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  • 1
    Online Resource
    Online Resource
    Genetic regulatory signatures underlying islet gene expression and type 2 diabetes
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 9 ( 2017-02-28), p. 2301-2306
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 9 ( 2017-02-28), p. 2301-2306
    Abstract: Genome-wide association studies (GWAS) have identified 〉 100 independent SNPs that modulate the risk of type 2 diabetes (T2D) and related traits. However, the pathogenic mechanisms of most of these SNPs remain elusive. Here, we examined genomic, epigenomic, and transcriptomic profiles in human pancreatic islets to understand the links between genetic variation, chromatin landscape, and gene expression in the context of T2D. We first integrated genome and transcriptome variation across 112 islet samples to produce dense cis -expression quantitative trait loci ( cis -eQTL) maps. Additional integration with chromatin-state maps for islets and other diverse tissue types revealed that cis -eQTLs for islet-specific genes are specifically and significantly enriched in islet stretch enhancers. High-resolution chromatin accessibility profiling using assay for transposase-accessible chromatin sequencing (ATAC-seq) in two islet samples enabled us to identify specific transcription factor (TF) footprints embedded in active regulatory elements, which are highly enriched for islet cis -eQTL. Aggregate allelic bias signatures in TF footprints enabled us de novo to reconstruct TF binding affinities genetically, which support the high-quality nature of the TF footprint predictions. Interestingly, we found that T2D GWAS loci were strikingly and specifically enriched in islet Regulatory Factor X (RFX) footprints. Remarkably, within and across independent loci, T2D risk alleles that overlap with RFX footprints uniformly disrupt the RFX motifs at high-information content positions. Together, these results suggest that common regulatory variations have shaped islet TF footprints and the transcriptome and that a confluent RFX regulatory grammar plays a significant role in the genetic component of T2D predisposition.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1621192114
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
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  • 2
    Online Resource
    Online Resource
    Mount St. Helens Ash from the 18 May 1980 Eruption: Chemical, Physical, Mineralogical, and Biological Properties
    American Association for the Advancement of Science (AAAS) ; 1980
    In:  Science Vol. 209, No. 4461 ( 1980-09-05), p. 1116-1125
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 209, No. 4461 ( 1980-09-05), p. 1116-1125
    Abstract: Samples of ash from the 18 May 1980 eruption of Mount St. Helens were collected from several locations in eastern Washington and Montana. The ash was subjected to a variety of analyses to determine its chemical, physical, mineralogical, and biological characteristics. Chemically, the ash samples were of dacitic composition. Particle size data showed bimodal distributions and differed considerably with location. However, all samples contained comparable amounts of particles less than 3.5 micrometers in diameter (respirable fraction). Mineralogically, the samples ranged from almost totally glassy to almost totally crystalline. Crystalline samples were dominated by plagioclase feldspar (andesine) and orthopyroxene (hypersthene), with smaller amounts of titanomagnetite and hornblende. All but one of the samples contained from less than 1 percent to 3 percent free crystalline silica (quartz, trydimite, or cristobalite) in both the bulk samples and 1 to 2 percent in the fractions smaller than 3.5 micrometers. The long-lived natural radionuclide content of the ash was comparable to that of crustal material; however, relatively large concentrations of short-lived radon daughters were present and polonium-210 content was inversely correlated with particle size. In vitro biological tests showed the ash to be nontoxic to alveolar macrophages, which are an important part of the lungs' natural clearance mechanism. On the basis of a substantial body of data that has shown a correlation between macrophage cytotoxicity and fibrogenicity of minerals, the ash is not predicted to be highly fibrogenic.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.209.4461.1116
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 1980
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
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  • 3
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    Online Resource
    Global fishery prospects under contrasting management regimes
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 18 ( 2016-05-03), p. 5125-5129
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 18 ( 2016-05-03), p. 5125-5129
    Abstract: Data from 4,713 fisheries worldwide, representing 78% of global reported fish catch, are analyzed to estimate the status, trends, and benefits of alternative approaches to recovering depleted fisheries. For each fishery, we estimate current biological status and forecast the impacts of contrasting management regimes on catch, profit, and biomass of fish in the sea. We estimate unique recovery targets and trajectories for each fishery, calculate the year-by-year effects of alternative recovery approaches, and model how alternative institutional reforms affect recovery outcomes. Current status is highly heterogeneous—the median fishery is in poor health (overfished, with further overfishing occurring), although 32% of fisheries are in good biological, although not necessarily economic, condition. Our business-as-usual scenario projects further divergence and continued collapse for many of the world’s fisheries. Applying sound management reforms to global fisheries in our dataset could generate annual increases exceeding 16 million metric tons (MMT) in catch, $53 billion in profit, and 619 MMT in biomass relative to business as usual. We also find that, with appropriate reforms, recovery can happen quickly, with the median fishery taking under 10 y to reach recovery targets. Our results show that commonsense reforms to fishery management would dramatically improve overall fish abundance while increasing food security and profits.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1520420113
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
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  • 4
    Online Resource
    Online Resource
    Global change effects on plant communities are magnified by time and the number of global change factors imposed
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 36 ( 2019-09-03), p. 17867-17873
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 36 ( 2019-09-03), p. 17867-17873
    Abstract: Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term ( 〈 10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity–ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1819027116
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
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  • 5
    Online Resource
    Online Resource
    Toward product-based regulation of crops
    American Association for the Advancement of Science (AAAS) ; 2022
    In:  Science Vol. 377, No. 6610 ( 2022-09-02), p. 1051-1053
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 377, No. 6610 ( 2022-09-02), p. 1051-1053
    Abstract: Much effort has been expended globally over the past four decades to craft and update country-specific and multinational safety regulations that can be applied to crops developed by genetic engineering processes, while exempting conventionally bred crops. This differentiation made some sense in the 1980s, but in light of technological advances, it is no longer scientifically defensible. In the coming decades, innovations in genetic engineering and modern “conventional” processes of crop development will enable use of these approaches to alter more crops and more traits. Future governance of new plant varieties and foods, regardless of the processes and techniques used to develop them, will require new, scientifically sound assessment methodologies, developed in a manner acceptable to society. Here, we provide a rationale for one governance approach that moves away from current process-based regulation and uses newly developed molecular techniques that enable detailed characterization of the new crops and foods themselves.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abo3034
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
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  • 6
    Online Resource
    Online Resource
    Coupling between oxidation state and hydrogen bond conformation in heme proteins
    Proceedings of the National Academy of Sciences ; 1979
    In:  Proceedings of the National Academy of Sciences Vol. 76, No. 3 ( 1979-03), p. 1009-1013
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 76, No. 3 ( 1979-03), p. 1009-1013
    Abstract: In all heme proteins for which crystal structures are available, the N ε of a histidyl residue is bonded to the heme iron and N δ is hydrogen bonded to a carbonyl oxygen of the peptide backbone. We investigate here the possibility that a change in oxidation state of the iron or a change in the geometry of this hydrogen bond might change the hydrogen bond strength in a functionally significant way. Dimerization energies obtained from ab initio molecular orbital calculations on the hydrogen-bonded dimer of imidazole and planar formamide are used to represent the strength of this hydrogen bond in heme proteins. The effect of a change in iron oxidation state is modeled by varying the positive charge on imidazole. The effect of a change in hydrogen bond geometry is studied by employing x-ray coordinates for reduced and oxidized cytochrome c , deoxy- and metmyoglobin, and deoxy- and methemoglobin. Our conclusions are that the strength of this hydrogen bond in heme proteins is sensitive to both the oxidation state of the iron atom and to geometry changes on the order of those obtained from the x-ray coordinates. We speculate that the changes in oxidation state may be functionally coupled with changes in hydrogen bond geometry and that this hydrogen bond represents a feasible pathway to link protein conformation with redox potential or reactivity of the iron atom.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.76.3.1009
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1979
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  • 7
    Online Resource
    Online Resource
    Augmentation of lymphocyte reactivity in guinea pigs, mice, monkeys and humans sensitised to BCG, dinitrochlorobenzene or nitrogen mustard
    Springer Science and Business Media LLC ; 1974
    In:  Nature Vol. 249, No. 5458 ( 1974-6), p. 656-658
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 249, No. 5458 ( 1974-6), p. 656-658
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/249656a0
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1974
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
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  • 8
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    Online Resource
    Binding of Xenon to Halogens, to Alkali Metals, and to Itself
    Springer Science and Business Media LLC ; 1963
    In:  Nature Vol. 197, No. 4870 ( 1963-3), p. 897-897
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 197, No. 4870 ( 1963-3), p. 897-897
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/197897a0
    RVK:
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1963
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
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  • 9
    Online Resource
    Online Resource
    Helical structure, stability, and dynamics in human apolipoprotein E3 and E4 by hydrogen exchange and mass spectrometry
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 5 ( 2017-01-31), p. 968-973
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 5 ( 2017-01-31), p. 968-973
    Abstract: Apolipoprotein E (apoE) plays a critical role in cholesterol transport in both peripheral circulation and brain. Human apoE is a polymorphic 299-residue protein in which the less common E4 isoform differs from the major E3 isoform only by a C112R substitution. ApoE4 interacts with lipoprotein particles and with the amyloid-β peptide, and it is associated with increased incidence of cardiovascular and Alzheimer’s disease. To understand the structural basis for the differences between apoE3 and E4 functionality, we used hydrogen−deuterium exchange coupled with a fragment separation method and mass spectrometric analysis to compare their secondary structures at near amino acid resolution. We determined the positions, dynamics, and stabilities of the helical segments in these two proteins, in their normal tetrameric state and in mutation-induced monomeric mutants. Consistent with prior X-ray crystallography and NMR results, the N-terminal domain contains four α-helices, 20 to 30 amino acids long. The C-terminal domain is relatively unstructured in the monomeric state but forms an α-helix ∼70 residues long in the self-associated tetrameric state. Helix stabilities are relatively low, 4 kcal/mol to 5 kcal/mol, consistent with flexibility and facile reversible unfolding. Secondary structure in the tetrameric apoE3 and E4 isoforms is similar except that some helical segments in apoE4 spanning residues 12 to 20 and 204 to 210 are unfolded. These conformational differences result from the C112R substitution in the N-terminal helix bundle and likely relate to a reduced ability of apoE4 to form tetramers, thereby increasing the concentration of functional apoE4 monomers, which gives rise to its higher lipid binding compared with apoE3.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1617523114
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
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    detail.hit.zdb_id: 1461794-8
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  • 10
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    Origin of long lifetime of band-edge charge carriers in organic–inorganic lead iodide perovskites
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 29 ( 2017-07-18), p. 7519-7524
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 29 ( 2017-07-18), p. 7519-7524
    Abstract: Long carrier lifetime is what makes hybrid organic–inorganic perovskites high-performance photovoltaic materials. Several microscopic mechanisms behind the unusually long carrier lifetime have been proposed, such as formation of large polarons, Rashba effect, ferroelectric domains, and photon recycling. Here, we show that the screening of band-edge charge carriers by rotation of organic cation molecules can be a major contribution to the prolonged carrier lifetime. Our results reveal that the band-edge carrier lifetime increases when the system enters from a phase with lower rotational entropy to another phase with higher entropy. These results imply that the recombination of the photoexcited electrons and holes is suppressed by the screening, leading to the formation of polarons and thereby extending the lifetime. Thus, searching for organic–inorganic perovskites with high rotational entropy over a wide range of temperature may be a key to achieve superior solar cell performance.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1704421114
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
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