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  • 1
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    Chronic coronary syndromes without standard modifiable cardiovascular risk factors and outcomes: the CLARIFY registry
    Oxford University Press (OUP) ; 2024
    In:  European Heart Journal ( 2024-05-20)
    Details
    In: European Heart Journal, Oxford University Press (OUP), ( 2024-05-20)
    Abstract: It has been reported that patients without standard modifiable cardiovascular (CV) risk factors (SMuRFs—diabetes, dyslipidaemia, hypertension, and smoking) presenting with first myocardial infarction (MI), especially women, have a higher in-hospital mortality than patients with risk factors, and possibly a lower long-term risk provided they survive the post-infarct period. This study aims to explore the long-term outcomes of SMuRF-less patients with stable coronary artery disease (CAD). Methods CLARIFY is an observational cohort of 32 703 outpatients with stable CAD enrolled between 2009 and 2010 in 45 countries. The baseline characteristics and clinical outcomes of patients with and without SMuRFs were compared. The primary outcome was a composite of 5-year CV death or non-fatal MI. Secondary outcomes were 5-year all-cause mortality and major adverse cardiovascular events (MACE—CV death, non-fatal MI, or non-fatal stroke). Results Among 22 132 patients with complete risk factor and outcome information, 977 (4.4%) were SMuRF-less. Age, sex, and time since CAD diagnosis were similar across groups. SMuRF-less patients had a lower 5-year rate of CV death or non-fatal MI (5.43% [95% CI 4.08–7.19] vs. 7.68% [95% CI 7.30–8.08] , P = 0.012), all-cause mortality, and MACE. Similar results were found after adjustments. Clinical event rates increased steadily with the number of SMuRFs. The benefit of SMuRF-less status was particularly pronounced in women. Conclusions SMuRF-less patients with stable CAD have a substantial but significantly lower 5-year rate of CV death or non-fatal MI than patients with risk factors. The risk of CV outcomes increases steadily with the number of risk factors.
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    URL: Article
    DOI: 10.1093/eurheartj/ehae299
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
    detail.hit.zdb_id: 2001908-7
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  • 2
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    Adjuvanted Intranasal Norwalk Virus‐Like Particle Vaccine Elicits Antibodies and Antibody‐Secreting Cells That Express Homing Receptors for Mucosal and Peripheral Lymphoid Tissues
    Oxford University Press (OUP) ; 2010
    In:  The Journal of Infectious Diseases Vol. 202, No. 11 ( 2010-12), p. 1649-1658
    Details
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 202, No. 11 ( 2010-12), p. 1649-1658
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Issue
    URL: Article
    DOI: 10.1086/653023
    DOI: 10.1086/657087
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
    detail.hit.zdb_id: 1473843-0
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  • 3
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    Probing the thermal state of the intergalactic medium at z 〉 5 with the transmission spikes in high-resolution  Ly α forest spectra
    Oxford University Press (OUP) ; 2020
    In:  Monthly Notices of the Royal Astronomical Society Vol. 494, No. 4 ( 2020-06-01), p. 5091-5109
    Details
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP), Vol. 494, No. 4 ( 2020-06-01), p. 5091-5109
    Abstract: We compare a sample of five high-resolution, high S/N  Ly α forest spectra of bright 6 & lt; z & lt; ∼6.5 QSOs aimed at spectrally resolving the last remaining transmission spikes at z & gt; 5 with those obtained from mock absorption spectra from the Sherwoodand Sherwood–Relics simulation suites of hydrodynamical simulations of the intergalactic medium (IGM). We use a profile-fitting procedure for the inverted transmitted flux, 1 − F, similar to the widely used Voigt profile fitting of the transmitted flux F at lower redshifts, to characterize the transmission spikes that probe predominately underdense regions of the IGM. We are able to reproduce the width and height distributions of the transmission spikes, both with optically thin simulations of the post-reionization Universe using a homogeneous UV background and full radiative transfer simulations of a late reionization model. We find that the width of the fitted components of the simulated transmission spikes is very sensitive to the instantaneous temperature of the reionized IGM. The internal structures of the spikes are more prominent in low temperature models of the IGM. The width distribution of the observed transmission spikes, which require high spectral resolution (≤ 8  km s−1) to be resolved, is reproduced for optically thin simulations with a temperature at mean density of T0 = (11 000 ± 1600, 10 500 ± 2100, 12 000 ± 2200) K at z = (5.4, 5.6, 5.8). This is weakly dependent on the slope of the temperature-density relation, which is favoured to be moderately steeper than isothermal. In the inhomogeneous, late reionization, full radiative transfer simulations where islands of neutral hydrogen persist to z ∼ 5.3, the width distribution of the observed transmission spikes is consistent with the range of T0 caused by spatial fluctuations in the temperature–density relation.
    Type of Medium: Online Resource
    ISSN: 0035-8711 , 1365-2966
    URL: Article
    DOI: 10.1093/mnras/staa907
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2016084-7
    SSG: 16,12
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  • 4
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    Sweet taste perception in mice is blunted by PTBP1-regulated skipping of Tas1r2 exon 4
    Oxford University Press (OUP) ; 2022
    In:  Chemical Senses Vol. 47 ( 2022-01-01)
    Details
    In: Chemical Senses, Oxford University Press (OUP), Vol. 47 ( 2022-01-01)
    Abstract: Taste perception, initiated by activation of taste receptors in taste bud cells, is crucial for regulating nutrient intake. Genetic polymorphisms in taste receptor genes cannot fully explain the wide individual variations of taste sensitivity. Alternative splicing (AS) is a ubiquitous posttranscriptional mode of gene regulation that enriches the functional diversity of proteins. Here, we report the identification of a novel splicing variant of sweet taste receptor gene Tas1r2 (Tas1r2_∆e4) in mouse taste buds and the mechanism by which it diminishes sweet taste responses in vitro and in vivo. Skipping of Tas1r2 exon 4 in Tas1r2_∆e4 led to loss of amino acids in the extracellular Venus flytrap domain, and the truncated isoform reduced the response of sweet taste receptors (STRs) to all sweet compounds tested by generating nonfunctional T1R2/T1R3 STR heterodimers. The splicing factor PTBP1 (polypyrimidine tract-binding protein 1) promoted Tas1r2_∆e4 generation through binding to a polypyrimidine-rich splicing silencer in Tas1r2 exon 4, thus decreasing STR function and sweet taste perception in mice. Taken together, these data reveal the existence of a regulated AS event in Tas1r2 expression and its effect on sweet taste perception, providing a novel mechanism for modulating taste sensitivity at the posttranscriptional level.
    Type of Medium: Online Resource
    ISSN: 0379-864X , 1464-3553
    URL: Article
    DOI: 10.1093/chemse/bjac034
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 1494617-8
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  • 5
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    Probing IGM accretion on to faint Lyα emitters at z ∼ 2.8
    Oxford University Press (OUP) ; 2019
    In:  Monthly Notices of the Royal Astronomical Society Vol. 486, No. 1 ( 2019-06-11), p. 1392-1403
    Details
    In: Monthly Notices of the Royal Astronomical Society, Oxford University Press (OUP), Vol. 486, No. 1 ( 2019-06-11), p. 1392-1403
    Abstract: Observing the signature of accretion from the intergalactic medium (IGM) on to galaxies at z ∼ 3 requires the detection of faint (L ≪ L*) galaxies embedded in a filamentary matrix of low-density ($\rho \lt 100\ \overline{\rho }$), metal-poor gas (Z ∼ 10−2.5 Z⊙) coherent over hundreds of kpc. We study the gaseous environment of three Lyα emitters (LAEs) at z = 2.7 − 2.8, found to be aligned in projection with a background QSO over ∼250 kpc along the slit of a long-slit spectrum. The lack of detection of the LAEs in deep continuum images and the low inferred Lyα luminosities show the LAEs to be intrinsically faint, low-mass galaxies ($L\lesssim 0.1\, L^*$, $M_\mathrm{star}\lesssim 0.1\, M^*$). An echelle spectrum of the QSO reveals strong Lyα absorption within ±200 km s−1 from the LAEs. Our absorption line analysis leads to $\rm{H\,{\small I}}$ column densities in the range of log $N\mathrm{(\rm{H\,{\small I}})}/\mbox{${\rm cm^{-2}}$}=16\!-\!18$. Associated absorption from ionic metal species $\rm{C\,{\small IV}}$ and $\rm{Si\,{\small IV}}$ constrains the gas metallicities to ∼0.01 solar if the gas is optically thin, and possibly as low as ∼0.001 solar if the gas is optically thick, assuming photoionization equilibrium. While the inferred metallicities are at least a factor of 10 lower than expected metallicities in the interstellar medium (ISM) of these LAEs, they are consistent with the observed chemical enrichment level in the IGM at the same epoch. Total metal abundances and kinematic arguments suggest that these faint galaxies have not been able to affect the properties of their surrounding gas. The projected spatial alignment of the LAEs, together with the kinematic quiescence and correspondence between the LAEs and absorbing gas in velocity space, suggests that these observations probe a possible filamentary structure. Taken together with the blue-dominant Lyα emission line profile of one of the objects, the evidence suggests that the absorbing gas is part of an accretion stream of low-metallicity gas in the IGM.
    Type of Medium: Online Resource
    ISSN: 0035-8711 , 1365-2966
    URL: Article
    DOI: 10.1093/mnras/stz861
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2016084-7
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  • 6
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    Austropuccinia psidii , causing myrtle rust, has a gigabase-sized genome shaped by transposable elements
    Oxford University Press (OUP) ; 2021
    In:  G3 Genes|Genomes|Genetics Vol. 11, No. 3 ( 2021-04-23)
    Details
    In: G3 Genes|Genomes|Genetics, Oxford University Press (OUP), Vol. 11, No. 3 ( 2021-04-23)
    Abstract: Austropuccinia psidii, originating in South America, is a globally invasive fungal plant pathogen that causes rust disease on Myrtaceae. Several biotypes are recognized, with the most widely distributed pandemic biotype spreading throughout the Asia-Pacific and Oceania regions over the last decade. Austropuccinia psidii has a broad host range with more than 480 myrtaceous species. Since first detected in Australia in 2010, the pathogen has caused the near extinction of at least three species and negatively affected commercial production of several Myrtaceae. To enable molecular and evolutionary studies into A. psidii pathogenicity, we assembled a highly contiguous genome for the pandemic biotype. With an estimated haploid genome size of just over 1 Gb (gigabases), it is the largest assembled fungal genome to date. The genome has undergone massive expansion via distinct transposable element (TE) bursts. Over 90% of the genome is covered by TEs predominantly belonging to the Gypsy superfamily. These TE bursts have likely been followed by deamination events of methylated cytosines to silence the repetitive elements. This in turn led to the depletion of CpG sites in TEs and a very low overall GC content of 33.8%. Compared to other Pucciniales, the intergenic distances are increased by an order of magnitude indicating a general insertion of TEs between genes. Overall, we show how TEs shaped the genome evolution of A. psidii and provide a greatly needed resource for strategic approaches to combat disease spread.
    Type of Medium: Online Resource
    ISSN: 2160-1836
    URL: Article
    DOI: 10.1093/g3journal/jkaa015
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2629978-1
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  • 7
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    De Novo Genome Assembly and Comparative Genomics of the Barley Leaf Rust Pathogen Puccinia hordei Identifies Candidates for Three Avirulence Genes
    Oxford University Press (OUP) ; 2019
    In:  G3 Genes|Genomes|Genetics Vol. 9, No. 10 ( 2019-10-01), p. 3263-3271
    Details
    In: G3 Genes|Genomes|Genetics, Oxford University Press (OUP), Vol. 9, No. 10 ( 2019-10-01), p. 3263-3271
    Abstract: Puccinia hordei (Ph) is a damaging pathogen of barley throughout the world. Despite its importance, almost nothing is known about the genomics of this pathogen, and a reference genome is lacking. In this study, the first reference genome was assembled for an Australian isolate of Ph (“Ph560”) using long-read SMRT sequencing. A total of 838 contigs were assembled, with a total size of 207 Mbp. This included both haplotype collapsed and separated regions, consistent with an estimated haploid genome size of about 150Mbp. An annotation pipeline that combined RNA-Seq of Ph-infected host tissues and homology to proteins from four other Puccinia species predicted 25,543 gene models of which 1,450 genes were classified as encoding secreted proteins based on the prediction of a signal peptide and no transmembrane domain. Genome resequencing using short-read technology was conducted for four additional Australian strains, Ph612, Ph626, Ph608 and Ph584, which are considered to be simple mutational derivatives of Ph560 with added virulence to one or two of three barley leaf rust resistance genes (viz. Rph3, Rph13 and Rph19). To identify candidate genes for the corresponding avirulence genes AvrRph3, AvrRph13 and AvrRph19, genetic variation in predicted secreted protein genes between the strains was correlated to the virulence profiles of each, identifying 35, 29 and 46 candidates for AvrRph13, AvrRph3 and AvrRph19, respectively. The identification of these candidate genes provides a strong foundation for future efforts to isolate these three avirulence genes, investigate their biological properties, and develop new diagnostic tests for monitoring pathogen virulence.
    Type of Medium: Online Resource
    ISSN: 2160-1836
    URL: Article
    DOI: 10.1534/g3.119.400450
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2629978-1
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  • 8
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    Surveillance for azole resistance in clinical and environmental isolates of Aspergillus fumigatus in Australia and cyp51A homology modelling of azole-resistant isolates
    Oxford University Press (OUP) ; 2018
    In:  Journal of Antimicrobial Chemotherapy Vol. 73, No. 9 ( 2018-09-01), p. 2347-2351
    Details
    In: Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), Vol. 73, No. 9 ( 2018-09-01), p. 2347-2351
    Type of Medium: Online Resource
    ISSN: 0305-7453 , 1460-2091
    URL: Article
    DOI: 10.1093/jac/dky187
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 1467478-6
    SSG: 15,3
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  • 9
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    Automated image analysis of protein localization in budding yeast
    Oxford University Press (OUP) ; 2007
    In:  Bioinformatics Vol. 23, No. 13 ( 2007-07-01), p. i66-i71
    Details
    In: Bioinformatics, Oxford University Press (OUP), Vol. 23, No. 13 ( 2007-07-01), p. i66-i71
    Abstract: Motivation: The yeast Saccharomyces cerevisiae is the first eukaryotic organism to have its genome completely sequenced. Since then, several large-scale analyses of the yeast genome have provided extensive functional annotations of individual genes and proteins. One fundamental property of a protein is its subcellular localization, which provides critical information about how this protein works in a cell. An important project therefore was the creation of the yeast GFP fusion localization database by the University of California, San Francisco, USA (UCSF). This database provides localization data for 75% of the proteins believed to be encoded by the yeast genome. These proteins were classified into 22 distinct subcellular location categories by visual examination. Based on our past success at building automated systems to classify subcellular location patterns in mammalian cells, we sought to create a similar system for yeast. Results: We developed computational methods to automatically analyze the images created by the UCSF yeast GFP fusion localization project. The system was trained to recognize the same location categories that were used in that study. We applied the system to 2640 images, and the system gave the same label as the previous assignments to 2139 images (81%). When only the highest confidence assignments were considered, 94.7% agreement was observed. Visual examination of the proteins for which the two approaches disagree suggests that at least some of the automated assignments may be more accurate. The automated method provides an objective, quantitative and repeatable assignment of protein locations that can be applied to new collections of yeast images (e.g. for different strains or the same strain under different conditions). It is also important to note that this performance could be achieved without requiring colocalization with any marker proteins. Availability: The original images analyzed in this article are available at http://yeastgfp.ucsf.edu, and source code and results are available at http://murphylab.web.cmu.edu/software Contact: murphy@cmu.edu
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    URL: Article
    DOI: 10.1093/bioinformatics/btm206
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2007
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 10
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    Large expert-curated database for benchmarking document similarity detection in biomedical literature search
    Oxford University Press (OUP) ; 2019
    In:  Database Vol. 2019 ( 2019-01-01)
    Details
    In: Database, Oxford University Press (OUP), Vol. 2019 ( 2019-01-01)
    Abstract: Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
    Type of Medium: Online Resource
    ISSN: 1758-0463
    URL: Article
    DOI: 10.1093/database/baz085
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2496706-3
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