No abstract

Preeclampsia (PE) is one of the main causes of maternal and fetal morbidity and mortality in the world, causing nearly 40% of births delivered before 35 weeks of gestation. PE begins with inadequate trophoblast invasion early in pregnancy, which produces an increase in oxidative stress contributing to the development of systemic endothelial dysfunction in the later phases of the disease, leading to the characteristic clinical manifestation of PE. Numerous methods have been used to predict the onset of PE with different degrees of efficiency. These methods have used fetal/placental and maternal markers in different stages of pregnancy. From an epidemiological point of view, many studies have shown that PE is a disease with a strong familiar predisposition, which also varies according to geographical, socioeconomic, and racial features, and this information can be used in the prediction process. Large amounts of research have shown a genetic association with a multifactorial polygenic inheritance in the development of this disease. Many biological candidate genes and polymorphisms have been examined in their relation with PE. We will discuss the most important of them, grouped by the different pathogenic mechanisms involved in PE.

In the adult mammal the circadian system, which allows predictive adaptation to daily environmental changes, comprises peripheral oscillators in most tissues, commanded by the suprachiasmatic nucleus (SCN) of the hypothalamus. The external environment of the fetus is provided by its mother. In primates, maternal melatonin is a candidate to entrain fetal circadian rhythms, including the SCN rhythms of metabolic activity. We found in the 90% of gestation capuchin monkey fetus expression of the clock genes Bmal-1, Per-2, Cry-2, and Clock in the SCN, adrenal, pituitary, brown fat, and pineal. Bmal-1, Per-2, and the melatonin 1 receptor (MT1) showed a robust oscillatory expression in SCN and adrenal gland, whereas a circadian rhythm of dehydroepiandrosterone sulphate was found in plasma. Maternal melatonin suppression changed the expression of Bmal-1, Per-2, and MT1 in the fetal SCN. These effects were reversed by maternal melatonin replacement. In contrast, neither maternal melatonin suppression nor its replacement had effects on the expression of Per-2 and Bmal-1 or MT1 in the fetal adrenal gland or the circadian rhythm of fetal plasma dehydroepiandrosterone sulphate. Our data suggest that maternal melatonin is a Zeitgeber for the fetal SCN but probably not for the adrenal gland.

In the past decade the 'circular economy' (CE) has established itself as an influential model for economic development, with the Chinese central and regional governments (Su et al. 2013) and the European Union (European Commission 2018) being early propagators and policy champions. The ambition of the model is to create 'circular' material flows that break with the current 'linear' economic rationale of take, make and dispose, creating business value for its participants (Lacy and Rutqvist 2015; Esposito, Tse, and Soufani 2018). Inspired, among other influences, by the cradle-to-cradle design methodology (McDonough and Braungart 2009), the CE is to create waste-free technical loops that resemble biological loops and make waste disappear at the same time as being restorative and regenerative by design. This ambition has attracted the open support from a wide range of economic and political actors: intergovernmental bodies (OECD), influential forums (World Economic Forum), advocacy associations (World Business Council for Sustainable Development-WBCSD, the Ellen MacArthur Foundation, Circle Economy), leading corporations and consulting firms (e.g. Accenture, Cisco, Dell, H&M, Hewlett Packard, Intel, IKEA, McKinsey, Renault, and Levy Strauss), cities (Amsterdam, Glasgow) and regions (Region Skåne in Southern Sweden). The CE comes with a promise that circular relationships among markets, customers and natural resources (Lacy and Rutqvist 2015) have a unique capacity to combine economic growth with sustainability (Ghisellini, Cialani, and Ulgiati 2016). We acknowledge that the CE is not one 'thing', but, rather, could be seen as an 'empty signifier' (Valenzuela and Böhm 2017), which allows for a whole range of interpretations and approaches to be bundled together under the term 'circular economy'. Indeed, the CE is said to have 114 definitions (Kirchherr, Reike, and Hekkert 2017), which implies that academics and practitioners do not necessarily agree on precisely what the CE entails and how it should be implemented. In short, the CE is a contested concept (Korhonen et al. 2018), which is not surprising as essentially all approaches that try to square the circle of business-society-nature relations can be questioned and challenged from a variety of different viewpoints (McManus 1996; Carew and Mitchell 2008). Despite this 'emptiness' of the CE, allowing for open interpretation and even free, creative associations between a range of economic, social and environmental factors (Murray, Skene, and Haynes 2017), influential economic and political actors have been allowed to hegemonize the CE discourse. The result has been the narrowing down of latent possibilities in the systems thinking that underpins the CE. At heart, the CE is a radical concept, as it is historically embedded in a critique of established systems relations that have produced the 'unsustainability' that characterizes contemporary, linear forms of global capitalism (Hobson 2016). At its best, CE thinking takes a whole-systems approach, aiming to redesign e...

The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000 -0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400 -2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9-to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3␤-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nM melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin.