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  • 1
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    Online Resource
    Strengthening the argument for a large Greater India
    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: The Sangdanlin section in southern Tibet represents a geologic Rosetta stone to constrain the initiation of the India–Asia collision from its sedimentary and paleomagnetic records. However, geoscientists have arrived at fundamentally divergent interpretations surrounding the age of the strata and its paleomagnetic record. Here, we report paleontologic, petrographic, and paleomagnetic data from the Sangdanlin section that recognize the sequence as a thrust complex containing interlaced Barremian–Albian (Early Cretaceous) and Paleocene strata, each separated by thrust faults. Recognizing two complexly interwoven formations of distinctly different ages contradicts a continuous stratigraphic superposition. Assigning an Early Cretaceous, instead of Paleocene, age to the units collected for paleomagnetic data revises paleogeographic models thereby supporting a large (2,000 to 3,000 km) extent of Greater India, with collision initiating at 55 ± 5 Ma in the western Himalayas. A contiguous plate in the Neotethys Ocean precludes that Asia’s southern margin was built through a succession of accreted terrains.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2305928120
    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
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    “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:
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2017
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  • 3
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    Reduced default mode network functional connectivity in patients with recurrent major depressive disorder
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 18 ( 2019-04-30), p. 9078-9083
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 18 ( 2019-04-30), p. 9078-9083
    Abstract: Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1900390116
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
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  • 4
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    Inhibition of soluble epoxide hydrolase attenuates a high-fat diet-mediated renal injury by activating PAX2 and AMPK
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 11 ( 2019-03-12), p. 5154-5159
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 11 ( 2019-03-12), p. 5154-5159
    Abstract: A high-fat diet (HFD) causes obesity-associated morbidities involved in macroautophagy and chaperone-mediated autophagy (CMA). AMPK, the mediator of macroautophage, has been reported to be inactivated in HFD-caused renal injury. However, PAX2, the mediator for CMA, has not been reported in HFD-caused renal injury. Here we report that HFD-caused renal injury involved the inactivation of Pax2 and Ampk, and the activation of soluble epoxide hydrolase (sEH), in a murine model. Specifically, mice fed on an HFD for 2, 4, and 8 wk showed time-dependent renal injury, the significant decrease in renal Pax2 and Ampk at both mRNA and protein levels, and a significant increase in renal sEH at mRNA, protein, and molecular levels. Also, administration of an sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea, significantly attenuated the HFD-caused renal injury, decreased renal sEH consistently at mRNA and protein levels, modified the renal levels of sEH-mediated epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) as expected, and increased renal Pax2 and Ampk at mRNA and/or protein levels. Furthermore, palmitic acid (PA) treatment caused significant increase in Mcp-1 , and decrease in both Pax2 and Ampk in murine renal mesangial cells (mRMCs) time- and dose-dependently. Also, 14(15)-EET (a major substrate of sEH), but not its sEH-mediated metabolite 14,15-DHET, significantly reversed PA-induced increase in Mcp-1 , and PA-induced decrease in Pax2 and Ampk. In addition, plasmid construction revealed that Pax2 may positively regulate Ampk transcriptionally in mRMCs. This study provides insights into and therapeutic target for the HFD-mediated renal injury.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1815746116
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
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  • 5
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    MicroRNA-224 promotes tumor progression in nonsmall cell lung cancer
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 31 ( 2015-08-04)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 31 ( 2015-08-04)
    Abstract: Lung cancer is the leading cause of cancer-related deaths worldwide. Despite advancements and improvements in surgical and medical treatments, the survival rate of lung cancer patients remains frustratingly poor. Local control for early-stage nonsmall cell lung cancer (NSCLC) has dramatically improved over the last decades for both operable and inoperable patients. However, the molecular mechanisms of NSCLC invasion leading to regional and distant disease spread remain poorly understood. Here, we identify microRNA-224 ( miR-224 ) to be significantly up-regulated in NSCLC tissues, particularly in resected NSCLC metastasis. Increased miR-224 expression promotes cell migration, invasion, and proliferation by directly targeting the tumor suppressors TNFα-induced protein 1 (TNFAIP1) and SMAD4. In concordance with in vitro studies, mouse xenograft studies validated that miR-224 functions as a potent oncogenic miRNA in NSCLC in vivo. Moreover, we found promoter hypomethylation and activated ERK signaling to be involved in the regulation of miR-224 expression in NSCLC. Up-regulated miR-224 , thus, facilitates tumor progression by shifting the equilibrium of the partially antagonist functions of SMAD4 and TNFAIP1 toward enhanced invasion and growth in NSCLC. Our findings indicate that targeting miR-224 could be effective in the treatment of certain lung cancer patients.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1502068112
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
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  • 6
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    A New Boson with a Mass of 125 GeV Observed with the CMS Experiment at the Large Hadron Collider
    American Association for the Advancement of Science (AAAS) ; 2012
    In:  Science Vol. 338, No. 6114 ( 2012-12-21), p. 1569-1575
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 338, No. 6114 ( 2012-12-21), p. 1569-1575
    Abstract: The Higgs boson was postulated nearly five decades ago within the framework of the standard model of particle physics and has been the subject of numerous searches at accelerators around the world. Its discovery would verify the existence of a complex scalar field thought to give mass to three of the carriers of the electroweak force—the W + , W – , and Z 0 bosons—as well as to the fundamental quarks and leptons. The CMS Collaboration has observed, with a statistical significance of five standard deviations, a new particle produced in proton-proton collisions at the Large Hadron Collider at CERN. The evidence is strongest in the diphoton and four-lepton (electrons and/or muons) final states, which provide the best mass resolution in the CMS detector. The probability of the observed signal being due to a random fluctuation of the background is about 1 in 3 × 10 6 . The new particle is a boson with spin not equal to 1 and has a mass of about 125 giga–electron volts. Although its measured properties are, within the uncertainties of the present data, consistent with those expected of the Higgs boson, more data are needed to elucidate the precise nature of the new particle.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1230816
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2012
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  • 7
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    APT1-Mediated Depalmitoylation Regulates Hippocampal Synaptic Plasticity
    Society for Neuroscience ; 2022
    In:  The Journal of Neuroscience Vol. 42, No. 13 ( 2022-03-30), p. 2662-2677
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 42, No. 13 ( 2022-03-30), p. 2662-2677
    Abstract: Palmitoylation may be relevant to the processes of learning and memory, and even disorders, such as post-traumatic stress disorder and aging-related cognitive decline. However, underlying mechanisms of palmitoylation in these processes remain unclear. Herein, we used acyl-biotin exchange, coimmunoprecipitation and biotinylation assays, and behavioral and electrophysiological methods, to explore whether palmitoylation is required for hippocampal synaptic transmission and fear memory formation, and involved in functional modification of synaptic proteins, such as postsynapse density-95 (PSD-95) and glutamate receptors, and detected if depalmitoylation by specific enzymes has influence on glutamatergic synaptic plasticity. Our results showed that global palmitoylation level, palmitoylation of PSD-95 and glutamate receptors, postsynapse density localization of PSD-95, surface expression of AMPARs, and synaptic strength of cultured hippocampal neurons were all enhanced by TTX pretreatment, and these can be reversed by inhibition of palmitoylation with palmitoyl acyl transferases inhibitors, 2-bromopalmitate and N-(tert-butyl) hydroxylamine hydrochloride. Importantly, we also found that acyl-protein thioesterase 1 (APT1)-mediated depalmitoylation is involved in palmitoylation of PSD-95 and glutamatergic synaptic transmission. Knockdown of APT1, not protein palmitoyl thioesterase 1, with shRNA, or selective inhibition, significantly increased AMPAR-mediated synaptic strength, palmitoylation levels, and synaptic or surface expression of PSD-95 and AMPARs. Results from hippocampal tissues and fear-conditioned rats showed that palmitoylation is required for synaptic strengthening and fear memory formation. These results suggest that palmitoylation and APT1-mediated depalmitoylation have critical effects on the regulation of glutamatergic synaptic plasticity, and it may serve as a potential target for learning and memory-associated disorders. SIGNIFICANCE STATEMENT Fear-related anxiety disorders, including post-traumatic stress disorder, are prevalent psychiatric conditions, and fear memory is associated with hyperexcitability in the hippocampal CA1 region. Palmitoylation is involved in learning and memory, but mechanisms coupling palmitoylation with fear memory acquisition remain poorly understood. This study demonstrated that palmitoylation is essential for postsynapse density-95 clustering and hippocampal glutamatergic synaptic transmission, and APT1-mediated depalmitoylation plays critical roles in the regulation of synaptic plasticity. Our study revealed that molecular mechanism about downregulation of APT1 leads to enhancement of AMPAR-mediated synaptic transmission, and that palmitoylation cycling is implicated in fear conditioning-induced synaptic strengthening and fear memory formation.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1523/JNEUROSCI.1741-21.2022
    DOI: 10.1523/JNEUROSCI.1741-21.2022.f1-1
    DOI: 10.1523/JNEUROSCI.1741-21.2022.f1-2
    DOI: 10.1523/JNEUROSCI.1741-21.2022.f2-1
    DOI: 10.1523/JNEUROSCI.1741-21.2022.f6-1
    DOI: 10.1523/JNEUROSCI.1741-21.2022.f7-1
    DOI: 10.1523/JNEUROSCI.1741-21.2022.f8-1
    DOI: 10.1523/JNEUROSCI.1741-21.2022.f9-1
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2022
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  • 8
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    Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target
    American Association for the Advancement of Science (AAAS) ; 2023
    In:  Science Vol. 381, No. 6657 ( 2023-08-04)
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 381, No. 6657 ( 2023-08-04)
    Abstract: Gut microbiota can regulate the physiology and pathophysiology of the host by producing enzymes with functions similar to those of the host. However, it is difficult to identify these microbial-host isozymes through sequencing-based studies because enzymes with similar functions in different species may lack sequence conservation. An activity-based functional protein screening framework is more reliable for the discovery and characterization of such microbial-host isozymes, which will help yield deeper insights into the gut microbiota–host cross-talk. RATIONALE To identify potential microbial-host isozymes, we set up an enzyme activity screening platform, including activity assays for 110 enzymes that are functional in various human diseases. These enzyme activities were measured in stool-derived ex vivo bacteria communities. Dipeptidyl peptidase 4 (DPP4) was a prominent microbial-host isozyme identified in our screen, but little is known about its pathophysiological effects on the host. We sought to determine whether gut microbial–derived DPP4, like host DPP4 (hDPP4), could decrease active GLP-1 and thus affect blood glucose homeostasis. RESULTS We identified 71 enzymes with positive activity in the human gut bacteria communities through our enzyme activity screening platform, most of which were validated in the protein extracts obtained from feces of germ-free and specific pathogen–free mice. Among these identified enzymes, DPP4 activity had the highest statistical effect size ( Z factor) among the 10 human samples. Through human gut bacteria isolation and DPP4 activity screening, we discovered that microbial DPP4 was mainly produced by Bacteroides spp. Gut microbial DPP4 (mDPP4) could degrade active GLP-1(7-37) in vitro. However, mDPP4 could not affect active GLP-1 levels in chow-fed mice but could decrease active GLP-1 activity and impair glucose homeostasis in high-fat diet (HFD)–fed mice or dextran sulfate sodium/indomethacin–treated mice, suggesting that a damaged gut barrier is required for mDPP4 to affect the activity of host GLP-1. We discovered that the clinical DPP4 inhibitor sitagliptin failed to efficiently inhibit mDPP4. And by solving the co-crystal of mDPP4 with sitagliptin at 1.97-anstrom resolution, we found differences in the nature of the binding between the drug and mDPP4 compared with its binding to hDPP4 that may explain this difference in inhibitory effects. A sitagliptin clinical trial ( www.clinicaltrials.gov identifer NCT04495881) among patients with type 2 diabetes (T2D) ( n = 57) and a related fecal microbiota transplant of stool from high responders and low responders in the present study to HFD-fed mice demonstrated that mDPP4 could limit the efficacy of sitagliptin in individuals with T2D and in glucose-intolerant mice. To identify a selective inhibitor of mDPP4, we screened ~107,000 compounds, and using structural modification we identified Dau-d4, a derivative of daurisoline, that could selectively inhibit mDPP4 activity compared with hDPP4. Dau-d4 could increase active GLP-1 levels and improve glucose metabolism in diabetic mice, and co-administration of Dau-d4 with sitagliptin further improved blood glucose homeostasis. CONCLUSION Here, we developed an activity-based strategy to identify uncharacterized gut microbial-host isozymes that provides a deeper understanding of gut microbiota–host interactions. Gut microbial DPP4 isozyme can impair host glucose homeostasis, and variations in microbial DPP4 activities could possibly contribute to the heterogeneous responses to sitagliptin observed among patients with T2D. Our findings highlight the promise of developing therapies that target both host and gut microbial enzymes to achieve greater clinical efficacy. Discovery and inhibition of a gut microbial–host isozyme to regulate host metabolism. Differences in the gut microbiota may explain why some individuals respond to antidiabetic DPP4 inhibitors but others do not. An activity-based enzyme activity screening system identified gut microbial DPP4 isozymes that can decrease active GLP-1 but cannot be inhibited by sitagliptin. High-throughput screening identified Dau-d4 as a selective inhibitor of microbial DPP4 to increase GLP-1 activity and improve glucose tolerance.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.add5787
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
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  • 9
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    Soliciting judgments of forgetting reactively enhances memory as well as making judgments of learning: Empirical and meta-analytic tests
    Springer Science and Business Media LLC ; 2022
    In:  Memory & Cognition Vol. 50, No. 5 ( 2022-07), p. 1061-1077
    Details
    In: Memory & Cognition, Springer Science and Business Media LLC, Vol. 50, No. 5 ( 2022-07), p. 1061-1077
    Type of Medium: Online Resource
    ISSN: 0090-502X , 1532-5946
    URL: Article
    DOI: 10.3758/s13421-021-01258-y
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2042908-3
    SSG: 5,2
    SSG: 7,11
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