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  • 1
    Online Resource
    Online Resource
    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
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Genomic and transcriptomic investigations of the evolutionary transition from oviparity to viviparity
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 9 ( 2019-02-26), p. 3646-3655
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 9 ( 2019-02-26), p. 3646-3655
    Abstract: Viviparous (live-bearing) vertebrates have evolved repeatedly within otherwise oviparous (egg-laying) clades. Over two-thirds of these changes in vertebrate reproductive parity mode happened in squamate reptiles, where the transition has happened between 98 and 129 times. The transition from oviparity to viviparity requires numerous physiological, morphological, and immunological changes to the female reproductive tract, including eggshell reduction, delayed oviposition, placental development for supply of water and nutrition to the embryo by the mother, enhanced gas exchange, and suppression of maternal immune rejection of the embryo. We performed genomic and transcriptomic analyses of a closely related oviparous–viviparous pair of lizards ( Phrynocephalus przewalskii and Phrynocephalus vlangalii ) to examine these transitions. Expression patterns of maternal oviduct through reproductive development of the egg and embryo differ markedly between the two species. We found changes in expression patterns of appropriate genes that account for each of the major aspects of the oviparity to viviparity transition. In addition, we compared the gene sequences in transcriptomes of four oviparous–viviparous pairs of lizards in different genera ( Phrynocephalus , Eremias , Scincella , and Sphenomorphus ) to look for possible gene convergence at the sequence level. We discovered low levels of convergence in both amino acid replacement and evolutionary rate shift. This suggests that most of the changes that produce the oviparity–viviparity transition are changes in gene expression, so occasional reversals to oviparity from viviparity may not be as difficult to achieve as has been previously suggested.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1816086116
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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    Online Resource
  • 3
    Online Resource
    Online Resource
    An allosteric PGAM1 inhibitor effectively suppresses pancreatic ductal adenocarcinoma
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 46 ( 2019-11-12), p. 23264-23273
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 46 ( 2019-11-12), p. 23264-23273
    Abstract: Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided “proof of concept” for the potential application of metabolic treatment in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1914557116
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Arsenic Trioxide Controls the Fate of the PML-RARα Oncoprotein by Directly Binding PML
    American Association for the Advancement of Science (AAAS) ; 2010
    In:  Science Vol. 328, No. 5975 ( 2010-04-09), p. 240-243
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 328, No. 5975 ( 2010-04-09), p. 240-243
    Abstract: Arsenic, an ancient drug used in traditional Chinese medicine, has attracted worldwide interest because it shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Arsenic trioxide (As 2 O 3 ) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARα (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). PML and PML-RARα degradation is triggered by their SUMOylation, but the mechanism by which As 2 O 3 induces this posttranslational modification is unclear. Here we show that arsenic binds directly to cysteine residues in zinc fingers located within the RBCC domain of PML-RARα and PML. Arsenic binding induces PML oligomerization, which increases its interaction with the small ubiquitin-like protein modifier (SUMO)–conjugating enzyme UBC9, resulting in enhanced SUMOylation and degradation. The identification of PML as a direct target of As 2 O 3 provides new insights into the drug’s mechanism of action and its specificity for APL.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1183424
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2010
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 5
    Online Resource
    Online Resource
    Whole-genome sequence of the Tibetan frog Nanorana parkeri and the comparative evolution of tetrapod genomes
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 11 ( 2015-03-17)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 11 ( 2015-03-17)
    Abstract: The development of efficient sequencing techniques has resulted in large numbers of genomes being available for evolutionary studies. However, only one genome is available for all amphibians, that of Xenopus tropicalis , which is distantly related from the majority of frogs. More than 96% of frogs belong to the Neobatrachia, and no genome exists for this group. This dearth of amphibian genomes greatly restricts genomic studies of amphibians and, more generally, our understanding of tetrapod genome evolution. To fill this gap, we provide the de novo genome of a Tibetan Plateau frog, Nanorana parkeri , and compare it to that of X. tropicalis and other vertebrates. This genome encodes more than 20,000 protein-coding genes, a number similar to that of Xenopus . Although the genome size of Nanorana is considerably larger than that of Xenopus (2.3 vs. 1.5 Gb), most of the difference is due to the respective number of transposable elements in the two genomes. The two frogs exhibit considerable conserved whole-genome synteny despite having diverged approximately 266 Ma, indicating a slow rate of DNA structural evolution in anurans. Multigenome synteny blocks further show that amphibians have fewer interchromosomal rearrangements than mammals but have a comparable rate of intrachromosomal rearrangements. Our analysis also identifies 11 Mb of anuran-specific highly conserved elements that will be useful for comparative genomic analyses of frogs. The Nanorana genome offers an improved understanding of evolution of tetrapod genomes and also provides a genomic reference for other evolutionary studies.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1501764112
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
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  • 6
    Online Resource
    Online Resource
    β2-Microglobulin coaggregates with Aβ and contributes to amyloid pathology and cognitive deficits in Alzheimer’s disease model mice
    Springer Science and Business Media LLC ; 2023
    In:  Nature Neuroscience Vol. 26, No. 7 ( 2023-07), p. 1170-1184
    Details
    In: Nature Neuroscience, Springer Science and Business Media LLC, Vol. 26, No. 7 ( 2023-07), p. 1170-1184
    Type of Medium: Online Resource
    ISSN: 1097-6256 , 1546-1726
    URL: Article
    DOI: 10.1038/s41593-023-01352-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1494955-6
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    METTL3 is essential for normal progesterone signaling during embryo implantation via m 6 A-mediated translation control of progesterone receptor
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 5 ( 2023-01-31)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 5 ( 2023-01-31)
    Abstract: Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P 4 ) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N 6 -methyladenosine (m 6 A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P 4  signaling. Conditional deletion of methyltransferase-like 3 ( Mettl3 ), encoding the m 6 A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter ( Pgr-Cre ) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m 6 A modification. A luciferase assay revealed that the m 6 A modification in the 5′ untranslated region (5′-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P 4 signaling during embryo implantation via m 6 A-mediated translation control of Pgr mRNA.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2214684120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Structural insight into the SAM-mediated assembly of the mitochondrial TOM core complex
    American Association for the Advancement of Science (AAAS) ; 2021
    In:  Science Vol. 373, No. 6561 ( 2021-09-17), p. 1377-1381
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 373, No. 6561 ( 2021-09-17), p. 1377-1381
    Abstract: β barrel outer membrane proteins (β-OMPs) play vital roles in mitochondria, chloroplasts, and Gram-negative bacteria. Evolutionarily conserved complexes such as the mitochondrial sorting and assembly machinery (SAM) mediate the assembly of β-OMPs. We investigated the SAM-mediated assembly of the translocase of the outer membrane (TOM) core complex. Cryo–electron microscopy structures of SAM–fully folded Tom40 and the SAM-Tom40/Tom5/Tom6 complexes at ~3-angstrom resolution reveal that Sam37 stabilizes the mature Tom40 mainly through electrostatic interactions, thus facilitating subsequent TOM assembly. These results support the β barrel switching model and provide structural insights into the assembly and release of β barrel complexes.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.abh0704
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 9
    Online Resource
    Online Resource
    Ancient DNA and multimethod dating confirm the late arrival of anatomically modern humans in southern China
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 8 ( 2021-02-23)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 8 ( 2021-02-23)
    Abstract: The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U–Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14 C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14 C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2019158118
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Intermittent Hypoxia Promotes Hippocampal Neurogenesis and Produces Antidepressant-Like Effects in Adult Rats
    Society for Neuroscience ; 2010
    In:  The Journal of Neuroscience Vol. 30, No. 38 ( 2010-09-22), p. 12653-12663
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 30, No. 38 ( 2010-09-22), p. 12653-12663
    Abstract: Increasing evidence indicates that stimulating hippocampal neurogenesis could provide novel avenues for the treatment of depression, and recent studies have shown that in vitro neurogenesis is enhanced by hypoxia. The aim of this study was to investigate the potential regulatory capacity of an intermittent hypobaric hypoxia (IH) regimen on hippocampal neurogenesis and its possible antidepressant-like effect. Here, we show that IH promotes the proliferation of endogenous neuroprogenitors leading to more newborn neurons in hippocampus in adult rats. Importantly, IH produces antidepressant-like effects in multiple animal models screening for antidepressant activity, including the forced swimming test, chronic mild stress paradigm, and novelty-suppressed feeding test. Hippocampal x-ray irradiation blocked both the neurogenic and behavioral effects of IH, indicating that IH likely produces antidepressant-like effects via promoting neurogenesis in adult hippocampus. Furthermore, IH stably enhanced the expression of BDNF in hippocampus; both the antidepressant-like effect and the enhancement of cell proliferation induced by IH were totally blocked by pharmacological and biological inhibition of BDNF–TrkB (tyrosine receptor kinase B) signaling, suggesting that the neurogenic and antidepressant-like effects of IH may involve BDNF signaling. These observations might contribute to both a better understanding of physiological responses to IH and to developing IH as a novel therapeutic approach for depression.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.6414-09.2010
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2010
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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