Cellular localization of monoamine oxidase A and B in human tissues outside of the central nervous system

We studied the localization of monoamine oxidase (MAO) A and B in human heart, liver, duodenum, blood vessels and kidney by immunohistochemistry. The primary antibodies used were mouse monoclonal anti-human MAO-A (6G11/E1) and anti-human MAO-B (3F12/G10/2E3). Samples were obtained from six routine autopsy cases and fixed in 2% paraformaldehyde. All cardiomyocytes and hepatocytes showed MAO-A and MAO-B immunoreactivity. In the duodenum, both immunoreactivities were present in all cells of the villi, Lieberkühn crypts, muscularis mucosae and muscular layers, whereas Brunner glands were devoid of MAO-A and MAO-B staining. Endothelial cells of lymphatic vessels showed MAO-A but no MAO-B immunoreactivity, whereas arteries and veins presented MAO-A and MAO-B staining in muscular layers and fibroblasts but not in endothelial cells. In the kidney, renal tubuli showed MAO-A and MAO-B immunoreactivities, whereas collecting ducts and the Bowman's capsule showed only MAO-A staining. These data represent the first study of the cellular distribution of MAO-A and MAO-B in these human tissues. They show that both enzymes have a widespread distribution in the human body with a matching pattern in many, but not all tissues, and with strong differences from the pattern of distribution in rodents.     

NMR Structure Determination and Structure-Based Functional Characterization of Conserved Hypothetical Protein MTH1175 from Methanobacterium thermoautotrophicum

The solution structure of MTH1175, a 124-residue protein from the archaeon Methanobacterium thermoautotrophicum has been determined by NMR spectroscopy. MTH1175 is part of a family of conserved hypothetical proteins (COG1433) with unknown functions which contains multiple paralogs from all complete archaeal genomes and the archaeal gene-rich bacterium Thermotoga maritima. Sequence similarity indicates this protein family may be related to the nitrogen fixation proteins NifB and NifX. MTH1175 adopts an α/β topology with a single mixed β-sheet, and contains two flexible loops and an unstructured C-terminal tail. The fold resembles that of Ribonuclease H and similar proteins, but differs from these in several respects, and is not likely to have a nuclease activity. This revised version was published online in July 2006 with corrections to the Cover Date.     

Author Index, Volume 7

Authors Index

Author Index, Volume 7     

Soil phosphorus fractions and adsorption as affected by organic and inorganic sources

The effect of organic and inorganic sources of phosphorus (P) on soil P fractions and P adsorption was studied in a field without plant growth on a Kandiudalf in western Kenya. A high-quality organic source, Tithonia diversifolia (Hemsley) A. Gray leaves, and a low-quality source, maize (Zea mays L.) stover, were applied alone or in combination with triple superphosphate (TSP). The P rate was kept constant at 15 kg P ha^-1. Soil extractable P (resin, bicarbonate and sodium hydroxide), microbial biomass P and C and P adsorption isotherms were determined during 16 weeks after application of treatments. Application of tithonia either alone or with TSP increased resin P, bicarbonate P, microbial P, and sodium hydroxide inorganic P. Tithonia alone reduced P adsorption at 2–16 weeks. Maize stover had no effect on any of the P fractions or P adsorption. At 8 weeks, the application of tithonia reduced microbial C-to-P ratio (20) as compared to maize stover, TSP and the control (31–34). The reduction in P adsorption by tithonia was accompanied by increases in all measured P fractions, the sum of P in those fractions (resin, bicarbonate and sodium hydroxide) being larger than the P added. The reduction in P adsorption apparently resulted from competition for adsorption sites, probably by organic anions produced during decomposition of the high quality tithonia. Integration of inorganic P (TSP) with organic materials had little added benefit compared to sole application of TSP, except that combination of tithonia with TSP increased microbial biomass. The results indicate that a high quality organic input can be comparable to or more effective than inorganic P in increasing P availability in the soil.     

Design and synthesis of 4-[3,5-dioxo-11-oxa-4,9-diazatricyclo[5.3.1.02,6]undec-4-yl]-2-trifluoromethyl-benzonitriles as androgen receptor antagonists

A novel series of 4-[3,5-dioxo-11-oxa-4,9-diazatricyclo[5.3.1.0^2,6]undec-4-yl]-2-trifluoromethyl-benzonitriles has been synthesized. The ability of these compounds to act as antagonists of the androgen receptor was investigated and several were found to have potent activity in vitro and in vivo.     

Linkage mapping of powdery mildew and greenbug resistance genes on recombinant 1RS from 'Amigo' and 'Kavkaz' wheat-rye translocations of chromosome 1RS.1AL.

Cultivated rye (Secale cereale L., 2n = 2x = 14, RR) is an important source of genes for insect and disease resistance in wheat (Triticum aestivum L., 2n = 6x = 42). Rye chromosome arm 1RS of S. cereale 'Kavkaz' originally found as a 1BL.1RS translocation, carries genes for disease resistance (e.g., Lr26, Sr31, Yr9, and Pm8), while 1RS of the S. cereale 'Amigo' translocation (1RSA) carries a single resistance gene for greenbug (Schizaphis graminum Rondani) biotypes B and C and also carries additional disease-resistance genes. The purpose of this research was to identify individual plants that were recombinant in the homologous region of.1AL.1RSV and 1AL.1RSA using both molecular and phenotypic markers. Secale cereale 'Nekota' (1AL.1RSA) and S. cereale 'Pavon 76' (1AL.1RSV) were mated and the F1 was backcrossed to 'Nekota' (1AL.1AS) to generate eighty BC1F2:3 families (i.e., ('Nekota' 1AL.1RSA x 'Pavon 76' 1AL.1RSV) x 'Nekota' 1AL.1AS). These families were genotyped using the secalin-gliadin grain storage protein banding pattern generated with polyacrylamide gel electrophoresis to discriminate 1AL.1AS/1AL.1RS heterozygotes from the 1AL.1RSA+V and 1AL.1AS homozygotes. Segregation of the secalin locus and PCR markers based on the R173 family of rye specific repeated DNA sequences demonstrated the presence of recombinant 1AL.1RSA+V families. Powdery mildew (Blumeria graminis) and greenbug resistance genes on the recombinant 1RSA+V arm were mapped in relation to the Sec-1 locus, 2 additional protein bands, 3 SSRs, and 13 RFLP markers. The resultant linkage map of 1RS spanned 82.4 cM with marker order and spacing showing reasonable agreement with previous maps of 1RS. Fifteen markers lie within a region of 29.7 cM next to the centromere, yet corresponded to just 36% of the overall map length. The map position of the RFLP marker probe mwg68 was 10.9 cM distal to the Sec-1 locus and 7.8 cM proximal to the powdery mildew resistance locus. The greenbug resistance gene was located 2.7 cM proximal to the Sec-1 locus.     

Pharmacological Inhibition of FTO

In 2007, a genome wide association study identified a SNP in intron one of the gene encoding human FTO that was associated with increased body mass index. Homozygous risk allele carriers are on average three kg heavier than those homozygous for the protective allele. FTO is a DNA/RNA demethylase, however, how this function affects body weight, if at all, is unknown. Here we aimed to pharmacologically inhibit FTO to examine the effect of its demethylase function in vitro and in vivo as a first step in evaluating the therapeutic potential of FTO. We showed that IOX3, a known inhibitor of the HIF prolyl hydroxylases, decreased protein expression of FTO (in C2C12 cells) and reduced maximal respiration rate in vitro. However, FTO protein levels were not significantly altered by treatment of mice with IOX3 at 60 mg/kg every two days. This treatment did not affect body weight, or RER, but did significantly reduce bone mineral density and content and alter adipose tissue distribution. Future compounds designed to selectively inhibit FTO’s demethylase activity could be therapeutically useful for the treatment of obesity.