301 research outputs found
Pregnancies in Diabetes and Obesity: The Capacity-Load Model of Placental Adaptation
Excess nutritional supply to the growing fetus, resulting from maternal diabetes and obesity, is associated with increased risks of fetal maldevelopment and adverse metabolic conditions in postnatal life. The placenta, interposed between mother and fetus, serves as the gateway between the two circulations and is usually considered to mediate maternal exposures to the fetus through a direct supply line. In this Perspective, however, we argue that the placenta is not an innocent bystander and mounts responses to fetal βsignals of distressβ to sustain its own adequate function and protect the fetus. We describe several types of protection that the placenta can offer the fetus against maternal metabolic perturbations and offer a theoretical model of how the placenta responds to the intrauterine environment in maternal diabetes and obesity to stabilize the fetal environment. Our approach supports growing calls for early screening and control of pregnancy metabolism to minimize harmful fetal outcomes
Defining signal thresholds in DNA microarrays: exemplary application for invasive cancer
BACKGROUND: Genome-wide or application-targeted microarrays containing a subset of genes of interest have become widely used as a research tool with the prospect of diagnostic application. Intrinsic variability of microarray measurements poses a major problem in defining signal thresholds for absent/present or differentially expressed genes. Most strategies have used fold-change threshold values, but variability at low signal intensities may invalidate this approach and it does not provide information about false-positives and false negatives. RESULTS: We introduce a method to filter false-positives and false-negatives from DNA microarray experiments. This is achieved by evaluating a set of positive and negative controls by receiver operating characteristic (ROC) analysis. As an advantage of this approach, users may define thresholds on the basis of sensitivity and specificity considerations. The area under the ROC curve allows quality control of microarray hybridizations. This method has been applied to custom made microarrays developed for the analysis of invasive melanoma derived tumor cells. It demonstrated that ROC analysis yields a threshold with reduced missclassified genes in microarray experiments. CONCLUSIONS: Provided that a set of appropriate positive and negative controls is included on the microarray, ROC analysis obviates the inherent problem of arbitrarily selecting threshold levels in microarray experiments. The proposed method is applicable to both custom made and commercially available DNA microarrays and will help to improve the reliability of predictions from DNA microarray experiments
Solar energy for self-contained power supply
Solar energy relevance in self-contained utility system as well as economic feasibility for each class of consumers considered. The article will outline utilising features of self-contained photovoltaic stations in Middle East and Northern Africa
Performance of early pregnancy HbA1c for predicting gestational diabetes mellitus and adverse pregnancy outcomes in obese European women
Aims: To investigate the performance of early pregnancy HbA1c for predicting gestational diabetes mellitus (GDM) and adverse pregnancy outcomes in obese women. Methods: Post hoc analysis using data from the Vitamin D And Lifestyle Intervention for GDM prevention trials conducted across 9 European countries (2012β2014). Pregnant women (BMI β₯ 29 kg/m2) underwent a baseline HbA1c and oral glucose tolerance tests at \u3c 20 weeks, 24β28 weeks, and 35β37 weeks. Women with GDM were referred for treatment. Results: Among the 869 women tested, the prevalence of GDM was 25.9% before 20 weeks, with a further 8.6% at 24β28 weeks. The areas under the curves for HbA1c at the two time points were 0.55 (0.50β0.59) and 0.54 (0.47β0.61), respectively. An early HbA1c β₯ 5.7% (39 mmol/mol) (N = 111) showed low sensitivity (18.2%) with 89.1% specificity for GDM before 20 weeks, at 24β28 weeks (sensitivity of 8.0% and specificity of 88.6% after excluding early GDM), and throughout gestation (sensitivity of 15.9% and specificity of 89.4%). The β₯ 5.7% (39 mmol/mol) threshold was significantly associated with concurrent GDM before 20 weeks (adjusted OR (aOR) 2.77(1.39β5.51)) and throughout gestation (aOR 1.72 (1.02β2.89)), but not adverse pregnancy outcomes. Conclusions: Early pregnancy HbA1c is of limited use for predicting either GDM or adverse outcomes in overweight/obese European women
P171Elevated free fetal haemoglobin threatens vasculoprotection in the fetal circulation of preeclamptic pregnancy
Placental up-regulation of free fetal haemoglobin (fHbF) occurs in preeclamptic (PE) pregnancy. Heme oxygenase-1 (HO-1) is an important vasculoprotective enzyme in the catabolism of the associated heme porphyrin structure. We have previously shown that fHbF negatively influences the vasculoprotective capacity of the fetal circulation. Here we study fHbF levels in the fetal cord blood of pregnancies complicated by PE; a pathology associated with dysregulated fetoplacental vascular tone. We have previously shown that fHbF binds nitric oxide (NO) to elicit elevated vascular resistance in the fetoplacental circulation, using ex vivo human dual placental perfusion and in vitro placental endothelial cell shear stress studies. Furthermore, fHbF causes morphological changes to the fetoplacental endothelium. Here we hypothesise that elevated levels of fHbF in fetal plasma associated with placental pathology contribute to fetoplacental hypertension. Purpose: To evaluate and derive a robust cord blood collection and processing protocol for the accurate measurement of fetal plasma fHbF levels in normal and PE pregnancies. Methods: Fetal venous cord blood was collected by syringe and needle, or Vacutainer method into either EDTA or citrate tubes, within 10 minutes of partum. Plasma recovery occurred immediately, or after 30 minutes, prior to centrifugation at 2000g x 10 min at room temperature. Following evaluation to reduce mechanical haemolysis, newly collected normal & PE plasma (n=13 & 6, respectively) was subjected to ELISAs for HbF and HO-1. Results: Venipuncture collection of cord venous blood taken from the cord-placenta insertion point by Vacutainer system with a 21G needle, into citrate collection tubes with immediate centrifugation prevented mechanical haemolysis. There was no difference in plasma HO-1 between groups (medians = 5.9 & 5.3 ng/mL; normal & PE, respectively; Mann-Whitney). Whilst there was no difference in fHbF between groups (Mann-Whitney), variability was high in the PE group and there were some very high values for fHbF compared to the normal range, whilst fHbF values in the control group were within a tighter lower range (medians & ranges = 45.9 & 0-206 and 118.8 & 29-640 ΞΌg/mL). Conclusion: Fetal plasma HO-1 levels appear stable in preeclamptic fetal plasma, permitting fHbF to remain unchecked in some cases. High pathophysiological levels of fHbF in some cases of PE pregnancies are capable of evoking elevated vascular resistance within the fetoplacental circulation, caused by nitric oxide sequestration and disruption to the endothelium. Further evaluation is require
Downregulation of p53 drives autophagy during human trophoblast differentiation
The placental barrier is crucial for the supply of nutrients and oxygen to the developing fetus and is maintained by differentiation and fusion of mononucleated cytotrophoblasts into the syncytiotrophoblast, a process only partially understood. Here transcriptome and pathway analyses during differentiation and fusion of cultured trophoblasts yielded p53 signaling as negative upstream regulator and indicated an upregulation of autophagy-related genes. We further showed p53 mRNA and protein levels decreased during trophoblast differentiation. Reciprocally, autophagic flux increased and cytoplasmic LC3B-GFP puncta became more abundant, indicating enhanced autophagic activity. In line, in human first trimester placenta p53 protein mainly localized to the cytotrophoblast, while autophagy marker LC3B as well as late autophagic compartments were predominantly detectable in the syncytiotrophoblast. Importantly, ectopic overexpression of p53 reduced levels of LC3B-II, supporting a negative regulatory role on autophagy in differentiating trophoblasts. This was also shown in primary trophoblasts and human first trimester placental explants, where pharmacological stabilization of p53 decreased LC3B-II levels. In summary our data suggest that differentiation-dependent downregulation of p53 is a prerequisite for activating autophagy in the syncytiotrophoblast
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Endothelin-1 down-regulates matrix metalloproteinase 14 and 15 expression in human first trimester trophoblasts via endothelin receptor type B
: Does endothelin-1 (ET-1) regulate matrix metalloproteinase (MMP) 14 and 15 production and invasion of human first trimester trophoblasts?
: ET-1 in pathophysiological concentrations down-regulates MMP14 and MMP15 expression via endothelin receptor (ETR) type B and decreases trophoblast migration and invasion.
: MMP14 and MMP15 are involved in trophoblast invasion. Impairment of invasion has been linked to pregnancy complications such as pre-eclampsia (PE). ET-1 is up-regulated in PE.
: study using primary human trophoblasts from 50 first trimester placentas (gestational week 7-12).
: Trophoblasts were cultured in the absence or presence of 10-100 nM ET-1. MMP14 and MMP15 mRNA and protein were quantified by RT-qPCR and Western blotting, respectively. Selective antagonists for ETRA (BQ-123) or ETRB (BQ-788) were used to identify ETR subtypes involved. Functional ET-1 effects were tested in first trimester chorionic villous explants and transwell invasion assays. The roles of tumor necrosis factor (TNF)-Ξ± (25 ng/ml) and oxygen (1%) in ET-1 regulation of MMP14 and 15 expression were assessed by Western blotting.
: ET-1 down-regulated MMP14 and MMP15 mRNA (-21% and -26%, respectively, < 0.05) and protein levels (-18% and -22%, respectively, < 0.05). This effect was mediated via ETRB. ET-1 decreased trophoblast outgrowth in placental explants (-24%, < 0.05) and trophoblast invasion (-26%, β€ 0.01). TNF-Ξ± enhanced ET-1 mediated MMP15 down-regulation (by 10%, < 0.05), whereas hypoxia abolished the effect of ET-1 on both MMPs.
: N/A.
: Only primary trophoblasts were used in this study. Since trophoblast yield from first trimester placental material is limited, further aspects of MMP14 and 15 regulation could not be characterized. Other anti-invasive factors may be altered by ET-1 in trophoblasts and, thus, contribute to the reduced invasion, but have not been investigated. Oxygen levels similar to those found in the decidua (5-8% O2) were not analyzed in this study.
: ET-1 modifies placental function already during the first trimester of pregnancy, the time-window when the placental changes implicated in PE occur. Thus, our results improve the understanding of the placental mechanisms underlying trophoblast invasion and PE.The study was funded by the Oesterreichische Nationalbank (Anniversary Fund, project number: 14796) and the Herzfelder'sche Familienstiftung (to J.P.; number: 00685). AMM received funding from the Austrian Science Fund FWF (W1241) and the Medical University Graz through the PhD Program Molecular Fundamentals of Inflammation (DK-MOLIN)
ΠΠΈΠ½Π³Π²ΠΎΡΡΠΈΠ»ΠΈΡΡΠΈΡΠ΅ΡΠΊΠ°Ρ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΡ Π΄ΠΈΡΠΊΡΡΡΠΈΠ²Π½ΠΎΠΉ ΡΡΡΠ°ΡΠ΅Π³ΠΈΠΈ ΠΏΡΠΎΠ΄Π²ΠΈΠΆΠ΅Π½ΠΈΡ ΡΠ½ΠΈΠ²Π΅ΡΡΠΈΡΠ΅ΡΠ° Π² ΡΠΎΠΏΠΎΡΡΠ°Π²ΠΈΡΠ΅Π»ΡΠ½ΠΎΠΌ Π°ΡΠΏΠ΅ΠΊΡΠ΅ (Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Π°Π½Π°Π»ΠΈΠ·Π° ΡΠ°ΠΉΡΠΎΠ² ΡΠΎΡΡΠΈΠΉΡΠΊΠΎΠ³ΠΎ ΠΈ ΠΊΠΈΡΠ°ΠΉΡΠΊΠΎΠ³ΠΎ Π²ΡΠ·ΠΎΠ²)
ΠΠ±ΡΠ΅ΠΊΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ - ΡΠ½ΠΈΠ²Π΅ΡΡΠΈΡΠ΅ΡΡΠΊΠΈΠΉ Π΄ΠΈΡΠΊΡΡΡ.
Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β Π²ΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ Π»ΠΈΠ½Π³Π²ΠΎΡΡΠΈΠ»ΠΈΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΎΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΠΈ Π΄ΠΈΡΠΊΡΡΡΠΈΠ²Π½ΠΎΠΉ ΡΡΡΠ°ΡΠ΅Π³ΠΈΠΈ ΠΏΡΠΎΠ΄Π²ΠΈΠΆΠ΅Π½ΠΈΡ Π½Π° ΡΠ°ΠΉΡΠ°Ρ
Π²ΡΠ·ΠΎΠ² Π Π€ ΠΈ ΠΠΠ .
Π ΠΏΡΠΎΡΠ΅ΡΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈΡΡ Π΄ΠΈΡΠΊΡΡΡΠΈΠ²Π½ΡΠΉ, Π»ΠΈΠ½Π³Π²ΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈΠΉ, ΡΡΠΈΠ»ΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈΠΉ, ΡΠΎΠΏΠΎΡΡΠ°Π²ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΊΠΎΠΌΠΌΡΠ½ΠΈΠΊΠ°ΡΠΈΠ²Π½ΠΎΠΉ ΡΡΡΠ°ΡΠ΅Π³ΠΈΠΈ ΠΏΡΠΎΠ΄Π²ΠΈΠΆΠ΅Π½ΠΈΡ Π²ΡΠ·ΠΎΠ².
Π ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π±ΡΠ»ΠΈ Π²ΡΡΠ²Π»Π΅Π½Ρ Π»ΠΈΠ½Π³Π²ΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ ΡΡΠΈΠ»ΠΈΡΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΠΎΡΠΎΡΠΌΠ»Π΅Π½ΠΈΡ ΠΆΠ°Π½ΡΠΎΠ² ΡΠ°ΠΉΡΠΎΠ² Π²ΡΠ·ΠΎΠ², ΡΠ΅Π°Π»ΠΈΠ·ΡΡΡΠΈΡ
ΡΡΡΠ°ΡΠ΅Π³ΠΈΡ ΠΏΡΠΎΠ΄Π²ΠΈΠΆΠ΅Π½ΠΈΡ, ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΡΠΎΠΏΠΎΡΡΠ°Π²ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ·, Π²ΡΡΠ°Π±ΠΎΡΠ°Π½Ρ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΈ ΠΏΠΎ ΠΏΠ΅ΡΠ΅Π²ΠΎΠ΄Ρ.
ΠΠ±Π»Π°ΡΡΡ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ: ΠΏΠ΅ΡΠ΅Π²ΠΎΠ΄ΡΠ΅ΡΠΊΠ°Ρ ΠΏΡΠ°ΠΊΡΠΈΠΊΠ° ΠΏΠ΅ΡΠ΅Π²ΠΎΠ΄ΠΎΠ² ΠΈ ΡΠ°Π·ΡΠ°Π±ΠΎΡΠΊΠΈ Π²Π½Π΅ΡΠ½ΠΈΡ
Π²Π΅ΡΡΠΈΠΉ ΡΠ°ΠΉΡΠΎΠ² Π²ΡΠ·ΠΎΠ².
ΠΠΊΠΎΠ½ΠΎΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ/Π·Π½Π°ΡΠΈΠΌΠΎΡΡΡ ΡΠ°Π±ΠΎΡΡ Π·Π°ΠΊΠ»ΡΡΠ°Π΅ΡΡΡ Π² ΠΏΡΠ΅Π΄ΠΎΡΡΠ°Π²Π»Π΅Π½ΠΈΠΈ ΡΠ΅ΠΊΠΎΠΌΠ΅Π½Π΄Π°ΡΠΈΠΉ ΠΏΠΎ ΠΏΠ΅ΡΠ΅Π²ΠΎΠ΄Ρ ΡΠ°ΠΉΡΠΎΠ² Π² Π°ΡΠΏΠ΅ΠΊΡΠ΅ ΠΏΡΠΎΠ΄Π²ΠΈΠΆΠ΅Π½ΠΈΡ Π²ΡΠ·Π°.Object of research: university discourse.
Aim of research is to determine linguistic and stylistic features of promotion as a discourse strategy conducted on websites of Russian and Chinese universities.
The following activities were carried out inn the course of the research: discourse analysis, linguistic, stylistic and comparative analysis of the communication strategy of universities promotion.
Research results: linguistic and stylistic features of universities websites genres that use communication strategy of promotion were determined, comparative analysis was carried out, translation recommendations were provided.
Appliance scope: translational practice of translation and design of universities foreign language versions
Placental transport and metabolism in fetal overgrowth \u2013 a workshop report
Fetal overgrowth in pregnancies complicated by diabetes is the result of an increased substrate availability which stimulates fetal
insulin secretion and fetal growth. However, despite strict glycemic control in modern clinical management of the pregnant woman
with diabetes, fetal overgrowth remains an important clinical problem. Recent studies in vivo provide evidence for increased
delivery of amino acids to the fetus in gestational diabetes (GDM) even when metabolic control is strict. This could be due to that
truly normal maternal substrate levels cannot be achieved in diabetic pregnancies and/or caused by altered placental nutrient
transport and metabolism. Studies in vitro demonstrate an up-regulation of placental transport systems for certain amino acids
in GDM associated with fetal overgrowth. GDM is also characterized by changes in placental gene expression, including upregulation
of inflammatory mediators and Leptin. In type-I diabetes with fetal overgrowth the in vitro activity of placental transporters
for both glucose and certain amino acids as well as placental lipoprotein lipase is increased. Furthermore, both clinical
observations in type-I diabetic pregnancies and preliminary animal experimental studies suggest that even brief periods of metabolic
perturbation early in pregnancy may affect placental growth and transport function for the remainder of pregnancy, thereby
contributing to fetal overgrowth. Ultrasound measurements of fetal fat deposits and abdominal circumference as well as 3D
ultrasound assessment of placental volume represent non-invasive techniques for in utero diagnosis of fetal and placental overgrowth.
It is proposed that these methods represent valuable additions to the clinical management of the diabetic pregnancy.
In conclusion, altered placental function may be a mechanism contributing to fetal overgrowth in diabetic pregnancies with
apparent optimal metabolic control. It is proposed that detailed information on placental metabolism and transport functions
obtained in vitro and in vivo represent a placental phenotype that provides important information and may facilitate diagnosis
and improve clinical management of fetal overgrowth
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