170 research outputs found

    Towards a structural and functional understanding of the MIER1 co-repressor complex

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    Histone deacetylase enzymes (HDACs) are interesting as potential cancer drug targets because they are able to regulate the expression of genes by removing acetyl groups from lysine residues in histone tails, and are therefore linked to gene silencing. Altered gene expression and the formation of mutations encoding HDACs have been connected to the development of tumours as they both cause abnormal transcription of genes which control important cell functions like cell proliferation, cell-cycle regulation and cell death (apoptosis). Therefore, HDAC inhibitors are a fertile ground for investigation and research in the quest for more effective epigenetic anti-cancer drugs. MIER1 (mesoderm induction early response) which was previously known as er1 was first isolated as a fibroblast growth factor regulated gene in Xenopus lavis. The MIER family contains MIER1, 2 and 3. The function of MIER1 depends on its localization in the nucleus, however it contains no functioning NLS and so it relies on interaction and co-transport with HDAC1 and 2 for translocation to the nucleus. The MIER1 complex is one of the class I HDAC co-repressor complexes containing HDAC1 and part of BAHD1(Bromo adjacent homology domain containing protein 1). MIER1 regulates gene expression in fibroblast growth. However, the mechanism of how MIER1 recruits HDAC1 and BAHD1 has not been well characterised. The MIER1/HDAC1 complex has been successfully expressed using HEK293F suspension cells. The complex has been found to co-purify the endogenous H2A and H2B. Mapping experiments and NMR have demonstrated that MIER1 recruits H2A and H2B through its N-terminal region. It has also been determined that the BAH domain of BAHD1 can form a complex with MIER1/HDAC1. The structure of the MIER1 complex has been studied using negative stain electron microscopy and X-ray crystallography.</div

    Additional file 1 of Type 2 diabetes mellitus plays a protective role against osteoporosis --mendelian randomization analysis

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    Supporting Information: FIGURE S1 Funnel plots to the causal association of Type 2 diabetes mellitus on osteoporosis

    Additional file 3 of Characterization of fungal communities on shared bicycles in Southwest China

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    Additional file 3: Figure 3. Fungal alpha diversity of shared bicycles and nearby air. Chao 1 analysis (A), ACE analysis (B) (Chao 1 and ACE indices are positively correlated with the richness of the fungal community)

    Additional file 4 of Characterization of fungal communities on shared bicycles in Southwest China

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    Additional file 4: Figure 4. Fungal diversity comparison between shared bicycles and nearby air by t-tests at the species level (A-C). The top 12 significantly different species as confirmed by the MetaStat analysis (D)

    Additional file 1 of Characterization of fungal communities on shared bicycles in Southwest China

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    Additional file 1: Figure 1. Ternary plot of fungi among the three groups. (A: air, H: handle, S: saddle)

    Short Oligonucleotides Facilitate Co-transcriptional Labeling of RNA at Specific Positions

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    Labeling RNA molecules at specific positions is critical for RNA research and applications. Such methods are in high demand but still a challenge, especially those that enable native co-synthesis rather than post-synthesis labeling of long RNAs. The method we developed in this work meets these requirements, in which a leader RNA is extended on the hybrid solid–liquid phase by an engineered transcriptional complex following the pause–restart mode. A custom-designed short oligonucleotide is used to functionalize the engineered complex. This remarkable co-transcriptional labeling method incorporates labels into RNAs in high yields with great flexibility. We demonstrate the method by successfully introducing natural modifications, a fluorescent nucleotide analogue and a donor–acceptor fluorophore pair to specific sites located at an internal loop, a pseudoknot, a junction, a helix, and the middle of consecutive identical nucleotides of various RNAs. This newly developed method overcomes efficiency and position-choosing constraints that have hampered routine strategies to label RNAs beyond 200 nucleotides (nt)

    Additional file 5 of Characterization of fungal communities on shared bicycles in Southwest China

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    Additional file 5: Figure 5. Relative abundances of fungal trophic modes among the three groups

    Growth Mechanism and Properties of Nanostructure Cu<sub>2</sub>ZnSnSe<sub>4</sub> Thin Films and Solar Cells

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    The quality of the absorber layer is considerably important in thin-film solar cells. The precursor stacking with uniform distribution of metal elements is usually considered to be critical while preparing high-quality kesterite-structured thin-film solar cells. However, the Mo/Zn/Cu/Sn/Cu stacking order may be more reasonable after considering the growth mechanism of films. Herein, the growth mechanism and thus the solar cells prepared with these two stacking sequences Mo/Zn/Cu/Sn/Cu and Mo/Sn/Cu/Zn/Sn/Cu are studied in-depth. The cross-sectional images reveal that the Cu2ZnSnSe4 (CZTSe) film prepared with the precursor stacking order of Mo/Zn/Cu/Sn/Cu shows large grains without nanoscale small grains at the bottom of the film, which is attributed to a top-to-bottom growth mechanism. However, the CZTSe film prepared with the precursor stacking order Mo/Sn/Cu/Zn/Sn/Cu has a bilayer structure. The crystallization of CZTSe at the top of the film is good, but its crystallization at the bottom of the film is poor because the SnSe2 liquid phase that assists the growth of CZTSe grains is absent in the bottom layer. The difference in nanoscale morphology and the growth mechanism of CZTSe films is mainly due to the difference in the locations of Zn layers in the precursor films. Therefore, the best CZTSe solar cells have been fabricated with the selenized Mo/Zn/Cu/Sn/Cu films and exhibit an efficiency of 10.28%. Further development of a high-quality kesterite-structured thin film is expected based on the growth mechanism studied herein
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