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  • 1
    Online Resource
    Online Resource
    De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 5 ( 2020-02-04), p. 2560-2569
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 5 ( 2020-02-04), p. 2560-2569
    Abstract: De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains 〈 1% of variation. While we are underpowered to see small differences, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, we did find significantly fewer DNMs in Amish individuals, even when compared with other Europeans, and even after accounting for parental age and sequencing center. Specifically, we found significant reductions in the number of C→A and T→C mutations in the Amish, which seem to underpin their overall reduction in DNMs. Finally, we calculated near-zero estimates of narrow sense heritability ( h 2 ), which suggest that variation in DNM rate is significantly shaped by nonadditive genetic effects and the environment.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1902766117
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
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  • 2
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    Cross-species recognition of SARS-CoV-2 to bat ACE2
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 1 ( 2021-01-05)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 1 ( 2021-01-05)
    Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a major threat to global health. Although varied SARS-CoV-2–related coronaviruses have been isolated from bats and SARS-CoV-2 may infect bat, the structural basis for SARS-CoV-2 to utilize the human receptor counterpart bat angiotensin-converting enzyme 2 (bACE2) for virus infection remains less understood. Here, we report that the SARS-CoV-2 spike protein receptor binding domain (RBD) could bind to bACE2 from Rhinolophus macrotis (bACE2-Rm) with substantially lower affinity compared with that to the human ACE2 (hACE2), and its infectivity to host cells expressing bACE2-Rm was confirmed with pseudotyped SARS-CoV-2 virus and SARS-CoV-2 wild virus. The structure of the SARS-CoV-2 RBD with the bACE2-Rm complex was determined, revealing a binding mode similar to that of hACE2. The analysis of binding details between SARS-CoV-2 RBD and bACE2-Rm revealed that the interacting network involving Y41 and E42 of bACE2-Rm showed substantial differences with that to hACE2. Bats have extensive species diversity and the residues for RBD binding in bACE2 receptor varied substantially among different bat species. Notably, the Y41H mutant, which exists in many bats, attenuates the binding capacity of bACE2-Rm, indicating the central roles of Y41 in the interaction network. These findings would benefit our understanding of the potential infection of SARS-CoV-2 in varied species of bats.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2020216118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
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  • 3
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    Characterization and application of single fluorescent nanodiamonds as cellular biomarkers
    Proceedings of the National Academy of Sciences ; 2007
    In:  Proceedings of the National Academy of Sciences Vol. 104, No. 3 ( 2007-01-16), p. 727-732
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 3 ( 2007-01-16), p. 727-732
    Abstract: Type Ib diamonds emit bright fluorescence at 550–800 nm from nitrogen-vacancy point defects, (N-V) 0 and (N-V) − , produced by high-energy ion beam irradiation and subsequent thermal annealing. The emission, together with noncytotoxicity and easiness of surface functionalization, makes nano-sized diamonds a promising fluorescent probe for single-particle tracking in heterogeneous environments. We present the result of our characterization and application of single fluorescent nanodiamonds as cellular biomarkers. We found that, under the same excitation conditions, the fluorescence of a single 35-nm diamond is significantly brighter than that of a single dye molecule such as Alexa Fluor 546. The latter photobleached in the range of 10 s at a laser power density of 10 4 W/cm 2 , whereas the nanodiamond particle showed no sign of photobleaching even after 5 min of continuous excitation. Furthermore, no fluorescence blinking was detected within a time resolution of 1 ms. The photophysical properties of the particles do not deteriorate even after surface functionalization with carboxyl groups, which form covalent bonding with poly l -lysines that interact with DNA molecules through electrostatic forces. The feasibility of using surface-functionalized fluorescent nanodiamonds as single-particle biomarkers is demonstrated with both fixed and live HeLa cells.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0605409104
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2007
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  • 4
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    Online Resource
    The Role of N ‐Methyl‐d‐aspartate Receptors in Neurobehavioral Changes Induced by Toluene Exposure during Synaptogenesis
    Wiley ; 2004
    In:  Annals of the New York Academy of Sciences Vol. 1025, No. 1 ( 2004-10), p. 552-555
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1025, No. 1 ( 2004-10), p. 552-555
    Abstract: A bstract : Toluene abuse during pregnancy results in newborns with fetal solvent syndrome. N ‐Methyl‐d‐aspartate (NMDA) receptor has been identified as a target site for toluene. Since the normal function of NMDA receptor is critical for synaptogenesis, the long‐term effects of toluene exposure during synaptogenesis on the neurobehavioral function and the expression of NMDA receptor subunits (NR1, NR2A, and NR2B) were examined. Rats exposed to l g/kg of toluene (i.p.) over postnatal days 4 to 9 were found to exhibit reduction in body weight, NMDA‐induced seizure thresholds, and MK‐801‐induced hyperlocomotor activity. Furthermore, immunoblotting and immunohistochemical analysis revealed a significant increase in NR2A subunit expression in the hippocampus and cerebellum of toluene‐exposed rats on PN30. These results suggest that the region‐specific changes in the expression of NMDA receptor subunits may play a role in the neurobehavioral dysfunction following toluene exposure during synaptogenesis.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Article
    DOI: 10.1196/annals.1316.067
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 2004
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    SSG: 11
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  • 5
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    A machine learning–based biological aging prediction and its associations with healthy lifestyles: the Dongfeng–Tongji cohort
    Wiley ; 2022
    In:  Annals of the New York Academy of Sciences Vol. 1507, No. 1 ( 2022-01), p. 108-120
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 1507, No. 1 ( 2022-01), p. 108-120
    Abstract: This study aims to establish a biological age (BA) predictor and to investigate the roles of lifestyles on biological aging. The 14,848 participants with the available information of multisystem measurements from the Dongfeng–Tongji cohort were used to estimate BA. We developed a composite BA predictor showing a high correlation with chronological age (CA) ( r =  0.82) by using an extreme gradient boosting (XGBoost) algorithm. The average frequency hearing threshold, forced expiratory volume in 1 second (FEV 1 ), gender, systolic blood pressure, and homocysteine ranked as the top five important features for the BA predictor. Two aging indexes, recorded as the AgingAccel (the residual from regressing predicted age on CA) and aging rate (the ratio of predicted age to CA), showed positive associations with the risks of all‐cause (HR (95% CI) = 1.12 (1.10–1.14) and 1.08 (1.07–1.10), respectively) and cause‐specific (HRs ranged from 1.06 to ∼1.15) mortality. Each 1‐point increase in healthy lifestyle score (including normal body mass index, never smoking, moderate alcohol drinking, physically active, and sleep 7–9 h/night) was associated with a 0.21‐year decrease in the AgingAccel (95% CI: −0.27 to −0.15) and a 0.4% decrease in the aging rate (95% CI: −0.5% to −0.3%). This study developed a machine learning–based BA predictor in a prospective Chinese cohort. Adherence to healthy lifestyles showed associations with delayed biological aging, which highlights potential preventive interventions.
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Issue
    URL: Article
    DOI: 10.1111/nyas.v1507.1
    DOI: 10.1111/nyas.14685
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 2022
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    detail.hit.zdb_id: 211003-9
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  • 6
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    Online Resource
    Bioactive Small Peptides from Soybean Protein
    Wiley ; 1998
    In:  Annals of the New York Academy of Sciences Vol. 864, No. 1 ( 1998-12), p. 640-645
    Details
    In: Annals of the New York Academy of Sciences, Wiley, Vol. 864, No. 1 ( 1998-12), p. 640-645
    Type of Medium: Online Resource
    ISSN: 0077-8923 , 1749-6632
    URL: Issue
    URL: Article
    DOI: 10.1111/nyas.1998.864.issue-1
    DOI: 10.1111/j.1749-6632.1998.tb10396.x
    RVK:
    TD 7650
    Language: English
    Publisher: Wiley
    Publication Date: 1998
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  • 7
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    Online Resource
    Generation of influenza A viruses as live but replication-incompetent virus vaccines
    American Association for the Advancement of Science (AAAS) ; 2016
    In:  Science Vol. 354, No. 6316 ( 2016-12-02), p. 1170-1173
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 354, No. 6316 ( 2016-12-02), p. 1170-1173
    Abstract: The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)–harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell–mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aah5869
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2016
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  • 8
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    Sugar status in preexisting leaves determines systemic stomatal development within newly developing leaves
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 24 ( 2023-06-13)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 24 ( 2023-06-13)
    Abstract: Stomata are pores found in the epidermis of stems or leaves that modulate both plant gas exchange and water/nutrient uptake. The development and function of plant stomata are regulated by a diverse range of environmental cues. However, how carbohydrate status in preexisting leaves might determine systemic stomatal formation within newly developing leaves has remained obscure. The glucose (Glc) sensor HEXOKINASE1 (HXK1) has been reported to decrease the stability of an ethylene/Glc signaling transcriptional regulator, EIN3 (ETHYLENE INSENSITIVE3). EIN3 in turn directly represses the expression of SUC2 ( sucrose transporter 2 ), encoding a master transporter of sucrose (Suc). Further, KIN10, a nuclear regulator involved in energy homeostasis, has been reported to repress the transcription factor SPCH (SPEECHLESS), a master regulator of stomatal development. Here, we demonstrate that the Glc status of preexisting leaves determines systemic stomatal development within newly developing leaves by the HXK1—¦EIN3—¦SUC2 module. Further, increasing Glc levels in preexisting leaves results in a HXK1-dependent decrease of EIN3 and increase of SUC2, triggering the perception, amplification and relay of HXK1-dependent Glc signaling and thereby triggering Suc transport from mature to newly developing leaves. The HXK1—¦EIN3—¦SUC2 molecular module thereby drives systemic Suc transport from preexisting leaves to newly developing leaves. Subsequently, increasing Suc levels within newly developing leaves promotes stomatal formation through the established KIN10⟶ SPCH module. Our findings thus show how a carbohydrate signal in preexisting leaves is sensed, amplified and relayed to determine the extent of systemic stomatal development within newly developing leaves.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2302854120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
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  • 9
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    Erratum: Corrigendum: The formation and fate of internal waves in the South China Sea
    Springer Science and Business Media LLC ; 2015
    In:  Nature Vol. 528, No. 7580 ( 2015-12), p. 152-152
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 528, No. 7580 ( 2015-12), p. 152-152
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/nature16157
    RVK:
    TA 1000
    RVK:
    UA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2015
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  • 10
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    Electron mean-free-path filtering in Dirac material for improved thermoelectric performance
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 5 ( 2018-01-30), p. 879-884
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 5 ( 2018-01-30), p. 879-884
    Abstract: Recent advancements in thermoelectric materials have largely benefited from various approaches, including band engineering and defect optimization, among which the nanostructuring technique presents a promising way to improve the thermoelectric figure of merit ( zT ) by means of reducing the characteristic length of the nanostructure, which relies on the belief that phonons’ mean free paths (MFPs) are typically much longer than electrons’. Pushing the nanostructure sizes down to the length scale dictated by electron MFPs, however, has hitherto been overlooked as it inevitably sacrifices electrical conduction. Here we report through ab initio simulations that Dirac material can overcome this limitation. The monotonically decreasing trend of the electron MFP allows filtering of long-MFP electrons that are detrimental to the Seebeck coefficient, leading to a dramatically enhanced power factor. Using SnTe as a material platform, we uncover this MFP filtering effect as arising from its unique nonparabolic Dirac band dispersion. Room-temperature zT can be enhanced by nearly a factor of 3 if one designs nanostructures with grain sizes of ∼10 nm. Our work broadens the scope of the nanostructuring approach for improving the thermoelectric performance, especially for materials with topologically nontrivial electronic dynamics.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1715477115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
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    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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