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.     

In-vivo dosimetry for field sizes down to 6 × 6 mm2 in shaped beam radiosurgery with microMOSFET

The aim of this study is to evaluate microMOSFET as in-vivo dosimeter in 6 MV shaped-beam radiosurgery for field sizes down to 6 × 6 mm². A homemade build-up cap was developed and its use with microMOSFET was evaluated down to 6 × 6 mm². The study with the homemade build-up cap was performed considering its influence on field size over-cover occurring at surface, achievement of the overall process of electronic equilibrium, dose deposition along beam axis and dose attenuation. An optimized calibration method has been validated using MOSFET in shaped-beam radiosurgery for field sizes from 98 × 98 down to 18 × 18 mm². The method was detailed in a previous study and validated in irregular field shapes series measurements performed on a head phantom. The optimized calibration method was applied to microMOSFET equipped with homemade build-up cap down to 6 × 6 mm². Using the same irregular field shapes, dose measurements were performed on head phantom. MicroMOSFET results were compared to previous MOSFET ones. Additional irregular field shapes down to 8.8 × 8.8 mm² were studied with microMOSFET. Isocenter dose attenuation due to the homemade build-up cap over the microMOSFET was near 2% irrespective of field size. Our results suggested that microMOSFET equipped with homemade build-up cap is suitable for in-vivo dosimetry in shaped-beam radiosurgery for field sizes down to 6 × 6 mm² and therefore that the required build-up cap dimensions to perform entrance in-vivo dosimetry in small-fields have to ensure only partial charge particle equilibrium.     

Genotype × region and genotype × production level interactions in Holstein cows

The identification of the presence of genotype by environment interaction effects on important traits in Holstein cattle allows for the use of international genetic evaluations and a more efficient design of regional genetic evaluation programmes. The aim of this study was to determine the genotype × environment interaction effects in Chilean Holstein dairy cattle through the analysis of records corresponding to calvings between 1998 and 2015. Herds were classified in the central and southern regions of Chile based on herd location as well as by high and low levels of production environments based on the fat plus protein yield averages per herd within each region. The central region has a Mediterranean climate and a confined production system while the southern region has a humid temperate climate and a production system based on grazing with supplementation. Traits studied were milk yield (MY), fat yield (FY), protein yield (PY), fat content (FC) and protein content (PC) by lactation, age at first calving (AFC) and calving interval (CI). Several four-trait mixed animal models were applied to environmental category data as different traits, which included herd-year-calving season (herd-year-birth season for AFC) and lactation number as fixed effects, and animal additive genetic, sire-herd, permanent environment and residual effects as random effects. Genetic correlations (r_g) for MY, FY, FC, PC and CI were found to decrease as differences between environmental categories increased. The r_g between the most extreme environmental categories considered in this study for AFC (0.26) was the only one found statistically lower than 0.60. Genetic correlation values statistically lower than 0.80 (P < 0.05) were observed for AFC, CI, MY, FY and PY between some environmental categories. If separate genetic evaluations are adopted as practical criteria when the value of r_g is lower than 0.60, the consequence of improving a multi-trait economic breeding objective in this population is likely to be small unless extreme environmental categories are considered. However, a moderate decrease in selection response and re-ranking of selection candidates is expected for AFC, CI and yield traits when selection is performed in different environmental conditions. Genotype × environment interaction effects involving production systems in a Mediterranean climate and confinement vs. Temperate Oceanic climate and grazing with supplementation, and between two fat plus protein yield level categories within each environment, were at most moderate for the studied traits.     

Novel screening methods — biosensors

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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.     

Translational biomaterials — the journey from the bench to the market — think ‘product’

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Molecular pharming — VLPs made in plants

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La vitamine D : effets « classiques », « non classiques » et évaluation du statut du patient

Knowledge about vitamin D has greatly improved during the last few years. Vitamin D cannot any more be considered as exclusively necessary to prevent ricket/osteomalacia. Its role in the prevention of some osteoporotic fractures in the elderly (in association with calcium nutrition) is now well-demonstrated and many epidemiologic and laboratory data argue for a role in the prevention of several diseases or anomalies (cancer, auto-immune diseases, cardiovascular events, sarcopenia…). A few intervention studies confirming some of these effects also exist. Vitamin D status can easily be assessed by measuring serum 25-OH vitamin D level. However, many experts have claimed that the population-based reference values for 25OHD are too low and that the cut-off value below which vitamin D insufficiency can be present is somewhere between 20 and 40 ng/mL with a clear tendency to target values above 30 ng/mL (75 nmol/L). The main consequences are that vitamin D insufficiency is highly frequent whereas the currently recommended supplementation doses are not sufficient.     

SYNE1-QK1 SNPs,G × G and G × E interactions on the risk of hyperlipidaemia

This study aimed to assess the relationship of 3 spectrin repeat containing nuclear envelope protein 1 (SYNE1) and 4 KH domain containing RNA binding (QK1) single nucleotide polymorphisms (SNPs), their haplotypes, gene-gene (G × G), gene-environment (G × E) interactions and hypercholesterolaemia (HCH) and hypertriglyceridaemia (HTG) in the Chinese Maonan minority. The genetic make-up of the SYNE1-QK1 SNPs in 1932 unrelated subjects (normal, 641; HCH, 649; and HTG, 642) was obtained by next-generation sequencing technologies. The genotypic frequencies of following SNPs were suggestively distinctive between the control and HCH groups (rs2623963, rs7745725, rs9459317, rs16897566), or between the control and HTG groups (rs2623963, rs1358317, rs7745725, rs1923608, rs16897566 SNPs; P < .05, respectively). Multiple-locus linkage disequilibrium analysis indicated that the identified SNPs were not inherited independently. Several haplotypes and gene-gene interaction haplotypes among the detected SNPs may be related with an increased morbidity of HCH (C-G-A, C-G-G and C-G-G-T-C-A-T) and HTG (C-G-G, G-T-G-C, C-G-G-G-T-G-C and C-G-G-T-C-A-T), whereas others may be related with an decreased risk of HCH (G-A-A, G-C-A-T, C-A-A-T-C-A-T and G-A-A-G-C-A-T) and HTG (G-A-A, G-C-A-T, C-A-A-T-C-A-T and G-A-A-G-C-A-T). The association evaluation based on haplotypes and gene-gene interactions could improve the power of detecting the risk of dyslipidaemia than anyone of SNP alone. There was significant three-locus model involving SNP-SNP, haplotype-haplotype/environment and G × G interactions (P < .05-0.001) that were detected by GMDR in HCH and HTG groups. Different interactions between genetic and environmental factors would produce different redundancy or synergy effects on the morbidity of HCH and/or HTG.     

Drinking water microbiology — from measurement to management

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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.     

TMC8 (EVER2) attenuates intracellular signaling by Zn2 + and Ca2 + and suppresses activation of Cl− currents

Eight paralogue members form the family of transmembrane channel-like (TMC) proteins that share considerable sequence homology to anoctamin 1 (Ano1, TMEM16A). Ano1 is a Ca^2 + activated Cl⁻ channel that is related to head and neck cancer, often caused by human papilloma virus (HPV) infection. Mutations in TMC 6 and 8 (EVER1, EVER2) cause epidermodysplasia verruciformis. This rare skin disease is characterized by abnormal susceptibility to HPV infection and cancer. We found that in contrast to Ano1 the common paralogues TMC4–TMC8 did not produce Ca^2 + activated Cl⁻ currents when expressed in HEK293 cells. On the contrary, TMC8 was found to be localized in the endoplasmic reticulum (ER), where it inhibited receptor mediated Ca^2 + release, activation of Ano1 and volume regulated LRRC8-related Cl⁻ currents. Zn^2 + is co-released from the ER together with Ca^2 + and thereby further augments Ca^2 + store release. Because TMC8 is required to lower cytosolic Zn^2 + concentrations by the Zn^2 + transporter ZnT-1, we hypothesize that HPV infections and cancer caused by mutations in TMC8 are related to upregulated Zn^2 +/Ca^2 + signaling and activation of Ano1.     

Metal–organic chemical vapor deposition of Bi2Mn4O10 films on SrTiO3 〈1 0 0〉

Bi₂Mn₄O₁₀ films were deposited on SrTiO₃ (1 0 0) substrates via metal–organic chemical vapor deposition (MOCVD) from the Bi(phenyl)₃ and Mn(tmhd)₃ (Htmhd = 2,2,6,6-tetramethyl-3,5-heptanedione) precursors. The films were deposited in the temperature range of 600–800 °C. The X-ray diffraction (XRD) characterization indicates that the Bi₂Mn₄O₁₀ phase is stable within the investigated range, but the temperature plays a crucial role in determining the out-of-plane orientation of the films. The SEM shows very homogeneous surfaces with a fiber texture morphology at the highest deposition temperature. The AFM data indicate a textured surface with a root mean square roughness of 77.67 nm for films deposited at 800 °C.     

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.     

When did Cuon reach Java? – Reinvestigation of canid fossils from Homo erectus faunas

The presence of the genus Cuon during the Pleistocene of Java is attested by the endemic species C. sangiranensis and C. crassidens, sometimes classified as C. alpinus, a species that is also part of the Holocene fauna and has persisted until today. The current study revises the fossil canid material from the Sangiran Dome, previously assigned variously to C. sangiranensis, C. crassidens, C. alpinus, C. javanicus, and C. trinilensis. It aims to reinvestigate the arrival of Cuon in Java, in particular in relation to the late early Pleistocene endemic canid of Java: the Cuon-sized Xenocyon trinilensis, which had evolved in situ on Java from the large X. merriami, and which could be a potential competitor to early Cuon in case of contemporaneity. We found that a mandible fragment from Pandejan (holotype of C. crassidens) shows a morphology typical for C. alpinus. However, a maxilla and a mandible from the Bapang Formation at Sangiran, including the holotype of C. sangiranensis, is here assigned to the early dhole species C. priscus. Our results indicate that Cuon was already present in Java during the early middle Pleistocene and probably arrived as part of the immigration events during the Kedung Brubus faunal stage. Since X. trinilensis and Cuon are both hypercarnivorous medium-sized dogs, similar ecological niches are expected for both species. Thus, X. trinilensis probably was outcompeted and replaced by C. priscus. In turn, the latter species was replaced by the extant species, C. alpinus, during the Nangdong faunal stage, likely as part of the next immigration phase, which then disappeared during the tropical rainforest fauna of the Punung faunal stage and re-entered at the onset of the Holocene.     

Nanostructured sensors for biomedical applications — a current perspective

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Protein homeostasis — more than resisting a hot bath

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Extremozymes — biocatalysts with unique properties from extremophilic microorganisms

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