105 research outputs found
Does maternal obesity change cardiomyocyte endowment?
No full textEditorialJanna L Morrison, Catherine Suter, Kimberley J Botting & Jens R Nyengaar
Season 10 Episode 9: Ethics of Hostage Negotiation
No full textAn angry criminal takes a hostage and demands to speak with authorities. Who’s most qualified to take the phone? What strategy might have worked with David Koresh? Jim Botting, author of Bullets, Bombs and Fast Talk: 25 Years of FBI War Stories, describes the adventures and dilemmas of his seventeen years as hostage negotiator for the FBI. Shirley Hoogstra hosts. Episode #1009
Maternal undernutrition alters fat cell size distribution, but not lipogenic gene expression, in the visceral fat of the late gestation guinea pig fetus
No full textThis study investigated the development of adipose tissue in the guinea pig and the impact of maternal undernutrition on the structural and functional characteristics of perirenal adipose tissue in the dam and fetus. Date-mated guinea pigs were provided with either ad libitum feed (Control, C) or 85% of food intake per body weight of the Controls (Undernutrition, UN). Maternal (C, n = 6; UN, n = 7) perirenal adipose tissue (PAT) was collected at 60 d gestation and fetal PAT was collected at 50 d (C, n = 4) and 60 d (C, n = 8 and UN, n = 7) gestation (term, 69 d). The expression of stearoyl-CoA desaturase (SCD-1), fatty acid synthase (FAS), lipoprotein lipase (LPL), leptin and glycerol 3 phosphate dehydrogenase (G3PDH) mRNA and glucose transporters 1 and 4 (GLUT1 and GLUT4) was determined by Real Time PCR. There was no effect of maternal UN on total or relative PAT mass in the pregnant dam. There was an increase in G3PDH, but not LPL, leptin, FAS or GLUT4 mRNA expression, in UN dams compared to Controls (P < 0.05). In the fetal guinea pig there was no effect of maternal UN on total or relative PAT mass, however, the UN fetuses had a higher percentage of larger lipid locules in their PAT compared to Controls (P < 0.05). The expression of FAS, LPL, SCD-1, leptin, G3PDH and GLUT4 mRNA in PAT was not different between the Control and UN fetuses. These results support previous studies which have demonstrated that maternal undernutrition is associated with an increased accumulation of visceral adipose tissue in utero, and extend them by showing that maternal undernutrition results in early changes in the size distribution of lipid locules in visceral fat depots that precede changes in lipogenic gene expression.L.T. Nguyen, B.S. Muhlhausler, K.J. Botting, J.L. Morriso
MitoQ Treatment During Pregnancy Rescues Antenatal Dexamethasone- Induced Programming of Impaired Hepatic CYP Activity in Young Adult Sheep
No full textPosterMillicent G.A Bennett, Ashley S Meakin, Kimberley J Botting, Youguo Niu, Sage G Ford, Michael P Murphy, Michael D Wiese, Dino A Giussani, Janna L Morriso
Contractile and Ca2+-handling properties of the right ventricular papillary muscle in the late-gestation sheep fetus
No full textThe force-generating capacity of cardiomyocytes rapidly changes during gestation and early postnatal life coinciding with a transition in cardiomyocyte nucleation in both mice and rats. Changes in nucleation, in turn, appear to coincide with important changes in the excitation-contraction coupling architecture. However, it is not clear whether similar changes are observed in other mammals in which this transition occurs prenatally, such as sheep. Using small (70–300 µM diameter) chemically skinned cardiomyocyte bundles from the right ventricular papillary muscle of sheep fetuses at 126–132 and 137–140 days (d) gestational age (GA), we aimed to examine whether changes in cardiomyocyte nucleation during late gestation coincided with developmental changes in excitation-contraction coupling parameters (e.g., Ca2+ uptake, Ca2+ release, and force development). All experiments were conducted at room temperature (23 ± 1°C). We found that the proportion of mononucleate cardiomyocytes decreased significantly with GA (126–132d, 45.7 ± 4.7%, n = 7; 137–140d, 32.8 ± 1.6%, n = 6; P < 0.05). When we then examined force development between the two groups, there was no significant difference in either the maximal Ca2+-activated force (6.73 ± 1.54 mN/mm2, n = 14 vs. 6.55 ± 1.25 mN/mm2, n = 7, respectively) or the Ca2+ sensitivity of the contractile apparatus (pCa at 50% maximum Ca2+-activated force: 126–132d, 6.17 ± 0.06, n = 14; 137–140d, 6.24 ± 0.08, n = 7). However, sarcoplasmic reticulum (SR) Ca2+ uptake rates (but not Ca2+ release) increased with GA (P < 0.05). These data reveal that during late gestation in sheep when there is a major transition in cardiomyocyte nucleation, SR Ca2+ uptake rates increase, which would influence total SR Ca2+ content and force production.T. N. Spencer, K. J. Botting, J. L. Morrison, and G. S. Posterin
The role of miRNA regulation in fetal cardiomyocytes, cardiac maturation and the risk of heart disease in adults
No full textMyocardial infarction is a primary contributor towards the global burden of cardiovascular disease. Rather than repairing the existing damage of myocardial infarction, current treatments only address the symptoms of the disease and reducing the risk of a secondary infarction. Cardiac regenerative capacity is dependent on cardiomyocyte proliferation, which concludes soon after birth in humans and precocial species such as sheep. Human fetal cardiac tissue has some ability to repair following tissue damage, whereas a fully matured human heart has minimal capacity for cellular regeneration. This is in contrast to neonatal mice and adult zebrafish hearts, which retain the ability to undergo cardiomyocyte proliferation and can regenerate cardiac tissue after birth. In mice and zebrafish models, microRNAs (miRNAs) have been implicated in the regulation of genes involved in cardiac cell cycle progression and regeneration. However, the significance of miRNA regulation in cardiomyocyte proliferation for humans and other large mammals, where the timing of heart development in relation to birth is similar, remains unclear. miRNAs may be valuable targets for therapies that promote cardiac repair after injury. Therefore, elucidating the role of specific miRNAs in large animals, where heart development closely resembles that of humans, remains vitally important for identifying therapeutic targets that may be translated into clinical practice focussed on tissue repair.Mitchell C. Lock, Ross L. Tellam, Kimberley J. Botting, Kimberley C.W.Wang, Joseph B. Selvanayagam, Doug A. Brooks, Mike Seed and Janna L. Morriso
Programming of Impaired Hepatic Drug Metabolism in Adult Offspring: Effects of Hypoxic Pregnancy and Antioxidant Treatment
No full textIntrauterine growth restriction (IUGR) is a pathological condition affecting 10% of pregnancies globally. IUGR fetuses are often hypoxemic in utero, leading to excess production of reactive oxygen species and increased risk of chronic disease in later life. Hepatic cytochrome P450 (CYP) enzymes metabolise 70-80% of all clinical drugs,and we have shown that hepatic CYP3A4 activity is reduced in IUGR neonates (Soo et al. Pharmacol Res 134:68-78, 2018). Mitochondriatargeted antioxidant treatment (MitoQ) in IUGR animal models has protective effects against programmed hypertension in the adult offspring(Botting et al. Sci Adv 6(34): eabb1929, 2020). However, the effect of chronic fetal hypoxemia with or without MitoQ on offspring hepatic CYP activity is unknown. We hypothesised that hypoxic pregnancy would impair hepatic CYP activity in adult offspring and that maternal MitoQ treatment in hypoxic pregnancy will be protective
Language in autism and specific language impairment: Where are the links?
No full textIt has been suggested that language impairment in autism is behaviourally, neurobiologically, and etiologically related to specific language impairment (SLI). In this paper, we review evidence at each level and argue that the vast majority of data does not support the view that language impairment in autism can be explained in terms of co-morbid SLI. We make recommendations for how this debate might be resolved and we suggest a shift in research focus. We recommend that researchers concentrate on those aspects of language impairment that predominate in each disorder rather than on those comparatively small areas of potential overlap
Acknowledgements
No full textI hereby declare that I am the sole author of this thesis. This is a true copy of the thesis, including any required final revisions, as accepted by my examiners. I understand that my thesis may be made electronically available to the public
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