Dynamics of the STAT3 Transcription Factor: Nuclear Import Dependent on Ran and Importin-β1

The signal transducer and activator of transcription-3 (STAT3) induces transcription of genes that control differentiation, inflammation, proliferation, and tumor cell invasion. Cytokines such as interleukin-6 and interferon stimulate the specific tyrosine phosphorylation of STAT3, which confers its ability to bind consensus DNA targets. In addition, unphosphorylated STAT3 has been demonstrated to induce specific gene expression. STAT3 must gain entrance to the nucleus to impact transcription, however access to the nucleus is a tightly regulated process. Because nuclear trafficking is critical to the function of STAT3, we investigated the molecular mechanisms by which STAT3 is imported to the nucleus. Live cell imaging techniques were used with STAT3 tagged with green fluorescence protein (GFP) or photoactivatable GFP to follow the cellular dynamics of both unphosphorylated and tyrosine phosphorylated forms. Cytokine activation did not alter the rate of STAT3 nuclear import or nuclear export. In addition, Förster resonance energy transfer experiments revealed homomeric interaction of unphosphorylated STAT3 dependent on its amino terminus, but this dimerization is not necessary for its nuclear import. Previous work demonstrated the adapter importin-α3 binds to STAT3 and is required for nuclear import. To determine whether STAT3 nuclear import is mediated by the importin-α/importin-β1 heterodimer, the effects of siRNA to importin-β1 were evaluated. Results indicate STAT3 nuclear import is dependent on the function of importin-β1. Since the Ran GTPase is necessary to bind importin-β1 in the nucleus for release of importin-α-cargo, the effect of a GTPase deficient mutant of Ran was tested. Expression of the Ran interfering mutant inhibited STAT3 nuclear import. This study defines importin-α/importin-β1/Ran as the molecular mechanism by which STAT3 traffics to the nucleus

Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis

AIM: To investigate gender-specific liver estrogen receptor (ER) expression in normal subjects and patients with hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC).METHODS: Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERa and ERB, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERa and ERB was further determined in nuclear and cytoplasmic tissue lysates along with the expression of inflammatory [activated NF-KB and IKB-kinase (IKK)] and oncogenic (cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERa and ERB was correlated with the expression of activated NF-KB, activated IKK and cyclin D1 by Spearman's correlation.RESULTS: Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERa than females (P < 0.05). We observed significantly higher mRNA expression of ERa in HCV-related HCC liver tissues as compared to normals (P < 0.05) and ERB in livers of HCV-related cirrhosis and HCV-related HCC subjects (P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERa in livers of HCV-related HCC patients and nuclear ERB in HCV-related cirrhosis patients as compared to normals (P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-KB and cyclin D1 in diseased livers (P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCV-infection may contribute to the progression of HCV-related cirrhosis to HCV-related HCC.CONCLUSION: Gender differences were observed in ERa expression in normal livers. Alterations in ER subtype expression observed in diseased livers may influence gender-related disparity in HCV-related pathogenesis.Peer reviewedBiochemistry and MicrobiologyHealth Care AdministrationStatistic

Some Comments on the Power-Law Dashpot Model for Creep in Wool Fibres

98-100<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "times="" new="" roman";mso-fareast-theme-font:minor-fareast;mso-hansi-theme-font:="" minor-latin;mso-bidi-font-family:"times="" roman";mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">The viscoelastic model comprising two springs and a dashpot connected in parallel is generally used to explain the creep behaviour of textile fibres. In the classical model, the dashpot liquid obeyed the Newtonian law. Later models incorporated a dashpot obeying either a hyperbolic sine law or a power law, both leading to creep equations containing four model constants. </span

Estimation of fibre maturity from micronaire value

335-341Cross-sectional perimeter, degree of thickening and micronaire values for 25 Indian cotton varieties covering the entire spectrum of fineness levels have been estimated. It is observed that for a given variety, the cross-sectional perimeter remains fairly constant irrespective of the degree of maturation. This leads to a direct relationship between the micronaire value and the degree of thickening which represents the true and botanical maturity for a given variety. It is also possible to pool the varieties having perimeter within a specified range and establish the relationship between micronaire value and degree of thickening for each perimeter range. The relationships linking the above two parameters variet y-wise as well as perimeterwise have been presented. Micronaire values for gradation of varieties into three categories, namely low, normal and high, have been indicated

Efficacy and safety of next-generation tick transcriptome-derived direct thrombin inhibitors

10.1038/s41467-021-27275-8Nature Communications12