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  • 1
    Online Resource
    Online Resource
    Integrative functional genomic analysis of human brain development and neuropsychiatric risks
    American Association for the Advancement of Science (AAAS) ; 2018
    In:  Science Vol. 362, No. 6420 ( 2018-12-14)
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 362, No. 6420 ( 2018-12-14)
    Abstract: To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type–specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C , SATB2 , SOX5 , TCF4 , and TSHZ3 ) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aat7615
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2018
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  • 2
    Online Resource
    Online Resource
    “Perfect” designer chromosome V and behavior of a ring derivative
    American Association for the Advancement of Science (AAAS) ; 2017
    In:  Science Vol. 355, No. 6329 ( 2017-03-10)
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 355, No. 6329 ( 2017-03-10)
    Abstract: Perfect matching of an assembled physical sequence to a specified designed sequence is crucial to verify design principles in genome synthesis. We designed and de novo synthesized 536,024–base pair chromosome synV in the “Build-A-Genome China” course. We corrected an initial isolate of synV to perfectly match the designed sequence using integrative cotransformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)–mediated editing in 22 steps; synV strains exhibit high fitness under a variety of culture conditions, compared with that of wild-type V strains. A ring synV derivative was constructed, which is fully functional in Saccharomyces cerevisiae under all conditions tested and exhibits lower spore viability during meiosis. Ring synV chromosome can extends Sc2.0 design principles and provides a model with which to study genomic rearrangement, ring chromosome evolution, and human ring chromosome disorders.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aaf4704
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2017
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 3
    Online Resource
    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:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 4
    Online Resource
    Online Resource
    Coding mutations in NUS1 contribute to Parkinson’s disease
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 45 ( 2018-11-06), p. 11567-11572
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 45 ( 2018-11-06), p. 11567-11572
    Abstract: Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson’s disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD. We identified 12 genes with de novo mutations ( MAD1L1 , NUP98 , PPP2CB , PKMYT1 , TRIM24 , CEP131 , CTTNBP2 , NUS1 , SMPD3 , MGRN1 , IFI35 , and RUSC2 ), which could be functionally relevant to PD pathogenesis. Further analyses of two independent case-control cohorts (1,852 patients and 1,565 controls in one cohort and 3,237 patients and 2,858 controls in the other) revealed that NUS1 harbors significantly more rare nonsynonymous variants ( P = 1.01E-5, odds ratio = 11.3) in PD patients than in controls. Functional studies in Drosophila demonstrated that the loss of NUS1 could reduce the climbing ability, dopamine level, and number of dopaminergic neurons in 30-day-old flies and could induce apoptosis in fly brain. Together, our data suggest that de novo mutations could contribute to early onset PD pathogenesis and identify NUS1 as a candidate gene for PD.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1809969115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
    detail.hit.zdb_id: 209104-5
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    SSG: 11
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Steady-state BOLD Response to Higher-order Cognition Modulates Low-Frequency Neural Oscillations
    MIT Press ; 2015
    In:  Journal of Cognitive Neuroscience Vol. 27, No. 12 ( 2015-12-01), p. 2406-2415
    Details
    In: Journal of Cognitive Neuroscience, MIT Press, Vol. 27, No. 12 ( 2015-12-01), p. 2406-2415
    Abstract: Steady-state responses (SSRs) reflect the synchronous neural oscillations evoked by noninvasive and consistently repeated stimuli at the fundamental or harmonic frequencies. The steady-state evoked potentials (SSEPs; the representative form of the SSRs) have been widely used in the cognitive and clinical neurosciences and brain–computer interface research. However, the steady-state evoked potentials have limitations in examining high-frequency neural oscillations and basic cognition. In addition, synchronous neural oscillations in the low frequency range ( & lt;1 Hz) and in higher-order cognition have received a little attention. Therefore, we examined the SSRs in the low frequency range using a new index, the steady-state BOLD responses (SSBRs) evoked by semantic stimuli. Our results revealed that the significant SSBRs were induced at the fundamental frequency of stimuli and the first harmonic in task-related regions, suggesting the enhanced variability of neural oscillations entrained by exogenous stimuli. The SSBRs were independent of neurovascular coupling and characterized by sensorimotor bias, an indication of regional-dependent neuroplasticity. Furthermore, the amplitude of SSBRs may predict behavioral performance and show the psychophysiological relevance. Our findings provide valuable insights into the understanding of the SSRs evoked by higher-order cognition and how the SSRs modulate low-frequency neural oscillations.
    Type of Medium: Online Resource
    ISSN: 0898-929X , 1530-8898
    URL: Article
    DOI: 10.1162/jocn_a_00864
    Language: English
    Publisher: MIT Press
    Publication Date: 2015
    SSG: 5,2
    SSG: 7,11
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  • 6
    Online Resource
    Online Resource
    All-oxide–based synthetic antiferromagnets exhibiting layer-resolved magnetization reversal
    American Association for the Advancement of Science (AAAS) ; 2017
    In:  Science Vol. 357, No. 6347 ( 2017-07-14), p. 191-194
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 357, No. 6347 ( 2017-07-14), p. 191-194
    Abstract: Synthesizing antiferromagnets with correlated oxides has been challenging, owing partly to the markedly degraded ferromagnetism of the magnetic layer at nanoscale thicknesses. Here we report on the engineering of an antiferromagnetic interlayer exchange coupling (AF-IEC) between ultrathin but ferromagnetic La 2/3 Ca 1/3 MnO 3 layers across an insulating CaRu 1/2 Ti 1/2 O 3 spacer. The layer-resolved magnetic switching leads to sharp steplike hysteresis loops with magnetization plateaus depending on the repetition number of the stacking bilayers. The magnetization configurations can be switched at moderate fields of hundreds of oersted. Moreover, the AF-IEC can also be realized with an alternative magnetic layer of La 2/3 Sr 1/3 MnO 3 that possesses a Curie temperature near room temperature. The findings will add functionalities to devices with correlated-oxide interfaces.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aak9717
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2017
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  • 7
    Online Resource
    Online Resource
    Zika virus directly infects peripheral neurons and induces cell death
    Springer Science and Business Media LLC ; 2017
    In:  Nature Neuroscience Vol. 20, No. 9 ( 2017-09-01), p. 1209-1212
    Details
    In: Nature Neuroscience, Springer Science and Business Media LLC, Vol. 20, No. 9 ( 2017-09-01), p. 1209-1212
    Type of Medium: Online Resource
    ISSN: 1097-6256 , 1546-1726
    URL: Article
    DOI: 10.1038/nn.4612
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2017
    detail.hit.zdb_id: 1494955-6
    SSG: 12
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  • 8
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    Online Resource
    Trio-based exome sequencing arrests de novo mutations in early-onset high myopia
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 16 ( 2017-04-18), p. 4219-4224
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 16 ( 2017-04-18), p. 4219-4224
    Abstract: The etiology of the highly myopic condition has been unclear for decades. We investigated the genetic contributions to early-onset high myopia (EOHM), which is defined as having a refraction of less than or equal to −6 diopters before the age of 6, when children are less likely to be exposed to high educational pressures. Trios (two nonmyopic parents and one child) were examined to uncover pathogenic mutations using whole-exome sequencing. We identified parent-transmitted biallelic mutations or de novo mutations in as-yet-unknown or reported genes in 16 probands. Interestingly, an increased rate of de novo mutations was identified in the EOHM patients. Among the newly identified candidate genes, a BSG mutation was identified in one EOHM proband. Expanded screening of 1,040 patients found an additional four mutations in the same gene. Then, we generated Bsg mutant mice to further elucidate the functional impact of this gene and observed typical myopic phenotypes, including an elongated axial length. Using a trio-based exonic screening study in EOHM, we deciphered a prominent role for de novo mutations in EOHM patients without myopic parents. The discovery of a disease gene, BSG , provides insights into myopic development and its etiology, which expands our current understanding of high myopia and might be useful for future treatment and prevention.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1615970114
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
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    SSG: 11
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Telomerase Reverse Transcriptase and p53 Regulate Mammalian Peripheral Nervous System and CNS Axon Regeneration Downstream of c-Myc
    Society for Neuroscience ; 2019
    In:  The Journal of Neuroscience Vol. 39, No. 46 ( 2019-11-13), p. 9107-9118
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 39, No. 46 ( 2019-11-13), p. 9107-9118
    Abstract: Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration. SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo . Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.0419-19.2019
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2019
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 10
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    Online Resource
    Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice
    American Association for the Advancement of Science (AAAS) ; 2019
    In:  Science Vol. 364, No. 6437 ( 2019-04-19), p. 292-295
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 364, No. 6437 ( 2019-04-19), p. 292-295
    Abstract: Cytosine and adenine base editors (CBEs and ABEs) are promising new tools for achieving the precise genetic changes required for disease treatment and trait improvement. However, genome-wide and unbiased analyses of their off-target effects in vivo are still lacking. Our whole-genome sequencing analysis of rice plants treated with the third-generation base editor (BE3), high-fidelity BE3 (HF1-BE3), or ABE revealed that BE3 and HF1-BE3, but not ABE, induce substantial genome-wide off-target mutations, which are mostly the C→T type of single-nucleotide variants (SNVs) and appear to be enriched in genic regions. Notably, treatment of rice with BE3 or HF1-BE3 in the absence of single-guide RNA also results in the rise of genome-wide SNVs. Thus, the base-editing unit of BE3 or HF1-BE3 needs to be optimized in order to attain high fidelity.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aaw7166
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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