Bioarchaeology aids the cultural understanding of six characters in search of their agency (Tarquinia, ninth-seventh century BC, central Italy).

Etruria contained one of the great early urban civilisations in the Italian peninsula during the first millennium BC, much studied from a cultural, humanities-based, perspective, but relatively little with scientific data, and rarely in combination. We have addressed the unusual location of twenty inhumations found in the sacred heart of the Etruscan city of Tarquinia, focusing on six of these as illustrative, contrasting with the typical contemporary cremations found in cemeteries on the edge of the city. The cultural evidence suggests that the six skeletons were also distinctive in their ritualization and memorialisation. Focusing on the six, as a representative sample, the scientific evidence of osteoarchaeology, isotopic compositions, and ancient DNA has established that these appear to show mobility, diversity and violence through an integrated bioarchaeological approach. The combination of multiple lines of evidence makes major strides towards a deeper understanding of the role of these extraordinary individuals in the life of the early city of Etruria.

Analytical development for the assessment of pesticide contaminations in blood and plasma of wild birds: The case of grey partridges (Perdix perdix).

In this study, blood and plasma of grey partridges (Perdix perdix) were analyzed to assess their potential contamination by plant protection products (PPP) and especially pesticide compounds. The group of pesticides selected is composed of a huge variety of compounds. Therefore, in this study, two methods were optimized and validated to analyze 104 compounds including herbicides, insecticides, fungicides and photoprotectors or synergists. Various extraction methods found in the literature were compared and adapted for the extraction of pesticides from blood and plasma. After extraction, samples were concentrated then injected for quantification simultaneously in LC-MS/MS and ATD-GC-MS/MS with an automatic thermal desorption step (ATD). Both LC-MS/MS and ATD-GC-MS/MS analyses were performed using the MRM mode with 2 mass transitions for each compound.The two analytical methods achieved a good linearity for the calibration responses in plasma and blood. Methods allowed sensitive detection and quantification in complex biological matrices such as plasma and blood in both LC and GC. For plasma samples and considering all 104 compounds of the study, the average LOD was 0.005 ng mg-1 in LC-MS/MS and 0.035 ng mg-1 in ATD-GC-MS/MS and the average LOQ was 0.017 ng mg-1 and 0.116 ng mg-1 in LC-MS/MS and ATD-GC-MS/MS respectively. Accordingly, the average LOD for blood samples was 0.011 ng mg-1 in LC and 0.028 ng mg-1 in GC whereas the average LOQ was 0.038 ng mg-1 and 0.094 ng mg-1 in LC-MS/MS and ATD-GC-MS/MS respectively. Those analytical methods were then successfully applied to 70 blood samples and 35 plasma samples.

CXCR7 receptors facilitate the progression of colon carcinoma within lung not within liver.

BACKGROUND: Liver and lung metastases are the predominant cause of colorectal cancer (CRC)-related mortality. Chemokine-receptor pairs have a critical role in determining the metastatic progression of tumours. Our hypothesis was that disruption of CXCR7/CXCR7 ligands axis could lead to a decrease in CRC metastases. METHODS: Primary tumours and metastatic tissues from patients with CRC were tested for the expression of CXCR7 and its ligands. Relevance of CXCR7/CXCR7 ligands for CRC metastasis was then investigated in mice using small pharmacological CXCR7 antagonists and CRC cell lines of human and murine origins, which - injected into mice - enable the development of lung and liver metastases. RESULTS: Following injection of CRC cells, mice treated daily with CXCR7 antagonists exhibited a significant reduction in lung metastases. However, CXCR7 antagonists failed to reduce the extent of liver metastasis. Moreover, there were subtle differences in the expression of CXCR7 and its ligands between lung and liver metastases. CONCLUSION: Our study suggests that the activation of CXCR7 on tumour blood vessels by its ligands may facilitate the progression of CRC within lung but not within liver. Moreover, we provide evidence that targeting the CXCR7 axis may be beneficial to limit metastasis from colon cancer within the lungs.

Glyphosate, AMPA and glufosinate in soils and earthworms in a French arable landscape.

Although Glyphosate-based herbicides are often marketed as environmentally friendly and easily biodegradable, its bioavailability and risks to wildlife raise significant concerns. Among non-target organisms, earthworms which live in close contact with the soil can be directly exposed to pesticides and harmed. We investigated soil contamination and the exposure of earthworms to glyphosate, its metabolite AMPA, and glufosinate in an arable landscape in France, both in treated (i.e. temporary grasslands and cereal fields under conventional farming), and nontreated habitats (i.e. hedgerows, permanent grasslands and cereal fields under organic farming) (n = 120 sampling sites in total). Glyphosate, AMPA and glufosinate were detected in 88%, 58% and 35% of the soil samples, and in 74%, 38% and 12% of the earthworm samples, respectively. For both glyphosate and AMPA, concentrations in soils were at least 10 times lower than predicted environmental concentrations. However, the maximum glyphosate soil concentration measured (i.e., 0.598 mg kg-1) was only 2 to 3 times lower than the concentrations revealed to affect earthworms (survival and avoidance) in the literature. These compounds were found both in conventional and organic farming fields, thus supporting a recent study, and for the first time they were detected in hedgerows and grasslands. However, glyphosate and AMPA were more frequently detected in soils from cereal fields and hedgerows than in grasslands, and median concentrations measured in soils from cereal fields were significantly higher than in the two other habitats. Bioaccumulation of glyphosate and AMPA in earthworms was higher than expected according to the properties of the molecules. Our findings raised issues about the high occurrence of glyphosate and AMPA in soils from cropped and more natural areas in arable landscapes. They also highlight the potential for transfer of these molecules in terrestrial food webs as earthworms are prey for numerous animals.

Serum total periostin is an independent marker of overall survival in bone metastases of lung adenocarcinoma.

More than 35% of lung adenocarcinoma patients have bone metastases at diagnosis and have a poor survival. Periostin, a carboxylated matrix protein, mediates lung cancer cell dissemination by promoting epithelial-mesenchymal transition, and is involved in bone response to mechanical stress and bone formation regulation. This suggests that periostin may be used as a biomarker to predict survival in lung cancer patients. Serum periostin was assessed at diagnosis in a prospective cohort of 133 patients with lung adenocarcinoma of all stages. Patients were divided into localized and bone metastatic groups. Both groups were matched to healthy controls. Survival analysis and Cox proportional hazards models were conducted in the total population and in bone metastatic group. The median serum periostin level was higher in bone metastatic (n = 67; median: 1752 pmol/L) than in the localized group (n = 66; 861 pmol/L; p < 0.0001). Patients with high periostin (>median) had a poorer overall survival in the whole population (33.3 weeks vs. NR; p < 0.0001) and the bone metastatic group (24.4 vs. 66.1 weeks; p < 0.001). In multivariate analysis, patients with high periostin had increased risk of death (HR = 2.09, 95%CI [1.06-4.13]; p = 0.03). This was also found in the bone metastatic group (HR = 3.62, 95%CI [1.74-7.52]; p = 0.0005). Immunohistochemistry on bone metastasis biopsies showed periostin expression in the bone matrix and nuclear and cytoplasmic staining in cancer cells. Serum periostin was an independent survival biomarker in all-stage and in bone metastatic lung adenocarcinoma patients. IHC data suggest that periostin might be induced in cancer cells in bone metastatic niche in addition to bone microenvironment expression.

Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism.

Liver and lung metastases are the predominant cause of colorectal cancer (CRC)-related mortality. Recent research has indicated that CXCR3/chemokines interactions that orchestrate haematopoetic cell movement are implicated in the metastatic process of malignant tumours, including that of CRC cells to lymph nodes. To date, however, the contribution of CXCR3 to liver and lung metastasis in CRC has not been addressed. To determine whether CXCR3 receptors regulate malignancy-related properties of CRC cells, we have used CXCR3-expressing CRC cell lines of human (HT29 cells) and murine (C26 cells) origins that enable the development of liver and lung metastases when injected into immunodeficient and immunocompetent mice, respectively, and assessed the effect of CXCR3 blockade using AMG487, a small molecular weight antagonist. In vitro, activation of CXCR3 on human and mouse CRC cells by its cognate ligands induced migratory and growth responses, both activities being abrogated by AMG487. In vivo, systemic CXCR3 antagonism by preventive or curative treatments with AMG487 markedly inhibited the implantation and the growth of human and mouse CRC cells within lung without affecting that in the liver. In addition, we measured increased levels of CXCR3 and ligands expression within lung nodules compared with liver tumours. Altogether, our findings indicate that activation of CXCR3 receptors by its cognate ligands facilitates the implantation and the progression of CRC cells within lung tissues and that inhibition of this axis decreases pulmonary metastasis of CRC in two murine tumour models.

Is a quantitative risk assessment of air quality in underground parking garages possible?

UNLABELLED: Little information is available about the health risks associated with time spent in underground parking garages. The objective of this study was to determine whether it is possible to quantify the health risks associated with these garages without epidemiologic data on the subject. We followed the standard procedure for health risk assessment. We searched the literature for pollutant concentrations in the air samples of underground parking garages, the hazards associated with their inhalation, and their toxicological reference values. Conditions of occupational and user exposure were estimated by scenarios and taken into account to discuss toxicological reference values by modifying (with Haber's law) the adjustment factors for exposure frequency and duration. Risk quantification was possible for 39 pollutants. Acute exposures to CO and NO2 exceed toxicological reference values, as does chronic exposure to benzene for threshold effects. The risk of a carcinogenic effect associated with benzene may be greater than 10(-5). Excess exposure to air pollution indicators (PM and NO2) is also elevated, judging by the WHO Air Quality Guidelines, and also when comparing to levels with reported effects in epidemiologic studies. The risk associated with underground parking garages can be evaluated only in part. The information available is nonetheless sufficient to justify actions to reduce exposure. PRACTICAL IMPLICATIONS: The risks associated with exposure in underground parking garages cannot be thoroughly evaluated because of inadequate knowledge of exposures and of the toxicity of pollutants. The available knowledge is nonetheless sufficient to advise that risk management measures should be taken to reduce both acute and chronic exposures.

REE characteristics and Pb, Sr and Nd isotopic compositions of steel plant emissions.

A comprehensive Pb-Sr-Nd isotope and REE tracer study of atmospheric trace metal pollution by a steel plant situated to the north of the urban communities of Strasbourg (France) and Kehl (Germany) has been performed using tree barks as biomonitors. The 206Pb/207Pb and 208Pb/207Pb isotopic ratios of the steel plant's filter dust are similar to values found in dust of waste incinerators. The 87Sr/86Sr ratio is similar to present-day ratios of Phanerozoic or Precambrian granitic rocks. The 143Nd/144Nd isotopic composition is very low and corresponds to an (Nd) value of -17.5. Such a low value is characteristic of old Precambrian granitic rocks and banded iron formations. Thus, this low (Nd) value might point to the origin of the iron necessary for the steel production. The fact, that this isotopic composition does not occur in crustal rocks of Western Central Europe makes the Nd isotope ratio a powerful tool to trace steel plants atmospheric emissions. The rare earth element (REE) distribution pattern of the steel plant's filter dust shows very specific fractionations like La and Nd enrichments which are traceable in tree barks over a distance of 4 km. The Pb, Sr and Nd isotope ratios not only enable the steel plant's emissions to be traced in a north-easterly direction, along the principal wind pathway but also enables the interference of this emission at 4 km NE from the steel plant with another atmospheric component originating from the Strasbourg Rhine harbour to be identified.

Use of HPLC/UPLC-spectrophotometry for detection of formazan in in vitro Reconstructed human Tissue (RhT)-based test methods employing the MTT-reduction assay to expand their applicability to strongly coloured test chemicals.

A number of in vitro test methods using Reconstructed human Tissues (RhT) are regulatory accepted for evaluation of skin corrosion/irritation. In such methods, test chemical corrosion/irritation potential is determined by measuring tissue viability using the photometric MTT-reduction assay. A known limitation of this assay is possible interference of strongly coloured test chemicals with measurement of formazan by absorbance (OD). To address this, Cosmetics Europe evaluated use of HPLC/UPLC-spectrophotometry as an alternative formazan measurement system. Using the approach recommended by the FDA guidance for validation of bio-analytical methods, three independent laboratories established and qualified their HPLC/UPLC-spectrophotometry systems to reproducibly measure formazan from tissue extracts. Up to 26 chemicals were then tested in RhT test systems for eye/skin irritation and skin corrosion. Results support that: (1) HPLC/UPLC-spectrophotometry formazan measurement is highly reproducible; (2) formazan measurement by HPLC/UPLC-spectrophotometry and OD gave almost identical tissue viabilities for test chemicals not exhibiting colour interference nor direct MTT reduction; (3) independent of the test system used, HPLC/UPLC-spectrophotometry can measure formazan for strongly coloured test chemicals when this is not possible by absorbance only. It is therefore recommended that HPLC/UPLC-spectrophotometry to measure formazan be included in the procedures of in vitro RhT-based test methods, irrespective of the test system used and the toxicity endpoint evaluated to extend the applicability of these test methods to strongly coloured chemicals.

Preclinical and clinical evaluation of topical acid products for skin tumors.

Distinct differences between topical acid preparations can be detected by simple preclinical and clinical pharmacologic models designed to evaluate potential utility in the treatment of superficial skin tumors. The models distinguish a tissue-dissolving (ulcerating) effect from a tissue-fixation (mummifying) effect, as reflected by a distinct and lasting discoloration of hair in vitro or the skin surface in vivo. Double-blind clinical comparison of the response to different preparations of matched pairs of small superficial skin tumors in 33 subjects demonstrated for greater utility for nitric acid preparations of appropriate strength (6 to 7N), with added oxidizable organic acids, over the mineral acid alone. The nitrate reduction products generated in such preparations markedly speed up discoloration in the models and apparently contribute to the improved clinical utility of the topical treatment by enhancing the speed and intensity of tissue fixation, but not tissue erosion. The architecture of lesions eradicated by such mixtures is generally adequately preserved for histologic diagnosis of the extruded tissue.

Diversity of the transferrin-binding protein Tbp2 of Neisseria meningitidis.

In order to investigate the genetic basis for the observed polymorphism amongst meningococcal transferrin-binding proteins, Tbp2, the corresponding genes of different Neisseria meningitidis strains were cloned and sequenced. Comparison of the deduced amino acid (aa) sequences indicated that the Tbp2 were 76.6 to 81.2% homologous. Several stretches of aa have been found repeated both in the N- and C-terminal halves of the molecule.

Cloning and characterization of Neisseria meningitidis genes encoding the transferrin-binding proteins Tbp1 and Tbp2.

Genes tbp1 and tbp2, encoding the transferrin-binding proteins Tbp1 and Tbp2, have been isolated from two strains of Neisseria meningitidis. The tbp2 and tbp1 open reading frames are tandemly arranged in the genome with an 87-bp intergenic region, and the DNA region upstream from the tbp2-coding sequence contains domains homologous to Escherichia coli promoter consensus motives. Nucleotide sequence analysis suggests the existence of a Tbp1 precursor carrying an N-terminal signal peptide with a peptidase I cleavage site and of a Tbp2 precursor with N-terminal homology to lipoproteins, including a peptidase II cleavage site. Comparison of the Tbp1 deduced amino acid (aa) sequences from both strains showed about 76% aa homology, while those of Tbp2 revealed only about 47% aa homology. These comparisons should be extended to other Neisseria strains in order to evaluate further this genetic divergence further.

Gradual versus rapid dawn simulation treatment of winter depression.

BACKGROUND: Bright light therapy has been shown to be effective in treating winter depression. Dawn simulation, a low-illuminance light that gradually increases in intensity while the person sleeps, decreased depression in an uncontrolled study. The present study compares a gradual dawn signal with a hypothesized placebo condition, a rapid dawn signal. METHOD: In a 4-week, randomized crossover design, nine patients with winter depression were treated with a gradual, 2.5-hour dawn simulation for 1 week and a rapid, 10-minute dawn simulation for 1 week. Both dawns had a maximum illuminance of 275 lux. At the end of each baseline week and treatment week, blind raters assessed the level of depression. RESULTS: Hamilton Rating Scale for Depression mean scores significantly decreased for both the gradual dawn (17.7 to 5.9, p < .05) and the rapid dawn (17.2 to 7.0, p < .05) condition. The improvement was similar for both treatments. Early morning awakening was significantly (p < .01) more common with the gradual dawn (7/9) than with the rapid dawn (1/9) condition. CONCLUSION: Depression decreased under both dawn simulations. Because the degree of improvement was similar, a placebo effect rather than the efficacy of dawn simulation might explain the results. However, a mere placebo effect is an unlikely explanation. The degree of improvement was similar to that shown in studies of bright light therapy and clearly superior to previous "placebo" control conditions. The side effects from the gradual dawn may have obscured a potential superiority of the gradual dawn over the rapid dawn.

Factors affecting the development of skin cancer after scalp irradiation.

A nested case control study of persons who developed skin cancer after scalp irradiation in childhood revealed two risk factors for the appearance of radiation-induced skin cancer: (a) an apparently higher radiation dose delivered inadvertently, manifested by a higher prevalence of alopecia and radiation dermatitis (RR = 3.4; CI 1.3-8.8); (b) a more frequent exposure to the sun, manifested by summer sunbathing (RR = 2.6; CI 1.1-6.1). These findings may have certain implications with regard to the understanding of radiation-induced cancer, after low-dose radiation exposure, in general.

Identification of two major families of transferrin receptors among Neisseria meningitidis strains based on antigenic and genomic features.

The transferrin receptor or transferrin-binding proteins (Tbps) of 50 strains of Neisseria meningitidis belonging to different serogroups were examined by Western blotting using two rabbit antisera raised against Tbp purified from N. meningitidis strains B16B6 and M982. On the basis of the reactivity of Tbp2 with the antisera two patterns were observed and allowed the classification of 74% of the strains in group I (M982-like strains) and 26% in group II (B16B6-like strains). Southern blot analysis was performed on the genomic DNA of 16 meningococcal strains and showed that under stringent conditions, the tbp2 probes were specific for each group identified. Both immunological and genomic analyses have led to the identification within N. meningitidis strains of two major families distinguished on the basis of the characteristics of Tbp2 molecules, independently of serogroup, type or subtype.

Variable sequences in a mosaic-like domain of meningococcal tbp2 encode immunoreactive epitopes.

Transferrin-binding proteins from Neisseria meningitidis vary among different isolates. We have identified and studied a hypervariable region adjacent to the carboxyl-end of the transferrin-binding domain of the Tbp2 molecule. The tbp2 genes from six strains of N. meningitidis were cloned and sequenced in this particular region. Sequence analysis of these regions along with five other sequences available from pathogenic Neisseria showed a common organisation of seven highly variable nucleotide stretches interspersed with six conserved nucleotide stretches. The variable regions correlated with the location of immunoreactive epitopes in polyclonal antisera raised to transferrin-binding proteins identified by peptide pin technology. Sequence analysis suggested a mosaic-like organisation of the tbp2 genes. Taken together, these data suggest that the antigenic variation in this part of the protein may result from a strong host immune pressure.

Both the full-length and the N-terminal domain of the meningococcal transferrin-binding protein B discriminate between human iron-loaded and apo-transferrin.

We have readdressed the ability of the transferrin-binding protein B (TbpB) from Neisseria meningitidis to discriminate between the iron-loaded and the iron-free human transferrin (hTf) by using the BIAcore technology, a powerful experimental technique for the observation of direct interactions between a receptor and its ligands, without the use of labels. Recombinant full-length TbpB from five N. meningitidis strains were produced and purified from Escherichia coli as fusion proteins. They showed a preference for the binding to iron-loaded hTf. As for the full-length molecule, we have demonstrated that the minimal N-terminal hTf binding domain of meningococcal TbpB from B16B6 and M982 strains was able to discriminate between both hTf forms.

Multiple clear cell acanthomas.

Clear cell acanthoma is usually a solitary benign epidermal tumor. Multiple lesions are rarely encountered, and only 11 such cases could be found in the literature. In all cases, the lesions were limited to the lower extremities. A few of the patients have had ichthyosis and/or varicose veins. We describe a 12th patient who, in addition to leg lesions, had lesions on the trunk and associated dry skin.

Modification of the rat aortic wall during ageing; possible relation with decrease of peptidergic innervation.

Structural changes of the male rat aorta were followed from birth to old age in male and female rats. In males, the vessel media width and area progressively increase concomitantly with a decrease of nuclei density during ageing, suggesting an hypertrophy of the smooth muscle cells. These correlations were however not evidenced in females. TUNEL-positive cells were found in media of 4 and 6 months in both sexes, mainly on the luminal side and in the adventitia. When biochemical markers were investigated with immunohistochemistry, media was uniformly stained by the anti-vimentin and anti-alpha-smooth actin at all stages investigated. On the contrary, the surface of media stained with anti-desmin decreased during ageing, especially on the luminal side. As observed with electron microscopy, with ageing the endothelium is replaced by small cells with pseudopodia adhering to the vestigial elastic lamina and infiltrating into the extracellular matrix left after the disappearance of smooth muscle cells. In addition, in the older rats (25-29 months) the elastic laminae are completely disorganised. Hypertrophy of the smooth muscle cells was confirmed by this approach. In parallel to this study, perivascular peptidergic innervation was stained with antibodies against calcitonin gene-related peptide (CGRP), substance P (SP), neuropeptide Y (NPY), and vasoactive intestinal polypeptide (VIP) at different ages during the whole life of rats. These peptides are present in stages younger than 6 months, then gradually disappear. In one year animals and older, the peptidergic innervation has totally disappeared. We discuss the possible role of peptidergic innervation in the control of the vessel wall cellular stability during ageing.

Chemical composition of fogwater in an urban area: Strasbourg (France).

To investigate the acidity and to identify the predominant compounds, this work presents the chemical analysis of 18 fogwater samples collected during the year 1991 in Strasbourg, in the east of France. For each fog event, two droplet size categories (2-6 microm and 5-8 microm) have been separately collected and 16 ionic components have been analysed. These two fraction sizes were chosen because they correspond approximately to the size range that can penetrate the human lung and they may have possible health effects. The dominant species were NH4+, NO3-, SO4(2-) and Cl-, with a maximum level of 12,640, 17,270, 21,620 and 13,540 microeq litre(-1), respectively. For most of the fog events the highest concentrations of all analysed species were observed in the 2-6 microm droplets. pH values ranged between 2.79 and 5.70 and the fogwater acidity was governed by three strong acids, H2SO4, HNO3 and HCl and was partially neutralised by NH3 and probably by the presence of CaCO3 in the 'loess', which is the major constituent of soils in the upper Rhine valley. In other respects the acetate/formate ratio (methanoate/ethanoate), generally lower than 1, indicates an important pollution due to automobile exhaust, although the Pb concentrations are moderate due to the general use of unleaded gasoline in France since 1989.