A single-atom-sized gold wire was successfully observed in real time by a newly developed defocus-image modulation processing electron microscope. Because of phase retrieval processing with spherical aberration correction, the single-atom strand wire was observed with high contrast and without contrast blurring. By carefully looking at the atomic distance, the contrast, and the dynamic behavior of the wire, we recognized that there are two stages of the wire. In the first stage the wire maintained the atomic distance in the bulk crystal, but in the second stage the wire showed the atomic distance of the nearest-neighbor atoms with weaker contrast. The gold wire was rather stable for a few seconds under strong electron beam illumination.
Studies on the inhibitory mechanism of acetogenins, the most potent inhibitors of mitochondrial complex I (NADH-ubiquinone oxidoreductase), are useful for elucidating the structural and functional features of the terminal electron transfer step of this enzyme. Previous studies of the structure-activity relationship revealed that except for the alkyl spacer linking the two toxophores (i.e., the hydroxylated THF and the gamma-lactone rings), none of the multiple functional groups of these inhibitors is essential for potent inhibition. To elucidate the function of the alkyl spacer, two sets of systematically selected analogues were synthesized. First, the length of the spacer was varied widely. Second, the local flexibility of the spacer was specifically reduced by introducing multiple bond(s) into different regions of the spacer. The optimal length of the spacer for inhibition was approximately 13 carbon atoms. The decrease in the strength of the inhibitory effect caused by elongating the spacer from 13 carbons was much more drastic than that caused by shortening. Local flexibility in a specific region of the spacer was not important for the inhibition. These observations indicate that the active conformation of the spacer is not an extended form, and is not necessarily restricted to a certain rigid shape. Moreover, an analogue in which a spacer covering 10 carbon atoms was hardened into a rodlike shape still maintained a potent inhibitory effect. Our results strongly suggest that the spacer portion is free from steric congestion arising from the putative binding site probably because there is no cavity-like binding site for the spacer portion. The manner of acetogenin binding to the enzyme may not be explained by a simple "key and keyhole" analogy.
Herein, we designed chiral photoresponsive tetra(2-phenylthiazole)s, which induce a diastereoselective 6π-electrocyclization reaction in a helically folded structure to freeze the conformational interconversions. The folding conformation with one helical turn of tetra(2-phenylthiazole)s was supported by multiple intramolecular noncovalent interactions including vicinal S···N interheteroatom interactions and CH-π and π-π stacking interactions between nonadjacent units, as found in X-ray crystal structures as well as quantum chemical calculations. The introduction of a chiral group at both ends of tetra(2-phenylthiazole) dictates the preferential folding into a one-handed helix conformation by the simultaneous operation of S···O and multiple CH-π interactions that involve the chiral end groups. Since the tetra(2-phenylthiazole)s possess two equivalent photoreactive 6π-electron systems and the folded conformation is suitable for photoinduced electrocyclization reaction, they undergo a photocyclization reaction in a stereoselective manner to memorize the chirality of the helix in a resulting diastereomeric closed form.
Objective. The aim of this study was to investigate the prognostic value of MicroRNA-210 (miR-210) expression in patients with non-small-cell lung cancer (NSCLC). Methods. We examined the miR-210 expression of samples of 80 patients, who underwent surgical resection at Fukushima Medical University from 2004 to 2007, by using quantitative RT-PCR. The relationship between miR-210 expression and clinicopathological factors as well as histological subtype was statistically analyzed. Results. miR-210 expression showed an inverse correlation with disease-free and overall survival in patients with NSCLC. Significant correlations were found between miR-210 expression and lymph node metastasis, late disease stages, and poor prognosis in patients with adenocarcinoma. Multivariate Cox analysis indicated that miR-210 expression was an independent prognostic factor for disease-free survival in patients with adenocarcinoma. Conclusions. We showed that miR-210 may be a prognostic biomarker for patients with NSCLC, especially for those with lung adenocarcinoma.
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