Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences
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    Deactivation of Mcl-1 by Dual-Function Small-Molecule Inhibitors Targeting the Bcl-2 Homology 3 Domain and Facilitating Mcl-1 Ubiquitination

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    By means of limited proteolysis assay, three-dimensional NMR, X-ray crystallography and alanine mutations, a dynamic region at the Q221R222N223 motif in the Bcl-2 homology 3 (BH3) domain of Mcl-1 has been identified as a conformational switch which controls Mcl-1 ubiquitination. Noxa(BH3) binding biases the QRN motif toward a helical conformation, thus leading to an enhanced in vitro ubiquitination of Mcl-1. In contrast, Bim(BH3) binding biases the QRN motif toward a nonhelical conformation, thus leading to the inhibition of ubiquitination. A dual function Mcl-1 inhibitor, which locates at the (BH3) domain of Mcl-1 and forms hydrogen bond with His224 to drive a helical QRN conformation, so that it not only interferes with the pro-apoptotic partners, but also facilitates Mcl-1 ubiquitination in living cells, is described. As a result, this inhibitor manifests a more effective apoptosis induction in Mcl-1-dependent cancer cells than other inhibitors exhibiting a similar binding affinity with it

    Benzodithiophene-Based Polymers Containing Alkylthiophenyl Side Chains with Lowered HOMO Energy Levels for Organic Solar Cells

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    In this paper, a novel donor based on alkylthiophenyl side-chained benzodithiophene (BDT) (M1) was first designed and synthesized to construct a series of conjugated polymers (P1, P2, P3) used in polymer solar cells (PSCs). P1, P2, and P3 were prepared by copolymerizing M1 with 4,7-di(4-(2-ethylhexyl)-2-thienyl)-2,1,3-benzothiadiazole (DTBT), quinoxaline, and diketopyrrolopyrrole (DPP), respectively. The optical electrochemical and photovoltaic properties of these polymers were investigated. Alkylthiophenyl substitution on the BDT building block is favorable for the low-lying highest occupied orbital (HOMO) level of polymers. The HOMO of these copolymers is clearly lowered to -5.49 eV, -5.34 eV, and -5.50 eV, respectively. Compared with reference polymers, our polymers show lowered HOMO energy levels (by 0.14 eV at least). This is very helpful to enhance the open-circuit voltage (V-oc) of the devices. Further, P2:PC61BM exhibited an optimized power conversion efficiency (PCE) of 4.28 %, which is clearly higher than that of P1 (1.48%) and P3 (1.9 %)

    Sucrose Secreted by the Engineered Cyanobacterium and Its Fermentability

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    The unicellular cyanobacterium, Synechococcus elongatus PCC 7942 (Syn7942), synthesizes sucrose as the only compatible solute under salt stress. A series of engineered Syn7942 strains for sucrose production were constructed. The overexpression of the native sps (encoding a natively fused protein of sucrose phosphate synthase SPS and sucrose phosphate phosphatase SPP) in Syn7942 wild type caused a 93% improvement of sucrose productivity. The strain FL130 co-overexpressing sps and cscB (encoding a sucrose transporter) exhibited a 74% higher extracellular sucrose production than that overexpressing cscB only. Both results showed the significant improvement of sucrose productivity by the double functional protein SPS-SPP. Afterwards, FL130 was cultivated under a modified condition, and the cell-free culture medium containing 1.5 g L-1 sucrose was pre-treated with an acid hydrolysis technique. Cultivated with the neutralized hydrolysates as the starting media, two widely used microorganisms, Escherichia coli and Saccharomyces cerevisiae, showed a comparable growth with that in the control media supplemented with glucose. These results clearly demonstrated that the cell-free culture of sucrose-secreting cyanobacteria can be applied as starting media in microbial cultivation

    UDP-glycosyltransferase 72B1 catalyzes the glucose conjugation of monolignols and is essential for the normal cell wall lignification in Arabidopsis thaliana

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    Glycosylation of monolignols has been found to be widespread in land plants since the 1970s. However, whether monolignol glycosylation is crucial for cell wall lignification and how it exerts effects are still unknown. Here, we report the identification of a mutant ugt72b1 showing aggravated and ectopic lignification in floral stems along with arrested growth and anthocyanin accumulation. Histochemical assays and thioacidolysis analysis confirmed the enhanced lignification and increased lignin biosynthesis in the ugt72b1 mutant. The loss of UDP-glycosyltransferase UGT72B1 function was responsible for the lignification phenotype, as demonstrated by complementation experiments. Enzyme activity analysis indicated that UGT72B1 could catalyze the glucose conjugation of monolignols, especially coniferyl alcohol and coniferyl aldehyde, which was confirmed by analyzing monolignol glucosides of UGT72B1 transgenic plants. Furthermore, the UGT72B1 gene was strongly expressed in young stem tissues, especially xylem tissues. However, UGT72B1 paralogs, such as UGT72B2 and UGT72B3, had weak enzyme activity toward monolignols and weak expression in stem tissues. Transcriptomic profiling showed that UGT72B1 knockout resulted in extensively increased transcript levels of genes involved in monolignol biosynthesis, lignin polymerization and cell wall-related transcription factors, which was confirmed by quantitative real-time PCR assays. These results provided evidence that monolignol glucosylation catalyzed by UGT72B1 was essential for normal cell wall lignification, thus offering insight into the molecular mechanism of cell wall development and cell wall lignification

    Comparison and Interpretation of Taxonomical Structure of Bacterial Communities in Two Types of Lakes on Yun-Gui plateau of China

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    Bacterial communities from freshwater lakes are shaped by various factors such as nutrients, pH value, temperature, etc. Their compositions and relative abundances would undergo changes to adapt the changing environments, and in turn could affect the environments of freshwater lakes. Analyses of the freshwater lake's bacterial communities under different environments would be of pivotal importance to monitor the condition of waterbody. In this study, we have collected freshwater samples from two lakes on Yun-Gui plateau of China, Lake Dianchi and Lake Haixihai, and analyzed the bacterial community structures from these samples based on 16S rRNA sequencing. Results have shown that: Firstly, the bacterial community of these samples have very different taxonomical structures, not only between two lakes but also among the intra-groups for samples collected from Dianchi. Secondly, the differences between samples from two lakes are highly associated with the chemical-geographical properties of the two lakes. Thirdly, for samples of Dianchi and Haixihai, analytical results of physicochemical, taxonomical structure and relative abundance of community revealed that extreme physicochemical factors caused by human activities have strongly affected the bacterial ecosystem in Dianchi. These results have clearly indicated the importance of combining biological profiling and chemical-geographical properties for monitoring Chinese plateau freshwater bacterial ecosystem, which could provide clues for Chinese freshwater ecosystem remediation on plateau

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    Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences
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