSpinacia oleracea have been investigated quantitatively. They contain many polyenoic fatty acids (more than 70% of the total fatty acids); amongst these, a relatively high content of C¹⁶-trienoic acid is remarkable. Moreover, the presence of the ³-trans-hexadecenoic acid, recently detected in plants, is noteworthy.     

Zur Wirkung von Strahlenschutzstoffen an Thymuszellen

Summary Lymphocytes of the thymus can be protected against early pycnotic degeneration by several SH-compounds. Protective and non-protective SH-compounds induce the same reaction in the non-irradiated mouse, weight loss caused by cell migration, stimulation of the reticulum. A direct relationship between the activity of the reticulum and the radioresistance of lymphocytes was not found.     

α-Tocopherol reduces fluorescent age pigment levels in heart and brain of young mice

Summary The levels of fluorometrically measured lipofuscin, or age pigment, were significantly lower in the brain and the heart of -tocopherol (vitamin E)-injected mice as compared to untreated control mice at 3 and at 5 months of age.     

Cytoplasmic DNA of hepatoma tumor cells studied by3H-actinomycin D binding

Résumé L'ADN cytoplasmique d'hépatome fixe deux fois plus de³H-actinomycin D que le foie normal. Cette différence peut être expliquée soit par l'augmentation de l'ADN cytoplasmique du tumeur ou par l'augmentation de fixation de³H-actinomycin D à l'ADN du tumeur.     

Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment

The stress hormone-regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor-regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant-dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.     

Conservation of hotspots for recombination in low-copy repeats associated with the NF1 microdeletion

Several large-scale studies of human genetic variation have provided insights into processes such as recombination that have shaped human diversity. However, regions such as low-copy repeats (LCRs) have proven difficult to characterize, hindering efforts to understand the processes operating in these regions. We present a detailed study of genetic variation and underlying recombination processes in two copies of an LCR (NF1REPa and NF1REPc) on chromosome 17 involved in the generation of NF1 microdeletions and in a third copy (REP19) on chromosome 19 from which the others originated over 6.7 million years ago. We find evidence for shared hotspots of recombination among the LCRs. REP19 seems to contain hotspots in the same place as the nonallelic recombination hotspots in NF1REPa and NF1REPc. This apparent conservation of patterns of recombination hotspots in moderately diverged paralogous regions contrasts with recent evidence that these patterns are not conserved in less-diverged orthologous regions of chimpanzees.     

Soluble polysialylated NCAM: a novel player of the innate immune system in the lung

Posttranslational modification of the neural cell adhesion molecule (NCAM) by polysialic acid (polySia) is well studied in the nervous system and described as a dynamic modulator of plastic processes like precursor cell migration, axon fasciculation, and synaptic plasticity. Here, we describe a novel function of polysialylated NCAM (polySia-NCAM) in innate immunity of the lung. In mature lung tissue of healthy donors, polySia was exclusively attached to the transmembrane isoform NCAM-140 and located to intracellular compartments of epithelial cells. In patients with chronic obstructive pulmonary disease, however, increased polySia levels and processing of the NCAM carrier were observed. Processing of polysialylated NCAM was reproduced in a mouse model by bleomycin administration leading to an activation of the inflammasome and secretion of interleukin (IL)-1β. As shown in a cell culture model, polySia-NCAM-140 was kept in the late trans-Golgi apparatus of lung epithelial cells and stimulation by IL-1β or lipopolysaccharide induced metalloprotease-mediated ectodomain shedding, resulting in the secretion of soluble polySia-NCAM. Interestingly, polySia chains of secreted NCAM neutralized the cytotoxic activity of extracellular histones as well as DNA/histone-network-containing “neutrophil extracellular traps”, which are formed during invasion of microorganisms. Thus, shedding of polySia-NCAM by lung epithelial cells may provide a host-protective mechanism to reduce tissue damage during inflammatory processes.     

The synthesis of total and specific glycosaminoglycans during development of experimental liver cirrhosis

Summary During hepatic fibrogenesis induced by long-term administration of thioacetamide, the synthsis of chondroitin 4,6-sulfate and hyaluronic acid was strongly enhanced; the formation of heparan sulfate comprising at least 70% of total liver GAG synthesis and of a keratan-sulfate-like fraction was stimulated 1.7fold. Formation of dermatan-sulfate in liver could not be detected.We are grateful to Prof. W. Kühnel, Department of Anatomy, and to Prof. R. Lindenfelser, Department of Pathology, RWTH Aachen, for critical examination of the histology.     

Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humans

Fibrogenesis or scarring of the liver is a common consequence of all chronic liver diseases. Here we refine a quantitative trait locus that confers susceptibility to hepatic fibrosis by in silico mapping and show, using congenic mice and transgenesis with recombined artificial chromosomes, that the gene Hc (encoding complement factor C5) underlies this locus. Small molecule inhibitors of the C5a receptor had antifibrotic effects in vivo, and common haplotype-tagging polymorphisms of the human gene C5 were associated with advanced fibrosis in chronic hepatitis C virus infection. Thus, the mouse quantitative trait gene led to the identification of an unknown gene underlying human susceptibility to liver fibrosis, supporting the idea that C5 has a causal role in fibrogenesis across species.