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  • 1
    Online Resource
    Online Resource
    Nuclear envelope proteins modulate proliferation of vascular smooth muscle cells during cyclic stretch application
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 19 ( 2016-05-10), p. 5293-5298
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 19 ( 2016-05-10), p. 5293-5298
    Abstract: Cyclic stretch is an important inducer of vascular smooth muscle cell (VSMC) proliferation, which is crucial in vascular remodeling during hypertension. However, the molecular mechanism remains unclear. We studied the effects of emerin and lamin A/C, two important nuclear envelope proteins, on VSMC proliferation in hypertension and the underlying mechano-mechanisms. In common carotid artery of hypertensive rats in vivo and in cultured cells subjected to high (15%) cyclic stretch in vitro, VSMC proliferation was increased significantly, and the expression of emerin and lamin A/C was repressed compared with normotensive or normal (5%) cyclic stretch controls. Using targeted siRNA to mimic the repressed expression of emerin or lamin A/C induced by 15% stretch, we found that VSMC proliferation was enhanced under static and 5%-stretch conditions. Overexpression of emerin or lamin A/C reversed VSMC proliferation induced by 15% stretch. Hence, emerin and lamin A/C play critical roles in suppressing VSMC hyperproliferation induced by hyperstretch. ChIP-on-chip and MOTIF analyses showed that the DNAs binding with emerin contain three transcription factor motifs: CCNGGA, CCMGCC, and ABTTCCG; DNAs binding with lamin A/C contain the motifs CVGGAA, GCCGCYGC, and DAAGAAA. Protein/DNA array proved that altered emerin or lamin A/C expression modulated the activation of various transcription factors. Furthermore, accelerating local expression of emerin or lamin A/C reversed cell proliferation in the carotid artery of hypertensive rats in vivo. Our findings establish the pathogenetic role of emerin and lamin A/C repression in stretch-induced VSMC proliferation and suggest mechanobiological mechanism underlying this process that involves the sequence-specific binding of emerin and lamin A/C to specific transcription factor motifs.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1604569113
    RVK:
    TA 1000
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
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  • 2
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    Online Resource
    Evidence for nitrite-dependent anaerobic methane oxidation as a previously overlooked microbial methane sink in wetlands
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 12 ( 2014-03-25), p. 4495-4500
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 12 ( 2014-03-25), p. 4495-4500
    Abstract: The process of nitrite-dependent anaerobic methane oxidation (n-damo) was recently discovered and shown to be mediated by “ Candidatus Methylomirabilis oxyfera” ( M. oxyfera ). Here, evidence for n-damo in three different freshwater wetlands located in southeastern China was obtained using stable isotope measurements, quantitative PCR assays, and 16S rRNA and particulate methane monooxygenase gene clone library analyses. Stable isotope experiments confirmed the occurrence of n-damo in the examined wetlands, and the potential n-damo rates ranged from 0.31 to 5.43 nmol CO 2 per gram of dry soil per day at different depths of soil cores. A combined analysis of 16S rRNA and particulate methane monooxygenase genes demonstrated that M. oxyfera -like bacteria were mainly present in the deep soil with a maximum abundance of 3.2 × 10 7 gene copies per gram of dry soil. It is estimated that ∼0.51 g of CH 4 m −2 per year could be linked to the n-damo process in the examined wetlands based on the measured potential n-damo rates. This study presents previously unidentified confirmation that the n-damo process is a previously overlooked microbial methane sink in wetlands, and n-damo has the potential to be a globally important methane sink due to increasing nitrogen pollution.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1318393111
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
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  • 3
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    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:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
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  • 4
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    Online Resource
    A Memory Retrieval-Extinction Procedure to Prevent Drug Craving and Relapse
    American Association for the Advancement of Science (AAAS) ; 2012
    In:  Science Vol. 336, No. 6078 ( 2012-04-13), p. 241-245
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 336, No. 6078 ( 2012-04-13), p. 241-245
    Abstract: Drug use and relapse involve learned associations between drug-associated environmental cues and drug effects. Extinction procedures in the clinic can suppress conditioned responses to drug cues, but the extinguished responses typically reemerge after exposure to the drug itself (reinstatement), the drug-associated environment (renewal), or the passage of time (spontaneous recovery). We describe a memory retrieval-extinction procedure that decreases conditioned drug effects and drug seeking in rat models of relapse, and drug craving in abstinent heroin addicts. In rats, daily retrieval of drug-associated memories 10 minutes or 1 hour but not 6 hours before extinction sessions attenuated drug-induced reinstatement, spontaneous recovery, and renewal of conditioned drug effects and drug seeking. In heroin addicts, retrieval of drug-associated memories 10 minutes before extinction sessions attenuated cue-induced heroin craving 1, 30, and 180 days later. The memory retrieval-extinction procedure is a promising nonpharmacological method for decreasing drug craving and relapse during abstinence.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1215070
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2012
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  • 5
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    Online Resource
    Chinese Addiction Study and Human Rights—Response
    American Association for the Advancement of Science (AAAS) ; 2012
    In:  Science Vol. 337, No. 6094 ( 2012-08-03), p. 523-523
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 337, No. 6094 ( 2012-08-03), p. 523-523
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.337.6094.523-a
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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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    Bug mapping and fitness testing of chemically synthesized chromosome X
    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: Debugging a genome sequence is imperative for successfully building a synthetic genome. As part of the effort to build a designer eukaryotic genome, yeast synthetic chromosome X (synX), designed as 707,459 base pairs, was synthesized chemically. SynX exhibited good fitness under a wide variety of conditions. A highly efficient mapping strategy called pooled PCRTag mapping (PoPM), which can be generalized to any watermarked synthetic chromosome, was developed to identify genetic alterations that affect cell fitness (“bugs”). A series of bugs were corrected that included a large region bearing complex amplifications, a growth defect mapping to a recoded sequence in FIP1 , and a loxPsym site affecting promoter function of ATP2 . PoPM is a powerful tool for synthetic yeast genome debugging and an efficient strategy for phenotype-genotype mapping.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aaf4706
    RVK:
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2017
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  • 7
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    In situ structures of polymerase complex of mammalian reovirus illuminate RdRp activation and transcription regulation
    Proceedings of the National Academy of Sciences ; 2022
    In:  Proceedings of the National Academy of Sciences Vol. 119, No. 50 ( 2022-12-13)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 50 ( 2022-12-13)
    Abstract: Mammalian reovirus (reovirus) is a multilayered, turreted member of Reoviridae characterized by transcription of dsRNA genome within the innermost capsid shell. Here, we present high-resolution in situ structures of reovirus transcriptase complex in an intact double-layered virion, and in the uncoated single-layered core particles in the unloaded, reloaded, pre-elongation, and elongation states, respectively, obtained by cryo-electron microscopy and sub-particle reconstructions. At the template entry of RNA-dependent RNA polymerase (RdRp), the RNA-loading region gets flexible after uncoating resulting in the unloading of terminal genomic RNA and inactivity of transcription. However, upon adding transcriptional substrates, the RNA-loading region is recovered leading the RNAs loaded again. The priming loop in RdRp was found to play a critical role in regulating transcription, which hinders the elongation of transcript in virion and triggers the rearrangement of RdRp C-terminal domain (CTD) during elongation, resulting in splitting of template-transcript hybrid and opening of transcript exit. With the integration of these structures, a transcriptional model of reovirus with five states is proposed. Our structures illuminate the RdRp activation and regulation of the multilayered turreted reovirus.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2203054119
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
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  • 8
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    Online Resource
    Abnormal Vascular Function and Hypertension in Mice Deficient in Estrogen Receptor β
    American Association for the Advancement of Science (AAAS) ; 2002
    In:  Science Vol. 295, No. 5554 ( 2002-01-18), p. 505-508
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 295, No. 5554 ( 2002-01-18), p. 505-508
    Abstract: Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor β (ERβ)–deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERβ-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERβ-deficient mice. Vascular smooth muscle cells isolated from ERβ-deficient mice show multiple abnormalities of ion channel function. Furthermore, ERβ-deficient mice develop sustained systolic and diastolic hypertension as they age. These data support an essential role for ERβ in the regulation of vascular function and blood pressure.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1065250
    RVK:
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2002
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  • 9
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    Selection and environmental adaptation along a path to speciation in the Tibetan frog Nanorana parkeri
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 22 ( 2018-05-29)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 22 ( 2018-05-29)
    Abstract: Tibetan frogs, Nanorana parkeri , are differentiated genetically but not morphologically along geographical and elevational gradients in a challenging environment, presenting a unique opportunity to investigate processes leading to speciation. Analyses of whole genomes of 63 frogs reveal population structuring and historical demography, characterized by highly restricted gene flow in a narrow geographic zone lying between matrilines West (W) and East (E). A population found only along a single tributary of the Yalu Zangbu River has the mitogenome only of E, whereas nuclear genes of W comprise 89–95% of the nuclear genome. Selection accounts for 579 broadly scattered, highly divergent regions (HDRs) of the genome, which involve 365 genes. These genes fall into 51 gene ontology (GO) functional classes, 14 of which are likely to be important in driving reproductive isolation. GO enrichment analyses of E reveal many overrepresented functional categories associated with adaptation to high elevations, including blood circulation, response to hypoxia, and UV radiation. Four genes, including DNAJC8 in the brain, TNNC1 and ADORA1 in the heart, and LAMB3 in the lung, differ in levels of expression between low- and high-elevation populations. High-altitude adaptation plays an important role in maintaining and driving continuing divergence and reproductive isolation. Use of total genomes enabled recognition of selection and adaptation in and between populations, as well as documentation of evolution along a stepped cline toward speciation.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1716257115
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
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  • 10
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    Crystal structure of desheptapeptide(B24–B30)insulin at 1.6 Å resolution: Implications for receptor binding
    Proceedings of the National Academy of Sciences ; 1997
    In:  Proceedings of the National Academy of Sciences Vol. 94, No. 7 ( 1997-04), p. 2975-2980
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 94, No. 7 ( 1997-04), p. 2975-2980
    Abstract: The crystal structure of desheptapeptide (B24–B30) insulin (DHPI), a virtually inactive analog of insulin, was determined at 1.6 Å resolution. In the refined structure model, DHPI retains three α-helices (A1–A8, A12–A18, and B9–B19) as its structural framework, while great conformational changes occur in the N and C termini of B-chain. The β-turn, which lies in B20–B30 in insulin and insulin analogs with high potency, no longer exists in DHPI. Relative motion is observed among the three α-helices, each as a rigid functional group. In contrast, a region covering B5–B6 and A6–A11 exhibits a relatively stable conformation. We interpret our results as identifying: ( i ) the importance of β-turn in determining the receptor-binding potency of insulin and ( ii ) a leading role of Phe B24 in maintaining the β-turn structure.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.94.7.2975
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1997
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