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  • 1
    Online Resource
    Online Resource
    Interpreting Viral Deep Sequencing Data with GLUE
    MDPI AG ; 2019
    In:  Viruses Vol. 11, No. 4 ( 2019-04-03), p. 323-
    Details
    In: Viruses, MDPI AG, Vol. 11, No. 4 ( 2019-04-03), p. 323-
    Abstract: Using deep sequencing technologies such as Illumina’s platform, it is possible to obtain reads from the viral RNA population revealing the viral genome diversity within a single host. A range of software tools and pipelines can transform raw deep sequencing reads into Sequence Alignment Mapping (SAM) files. We propose that interpretation tools should process these SAM files, directly translating individual reads to amino acids in order to extract statistics of interest such as the proportion of different amino acid residues at specific sites. This preserves per-read linkage between nucleotide variants at different positions within a codon location. The samReporter is a subsystem of the GLUE software toolkit which follows this direct read translation approach in its processing of SAM files. We test samReporter on a deep sequencing dataset obtained from a cohort of 241 UK HCV patients for whom prior treatment with direct-acting antivirals has failed; deep sequencing and resistance testing have been suggested to be of clinical use in this context. We compared the polymorphism interpretation results of the samReporter against an approach that does not preserve per-read linkage. We found that the samReporter was able to properly interpret the sequence data at resistance-associated locations in nine patients where the alternative approach was equivocal. In three cases, the samReporter confirmed that resistance or an atypical substitution was present at NS5A position 30. In three further cases, it confirmed that the sofosbuvir-resistant NS5B substitution S282T was absent. This suggests the direct read translation approach implemented is of value for interpreting viral deep sequencing data.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v11040323
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2516098-9
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  • 2
    Online Resource
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    CORNERSTONE’s Silicon Photonics Rapid Prototyping Platforms: Current Status and Future Outlook
    MDPI AG ; 2020
    In:  Applied Sciences Vol. 10, No. 22 ( 2020-11-19), p. 8201-
    Details
    In: Applied Sciences, MDPI AG, Vol. 10, No. 22 ( 2020-11-19), p. 8201-
    Abstract: The field of silicon photonics has experienced widespread adoption in the datacoms industry over the past decade, with a plethora of other applications emerging more recently such as light detection and ranging (LIDAR), sensing, quantum photonics, programmable photonics and artificial intelligence. As a result of this, many commercial complementary metal oxide semiconductor (CMOS) foundries have developed open access silicon photonics process lines, enabling the mass production of silicon photonics systems. On the other side of the spectrum, several research labs, typically within universities, have opened up their facilities for small scale prototyping, commonly exploiting e-beam lithography for wafer patterning. Within this ecosystem, there remains a challenge for early stage researchers to progress their novel and innovate designs from the research lab to the commercial foundries because of the lack of compatibility of the processing technologies (e-beam lithography is not an industry tool). The CORNERSTONE rapid-prototyping capability bridges this gap between research and industry by providing a rapid prototyping fabrication line based on deep-UV lithography to enable seamless scaling up of production volumes, whilst also retaining the ability for device level innovation, crucial for researchers, by offering flexibility in its process flows. This review article presents a summary of the current CORNERSTONE capabilities and an outlook for the future.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app10228201
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704225-X
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  • 3
    Online Resource
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    Skeletal Muscle and the Maintenance of Vitamin D Status
    MDPI AG ; 2020
    In:  Nutrients Vol. 12, No. 11 ( 2020-10-26), p. 3270-
    Details
    In: Nutrients, MDPI AG, Vol. 12, No. 11 ( 2020-10-26), p. 3270-
    Abstract: Vitamin D, unlike the micronutrients, vitamins A, E, and K, is largely obtained not from food, but by the action of solar ultraviolet (UV) light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Since no defined storage organ or tissue has been found for vitamin D, it has been assumed that an adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D), which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into the blood. This uptake and release of 25(OH)D by muscle accounts for the very long half-life of this metabolite in the circulation. Since 25(OH)D concentration in the blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain an adequate vitamin D status in winter.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu12113270
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518386-2
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  • 4
    Online Resource
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    VetCompass Australia: A National Big Data Collection System for Veterinary Science
    MDPI AG ; 2017
    In:  Animals Vol. 7, No. 12 ( 2017-09-26), p. 74-
    Details
    In: Animals, MDPI AG, Vol. 7, No. 12 ( 2017-09-26), p. 74-
    Type of Medium: Online Resource
    ISSN: 2076-2615
    URL: Article
    DOI: 10.3390/ani7100074
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2606558-7
    SSG: 23
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  • 5
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    Vascular Lipidomic Profiling of Potential Endogenous Fatty Acid PPAR Ligands Reveals the Coronary Artery as Major Producer of CYP450-Derived Epoxy Fatty Acids
    MDPI AG ; 2020
    In:  Cells Vol. 9, No. 5 ( 2020-04-29), p. 1096-
    Details
    In: Cells, MDPI AG, Vol. 9, No. 5 ( 2020-04-29), p. 1096-
    Abstract: A number of oxylipins have been described as endogenous PPAR ligands. The very short biological half-lives of oxylipins suggest roles as autocrine or paracrine signaling molecules. While coronary arterial atherosclerosis is the root of myocardial infarction, aortic atherosclerotic plaque formation is a common readout of in vivo atherosclerosis studies in mice. Improved understanding of the compartmentalized sources of oxylipin PPAR ligands will increase our knowledge of the roles of PPAR signaling in diverse vascular tissues. Here, we performed a targeted lipidomic analysis of ex vivo-generated oxylipins from porcine aorta, coronary artery, pulmonary artery and perivascular adipose. Cyclooxygenase (COX)-derived prostanoids were the most abundant detectable oxylipin from all tissues. By contrast, the coronary artery produced significantly higher levels of oxylipins from CYP450 pathways than other tissues. The TLR4 ligand LPS induced prostanoid formation in all vascular tissue tested. The 11-HETE, 15-HETE, and 9-HODE were also induced by LPS from the aorta and pulmonary artery but not coronary artery. Epoxy fatty acid (EpFA) formation was largely unaffected by LPS. The pig CYP2J homologue CYP2J34 was expressed in porcine vascular tissue and primary coronary artery smooth muscle cells (pCASMCs) in culture. Treatment of pCASMCs with LPS induced a robust profile of pro-inflammatory target genes: TNFα, ICAM-1, VCAM-1, MCP-1 and CD40L. The soluble epoxide hydrolase inhibitor TPPU, which prevents the breakdown of endogenous CYP-derived EpFAs, significantly suppressed LPS-induced inflammatory target genes. In conclusion, PPAR-activating oxylipins are produced and regulated in a vascular site-specific manner. The CYP450 pathway is highly active in the coronary artery and capable of providing anti-inflammatory oxylipins that prevent processes of inflammatory vascular disease progression.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells9051096
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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  • 6
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    Sensory and Physical Characteristics of M. biceps femoris from Older Cows Using Ginger Powder (Zingibain) and Sous Vide Cooking
    MDPI AG ; 2021
    In:  Foods Vol. 10, No. 8 ( 2021-08-20), p. 1936-
    Details
    In: Foods, MDPI AG, Vol. 10, No. 8 ( 2021-08-20), p. 1936-
    Abstract: This study aimed to evaluate the sensory and physical characteristics of zingibain-injected meat combined with sous vide cooking. M. biceps femoris (BF; n = 12) acquired from 6–7 year old Angus cows were cooked using the sous vide method at 65 °C, for 8 h or 12 h, either with ginger powder (GP) injected in a 2 g/L solution in water (treatment) or un-injected (control). The sensory attributes included flavour, juiciness, tenderness, and physicochemical characteristics were Warner-Bratzler shear (WBSF), hardness, total water content (TWC), cooking loss (CL) and collagen content. A significant improvement in tenderness with injection treatment and cooking time was observed, as evaluated through trained sensory panellists, and reduced WBSF and hardness (p 〈 0.05 for all). The flavour of the meat was not affected by injection treatment or cooking time (p 〉 0.05), but juiciness and TWC were reduced with longer cooking times (p 〈 0.01 for both). Soluble collagen increased with injection treatment and cooking time (both p 〈 0.05). Moderate to high correlations were found between sensory and physical measurements for tenderness and juiciness. The longer cooking time (12 h) with GP injection treatment caused over tenderization of the meat. The soft texture associated with over-tenderization may be suitable for some specialised consumer markets, for instance, the elderly population with chewing difficulties. Improving the eating quality of low-quality meat from old animals through sous vide cooking and the use of ginger proteases may increase the acceptability of lower value beef, potentially enhancing the commercial value of carcasses typically produced in the beef industry.
    Type of Medium: Online Resource
    ISSN: 2304-8158
    URL: Article
    DOI: 10.3390/foods10081936
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2704223-6
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  • 7
    Online Resource
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    Aerodynamic Uncertainty Quantification for Tiltrotor Aircraft
    MDPI AG ; 2022
    In:  Aerospace Vol. 9, No. 5 ( 2022-05-18), p. 271-
    Details
    In: Aerospace, MDPI AG, Vol. 9, No. 5 ( 2022-05-18), p. 271-
    Abstract: The tiltrotor has unique flight dynamics due to the aerodynamic interference characteristics. Multiple aerodynamics calculation approaches, such as the CFD method, are utilised to characterise this feature. The calculation process is usually time-consuming, and the obtained results are generally varied from each other. Thus, the uncertainty quantification (UQ) method will be utilised in this research to identify the aerodynamic inaccuracy effect on the handling qualities of the tiltrotor aircraft. The study aims to quantify the influence of the aerodynamic interference on the tiltrotor flight dynamics in different flight states, such as forward speeds and nacelle tilting angles, which can guide the flight dynamics modelling simplification to improve the simulation efficiency. Therefore, uncertainty identification and full factorial numerical integration (FFNI) methods are introduced to scale these aerodynamic uncertainties. The eigenvalue and bandwidth and phase delay requirements are presented as the failure criteria. The UQ calculation indicates that the uncertainties of the aerodynamic calculation significantly affect the handling quality ratings in two flight ranges: the helicopter mode and the conversion and aeroplane modes with higher forward speed (close to the conversion envelope). Furthermore, a sensitivity analysis is performed to identify the mechanism behind these influences. The results demonstrate that aerodynamics affect the pitching attitude, the pitching damping, and the velocity and incidence stability derivatives. However, the effects of the velocity stability and the incidence stability are the reason causing the handling qualities’ degradation in the helicopter mode and high-speed mode, respectively.
    Type of Medium: Online Resource
    ISSN: 2226-4310
    URL: Article
    DOI: 10.3390/aerospace9050271
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2756091-0
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  • 8
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    A Pathway-Based Genetic Score for Oxidative Stress: An Indicator of Host Vulnerability to Phthalate-Associated Adverse Neurodevelopment
    MDPI AG ; 2022
    In:  Antioxidants Vol. 11, No. 4 ( 2022-03-29), p. 659-
    Details
    In: Antioxidants, MDPI AG, Vol. 11, No. 4 ( 2022-03-29), p. 659-
    Abstract: The developing brain is highly sensitive to environmental disturbances, and adverse exposures can act through oxidative stress. Given that oxidative stress susceptibility is determined partly by genetics, multiple studies have employed genetic scores to explore the role of oxidative stress in human disease. However, traditional approaches to genetic score construction face a range of challenges, including a lack of interpretability, bias towards the disease outcome, and often overfitting to the study they were derived on. Here, we develop an alternative strategy by first generating a genetic pathway function score for oxidative stress (gPFSox) based on the transcriptional activity levels of the oxidative stress response pathway in brain and other tissue types. Then, in the Barwon Infant Study (BIS), a population-based birth cohort (n = 1074), we show that a high gPFSox, indicating reduced ability to counter oxidative stress, is linked to higher autism spectrum disorder risk and higher parent-reported autistic traits at age 4 years, with AOR values (per 2 additional pro-oxidant alleles) of 2.10 (95% CI (1.12, 4.11); p = 0.024) and 1.42 (95% CI (1.02, 2.01); p = 0.041), respectively. Past work in BIS has reported higher prenatal phthalate exposure at 36 weeks of gestation associated with offspring autism spectrum disorder. In this study, we examine combined effects and show a consistent pattern of increased neurodevelopmental problems for individuals with both a high gPFSox and high prenatal phthalate exposure across a range of outcomes, including high gPFSox and high DEHP levels against autism spectrum disorder (attributable proportion due to interaction 0.89; 95% CI (0.62, 1.16); p 〈 0.0001). The results highlight the utility of this novel functional genetic score and add to the growing evidence implicating gestational phthalate exposure in adverse neurodevelopment.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox11040659
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 9
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    β-Hydroxybutyrate Elicits Favorable Mitochondrial Changes in Skeletal Muscle
    MDPI AG ; 2018
    In:  International Journal of Molecular Sciences Vol. 19, No. 8 ( 2018-08-01), p. 2247-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 19, No. 8 ( 2018-08-01), p. 2247-
    Abstract: The clinical benefit of ketosis has historically and almost exclusively centered on neurological conditions, lending insight into how ketones alter mitochondrial function in neurons. However, there is a gap in our understanding of how ketones influence mitochondria within skeletal muscle cells. The purpose of this study was to elucidate the specific effects of β-hydroxybutyrate (β-HB) on muscle cell mitochondrial physiology. In addition to increased cell viability, murine myotubes displayed beneficial mitochondrial changes evident in reduced H2O2 emission and less mitochondrial fission, which may be a result of a β-HB-induced reduction in ceramides. Furthermore, muscle from rats in sustained ketosis similarly produced less H2O2 despite an increase in mitochondrial respiration and no apparent change in mitochondrial quantity. In sum, these results indicate a general improvement in muscle cell mitochondrial function when β-HB is provided as a fuel.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms19082247
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
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    The Role of AMPK in the Regulation of Skeletal Muscle Size, Hypertrophy, and Regeneration
    MDPI AG ; 2018
    In:  International Journal of Molecular Sciences Vol. 19, No. 10 ( 2018-10-11), p. 3125-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 19, No. 10 ( 2018-10-11), p. 3125-
    Abstract: AMPK (5’-adenosine monophosphate-activated protein kinase) is heavily involved in skeletal muscle metabolic control through its regulation of many downstream targets. Because of their effects on anabolic and catabolic cellular processes, AMPK plays an important role in the control of skeletal muscle development and growth. In this review, the effects of AMPK signaling, and those of its upstream activator, liver kinase B1 (LKB1), on skeletal muscle growth and atrophy are reviewed. The effect of AMPK activity on satellite cell-mediated muscle growth and regeneration after injury is also reviewed. Together, the current data indicate that AMPK does play an important role in regulating muscle mass and regeneration, with AMPKα1 playing a prominent role in stimulating anabolism and in regulating satellite cell dynamics during regeneration, and AMPKα2 playing a potentially more important role in regulating muscle degradation during atrophy.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms19103125
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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