1,460 research outputs found
Nitrite mediated vasorelaxation in human chorionic plate vessels is enhanced by hypoxia and dependent on the NO-sGC-cGMP pathway
No full textAdequate perfusion of the placental vasculature is essential to meet the metabolic demands of fetal growth and development. Lacking neural control, local tissue metabolites, circulating and physical factors contribute significantly to blood flow regulation. Nitric oxide (NO) is a key regulator of fetoplacental vascular tone. Nitrite, previously considered an inert end-product of NO oxidation, has been shown to provide an important source of NO. Reduction of nitrite to NO may be particularly relevant in tissue when the oxygen-dependent NO synthase (NOS) activity is compromised, e.g. in hypoxia. The contribution of this pathway in the placenta is currently unknown. We hypothesised that nitrite vasodilates human placental blood vessels, with enhanced efficacy under hypoxia. Placentas were collected from uncomplicated pregnancies and the vasorelaxant effect of nitrite (10−6–5x10−3 M) was assessed using wire myography on isolated pre-constricted chorionic plate arteries (CPAs) and veins (CPVs) under normoxic (pO2 ∼5%) and hypoxic (pO2 ∼1%) conditions. The dependency on the NO–sGC–cGMP pathway and known nitrite reductase (NiR) activities was also investigated. Nitrite caused concentration-dependent vasorelaxation in both arteries and veins, and this effect was enhanced by hypoxia, significantly in CPVs (P < 0.01) and with a trend in CPAs (P = 0.054). Pre-incubation with NO scavengers (cPTIO and oxyhemoglobin) attenuated (P < 0.01 and P < 0.0001, respectively), and the sGC inhibitor ODQ completely abolished nitrite-mediated vasorelaxation, confirming the involvement of NO and sGC. Inhibition of potential NiR enzymes xanthine oxidoreductase, mitochondrial aldehyde dehydrogenase and mitochondrial bc1 complex did not attenuate vasorelaxation. This data suggests that nitrite may provide an important reservoir of NO bioactivity within the placenta to enhance blood flow when fetoplacental oxygenation is impaired, as occurring in pregnancy diseases such as pre-eclampsia and fetal growth restriction.</p
Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms
No full textUptake of system L amino acid substrates into isolated placental plasma membrane vesicles in the absence of opposing side amino acid (zero-trans uptake) is incompatible with the concept of obligatory exchange, where influx of amino acid is coupled to efflux. We therefore hypothesized that system L amino acid exchange transporters are not fully obligatory and/or that amino acids are initially present inside the vesicles. To address this, we combined computational modeling with vesicle transport assays and transporter localization studies to investigate the mechanism(s) mediating [14C]L-serine (a system L substrate) transport into human placental microvillous plasma membrane (MVM) vesicles. The carrier model provided a quantitative framework to test the 2 hypotheses that L-serine transport occurs by either obligate exchange or nonobligate exchange coupled with facilitated transport (mixed transport model). The computational model could only account for experimental [14C]L-serine uptake data when the transporter was not exclusively in exchange mode, best described by the mixed transport model. MVM vesicle isolates contained endogenous amino acids allowing for potential contribution to zero-trans uptake. Both L-type amino acid transporter (LAT)1 and LAT2 subtypes of system L were distributed to MVM, with L-serine transport attributed to LAT2. These findings suggest that exchange transporters do not function exclusively as obligate exchangers.—Widdows, K. L., Panitchob, N., Crocker, I. P., Please, C. P., Hanson, M. A., Sibley, C. P., Johnstone, E. D., Sengers, B. G., Lewis, R. M., Glazier, J. D. Integration of computational modeling with membrane transport studies reveals new insights into amino acid exchange transport mechanisms
Modification of fetal plasma amino acid composition by placental amino acid exchangers in vitro
No full textFetal growth is dependent on both the quantity and relative composition of amino acids delivered to the fetal circulation, and impaired placental amino acid supply is associated with restricted fetal growth. Amino acid exchangers can alter the composition, but not the quantity, of amino acids in the intra- and extracellular amino acid pools. In the placenta, exchangers may be important determinants of the amino acid composition in the fetal circulation. This study investigates the substrate specificity of exchange between the placenta and the feto-placental circulation. Maternal-fetal transfer of radiolabelled amino acids and creatinine were measured in the isolated perfused human placental cotyledon. Transfer of L-[14C]serine or L-[14C]leucine, and [3H]glycine, were measured in the absence of amino acids in the fetal circulation (transfer by non-exchange mechanisms) and following 10-20 micromol boluses of unlabelled amino acids into the fetal circulation to provide substrates for exchange (transfer by exchange and non-exchange mechanisms). The ability of fetal arterial boluses of L-alanine and L-leucine to stimulate release of amino acids from the placenta was also determined using HPLC in order to demonstrate the overall pattern of amino acid release. Experiments with radiolabelled amino acids demonstrated increased maternal-fetal transfer of L-serine and L-leucine, but not glycine, following boluses of specific amino acids into the fetal circulation. L-[14C]Leucine, but not L-[14C]serine or [3H]glycine, was transferred from the maternal to the fetal circulation by non-exchange mechanisms also (P<0.01). HPLC analysis demonstrated that fetal amino acid boluses stimulated increased transport of a range of different amino acids by 4-7 micromol l(-1) (P<0.05). Amino acid exchange provides a mechanism to supply the fetus with amino acids that it requires for fetal growth. This study demonstrates that these transporters have the capacity to exchange micromolar amounts of specific amino acids, and suggests that they play an important role in regulating fetal plasma amino acid composition
Orbit design for future SpaceChip swarm missions in a planetary atmosphere
No full textThe effect of solar radiation pressure and atmospheric drag on the orbital dynamics of satellites-on-a-chip (SpaceChips) is exploited to design equatorial long-lived orbits about the oblate Earth. The orbit energy gain due to asymmetric solar radiation pressure, considering the Earth's shadow, is used to balance the energy loss due to atmospheric drag. Future missions for a swarm of SpaceChips are proposed, where a number of small devices are released from a conventional spacecraft to perform spatially distributed measurements of the conditions in the ionosphere and exosphere. It is shown that the orbit lifetime can be extended and indeed selected through solar radiation pressure and the end-of-life re-entry of the swarm can be ensured, by exploiting atmospheric drag
Public Policy in a Private Arena: The Case of Vocational Education and Training
Get PDFM.21586-1998 Colin Crouch. 30 cm. This paper is based on a seminar that he presented at the Center for Advanced Study in the Social Sciences of the Juan March Institute, Madrid, on 9 May 1995, entitled Diversity in Modern Capitalism: Examples from Vocational Education." -- T.p. Includes bibliographical references (p. 35-37
Golden Age Jesuit: Juan Eusebio Nieremberg and the rhetoric of discernment in seventeenth-century Spain
Get PDFThis thesis examines the Jesuit and Ignatian influence on the works of Juan Eusebio Nieremberg (1595-1658), who was a prolific and widely published author and a member of the Society of Jesus in Spain. He wrote several works across different literary genres both in Spanish and Latin, but was best known for his popular works in Spanish: two miscellanies of natural philosophy, Curiosa filosofía (1630) and Oculta filosofía (1633); a catechism, the Práctica del catecismo romano (1640); his ascetical treatises, especially De la diferencia entre lo temporal y eterno (1640); and his ‘advice-books’ to princes and nobles, most notably Causa y remedio de los males públicos (1642). As a member of the Jesuit Order, Nieremberg wrote these works with the intention to ‘save souls’, this being the main apostolic goal of the Society. While they provide people with knowledge (‘noticia’) – whether doctrinal, natural, spiritual, or political – these works teach readers to view human existence according to its true end: God’s will of salvation. All things of the temporal world are portrayed as a means to that end. In order to accomplish this goal, Nieremberg incorporates elements from Loyola’s Ejercicios espirituales (1548), the spiritual foundation of the Jesuit Order, and develops a rhetorical strategy which encourages readers to discern the will of God in the world they inhabit. He also develops this rhetoric according to some of the principal literary and artistic conventions of the seventeenth century, and provides an important example of how a prominent Jesuit writer came to express the apostolic and spiritual principles of his Order, but in the language and imagery of Spain’s Siglo de Oro
White empty Earth: photography and the imagined world
No full textMy use of photography is rooted in the complexities of the photograph, its making, meaning and function. Human understanding and perception of the physical world (as Landscape and Nature) are sole concerns as I address the ambivalence that coincides with these ideas and the space in between. Can one achieve a work that illuminates both personally and collectively, privately and socially? By photographing constructed environments in the studio, can I challenge the photograph as "document" and the environment as fundamentally separate from human? With this work, I am hoping to accomplish several things through a hermeneutic based exploration: An engagement in a meditative, slow process, the revealing of a mindful, personal space,a deeper understanding of the environment and my place in it and the capability, functionality, conscious/unconscious uses of and meaning in photography and the photograph and, lastly, how the image affects human consciousness of and relationship to the physical world.M.F.A.Includes bibliographical references (p. 65)by Colin Jon Edgingto
Understanding placental nutrient transfer - Why bother? New biomarkers of fetal growth
No full textThe placenta, in general and the physiology of maternofetal nutrient transfer is under-researched compared to other organs with epithelial transport function, as evidenced, for example, by publication numbers. This report provides reasons why more researchers should become involved in this topic. First, the syncytiotrophoblast, the transporting epithelium of the placenta, though having many basic cell physiology properties similar to those of other transporting epithelia, has several properties which are markedly different. Better information on these might help fundamental understanding of how epithelia in general function as well as improving knowledge of how the syncytiotrophoblast operates. Second, the synctiotrophoblast has a key role in controlling fetal growth, not only by transporting nutrients and waste products of metabolism but also because it increasingly appears to be one site, perhaps even the dominant site, in which integration of, sometimes conflicting, signals between mother and fetus takes place. Finally, better understanding of placental nutrient transfer and especially of how it is regulated by maternal and fetal signals could provide better information on the placental phenotype in fetal growth disorders - information which might contribute to providing better biomarkers which the obstetrician could use to improve early diagnosis of these disorders. © 2009 The Author. Journal compilation © 2009 The Physiological Society
Relation of placental alkaline phosphatase expression in human term placental to maternal and offspring fat mass
Get PDFIntroduction: alkaline phosphatase is implicated in intestinal lipid transport and to the development of obesity. Placental alkaline phosphatase is localised to the microvillous plasma membrane of the placental syncytiotrophoblast at the maternal-fetal interface, but its role is unclear. We investigated the relations of placental alkaline phosphatase activity and mRNA expression with maternal body composition and offspring fat mass in humans. Methods: term human placentas from the UK Birthright cohort (n=52) and the Southampton Women’s Survey (SWS)(n=95) were studied. In the Birthright cohort, alkaline phosphatase activity was measured in placental microvillous plasma membrane vesicles. In the SWS, alkaline phosphatase mRNA was measured using Nanostring. Alkaline phosphatase gene expression was compared to other lipid related genes. Results: in Birthright samples placental microvillous plasma membrane alkaline phosphatase activity was positively associated with maternal triceps skinfold thickness and BMI (β=0.04 (95%CI 0.01, 0.06) and β=0.02 (0.00, 0.03) µmol/mg protein/min per SD, P=0.002 and P=0.05, respectively) adjusting for potential confounders. In SWS samples placental alkaline phosphatase mRNA expression in term placenta was positively associated with maternal triceps skinfold (β=0.24 (0.04, 0.44) SD/SD, P=0.02), had no association with neonatal %fat mass (β=0.01 (-0.20, 0.21) SD/SD, P=0.93) and was negatively correlated with %fat mass at ages 4 (β=-0.28 (-0.52, -0.04) SD/SD, P=0.02), 6-7 (β=-0.25 (-0.49, -0.02) SD/SD, P=0.03) years. When compared with placental expression of other genes, alkaline phosphatase expression was positively related to genes including the lysophosphatidylcholine transporter MFSD2A (major facilitator superfamily domain containing 2A, P<0.001) and negatively related to genes including the fatty acid transport proteins 2 and 3 (P=0.001, P<0.001). Conclusions: our findings suggest relationships between placental alkaline phosphatase and both maternal and childhood adiposity. The inverse relationship between placental alkaline phosphatase gene expression and childhood %fat mass suggests placental alkaline phosphatase may help to protect the fetus from the adverse effects of maternal obesity
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