36,499 research outputs found
Caffeine Inhibits EGF-Stimulated Trophoblast Cell Motility through the Inhibition of mTORC2 and Akt.
No full textImpaired trophoblast invasion is associated with pregnancy disorders such as early pregnancy loss and preeclampsia. There is evidence to suggest that the consumption of caffeine during pregnancy may increase the risk of pregnancy loss; however, little is known about the direct effect of caffeine on normal trophoblast biology. Our objectives were to examine the effect of caffeine on trophoblast migration and motility after stimulation with epidermal growth factor (EGF) and to investigate the intracellular signaling pathways involved in this process. Primary first-trimester extravillous trophoblasts (EVT) and the EVT-derived cell line SGHPL-4 were used to study the effect of caffeine on EGF-stimulated cellular motility using time-lapse microscopy. SGHPL-4 cells were further used to study the effect of caffeine and cAMP on EGF-stimulated invasion of fibrin gels. The influence of caffeine and cAMP on EGF-stimulated intracellular signaling pathways leading to the activation of Akt were investigated by Western blot analysis. Caffeine inhibits both EGF-stimulated primary EVT and SGHPL-4 cell motility. EGF stimulation activates phosphatidylinositol 3-kinase, and Akt and caffeine inhibit this activation. Although cAMP inhibits both motility and invasion, it does not inhibit the activation of Akt, indicating that the effects of caffeine seen in this study are independent of cAMP. Further investigation indicated a role for mammalian target of rapamycin complex 2 (mTORC2) as a target for the inhibitory effect of caffeine. In conclusion, we demonstrate that caffeine inhibits EGF-stimulated trophoblast invasion and motility in vitro and so could adversely influence trophoblast biology in vivo
Woud: Trek je even terug in je concentratiebubbel
No full textHet was zo’n zonnige lentedag; heerlijk om lekker buiten te zijn. Ik zat binnen, in een vergadering – met de nodige moeite om mijn aandacht erbij te houden. Liever keek ik door het raam naar kersenbloesems. Afgeleid raken, wegdromen ofjuist onrustig zijn en niet stil kunnen zitten. Herkenbaar? Vast wel; iedereen heeft wel eens moeite om zich te concentreren. Maar voor sommige kinderen is dit een dagelijkse worsteling. Hoe ga je daar op een goede manier mee om in eenklaslokaal, een omgeving met constante prikkels en afleiding? Ontwerper Shion Ito ontwierp een mini-bos waar je je even in kunt terugtrekken om je rust terug te vindenGreen Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Human-Centered DesignDesign Aesthetic
Altered placental expression of kisspeptin and its receptor in pre-eclampsia
No full textKisspeptin, originally identified as metastatin, important in preventing cancer metastasis, has more recently been shown to be important in pregnancy. Roles indicated for kisspeptin in pregnancy include regulating trophoblast invasion and migration during placentation. The pregnancy-specific disorder pre-eclampsia (PE) is now accepted to begin with inadequate trophoblast invasion and the current study therefore sets out to characterise placental expression of both kisspeptin (KISS1) and its receptor (KISS1R) throughout pregnancy and in PE. Placental tissue was obtained from women undergoing elective surgical termination of early pregnancy (n=10) and from women following Caesarean section at term in normal pregnancy (n=10) and with PE (n=10). Immunohistochemistry of paraffin embedded sections and western immunoblotting were performed to assess protein localisation and expression. Quantitative real-time PCR was carried out to evaluate mRNA expression of both KISS1 and KISS1R. Protein and mRNA expression was found to mirror each other with KISS1 expression found to be reduced in PE compared with that in normal term pregnancy. Interestingly, KISS1R expression at both the mRNA and protein levels was found to be increased in PE compared with that in normal term pregnancy. The current findings of increased KISS1R expression may represent a mechanism by which functional activity of KISS1 is higher in PE than in normal pregnancy. Higher levels of activity of KISS1R may be involved in inhibition of trophoblast invasion and angiogenesis, which are associated with PE
Londen laat zien: verstedelijking kun je privaat bekostigen
No full textSimon van Zoest en Tom Daamen doen bij de leerstoel Gebiedsontwikkeling onderzoek naar de financiering en bekostiging van grootstedelijk openbaar vervoer. Zij kijken daarbij voorbij de instrumenten en verdiept zich in de motieven en succesfactoren achter de invoer van alternatieve bekostiging. Zo maakt Londen duidelijk dat een private bijdrage aan ov-investeringen mogelijk én wenselijk kan zijnPractice Chair Urban Area DevelopmentUrban Development Managemen
Tam Tam in je broekzak
No full textDit is het eindverslag van de stage "Tam Tam in je broekzak", die wij hebben uitgevoerd in het kader van IN3405 Bachelorproject. Deze stage is uitgevoerd bij Tam Tam B.V. te Rijswijk.Technische InformaticaComputer ScienceElectrical Engineering, Mathematics and Computer Scienc
Fetal-derived trophoblast use the apoptotic cytokine tumor necrosis factor-alpha-related apoptosis-inducing ligand to induce smooth muscle cell death.
No full textRemodeling of the uterine spiral arteries during pregnancy transforms them from high to low resistance vessels that lack vasoconstrictive properties. This process is essential to meet the demand for increased blood flow imposed by the growing fetus. Loss of endothelial and smooth muscle cells (SMC) is evident in remodeled arteries but the mechanisms underlying this transformation remain unknown. This study investigated the hypothesis that fetal trophoblast invading from the placenta instigate remodeling by triggering cell death in vascular SMC. Specifically, a role for trophoblast-derived death inducing cytokine tumor necrosis factor-α–related apoptosis-inducing ligand (TRAIL) was investigated. Expression of the activating TRAIL receptors R1 and R2 was detected by flow cytometry on human aortic SMC and by immunohistochemistry on spiral artery SMC. Recombinant human TRAIL induced human aortic SMC apoptosis, which was inhibited by antibodies against TRAIL-R1 or -R2. Perfusion of denuded spiral artery segments with recombinant human TRAIL also induced SMC apoptosis. Trophoblasts isolated from first trimester placenta expressed membrane-associated TRAIL and induced apoptosis of human aortic SMC; apoptosis was significantly inhibited by a recombinant human TRAIL-R1:Fc construct. Trophoblast within the first trimester placental bed also expressed TRAIL. These data show that: 1) TRAIL causes SMC death; 2) trophoblast produce the apoptotic cytokine TRAIL; and 3) trophoblast induce SMC apoptosis via a TRAIL-dependent mechanism. We conclude that TRAIL produced by trophoblast causes apoptosis of SMC and thus may contribute to SMC loss during spiral artery remodeling in pregnancy
Melk in je koffie: Een onderzoek met mogelijkheden
No full textIn 1999 stond in de NRC een column van Karel Knip over de vraag uit de wetenschapsquiz of je direct een wolkje melk in je koffie moet doen als de bel gaat of dat je dat beter kunt doen als je terugkomt van de buitendeur. De column geeft een mooi beeld van wat er allemaal kan komen kijken als je wat dieper op de vraag ingaat. Er blijken veel mogelijkheden te zijn om ook in de klas met deze vraag aan de slag te gaan!ImPhys/Docente
Zo meet je de waarde van sociale investeringen
No full textWat leveren investeringen in de zachte, sociale kant van gebiedsontwikkeling op? Deze vraag houdt ontwikkelaars, gemeenten en beleggers al langer bezig. Een antwoord is te vinden via de capability-benadering. Hierbij staan niet de kwantitatieve fysieke functies centraal, maar de kwalitatieve mate waarin mensen in staat zijn deze te gebruiken.Practice Chair Urban Area Developmen
Als je oud wordt moet je de buurt uit
No full text"Als je oud wordt moet je de buurt uit" is een beschrijving van een planologisch onderzoek onder ouderen in de Da Costabuurt, een stadsvernieuwingsbuurt in Amsterdam Oud-West. Ervaringen en meningen van ouderen zij het uitgangspunt van dit onderzoek. Door groepsgesprekken en individuele interviews worden de knelpunten die zij ervaren in het zelfstandig wonen geïnventariseerd. Daaruit blijkt dat deze knelpunten zo urgent zijn, dat vele ouderen hierdoor worden gedwongen uit de buurt te verhuizen. In de aanbevelingsfeer ligt de nadruk op het versterken van de positie van ouderen in het stadsvernieuwingsproces. Ouderen zullen zich als groep actiever moeten opstellen, om meer greep te krijgen op de inrichting van hun directe omgeving.Delft University of Technolog
Uterine spiral artery remodeling involves endothelial apoptosis induced by extravillous trophoblasts through Fas/FasL interactions.
No full textObjective— Invasion of uterine spiral arteries by extravillous trophoblasts in the first trimester of pregnancy results in loss of endothelial and musculoelastic layers. This remodeling is crucial for an adequate blood supply to the fetus with a failure to remodel implicated in the etiology of the hypertensive disorder preeclampsia. The mechanism by which trophoblasts induce this key process is unknown. This study gives the first insights into the potential mechanisms involved.
Methods and Results— Spiral arteries were dissected from nonplacental bed biopsies obtained at Caesarean section, and a novel model was used to mimic in vivo events. Arteries were cultured with trophoblasts in the lumen, and apoptotic changes in the endothelial layer were detected after 20 hours, leading to loss of endothelium by 96 hours. In vitro, coculture experiments showed that trophoblasts stimulated apoptosis of primary decidual endothelial cells and an endothelial cell line. This was blocked by caspase inhibition and NOK2, a FasL blocking antibody. NOK2 also abrogated trophoblast-induced endothelial apoptosis in the vessel model.
Conclusions— Extravillous trophoblast induction of endothelial apoptosis is a possible mechanism by which the endothelium is removed, and vascular remodeling may occur in uterine spiral arteries. Fas/FasL interactions have an important role in trophoblast-induced endothelial apoptosis
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