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  • 1
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    Exploded view of higher order G-quadruplex structures through click-chemistry assisted single-molecule mechanical unfolding (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-09
    Description: Due to the long-range nature of high-order interactions between distal components in a biomolecule, transition dynamics of tertiary structures is often too complex to profile using conventional methods. Inspired by the exploded view in mechanical drawing, here, we used laser tweezers to mechanically dissect high-order DNA structures into two constituting G-quadruplexes in the promoter of the human telomerase reverse transcriptase (hTERT) gene. Assisted with click-chemistry coupling, we sandwiched one G-quadruplex with two dsDNA handles while leaving the other unit free. Mechanical unfolding through these handles revealed transition dynamics of the targeted quadruplex in a native environment, which is named as native mechanical segmentation (NMS). Comparison between unfolding of an NMS construct and that of truncated G-quadruplex constructs revealed a quadruplex–quadruplex interaction with 2 kcal/mol stabilization energy. After mechanically targeting the two G-quadruplexes together, the same interaction was observed during the first unfolding step. The unfolding then proceeded through disrupting the weaker G-quadruplex at the 5'-end, followed by the stronger G-quadruplex at the 3'-end via various intermediates. Such a pecking order in unfolding well reflects the hierarchical nature of nucleic acid structures. With surgery-like precisions, we anticipate this NMS approach offers unprecedented perspective to decipher dynamic transitions in complex biomacromolecules.
    Keywords: Nucleic acid structure, Phsyical and Biochemical Characterisation of DNA
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Human impact overwhelms long-term climate control of weathering and erosion in southwest China (2015)
    Geological Society of America (GSA)
    In: Geology
    Details
    Publication Date: 2015-04-25
    Description: During the Holocene there has been a gradual increase in the influence of humans on Earth systems. High-resolution sedimentary records can help us to assess how erosion and weathering have evolved in response to recent climatic and anthropogenic disturbances. Here we present data from a high-resolution (~75 cm/k.y.) sedimentary archive from the South China Sea. Provenance data indicate that the sediment was derived from the Red River, and can be used to reconstruct the erosion and/or weathering history in this river basin. Accelerator mass spectrometry 14 C dating provides direct age control and reveals coherent variations in clay mineralogy, geochemistry, and terrigenous flux, indicative of strong chemical weathering and physical erosion during the mid-Holocene warm period (6400–4000 cal [calibrated] yr B.P.), followed by weakening from ca. 4000–1800 cal yr B.P., and renewed intensification since 1800 cal yr B.P.. Comparison with climatic records from China indicates that precipitation and temperature controlled both physical erosion and chemical weathering intensity before 1800 cal yr B.P.. However, weathering proxies in the offshore sediment indicate recent increased soil erosion. We suggest that enhanced human activity (deforestation, cultivation, and mining) since the end of the Chinese Han Dynasty (220 CE) has overwhelmed the natural climatic controls on erosion in the Red River.
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
    Published by Geological Society of America (GSA)
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  • 3
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    A fly model for the CCUG-repeat expansion of myotonic dystrophy type 2 reveals a novel interaction with MBNL1 (2015)
    Oxford University Press
    Details
    Publication Date: 2015-01-25
    Description: Expanded non-coding RNA repeats of CUG and CCUG are the underlying genetic causes for myotonic dystrophy type 1 (DM1) and type 2 (DM2), respectively. A gain-of-function of these pathogenic repeat expansions is mediated at least in part by their abnormal interactions with RNA-binding proteins such as MBNL1 and resultant loss of activity of these proteins. To study pathogenic mechanisms of CCUG-repeat expansions in an animal model, we created a fly model of DM2 that expresses pure, uninterrupted CCUG-repeat expansions ranging from 16 to 720 repeats in length. We show that this fly model for DM2 recapitulates key features of human DM2 including RNA repeat-induced toxicity, ribonuclear foci formation and changes in alternative splicing. Interestingly, expression of two isoforms of MBNL1, MBNL1 35 and MBNL1 40 , leads to cleavage and concurrent upregulation of the levels of the RNA-repeat transcripts, with MBNL1 40 having more significant effects than MBNL1 35 . This property is shared with a fly CUG-repeat expansion model. Our results suggest a novel mechanism for interaction between the pathogenic RNA repeat expansions of myotonic dystrophy and MBNL1.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 4
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    DeAnnCNV: a tool for online detection and annotation of copy number variations from whole-exome sequencing data (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-02
    Description: With the decrease in costs, whole-exome sequencing (WES) has become a very popular and powerful tool for the identification of genetic variants underlying human diseases. However, integrated tools to precisely detect and systematically annotate copy number variations (CNVs) from WES data are still in great demand. Here, we present an online tool, DeAnnCNV ( De tection and Ann otation of C opy N umber V ariations from WES data), to meet the current demands of WES users. Upon submitting the file generated from WES data by an in-house tool that can be downloaded from our server, DeAnnCNV can detect CNVs in each sample and extract the shared CNVs among multiple samples. DeAnnCNV also provides additional useful supporting information for the detected CNVs and associated genes to help users to find the potential candidates for further experimental study. The web server is implemented in PHP + Perl + MATLAB and is online available to all users for free at http://mcg.ustc.edu.cn/db/cnv/ .
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    Requirement for human Mps1/TTK in oxidative DNA damage repair and cell survival through MDM2 phosphorylation (2016)
    Oxford University Press
    Details
    Publication Date: 2016-02-20
    Description: Human Mps1 (hMps1) is a protein kinase essential for mitotic checkpoints and the DNA damage response. Here, we present new evidence that hMps1 also participates in the repair of oxidative DNA lesions and cell survival through the MDM2-H2B axis. In response to oxidative stress, hMps1 phosphorylates MDM2, which in turn promotes histone H2B ubiquitination and chromatin decompaction. These events facilitate oxidative DNA damage repair and ATR-CHK1, but not ATM-CHK2 signaling. Depletion of hMps1 or MDM2 compromised H2B ubiquitination, DNA repair and cell survival. The impairment could be rescued by re-expression of WT but not the phospho-deficient MDM2 mutant, supporting the involvement of hMps1-dependent MDM2 phosphorylation in the oxidative stress response. In line with these findings, localization of RPA and base excision repair proteins to damage foci also requires MDM2 and hMps1. Significantly, like MDM2, hMps1 is upregulated in human sarcoma, suggesting high hMps1 and MDM2 expression may be beneficial for tumors constantly challenged by an oxidative micro-environment. Our study therefore identified an hMps1-MDM2-H2B signaling axis that likely plays a relevant role in tumor progression.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Centennial-scale dynamics of the Southern Hemisphere Westerly Winds across the Drake Passage over the past two millennia (2018)
    Geological Society of America (GSA)
    In: Geology
    Details
    Publication Date: 2018
    Description: 〈span〉〈div〉Abstract〈/div〉The Southern Hemisphere Westerly Winds (SHWW) exert important controls on regional and global climate. Instrumental and reanalysis records indicate strengthening and poleward contraction of the SHWW belt since the late twentieth century. Such changes also have implications for Southern Ocean upwelling and CO〈sub〉2〈/sub〉 degassing. Therefore, a better understanding of the long-term SHWW behaviors and dynamics beyond recent decades is critical for projecting future changes. Here, we applied isotope analysis of 〈span〉Sphagnum〈/span〉 moss cellulose from a peat bog in southernmost Patagonia (∼54°S) to reconstruct changes in oxygen isotope composition of precipitation (δ〈sup〉18〈/sup〉O〈sub〉p〈/sub〉) that could elucidate past shifts in moisture sources and trajectories. We interpreted the positive shifts in δ〈sup〉18〈/sup〉O〈sub〉p〈/sub〉 to indicate weaker SHWW and, importantly, more frequent easterly flows that enhance moisture supply sourced from the Atlantic Ocean. In contrast, negative shifts in δ〈sup〉18〈/sup〉O〈sub〉p〈/sub〉 indicate stronger SHWW and intensification of the Andean rain shadow. Our data, along with other evidence from southernmost Patagonia and the Antarctic Peninsula, suggest a coherent pattern of centennial-scale variability in SHWW strength on either side of the Drake Passage over the past two millennia, probably as a teleconnection response to El Niño–Southern Oscillation–like variability. Our study implies that investigations of past changes in the SHWW and associated teleconnection mechanisms should consider synoptic-scale atmospheric circulation patterns, rather than seeing SHWW as a simplistic west-to-east (zonal) wind-flow pattern, particularly on the time scales over which the SHWW express zonal asymmetry among different sectors of the Southern Ocean.〈/span〉
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
    Published by Geological Society of America (GSA)
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  • 7
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    Novel groups of cyanobacterial podovirus DNA polymerase (pol) genes exist in paddy waters in northeast China (2016)
    Oxford University Press
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    Publication Date: 2016-10-08
    Description: In this study, we surveyed cyanopodovirus DNA polymerase ( pol ) sequences in paddy waters using the culture-independent PCR and Sanger sequencing methods. Four paddy waters generated from a pot experiment with different soil types collected from op e n paddy fields in northeast China were used in this study. A total of 438 DNA pol clones were identified as cyanopodoviruses. The clones from the paddy waters formed nine unique groups of cyanopodoviruses either exclusively or with clones from East Lake in China (subclusters α-1 to α-8 and cluster β). None of the clones from open oceans or coastal waters fell into these unique groups. Additionally, the distribution proportions of the clones into different cyanopodovirus groups varied among paddy water samples, which suggested that the cyanopodovirus compositions were spatially distributed in the paddy fields. The comparison of clone libraries in different studies indicated that the diversity of cyanopodoviruses in paddy waters was comparable to the diversity in the open oceans but was less than the diversity in the coastal estuary of Chesapeake Bay. Non-metric multidimensional scaling analysis indicated that the cyanopodovirus communities in paddy waters were similar to those in lake freshwater but distinct from the communities in marine and coastal waters.
    Print ISSN: 0168-6496
    Electronic ISSN: 1574-6941
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Millennial-scale hydroclimate variations in southwest China linked to tropical Indian Ocean since the Last Glacial Maximum (2017)
    Geological Society of America (GSA)
    In: Geology
    Details
    Publication Date: 2017-04-12
    Description: Indian summer monsoon (ISM) variations have been linked to the orbital-scale boreal summer insolation and millennial-scale North Atlantic climates. Recent studies show the critical role of Indian Ocean sea-surface temperatures (SSTs) in affecting deglacial millennial-scale monsoon oscillations. However, it is unclear whether SSTs can affect monsoon rainfall and terrestrial hydroclimate during the Holocene. Here we report multiproxy evidence of hydroclimate changes in southwest China since the Last Glacial Maximum. Similar to the often-documented gradual decrease in Holocene monsoon rainfall with superimposed millennial-scale variations, our records particularly show pronounced hydroclimate fluctuations including wet conditions at ~5000-4000 yr ago, and perhaps over the past 1000 yr. We also find coherent variations between our records and sea-surface salinities in the eastern Indian Ocean, suggesting that terrestrial hydroclimate and resultant continental drainage have affected surface ocean conditions. These fluctuations are likely linked to changes in SSTs downstream of the monsoon source in the tropical western Indian Ocean, i.e., a warmer ocean and more monsoon rainfall. We conclude that the influence of both insolation and tropical SSTs on the ISM has persisted from the last deglaciation into Holocene.
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
    Published by Geological Society of America (GSA)
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  • 9
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    The Shu complex promotes error-free tolerance of alkylation-induced base excision repair products (2016)
    Oxford University Press
    Details
    Publication Date: 2016-10-08
    Description: Here, we investigate the role of the budding yeast Shu complex in promoting homologous recombination (HR) upon replication fork damage. We recently found that the Shu complex stimulates Rad51 filament formation during HR through its physical interactions with Rad55-Rad57. Unlike other HR factors, Shu complex mutants are primarily sensitive to replicative stress caused by MMS and not to more direct DNA breaks. Here, we uncover a novel role for the Shu complex in the repair of specific MMS-induced DNA lesions and elucidate the interplay between HR and translesion DNA synthesis. We find that the Shu complex promotes high-fidelity bypass of MMS-induced alkylation damage, such as N3-methyladenine, as well as bypassing the abasic sites generated after Mag1 removes N3-methyladenine lesions. Furthermore, we find that the Shu complex responds to ssDNA breaks generated in cells lacking the abasic site endonucleases. At each lesion, the Shu complex promotes Rad51-dependent HR as the primary repair/tolerance mechanism over error-prone translesion DNA polymerases. Together, our work demonstrates that the Shu complex's promotion of Rad51 pre-synaptic filaments is critical for high-fidelity bypass of multiple replication-blocking lesion.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Correlation between the photon index and X-ray luminosity of black hole X-ray binaries and active galactic nuclei: observations and interpretation (2015)
    Oxford University Press
    Details
    Publication Date: 2015-01-04
    Description: We investigate the observed correlation between the 2–10 keV X-ray luminosity (in unit of the Eddington luminosity; l X L X / L Edd ) and the photon index () of the X-ray spectrum for both black hole X-ray binaries (BHBs) and active galactic nuclei (AGNs). We construct a large sample, with 10 – 9 l X 10 – 1 . We find that is positively and negatively correlated with l X when l X 10 – 3 and 10 – 6.5 l X 10 – 3 , respectively, while is nearly a constant when l X 10 – 6.5 . We explain the above correlation in the framework of a coupled hot accretion flow–jet model. The radio emission always comes from the jet while the X-ray emission comes from the accretion flow and jet when l X is above and below 10 –6.5 , respectively. More specifically, we assume that with the increase of mass accretion rate, the hot accretion flow develops into a clumpy and further a disc–corona two-phase structure because of thermal instability. We argue that such kind of two-phase accretion flow can explain the observed positive correlation.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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