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  • Oxford University Press (OUP)  (20)
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  • Oxford University Press (OUP)  (20)
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  • 1
    Online Resource
    Online Resource
    Estimating and testing high-dimensional mediation effects in epigenetic studies
    Oxford University Press (OUP) ; 2016
    In:  Bioinformatics Vol. 32, No. 20 ( 2016-10-15), p. 3150-3154
    Details
    In: Bioinformatics, Oxford University Press (OUP), Vol. 32, No. 20 ( 2016-10-15), p. 3150-3154
    Abstract: Motivation: High-dimensional DNA methylation markers may mediate pathways linking environmental exposures with health outcomes. However, there is a lack of analytical methods to identify significant mediators for high-dimensional mediation analysis. Results: Based on sure independent screening and minimax concave penalty techniques, we use a joint significance test for mediation effect. We demonstrate its practical performance using Monte Carlo simulation studies and apply this method to investigate the extent to which DNA methylation markers mediate the causal pathway from smoking to reduced lung function in the Normative Aging Study. We identify 2 CpGs with significant mediation effects. Availability and implementation: R package, source code, and simulation study are available at https://github.com/YinanZheng/HIMA. Contact:  lei.liu@northwestern.edu
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    URL: Article
    DOI: 10.1093/bioinformatics/btw351
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    StMYB44 negatively regulates anthocyanin biosynthesis at high temperatures in tuber flesh of potato
    Oxford University Press (OUP) ; 2019
    In:  Journal of Experimental Botany Vol. 70, No. 15 ( 2019-08-07), p. 3809-3824
    Details
    In: Journal of Experimental Botany, Oxford University Press (OUP), Vol. 70, No. 15 ( 2019-08-07), p. 3809-3824
    Abstract: High temperatures are known to reduce anthocyanin accumulation in a number of diverse plant species. In potato (Solanum tuberosum L.), high temperature significantly reduces tuber anthocyanin pigment content. However, the mechanism of anthocyanin biosynthesis in potato tuber under heat stress remains unknown. Here we show that high temperature causes reduction of anthocyanin biosynthesis in both potato tuber skin and flesh, with white areas forming between the vasculature and periderm. Heat stress reduced the expression of the R2R3 MYB transcription factors (TFs) StAN1 and StbHLH1, members of the transcriptional complex responsible for coordinated regulation of the skin and flesh pigmentation, as well as anthocyanin biosynthetic pathway genes in white regions. However, the core phenylpropanoid pathway, lignin, and chlorogenic acid (CGA) pathway genes were up-regulated in white areas, suggesting that suppression of the anthocyanin branch may result in re-routing phenylpropanoid flux into the CGA or lignin biosynthesis branches. Two R2R3 MYB TFs, StMYB44-1 and StMYB44-2, were highly expressed in white regions under high temperature. In transient assays, StMYB44 represses anthocyanin accumulation in leaves of Nicotiana tabacum and N. benthamiana by directly suppressing the activity of the dihydroflavonol reductase (DFR) promoter. StMYB44-1 showed stronger repressive capacity than StMYB44-2, with both predicted proteins containing the repression-associated EAR motif with some variation. StMYB44-1 conferred repression without a requirement for a basic helix–loop–helix (bHLH) partner, suggesting a different repression mechanism from that of reported anthocyanin repressors. We propose that temperature-induced reduction of anthocyanin accumulation in potato flesh is caused by down-regulation of the activating anthocyanin regulatory complex, by enhancing the expression of flesh-specific StMYB44 and alteration of phenylpropanoid flux.
    Type of Medium: Online Resource
    ISSN: 0022-0957 , 1460-2431
    URL: Article
    DOI: 10.1093/jxb/erz194
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1466717-4
    SSG: 12
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  • 3
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    Direct Determination of Coagulation Factor IIa and Plasmin Activities for Monitoring of Thrombotic State
    Oxford University Press (OUP) ; 2020
    In:  The Journal of Applied Laboratory Medicine Vol. 5, No. 6 ( 2020-11-01), p. 1265-1276
    Details
    In: The Journal of Applied Laboratory Medicine, Oxford University Press (OUP), Vol. 5, No. 6 ( 2020-11-01), p. 1265-1276
    Abstract: Current laboratory examinations for hypercoagulable diseases focus on the biomarker content of the activated coagulation cascade and fibrinolytic system. Direct detection of physiologically important protease activities in blood remains a challenge. This study aims to develop a general approach that enables the determination of activities of crucial coagulation factors and plasmin in blood. Methods This assay is based on the proteolytic activation of an engineered zymogen of l-phenylalanine oxidase (proPAO), for which the specific blood protease cleavage sites were engineered between the inhibitory and activity domains of proPAO. Specific cleavage of the recombinant proenzyme leads to the activation of proPAO, followed by oxidation and oxygenation of l-phenylalanine, resulting in an increase of chromogenic production when coupled with the Trinder reaction. Results We applied this method to determine the activities of both coagulation factor IIa and plasmin in their physiologically relevant basal state and fully activated state in sodium citrate–anticoagulated plasma respectively. Factor IIa and plasmin activities could be dynamically monitored in patients with thrombotic disease who were taking oral anticoagulants and used for assessing the hypercoagulable state in pregnant women. Conclusions The high specificity, sensitivity, and stability of this novel assay not only makes it useful for determining clinically important protease activities in human blood and diagnosing thrombotic diseases but also provides a new way to monitor the effectiveness and safety of anticoagulant drugs.
    Type of Medium: Online Resource
    ISSN: 2576-9456 , 2475-7241
    URL: Article
    DOI: 10.1093/jalm/jfaa060
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 4
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    Development and Validation of a Deep Learning–Based Histologic Diagnosis System for Diagnosing Colorectal Sessile Serrated Lesions
    Oxford University Press (OUP) ; 2023
    In:  American Journal of Clinical Pathology Vol. 160, No. 4 ( 2023-10-03), p. 394-403
    Details
    In: American Journal of Clinical Pathology, Oxford University Press (OUP), Vol. 160, No. 4 ( 2023-10-03), p. 394-403
    Abstract: The histopathologic diagnosis of colorectal sessile serrated lesions (SSLs) and hyperplastic polyps (HPs) is of low consistency among pathologists. This study aimed to develop and validate a deep learning (DL)–based logical anthropomorphic pathology diagnostic system (LA-SSLD) for the differential diagnosis of colorectal SSL and HP. Methods The diagnosis framework of the LA-SSLD system was constructed according to the current guidelines and consisted of 4 DL models. Deep convolutional neural network (DCNN) 1 was the mucosal layer segmentation model, DCNN 2 was the muscularis mucosa segmentation model, DCNN 3 was the glandular lumen segmentation model, and DCNN 4 was the glandular lumen classification (aberrant or regular) model. A total of 175 HP and 127 SSL sections were collected from Renmin Hospital of Wuhan University during November 2016 to November 2022. The performance of the LA-SSLD system was compared to 11 pathologists with different qualifications through the human-machine contest. Results The Dice scores of DCNNs 1, 2, and 3 were 93.66%, 58.38%, and 74.04%, respectively. The accuracy of DCNN 4 was 92.72%. In the human-machine contest, the accuracy, sensitivity, and specificity of the LA-SSLD system were 85.71%, 86.36%, and 85.00%, respectively. In comparison with experts (pathologist D: accuracy 83.33%, sensitivity 90.91%, specificity 75.00%; pathologist E: accuracy 85.71%, sensitivity 90.91%, specificity 80.00%), LA-SSLD achieved expert-level accuracy and outperformed all the senior and junior pathologists. Conclusions This study proposed a logical anthropomorphic diagnostic system for the differential diagnosis of colorectal SSL and HP. The diagnostic performance of the system is comparable to that of experts and has the potential to become a powerful diagnostic tool for SSL in the future. It is worth mentioning that a logical anthropomorphic system can achieve expert-level accuracy with fewer samples, providing potential ideas for the development of other artificial intelligence models.
    Type of Medium: Online Resource
    ISSN: 0002-9173 , 1943-7722
    URL: Article
    DOI: 10.1093/ajcp/aqad058
    RVK:
    YV 2000
    RVK:
    XA 18700
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2039921-2
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  • 5
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    A 21-bp InDel in the promoter of STP1 selected during tomato improvement accounts for soluble solid content in fruits
    Oxford University Press (OUP) ; 2023
    In:  Horticulture Research Vol. 10, No. 3 ( 2023-03-03)
    Details
    In: Horticulture Research, Oxford University Press (OUP), Vol. 10, No. 3 ( 2023-03-03)
    Abstract: Domestication and improvement are important processes that generate the variation in genome and phonotypes underlying crop improvement. Unfortunately, during selection for certain attributes, other valuable traits may be inadvertently discarded. One example is the decline in fruit soluble solids content (SSC) during tomato breeding. Several genetic loci for SSC have been identified, but few reports on the underlying mechanisms are available. In this study we performed a genome-wide association study (GWAS) for SSC of the red-ripe fruits in a population consisting of 481 tomato accessions with large natural variations and found a new quantitative trait locus, STP1, encoding a sugar transporter protein. The causal variation of STP1, a 21-bp InDel located in the promoter region 1124 bp upstream of the start codon, alters its expression. STP1Insertion accessions with an 21-bp insertion have higher SSC than STP1Deletion accessions with the 21-bp deletion. Knockout of STP1 in TS-23 with high SSC using CRISPR/Cas9 greatly decreased SSC in fruits. In vivo and in vitro assays demonstrated that ZAT10-LIKE, a zinc finger protein transcription factor (ZFP TF), can specifically bind to the promoter of STP1Insertion to enhance STP1 expression, but not to the promoter of STP1Deletion, leading to lower fruit SSC in modern tomatoes. Diversity analysis revealed that STP1 was selected during tomato improvement. Taking these results together, we identified a naturally occurring causal variation underlying SSC in tomato, and a new role for ZFP TFs in regulating sugar transporters. The findings enrich our understanding of tomato evolution and domestication, and provide a genetic basis for genome design for improving fruit taste.
    Type of Medium: Online Resource
    ISSN: 2052-7276
    URL: Article
    DOI: 10.1093/hr/uhad009
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2781828-7
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  • 6
    Online Resource
    Online Resource
    Association of impaired lung function with dementia, and brain magnetic resonance imaging indices: a large population-based longitudinal study
    Oxford University Press (OUP) ; 2022
    In:  Age and Ageing Vol. 51, No. 11 ( 2022-11-02)
    Details
    In: Age and Ageing, Oxford University Press (OUP), Vol. 51, No. 11 ( 2022-11-02)
    Abstract: to examine the association between different patterns of impaired lung function with the incident risk of dementia and magnetic resonance imaging (MRI)-based brain structural features. Methods in UK Biobank, a total of 308,534 dementia-free participants with valid lung function measures (forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC] ) were included. Association was assessed using Cox proportional hazards regression model. Furthermore, the association between impaired lung function and brain MRI biomarkers related to cognitive function was analysed among 30,159 participants. Results during a median follow-up of 12.6 years, 3,607 incident all-cause dementia cases were recorded. Restrictive impairment (hazard ratio [HR], 1.42; 95% confidence interval [CI] , 1.27–1.60) and obstructive impairment (HR, 1.28; 95% CI, 1.15–1.42) were associated with higher risk of all-cause dementia. The restricted cubic splines indicated FEV1% predicted and FVC % predicted had reversed J-shaped associations with dementia. Participants with impaired lung function have higher risks of all-cause dementia across all apolipoprotein E (APOE) risk categories, whereas associations were stronger among those of low APOE risk (P for interaction = 0.034). In addition, restrictive and obstructive impairment were linked to lower total (β: −0.075, SE: 0.021, Pfdr = 0.002; β: −0.033, SE: 0.017, Pfdr = 0.069) and frontoparietal grey matter volumes, higher white matter hyperintensity, poorer white matter integrity, lower hippocampus (β: –0.066, SE: 0.024, Pfdr = 0.017; β: –0.051, SE: 0.019, Pfdr = 0.019) and other subcortical volumes. Conclusions participants with restrictive and obstructive impairments had a higher risk of dementia. Brain MRI indices further supported adverse effects and provided insight into potential pathophysiology biomarkers.
    Type of Medium: Online Resource
    ISSN: 0002-0729 , 1468-2834
    URL: Article
    DOI: 10.1093/ageing/afac269
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2065766-3
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  • 7
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    A precise and efficient circular RNA synthesis system based on a ribozyme derived from Tetrahymena thermophila
    Oxford University Press (OUP) ; 2023
    In:  Nucleic Acids Research Vol. 51, No. 14 ( 2023-08-11), p. e78-e78
    Details
    In: Nucleic Acids Research, Oxford University Press (OUP), Vol. 51, No. 14 ( 2023-08-11), p. e78-e78
    Abstract: Classic strategies for circular RNA (circRNA) preparation always introduce large numbers of linear transcripts or extra nucleotides to the circularized product. In this study, we aimed to develop an efficient system for circRNA preparation based on a self-splicing ribozyme derived from an optimized Tetrahymena thermophila group Ⅰ intron. The target RNA sequence was inserted downstream of the ribozyme and a complementary antisense region was added upstream of the ribozyme to assist cyclization. Then, we compared the circularization efficiency of ribozyme or flanking intronic complementary sequence (ICS)-mediated methods through the DNMT1, CDR1as, FOXO3, and HIPK3 genes and found that the efficiency of our system was remarkably higher than that of flanking ICS-mediated method. Consequently, the circularized products mediated by ribozyme are not introduced with additional nucleotides. Meanwhile, the overexpressed circFOXO3 maintained its biological functions in regulating cell proliferation, migration, and apoptosis. Finally, a ribozyme-based circular mRNA expression system was demonstrated with a split green fluorescent protein (GFP) using an optimized Coxsackievirus B3 (CVB3) internal ribosome entry site (IRES) sequence, and this system achieved successful translation of circularized mRNA. Therefore, this novel, convenient, and rapid engineering RNA circularization system can be applied for the functional study and large-scale preparation of circular RNA in the future.
    Type of Medium: Online Resource
    ISSN: 0305-1048 , 1362-4962
    URL: Article
    DOI: 10.1093/nar/gkad554
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1472175-2
    SSG: 12
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  • 8
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    AaWRKY17, a positive regulator of artemisinin biosynthesis, is involved in resistance to Pseudomonas syringae in Artemisia annua
    Oxford University Press (OUP) ; 2021
    In:  Horticulture Research Vol. 8, No. 1 ( 2021-12)
    Details
    In: Horticulture Research, Oxford University Press (OUP), Vol. 8, No. 1 ( 2021-12)
    Abstract: Artemisia annua , a traditional Chinese medicinal plant, remains the only plant source for artemisinin production, yet few genes have been identified to be involved in both the response to biotic stresses, such as pathogens, and artemisinin biosynthesis. Here, we isolated and identified the WRKY transcription factor (TF) AaWRKY17, which could significantly increase the artemisinin content and resistance to Pseudomonas syringae in A. annua . Yeast one-hybrid (Y1H), dual-luciferase (dual-LUC), and electrophoretic mobility shift assay (EMSA) results showed that AaWRKY17 directly bound to the W-box motifs in the promoter region of the artemisinin biosynthetic pathway gene amorpha-4,11-diene synthase ( ADS ) and promoted its expression. Real-time quantitative PCR (RT-qPCR) analysis revealed that the transcript levels of two defense marker genes, Pathogenesis-Related 5 ( PR5 ) and NDR1/HIN1-LIKE 10 ( NHL10 ), were greatly increased in AaWRKY17- overexpressing transgenic A. annua plants. Additionally, overexpression of AaWRKY17 in A. annua resulted in decreased susceptibility to P. syringae . These results indicated that AaWRKY17 acted as a positive regulator in response to P. syringae infection. Together, our findings demonstrated that the novel WRKY transcription factor AaWRKY17 could potentially be used in transgenic breeding to improve the content of artemisinin and pathogen tolerance in A. annua .
    Type of Medium: Online Resource
    ISSN: 2662-6810 , 2052-7276
    URL: Article
    DOI: 10.1038/s41438-021-00652-6
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2781828-7
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  • 9
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    Continue or not to continue? Attitudes towards deprescription among community-dwelling older adults in China
    Oxford University Press (OUP) ; 2021
    In:  Innovation in Aging Vol. 5, No. Supplement_1 ( 2021-12-17), p. 830-830
    Details
    In: Innovation in Aging, Oxford University Press (OUP), Vol. 5, No. Supplement_1 ( 2021-12-17), p. 830-830
    Abstract: Inappropriate prescribing of medications and polypharmacy among older adults could lead to avoidable harms. It is hence vital to stop potentially inappropriate medications in this vulnerable group. An approach coined 'deprescribing' has been used to describe a patient-centerd process of optimizing medication regimens. But patient resistance to discontinuing medication use is a significant barrier to deprescribing. The present study aims to describe attitudes towards deprescribing and to examine individual-based characteristics that might be associated with these attitudes among community-dwelling older adults in China. We conducted a cross-sectional study through in-person interviews using the validated Patients’ Attitudes Towards Deprescribing questionnaire in two communities through the community-based physical examination platform. Participants were 65 years and older and had at least one chronic disease and one regular prescription medication. Of the 1,897 participants in the study, the average age was 74 years and 1,023 (53.9%) were women. The majority had one chronic disease (n=1,364 [71.9%]) and took 1-2 medications (n=1,483 [78.2%] ). A total of 947 (50.0%) older adults reported being willing to stop taking one or more of their medicines if their physician said it was possible, and 1204 (63.5%) older adults wanted to stop a medicine been taking for a long time. Chronological age, marital status, number of chronic diseases, and self-rated health status were associated with the attitudes towards deprescribing. This study showed that half of the participants were willing to cease a medication that their physician though was no longer required. Individual-level factors were associated with attitudes towards deprescribing.
    Type of Medium: Online Resource
    ISSN: 2399-5300
    URL: Article
    DOI: 10.1093/geroni/igab046.3043
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2905697-4
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  • 10
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    Suppression of glioblastoma by targeting the overactivated protein neddylation pathway
    Oxford University Press (OUP) ; 2015
    In:  Neuro-Oncology Vol. 17, No. 10 ( 2015-10), p. 1333-1343
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 17, No. 10 ( 2015-10), p. 1333-1343
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/nov066
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2094060-9
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