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  • 1
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    Nascent RNA transcripts facilitate the formation of G-quadruplexes (2014)
    Oxford University Press
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    Publication Date: 2014-06-21
    Description: Recent discovery of the RNA/DNA hybrid G-quadruplexes (HQs) and their potential wide-spread occurrence in human genome during transcription have suggested a new and generic transcriptional control mechanism. The G-rich sequence in which HQ may form can coincide with that for DNA G-quadruplexes (GQs), which are well known to modulate transcriptions. Understanding the molecular interaction between HQ and GQ is, therefore, of pivotal importance to dissect the new mechanism for transcriptional regulation. Using a T7 transcription model, herein we found that GQ and HQ form in a natural sequence, (GGGGA) 4 , downstream of many transcription start sites. Using a newly-developed single-molecular stalled-transcription assay, we revealed that RNA transcripts helped to populate quadruplexes at the expense of duplexes. Among quadruplexes, HQ predominates GQ in population and mechanical stabilities, suggesting HQ may serve as a better mechanical block during transcription. The fact that HQ and GQ folded within tens of milliseconds in the presence of RNA transcripts provided justification for the co-transcriptional folding of these species. The catalytic role of RNA transcripts in the GQ formation was strongly suggested as the GQ folded 〉7 times slower without transcription. These results shed light on the possible synergistic effect of GQs and HQs on transcriptional controls.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Level density and mechanism of deuteron-induced reactions on ^{54,56,58} Fe (2015)
    American Physical Society (APS)
    Details
    Publication Date: 2015-07-08
    Description: Author(s): A. P. D. Ramirez, A. V. Voinov, S. M. Grimes, Y. Byun, C. R. Brune, T. N. Massey, S. Akhtar, S. Dhakal, and C. E. Parker Deuteron elastic cross sections, as well as neutron, proton, and α -particle emission spectra, from d + Fe 54 , 56 , 58 reactions have been measured with deuteron beam energies of 5, 7, and 9 MeV. Optical model parameters have been tested against our experimental data. The fraction of total reaction cross s… [Phys. Rev. C 92, 014303] Published Mon Jul 06, 2015
    Keywords: Nuclear Structure
    Print ISSN: 0556-2813
    Electronic ISSN: 1089-490X
    Topics: Physics
    Published by American Physical Society (APS)
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  • 3
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    Shallow Groundwater Response to Rainfall on a Forested Headwater Catchment in Northern Coastal California: Implications of Topography, Rainfall and Throughfall Intensities on Peak Pressure Head Generation (2012)
    Wiley
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    Publication Date: 2012-09-08
    Description: The pore water pressure head that builds in the soil during storms is a critical factor for the prediction of potential slope instability. We report findings from a 3-year study of pressure head in 83 piezometers distributed within a 13-ha forested catchment on the northern coast of California. The study's primary objective was to observe the seasonal and storm-based dynamics of pressure head at a catchment scale in relation to observed rainfall characteristics and in situ topography to better understand landscape patterns of pressure head. An additional goal was to determine the influence of the interaction between rainfall and forest canopy in altering delivery of water and pressure head during the large storms necessary to induce landsliding. We found that pressure head was highly variable in space and time at the catchment scale. Pore pressures peaked close to maximum rainfall intensity during the largest storms measured. The difference between rainfall and throughfall delivered through the canopy was negligible during the critical landslide producing peak rainfall periods. Pore pressure was spatially variable within the catchment and did not strongly correlate with surficial topographic features. Only 23% of the piezometers located in a variety of slope positions were found to be highly responsive to rainfall. Topographic index statistically explained peak pressure head at responsive locations during common storms, but not during the larger storms with potential to produce landslides. Drainage efficiency throughout the catchment increased significantly in storms exceeding 2 to 7 months peak pressure head return period indicated by slowing or cessation of the rate of increase of pressure head with increasing storm magnitude. This asymptotic piezometric pattern persisted through the largest storm measured during the study. Faster soil drainage suppressed pressure head response in larger storms with important process implications for pore pressure development and landslide hazard modeling. Copyright © 2012 John Wiley & Sons, Ltd.
    Print ISSN: 0885-6087
    Electronic ISSN: 1099-1085
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Published by Wiley
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  • 4
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    GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-06-26
    Description: Genome-wide copy number analyses of human cancers identified a frequent 5p13 amplification in several solid tumour types, including lung (56%), ovarian (38%), breast (32%), prostate (37%) and melanoma (32%). Here, using integrative analysis of a genomic profile of the region, we identify a Golgi protein, GOLPH3, as a candidate targeted for amplification. Gain- and loss-of-function studies in vitro and in vivo validated GOLPH3 as a potent oncogene. Physically, GOLPH3 localizes to the trans-Golgi network and interacts with components of the retromer complex, which in yeast has been linked to target of rapamycin (TOR) signalling. Mechanistically, GOLPH3 regulates cell size, enhances growth-factor-induced mTOR (also known as FRAP1) signalling in human cancer cells, and alters the response to an mTOR inhibitor in vivo. Thus, genomic and genetic, biological, functional and biochemical data in yeast and humans establishes GOLPH3 as a new oncogene that is commonly targeted for amplification in human cancer, and is capable of modulating the response to rapamycin, a cancer drug in clinical use.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753613/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753613/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scott, Kenneth L -- Kabbarah, Omar -- Liang, Mei-Chih -- Ivanova, Elena -- Anagnostou, Valsamo -- Wu, Joyce -- Dhakal, Sabin -- Wu, Min -- Chen, Shujuan -- Feinberg, Tamar -- Huang, Joseph -- Saci, Abdel -- Widlund, Hans R -- Fisher, David E -- Xiao, Yonghong -- Rimm, David L -- Protopopov, Alexei -- Wong, Kwok-Kin -- Chin, Lynda -- 5-T32-AR07098-31/AR/NIAMS NIH HHS/ -- P50 CA090578/CA/NCI NIH HHS/ -- P50 CA093683/CA/NCI NIH HHS/ -- P50 CA093683-06A20011/CA/NCI NIH HHS/ -- P50 CA93683/CA/NCI NIH HHS/ -- R0-1 CA 114277/CA/NCI NIH HHS/ -- R01 AG2400401/AG/NIA NIH HHS/ -- R01 CA093947/CA/NCI NIH HHS/ -- R01 CA093947-08/CA/NCI NIH HHS/ -- R01 CA114277/CA/NCI NIH HHS/ -- R01 CA114277-04/CA/NCI NIH HHS/ -- R01 CA122794/CA/NCI NIH HHS/ -- R01 CA122794-03/CA/NCI NIH HHS/ -- R01 CA93947/CA/NCI NIH HHS/ -- T32 AR007098/AR/NIAMS NIH HHS/ -- T32 AR007098-32/AR/NIAMS NIH HHS/ -- England -- Nature. 2009 Jun 25;459(7250):1085-90. doi: 10.1038/nature08109.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19553991" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibiotics, Antineoplastic/*pharmacology ; Cell Line, Tumor/drug effects ; DNA-Binding Proteins/genetics ; Female ; Gene Knockdown Techniques ; Humans ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Nude ; Neoplasms/*physiopathology ; Protein Kinases/genetics/*metabolism ; Saccharomyces cerevisiae/genetics ; *Signal Transduction ; Sirolimus/*pharmacology ; TOR Serine-Threonine Kinases ; Transcription Factors/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 5
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    Level densities of Ge74,76 from compound nuclear reactions (2019)
    American Physical Society
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    Publication Date: 2019-05-08
    Print ISSN: 2469-9985
    Electronic ISSN: 2469-9993
    Topics: Physics
    Published by American Physical Society
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  • 6
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    Structural and mechanical properties of individual human telomeric G-quadruplexes in molecularly crowded solutions (2013)
    Oxford University Press
    Details
    Publication Date: 2013-04-02
    Description: Recent experiments provided controversial observations that either parallel or non-parallel G-quadruplex exists in molecularly crowded buffers that mimic cellular environment. Here, we used laser tweezers to mechanically unfold structures in a human telomeric DNA fragment, 5'-(TTAGGG) 4 TTA, along three different trajectories. After the end-to-end distance of each unfolding geometry was measured, it was compared with PDB structures to identify the best-matching G-quadruplex conformation. This method is well-suited to identify biomolecular structures in complex settings not amenable to conventional approaches, such as in a solution with mixed species or at physiologically significant concentrations. With this approach, we found that parallel G-quadruplex coexists with non-parallel species (1:1 ratio) in crowded buffers with dehydrating cosolutes [40% w/v dimethyl sulfoxide (DMSO) or acetonitrile (ACN)]. In crowded solutions with steric cosolutes [40% w/v bovine serum albumin (BSA)], the parallel G-quadruplex constitutes only 10% of the population. This difference unequivocally supports the notion that dehydration promotes the formation of parallel G-quadruplexes. Compared with DNA hairpins that have decreased unfolding forces in crowded (9 pN) versus diluted (15 pN) buffers, those of G-quadruplexes remain the same (20 pN). Such a result implies that in a cellular environment, DNA G-quadruplexes, instead of hairpins, can stop DNA/RNA polymerases with stall forces often 〈20 pN.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    Lateral variation of the Main Himalayan Thrust controls the rupture length of the 2015 Gorkha earthquake in Nepal (2019)
    American Association for the Advancement of Science (AAAS)
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    Publication Date: 2019
    Description: 〈p〉The Himalaya orogenic belt produces frequent large earthquakes that affect population centers along a length of over 2500 km. The 2015 Gorkha, Nepal earthquake (〈i〉M〈/i〉〈sub〉w〈/sub〉 7.8) ruptured the Main Himalayan Thrust (MHT) and allows direct measurements of the behavior of the continental collision zone. We study the MHT using seismic waveforms recorded by local stations that completely cover the aftershock zone. The MHT exhibits clear lateral variation along geologic strike, with the Lesser Himalayan ramp having moderate dip on the MHT beneath the mainshock area and a flatter and deeper MHT beneath the eastern end of the aftershock zone. East of the aftershock zone, seismic wave speed increases at MHT depths, perhaps due to subduction of an Indian basement ridge. A similar magnitude wave speed change occurs at the western end of the aftershock zone. These gross morphological structures of the MHT controlled the rupture length of the Gorkha earthquake.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 8
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    Molecular population dynamics of DNA structures in a bcl-2 promoter sequence is regulated by small molecules and the transcription factor hnRNP LL (2014)
    Oxford University Press
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    Publication Date: 2014-05-20
    Description: Minute difference in free energy change of unfolding among structures in an oligonucleotide sequence can lead to a complex population equilibrium, which is rather challenging for ensemble techniques to decipher. Herein, we introduce a new method, molecular population dynamics (MPD), to describe the intricate equilibrium among non-B deoxyribonucleic acid (DNA) structures. Using mechanical unfolding in laser tweezers, we identified six DNA species in a cytosine (C)-rich bcl-2 promoter sequence. Population patterns of these species with and without a small molecule (IMC-76 or IMC-48) or the transcription factor hnRNP LL are compared to reveal the MPD of different species. With a pattern recognition algorithm, we found that IMC-48 and hnRNP LL share 80% similarity in stabilizing i-motifs with 60 s incubation. In contrast, IMC-76 demonstrates an opposite behavior, preferring flexible DNA hairpins. With 120–180 s incubation, IMC-48 and hnRNP LL destabilize i-motifs, which has been previously proposed to activate bcl-2 transcriptions. These results provide strong support, from the population equilibrium perspective, that small molecules and hnRNP LL can modulate bcl-2 transcription through interaction with i-motifs. The excellent agreement with biochemical results firmly validates the MPD analyses, which, we expect, can be widely applicable to investigate complex equilibrium of biomacromolecules.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    Spatial orientation of angular momentum vectors of galaxies in six rotating clusters (2013)
    Oxford University Press
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    Publication Date: 2013-08-22
    Description: We study the spatial orientations of angular momentum vectors of galaxies in six rotating clusters (A954, A1139, A1399, A2162, A2169 and A2366) that show a single number-density peak around the cluster centre with a spatial segregation of high- and low-velocity galaxies. The positions, position angles and inclination angles are used to covert two-dimensional observed parameters into three-dimensional angular momentum vectors of the galaxy. The expected isotropic distribution curves are determined by running numerical simulations. The chi-square, autocorrelation, Fourier, Kolmogorov–Smirnov and Kuiper V tests are carried out in order to examine non-random effects in the expected isotropic distributions. In general a random orientation of angular momentum vectors of galaxies is found in all six rotating clusters supporting hierarchy model of galaxy formation. It is found that the vanishing angular momenta is preferred by the rotating clusters which are in dynamical equilibrium and have larger value of velocity dispersion. Possible explanations of the results will be discussed.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 10
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    Level density and mechanism of deuteron-induced reactions onFe54,56,58 (2015)
    American Physical Society
    Details
    Publication Date: 2015-07-06
    Print ISSN: 0556-2813
    Electronic ISSN: 1089-490X
    Topics: Physics
    Published by American Physical Society
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