66 research outputs found
Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity
The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency
Differential and synergistic effects of low birth weight and western diet on skeletal muscle vasculature, mitochondrial lipid metabolism and insulin signaling in male guinea pigs
Low birth weight (LBW) offspring are at increased risk for developing insulin resistance, a key precursor in metabolic syndrome and type 2 diabetes mellitus. Altered skeletal muscle vasculature, extracellular matrix, amino acid and mitochondrial lipid metabolism, and insulin signaling are implicated in this pathogenesis. Using uteroplacental insufficiency (UPI) to induce intrauterine growth restriction (IUGR) and LBW in the guinea pig, we investigated the relationship between UPI-induced IUGR/LBW and later life skeletal muscle arteriole density, fibrosis, amino acid and mitochondrial lipid metabolism, markers of insulin signaling and glucose uptake, and how a postnatal high-fat, high-sugar âWesternâ diet (WD) modulates these changes. Muscle of 145-day-old male LBW glucose-tolerant offspring displayed diminished vessel density and altered acylcarnitine levels. Disrupted muscle insulin signaling despite maintained whole-body glucose homeostasis also occurred in both LBW and WD-fed male âleanâ offspring. Additionally, postnatal WD unmasked LBW-induced impairment of mitochondrial lipid metabolism, as reflected by increased acylcarnitine accumulation. This study provides evidence that early markers of skeletal muscle metabolic dysfunction appear to be influenced by the in utero environment and interact with a high-fat/high-sugar postnatal environment to exacerbate altered mitochondrial lipid metabolism, promoting mitochondrial overload
Age Constraints on Brane Models of Dark Energy
Inspired by recent developments in particle physics, the so-called brane
world cosmology seems to provide an alternative explanation for the present
dark energy problem. In this paper, we use the estimated age of high-
objects to constrain the value of the cosmological parameters in some
particular scenarios based on this large scale modification of gravity. We show
that such models are compatible with these observations for values of the
crossover distance between the 4 and 5 dimensions of the order of .Comment: 4 pages, 2 figures, 1 table, to appear in Phys. Rev.
Quasars and their host galaxies
This review attempts to describe developments in the fields of quasar and
quasar host galaxies in the past five. In this time period, the Sloan and 2dF
quasar surveys have added several tens of thousands of quasars, with Sloan
quasars being found to z>6. Obscured, or partially obscured quasars have begun
to be found in significant numbers. Black hole mass estimates for quasars, and
our confidence in them, have improved significantly, allowing a start on
relating quasar properties such as radio jet power to fundamental parameters of
the quasar such as black hole mass and accretion rate. Quasar host galaxy
studies have allowed us to find and characterize the host galaxies of quasars
to z>2. Despite these developments, many questions remain unresolved, in
particular the origin of the close relationship between black hole mass and
galaxy bulge mass/velocity dispersion seen in local galaxies.Comment: Review article, to appear in Astrophysics Update
Observing Supermassive Black Holes across cosmic time: from phenomenology to physics
In the last decade, a combination of high sensitivity, high spatial
resolution observations and of coordinated multi-wavelength surveys has
revolutionized our view of extra-galactic black hole (BH) astrophysics. We now
know that supermassive black holes reside in the nuclei of almost every galaxy,
grow over cosmological times by accreting matter, interact and merge with each
other, and in the process liberate enormous amounts of energy that influence
dramatically the evolution of the surrounding gas and stars, providing a
powerful self-regulatory mechanism for galaxy formation. The different
energetic phenomena associated to growing black holes and Active Galactic
Nuclei (AGN), their cosmological evolution and the observational techniques
used to unveil them, are the subject of this chapter. In particular, I will
focus my attention on the connection between the theory of high-energy
astrophysical processes giving rise to the observed emission in AGN, the
observable imprints they leave at different wavelengths, and the methods used
to uncover them in a statistically robust way. I will show how such a combined
effort of theorists and observers have led us to unveil most of the SMBH growth
over a large fraction of the age of the Universe, but that nagging
uncertainties remain, preventing us from fully understating the exact role of
black holes in the complex process of galaxy and large-scale structure
formation, assembly and evolution.Comment: 46 pages, 21 figures. This review article appears as a chapter in the
book: "Astrophysical Black Holes", Haardt, F., Gorini, V., Moschella, U and
Treves A. (Eds), 2015, Springer International Publishing AG, Cha
Observations of the High Redshift Universe
(Abridged) In these lectures aimed for non-specialists, I review progress in
understanding how galaxies form and evolve. Both the star formation history and
assembly of stellar mass can be empirically traced from redshifts z~6 to the
present, but how the various distant populations inter-relate and how stellar
assembly is regulated by feedback and environmental processes remains unclear.
I also discuss how these studies are being extended to locate and characterize
the earlier sources beyond z~6. Did early star-forming galaxies contribute
significantly to the reionization process and over what period did this occur?
Neither theory nor observations are well-developed in this frontier topic but
the first results presented here provide important guidance on how we will use
more powerful future facilities.Comment: To appear in `First Light in Universe', Saas-Fee Advanced Course 36,
Swiss Soc. Astrophys. Astron. in press. 115 pages, 64 figures (see
http://www.astro.caltech.edu/~rse/saas-fee.pdf for hi-res figs.) For lecture
ppt files see
http://obswww.unige.ch/saas-fee/preannouncement/course_pres/overview_f.htm
Genome-wide by Environment Interaction Studies of Depressive Symptoms and Psychosocial Stress in UK Biobank and Generation Scotland
Stress is associated with poorer physical and mental health. To improve our understanding of this link, we performed genome-wide association studies (GWAS) of depressive symptoms and genome-wide by environment interaction studies (GWEIS) of depressive symptoms and stressful life events (SLE) in two UK population-based cohorts (Generation Scotland and UK Biobank). No SNP was individually significant in either GWAS, but gene-based tests identified six genes associated with depressive symptoms in UK Biobank (DCC, ACSS3, DRD2, STAG1, FOXP2 and KYNU; p < 2.77 x 10(-6)). Two SNPs with genome-wide significant GxE effects were identified by GWEIS in Generation Scotland: rs12789145 (53-kb downstream PIWIL4; p = 4.95 x 10(-9); total SLE) and rs17070072 (intronic to ZCCHC2; p = 1.46 x 10(-8); dependent SLE). A third locus upstream CYLC2 (rs12000047 and rs12005200, p < 2.00 x 10(-8); dependent SLE) when the joint effect of the SNP main and GxE effects was considered. GWEIS gene-based tests identified: MTNR1B with GxE effect with dependent SLE in Generation Scotland; and PHF2 with the joint effect in UK Biobank (p < 2.77 x 10(-6)). Polygenic risk scores (PRSs) analyses incorporating GxE effects improved the prediction of depressive symptom scores, when using weights derived from either the UK Biobank GWAS of depressive symptoms (p = 0.01) or the PGC GWAS of major depressive disorder (p = 5.91 x 10(-3)). Using an independent sample, PRS derived using GWEIS GxE effects provided evidence of shared aetiologies between depressive symptoms and schizotypal personality, heart disease and COPD. Further such studies are required and may result in improved treatments for depression and other stress-related conditions
Vistas of veterinary biology and medicine - 1975 Murdoch University Inaugural Lecture
A lecture given by Professor Bob Dunlop for the 1975 Murdoch University Inaugural Lecture series held at Murdoch University. This was the fifth lecture of the 1975 Murdoch University Inaugural Lecture series.
This sound recording is part of the History of Murdoch University Collection
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