655 research outputs found

    Substrate specificity provides insights into the sugar donor recognition mechanism of O-GlcNAc transferase (OGT).

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    O-Linked β-N-acetylglucosaminyl transferase (OGT) plays an important role in the glycosylation of proteins, which is involved in various cellular events. In human, three isoforms of OGT (short OGT [sOGT]; mitochondrial OGT [mOGT]; and nucleocytoplasmic OGT [ncOGT]) share the same catalytic domain, implying that they might adopt a similar catalytic mechanism, including sugar donor recognition. In this work, the sugar-nucleotide tolerance of sOGT was investigated. Among a series of uridine 5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) analogs tested using the casein kinase II (CKII) peptide as the sugar acceptor, four compounds could be used by sOGT, including UDP-6-deoxy-GlcNAc, UDP-GlcNPr, UDP-6-deoxy-GalNAc and UDP-4-deoxy-GlcNAc. Determined values of Km showed that the substitution of the N-acyl group, deoxy modification of C6/C4-OH or epimerization of C4-OH of the GlcNAc in UDP-GlcNAc decreased its affinity to sOGT. A molecular docking study combined with site-directed mutagenesis indicated that the backbone carbonyl oxygen of Leu653 and the hydroxyl group of Thr560 in sOGT contributed to the recognition of the sugar moiety via hydrogen bonds. The close vicinity between Met501 and the N-acyl group of GlcNPr, as well as the hydrophobic environment near Met501, were responsible for the selective binding of UDP-GlcNPr. These findings illustrate the interaction of OGT and sugar nucleotide donor, providing insights into the OGT catalytic mechanism

    Magnetic Activities of M-type Stars Based on LAMOST DR5 and Kepler and K2 Missions

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    We performed a statistical study of magnetic activities of M-type stars by combining the spectra of LAMOST DR5 with light curves from the Kepler and K2 missions. We mainly want to study the relationship between chromospheric activity and flares, and their relations of magnetic activity and rotation period. We have obtained the maximum catalog of 516,688 M-type stellar spectra of 480,912 M stars from LAMOST DR5 and calculated their equivalent widths of chromospheric activity indicators (Hα, Hβ, Hγ, Hδ, Ca II H&K, and He I D3). Using the Hα indicator, 40,464 spectra of 38,417 M stars show chromospheric activity, and 1791 of these 5499 M-type stars with repeated observations have Hα variability. We used an automatic detection plus visual inspection method to detect 17,432 flares on 8964 M-type stars from the catalog by cross-matching LAMOST DR5 and the Kepler and K2 databases. We used the Lomb–Scargle method to calculate their rotation periods. We find that the flare frequency is consistent with the ratio of activities of these chromospheric activity indicators as a function of spectral type in M0–M3. We find the equivalent widths of Hα and Ca II H have a significant statistical correlation with the flare amplitude in M-type stars. We confirm that the stellar flare is affected by both the stellar magnetic activity and the rotation period. Finally, using the Hα equivalent width equal to 0.75 Å and using the rotation period equal to 10 days as the threshold for the M-type stellar flare time frequency are almost equivalent

    New Record of the Leopard Gecko Goniurosaurus araneus (Squamata: Eublepharidae) for China and Habitat Partitioning between Geographically and Phylogenetically Close Leopard Geckos

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    Two specimens of the Leopard Gecko Goniurosaurus araneus (Squamata: Eublepharidae) were collected from Nonggang National Nature Reserve, Chongzuo Prefecture, Guangxi Zhuang Ethnicity Autonomous Region, China, in October 2011. This species is a new record for China and this report is a range extension for the species from northern Vietnam to southern Guangxi. A phylogenetic study demonstrated that Goniurosaurus araneus and G. luii are a species pair. We show for the first time that they coexist broadly but are narrowly allopatric in a small area in southern Guangxi, separated only by a river, similar to what had been reported previously for G. yingdeensis and Goniurosaurus indet. from northwestern Guangdong. A river as a geographical barrier, elevation, and aspect may have contributed to habitat partitioning between G. araneus and G. luii

    Highly surface electron-deficient Co9S8 nanoarrays for enhanced oxygen evolution

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    Tailoring valence electron delocalization of transition metal center is of importance to achieve highly-active electrocatalysts for oxygen evolution reaction (OER). Herein, we demonstrate a “poor sulfur” route to synthesize surface electron-deficient Co9S8 nanoarrays, where the binding energy (BE) of Co metal center is considerably higher than all reported Co9S8-based electrocatalysts. The resulting Co9S8 electrocatalysts only require the overpotentials (η) of 265 and 326 mV at 10 and 100 mA cm−2 with a low Tafel slope of 56 mV dec−1 and a 60 h-lasting stability in alkaline media. The OER kinetics are greatly expedited with a low reaction activation energy of 27.9 kJ mol−1 as well as abundant OOH∗ key intermediates (24%), thus exhibiting excellent catalytic performances. The surface electron-deficient engineering gives an available strategy to improve the catalytic activity of other advanced non-noble electrocatalysts. © 2020 Institute of Process Engineering, Chinese Academy of SciencesNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [21838003, 21808061, 91534122]; Social Development Program of Shanghai [17DZ1200900]; Shanghai Scientific and Technological Innovation Project [18JC1410600]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [222201718002

    Exploration of Potential Roles of a New LOXL2 Splicing Variant Using Network Knowledge in Esophageal Squamous Cell Carcinoma

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    LOXL2 (lysyl oxidase-like 2), an enzyme that catalyzes oxidative deamination of lysine residue, is upregulated in esophageal squamous cell carcinoma (ESCC). A LOXL2 splice variant LOXL2-e13 and its wild type were overexpressed in ESCC cells followed by microarray analyses. In this study, we explored the potential role and molecular mechanism of LOXL2-e13 based on known protein-protein interactions (PPIs), following microarray analysis of KYSE150 ESCC cells overexpressing a LOXL2 splice variant, denoted by LOXL2-e13, or its wild-type counterpart. The differentially expressed genes (DEGs) of LOXL2-WT and LOXL2-e13 were applied to generate individual PPI subnetworks in which hundreds of DEGs interacted with thousands of other proteins. These two DEG groups were annotated by Functional Annotation Chart analysis in the DAVID bioinformatics database and compared. These results found many specific annotations indicating the potential specific role or mechanism for LOXL2-e13. The DEGs of LOXL2-e13, comparing to its wild type, were prioritized by the Random Walk with Restart algorithm. Several tumor-related genes such as ERO1L, ITGA3, and MAPK8 were found closest to LOXL2-e13. These results provide helpful information for subsequent experimental identification of the specific biological roles and molecular mechanisms of LOXL2-e13. Our study also provides a work flow to identify potential roles of splice variants with large scale data

    Replication and Fine Mapping for Association of the C2orf43, FOXP4, GPRC6A and RFX6 Genes with Prostate Cancer in the Chinese Population

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    Prostate cancer represents the leading cause of male death across the world. A recent genome-wide association study (GWAS) identified five novel susceptibility loci for prostate cancer in the Japanese population. This study is to replicate and fine map the potential association of these five loci with prostate cancer in the Chinese Han population.In Phase I of the study, we tested the five single nucleotide polymorphisms (SNPs) which showed the strongest association evidence in the original GWAS in Japanese. The study sample consists of 1,169 Chinese Hans, comprising 483 patients and 686 healthy controls. Then in phase II, flanking SNPs of the successfully replicated SNPs in Phase I were genotyped and tested for association with prostate cancer to fine map those significant association signals.We successfully replicated the association of rs13385191 (located in the C2orf43 gene, P = 8.60×10(-5)), rs12653946 (P = 1.33×10(-6)), rs1983891 (FOXP4, P = 6.22×10(-5)), and rs339331 (GPRC6A/RFX6, P = 1.42×10(-5)) with prostate cancer. The most significant odds ratio (OR) was recorded as 1.41 (95% confidence interval 1.18-1.68) for rs12653946. Rs9600079 did not show significant association (P = 8.07×10(-2)) with prostate cancer in this study. The Phase II study refined these association signals, and identified several SNPs showing more significant association with prostate cancer than the very SNPs tested in Phase I.Our results provide further support for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in Eastern Asian populations. This study also characterized the novel loci reported in the original GWAS with more details. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms
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