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1.
Placenta ; 76: 6-9, 2019 01 15.
Article in English | MEDLINE | ID: mdl-30803713

ABSTRACT

Placental mediated fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. Heparan sulphate proteoglycans (HSPG) are highly expressed in placentae and regulate haemostasis. We hypothesise that altered expression of HSPGs, glypicans (GPC) may contribute to the development of FGR and small-for-gestational-age (SGA). GPC expression was determined in first-trimester chorionic villous samples collected from women with later SGA pregnancies and in placentae from third-trimester FGR and gestation-matched uncomplicated pregnancies. The expression of both GPC1 and GPC3 were significantly reduced in first-trimester SGA as well as in the third-trimester FGR placentae compared to controls. This is the first study to report a relationship between altered placental GPC expression and subsequent development of SGA/FGR.


Subject(s)
Fetal Growth Retardation/metabolism , Glypicans/metabolism , Placenta/metabolism , Adult , Case-Control Studies , Female , Humans , Infant, Newborn , Infant, Small for Gestational Age , Pregnancy , Pregnancy Trimester, First/metabolism , Pregnancy Trimester, Third/metabolism
2.
Placenta ; 45: 58-62, 2016 09.
Article in English | MEDLINE | ID: mdl-27577711

ABSTRACT

Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. FGR pregnancies are often associated with histological evidence of placental vascular thrombosis. The proteoglycans are important components and regulators of vascular homeostasis. Previous studies from our laboratory highlighted mRNA and protein expression differences in placental proteoglycan decorin (DCN), within a clinically well-characterised cohort of third-trimester idiopathic FGR compared with gestation-matched uncomplicated control pregnancies. We also showed that decorin contributes to abnormal angiogenesis and increased thrombin generation in vitro. These observations suggest that DCN gene expression may contribute to the etiology of FGR. Small for gestational age (SGA) is frequently used as a proxy for FGR and is defined as a birth weight below the 10th percentile of a birth weight curve. We therefore made use of a unique resource of first trimester tissues obtained via chorionic villus sampling during the first trimester to investigate the temporal relationship between altered DCN expression and any subsequent development of SGA. We hypothesized that placental DCN expression is decreased early in gestation in SGA pregnancies. Surplus chorionic villus specimens from 15 women subsequently diagnosed with FGR and 50 from women with uncomplicated pregnancies were collected. DCN mRNA and DCN protein were determined using real-time PCR and immunoblotting, respectively. Both DCN mRNA and protein were significantly decreased in placentae from first-trimester SGA-pregnancies compared with controls (p < 0.05). This is the first study to report a temporal relationship between altered placental DCN expression and subsequent development of SGA.


Subject(s)
Decorin/metabolism , Down-Regulation , Placenta/metabolism , Adult , Female , Humans , Infant, Small for Gestational Age , Maternal Age , Pregnancy , Pregnancy Trimester, First/metabolism
3.
Phys Rev Lett ; 116(16): 166801, 2016 Apr 22.
Article in English | MEDLINE | ID: mdl-27152817

ABSTRACT

We report on the realization of a single-electron source, where current is transported through a single-level quantum dot (Q) tunnel coupled to two superconducting leads (S). When driven with an ac gate voltage, the experiment demonstrates electron turnstile operation. Compared to the more conventional superconductor-normal-metal-superconductor turnstile, our superconductor-quantum-dot-superconductor device presents a number of novel properties, including higher immunity to the unavoidable presence of nonequilibrium quasiparticles in superconducting leads. Moreover, we demonstrate its ability to deliver electrons with a very narrow energy distribution.

4.
Nanotechnology ; 24(37): 375304, 2013 Sep 20.
Article in English | MEDLINE | ID: mdl-23974037

ABSTRACT

We report a novel method for the fabrication of superconducting nano-devices based on niobium. The well-known difficulties of lithographic patterning of high-quality niobium are overcome by replacing the usual organic resist mask by a metallic one. The quality of the fabrication procedure is demonstrated by the realization and characterization of long and narrow superconducting lines and niobium-gold-niobium proximity SQUIDs.

5.
Horm Metab Res ; 36(7): 501-5, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15305235

ABSTRACT

This study was designed to investigate the central neuroendocrine mechanisms by which exercise (EX) stimulates growth hormone (GH) release as a function of age. Twelve male subjects, six in their early-to-mid twenties and six in their late sixties or seventies, received a strong GH stimulus either as incremental EX until volitional exhaustion or by administration of GHRH alone or Hex alone two hours after a presumed maximal GH response to combined administration of GHRH plus hexarelin (Hex). Total GH availability was calculated as area under the curve (AUC) over time periods 0 - 120 and 120 - 240 min. The mean AUC in micro g/l x 120 min to GHRH+Hex in the younger group was approximately twice that in the older group (11,260, range 3,947 - 19,007 vs. 5,366, range 2,262 - 8,654). In younger males, the mean AUC to EX (509, range 0 - 1,151) was larger than to GHRH (119, range 0 - 543), but less than that to Hex (919, range 0 - 1,892). In the older group, GH responses to EX and GHRH were abolished (mean AUC: 112, range 0 - 285, and 156, range 30 - 493), respectively) in contrast to the response to Hex (1,077, range 189 - 1,780). These data indicate that maximal GH stimulation by GHRH+Hex results in greater desensitization of GHRH compared to Hex, irrespective of age. We postulate that the abolished responsiveness of GH to EX in older group is due to insufficient disinhibition of hypothalamic somatostatin activity and desensitization of GHRH, while the preserved activity of a central Hex-related pathway is not involved. The GH response to EX in younger males is due to complete inhibition of somatostatin activity and stimulation of a central Hex-related pathway in spite of GHRH desensitization. We conclude that a central Hex-related pathway is the primary factor for EX-induced GH release only in younger males.


Subject(s)
Exercise/physiology , Growth Hormone-Releasing Hormone/physiology , Growth Substances/pharmacology , Human Growth Hormone/blood , Oligopeptides/pharmacology , Physical Exertion/physiology , Adult , Age Factors , Aged , Area Under Curve , Human Growth Hormone/drug effects , Humans , Male , Matched-Pair Analysis , Statistics, Nonparametric , Stimulation, Chemical
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