99 research outputs found
Elevated circulating and placental SPINT2 is associated with placental dysfunction
Biomarkers for placental dysfunction are currently lacking. We recently identified SPINT1 as a novel biomarker; SPINT2 is a functionally related placental protease inhibitor. This study aimed to characterise SPINT2 expression in placental insufficiency. Circulating SPINT2 was assessed in three prospective cohorts, collected at the following: (1) term delivery (n = 227), (2) 36 weeks (n = 364), and (3) 24â34 weeksâ (n = 294) gestation. SPINT2 was also measured in the plasma and placentas of women with established placental disease at preterm (p = 0.028; median = 2233 pg/mL vs. controls, median = 1644 pg/mL), or delivered a small-for-gestational-age infant (p = 0.002; median = 2109 pg/mL vs. controls, median = 1614 pg/mL). SPINT2 was elevated in the placentas of patients who required delivery for preterm preeclampsia (p = 0.025). Though inflammatory cytokines had no effect, hypoxia increased SPINT2 in cytotrophoblast stem cells, and its expression was elevated in the placental labyrinth of growth-restricted rats. These findings suggest elevated SPINT2 is associated with placental insufficiency
Circulating syndecan-1 is reduced in pregnancies with poor fetal growth and its secretion regulated by matrix metalloproteinases and the mitochondria
Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomarkers may improve detection of pregnancies at risk. This study aimed to assess syndecan-1 as a biomarker for small for gestational age (SGA) or fetal growth restricted (FGR) pregnancies and determine its molecular regulation. Circulating maternal syndecan-1 was measured in several cohorts; a large prospective cohort collected around 36Â weeks' gestation (nâ=â1206), a case control study from the Manchester Antenatal Vascular service (285 women sampled at 24-34Â weeks' gestation); two prospective cohorts collected on the day of delivery (36â+â3-41â+â3Â weeks' gestation, nâ=â562 and nâ=â405 respectively) and a cohort who delivered for preterm FGR (<â34Â weeks). Circulating syndecan-1 was consistently reduced in women destined to deliver growth restricted infants and those delivering for preterm disease. Syndecan-1 secretion was reduced by hypoxia, and its loss impaired proliferation. Matrix metalloproteinases and mitochondrial electron transport chain inhibitors significantly reduced syndecan-1 secretion, an effect that was rescued by coadministration of succinate, a mitochondrial electron transport chain activator. In conclusion, circulating syndecan-1 is reduced among cases of term and preterm growth restriction and has potential for inclusion in multi-marker algorithms to improve detection of poorly grown fetuses
Testing population genetic structure using parametric bootstrapping and M IGRATE-N
We present a method for investigating genetic population structure using sequence data. Our hypothesis states that the parameters most responsible for the formation of genetic structure among different populations are the relative rates of mutation (ÎŒ) and migration (M). The evolution of genetic structure among different populations requires rates of M âȘ ÎŒ because this allows population-specific mutation to accumulate. Rates of ÎŒ âȘ M will result in populations that are effectively panmictic because genetic differentiation will not develop among demes. Our test is implemented by using a parametric bootstrap to create the null distribution of the likelihood of the data having been produced under an appropriate model of sequence evolution and a migration rate sufficient to approximate panmixia. We describe this test, then apply it to mtDNA data from 243 plethodontid salamanders. We are able to reject the null hypothesis of no population structure on all but smallest geographic scales, a result consistent with the apparent lack of migration in Plethodon idahoensis . This approach represents a new method of investigating population structure with haploid DNA, and as such may be particularly useful for preliminary investigation of non-model organisms in which multi-locus nuclear data are not available.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42796/1/10709_2004_Article_8358.pd
Review of magnetic gear technologies and their applications in marine energy
The marine energy industry is in its early stages but has a large potential for growth. One of the most significant challenges is the reduction of operation and maintenance costs. Magnetic gears (MGs) offer the potential for long periods between maintenance intervals due to their frictionless torque transmission which could reduce these costs. This study presents a summary of the state of the art in MG technology and then investigates its potential for marine energy applications. A brief overview is given of the state of the marine energy industry and the environment in which marine energy converters (MECs) operate. A short history of MG development over the past century is then presented followed by a discussion of the leading MG technologies and their relative advantages. In order to demonstrate the potential of MGs in marine applications, the current technologies, i.e. mechanically geared and direct drive machines, are examined in terms of sizing, reliability and economic value using previous studies on a similar technology, namely wind. MGs are applied to four types of MECs to demonstrate how the technology can be incorporated. The potential to deploy at scale and potential obstacles to this are then discussed
Effects of sleep deprivation on neural functioning: an integrative review
Sleep deprivation has a broad variety of effects on human performance and neural functioning that manifest themselves at different levels of description. On a macroscopic level, sleep deprivation mainly affects executive functions, especially in novel tasks. Macroscopic and mesoscopic effects of sleep deprivation on brain activity include reduced cortical responsiveness to incoming stimuli, reflecting reduced attention. On a microscopic level, sleep deprivation is associated with increased levels of adenosine, a neuromodulator that has a general inhibitory effect on neural activity. The inhibition of cholinergic nuclei appears particularly relevant, as the associated decrease in cortical acetylcholine seems to cause effects of sleep deprivation on macroscopic brain activity. In general, however, the relationships between the neural effects of sleep deprivation across observation scales are poorly understood and uncovering these relationships should be a primary target in future research
Do soil depth and plant community composition interact to modify the resistance and resilience of grassland ecosystem functioning to drought?
While the effect of drought on plant communities and their associated ecosystem functions is well studied, little research has considered how responses are modified by soil depth and depth heterogeneity. We conducted a mesocosm study comprising shallow and deep soils, and variable and uniform soil depths, and two levels of plant community composition, and exposed them to a simulated drought to test for interactive effects of these treatments on the resilience of carbon dioxide fluxes, plant functional traits, and soil chemical properties. We tested the hypotheses that: (a) shallow and variable depth soils lead to increased resistance and resilience of ecosystem functions to drought due to more exploitative plant trait strategies; (b) plant communities associated with intensively managed high fertility soils, will have more exploitative root traits than extensively managed, lower fertility plant communities. These traits will be associated with higher resistance and resilience to drought and may interact with soil depth and depth heterogeneity to amplify the effects on ecosystem functions. Our results showed that while there were strong soil depth/heterogeneity effects on plant-driven carbon fluxes, it did not affect resistance or resilience to drought, and there were no treatment effects on plant-available carbon or nitrogen. We did observe a significant increase in exploitative root traits in shallow and variable soils relative to deep and uniform, which may have resulted in a compensation effect which led to the similar drought responses. Plant community compositions representative of intensive management were more drought resilient than more diverse âextensiveâ communities irrespective of soil depth or soil depth heterogeneity. In intensively managed plant communities, root traits were more representative of exploitative strategies. Taken together, our results suggest that reorganization of root traits in response to soil depth could buffer drought effects on ecosystem functions
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