Metabolomics – an overview. From basic principles to potential biomarkers (part 2)

The metabolome, which represents the complete set of molecules (metabolites) of a biological sample (cell, tissue, organ, organism), is the final downstream product of the metabolic cell process that involves the genome and exogenous sources. The metabolome is characterized by a large number of small molecules with a huge diversity of chemical structures and abundances. Exploring the metabolome requires complementary analytical platforms to reach its extensive coverage. The metabolome is continually evolving, reflecting the continuous flux of metabolic and signaling pathways. Metabolomic research aims to study the biochemical processes by detecting and quantifying metabolites to obtain a metabolic picture able to give a functional readout of the physiological state. Recent advances in mass spectrometry (one of the mostly used technologies for metabolomics studies) have given the opportunity to determine the spatial distribution of metabolites in tissues. In a two-part article, we describe the usual metabolomics technologies, workflows and strategies leading to the implementation of new clinical biomarkers. In this second part, we first develop the steps of a metabolomic analysis from sample collection to biomarker validation. Then with two examples, autism spectrum disorders and Alzheimer's disease, we illustrate the contributions of metabolomics to clinical practice. Finally, we discuss the complementarity of in vivo (positron emission tomography) and in vitro (metabolomics) molecular explorations for biomarker research.     

Neumark-Nord 2 – A multiphase Middle Palaeolithic open-air site in the Geisel Valley (Central Germany)

The lake basin Neumark-Nord 2 (NN 2) is located in the Geisel Valley in Saxony-Anhalt (Germany). It was scientifically investigated between 2003 and 2008. The sediment sequence, which is about 10 to 11 m thick, consists of limnic deposits, mostly silts mixed with clays and sands. Sedimentological as well as palynological, malacological and palaeomagnetic investigations, supported by absolute datings, date the entire sequence into the Eemian and Early Weichselian. Within the deposits several archaeological find horizons were discovered. Neumark-Nord 2/2 (NN 2/2) at the beginning of the Eemian and Neumark-Nord 2/0 (NN 2/0) with an early Weichselian were the most important archaeological horizons. Both find horizons represent former lake shore sites, where numerous crushed animal bones and other faunal debris were found, which can be regarded as remains of hunted game. With regard to the rich lithic material, both find horizons differ remarkably. In NN2/2, a simple artefact spectrum with a certain Levallois component and a dominance of denticulated, notched and laterally retouched specimens. In NN 2/0, on the other hand, bifacial tools such as backed knives and sometimes finely retouched scrapers are dominant, while the Levallois component fades completely into the background. Thus, NN 2 is one of the few open-air sites in archaeological landscape of Central German where several middle Palaeolithic find horizons occur in superposition.     

L’homme-lion d’Hohlenstein – Stadel

The fragments of the figurine called “lion-man” were found in 1939 in the cave of Hohlenstein-Stadel, in southwestern Germany. Joachim Hahn was the first to assemble the figure in 1969; the statuette was then restored between 1987 and 1988 in the workshops of the regional museum of Württemberg in Stuttgart. New excavations, conducted by the State Office for Cultural Heritage of Baden-Württemberg (Esslingen, Germany), were held in the same cave between 2009 and 2013. Then, hundreds of small fragments were found; some of them clearly belonged to the lion-man. Following these excavations, a second restoration was undertaken in the workshops of the State office of Cultural Heritage in 2012 and 2013. The Lion-Man, the tallest of the figures from the last Ice Age, got a new appearance. After the refitting of the fragments, a large part of the figurine has been completed.     

Platachromone A–D: Cytotoxic 2-styrylchromones from the bark of Platanus × acerifolia (Aiton) Willd.

Four novel 2-styrylchromones, 4′,5,7-trihydroxy-6-isopentene-2-styrylchromone (1), 4′,5,7-trihydroxy-8-isopentene-2-styrylchromone (2), 4′,5,7-trihydroxy-6-(2-hydroxy-3-methylbut-3-enyl)-2-styrylchromone (3) and 4′,5,7-trihydroxy-8-(2-hydroxy-3-methylbut-3-enyl)-2-styrylchromone (4), were isolated from shed bark of Platanus × acerifolia (Aiton) Willd., as well as four known compounds, 4′,5,7-trihydroxy-2-styrylchromone (5), scutellarein (6), 4′,5,7-trihydroxy-6-prenylflavone (7), and 4′,5,7-trihydroxy-8-prenylflavone (8). The structures of compounds 1–4 were established by direct interpretation of their spectral data, mainly high resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D and 2D NMR (¹H–¹H COSY, HSQC and HMBC). The cytotoxicity of the compounds 1–8 was evaluated in four human carcinoma cell lines, including HepG2, SMMC-7721, MDA-MB-231, and KB. Compounds 1–4 exhibited significantly cytotoxic activity toward HepG2 and KB cells, with IC₅₀ values ranging from 3.0 to 9.7 μM.     

sHER-2 : un nouveau marqueur ?

The extracellular domain of the HER-2 (ERBB2) oncoprotein (p105^HER-2, ECD HER-2) is shed in the serum and can be detected by immunoassay. The currently approved cutoff for an elevated HER-2 ECD is greater than 15 ng/mL. HER-2 ECD is attractive as a potentially useful serum biomarker. In metastatic breast cancer, serum assay of HER-2 ECD is recommended to assess HER-2 status when unknown in primary tumor or metastatic biopsy is not feasible. In that case, it has been recommended to consider a 50 ng/mL serum HER-2 ECD cutoff as criteria to select patients for HER-2 targeted therapy. It might offer additional prognostic or predictive value compared with HER-2 tumor tissue testing. In addition, it can be measured serially and might be able to monitor treatment response, predict relapse or provide a real-time assessment of HER-2 status at metastatic disease.     

Differentiation of F1 hybrids P. nigra J. F. Arnold × P. sylvestris L., P. nigra J. F. Arnold × P. densiflora Siebold et Zucc., P. nigra J. F. Arnold × P. thunbergiana Franco and their parental species by needle volatile composition

The volatile composition of needles from three F₁ hard pine hybrids produced by the controlled hybridization and their parental species were researched with gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS) in order to explore the utility of terpenes in hybrid identification (their differentiation from the parental species) as well as confirmation of hybridity. The analysed hybrids were: 1. Pinus nigra J. F. Arnold × Pinus sylvestris L. (= nisy), 2. P. nigra × Pinus densiflora Siebold et Zucc. (= nide) and 3. P. nigra × Pinus thunbergiana Franco (= nith). A total of 55 compounds were identified. All identified compounds were terpenes, except trans-2-hexenal.Three analysed F₁ hybrids showed the same qualitative pattern of the needle volatile composition as their parental species. However, there were quantitative differences in several major terpenes. The volatile composition of the needles from the hybrids nisy were equally similar to both parents, the hybrids nide were more similar to the female parent (P. nigra), whereas the hybrids nith were more similar to the male parent (P. thunbergiana). According to the content of germacrene D, as the specific component of P. nigra (female parent of the three analysed F₁ hybrids), all hybrids were intermediary in relation to the parental species. The content of Δ-3-carene (the specific component of P. sylvestris) in the hybrids nisy was also intermediary. The hybrids nide had a higher content of thunbergol (specific component of P. densiflora) than the other analysed hybrids. In view of the content of β-pinene, the specific component of P. thunbergiana, the hybrids nith were intermediary to the parental species and that content was considerably higher than in the other analysed hybrids. The intermediary quality of F₁ hybrids for these specific components in relation to the parental species confirms their hybrid character.The needle volatile composition analysis as well as the previous morphometric analysis confirm the hybrid character of three F₁ hybrids, whose female parent is P. nigra, and male parents are P. sylvestris, P. densiflora, i.e. P. thunbergiana.     

Speckle characterization methods in ultrasound images – A review

Speckle has been widely considered a noisy feature in ultrasound images, thus it is intended to be suppressed and eliminated. On the other hand, speckle can be studied as a signal modeled by various statistical distributions or by analyzing its intensity with spatial relations in image space that characterize its nature, and hence, the nature of the underlying tissue. This knowledge can then be used in order to classify the different speckle regions into anatomical structures. In fact, speckle characterization in echocardiography and other ultrasonic images is important for motion tracking, tissue characterization, image segmentation, registration, and other medical applications for diagnosis, therapy planning and decision making. In this paper, we review and discuss various speckle characterization methods, which are often applied to confirm the speckle nature of the elements.     

Dwellings and workspaces at Strandvägen, 5600–5000 cal. BC

This paper describes identified workspaces and the manufacture of slotted bone points at the Late Mesolithic settlement Strandvägen in Motala, in eastern central Sweden. Several dwellings were documented, Dwelling 1 being typically round-oval in shape 9 × 5.5 meters, with a floor area covering 49.5 m². Radiocarbon dates fall between approximately 5600-5200 cal BC. A combined archaeological record, with lithics and bone artefacts as well as analyses of the osteological assemblage has shown that slotted bone tools with mounted lithic inserts have been produced adjacent of the dwelling. The spatial distribution of bone flakes, microblades, processed resin and slotted artefacts testify to a clearly and delimited craft area near the shoreline of the river Motala Ström. Analyses of the finds, e.g. birch bark resin and prepared bone preforms by direct percussion, also help in reconstructing the stages of manufacturing composite projectile points in this part of Eurasia.