Hormonal control of C. elegans dauer formation and life span by a Rieske-like oxygenase

C. elegans diapause, gonadal outgrowth, and life span are regulated by a lipophilic hormone, which serves as a ligand to the nuclear hormone receptor DAF-12. A key step in hormone production is catalyzed by the CYP450 DAF-9, but the extent of the biosynthetic pathway is unknown. Here, we identify a conserved Rieske-like oxygenase, DAF-36, as a component in hormone metabolism. Mutants display larval developmental and adult aging phenotypes, as well as patterns of epistasis similar to that of daf-9. Larval phenotypes are potently reversed by crude lipid extracts, 7-dehydrocholesterol, and a recently identified DAF-12 sterol ligand, suggesting that DAF-36 works early in the hormone biosynthetic pathway. DAF-36 is expressed primarily within the intestine, a major organ of metabolic and endocrine control, distinct from DAF-9. These results imply that C. elegans hormone production has multiple steps and is distributed, and that it may provide one way that tissues register their current physiological state during organismal commitments.     

Fusion of cultured dog kidney (MDCK) cells: I. Technique,fate of plasma membranes and of cell nuclei

Summary The evaluation of the intracellular signal train and its regulatory function in controlling transepithelial transport with electrophysiological methods often requires intracellular measurements with microelectrodes. However, multiple impalements in epithelial cells are hampered by the small size of the cells. In an attempt to avoid these problems we fused cells of an established cell line, Madin Darby canine kidney cells, originally derived from dog kidney, to giant cells by applying a modified polyethylene glycol method. During trypsin-induced detachment from the ground of the petri dish, individual cells grown in a monolayer incorporate volume and mainly lose basolateral plasma membrane by extrusion. By isovolumetric cell-to-cell fusion, spherical giant cells are formed within 2 hr. During this process a major part of the individual cell plasma membranes is internalized. Over three weeks following cell plasma membrane fusion degradation of single cell nuclei and cell nuclear fusion occurs. We conclude that this experimental approach opens the possibility to investigate ion transport of epithelia in culture by somatic cell genetic techniques.     

New energetic materials: Synthesis and characterization of copper 5-nitriminotetrazolates

The energetic compounds 5-nitriminotetrazole (H₂AtNO₂, 1), 1-methyl-5-nitriminotetrazole (1MeHAtNO₂, 2) and 2-methyl-5-nitraminotetrazole (2MeHAtNO₂, 3), were reacted with Cu(NO₃)₂ · 3H₂O and CuCl₂ · 2H₂O, respectively, in water as well as in aqueous ammonia solution. The syntheses yielded the complexes [Cu(HAtNO₂)₂(H₂O)₄] (4), [Cu(AtNO₂)(NH₃)₃]₂ (5), (NH₄)₂[Cu(AtNO₂)₂(H₂O)₂] (6), [Cu(1MeAtNO₂)₂(NH₃)₂] (7), [Cu(2-MeAtNO₂)₂(2-MeHAtNO₂)₂] (8), [Cu(2MeAtNO₂)₂]_∞ (9), [Cu(2-MeAtNO₂)₂(NH₃)₂] (10), and [Cu(2MeAtNO₂)₂(NH₃)₄] · H₂O (11). All complexes were characterized using low temperature single crystal X-ray diffraction, IR spectroscopy, elemental analysis, and differential scanning calorimetry. The magnetic properties of six of the complexes were investigated. Due to the energetic characters, the sensitivities towards impact and friction were investigated using the BAM drophammer and friction tester. The values range from “very sensitive”, comparable to primary explosives, to “insensitive” depending on the amount of water or ammonia coordinated. Since Cu(II) salts can be used for colorants in pyrotechnics, the combustions and flame colors were discovered to be intensively green.     

Changes in macromolecule syntheses under special consideration of UNA and the energy providing system in imbibing embryos of different agedagrostemma githago L. Seeds

Changes in macromolecule syntheses, especially RNA synthesis, and the energy providing system were investigated in seeds ofAgrostemma githago aged for different periods. In embryos of aged seeds all macromolecule syntheses start later and reach a lower level than young ones. It was found that the synthesis of rRNA in embryos of aged seeds is reduced whereas the synthesis of poly (A⁺) RNA in relation to the total RNA synthesis is highly increased as well as the amount of this RNA species with long poly (A) chains. The results are discussed in connection with the decreased protein synthesis and the reduced ATP content and ATP formation ability in embryos during the long time storage of seeds.     

Effects of dietary supplementation of nickel and nickel-zinc on femoral bone structure in rabbits

Background  

Nickel (Ni) and zinc (Zn) are trace elements present at low concentrations in agroecosystems. Nickel, however, may have toxic effects on living organisms and is often considered as a contaminant. This study reports the effect of peroral administrated Ni or a combination of Ni and Zn on femoral bone structure in rabbits.     

Imbricaric Acid and Perlatolic Acid: Multi-Targeting Anti-Inflammatory Depsides from Cetrelia monachorum

In vitro screening of 17 Alpine lichen species for their inhibitory activity against 5-lipoxygenase, microsomal prostaglandin E₂ synthase-1 and nuclear factor kappa B revealed Cetrelia monachorum (Zahlbr.) W.L. Culb. & C.F. Culb. As conceivable source for novel anti-inflammatory compounds. Phytochemical investigation of the ethanolic crude extract resulted in the isolation and identification of 11 constituents, belonging to depsides and derivatives of orsellinic acid, olivetolic acid and olivetol. The two depsides imbricaric acid (4) and perlatolic acid (5) approved dual inhibitory activities on microsomal prostaglandin E₂ synthase-1 (IC₅₀ = 1.9 and 0.4 µM, resp.) and on 5-lipoxygenase tested in a cell-based assay (IC₅₀ = 5.3 and 1.8 µM, resp.) and on purified enzyme (IC₅₀ = 3.5 and 0.4 µM, resp.). Additionally, these two main constituents quantified in the extract with 15.22% (4) and 9.10% (5) showed significant inhibition of tumor necrosis factor alpha-induced nuclear factor kappa B activation in luciferase reporter cells with IC₅₀ values of 2.0 and 7.0 µM, respectively. In a murine in vivo model of inflammation, 5 impaired the inflammatory, thioglycollate-induced recruitment of leukocytes to the peritoneum. The potent inhibitory effects on the three identified targets attest 4 and 5 a pronounced multi-target anti-inflammatory profile which warrants further investigation on their pharmacokinetics and in vivo efficacy.     

Discovery of a novel class of biphenyl pyrazole sodium channel blockers for treatment of neuropathic pain

A series of novel biphenyl pyrazole dicarboxamides were identified as potential sodium channel blockers for treatment of neuropathic pain. Compound 20 had outstanding efficacy in the Chung rat spinal nerve ligation (SNL) model of neuropathic pain.