Differential inhibition of postnatal brain,spinal cord and body growth by a growth hormone antagonist

Background  

Growth hormone (GH) plays an incompletely understood role in the development of the central nervous system (CNS). In this study, we use transgenic mice expressing a growth hormone antagonist (GHA) to explore the role of GH in regulating postnatal brain, spinal cord and body growth into adulthood. The GHA transgene encodes a protein that inhibits the binding of GH to its receptor, specifically antagonizing the trophic effects of endogenous GH.     

Transfer measurements for the Ti+Ni systems at near barrier energies

Large enhancements have been observed in the sub-barrier fusion cross sections for Ti+Ni systems in our previous studies. Coupled channel calculations incorporating couplings to 2⁺ and 3⁻ states failed to explain these enhancements completely. A possibilty of transfer channels contributing to the residual enhancements had been suggested. In order to investigate the role of relevant transfer channels, measurements of one- and two-nucleon transfer were carried out for ^46,48Ti+⁶¹Ni systems. The present paper gives the results of these studies.     

Using FTIR spectroscopy to detect sericin on historic silk

Silks represent some of the most precious ancient and historic textile artefacts in collections worldwide.Their optimum preservation demands an appreciation of their characteristics.One important concern,especially with regard to ancient Chinese silks,is whether the fabrics have been degummed.Silks with remnant sericin gum coating the fibroin fibres would require different conservation protocol.In previous research on aged silks,the presence of sericin has been inferred from amino acid analysis of hydrolysa...     

Iron-catalyzed Doyle-Kirmse reaction of allyl sulfides with (trimethylsilyl)diazomethane

[formula: see text] Iron salts efficiently catalyze the Doyle-Kirmse reaction of allyl sulfides with (trimethylsilyl)diazomethane and ethyl diazoacetate in dichloroethane at 83 degrees C. Competitive dimerization is less of a problem with (trimethylsilyl)diazomethane than with ethyl diazoacetate. Good results are obtained using only 1.5 equiv of (trimethylsilyl)diazomethane, even without slow addition. Phosphine ligands affect the kinetics, but not the diastereoselectivity. Dppe and BINAP lead to higher yields than dppp, but no enantioselection was detected with R-(+)-BINAP.     

Suppression of nitric oxide production in mouse macrophages by soybean flavonoids accumulated in response to nitroprusside and fungal elicitation

Background

The anti-inflammatory properties of some flavonoids have been attributed to their ability to inhibit the production of NO by activated macrophages. Soybean cotyledons accumulate certain flavonoids following elicitation with an extract of the fungal pathogen Diaporthe phaseolorum f. sp. meridionalis (Dpm). Sodium nitroprusside (SNP), a nitric oxide donor, can substitute for Dpm in inducing flavonoid production. In this study, we investigated the effect of flavonoid-containing diffusates obtained from Dpm- and SNP-elicited soybean cotyledons on NO production by lipopolysaccharide (LPS)- and LPS plus interferon-γ (IFNγ)-activated murine macrophages.

Results

Significant inhibition of NO production, measured as nitrite formation, was observed when macrophages were activated in the presence of soybean diffusates from Dpm- or SNP-elicited cotyledons. This inhibition was dependent on the duration of exposure to the elicitor. Daidzein, genistein, luteolin and apigenin, the main flavonoids present in diffusates of elicited cotyledons, suppressed the NO production by LPS + IFNγ activated macrophages in a concentration-dependent manner, with IC₅₀ values of 81.4 μM, 34.5 μM, 38.6 μM and 10.4 μM respectively. For macrophages activated with LPS alone, the IC₅₀ values were 40.0 μM, 16.6 μM, 10.4 μM and 2.8 μM, respectively. Western blot analysis showed that iNOS expression was not affected by daidzein, was reduced by genistein, and was abolished by apigenin, luteolin and Dpm- and SNP-soybean diffusates at concentrations that significantly inhibited NO production by activated macrophages.

Conclusions

These results suggest that the suppressive effect of flavonoids on iNOS expression could account for the potent inhibitory effect of Dpm- and SNP-diffusates on NO production by activated macrophages. Since the physiological concentration of flavonoids in plants is normally low, the treatment of soybean tissues with SNP may provide a simple method for substantially increasing the concentration of metabolites that are beneficial for the treatment of chronic inflammatory diseases associated with NO production.

     

Homology modeling of a human glycine alpha 1 receptor reveals a plausible anesthetic binding site

The superfamily of ligand-gated ion channels (LGICs) has been implicated in anesthetic and alcohol responses. Mutations within glycine and GABA receptors have demonstrated that possible sites of anesthetic action exist within the transmembrane subunits of these receptors. The exact molecular arrangement of this transmembrane region remains at intermediate resolution with current experimental techniques. Homology modeling methods were therefore combined with experimental data to produce a more exact model of this region. A consensus from multiple bioinformatics techniques predicted the topology within the transmembrane domain of a glycine alpha one receptor (GlyRa1) to be alpha helical. This fold information was combined with sequence information using the SeqFold algorithm to search for modeling templates. Independently, the FoldMiner algorithm was used to search for templates that had structural folds similar to published coordinates of the homologous nAChR (1OED). Both SeqFold and Foldminer identified the same modeling template. The GlyRa1 sequence was aligned with this template using multiple scoring criteria. Refinement of the alignment closed gaps to produce agreement with labeling studies carried out on the homologous receptors of the superfamily. Structural assignment and refinement was achieved using Modeler. The final structure demonstrated a cavity within the core of a four-helix bundle. Residues known to be involved in modulating anesthetic potency converge on and line this cavity. This suggests that the binding sites for volatile anesthetics in the LGICs are the cavities formed within the core of transmembrane four-helix bundles.