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  • 1
    Online Resource
    Online Resource
    Elsevier BV ; 2020
    In:  Information Sciences Vol. 535 ( 2020-10), p. 225-241
    In: Information Sciences, Elsevier BV, Vol. 535 ( 2020-10), p. 225-241
    Type of Medium: Online Resource
    ISSN: 0020-0255
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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  • 2
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2021
    In:  Proceedings of the National Academy of Sciences Vol. 118, No. 8 ( 2021-02-23)
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 8 ( 2021-02-23)
    Abstract: Repeated blood feedings are required for adult female mosquitoes to maintain their gonadotrophic cycles, enabling them to be important pathogen carriers of human diseases. Elucidating the molecular mechanism underlying developmental switches between these mosquito gonadotrophic cycles will provide valuable insight into mosquito reproduction and could aid in the identification of targets to disrupt these cycles, thereby reducing disease transmission. We report here that the transcription factor ecdysone-induced protein 93 (E93), previously implicated in insect metamorphic transitions, plays a key role in determining the gonadotrophic cyclicity in adult females of the major arboviral vector Aedes aegypti . Expression of the E93 gene in mosquitoes is down-regulated by juvenile hormone (JH) and up-regulated by 20-hydroxyecdysone (20E). We find that E93 controls Hormone Receptor 3 (HR3), the transcription factor linked to the termination of reproductive cycles. Moreover, knockdown of E93 expression via RNAi impaired fat body autophagy, suggesting that E93 governs autophagy-induced termination of vitellogenesis. E93 RNAi silencing prior to the first gonadotrophic cycle affected normal progression of the second cycle. Finally, transcriptomic analysis showed a considerable E93-dependent decline in the expression of genes involved in translation and metabolism at the end of a reproductive cycle. In conclusion, our data demonstrate that E93 acts as a crucial factor in regulating reproductive cycle switches in adult female mosquitoes.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
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  • 3
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 24 ( 2009-06-16), p. 9820-9825
    Abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. We have generated a neutralizing anti-PCSK9 antibody, mAb1, that binds to an epitope on PCSK9 adjacent to the region required for LDLR interaction. In vitro, mAb1 inhibits PCSK9 binding to the LDLR and attenuates PCSK9-mediated reduction in LDLR protein levels, thereby increasing LDL uptake. A combination of mAb1 with a statin increases LDLR levels in HepG2 cells more than either treatment alone. In wild-type mice, mAb1 increases hepatic LDLR protein levels ≈2-fold and lowers total serum cholesterol by up to 36%: this effect is not observed in LDLR −/− mice. In cynomolgus monkeys, a single injection of mAb1 reduces serum LDL-C by 80%, and a significant decrease is maintained for 10 days. We conclude that anti-PCSK9 antibodies may be effective therapeutics for treating hypercholesterolemia.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2009
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  • 4
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 37 ( 2022-09-13)
    Abstract: Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β plaques and Tau tangles in brain tissues. Recent studies indicate that aberrant splicing and increased level of intron retention is linked to AD pathogenesis. Bioinformatic analysis revealed increased retention of intron 11 at the Tau gene in AD female dorsal lateral prefrontal cortex as compared to healthy controls, an observation validated by quantitative polymerase chain reaction using different brain tissues. Retention of intron 11 introduces a premature stop codon, resulting in the production of truncated Tau11i protein. Probing with customized antibodies designed against amino acids encoded by intron 11 showed that Tau11i protein is more enriched in AD hippocampus, amygdala, parietal, temporal, and frontal lobe than in healthy controls. This indicates that Tau messenger RNA with the retained intron is translated in vivo instead of being subjected to nonsense-mediated decay. Compared to full-length Tau441 isoform, ectopically expressed Tau11i forms higher molecular weight species, is enriched in Sarkosyl-insoluble fraction, and exhibits greater protein stability in cycloheximide assay. Stably expressed Tau11i also shows weaker colocalization with α-tubulin of microtubule network in human mature cortical neurons as compared to Tau441. Endogenous Tau11i is enriched in Sarkosyl-insoluble fraction in AD hippocampus and forms aggregates that colocalize weakly with Tau4R fibril-like structure in AD temporal lobe. The elevated level of Tau11i protein in AD brain tissues tested, coupled with biochemical properties resembling pathological Tau species suggest that retention of intron 11 of Tau gene might be an early biomarker of AD pathology.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2011
    In:  Proceedings of the National Academy of Sciences Vol. 108, No. 16 ( 2011-04-19), p. 6399-6404
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 16 ( 2011-04-19), p. 6399-6404
    Abstract: China and other rapidly developing economies face the dual challenge of substantially increasing yields of cereal grains while at the same time reducing the very substantial environmental impacts of intensive agriculture. We used a model-driven integrated soil–crop system management approach to develop a maize production system that achieved mean maize yields of 13.0 t ha −1 on 66 on-farm experimental plots—nearly twice the yield of current farmers’ practices—with no increase in N fertilizer use. Such integrated soil–crop system management systems represent a priority for agricultural research and implementation, especially in rapidly growing economies.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2011
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Acoustical Society of America (ASA) ; 1995
    In:  The Journal of the Acoustical Society of America Vol. 98, No. 5_Supplement ( 1995-11-01), p. 2918-2918
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 98, No. 5_Supplement ( 1995-11-01), p. 2918-2918
    Abstract: In order to get the mathematic model of a noise control system in space, which is the impulse response of a speaker–microphone system, a square impulse modulated by a single frequency signal has been used. In the paper, a pseudorandom correlation identification method is used to get the impulse response of a MIMO speaker microphone system in the spatial field. The dynamic process and the time delay of sound waves in the spatial field and speaker coils are presented exactly. The model is used for digital simulation and a space sound experiment using a developed adaptive filter algorithm presented by the authors which is the recursive algorithm with interlacing cycle and increasing phase. The sampled noise signal from the motor driver cabin is used as the input of the system. The simulation and the experiment have proved the correctness of the model and the effectiveness of the developed adaptive fillter algorithm.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    RVK:
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 1995
    detail.hit.zdb_id: 1461063-2
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  • 7
    Online Resource
    Online Resource
    Elsevier BV ; 2015
    In:  Information Sciences Vol. 298 ( 2015-03), p. 274-287
    In: Information Sciences, Elsevier BV, Vol. 298 ( 2015-03), p. 274-287
    Type of Medium: Online Resource
    ISSN: 0020-0255
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
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    SSG: 24,1
    SSG: 7,11
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  • 8
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 35 ( 2013-08-27), p. 14492-14497
    Abstract: The growing world population and shrinkage of arable land demand yield improvement of rice, one of the most important staple crops. To elucidate the genetic basis of yield and uncover its associated loci in rice, we resequenced the core recombinant inbred lines of Liang–You–Pei–Jiu , the widely cultivated super hybrid rice, and constructed a high-resolution linkage map. We detected 43 yield-associated quantitative trait loci, of which 20 are unique. Based on the high-density physical map, the genome sequences of paternal variety 93–11 and maternal cultivar PA64s of Liang–You–Pei–Jiu were significantly improved. The large recombinant inbred line population combined with plentiful high-quality single nucleotide polymorphisms and insertions/deletions between parental genomes allowed us to fine-map two quantitative trait loci, qSN8 and qSPB1 , and to identify days to heading8 and lax panicle1 as candidate genes, respectively. The quantitative trait locus qSN8 was further confirmed to be days to heading8 by a complementation test. Our study provided an ideal platform for molecular breeding by targeting and dissecting yield-associated loci in rice.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 17 ( 2018-04-24)
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 17 ( 2018-04-24)
    Abstract: Oxidative stress (OS)-induced retinal pigment epithelium (RPE) cell apoptosis is critically implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Heterochromatin, a compact and transcriptional inert chromatin structure, has been recently shown to be dynamically regulated in response to stress stimuli. The functional mechanism of heterochromatin on OS exposure is unclear, however. Here we show that OS increases heterochromatin formation both in vivo and in vitro, which is essential for protecting RPE cells from oxidative damage. Mechanistically, OS-induced heterochromatin selectively accumulates at p53-regulated proapoptotic target promoters and inhibits their transcription. Furthermore, OS-induced desumoylation of p53 promotes p53–heterochromatin interaction and regulates p53 promoter selection, resulting in the locus-specific recruitment of heterochromatin and transcription repression. Together, our findings demonstrate a protective function of OS-induced heterochromatin formation in which p53 desumoylation-guided promoter selection and subsequent heterochromatin recruitment play a critical role. We propose that targeting heterochromatin provides a plausible therapeutic strategy for the treatment of AMD.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
    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
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 43 ( 2013-10-22), p. 17480-17485
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 43 ( 2013-10-22), p. 17480-17485
    Abstract: Menin is a scaffold protein encoded by the multiple endocrine neoplasia type 1 ( MEN1 ) gene in humans, and it interacts with a variety of transcriptional proteins to control active or repressive cellular processes. Here, we show that heterozygous ablation of Men1 in female mice reduces chemical carcinogen-induced liver carcinogenesis and represses the activation of the inflammation pathway. Using ChIP-on-chip screens and ChIP assays, we find that menin occupancy frequently coincides with H3K4me3 at the promoter of many liver cancer-related genes, such as Yes-associated protein (Yap1). Increased menin and Yap1 expression in human hepatocellular carcinoma specimens was associated with poor prognosis. Our findings reveal that menin plays an important epigenetic role in promoting liver tumorigenesis, and support the notion that H3K4me3, which is regulated by the menin–mixed-lineage leukemia complex, is a potential therapeutic target in hepatocellular carcinoma.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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