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  • Oxford University Press (OUP)  (27)
  • 1
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    Comprehensive Characterization of the Genomic Landscape in Chinese Pulmonary Neuroendocrine Tumors Reveals Prognostic and Therapeutic Markers (CSWOG-1901)
    Oxford University Press (OUP) ; 2022
    In:  The Oncologist Vol. 27, No. 2 ( 2022-03-04), p. e116-e125
    Details
    In: The Oncologist, Oxford University Press (OUP), Vol. 27, No. 2 ( 2022-03-04), p. e116-e125
    Abstract: Pulmonary neuroendocrine tumors (pNETs) include typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). The optimal treatment strategy for each subtype remains elusive, partly due to the lack of comprehensive understanding of their molecular features. We aimed to explore differential genomic signatures in pNET subtypes and identify potential prognostic and therapeutic biomarkers. Methods We investigated genomic profiles of 57 LCNECs, 49 SCLCs, 18 TCs, and 24 ACs by sequencing tumor tissues with a 520-gene panel and explored the associations between genomic features and prognosis. Results Both LCNEC and SCLC displayed higher mutation rates for TP53, PRKDC, SPTA1, NOTCH1, NOTCH2, and PTPRD than TC and AC. Small cell lung carcinoma harbored more frequent co-alterations in TP53-RB1, alterations in PIK3CA and SOX2, and mutations in HIF-1, VEGF and Notch pathways. Large cell neuroendocrine carcinoma (12.7 mutations/Mb) and SCLC (11.9 mutations/Mb) showed higher tumor mutational burdens than TC (2.4 mutations/Mb) and AC (7.1 mutations/Mb). 26.3% of LCNECs and 20.8% of ACs harbored alterations in classical non-small cell lung cancer driver genes. The presence of alterations in the homologous recombination pathway predicted longer progression-free survival in advanced LCNEC patients with systemic therapy (P = .005) and longer overall survival (OS) in SCLC patients with resection (P = .011). The presence of alterations in VEGF (P = .048) and estrogen (P = .018) signaling pathways both correlated with better OS in patients with resected SCLC. Conclusion We performed a comprehensive genomic investigation on 4 pNET subtypes in the Chinese population. Our data revealed distinctive genomic signatures in subtypes and provided new insights into the prognostic and therapeutic stratification of pNETs.
    Type of Medium: Online Resource
    ISSN: 1083-7159 , 1549-490X
    URL: Article
    DOI: 10.1093/oncolo/oyab044
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2023829-0
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  • 2
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    Chinese experts recommendation on the monitoring and management of variability in responsiveness to antiplatelet therapy
    Oxford University Press (OUP) ; 2015
    In:  European Heart Journal Supplements Vol. 17, No. suppl B ( 2015-03-01), p. B5-B12
    Details
    In: European Heart Journal Supplements, Oxford University Press (OUP), Vol. 17, No. suppl B ( 2015-03-01), p. B5-B12
    Type of Medium: Online Resource
    ISSN: 1520-765X
    URL: Article
    DOI: 10.1093/eurheartj/suv025
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 2141255-8
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  • 3
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    Association of Psychological Stress with Physical Fitness in a Military Cohort: The CHIEF Study
    Oxford University Press (OUP) ; 2020
    In:  Military Medicine Vol. 185, No. 7-8 ( 2020-08-14), p. e1240-e1246
    Details
    In: Military Medicine, Oxford University Press (OUP), Vol. 185, No. 7-8 ( 2020-08-14), p. e1240-e1246
    Abstract: Psychological stress is associated with sedentary behavior, which may impair exercise performance. The aim of our study was to examine the association between psychological stress and physical fitness in military personnel. Method A military cohort of 4080 subjects in Taiwan was used for the analysis. The Brief Symptoms Rating Scale (BSRS-5) includes items of anxiety, depression, hostility, interpersonal sensitivity, and insomnia measured by a five-point Likert-type scale of 0–4. Psychological stress was defined as normal (n = 3657), slight (n = 314), and great (n = 109) by BSRS-5 score ≤5, 6–9, and ≥10, respectively. Aerobic fitness and anaerobic fitness were evaluated by the time of 3000-meter running and the numbers of 2-min sit-ups and 2-min push-ups, respectively. Multiple linear and logistic regression analyses were used to determine the relationship. Results As compared with normal stress, slight and great stress were positive dose-dependently correlated with 3000-meter running time (β = 9.09 and 14.44; P = 0.0032 and 0.048, respectively) after adjusting for age, sex, service specialty, body mass index, systolic blood pressure, cigarette smoking, alcohol intake, hemoglobin levels, and exercise frequency. Similarly, those with slight stress were more likely to be the worst 10% performers in the 3000-meter run test relative to the normal individuals (odds ratio and 95% confidence intervals: 1.50, 1.00–2.24). By contrast, there was no relationship of psychological stress with the numbers of 2-min sit-ups and 2-min push-ups. Conclusions Our findings suggest that the presence of higher psychological stress on military personnel may reduce their cardiorespiratory fitness but not affect the anaerobic fitness.
    Type of Medium: Online Resource
    ISSN: 0026-4075 , 1930-613X
    URL: Article
    DOI: 10.1093/milmed/usz469
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2130577-8
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  • 4
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    Seasonal nitrogen remobilization and the role of auxin transport in poplar trees
    Oxford University Press (OUP) ; 2020
    In:  Journal of Experimental Botany Vol. 71, No. 15 ( 2020-07-25), p. 4512-4530
    Details
    In: Journal of Experimental Botany, Oxford University Press (OUP), Vol. 71, No. 15 ( 2020-07-25), p. 4512-4530
    Abstract: Seasonal nitrogen (N) cycling in Populus, involves bark storage proteins (BSPs) that accumulate in bark phloem parenchyma in the autumn and decline when shoot growth resumes in the spring. Little is known about the contribution of BSPs to growth or the signals regulating N remobilization from BSPs. Knockdown of BSP accumulation via RNAi and N sink manipulations were used to understand how BSP storage influences shoot growth. Reduced accumulation of BSPs delayed bud break and reduced shoot growth following dormancy. Further, 13N tracer studies also showed that BSP accumulation is an important factor in N partitioning from senescing leaves to bark. Thus, BSP accumulation has a role in N remobilization during N partitioning both from senescing leaves to bark and from bark to expanding shoots once growth commences following dormancy. The bark transcriptome during BSP catabolism and N remobilization was enriched in genes associated with auxin transport and signaling, and manipulation of the source of auxin or auxin transport revealed a role for auxin in regulating BSP catabolism and N remobilization. Therefore, N remobilization appears to be regulated by auxin produced in expanding buds and shoots that is transported to bark where it regulates protease gene expression and BSP catabolism.
    Type of Medium: Online Resource
    ISSN: 0022-0957 , 1460-2431
    URL: Article
    DOI: 10.1093/jxb/eraa130
    RVK:
    WA 15000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1466717-4
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  • 5
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    Photoevaporation of protoplanetary gas discs due to flybys of external single stars in different orbits
    Oxford University Press (OUP) ; 2018
    In:  Monthly Notices of the Royal Astronomical Society Vol. 480, No. 3 ( 2018-11-01), p. 4080-4098
    Details
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP), Vol. 480, No. 3 ( 2018-11-01), p. 4080-4098
    Type of Medium: Online Resource
    ISSN: 0035-8711 , 1365-2966
    URL: Article
    DOI: 10.1093/mnras/sty2142
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2016084-7
    SSG: 16,12
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  • 6
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    An Evaluation of High-Throughput Approaches to QTL Mapping in Saccharomyces cerevisiae
    Oxford University Press (OUP) ; 2014
    In:  Genetics Vol. 196, No. 3 ( 2014-03-01), p. 853-865
    Details
    In: Genetics, Oxford University Press (OUP), Vol. 196, No. 3 ( 2014-03-01), p. 853-865
    Abstract: Dissecting the molecular basis of quantitative traits is a significant challenge and is essential for understanding complex diseases. Even in model organisms, precisely determining causative genes and their interactions has remained elusive, due in part to difficulty in narrowing intervals to single genes and in detecting epistasis or linked quantitative trait loci. These difficulties are exacerbated by limitations in experimental design, such as low numbers of analyzed individuals or of polymorphisms between parental genomes. We address these challenges by applying three independent high-throughput approaches for QTL mapping to map the genetic variants underlying 11 phenotypes in two genetically distant Saccharomyces cerevisiae strains, namely (1) individual analysis of & gt;700 meiotic segregants, (2) bulk segregant analysis, and (3) reciprocal hemizygosity scanning, a new genome-wide method that we developed. We reveal differences in the performance of each approach and, by combining them, identify eight polymorphic genes that affect eight different phenotypes: colony shape, flocculation, growth on two nonfermentable carbon sources, and resistance to two drugs, salt, and high temperature. Our results demonstrate the power of individual segregant analysis to dissect QTL and address the underestimated contribution of interactions between variants. We also reveal confounding factors like mutations and aneuploidy in pooled approaches, providing valuable lessons for future designs of complex trait mapping studies.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    URL: Article
    DOI: 10.1534/genetics.113.160291
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2014
    detail.hit.zdb_id: 1477228-0
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  • 7
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    Variation in Crossover Frequencies Perturb Crossover Assurance Without Affecting Meiotic Chromosome Segregation in Saccharomyces cerevisiae
    Oxford University Press (OUP) ; 2015
    In:  Genetics Vol. 199, No. 2 ( 2015-02-01), p. 399-412
    Details
    In: Genetics, Oxford University Press (OUP), Vol. 199, No. 2 ( 2015-02-01), p. 399-412
    Abstract: The segregation of homologous chromosomes during the Meiosis I division requires an obligate crossover per homolog pair (crossover assurance). In Saccharomyces cerevisiae and mammals, Msh4 and Msh5 proteins stabilize Holliday junctions and its progenitors to facilitate crossing over. S. cerevisiae msh4/5 hypomorphs that reduce crossover levels up to twofold at specific loci on chromosomes VII, VIII, and XV without affecting homolog segregation were identified recently. We use the msh4–R676W hypomorph to ask if the obligate crossover is insulated from variation in crossover frequencies, using a S. cerevisiae S288c/YJM789 hybrid to map recombination genome-wide. The msh4–R676W hypomorph made on average 64 crossovers per meiosis compared to 94 made in wild type and 49 in the msh4Δ mutant confirming the defect seen at individual loci on a genome-wide scale. Crossover reductions in msh4–R676W and msh4Δ were significant across chromosomes regardless of size, unlike previous observations made at specific loci. The msh4–R676W hypomorph showed reduced crossover interference. Although crossover reduction in msh4–R676W is modest, 42% of the four viable spore tetrads showed nonexchange chromosomes. These results, along with modeling of crossover distribution, suggest the significant reduction in crossovers across chromosomes and the loss of interference compromises the obligate crossover in the msh4 hypomorph. The high spore viability of the msh4 hypomorph is maintained by efficient segregation of the natural nonexchange chromosomes. Our results suggest that variation in crossover frequencies can compromise the obligate crossover and also support a mechanistic role for interference in obligate crossover formation.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    URL: Article
    DOI: 10.1534/genetics.114.172320
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
    detail.hit.zdb_id: 1477228-0
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  • 8
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    Meiotic Interactors of a Mitotic Gene TAO3 Revealed by Functional Analysis of its Rare Variant
    Oxford University Press (OUP) ; 2016
    In:  G3 Genes|Genomes|Genetics Vol. 6, No. 8 ( 2016-08-01), p. 2255-2263
    Details
    In: G3 Genes|Genomes|Genetics, Oxford University Press (OUP), Vol. 6, No. 8 ( 2016-08-01), p. 2255-2263
    Abstract: Studying the molecular consequences of rare genetic variants has the potential to identify novel and hitherto uncharacterized pathways causally contributing to phenotypic variation. Here, we characterize the functional consequences of a rare coding variant of TAO3, previously reported to contribute significantly to sporulation efficiency variation in Saccharomyces cerevisiae. During mitosis, the common TAO3 allele interacts with CBK1—a conserved NDR kinase. Both TAO3 and CBK1 are components of the RAM signaling network that regulates cell separation and polarization during mitosis. We demonstrate that the role of the rare allele TAO3(4477C) in meiosis is distinct from its role in mitosis by being independent of ACE2—a RAM network target gene. By quantitatively measuring cell morphological dynamics, and expressing the TAO3(4477C) allele conditionally during sporulation, we show that TAO3 has an early role in meiosis. This early role of TAO3 coincides with entry of cells into meiotic division. Time-resolved transcriptome analyses during early sporulation identified regulators of carbon and lipid metabolic pathways as candidate mediators. We show experimentally that, during sporulation, the TAO3(4477C) allele interacts genetically with ERT1 and PIP2, regulators of the tricarboxylic acid cycle and gluconeogenesis metabolic pathways, respectively. We thus uncover a meiotic functional role for TAO3, and identify ERT1 and PIP2 as novel regulators of sporulation efficiency. Our results demonstrate that studying the causal effects of genetic variation on the underlying molecular network has the potential to provide a more extensive understanding of the pathways driving a complex trait.
    Type of Medium: Online Resource
    ISSN: 2160-1836
    URL: Article
    DOI: 10.1534/g3.116.029900
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2629978-1
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  • 9
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    Modulating Crossover Frequency and Interference for Obligate Crossovers in Saccharomyces cerevisiae Meiosis
    Oxford University Press (OUP) ; 2017
    In:  G3 Genes|Genomes|Genetics Vol. 7, No. 5 ( 2017-05-01), p. 1511-1524
    Details
    In: G3 Genes|Genomes|Genetics, Oxford University Press (OUP), Vol. 7, No. 5 ( 2017-05-01), p. 1511-1524
    Abstract: Meiotic crossover frequencies show wide variation among organisms. But most organisms maintain at least one crossover per homolog pair (obligate crossover). In Saccharomyces cerevisiae, previous studies have shown crossover frequencies are reduced in the mismatch repair related mutant mlh3Δ and enhanced in a meiotic checkpoint mutant pch2Δ by up to twofold at specific chromosomal loci, but both mutants maintain high spore viability. We analyzed meiotic recombination events genome-wide in mlh3Δ, pch2Δ, and mlh3Δ pch2Δ mutants to test the effect of variation in crossover frequency on obligate crossovers. mlh3Δ showed ∼30% genome-wide reduction in crossovers (64 crossovers per meiosis) and loss of the obligate crossover, but nonexchange chromosomes were efficiently segregated. pch2Δ showed ∼50% genome-wide increase in crossover frequency (137 crossovers per meiosis), elevated noncrossovers as well as loss of chromosome size dependent double-strand break formation. Meiotic defects associated with pch2∆ did not cause significant increase in nonexchange chromosome frequency. Crossovers were restored to wild-type frequency in the double mutant mlh3Δ pch2Δ (100 crossovers per meiosis), but obligate crossovers were compromised. Genetic interference was reduced in mlh3Δ, pch2Δ, and mlh3Δ pch2Δ. Triple mutant analysis of mlh3Δ pch2Δ with other resolvase mutants showed that most of the crossovers in mlh3Δ pch2Δ are made through the Mus81-Mms4 pathway. These results are consistent with a requirement for increased crossover frequencies in the absence of genetic interference for obligate crossovers. In conclusion, these data suggest crossover frequencies and the strength of genetic interference in an organism are mutually optimized to ensure obligate crossovers.
    Type of Medium: Online Resource
    ISSN: 2160-1836
    URL: Article
    DOI: 10.1534/g3.117.040071
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
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  • 10
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    Association Between Dental Calculus and Hypertension Phenotypes in Highly Fit Adults: CHIEF Oral Health Study
    Oxford University Press (OUP) ; 2023
    In:  American Journal of Hypertension Vol. 36, No. 2 ( 2023-02-13), p. 102-108
    Details
    In: American Journal of Hypertension, Oxford University Press (OUP), Vol. 36, No. 2 ( 2023-02-13), p. 102-108
    Abstract: Poor oral health evaluated by presence of dental calculus has been associated with hypertension (HTN) among middle- and old-aged adults. However, it is unclear for the association of HTN phenotypes with dental calculus in young adults. Methods This study examined the association between dental calculus and HTN in 5,345 military personnel, aged 19–45 years, without antihypertensive medications therapy in Taiwan from 2018 to 2021. Dental calculus was defined as presence of supragingival calculus in any teeth, except impacted teeth, and third molar. Combined HTN (CHTN) was diagnosed as systolic blood pressure (SBP) ≥130 mm Hg and diastolic blood pressure (DBP) ≥80 mm Hg. Isolated systolic and diastolic HTN were, respectively, defined as SBP ≥130 mm Hg only (ISHTN) and DBP ≥80 mm Hg only (IDHTN). Multiple logistic regression with adjustments for sex, age, toxic substance use, anthropometrics, lipid profiles, fasting glucose, and blood leukocyte counts were used to determine the association between dental calculus and HTN phenotypes in young adults. Results The prevalence of those with dental calculus, CHTN, ISHTN, and IDHTN was 20.8%, 10.8%, 10.2%, and 7.0%, respectively. The dental calculus was associated a greater possibility with CHTN [odds ratio (OR) and 95% confidence interval: 1.60 (1.31–1.95)]. However, the associations of dental calculus with ISHTN and IDHTN were null [OR: 1.05 (0.81–1.27) and 1.12 (0.86–1.46), respectively] . Conclusions Our findings suggest that among young adults, poor oral health manifested by presence of dental calculus was associated with a greater possibility of CHTN, while not for ISHTN and IDHTN.
    Type of Medium: Online Resource
    ISSN: 0895-7061 , 1941-7225
    URL: Article
    DOI: 10.1093/ajh/hpac119
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1479505-X
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