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  • 11
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    Cross-talk among writers, readers, and erasers of m6A regulates cancer growth and progression (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018
    Description: 〈p〉The importance of RNA methylation in biological processes is an emerging focus of investigation. We report that altering m〈sup〉6〈/sup〉A levels by silencing either 〈i〉N〈/i〉〈sup〉6〈/sup〉-adenosine methyltransferase METTL14 (methyltransferase-like 14) or demethylase ALKBH5 (ALKB homolog 5) inhibits cancer growth and invasion. METTL14/ALKBH5 mediate their protumorigenic function by regulating m〈sup〉6〈/sup〉A levels of key epithelial-mesenchymal transition and angiogenesis-associated transcripts, including transforming growth factor–β signaling pathway genes. Using MeRIP-seq (methylated RNA immunoprecipitation sequencing) analysis and functional studies, we find that these target genes are particularly sensitive to changes in m〈sup〉6〈/sup〉A modifications, as altered m〈sup〉6〈/sup〉A status leads to aberrant expression of these genes, resulting in inappropriate cell cycle progression and evasion of apoptosis. Our results reveal that METTL14 and ALKBH5 determine the m〈sup〉6〈/sup〉A status of target genes by controlling each other’s expression and by inhibiting m〈sup〉6〈/sup〉A reader YTHDF3 (YTH 〈i〉N〈/i〉〈sup〉6〈/sup〉-methyladenosine RNA binding protein 3), which blocks RNA demethylase activity. Furthermore, we show that ALKBH5/METTL14 constitute a positive feedback loop with RNA stability factor HuR to regulate the stability of target transcripts. We discover that hypoxia alters the level/activity of writers, erasers, and readers, leading to decreased m〈sup〉6〈/sup〉A and consequently increased expression of target transcripts in cancer cells. This study unveils a previously undefined role for m〈sup〉6〈/sup〉A in cancer and shows that the collaboration among writers-erasers-readers sets up the m〈sup〉6〈/sup〉A threshold to ensure the stability of progrowth/proliferation-specific genes, and protumorigenic stimulus, such as hypoxia, perturbs that m〈sup〉6〈/sup〉A threshold, leading to uncontrolled expression/activity of those genes, resulting in tumor growth, angiogenesis, and progression.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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  • 12
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    Controlling complex networks (2016)
    Royal Society
    Details
    Publication Date: 2016-04-28
    Description: Recent works revealed that the energy required to control a complex network depends on the number of driving signals and the energy distribution follows an algebraic scaling law. If one implements control using a small number of drivers, e.g. as determined by the structural controllability theory, there is a high probability that the energy will diverge. We develop a physical theory to explain the scaling behaviour through identification of the fundamental structural elements, the longest control chains (LCCs), that dominate the control energy. Based on the LCCs, we articulate a strategy to drastically reduce the control energy (e.g. in a large number of real-world networks). Owing to their structural nature, the LCCs may shed light on energy issues associated with control of nonlinear dynamical networks.
    Keywords: mathematical physics, complexity
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 13
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    Species-specific responses of Late Quaternary megafauna to climate and humans (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-11-04
    Description: Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070744/" 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/PMC4070744/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lorenzen, Eline D -- Nogues-Bravo, David -- Orlando, Ludovic -- Weinstock, Jaco -- Binladen, Jonas -- Marske, Katharine A -- Ugan, Andrew -- Borregaard, Michael K -- Gilbert, M Thomas P -- Nielsen, Rasmus -- Ho, Simon Y W -- Goebel, Ted -- Graf, Kelly E -- Byers, David -- Stenderup, Jesper T -- Rasmussen, Morten -- Campos, Paula F -- Leonard, Jennifer A -- Koepfli, Klaus-Peter -- Froese, Duane -- Zazula, Grant -- Stafford, Thomas W Jr -- Aaris-Sorensen, Kim -- Batra, Persaram -- Haywood, Alan M -- Singarayer, Joy S -- Valdes, Paul J -- Boeskorov, Gennady -- Burns, James A -- Davydov, Sergey P -- Haile, James -- Jenkins, Dennis L -- Kosintsev, Pavel -- Kuznetsova, Tatyana -- Lai, Xulong -- Martin, Larry D -- McDonald, H Gregory -- Mol, Dick -- Meldgaard, Morten -- Munch, Kasper -- Stephan, Elisabeth -- Sablin, Mikhail -- Sommer, Robert S -- Sipko, Taras -- Scott, Eric -- Suchard, Marc A -- Tikhonov, Alexei -- Willerslev, Rane -- Wayne, Robert K -- Cooper, Alan -- Hofreiter, Michael -- Sher, Andrei -- Shapiro, Beth -- Rahbek, Carsten -- Willerslev, Eske -- R01 HG003229/HG/NHGRI NIH HHS/ -- England -- Nature. 2011 Nov 2;479(7373):359-64. doi: 10.1038/nature10574.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for GeoGenetics, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22048313" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bayes Theorem ; *Biota ; Bison ; Climate Change/*history ; DNA, Mitochondrial/analysis/genetics ; Europe ; *Extinction, Biological ; Fossils ; Genetic Variation ; Geography ; History, Ancient ; Horses ; Human Activities/*history ; Humans ; Mammals/genetics/*physiology ; Mammoths ; Molecular Sequence Data ; Population Dynamics ; Reindeer ; Siberia ; Species Specificity ; Time Factors
    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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  • 14
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    Volcanism, mass extinction, and carbon isotope fluctuations in the Middle Permian of China (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-05-30
    Description: The 260-million-year-old Emeishan volcanic province of southwest China overlies and is interbedded with Middle Permian carbonates that contain a record of the Guadalupian mass extinction. Sections in the region thus provide an opportunity to directly monitor the relative timing of extinction and volcanism within the same locations. These show that the onset of volcanism was marked by both large phreatomagmatic eruptions and extinctions amongst fusulinacean foraminifers and calcareous algae. The temporal coincidence of these two phenomena supports the idea of a cause-and-effect relationship. The crisis predates the onset of a major negative carbon isotope excursion that points to subsequent severe disturbance of the ocean-atmosphere carbon cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wignall, Paul B -- Sun, Yadong -- Bond, David P G -- Izon, Gareth -- Newton, Robert J -- Vedrine, Stephanie -- Widdowson, Mike -- Ali, Jason R -- Lai, Xulong -- Jiang, Haishui -- Cope, Helen -- Bottrell, Simon H -- New York, N.Y. -- Science. 2009 May 29;324(5931):1179-82. doi: 10.1126/science.1171956.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Earth and Environment, University of Leeds, Leeds LS2 9JT, UK. p.wignall@see.leeds.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19478179" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Atmosphere ; Carbon Isotopes/*analysis ; Carbonates/analysis ; China ; Ecosystem ; Eukaryota ; *Extinction, Biological ; Fossils ; Geologic Sediments/analysis ; Seawater ; *Volcanic Eruptions
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 15
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    Lethally hot temperatures during the Early Triassic greenhouse (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-10-23
    Description: Global warming is widely regarded to have played a contributing role in numerous past biotic crises. Here, we show that the end-Permian mass extinction coincided with a rapid temperature rise to exceptionally high values in the Early Triassic that were inimical to life in equatorial latitudes and suppressed ecosystem recovery. This was manifested in the loss of calcareous algae, the near-absence of fish in equatorial Tethys, and the dominance of small taxa of invertebrates during the thermal maxima. High temperatures drove most Early Triassic plants and animals out of equatorial terrestrial ecosystems and probably were a major cause of the end-Smithian crisis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Yadong -- Joachimski, Michael M -- Wignall, Paul B -- Yan, Chunbo -- Chen, Yanlong -- Jiang, Haishui -- Wang, Lina -- Lai, Xulong -- New York, N.Y. -- Science. 2012 Oct 19;338(6105):366-70. doi: 10.1126/science.1224126.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Geobiology and Environmental Geology, China University of Geosciences (Wuhan), Wuhan 430074, People's Republic of China. eeys@leeds.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23087244" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Aquatic Organisms ; *Extinction, Biological ; *Global Warming ; *Greenhouse Effect ; *Hot Temperature
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 16
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    Long-term east-west asymmetry in monsoon rainfall on the Tibetan Plateau: COMMENT (2013)
    Geological Society of America (GSA)
    In: Geology
    Details
    Publication Date: 2013-11-22
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
    Published by Geological Society of America (GSA)
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  • 17
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    Experimental and Numerical Analysis of Performance Discontinuity of a Pump-Turbine under Pumping Mode (2016)
    Institute of Physics (IOP)
    Details
    Publication Date: 2016-12-14
    Description: The performance discontinuity of a pump-turbine under pumping mode is harmful to stable operation of units in hydropower station. In this paper, the performance discontinuity phenomenon of the pump-turbine was studied by means of experiment and numerical simulation. In the experiment, characteristics of the pump-turbine with different diffuser vane openings were tested in order to investigate the effect of pumping casing to the performance discontinuity. While other effects such as flow separation and rotating stall are known to have an effect on the discontinuity, the present studied test cases show that prerotation is the dominating effect for the instability, positions of the positive slope of characteristics are almost the same in different diffuser vane opening conditions. The impeller has principal effect to the performance discontinuity. In the numerical simulation, CFD analysis of tested pump-turbine has been done with k-ω and SST turbulence model. It is found tha...
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
    Published by Institute of Physics (IOP)
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  • 18
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    TCF7L2 gene polymorphisms and type 2 diabetes risk: a comprehensive and updated meta-analysis involving 121 174 subjects (2012)
    Oxford University Press
    Details
    Publication Date: 2012-12-20
    Description: Recently, many new loci associated with type 2 diabetes have been uncovered by genetic association studies and genome-wide association studies. As more reports are made, particularly with respect to varying ethnicities, there is a need to determine more precisely the effect sizes in each major racial group. In addition, some reports have claimed ethnic-specific associations with alternative single-nucleotide polymorphisms (SNPs), and to that end there has been a degree of confusion. We conducted a meta-analysis using an additive genetic model. Eight polymorphisms in 155 studies with 121174 subjects (53385 cases and 67789 controls) were addressed in this meta-analysis. Significant associations were found between type 2 diabetes and rs7903146, rs12255372, rs11196205, rs7901695, rs7895340 and rs4506565, with summary odds ratios (ORs) (95% confidence interval) of 1.39 (1.34–1.45), 1.33 (1.27–1.40), 1.20 (1.14–1.26), 1.32 (1.25–1.39), 1.21 (1.13–1.29) and 1.39 (1.29–1.49), respectively. In addition, no significant associations were found between the two polymorphisms (rs290487 and rs11196218) and type 2 diabetes. The summary ORs for the six statistically significant associations ( P 〈 0.05) were further evaluated by estimating the false-positive report probability, with results indicating that all of the six significant associations were considered noteworthy, and may plausibly be true associations. Significant associations were found between the six polymorphisms (rs7903146, rs12255372, rs11196205, rs7901695, rs7895340 and rs4506565) in the TCF7L2 gene and type 2 diabetes risk, and the other two polymorphisms (rs11196218 and rs290487) were not found to be significantly associated with type 2 diabetes. Subgroups analyses show that significant associations are not found between the six SNPs (rs7903146, rs12255372, rs11196205, rs7901695, rs7895340, and rs4506565) and the type 2 diabetes in some ethnic populations.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 19
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    Optimal localization of diffusion sources in complex networks (2017)
    Royal Society
    Details
    Publication Date: 2017-04-13
    Description: Locating sources of diffusion and spreading from minimum data is a significant problem in network science with great applied values to the society. However, a general theoretical framework dealing with optimal source localization is lacking. Combining the controllability theory for complex networks and compressive sensing, we develop a framework with high efficiency and robustness for optimal source localization in arbitrary weighted networks with arbitrary distribution of sources. We offer a minimum output analysis to quantify the source locatability through a minimal number of messenger nodes that produce sufficient measurement for fully locating the sources. When the minimum messenger nodes are discerned, the problem of optimal source localization becomes one of sparse signal reconstruction, which can be solved using compressive sensing. Application of our framework to model and empirical networks demonstrates that sources in homogeneous and denser networks are more readily to be located. A surprising finding is that, for a connected undirected network with random link weights and weak noise, a single messenger node is sufficient for locating any number of sources. The framework deepens our understanding of the network source localization problem and offers efficient tools with broad applications.
    Keywords: complexity, graph theory
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 20
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    Cross-talk among writers, readers, and erasers of m6A regulates cancer growth and progression (2018)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2018-10-04
    Description: The importance of RNA methylation in biological processes is an emerging focus of investigation. We report that altering m 6 A levels by silencing either N 6 -adenosine methyltransferase METTL14 (methyltransferase-like 14) or demethylase ALKBH5 (ALKB homolog 5) inhibits cancer growth and invasion. METTL14/ALKBH5 mediate their protumorigenic function by regulating m 6 A levels of key epithelial-mesenchymal transition and angiogenesis-associated transcripts, including transforming growth factor–β signaling pathway genes. Using MeRIP-seq (methylated RNA immunoprecipitation sequencing) analysis and functional studies, we find that these target genes are particularly sensitive to changes in m 6 A modifications, as altered m 6 A status leads to aberrant expression of these genes, resulting in inappropriate cell cycle progression and evasion of apoptosis. Our results reveal that METTL14 and ALKBH5 determine the m 6 A status of target genes by controlling each other’s expression and by inhibiting m 6 A reader YTHDF3 (YTH N 6 -methyladenosine RNA binding protein 3), which blocks RNA demethylase activity. Furthermore, we show that ALKBH5/METTL14 constitute a positive feedback loop with RNA stability factor HuR to regulate the stability of target transcripts. We discover that hypoxia alters the level/activity of writers, erasers, and readers, leading to decreased m 6 A and consequently increased expression of target transcripts in cancer cells. This study unveils a previously undefined role for m 6 A in cancer and shows that the collaboration among writers-erasers-readers sets up the m 6 A threshold to ensure the stability of progrowth/proliferation-specific genes, and protumorigenic stimulus, such as hypoxia, perturbs that m 6 A threshold, leading to uncontrolled expression/activity of those genes, resulting in tumor growth, angiogenesis, and progression.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Published by American Association for the Advancement of Science (AAAS)
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