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Biomedical subjects

S Nehls

Publications and source records attributed to S Nehls.

7 recordsLinked to original sources

Detection and imaging of atmospheric radio flashes from cosmic ray air showers.

The nature of ultrahigh-energy cosmic rays (UHECRs) at energies >10(20) eV remains a mystery. They are likely to be of extragalactic origin, but should be absorbed within approximately 50 Mpc through interactions with the cosmic microwave background. As there are no sufficiently powerful accelerators within this distance from the Galaxy, explanations for UHECRs range from unusual astrophysical sources to exotic string physics. Also unclear is whether UHECRs consist of protons, heavy nuclei, neutrinos or gamma-rays. To resolve these questions, larger detectors with higher duty cycles and which combine multiple detection techniques are needed. Radio emission from UHECRs, on the other hand, is unaffected by attenuation, has a high duty cycle, gives calorimetric measurements and provides high directional accuracy. Here we report the detection of radio flashes from cosmic-ray air showers using low-cost digital radio receivers. We show that the radiation can be understood in terms of the geosynchrotron effect. Our results show that it should be possible to determine the nature and composition of UHECRs with combined radio and particle detectors, and to detect the ultrahigh-energy neutrinos expected from flavour mixing.

Journal Article↗

Multibiomarker responses in fish from the Moselle River (France).

The response of wild fish to pollutants was studied using two biomarkers in chub (Leuciscus cephalus) at five stations in the Moselle River (France) in 1998 and in 1999. The induction of cytochrome P450 1A was quantified by the ethoxyresorufin O-deethylase (EROD) activity in the liver and the level of DNA single-strand breaks was determined in erythrocytes using the comet assay. EROD activity was observed to be up to 10-fold induced in both males and females from the downstream stations in comparison to the fish from the upstream station. Levels of DNA damage did not parallel EROD induction. Chemical analyses did not clearly explain the responses of the studied biomarkers, confirming the great difficulty in relating chemical and biological information in the field. This study confirms the difficulty in assessing the biological effects of mixtures of pollutants and points out the usefulness of a large array of biomarkers.

Animals↗

Detection of DNA damage in two cell lines from rainbow trout, RTG-2 and RTL-W1, using the comet assay.

Screening methods to indicate the genotoxic potential of individual chemicals or environmental mixtures rely mainly on short-term bacterial tests. Differences in the genotoxic response of prokaryotic and eukaryotic cells necessitate the development of nonbacterial screening assays. A promising approach for this purpose could be the comet (single-cell gel electrophoresis) assay performed with fish cells in vitro. In the present study, we evaluated the comet assay with two different fish cell lines from rainbow trout (Oncorhyhnchus mykiss), the fibroblast-like RTG-2 cell line established from gonad tissue, and the epitheloid RTL-W1 cell line established from liver tissue. The cells were exposed in vitro during 2 hr to the genotoxins, 4-nitroquinoline-1-oxide (NQO), and benzo(a)pyrene (BaP), as well as to environmental samples. The LOEC values for NQO were similar in both cell lines, whereas for BaP, the RTL-W1 cells were found to be more sensitive than the RTG-2 cells. The slopes of the concentration-response curves of the two test compounds differed between the two cell lines, with RTG-2 cells showing a steeper slope for NQO, and RTL-W1 cells showing a steeper slope for BaP. When exposed to environmental samples from a remediation site, the RTL-W1 cell line, but not the RTG-2 cell line, indicated a genotoxic potential of the samples. The differences in the genotoxic response pattern of the two cell lines could be only partly explained in relation to metabolic enzymes, cytochrome P4501A, glutathione-S-transferase, and xenobiotic reductase. The findings of this study demonstrate that the comet assay with fish cell lines is suitable as in vitro screening assay in environmental genotoxicity testing, but the choice of test cell line may be critical.

Animals↗

Dynamics and retention of misfolded proteins in native ER membranes.

When co-translationally inserted into endoplasmic reticulum (ER) membranes, newly synthesized proteins encounter the lumenal environment of the ER, which contains chaperone proteins that facilitate the folding reactions necessary for protein oligomerization, maturation and export from the ER. Here we show, using a temperature-sensitive variant of vesicular stomatitis virus G protein tagged with green fluorescent protein (VSVG-GFP), and fluorescence recovery after photobleaching (FRAP), the dynamics of association of folded and misfolded VSVG complexes with ER chaperones. We also investigate the potential mechanisms underlying protein retention in the ER. Misfolded VSVG-GFP complexes at 40 degrees C are highly mobile in ER membranes and do not reside in post-ER compartments, indicating that they are not retained in the ER by immobilization or retrieval mechanisms. These complexes are immobilized in ATP-depleted or tunicamycin-treated cells, in which VSVG-chaperone interactions are no longer dynamic. These results provide insight into the mechanisms of protein retention in the ER and the dynamics of protein-folding complexes in native ER membranes.

Adenosine Triphosphate↗

Relationship between estrogen structure and conformational changes in estrogen receptor/DNA complexes.

The effect of estrogen structure on the conformation of the complex formed with estrogen receptor (ER) and the consensus estrogen response element (EREc) has been examined with gel mobility shift assay. Proteins in MCF-7 cell extracts formed three distinct complexes with ERE. Only the slowest moving complex contained ER as indicated by binding with anti-ER antibodies H222 and D547. This ER-ERE complex displayed increased electrophoretic mobility when formed in the presence of estradiol (E2) and bound radiolabeled 16 alpha-iodoestradiol. The antiestrogen ICI 164,384 decreased the mobility of the ER-ERE complex and blocked the effect of E2. The results reported here indicate that the position and location of hydroxyl groups on the estratriene nucleus is an important factor in determining the mobility of ER-EREc (or a variant ERE) in gel shift assays. The ability of E2 analogs to cause conformational changes detectable as altered mobility was not directly related either to their binding affinity for ER or to their ability to activate E2 responsive genes. Although several dihydroxyestrogens (estradiol-16 alpha, 1- and 2-hydroxyestratrien-17 beta-ol) caused an increase in the mobility of the ER-EREc, other ligands (estradiol-17 alpha, 4-hydroxyestratriene-17 beta-ol, 3-hydroxy estratriene, estratrien-17 beta-ol and 5-androsten-3 beta, 17 beta-diol) with a capacity for activating at least some E2 responsive genes in MCF-7 cells had little or no effect. On the basis of these and previously published results, it can be concluded that specific structure features of estrogens are responsible for conformational changes of ER-ERE complexes detectable in gel-shift assays. Furthermore, the identified structural characteristics of the ligand which are required for gel-shift are not the same as those previously reported to be essential for stimulation of transcriptional activity of ER.

Base Sequence↗