Common pathway for the ubiquitination of IkappaBalpha, IkappaBbeta, and IkappaBepsilon mediated by the F-box protein FWD1.

FWD1 (the mouse homolog of Drosophila Slimb and Xenopus betaTrCP, a member of the F-box- and WD40 repeat-containing family of proteins, and a component of the SCF ubiquitin ligase complex) was recently shown to interact with IkappaBalpha and thereby to promote its ubiquitination and degradation. This protein has now been shown also to bind to IkappaBbeta and IkappaBepsilon as well as to induce their ubiquitination and proteolysis. FWD1 was shown to recognize the conserved DSGPsiXS motif (where Psi represents the hydrophobic residue) present in the NH(2)-terminal regions of these three IkappaB proteins only when the component serine residues are phosphorylated. However, in contrast to IkappaBalpha and IkappaBbeta, the recognition site in IkappaBepsilon for FWD1 is not restricted to the DSGPsiXS motif; FWD1 also interacts with other sites in the NH(2)-terminal region of IkappaBepsilon. Substitution of the critical serine residues in the NH(2)-terminal regions of IkappaBalpha, IkappaBbeta, and IkappaBepsilon with alanines also markedly reduced the extent of FWD1-mediated ubiquitination of these proteins and increased their stability. These data indicate that the three IkappaB proteins, despite their substantial structural and functional differences, all undergo ubiquitination mediated by the SCF(FWD1) complex. FWD1 may thus play an important role in NF-kappaB signal transduction through regulation of the stability of multiple IkappaB proteins.     

A novel oncostatin M-inducible gene OIG37 forms a gene family with MyD118 and GADD45 and negatively regulates cell growth.

Oncostatin M (OSM) is a member of the IL-6 family cytokines that use gp130 as a common signal transducer and exhibits both growth stimulatory as well as growth inhibitory activity depending on the cells. To analyze the mechanism of OSM function, we isolated immediate early responsive genes upon OSM stimulation. Here we describe the novel OSM-inducible gene OIG37 that is related to MyD118 and GADD45. The MyD118 gene has been described as an immediate early gene induced by IL-6 in M1 monocytic cells, and GADD45 was identified as a gene induced by UV or gamma-ray irradiation. Both are considered to function in growth arrest and/or DNA repair. Although the expression of OIG37, MyD118, and GADD45 was rather ubiquitous, it was differentially regulated. As the gp130 mutant defective for activating the STAT3 pathway showed the reduced induction of OIG37 by cytokine stimulation and expression of dominant negative STAT3 inhibited the induction of OIG37 by OSM, STAT3 is involved in OIG37 induction by IL-6 family cytokines. To examine the function of OIG37, we expressed it in NIH3T3 and IL-3-dependent BaF3 cells and found that OIG37 suppressed cell growth without any evidence of apoptosis. Whereas both MyD118 and OIG37 suppressed cell growth in both cell lines, suppression by OIG37 was more efficient than by MyD118. Immunoprecipitation experiments indicated that OIG37 associates with p21, a cyclin-dependent kinase inhibitor, and proliferating cell nuclear antigen.     

Suppression of Heme Oxygenase-1 mRNA Expression by Interferon-γ in Human Glioblastoma Cells

Heme oxygenase is a rate-limiting enzyme in heme catabolism that cleaves heme to form biliverdin, carbon monoxide, and iron. Heme oxygenase-1 is an inducible isozyme and is expressed in many types of cells and tissues. Large amounts of these heme degradation products may be noxious to the host, especially in the brain. We therefore searched for the factors that suppress the expression of heme oxygenase-1. Northern blot analysis showed that treatment with interferon-gamma and with interleukin-1beta for 24 h decreased the expression levels of heme oxygenase-1 mRNA to approximately 20 and approximately 50% of the control levels, respectively, in a human glioblastoma cell line, T98G. Treatment with a combination of these two cytokines additively decreased the expression levels of heme oxygenase-1 mRNA. Western blot analysis showed that the expression level of heme oxygenase-1 protein was also decreased by treatment with interferon-gamma, but not with interleukin-1beta. Moreover, pretreatment with interferon-gamma partially suppressed the induction of heme oxygenase-1 mRNA expression caused by either sodium nitroprusside, cadmium, or hemin. These findings raise the possibility that the expression of heme oxygenase-1 is down-regulated by interferon-gamma in the nervous system.     

Possible role of xanthobaccins produced by Stenotrophomonas sp. strain SB-K88 in suppression of sugar beet damping-off disease.

Three antifungal compounds, designated xanthobaccins A, B, and C, were isolated from the culture fluid of Stenotrophomonas sp. strain SB-K88, a rhizobacterium of sugar beet that suppresses damping-off disease. Production of xanthobaccin A in culture media was compared with the disease suppression activities of strain SB-K88 and less suppressive strains that were obtained by subculturing. Strain SB-K88 was applied to sugar beet seeds, and production of xanthobaccin A in the rhizosphere of seedlings was confirmed by using a test tube culture system under hydroponic culture conditions; 3 microg of xanthobaccin A was detected in the rhizosphere on a per-plant basis. Direct application of purified xanthobaccin A to seeds suppressed damping-off disease in soil naturally infested by Pythium spp. We suggest that xanthobaccin A produced by strain SB-K88 plays a key role in suppression of sugar beet damping-off disease.     

A simple technique for experimental hepatic vein catheterization in swine

Hepatic vein catheterization is a valuable technique in studies of hepatic physiology and metabolism. A new technique for hepatic vein catheterization in swine is described which avoids fluoroscopy, incision, or puncture of the hepatic parenchyma. Experience with this new technique in over 40 studies of young pigs has confirmed the reliability of the technique. Management of hepatic vein catheters after insertion and potential sources of error in hepatic venous sampling are discussed.     

Ultrasound-Derived Abdominal Muscle Thickness Better Detects Metabolic Syndrome Risk in Obese Patients than Skeletal Muscle Index Measured by Dual-Energy X-Ray Absorptiometry

Sarcopenia has never been diagnosed based on site-specific muscle loss, and little is known about the relationship between site-specific muscle loss and metabolic syndrome (MetS) risk factors. To this end, this cross-sectional study aimed to investigate the relationship between site-specific muscle size and MetS risk factors. Subjects were 38 obese men and women aged 40–82 years. Total body fat and lean body mass were assessed by whole-body dual-energy X-ray absorptiometry (DXA) scan. Muscle thickness (MTH) was measured using B-mode ultrasound scanning in six body regions. Subjects were classified into general obesity (GO) and sarcopenic obesity (SO) groups using the threshold values of one standard deviation below the sex-specific means of either MTH or skeletal muscle index (SMI) measured by DXA. MetS risk score was acquired by standardizing and summing the following continuously distributed variables: visceral fat area, mean blood pressure, HbA1c, and serum triglyceride / high density lipoprotein cholesterol, to obtain the Z-score. Multiple regression analysis revealed that the MetS risk score was independently associated with abdominal MTH in all subjects, but not with MTH in other muscle regions, including the thigh. Although HbA1c and the number of MetS risk factors in the SO group were significantly higher than those in the GO group, there were no significant differences between GO and SO groups as defined by SMI. Ultrasound-derived abdominal MTH would allow a better assessment of sarcopenia in obese patients and can be used as an alternative to the conventionally-used SMI measured by DXA.     

Socio-ecological analysis of desertification in the Mu-Us Sandy Land with satellite remote sensing

To understand the contemporary process of desertification in the Mu-Us Sandy Land, China, we assessed the current status of desertification from satellite images. We analyzed the effect of land use by comparing desertification images and GIS-based thematic data. Socioeconomic factors were studied through interviews with local people. The desertified area ratio in each village was related to the sand dune ratio. Desertification in this region was affected by the activity of sand dunes. The revegetated area ratio had a close relationship with the cropland ratio. The development of cropland and surrounding woods contributed to revegetation of desertified land. Desertified areas were distributed mainly in pastoral regions. Critical carrying capacity of grassland for sheep and goats was approximately 2 head/ha. High population density of goats was evident in the severely desertified ranges. Goats were increasingly introduced to earn money through modernization, but they overgrazed fenced pastures. Further environmental education is needed to promote sustainable land use.