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  • 1
    Online Resource
    Online Resource
    Deep learning predicts DNA methylation regulatory variants in the human brain and elucidates the genetics of psychiatric disorders
    Proceedings of the National Academy of Sciences ; 2022
    In:  Proceedings of the National Academy of Sciences Vol. 119, No. 34 ( 2022-08-23)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 34 ( 2022-08-23)
    Abstract: There is growing evidence for the role of DNA methylation (DNAm) quantitative trait loci (mQTLs) in the genetics of complex traits, including psychiatric disorders. However, due to extensive linkage disequilibrium (LD) of the genome, it is challenging to identify causal genetic variations that drive DNAm levels by population-based genetic association studies. This limits the utility of mQTLs for fine-mapping risk loci underlying psychiatric disorders identified by genome-wide association studies (GWAS). Here we present INTERACT, a deep learning model that integrates convolutional neural networks with transformer, to predict effects of genetic variations on DNAm levels at CpG sites in the human brain. We show that INTERACT-derived DNAm regulatory variants are not confounded by LD, are concentrated in regulatory genomic regions in the human brain, and are convergent with mQTL evidence from genetic association analysis. We further demonstrate that predicted DNAm regulatory variants are enriched for heritability of brain-related traits and improve polygenic risk prediction for schizophrenia across diverse ancestry samples. Finally, we applied predicted DNAm regulatory variants for fine-mapping schizophrenia GWAS risk loci to identify potential novel risk genes. Our study shows the power of a deep learning approach to identify functional regulatory variants that may elucidate the genetic basis of complex traits.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2206069119
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Comparative proteomics reveal distinct chaperone–client interactions in supporting bacterial acid resistance
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 39 ( 2016-09-27), p. 10872-10877
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 39 ( 2016-09-27), p. 10872-10877
    Abstract: HdeA and HdeB constitute the essential chaperone system that functions in the unique periplasmic space of Gram-negative enteric bacteria to confer acid resistance. How this two-chaperone machinery cooperates to protect a broad range of client proteins from acid denaturation while avoiding nonspecific binding during bacterial passage through the highly acidic human stomach remains unclear. We have developed a comparative proteomic strategy that combines the genetically encoded releasable protein photocross-linker with 2D difference gel electrophoresis, which allows an unbiased side-by-side comparison of the entire client pools from these two acid-activated chaperones in Escherichia coli . Our results reveal distinct client specificities between HdeA and HdeB in vivo that are determined mainly by their different responses to pH stimulus. The intracellular acidity serves as an environmental cue to determine the folding status of both chaperones and their clients, enabling specific chaperone–client binding and release under defined pH conditions. This cooperative and synergistic mode of action provides an efficient, economical, flexible, and finely tuned protein quality control strategy for coping with acid stress.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1606360113
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Detecting grain rotation at the nanoscale
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 9 ( 2014-03-04), p. 3350-3353
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 9 ( 2014-03-04), p. 3350-3353
    Abstract: It is well-believed that below a certain particle size, grain boundary-mediated plastic deformation (e.g., grain rotation, grain boundary sliding and diffusion) substitutes for conventional dislocation nucleation and motion as the dominant deformation mechanism. However, in situ probing of grain boundary processes of ultrafine nanocrystals during plastic deformation has not been feasible, precluding the direct exploration of the nanomechanics. Here we present the in situ texturing observation of bulk-sized platinum in a nickel pressure medium of various particle sizes from 500 nm down to 3 nm. Surprisingly, the texture strength of the same-sized platinum drops rapidly with decreasing grain size of the nickel medium, indicating that more active grain rotation occurs in the smaller nickel nanocrystals. Insight into these processes provides a better understanding of the plastic deformation of nanomaterials in a few-nanometer length scale.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1324184111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Enhancement of visual dominance effects at the response level in children with attention-deficit/hyperactivity disorder
    Elsevier BV ; 2024
    In:  Journal of Experimental Child Psychology Vol. 242 ( 2024-06), p. 105897-
    Details
    In: Journal of Experimental Child Psychology, Elsevier BV, Vol. 242 ( 2024-06), p. 105897-
    Type of Medium: Online Resource
    ISSN: 0022-0965
    URL: Article
    DOI: 10.1016/j.jecp.2024.105897
    RVK:
    CL 1000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 1469602-2
    SSG: 5,2
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  • 5
    Online Resource
    Online Resource
    A symplectic method for structure-preserving modelling of damped acoustic waves
    The Royal Society ; 2015
    In:  Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences Vol. 471, No. 2183 ( 2015-11), p. 20150105-
    Details
    In: Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, The Royal Society, Vol. 471, No. 2183 ( 2015-11), p. 20150105-
    Abstract: In this paper, a symplectic method for structure-preserving modelling of the damped acoustic wave equation is introduced. The equation is traditionally solved using non-symplectic schemes. However, these schemes corrupt some intrinsic properties of the equation such as the conservation of both precision and the damping property in long-term calculations. In the method presented, an explicit second-order symplectic scheme is used for the time discretization, whereas physical space is discretized by the discrete singular convolution differentiator. The performance of the proposed scheme has been tested and verified using numerical simulations of the attenuating scalar seismic-wave equation. Scalar seismic wave-field modelling experiments on a heterogeneous medium with both damping and high-parameter contrasts demonstrate the superior performance of the approach presented for suppression of numerical dispersion. Long-term computational experiments display the remarkable capability of the approach presented for long-time simulations of damped acoustic wave equations. Promising numerical results suggest that the approach is suitable for high-precision and long-time numerical simulations of wave equations with damping terms, as it has a structure-preserving property for the damping term.
    Type of Medium: Online Resource
    ISSN: 1364-5021 , 1471-2946
    URL: Article
    DOI: 10.1098/rspa.2015.0105
    Language: English
    Publisher: The Royal Society
    Publication Date: 2015
    detail.hit.zdb_id: 209241-4
    detail.hit.zdb_id: 1460987-3
    SSG: 11
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  • 6
    Online Resource
    Online Resource
    Air pollution interacts with genetic risk to influence cortical networks implicated in depression
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 46 ( 2021-11-16)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 46 ( 2021-11-16)
    Abstract: Air pollution is a reversible cause of significant global mortality and morbidity. Epidemiological evidence suggests associations between air pollution exposure and impaired cognition and increased risk for major depressive disorders. However, the neural bases of these associations have been unclear. Here, in healthy human subjects exposed to relatively high air pollution and controlling for socioeconomic, genomic, and other confounders, we examine across multiple levels of brain network function the extent to which particulate matter (PM 2.5 ) exposure influences putative genetic risk mechanisms associated with depression. Increased ambient PM 2.5 exposure was associated with poorer reasoning and problem solving and higher-trait anxiety/depression. Working memory and stress-related information transfer (effective connectivity) across cortical and subcortical brain networks were influenced by PM 2.5 exposure to differing extents depending on the polygenic risk for depression in gene-by-environment interactions. Effective connectivity patterns from individuals with higher polygenic risk for depression and higher exposures with PM 2.5 , but not from those with lower genetic risk or lower exposures, correlated spatially with the coexpression of depression-associated genes across corresponding brain regions in the Allen Brain Atlas. These converging data suggest that PM 2.5 exposure affects brain network functions implicated in the genetic mechanisms of depression.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2109310118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Texture of Nanocrystalline Nickel: Probing the Lower Size Limit of Dislocation Activity
    American Association for the Advancement of Science (AAAS) ; 2012
    In:  Science Vol. 338, No. 6113 ( 2012-12-14), p. 1448-1451
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 338, No. 6113 ( 2012-12-14), p. 1448-1451
    Abstract: The size of nanocrystals provides a limitation on dislocation activity and associated stress-induced deformation. Dislocation-mediated plastic deformation is expected to become inactive below a critical particle size, which has been proposed to be between 10 and 30 nanometers according to computer simulations and transmission electron microscopy analysis. However, deformation experiments at high pressure on polycrystalline nickel suggest that dislocation activity is still operative in 3-nanometer crystals. Substantial texturing is observed at pressures above 3.0 gigapascals for 500-nanometer nickel and at greater than 11.0 gigapascals for 20-nanometer nickel. Surprisingly, texturing is also seen in 3-nanometer nickel when compressed above 18.5 gigapascals. The observations of pressure-promoted texturing indicate that under high external pressures, dislocation activity can be extended down to a few-nanometers-length scale.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1228211
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2012
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 8
    Online Resource
    Online Resource
    Cross-modal conflict deficit in children with attention-deficit/hyperactivity disorder
    Elsevier BV ; 2024
    In:  Journal of Experimental Child Psychology Vol. 243 ( 2024-07), p. 105917-
    Details
    In: Journal of Experimental Child Psychology, Elsevier BV, Vol. 243 ( 2024-07), p. 105917-
    Type of Medium: Online Resource
    ISSN: 0022-0965
    URL: Article
    DOI: 10.1016/j.jecp.2024.105917
    RVK:
    CL 1000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2024
    detail.hit.zdb_id: 1469602-2
    SSG: 5,2
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