Vascular Changes in Bleomycin-Induced Scleroderma

Systemic sclerosis (SSc) is characterized by vascular injury, immunological abnormalities, and fibrosis of the skin as well as various internal organs. Vascular impairment is the early manifestation and plays a fundamental role in the pathogenesis of SSc. Recent studies suggest that complex interactions among the endothelial cells, pericytes, smooth muscle cells, and fibroblasts are involved in the systemic vasculopathy in SSc, and histological feature of proliferation of vascular wall is seen in the lesional scleroderma skin at the late stage of disease. One of the most representative mouse models for scleroderma is the bleomycin-induced scleroderma; however, aspects of vascular alteration have not been described in detail so far. A number of studies have shown that bleomycin stimulates endothelial cells and fibroblasts to induce proinflammatory and fibrogenic cytokines, apoptosis, reactive oxygen species, and so on. This paper makes a focus on the vascular involvement in the bleomycin-induced murine scleroderma

A Subspace Identification of δ-Operator State-Space Model

This paper derives a subspace identification algorithm for a δ-operator state-space model by using the methods due to Moonen et al. [11], [12], [21]. Since the δ-operator model converges to a continuous-time model as the sampling interval goes to zero, the algorithm obtained is applicable to the identification of continuous-time medels. A method of computing the state vector from the block Hankel matrix is developed. Simulation studies show the present algorithm provides good results for the case of a low N/S ratio. Improvement of the algorithm for the case of a higher N/S ratio remains to be done

THE EXPRESSION OF THE fms GENE AND THE GENE PRODUCT IN THYROID TUMOR

The amplification of the fms gene DNA was investigated in 5 human thyroid tumors. No significant amplification or rearrangement was observed in tumor DNA. The expression of the fms gene product was also investigated in 20 thyroid tumor tissues embedded in paraffin using a polyclonal antibody to the fms oncogene product immunohistochemically. Ten out of 20 samples showed clearly positive, 6 out of 20 were weakly positive but 4 out of 20 were negative. Therefore, the fms oncogene might play an important role for thyroid carcinogenesis, and it might also be of possible importance for understanding the mechanism of thyroid carcinogenesis

Generation of a Mutant Mucor hiemalis Endoglycosidase That Acts on Core-fucosylated N-Glycans

Endo-β-N-acetylglucosaminidase M (Endo-M), an endoglycosidase from the fungus Mucor hiemalis, is a useful tool for chemoenzymatic synthesis of glycoconjugates, including glycoprotein-based therapeutics having a precisely defined glycoform, by virtue of its transglycosylation activity. Although Endo-M has been known to act on various N-glycans, it does not act on core-fucosylated N-glycans, which exist widely in mammalian glycoproteins, thus limiting its application. Therefore, we performed site-directed mutagenesis on Endo-M to isolate mutant enzymes that are able to act on mammalian-type core-α1,6-fucosylated glycans. Among the Endo-M mutant enzymes generated, those in which the tryptophan at position 251 was substituted with alanine or asparagine showed altered substrate specificities. Such mutant enzymes exhibited increased hydrolysis of a synthetic α1,6-fucosylated trimannosyl core structure, whereas their activity on the afucosylated form decreased. In addition, among the Trp-251 mutants, the W251N mutant was most efficient in hydrolyzing the core-fucosylated substrate. W251N mutants could act on the immunoglobulin G-derived core-fucosylated glycopeptides and human lactoferrin glycoproteins. This mutant was also capable of transferring the sialyl glycan from an activated substrate intermediate (sialyl glyco-oxazoline) onto an α1,6-fucosyl-N-acetylglucosaminyl biotin. Furthermore, the W251N mutant gained a glycosynthase-like activity when a N175Q substitution was introduced and it caused accumulation of the transglycosylation products. These findings not only give insights into the substrate recognition mechanism of glycoside hydrolase family 85 enzymes but also widen their scope of application in preparing homogeneous glycoforms of core-fucosylated glycoproteins for the production of potent glycoprotein-based therapeutics

Incorporation of cobalt into ZnO nanoclusters

The structural, optical and magnetic properties of nanostructured ZnO films co-doped with cobalt and aluminium have been studied. The nanocrystalline films, with cluster sizes in range 50 - 100 nm, were deposited by pulsed laser ablation in a mixed atmosphere of oxygen and helium. The nanocrystallites have the wurtzite structure and are highly oriented with the c-axis perpendicular to the substrate. Both optical and electron spin resonance (ESR) spectroscopy results show the substitutional incorporation of Co$^{2+}$ ions on the Zn site inside the ZnO nanoclusters. The temperature dependence of the ESR spectra follows Curie law corresponding to a paramagnetic material