Members of the myocyte enhancer factor-2 (MEF2) family of transcription factors associate with myogenic basic helix-loop-helix transcription factors such as MyoD to activate skeletal myogenesis. MEF2 proteins also interact with the class II histone deacetylases HDAC4 and HDAC5, resulting in repression of MEF2-dependent genes. Execution of the muscle differentiation program requires release of MEF2 from repression by HDACs, which are expressed constitutively in myoblasts and myotubes. Here we show that HDAC5 shuttles from the nucleus to the cytoplasm when myoblasts are triggered to differentiate. Calcium/calmodulin-dependent protein kinase (CaMK) signalling, which stimulates myogenesis and prevents formation of MEF2-HDAC complexes, also induces nuclear export of HDAC4 and HDAC5 by phosphorylation of these transcriptional repressors. An HDAC5 mutant lacking two CaMK phosphorylation sites is resistant to CaMK-mediated nuclear export and acts as a dominant inhibitor of skeletal myogenesis, whereas a cytoplasmic HDAC5 mutant is unable to block efficiently the muscle differentiation program. Our results highlight a mechanism for transcriptional regulation through signal- and differentiation-dependent nuclear export of a chromatin-remodelling enzyme, and suggest that nucleo-cytoplasmic trafficking of HDACs is involved in the control of cellular differentiation.
Due to their unique electronic and optoelectronic properties, tin selenide nanostructures show great promise for applications in energy storage and photovoltaic devices. Despite the great progress that has been achieved, the phase-controlled synthesis of two-dimensional (2D) tin selenide nanostructures remains a challenge, and their use in supercapacitors has not been explored. In this paper, 2D tin selenide nanostructures, including pure SnSe2 nanodisks (NDs), mixed-phase SnSe-SnSe2 NDs, and pure SnSe nanosheets (NSs), have been synthesized by reacting SnCl2 and trioctylphosphine (TOP)-Se with borane-tert-butylamine complex (BTBC) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone. Utilizing the interplay of TOP and BTBC and changing only the amount of BTBC, the phase-controlled synthesis of 2D tin selenide nanostructures is realized for the first time. Phase-dependent pseudocapacitive behavior is observed for the resulting 2D nanostructures. The specific capacitances of pure SnSe2 NDs (168 F g(-1)) and SnSe NSs (228 F g(-1)) are much higher than those of other reported materials (e.g., graphene-Mn3O4 nanorods and TiN mesoporous spheres); thus, these tin selenide materials were used to fabricate flexible, all-solid-state supercapacitors. Devices fabricated with these two tin selenide materials exhibited high areal capacitances, good cycling stabilities, excellent flexibilities, and desirable mechanical stabilities, which were comparable to or better than those reported recently for other solid-state devices based on graphene and 3D GeSe2 nanostructures. Additionally, the rate capability of the SnSe2 NDs device was much better than that of the SnSe NS device, indicating that SnSe2 NDs are promising active materials for use in high-performance, flexible, all-solid-state supercapacitors.
We present a density matrix approach for treating systems with a large or infinite number of degrees of freedom per site with exact diagonalization or the density matrix renormalization group. The method is demonstrated on the 1D Holstein model of electrons coupled to Einstein phonons. In this system, two or three optimized phonon modes per site give results as accurate as with 10-100 bare phonon levels per site.
Keywords Discogenic low back pain AE High-intensity zone AE Lumbar intervertebral disc AE Discography Eur Spine J (2006) 15: 583-587
A rat model of common bile duct ligation (BDL)-induced hepatic fibrosis was used to assess the expression and activities of collagen-degrading proteinases and their inhibitors during the progression of fibrosis. Expression of four members of the matrix metalloproteinase (MMP) family (MMP-2/gelatinase A, MMP-3, MMP-9/gelatinase B, and MMP-13) and three tissue inhibitors of metalloproteinases-1, -2, and -3 (TIMP-1, TIMP-2, and TIMP-3) were evaluated by Northern blot analysis of RNA from liver tissue isolated at 0, 2, 5, 10, 20, and 30 days after either a BDL or sham operation. In addition, we analyzed free gelatinase and TIMP activities by zymography and reverse zymography, respectively. We found that the proteolytic activities of MMP-2 and MMP-9 increased by 2 days after ligation, reached maximal levels at day 10, and remained high through the study period, whereas the gelatinolytic activities in plasma were unchanged. The increase in gelatinase activities was accompanied by an increase in the TIMP mRNA transcripts. TIMP-1 transcripts appeared at day 2, increased until day 10, and remained elevated throughout the study period. TIMP-2 and TIMP-3 transcripts become detectable on day 10 and remained stable afterwards. No corresponding increase in TIMP protein activity was detected by reverse zymography. This appears to result from the formation of TIMP/MMP complexes. These findings indicate a likely surplus in the BDL model of fibrosis of free gelatinases as compared with the TIMPs. Thus, excessive TIMP production is not a sufficient explanation for the observed extracellular matrix accumulation, but complex changes in the local MMP/TIMP balance may underlie the pathomechanisms of fibrosis.
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