| 1. |
- Andrews, Gregory, et al.
(author)
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Mammalian evolution of human cis-regulatory elements and transcription factor binding sites
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Journal article (peer-reviewed)abstract
- Understanding the regulatory landscape of the human genome is a long-standing objective of modern biology. Using the reference-free alignment across 241 mammalian genomes produced by the Zoonomia Consortium, we charted evolutionary trajectories for 0.92 million human candidate cis-regulatory elements (cCREs) and 15.6 million human transcription factor binding sites (TFBSs). We identified 439,461 cCREs and 2,024,062 TFBSs under evolutionary constraint. Genes near constrained elements perform fundamental cellular processes, whereas genes near primate-specific elements are involved in environmental interaction, including odor perception and immune response. About 20% of TFBSs are transposable element-derived and exhibit intricate patterns of gains and losses during primate evolution whereas sequence variants associated with complex traits are enriched in constrained TFBSs. Our annotations illuminate the regulatory functions of the human genome.
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| 2. |
- Christmas, Matthew, et al.
(author)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Journal article (peer-reviewed)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 3. |
- Ge, Jing, et al.
(author)
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Bringing light into the dark triplet space of molecular systems
- 2015
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 17:19, s. 13129-13136
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Journal article (peer-reviewed)abstract
- A molecule or a molecular system always consists of excited states of different spin multiplicities. With conventional optical excitations, only the (bright) states with the same spin multiplicity of the ground state could be directly reached. How to reveal the dynamics of excited (dark) states remains the grand challenge in the topical fields of photochemistry, photophysics, and photobiology. For a singlet-triplet coupled molecular system, the (bright) singlet dynamics can be routinely examined by conventional femtosecond pump-probe spectroscopy. However, owing to the involvement of intrinsically fast decay channels such as intramolecular vibrational redistribution and internal conversion, it is very difficult, if not impossible, to single out the (dark) triplet dynamics. Herein, we develop a novel strategy that uses an ultrafast broadband white-light continuum as a excitation light source to enhance the probability of intersystem crossing, thus facilitating the population flow from the singlet space to the triplet space. With a set of femtosecond time-reversed pump-probe experiments, we report on a proof-of-concept molecular system (i.e., the malachite green molecule) that the pure triplet dynamics can be mapped out in real time through monitoring the modulated emission that occurs solely in the triplet space. Significant differences in excited-state dynamics between the singlet and triplet spaces have been observed. This newly developed approach may provide a useful tool for examining the elusive dark-state dynamics of molecular systems and also for exploring the mechanisms underlying molecular luminescence/photonics and solar light harvesting.
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| 4. |
- Zhang, Qun, et al.
(author)
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The Realistic Domain Structure of As-Synthesized Graphene Oxide from Ultrafast Spectroscopy
- 2013
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 135:33, s. 12468-12474
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Journal article (peer-reviewed)abstract
- Graphene oxide (GO) is an attractive alternative for large-scale production of graphene, but its general structure is still under debate due to its complicated nonstoichiometric nature. Here we perform a set of femto-second pump-probe experiments on as-synthesized GO to extrapolate structural information in situ. Remarkably, it is observed that, in these highly oxidized GO samples, the ultrafast graphene-like dynamics intrinsic to pristine graphene is completely dominant over a wide energy region and can be modified by the localized impurity states and the electron-phonon coupling under certain conditions. These observations, combined with the X-ray photoelectron spectroscopy analysis and control experiments, lead to an important conclusion that GO consists of two types of domain, namely the carbon-rich graphene-like domain and the oxygen-rich domain. This study creates a new understanding of the realistic domain structure and properties of as-synthesized GO, offering useful guidance for future applications based on chemically modified/functionalized graphenes.
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