Fiona C. Denison

14-3-3 proteins in plant physiology.

Plant 14-3-3 isoforms, like their highly conserved homologues in mammals, function by binding to phosphorylated client proteins to modulate their function. Through the regulation of a diverse range of proteins including kinases, transcription factors, structural proteins, ion channels and pathogen defense-related proteins, they are being implicated in an expanding catalogue of physiological functions in plants. 14-3-3s themselves are affected, both transcriptionally and functionally, by the extracellular and intracellular environment of the plant. They can modulate signaling pathways that transduce inputs from the environment and also the downstream proteins that elicit the physiological response. This review covers some of the key emerging roles for plant 14-3-3s including their role in the response to the plant extracellular environment, particularly environmental stress, pathogens and light conditions. We also address potential key roles in primary metabolism, hormone signaling, growth and cell division.

Obesity, pregnancy, inflammation, and vascular function

Maternal obesity is associated with increased morbidity and mortality for both mother and offspring. The mechanisms underlying the increased risk associated with maternal obesity are not well understood. In non-pregnant populations, many of the complications of obesity are thought to be mediated in part by inflammation and its sequelae. Recent studies suggest that a heightened inflammatory response may also be involved in mediating adverse clinical outcomes during pregnancy. This review summarizes our current knowledge about adipose tissue biology, and its role as an endocrine and inflammatory organ. The evidence for inflammation as a key mediator of adverse pregnancy outcome is also presented, focusing on the role of inflammation in adipose tissue, systemic inflammation, the placenta, and vascular endothelium.

Influence of the Menstrual Cycle, Pregnancy, and Preeclampsia on Arterial Stiffness

Arterial stiffness and compliance are major predictors of adverse cardiovascular events and are influenced by female sex hormones, including estrogen and progesterone. The aim of this longitudinal study was to evaluate the effect of the menstrual cycle, normal pregnancy, and preeclampsia on central and systemic arterial stiffness. Ten healthy nulliparous women with regular menses were studied in the early and midfollicular, periovulatory, and luteal phases of a single menstrual cycle. Twenty-two primigravida pregnant women were studied throughout pregnancy at 16, 24, 32, and 37 weeks gestation and at 7 weeks postpartum. Fifteen primigravida women with preeclampsia were studied at diagnosis and 7 weeks postpartum. Augmentation index and carotid-radial and carotid-femoral pulse wave velocities were measured using applanation tonometry. Augmentation index fell during the luteal phase of the menstrual cycle (luteal phase versus periovulatory phase; P<0.05). In normal pregnancy, pulse wave velocity and augmentation index increased from 24 weeks over the third trimester (P≤0.01 for both). All of the measures were increased in women with preeclampsia (P≤0.01), with augmentation index and carotid-femoral pulse wave velocity remaining elevated 7 weeks postpartum (P≤0.02). We conclude that systemic arterial stiffness undergoes major changes during the menstrual cycle and pregnancy and that preeclampsia is associated with greater and more prolonged increases in arterial stiffness. These effects may contribute to adverse cardiovascular outcomes of pregnancy and preeclampsia.

The action of prostaglandin E2 on the human cervix: Stimulation of interleukin 8 and inhibition of secretory leukocyte protease inhibitor ☆ ☆☆ ★

OBJECTIVE The objective of this study was to investigate regulation of inflammatory mediators implicated in cervical ripening and to explore the mechanisms by which the clinically effective agent prostaglandin E2 may mediate cervical ripening. STUDY DESIGN Cervical biopsy specimens were taken from healthy, nonpregnant women undergoing a hysterectomy for a benign nonmalignant condition and were cultured, with treatments in quadruplicate, for 24 hours in media supplemented with progesterone, dexamethasone, nitric oxide, interleukin 8, and prostaglandin E2. Media were collected and assayed by enzyme-linked immunosorbent assay for interleukin 8, secretory leukocyte protease inhibitor, and prostaglandin E2. Ethical approval was obtained for this study from the local ethics committee. RESULTS Interleukin 8 release from cervical explants was stimulated by prostaglandin E2 and nitric oxide and inhibited by progesterone and dexamethasone. Secretory leukocyte protease inhibitor release from cervical explants was stimulated by progesterone and inhibited by prostaglandin E2. Prostaglandin E2 release from cervical explants was stimulated by nitric oxide. CONCLUSION Complex interactions occur between inflammatory cytokines within the cervix; these results further our understanding of the mechanism of cervical ripening.

Potential roles of the prokineticins in reproduction

Prokineticins are multifunctional secreted proteins that were originally identified as regulators of intestinal contraction but subsequently shown to affect vascular function, hyperalgesia, spermatogenesis, neuronal survival, circadian rhythm, nociception, feeding behaviour, immune responses, haematopoiesis and the development of the olfactory and gonadotropin-releasing hormone systems. Their role in the reproductive tract is still not fully elucidated, although they are reputed to increase microvascular permeability. Expression of prokineticins and their receptors has been reported in the ovary, uterus, placenta, testis and prostate. Their expression has also been reported in various pathologies of the reproductive tract, and future studies will highlight whether inhibition of prokineticin function in these pathologies would be a useful therapeutic target.

Association between maternal body mass index during pregnancy, short-term morbidity, and increased health service costs: a population-based study.

To investigate the impact of maternal body mass index (BMI, kg/m2) on clinical complications, inpatient admissions, and additional short‐term costs to the National Health Service (NHS) in Scotland.

14-3-3 phosphoprotein interaction networks – does isoform diversity present functional interaction specification?

The 14-3-3 proteins have emerged as major phosphoprotein interaction proteins and thereby constitute a key node in the Arabidopsis Interactome Map, a node through which a large number of important signals pass. Throughout their history of discovery and description, the 14-3-3s have been described as protein families and there has been some evidence that the different 14-3-3 family members within any organism might carry isoform-specific functions. However, there has also been evidence for redundancy of 14-3-3 function, suggesting that the perceived 14-3-3 diversity may be the accumulation of neutral mutations over evolutionary time and as some 14-3-3 genes develop tissue or organ-specific expression. This situation has led to a currently unresolved question – does 14-3-3 isoform sequence diversity indicate functional diversity at the biochemical or cellular level? We discuss here some of the key observations on both sides of the resulting debate, and present a set of contrastable observations to address the theory functional diversity does exist among 14-3-3 isoforms. The resulting model suggests strongly that there are indeed functional specificities in the 14-3-3s of Arabidopsis. The model further suggests that 14-3-3 diversity and specificity should enter into the discussion of 14-3-3 roles in signal transduction and be directly approached in 14-3-3 experimentation. It is hoped that future studies involving 14-3-3s will continue to address specificity in experimental design and analysis.

Assessing maternal anxiety in pregnancy with the State-Trait Anxiety Inventory (STAI): issues of validity, location and participation

The State Trait Anxiety Inventory (STAI) has been widely used in research with pregnant women. However, few studies have examined its validity for this group. In this paper the content validity of the STAI, the impact of location and consequences for further participation of higher STAI scores are investigated for 215 pregnant women who completed the STAI at hospital or community based clinics. The study participants answered the open ended question, ‘How do you feel about your pregnancy?’ and whether or not they would be willing to take part in further research. Results indicated that STAI state scores reflected the nature of womens spontaneous comments regarding their pregnancy, with lower anxiety related to more ‘positive’ comments. The state scores were also found to be sensitive to the risk level associated with the clinic where the inventory was completed; higher scores related to high‐risk localities. Women with the highest levels of state or trait anxiety were also less likely to wish to take part in further research. The study concludes that the STAI does reflect the anxiety‐related experiences of pregnant women and that its use with pregnant women is appropriate in this respect; however, we recommend that future research notes the issue of potential recruitment biases.

Influence of menstrual cycle on circulating endothelial progenitor cells

BACKGROUND Endothelial progenitor cells (EPCs) are circulating mononuclear cells that participate in angiogenesis. The aim of this study was to determine the influence of the menstrual cycle on the number and function of EPCs, and to investigate their relationship with circulating concentrations of sex steroids and inflammatory mediators. METHODS Ten healthy nulliparous, premenopausal, non-smoking women with regular menses were studied over a single menstrual cycle. Venepuncture was performed in the menstrual, follicular, peri-ovulatory and luteal phases. EPCs were quantified by flow cytometry (CD133(+)CD34(+)KDR(+) phenotype) and the colony-forming unit (CFU-EPC) functional assay. Circulating concentrations of estradiol, progesterone and inflammatory mediators (TNF-alpha, IL-6, sICAM-1 and VEGF) were measured by immunoassays. RESULTS The numbers of CD133(+)CD34(+)KDR(+) cells were higher in the follicular phase (0.99 +/- 0.3 x 10(6) cells/l) compared with the peri-ovulatory phase (0.29 +/- 0.1 x 10(6) cells/l; P < 0.05). In contrast, the numbers of CFU-EPCs did not vary over the menstrual cycle. There were no correlations between EPCs and concentrations of either circulating sex steroids or inflammatory mediators. CONCLUSIONS CD133(+)CD34(+)KDR(+) cells but not CFU-EPCs vary during the menstrual cycle. Our findings suggest a potential role for circulating EPCs in the normal cycle of physiological angiogenesis and repair of the uterine endometrium that is independent of circulating sex steroids or inflammatory mediators.

Endothelial progenitor cells in pregnancy

The discovery of endothelial progenitor cells has generated considerable interest in the field of vascular biology. These cells arise from a population of circulating mononuclear cells and have the capacity to form new blood vessels and contribute to vascular repair. Circulating endothelial progenitor cell numbers are reduced in patients with cardiovascular risk factors and in the presence of endothelial dysfunction, but are increased in response to ischaemia, oestrogens and drug therapy. They have been studied in pathologies from cardiovascular and renal disease to rheumatoid arthritis and pre-eclampsia. Pregnancy is a challenge to the maternal vascular system, requiring systemic adaptation and pronounced local changes in the uterus. Diseases of pregnancy such as pre-eclampsia and gestational diabetes increase the risk of pregnancy complications and are associated with endothelial dysfunction. We propose that endothelial progenitor cells have an important role in the regulation and maintenance of the vasculature during pregnancy. This review summarises our current understanding of endothelial progenitor cells, with specific reference to their role in angiogenesis and human pregnancy.