Function and control of human invasive trophoblast subtypes: Intrinsic vs. maternal control

ABSTRACT

The establishment of a functional placenta is pivotal for normal fetal development and the maintenance of pregnancy. In the course of early placentation, trophoblast precursors differentiate into highly invasive trophoblast subtypes. These cells, referred to as extravillous trophoblasts (EVTs), penetrate the maternal uterus reaching as far as the inner third of the myometrium. One of the most fundamental functions of EVTs is the transformation of spiral arteries to establish the uteroplacental blood circulation assuring an adequate nutrient and gas supply to the developing fetus. To achieve this, specialized EVT subpopulations interact with maternal immune cells, provoke elastolysis in the arterial wall and replace the endothelial cells lining the spiral arteries to induce intraluminal vascular remodeling. These and other trophoblast-mediated processes are tightly controlled by paracrine signals from the maternal decidua and furthermore underlie an intrinsic cell-type specific program. Various severe pregnancy complications such as preeclampsia or intrauterine growth retardation are associated with abnormal EVT function, shallow invasion, and decreased blood flow to the placenta. Hence a better understanding of human trophoblast invasion seems mandatory to improve therapeutic intervention. This approach, however, requires a profound knowledge of the human placenta, its various trophoblast subtypes and in particular a better understanding of the regulatory network that controls the invasive phenotype of EVTs.     

Endorsing Darwin: global biogeography of the epipelagic goose barnacles Lepas spp. (Cirripedia,Lepadomorpha) proves cryptic speciation

It was Darwin that noted the large intraspecific diversity of the goose barnacle Lepas Linnaeus, 1758 and thought about distinct regional varieties. Today, biogeographic compartmentation is known from marine species, but data from globally occurring species remain scarce. We analysed inter‐ and intraspecific divergence within the epipelagic rafter Lepas from tropical and temperate oceans by means of two mitochondrial and one nuclear DNA marker. Besides phylogenetic relations, we resolved biogeography and controlling factors. Inhabiting the Southern Hemisphere, Lepas australis Darwin, 1851 shows separate populations from coastal Chile and from circum‐Antarctic waters, most probably related to temperature differences in the current systems. The cosmopolitan Lepas anatifera Linnaeus, 1758 displays four regional subgroups (coastal Chile, Northeast Pacific/Oregon, the Southern Hemisphere Indopacific, and the Atlantic), and a global group, which might be an ancestral stem group. The differentiation reflects vicariance effects rooted in geological history: the closure of the Neogene Tethys in the Middle East and at the Panama Isthmus, the installation of the cool Benguela Current, differing Pleistocene currents and temperatures, and modern current systems. The extreme ecological generalists Lepas anserifera Linnaeus, 1767 and Lepas pectinata Spengler, 1793 are not differentiated, and might represent true global species. In conclusion, compartmentation of the oceans acts at the species level according to ecospace limits. For Lepas, the multitude of barriers favours allopatric speciation.     

Trait biogeography of marine copepods – an analysis across scales

Functional traits, rather than taxonomic identity, determine the fitness of individuals in their environment: traits of marine organisms are therefore expected to vary across the global ocean as a function of the environment. Here, we quantify such spatial and seasonal variations based on extensive empirical data and present the first global biogeography of key traits (body size, feeding mode, relative offspring size and myelination) for pelagic copepods, the major group of marine zooplankton. We identify strong patterns with latitude, season and between ocean basins that are partially (c. 50%) explained by key environmental drivers. Body size, for example decreases with temperature, confirming the temperature‐size rule, but surprisingly also with productivity, possibly driven by food‐chain length and size‐selective predation. Patterns unrelated to environmental predictors may originate from phylogenetic clustering. Our maps can be used as a test‐bed for trait‐based mechanistic models and to inspire next‐generation biogeochemical models.     

Metabolite targeting: development of a comprehensive targeted metabolomics platform for the assessment of diabetes and its complications

Biomarker studies for metabolic disorders like diabetes mellitus (DM) are an important approach towards a better understanding of the underlying pathophysiological mechanisms of diseases (Roberts and Gerszten in Cell Metab 18:43–50, 2013; Wilson et al. in Proteome Res 4:591–598, 2005). Furthermore, screening of potential metabolic biomarkers opens the opportunity of early diagnosis as well as therapy and drug monitoring of metabolic disorders (Rhee et al. in J Clin Invest 10:1–10, 2011; Wang et al. in Nat Med 17:448–458, 2011; Wenk in Nat Rev Drug Discov 4:594–610, 2005). The aim of the present study was to develop methods for the quantitative determination of 74 potential metabolite biomarkers for DM and diabetic nephropathy (DN) in serum. Several studies have shown that the concentrations of many polar metabolites like amino or organic acids are changed in subjects suffering from diabetes (Wang et al. in Nat Med 17:448–458, 2011; Yuan et al. in J Chromatogr B 813:53–58, 2007). Analyzing polar analytes presents a challenge in liquid chromatography (LC) coupled with ESI–MS/MS (Gika et al. in J Sep Sci 31:1598–1608, 2008; Spagou et al. in J Sep Sci 33:716–727, 2010). Considering those reasons we decided to develop a specific HILIC–ESI–QqQ–MS/MS-method for quantitative determination of these polar metabolites. A subsequent method validation was carried out for both HILIC and RP chromatography with respect to the guidelines of the Food and Drug Administration (FDA in Food and Drug Administration: Guidance for industry, bioanalytical method validation, 2001). The HILIC and RP LC–MS methods were successfully validated. Furthermore, the HILIC method presented here was applied to serum samples of GIPR^dn transgenic mice, a diabetic strain developing DN, and non transgenic littermate controls. Significant, diabetes-associated changes were observed for the concentrations of 21 out of 62 metabolites. The new methods described here accurately quantify 74 metabolites known to be regulated in diabetes, allowing for direct comparison between studies and laboratories. Thus, these methods may be highly adoptable in clinical research, providing a starting point for early diagnosis and metabolic screening.