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  • 1
    Online Resource
    Online Resource
    EphB2-dependent prefrontal cortex activation promotes long-range social approach and partner responsiveness
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 9 ( 2023-02-28)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 9 ( 2023-02-28)
    Abstract: Social behavior starts with dynamic approach prior to the final consummation. The flexible processes ensure mutual feedback across social brains to transmit signals. However, how the brain responds to the initial social stimuli precisely to elicit timed behaviors remains elusive. Here, by using real-time calcium recording, we identify the abnormalities of EphB2 mutant with autism-associated Q858X mutation in processing long-range approach and accurate activity of prefrontal cortex (dmPFC). The EphB2-dependent dmPFC activation precedes the behavioral onset and is actively associated with subsequent social action with the partner. Furthermore, we find that partner dmPFC activity is responsive coordinately to the approaching WT mouse rather than Q858X mutant mouse, and the social defects caused by the mutation are rescued by synchro-optogenetic activation in dmPFC of paired social partners. These results thus reveal that EphB2 sustains neuronal activation in the dmPFC that is essential for the proactive modulation of social approach to initial social interaction.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2219952120
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    Observation of an Antimatter Hypernucleus
    American Association for the Advancement of Science (AAAS) ; 2010
    In:  Science Vol. 328, No. 5974 ( 2010-04-02), p. 58-62
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 328, No. 5974 ( 2010-04-02), p. 58-62
    Abstract: Nuclear collisions recreate conditions in the universe microseconds after the Big Bang. Only a very small fraction of the emitted fragments are light nuclei, but these states are of fundamental interest. We report the observation of antihypertritons—comprising an antiproton, an antineutron, and an antilambda hyperon—produced by colliding gold nuclei at high energy. Our analysis yields 70 ± 17 antihypertritons ( H ¯ Λ ¯ 3 ) and 157 ± 30 hypertritons ( H Λ 3 ). The measured yields of H Λ 3 ( H ¯ Λ ¯ 3 ) and 3 He ( He ¯ 3 ) are similar, suggesting an equilibrium in coordinate and momentum space populations of up, down, and strange quarks and antiquarks, unlike the pattern observed at lower collision energies. The production and properties of antinuclei, and of nuclei containing strange quarks, have implications spanning nuclear and particle physics, astrophysics, and cosmology.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1183980
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2010
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  • 3
    Online Resource
    Online Resource
    Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human
    Proceedings of the National Academy of Sciences ; 2005
    In:  Proceedings of the National Academy of Sciences Vol. 102, No. 7 ( 2005-02-15), p. 2430-2435
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 7 ( 2005-02-15), p. 2430-2435
    Abstract: The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002–2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0409608102
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2005
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  • 4
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    Online Resource
    The N-Myc-responsive lncRNA MILIP promotes DNA double-strand break repair through non-homologous end joining
    Proceedings of the National Academy of Sciences ; 2022
    In:  Proceedings of the National Academy of Sciences Vol. 119, No. 49 ( 2022-12-06)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 49 ( 2022-12-06)
    Abstract: The protooncoprotein N-Myc, which is overexpressed in approximately 25% of neuroblastomas as the consequence of MYCN gene amplification, has long been postulated to regulate DNA double-strand break (DSB) repair in neuroblastoma cells, but experimental evidence of this function is presently scant. Here, we show that N-Myc transcriptionally activates the long noncoding RNA MILIP to promote nonhomologous end-joining (NHEJ) DNA repair through facilitating Ku70–Ku80 heterodimerization in neuroblastoma cells. High MILIP expression was associated with poor outcome and appeared as an independent prognostic factor in neuroblastoma patients. Knockdown of MILIP reduced neuroblastoma cell viability through the induction of apoptosis and inhibition of proliferation, retarded neuroblastoma xenograft growth, and sensitized neuroblastoma cells to DNA-damaging therapeutics. The effect of MILIP knockdown was associated with the accumulation of DNA DSBs in neuroblastoma cells largely due to decreased activity of the NHEJ DNA repair pathway. Mechanistical investigations revealed that binding of MILIP to Ku70 and Ku80 increased their heterodimerization, and this was required for MILIP-mediated promotion of NHEJ DNA repair. Disrupting the interaction between MILIP and Ku70 or Ku80 increased DNA DSBs and reduced cell viability with therapeutic potential revealed where targeting MILIP using Gapmers cooperated with the DNA-damaging drug cisplatin to inhibit neuroblastoma growth in vivo. Collectively, our findings identify MILIP as an N-Myc downstream effector critical for activation of the NHEJ DNA repair pathway in neuroblastoma cells, with practical implications of MILIP targeting, alone and in combination with DNA-damaging therapeutics, for neuroblastoma treatment.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2208904119
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
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  • 5
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    Online Resource
    The Coexistence of Superconductivity and Topological Order in the Bi 2 Se 3 Thin Films
    American Association for the Advancement of Science (AAAS) ; 2012
    In:  Science Vol. 336, No. 6077 ( 2012-04-06), p. 52-55
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 336, No. 6077 ( 2012-04-06), p. 52-55
    Abstract: Three-dimensional topological insulators (TIs) are characterized by their nontrivial surface states, in which electrons have their spin locked at a right angle to their momentum under the protection of time-reversal symmetry. The topologically ordered phase in TIs does not break any symmetry. The interplay between topological order and symmetry breaking, such as that observed in superconductivity, can lead to new quantum phenomena and devices. We fabricated a superconducting TI/superconductor heterostructure by growing dibismuth triselenide (Bi 2 Se 3 ) thin films on superconductor niobium diselenide substrate. Using scanning tunneling microscopy and angle-resolved photoemission spectroscopy, we observed the superconducting gap at the Bi 2 Se 3 surface in the regime of Bi 2 Se 3 film thickness where topological surface states form. This observation lays the groundwork for experimentally realizing Majorana fermions in condensed matter physics.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1216466
    RVK:
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2012
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  • 6
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    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
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    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
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  • 7
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    Online Resource
    A tera–electron volt afterglow from a narrow jet in an extremely bright gamma-ray burst
    American Association for the Advancement of Science (AAAS) ; 2023
    In:  Science Vol. 380, No. 6652 ( 2023-06-30), p. 1390-1396
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 380, No. 6652 ( 2023-06-30), p. 1390-1396
    Abstract: Observations of the bright gamma-ray burst GRB 221009A at tera–electron volt energies show that it contained a very narrow jet.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.adg9328
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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  • 8
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    Online Resource
    Edaravone alleviates Alzheimer’s disease-type pathologies and cognitive deficits
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 16 ( 2015-04-21), p. 5225-5230
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 16 ( 2015-04-21), p. 5225-5230
    Abstract: Alzheimer’s disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1422998112
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
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  • 9
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    Online Resource
    High thermoelectric performance in low-cost SnS 0.91 Se 0.09 crystals
    American Association for the Advancement of Science (AAAS) ; 2019
    In:  Science Vol. 365, No. 6460 ( 2019-09-27), p. 1418-1424
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 365, No. 6460 ( 2019-09-27), p. 1418-1424
    Abstract: Thermoelectric technology allows conversion between heat and electricity. Many good thermoelectric materials contain rare or toxic elements, so developing low-cost and high-performance thermoelectric materials is warranted. Here, we report the temperature-dependent interplay of three separate electronic bands in hole-doped tin sulfide (SnS) crystals. This behavior leads to synergistic optimization between effective mass ( m *) and carrier mobility (μ) and can be boosted through introducing selenium (Se). This enhanced the power factor from ~30 to ~53 microwatts per centimeter per square kelvin (μW cm −1 K −2 at 300 K), while lowering the thermal conductivity after Se alloying. As a result, we obtained a maximum figure of merit ZT ( ZT max ) of ~1.6 at 873 K and an average ZT ( ZT ave ) of ~1.25 at 300 to 873 K in SnS 0.91 Se 0.09 crystals. Our strategy for band manipulation offers a different route for optimizing thermoelectric performance. The high-performance SnS crystals represent an important step toward low-cost, Earth-abundant, and environmentally friendly thermoelectrics.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aax5123
    RVK:
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
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  • 10
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    Online Resource
    Tie2cre -induced inactivation of the miRNA-processing enzyme Dicer disrupts invariant NKT cell development
    Proceedings of the National Academy of Sciences ; 2009
    In:  Proceedings of the National Academy of Sciences Vol. 106, No. 25 ( 2009-06-23), p. 10266-10271
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 25 ( 2009-06-23), p. 10266-10271
    Abstract: MicroRNAs (miRNAs) are a class of evolutionarily conserved small noncoding RNAs that are increasingly being recognized as important regulators of gene expression. The ribonuclease III enzyme Dicer is essential for the processing of miRNAs. CD1d-restricted invariant natural killer T ( i NKT) cells are potent regulators of diverse immune responses. The role of Dicer-generated miRNAs in the development and function of immune regulatory i NKT cells is unknown. Here, we generated a mouse strain with a tissue-specific disruption of Dicer, and showed that lack of miRNAs after the deletion of Dicer by Tie2-Cre (expressed in hematopoietic cells and endothelial cells) interrupted the development and maturation of i NKT cells in the thymus and significantly decreased the number of i NKT cells in different immune organs. Thymic and peripheral i NKT cell compartments were changed in miRNA-deficient mice, with a significantly increased frequency of CD4 + CD8 + i NKT cells in the thymus and a significantly decreased frequency of CD4 + i NKT cells in the spleen. MiRNA-deficient i NKT cells display profound defects in α-GalCer-induced activation and cytokine production. Bone marrow (BM) from miRNA-deficient mice poorly reconstituted i NKT cells compared to BM from WT mice. Also, using a thymic iNKT cell transfer model, we found that i NKT cell homeostasis was impaired in miRNA-deficient recipient mice. Our data indicate that miRNAs expressed in hematopoietic cells and endothelial cells are potent regulators of i NKT cell development, function, and homeostasis.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0811119106
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2009
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