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  • 1
    Online Resource
    Online Resource
    Working Memory for Spatial Sequences: Developmental and Evolutionary Factors in Encoding Ordinal and Relational Structures
    Society for Neuroscience ; 2022
    In:  The Journal of Neuroscience Vol. 42, No. 5 ( 2022-02-02), p. 850-864
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 42, No. 5 ( 2022-02-02), p. 850-864
    Abstract: Sequence learning is a ubiquitous facet of human and animal cognition. Here, using a common sequence reproduction task, we investigated whether and how the ordinal and relational structures linking consecutive elements are acquired by human adults, children, and macaque monkeys. While children and monkeys exhibited significantly lower precision than adults for spatial location and temporal order information, only monkeys appeared to exceedingly focus on the first item. Most importantly, only humans, regardless of age, spontaneously extracted the spatial relations between consecutive items and used a chunking strategy to compress sequences in working memory. Monkeys did not detect such relational structures, even after extensive training. Monkey behavior was captured by a conjunctive coding model, whereas a chunk-based conjunctive model explained more variance in humans. These age- and species-related differences are indicative of developmental and evolutionary mechanisms of sequence encoding and may provide novel insights into the uniquely human cognitive capacities. SIGNIFICANCE STATEMENT Sequence learning, the ability to encode the order of discrete elements and their relationships presented within a sequence, is a ubiquitous facet of cognition among humans and animals. By exploring sequence-processing abilities at different human developmental stages and in nonhuman primates, we found that only humans, regardless of age, spontaneously extracted the spatial relations between consecutive items and used an internal language to compress sequences in working memory. The findings provided insights into understanding the origins of sequence capabilities in humans and how they evolve through development to identify the unique aspects of human cognitive capacity, which includes the comprehension, learning, and production of sequences, and perhaps, above all, language processing.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.0603-21.2021
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2022
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  • 2
    Online Resource
    Online Resource
    Increased neural activity of right temporo-parietal junction causes different effect on altruism in situations of advantageous and disadvantageous inequity
    Elsevier BV ; 2023
    In:  Brain and Cognition Vol. 171 ( 2023-10), p. 106061-
    Details
    In: Brain and Cognition, Elsevier BV, Vol. 171 ( 2023-10), p. 106061-
    Type of Medium: Online Resource
    ISSN: 0278-2626
    URL: Article
    DOI: 10.1016/j.bandc.2023.106061
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 3
    Online Resource
    Online Resource
    GFAP hyperpalmitoylation exacerbates astrogliosis and neurodegenerative pathology in PPT1-deficient mice
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 13 ( 2021-03-30)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 13 ( 2021-03-30)
    Abstract: The homeostasis of protein palmitoylation and depalmitoylation is essential for proper physiological functions in various tissues, in particular the central nervous system (CNS). The dysfunction of PPT1 (PPT1-KI, infantile neuronal ceroid lipofuscinosis [INCL] mouse model), which catalyze the depalmitoylation process, results in serious neurodegeneration accompanied by severe astrogliosis in the brain. Endeavoring to determine critical factors that might account for the pathogenesis in CNS by palm-proteomics, glial fibrillary acidic protein (GFAP) was spotted, indicating that GFAP is probably palmitoylated. Questions concerning if GFAP is indeed palmitoylated in vivo and how palmitoylation of GFAP might participate in neural pathology remain unexplored and are waiting to be investigated. Here we show that GFAP is readily palmitoylated in vitro and in vivo; specifically, cysteine-291 is the unique palmitoylated residue in GFAP. Interestingly, it was found that palmitoylated GFAP promotes astrocyte proliferation in vitro. Furthermore, we showed that PPT1 depalmitoylates GFAP, and the level of palmitoylated GFAP is overwhelmingly up-regulated in PPT1-knockin mice, which lead us to speculate that the elevated level of palmitoylated GFAP might accelerate astrocyte proliferation in vivo and ultimately led to astrogliosis in INCL. Indeed, blocking palmitoylation by mutating cysteine-291 into alanine in GFAP attenuate astrogliosis, and remarkably, the concurrent neurodegenerative pathology in PPT1-knockin mice. Together, these findings demonstrate that hyperpalmitoylated GFAP plays critical roles in regulating the pathogenesis of astrogliosis and neurodegeneration in the CNS, and most importantly, pinpointing that cysteine-291 in GFAP might be a valuable pharmaceutical target for treating INCL and other potential neurodegenerative diseases.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2022261118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
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  • 4
    Online Resource
    Online Resource
    Feedback regulation of ubiquitination and phase separation of HECT E3 ligases
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 33 ( 2023-08-15)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 33 ( 2023-08-15)
    Abstract: Lipid homeostasis is essential for normal cellular functions and dysregulation of lipid metabolism is highly correlated with human diseases including neurodegenerative diseases. In the ubiquitin-dependent autophagic degradation pathway, Troyer syndrome–related protein Spartin activates and recruits HECT-type E3 Itch to lipid droplets (LDs) to regulate their turnover. In this study, we find that Spartin promotes the formation of Itch condensates independent of LDs. Spartin activates Itch through its multiple PPAY-motif platform generated by self-oligomerization, which targets the WW12 domains of Itch and releases the autoinhibition of the ligase. Spartin-induced activation and subsequent autoubiquitination of Itch lead to liquid–liquid phase separation (LLPS) of the poly-, but not oligo-, ubiquitinated Itch together with Spartin and E2 both in vitro and in living cells. LLPS-mediated condensation of the reaction components further accelerates the generation of polyubiquitin chains, thus forming a positive feedback loop. Such Itch–Spartin condensates actively promote the autophagy-dependent turnover of LDs. Moreover, we show that the catalytic HECT domain of Itch is sufficient to interact and phase separate with poly-, but not oligo-ubiquitin chains. HECT domains from other HECT E3 ligases also exhibit LLPS-mediated the promotion of ligase activity. Therefore, LLPS and ubiquitination are mutually interdependent and LLPS promotes the ligase activity of the HECT family E3 ligases.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2302478120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
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  • 5
    Online Resource
    Online Resource
    SIRT7 promotes lung cancer progression by destabilizing the tumor suppressor ARF
    Proceedings of the National Academy of Sciences ; 2024
    In:  Proceedings of the National Academy of Sciences Vol. 121, No. 25 ( 2024-06-18)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 121, No. 25 ( 2024-06-18)
    Abstract: Sirtuin 7 (SIRT7) is a member of the mammalian family of nicotinamide adenine dinucleotide (NAD + )-dependent histone/protein deacetylases, known as sirtuins. It acts as a potent oncogene in numerous malignancies, but the molecular mechanisms employed by SIRT7 to sustain lung cancer progression remain largely uncharacterized. We demonstrate that SIRT7 exerts oncogenic functions in lung cancer cells by destabilizing the tumor suppressor alternative reading frame (ARF). SIRT7 directly interacts with ARF and prevents binding of ARF to nucleophosmin, thereby promoting proteasomal-dependent degradation of ARF. We show that SIRT7-mediated degradation of ARF increases expression of protumorigenic genes and stimulates proliferation of non-small-cell lung cancer (NSCLC) cells both in vitro and in vivo in a mouse xenograft model. Bioinformatics analysis of transcriptome data from human lung adenocarcinomas revealed a correlation between SIRT7 expression and increased activity of genes normally repressed by ARF. We propose that disruption of SIRT7–ARF signaling stabilizes ARF and thus attenuates cancer cell proliferation, offering a strategy to mitigate NSCLC progression.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2409269121
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2024
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    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Homogenized halides and alkali cation segregation in alloyed organic-inorganic perovskites
    American Association for the Advancement of Science (AAAS) ; 2019
    In:  Science Vol. 363, No. 6427 ( 2019-02-08), p. 627-631
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 363, No. 6427 ( 2019-02-08), p. 627-631
    Abstract: The role of the alkali metal cations in halide perovskite solar cells is not well understood. Using synchrotron-based nano–x-ray fluorescence and complementary measurements, we found that the halide distribution becomes homogenized upon addition of cesium iodide, either alone or with rubidium iodide, for substoichiometric, stoichiometric, and overstoichiometric preparations, where the lead halide is varied with respect to organic halide precursors. Halide homogenization coincides with long-lived charge carrier decays, spatially homogeneous carrier dynamics (as visualized by ultrafast microscopy), and improved photovoltaic device performance. We found that rubidium and potassium phase-segregate in highly concentrated clusters. Alkali metals are beneficial at low concentrations, where they homogenize the halide distribution, but at higher concentrations, they form recombination-active second-phase clusters.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aah5065
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
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    detail.hit.zdb_id: 2066996-3
    SSG: 11
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  • 7
    Online Resource
    Online Resource
    Determining structural and chemical heterogeneities of surface species at the single-bond limit
    American Association for the Advancement of Science (AAAS) ; 2021
    In:  Science Vol. 371, No. 6531 ( 2021-02-19), p. 818-822
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 371, No. 6531 ( 2021-02-19), p. 818-822
    Abstract: The structure determination of surface species has long been a challenge because of their rich chemical heterogeneities. Modern tip-based microscopic techniques can resolve heterogeneities from their distinct electronic, geometric, and vibrational properties at the single-molecule level but with limited interpretation from each. Here, we combined scanning tunneling microscopy (STM), noncontact atomic force microscopy (AFM), and tip-enhanced Raman scattering (TERS) to characterize an assumed inactive system, pentacene on the Ag(110) surface. This enabled us to unambiguously correlate the structural and chemical heterogeneities of three pentacene-derivative species through specific carbon-hydrogen bond breaking. The joint STM-AFM-TERS strategy provides a comprehensive solution for determining chemical structures that are widely present in surface catalysis, on-surface synthesis, and two-dimensional materials.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abd1827
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
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    detail.hit.zdb_id: 2066996-3
    SSG: 11
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