A high concentration of genistein down-regulates activin A, Smad3 and other TGF-β pathway genes in human uterine leiomyoma cells

Previously, we found that high doses of genistein show an inhibitory effect on uterine leiomyoma (UtLM) cell proliferation. In this study, using microarray analysis and Ingenuity Pathways Analysis™, we identified genes (up- or down-regulated, ≥ 1.5 fold, P ≤ 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 µg/ml) in UtLM cells. Downregulation of TGF-β signaling pathway genes, activin A, activin B, Smad3, TGF-β2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time RT-PCR studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitory effect of genistein was partially abrogated in the presence of activin A. Overexpression of activin A and Smad3 were found in tissue samples of leiomyoma compared to matched myometrium, supporting the contribution of activin A and Smad3 in promoting the growth of UtLM cells. Taken together, these results suggest that down-regulation of activin A and Smad3, both members of the TGF-β pathway, may offer a mechanistic explanation for the inhibitory effect of a high-dose of genistein on UtLM cells, and might be potential therapeutic targets for treatment of clinical cases of uterine leiomyomas.     

Polymer Intermediates and Polymers Derived from 5-t-Butyl-m-Xylene

Abstract

A series of condensation polymer intermediates, which included several new compositions, was prepared from 5-t-butyl-m-xylene (I) so that the effect of the bulky t-butyl group on polymer properties could be determined. Compound (I) was oxidized with nitric acid to obtain 5-t-butyl-isophthalic acid (II), which was converted successively to the diacid chloride, the diamide, the dinitrile, and finally to 5-t-butyl-m-xylene-α,α′-diamine (VI); the overall yield was 80%. The dimethyl ester of (II) was prepared and converted to 5-t-butyl-m-xylene-α,α′-diol (VIII), a new composition, in 79.5% overall yield; the diphenyl ester was also prepared. The sodium salt of (II) was catalytically reduced to obtain 5-t-butyl-1,3-cyclohexanedicarboxylic acid (IIa) in 95% yield. (IIa) was converted successively to the diacid chloride, the diamide, the dinitrile, and finally to 5-t-butyl-1,3-cyclohexanebis(methylamine) (VIa), a new composition; the overall yield was 37%. (IIa) was also converted to the dimethyl ester and finally to 5-t-butyl-1,3-cyclohexanedimethanol (VIIIa), a new composition; the overall yield was 64%. Condensation polymers were prepared from the intermediates (II), (IIa), (VI), (VIa), (VIII), and (VIIIa). These polymers had higher glass transition temperatures (T_g) than corresponding polymers containing no t-butyl groups. This general effect of the t-butyl group to increase the T_g value of the polymer was noted in all polymers prepared, regardless of whether the intermediate carrying the t-butyl group was a diacid, a diol, or a diamine, or whether the polymer was a polyamide, a polyester, or a polyurethane.     

Superconductive tunneling into niobium-tin thin films

Oxide-layer tunnel junctions exhibiting both quasi-particle and Josephson tunneling were produced by overlaying lead on niobium-tin thin films. The superconducting transition temperature and average energy gap of the Nb-Sn both increased as the tin concentration was increased toward Nb₃Sn and reached maximum values of 17.2 K and 3.2 meV, respectively, or 2Δ = 4.3 kT_c.     

Factors affecting the loudness of modulated sounds.

Loudness matches were obtained between unmodulated carriers and carriers that were amplitude modulated either periodically (rates between 2 and 32 Hz, modulation sinusoidal either on a linear amplitude scale or on a dB scale; the latter is called dB modulation) or with the envelope of the speech of a single talker. The carrier was a 4-kHz sinusoid, white noise, or speech-shaped noise. Both normally hearing subjects and subjects with cochlear hearing loss were tested. Results were expressed as the root-mean-square (rms) level of the modulated carrier minus the level of the unmodulated carrier at the point of equal loudness. If this difference is positive, this indicates that the modulated carrier has a higher rms level at the point of equal loudness. For normally hearing subjects, the results show: (1) For a 4000-Hz sinusoidal carrier, the difference was slightly positive (averaging about 0.7 dB). There was no significant effect of modulation rate or level over the range 20-80 dB SL. (2) For a speech-shaped noise or white noise carrier, the difference was close to zero, although for large modulation depths it tended to be negative. There was no clear effect of level (over the range 35-75 dB SPL) or modulation rate. For the hearing-impaired subjects, the differences were small, but tended to be slightly negative for both the 4000-Hz carrier and the noise carriers, when the modulation rate was above 2 Hz. Again, there was no clear effect of overall level. However, for dB modulation, the differences became more negative with increasing modulation depth. For modulation rates in the range 4-32 Hz, the results could be fitted reasonably well using the assumption that the loudness of modulated sounds is based on the rms value of the time-varying intensity of the response of the basilar membrane (taking into account the compression that occurs in the normal cochlea). The implications of the results for the fitting of multi-band compression hearing aids and for the design of loudness meters are discussed.     

Some theorems on graphs and posets

In this journal, Leclerc proved that the dimension of the partially ordered set consisting of all subtrees of a tree T, ordered by inclusion, is the number of end points of T. Leclerc posed the problem of determining the dimension of the partially ordered set P consisting of all induced connected subgraphs of a connected graph G for which P is a lattice.In this paper, we prove that the poset P consisting of all induced connected subgraphs of a nontrivial connected graph G, partially ordered by inclusion, has dimension n where n is the number of noncut vertices in G whether or not P is a lattice. We also determine the dimension of the distributive lattice of all subgraphs of a graph.