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  1. Article ; Online: Sildenafil: how to make a bad situation worse.

    Darby, Jack R T

    The Journal of physiology

    2020  Volume 598, Issue 19, Page(s) 4139–4140

    MeSH term(s) Animals ; Fetus ; Hypoxia ; Piperazines ; Sheep ; Sildenafil Citrate ; Sulfones
    Chemical Substances Piperazines ; Sulfones ; Sildenafil Citrate (BW9B0ZE037)
    Language English
    Publishing date 2020-08-04
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP280444
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  2. Article ; Online: A change of heart: understanding the mechanisms regulating cardiac proliferation and metabolism before and after birth.

    Dimasi, Catherine G / Darby, Jack R T / Morrison, Janna L

    The Journal of physiology

    2023  Volume 601, Issue 8, Page(s) 1319–1341

    Abstract: Mammalian cardiomyocytes undergo major maturational changes in preparation for birth and postnatal life. Immature cardiomyocytes contribute to cardiac growth via proliferation and thus the heart has the capacity to regenerate. To prepare for postnatal ... ...

    Abstract Mammalian cardiomyocytes undergo major maturational changes in preparation for birth and postnatal life. Immature cardiomyocytes contribute to cardiac growth via proliferation and thus the heart has the capacity to regenerate. To prepare for postnatal life, structural and metabolic changes associated with increased cardiac output and function must occur. This includes exit from the cell cycle, hypertrophic growth, mitochondrial maturation and sarcomeric protein isoform switching. However, these changes come at a price: the loss of cardiac regenerative capacity such that damage to the heart in postnatal life is permanent. This is a significant barrier to the development of new treatments for cardiac repair and contributes to heart failure. The transitional period of cardiomyocyte growth is a complex and multifaceted event. In this review, we focus on studies that have investigated this critical transition period as well as novel factors that may regulate and drive this process. We also discuss the potential use of new biomarkers for the detection of myocardial infarction and, in the broader sense, cardiovascular disease.
    MeSH term(s) Animals ; Humans ; Heart/physiology ; Myocytes, Cardiac/metabolism ; Myocardial Infarction/metabolism ; Heart Failure/metabolism ; Regeneration/physiology ; Cell Proliferation ; Mammals
    Language English
    Publishing date 2023-03-13
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP284137
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  3. Article ; Online: A no brainer: intervening early to protect against perinatal brain injury.

    Hammond, Sarah J / Darby, Jack R T

    The Journal of physiology

    2022  Volume 600, Issue 18, Page(s) 4059–4061

    MeSH term(s) Brain Injuries/prevention & control ; Female ; Humans ; Hypoxia-Ischemia, Brain ; Pregnancy
    Language English
    Publishing date 2022-08-19
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP283559
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  4. Article ; Online: Does the growth restricted fetal heart burn less fat?

    Dimasi, Catherine G / Darby, Jack R T

    The Journal of physiology

    2022  Volume 600, Issue 7, Page(s) 1585–1586

    MeSH term(s) Fetal Growth Retardation ; Fetal Heart ; Humans
    Language English
    Publishing date 2022-03-12
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP282900
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  5. Article ; Online: Something worth waiting for: is delayed cord clamping always beneficial?

    Robinson, Joshua L / Darby, Jack R T

    The Journal of physiology

    2022  Volume 600, Issue 16, Page(s) 3641–3642

    MeSH term(s) Constriction ; Female ; Humans ; Parturition ; Pregnancy ; Umbilical Cord ; Umbilical Cord Clamping
    Language English
    Publishing date 2022-07-21
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP283315
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  6. Article ; Online: Themed issue on the DOHaD workshop on Fetal, Placental and Pediatric Imaging.

    Morrison, Janna L / Darby, Jack R T / Michael, Navin

    Journal of developmental origins of health and disease

    2021  Volume 12, Issue 2, Page(s) 151–152

    MeSH term(s) Biomedical Research/trends ; Diagnostic Imaging/methods ; Female ; Fetal Diseases/diagnosis ; Fetal Diseases/diagnostic imaging ; Fetus/diagnostic imaging ; Fetus/pathology ; Humans ; Placenta/diagnostic imaging ; Placenta/pathology ; Placenta Diseases/diagnosis ; Placenta Diseases/diagnostic imaging ; Pregnancy ; Societies, Scientific
    Language English
    Publishing date 2021-01-28
    Publishing country England
    Document type Editorial
    ZDB-ID 2554780-X
    ISSN 2040-1752 ; 2040-1744
    ISSN (online) 2040-1752
    ISSN 2040-1744
    DOI 10.1017/S2040174421000015
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  7. Article ; Online: Maternal-placental-fetal drug metabolism is altered by late gestation undernutrition in the pregnant ewe.

    Meakin, Ashley S / Darby, Jack R T / Holman, Stacey L / Wiese, Michael D / Morrison, Janna L

    Life sciences

    2022  Volume 298, Page(s) 120521

    Abstract: Background: Maternal undernutrition during pregnancy disrupts both fetal growth and development with perturbations to certain physiological processes within the maternal-fetal-placental unit, including metabolic function. However, it is unknown if ... ...

    Abstract Background: Maternal undernutrition during pregnancy disrupts both fetal growth and development with perturbations to certain physiological processes within the maternal-fetal-placental unit, including metabolic function. However, it is unknown if hypoglycemia during pregnancy alters maternal-fetal-placental drug metabolism as mediated by cytochrome P450 (CYP) enzymes. Despite this, hypoglycemia reduces CYP enzyme activity in non-pregnant animals. We therefore hypothesised that in a sheep model of hypoglycemia induced by late gestation undernutrition (LGUN), maternal-fetal-placental CYP activity would be reduced, and that fetal glucose infusion (LGUN+G) would rescue reduced CYP activity.
    Methods: At 115d gestation (term, 150d), ewes were allocated to control (100% metabolic energy requirement (MER); n = 11), LGUN (50% MER; n = 7) or LGUN+G (50% MER + fetal glucose infusion; n = 6) and maintained on their diets until post-mortem. Maternal-fetal-placental CYP activity assays were performed at 131-133d gestation. Microsomes were isolated from placenta and fetal liver collected at 139-142d gestation and incubated with CYP-specific probe drugs. Metabolite concentrations were measured using Liquid Chromatography - tandem mass spectrometry (LC-MS/MS).
    Results: CYP2C19 and CYP3A were undetectable in placenta or fetal liver, and CYP1A2 was undetectable in the fetal liver. Placental-specific CYP1A2 and CYP2D6 activity and hepatic-specific CYP2D6 activity were unaffected by LGUN. Maternal-fetal-placental CYP1A2 activity was reduced in response to LGUN in the maternal compartment only.
    Conclusions: Reduced maternal-fetal-placental CYP1A2 activity, but not placental-specific CYP1A2 activity, may lead to the developing fetus being exposed to increased concentrations of CYP1A2-specific substrates and suggests further consideration of drug dosing is required in instances of late gestation maternal undernutrition.
    MeSH term(s) Animals ; Chromatography, Liquid ; Cytochrome P-450 CYP1A2/metabolism ; Cytochrome P-450 CYP2D6/metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Female ; Fetus/metabolism ; Glucose/metabolism ; Hypoglycemia/metabolism ; Malnutrition/metabolism ; Maternal-Fetal Exchange ; Placenta/metabolism ; Pregnancy ; Sheep ; Tandem Mass Spectrometry
    Chemical Substances Cytochrome P-450 Enzyme System (9035-51-2) ; Cytochrome P-450 CYP1A2 (EC 1.14.14.1) ; Cytochrome P-450 CYP2D6 (EC 1.14.14.1) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2022-03-31
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 3378-9
    ISSN 1879-0631 ; 0024-3205
    ISSN (online) 1879-0631
    ISSN 0024-3205
    DOI 10.1016/j.lfs.2022.120521
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  8. Article: Cardiac growth and metabolism of the fetal sheep are not vulnerable to a 10 day increase in fetal glucose and insulin concentrations during late gestation.

    Darby, Jack R T / Zhang, Song / Holman, Stacey L / Muhlhausler, Beverly S / McMillen, I Caroline / Morrison, Janna L

    Heliyon

    2023  Volume 9, Issue 7, Page(s) e18292

    Abstract: Aims: To evaluate the effects of fetal glucose infusion in late gestation on the mRNA expression and protein abundance of molecules involved in the regulation of cardiac growth and metabolism.: Main methods: Either saline or glucose was infused into ... ...

    Abstract Aims: To evaluate the effects of fetal glucose infusion in late gestation on the mRNA expression and protein abundance of molecules involved in the regulation of cardiac growth and metabolism.
    Main methods: Either saline or glucose was infused into fetal sheep from 130 to 140 days (d) gestation (term, 150 d). At 140 d gestation, left ventricle tissue samples were collected. Quantitative real-time RT-PCR and Western blot were used to determine the mRNA expression and protein abundance of key signalling molecules within the left ventricle of the fetal heart.
    Key findings: Although intra-fetal glucose infusion increased fetal plasma glucose and insulin concentrations, there was no change in the expression of molecules within the signalling pathways that regulate proliferation, hypertrophy, apoptosis or fibrosis in the fetal heart. Cardiac
    Significance: Despite a 10-day doubling of fetal plasma glucose and insulin concentrations, the present study suggests that within the fetal left ventricle, the mRNA and protein expression of the signalling molecules involved in cardiac growth, development and metabolism are relatively unaffected.
    Language English
    Publishing date 2023-07-14
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2023.e18292
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  9. Article ; Online: Automated Proteomics Workflows for High-Throughput Library Generation and Biomarker Detection Using Data-Independent Acquisition.

    Paramasivan, Selvam / Morrison, Janna L / Lock, Mitchell C / Darby, Jack R T / Barrero, Roberto A / Mills, Paul C / Sadowski, Pawel

    Journal of proteome research

    2023  Volume 22, Issue 6, Page(s) 2018–2029

    Abstract: Sequential window acquisition of all theoretical mass spectra-mass spectrometry underpinned by advanced bioinformatics offers a framework for comprehensive analysis of proteomes and the discovery of robust biomarkers. However, the lack of a generic ... ...

    Abstract Sequential window acquisition of all theoretical mass spectra-mass spectrometry underpinned by advanced bioinformatics offers a framework for comprehensive analysis of proteomes and the discovery of robust biomarkers. However, the lack of a generic sample preparation platform to tackle the heterogeneity of material collected from different sources may be a limiting factor to the broad application of this technique. We have developed universal and fully automated workflows using a robotic sample preparation platform, which enabled in-depth and reproducible proteome coverage and characterization of bovine and ovine specimens representing healthy animals and a model of myocardial infarction. High correlation (
    MeSH term(s) Animals ; Cattle ; Sheep ; Proteomics/methods ; Workflow ; Mass Spectrometry/methods ; Biomarkers ; Proteome/analysis
    Chemical Substances Biomarkers ; Proteome
    Language English
    Publishing date 2023-05-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2078618-9
    ISSN 1535-3907 ; 1535-3893
    ISSN (online) 1535-3907
    ISSN 1535-3893
    DOI 10.1021/acs.jproteome.3c00074
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  10. Article ; Online: Pulmonary Vascular Regulation in the Fetal and Transitional Lung.

    Holmes, Hannah / Saini, Brahmdeep S / Moir, Olivia J / Darby, Jack R T / Morrison, Janna L / Sun, Liqun / Seed, Mike

    Clinics in perinatology

    2023  Volume 51, Issue 1, Page(s) 1–19

    Abstract: Fetal lungs have fewer and smaller arteries with higher pulmonary vascular resistance (PVR) than a newborn. As gestation advances, the pulmonary circulation becomes more sensitive to changes in pulmonary arterial oxygen tension, which prepares them for ... ...

    Abstract Fetal lungs have fewer and smaller arteries with higher pulmonary vascular resistance (PVR) than a newborn. As gestation advances, the pulmonary circulation becomes more sensitive to changes in pulmonary arterial oxygen tension, which prepares them for the dramatic drop in PVR and increase in pulmonary blood flow (PBF) that occur when the baby takes its first few breaths of air, thus driving the transition from fetal to postnatal circulation. Dynamic and intricate regulatory mechanisms control PBF throughout development and are essential in supporting gas exchange after birth. Understanding these concepts is crucial given the role the pulmonary vasculature plays in the development of complications with transition, such as in the setting of persistent pulmonary hypertension of the newborn and congenital heart disease. An improved understanding of pulmonary vascular regulation may reveal opportunities for better clinical management.
    MeSH term(s) Pregnancy ; Infant, Newborn ; Female ; Humans ; Lung ; Fetus/physiology ; Pulmonary Circulation/physiology ; Prenatal Care ; Vascular Resistance/physiology
    Language English
    Publishing date 2023-12-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 193116-7
    ISSN 1557-9840 ; 0095-5108
    ISSN (online) 1557-9840
    ISSN 0095-5108
    DOI 10.1016/j.clp.2023.11.003
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