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Biomedical subjects

G Schepers

Publications and source records attributed to G Schepers.

At least 19 recordsLinked to original sources

First laser-controlled antihydrogen production.

Lasers are used for the first time to control the production of antihydrogen (H ). Sequential, resonant charge exchange collisions are involved in a method that is very different than the only other method used so far-producing slow H during positron cooling of antiprotons in a nested Penning trap. Two attractive features are that the laser frequencies determine the H binding energy, and that the production of extremely cold H should be possible in principle-likely close to what is needed for confinement in a trap, as needed for precise laser spectroscopy.

Journal Article↗

First measurement of the velocity of slow antihydrogen atoms.

The speed of antihydrogen atoms is deduced from the fraction that passes through an oscillating electric field without ionizing. The weakly bound atoms used for this first demonstration travel about 20 times more rapidly than the average thermal speed of the antiprotons from which they form, if these are in thermal equilibrium with their 4.2 K container. The method should be applicable to much more deeply bound states, which may well be moving more slowly, and should aid the quest to lower the speed of the atoms as required if they are to be trapped for precise spectroscopy.

Journal Article↗

Driven production of cold antihydrogen and the first measured distribution of antihydrogen states.

Cold antihydrogen is produced when antiprotons are repeatedly driven into collisions with cold positrons within a nested Penning trap. Efficient antihydrogen production takes place during many cycles of positron cooling of antiprotons. A first measurement of a distribution of antihydrogen states is made using a preionizing electric field between separated production and detection regions. Surviving antihydrogen is stripped in an ionization well that captures and stores the freed antiproton for background-free detection.

Journal Article↗

Background-free observation of cold antihydrogen with field-ionization analysis of its states.

A background-free observation of cold antihydrogen atoms is made using field ionization followed by antiproton storage, a detection method that provides the first experimental information about antihydrogen atomic states. More antihydrogen atoms can be field ionized in an hour than all the antimatter atoms that have been previously reported, and the production rate per incident high energy antiproton is higher than ever observed. The high rate and the high Rydberg states suggest that the antihydrogen is formed via three-body recombination.

Journal Article↗

Hybridization between "six-membered" nucleic acids: RNA as a universal information system.

Within the polyA:polyT recognition system, cross-pairing between several nucleic acids with a phosphorylated six-membered carbohydrate (mimic) as repeating unit in the backbone structure has been observed. All investigated nucleic acids (except for beta-homo-DNA) hybridize with RNA, leaving RNA as a versatile biopolymer for informational transfer. [reaction: see text]

Nucleic Acid Conformation↗

Improved hybridisation potential of oligonucleotides comprising O-methylated anhydrohexitol nucleoside congeners.

The hybridising potential of anhydrohexitol nucleoside analogues (HNAs) is well documented, but tedious synthesis of the monomers hampers their development. In a search for better analogues, the synthesis of two new methylated anhydrohexitol congeners 1 and 2 was accomplished and the physico-chemical properties of their respective oligomers were evaluated. Generally, oligonucleotides (ONs) containing the 3'-O-methyl derivative 1 showed a small increase in thermal stability towards complementary sequences as compared to HNA. Compared to the altritol modification, 3'-O-methylation seems to cause a small decrease in thermal stability of duplexes, especially when targeting RNA. These results suggest the possibility of derivatisation of the 3'-hydroxyl group of altritol-containing congeners without significantly affecting the thermal stability of the duplexes. The methyl glycosidic analogues 2 likewise increased the affinity for RNA in comparison with well-known HNA, while at the same time being economically more favorable monomers. However, homopolymers of 2 displayed self-pairing, but not so homopolymers of 1. Upon incorporation of the hexitols within RNA sequences in an effort to induce a beneficial pre-organised structure, the positive effect of the 3'-O-methyl derivative 1 proved larger than that of 2.

Methylation↗

Hemoglobin adducts in rats chronically exposed to room-aged cigarette sidestream smoke and diesel engine exhaust.

Under controlled conditions with exaggerated concentrations of environmental aerosols, the biologically effective dose markers suggested in the literature as being specific for ETS (i.e., HPB Hb adducts for TSNA exposure) and DEE (i.e., l-aminopyrene Hb adducts for l-nitropyrene exposure) did not respond. A slight but dose-dependent increase in 4-ABP Hb adduct levels was seen in RASS-exposed rats.

Animals↗

Mouse Sox8 is located between, not within,the t-complex deletions t(w18) and t(h20) on chromosome 17.

The SOX family of developmental transcription factors is known to play critical roles in cell lineage specification, fate determination and differentiation during development in diverse phyla. Their importance is underscored by their involvement in a number of human diseases and mouse mutants, and by targeted mutation in mice. SOX8 is broadly expressed during development and is located on human chromosome 16p and within the t-complex on mouse chromosome 17, in the vicinity of two mutations t(w18) and t(h20). Here we analyse mutant genomic DNA to show that the Sox8 gene locus lies outside the deletion regions of both t(w18) and t(h20) and between these deletions. These data exclude Sox8 from contributing to the t(w18) and t(h20) phenotypes, and provide an additional marker for structural characterization of this complex genomic region.

Animals↗

Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators.

Members of the SOX family of transcription factors are found throughout the animal kingdom, are characterized by the presence of a DNA-binding HMG domain, and are involved in a diverse range of developmental processes. Previous attempts to group SOX genes and deduce their structural, functional, and evolutionary relationships have relied largely on complete or partial HMG box sequence of a limited number of genes. In this study, we have used complete HMG domain sequence, full-length protein structure, and gene organization data to study the pattern of evolution within the family. For the first time, a substantial number of invertebrate SOX sequences have been included in the analysis. We find support for subdivision of the family into groups A-H, as has been suggested in some previous studies, and for the assignment of two new groups, I and J. For vertebrate genes, it appears that relatedness as suggested by HMG domain sequence is congruent with relatedness as indicated by overall structure of the full-length protein and intron-exon structure of the genes. Most of the SOX groups identified in vertebrates were represented by a single SOX sequence in each invertebrate species studied. We have named anonymous sequences and, where appropriate, have suggested systematic names for some previously identified sequences. In addition, we identify an HMG domain signature motif which may be considered representative of the SOX family. Based on our data, we propose a robust phylogeny of SOX genes that reflects their evolutionary history in metazoans.

Amino Acid Sequence↗

Base pairing of anhydrohexitol nucleosides with 2,6-diaminopurine, 5-methylcytosine and uracil asbase moiety.

Hexitol nucleic acids (HNAs) with modified bases (5-methylcytosine, 2,6-diaminopurine or uracil) were synthesized. The introduction of the 5-methylcytosine base demonstrates that N -benzoylated 5-methylcytosyl-hexitol occurs as the imino tautomer. The base pairing systems (G:CMe, U:D, T:D and U:A) obey Watson-Crick rules. Substituting hT for hU, hCMefor hC and hD for hA generally leads to increased duplex stability. In a single case, replacement of hC by hCMedid not result in duplex stabilization. This sequence-specific effect could be explained by the geometry of the model duplex used for carrying out the thermal stability study. Generally, polypurine HNA sequences give more stable duplexes with their RNA complement than polypyrimidine HNA sequences. This observation supports the hypothesis that, besides changes in stacking pattern, the difference in conformational stress between purine and pyrimidine nucleosides may contribute to duplex stability. Introduction of hCMeand hD in HNA sequences further increases the potential of HNA to function as a steric blocking agent.

2-Aminopurine↗

5'-hydroxycotinine-N-oxide, a new nicotine metabolite isolated from rat urine.

1. 5'-Hydroxycotinine-N-oxide, 5-(3-pyridyl-N-oxide)-5-hydroxy-1-methyl-pyrrolidone-2, was identified as a new in vivo metabolite of nicotine. 2. The new metabolite was isolated from the urine of rats treated with S-nicotine and characterized using chemical and spectrometric methods. 3. 5'-Hydroxycotinine-N-oxide was synthesized and characterized by MS and by infrared as well as 1H- and 13C-NMR spectroscopy. 4. Identity of the new metabolite with synthetic 5'-hydroxycotinine-N-oxide was demonstrated by comparing the MS and 1H-NMR spectroscopy data as well as by co-chromatography of a spiked urine sample.

Animals↗

Evidence for peroxynitrite as an oxidative stress-inducing compound of aqueous cigarette smoke fractions.

Previous studies have shown that exposure of Swiss 3T3 cells to mainstream cigarette smoke (CS) trapped in phosphate-buffered saline (smoke-bubbled PBS) resulted in the expression of stress response genes, i.e. haem oxygenase and c-fos, partial inhibition of protein phosphatases 1 and 2A, as well as partial depletion of the cellular glutathione (GSH) pool. Using c-fos gene expression in Swiss 3T3 cells as an indicator for a cellular response against oxidative stress, the following observations are consistent with peroxynitrite as an active principal formed by CS in aqueous solutions: (i) sustained c-fos expression was obtained for smoke-bubbled PBS, peroxynitrite itself and a compound known to stoichiometrically release superoxide and nitric oxide (NO) (3-morpholino-sydnonimine, SIN-1); (ii) c-fos expression in cells exposed to aqueous smoke fractions was inhibited by either the superoxide-scavenging enzyme superoxide dismutase (SOD), in combination with catalase, or the NO-scavenger oxyhaemoglobin (HbO2); and (iii) activation of guanylate cyclase in rat lung cells was observed only when bubbling was performed with filtered smoke and with whole smoke in the presence of SOD/catalase. These results are consistent with a rapid NO-consuming reaction coupled with superoxide-generating properties of the particulate phase of CS. Moreover, (iv) the half-life of the c-fos-inducing activity in smoke-bubbled PBS was found to be <1 h which can be explained by a sustained peroxynitrite formation. Finally, depletion of intracellular thiol levels by smoke-bubbled PBS appears to favour the activation of a redox-sensitive component of the c-fos-inducing pathway.

3T3 Cells↗

An acyclic 5-nitroindazole nucleoside analogue as ambiguous nucleoside.

Acyclic nucleoside analogues with carboxamido- or nitro-substituted heterocyclic bases have been evaluated for their possible use as universal bases in oligodeoxynucleotides. The acyclic moiety endows the constructs with enough flexibility to allow good base stacking. The 5-nitroindazole analogue afforded the most stable duplexes among the acyclic derivatives with the least spread in Tm versus the four natural bases. In spite of the acyclic moiety, stabilities are comparable with those of duplexes incorporating the recently described 5-nitroindole nucleoside analogue, but considerably exceed those for the 3-nitropyrrole analogue.

Base Sequence↗

Nicotine and cotinine accumulation in pigmented and unpigmented rat hair.

This study was performed to assess the contribution of systemic and external uptake to nicotine accumulation in hair. The systemic nicotine uptake in hair was determined in pigmented rats (Brown Norway) and albino rats (Sprague-Dawley) after subcutaneous administration of 3 doses of nicotine with osmotic minipumps [5, 10, and 20 mg/(kg x day) for 3 weeks], the highest dose also following metabolic enzyme induction. The external nicotine uptake was determined in cut hair of both strains after exposure to room-aged cigarette sidestream smoke, a surrogate for environmental tobacco smoke (nicotine concentration: 5 micrograms/liter for 1, 2, and 3 weeks). Nicotine and its metabolite cotinine were determined using capillary GC after complete alkaline digestion of the hair sample and solvent extraction. Systemic uptake: Nicotine and cotinine concentrations in hair were dose-dependent and correlated with plasma concentrations. The nicotine concentration was approximately 20 times higher in pigmented than in unpigmented hair. The cotinine concentration was approximately 10 times lower than the nicotine concentration in pigmented hair. After enzyme induction before administration, nicotine and cotinine concentrations in hair were significantly reduced in parallel to the reduced plasma concentrations, showing the influence of metabolism. External uptake: Nicotine was found in the hair of both strains, the concentration in pigmented hair being a factor of 1.5 higher than in unpigmented hair. Thus, hair pigmentation had a major influence on systemic uptake in hair and a minor influence on external uptake in hair.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

High-performance liquid chromatographic determination of nicotine and its urinary metabolites via their 1,3-diethyl-2-thiobarbituric acid derivatives.

The 1,3-diethyl-2-thiobarbituric acid (DETBA) assay for nicotine metabolites has been improved so that it can be used to determine the concentrations of nicotine and up to 12 metabolites in the urine of humans and laboratory animals, including phase 2 metabolites. The products of beta-glucuronidase cleavage found in human urine were mainly trans-3'-hydroxycotinine, cotinine, and a small amount of nicotine. Following isolation, spectroscopic analyses showed the structure of the nicotine DETBA derivative to be the one-to-one ring-opening product of DEBTA and the cyanopyridinium salt of nicotine.

Animals↗

Cotinine determination by immunoassays may be influenced by other nicotine metabolites.

Polyclonal rabbit anticotinine antiserum, which can be used for biomonitoring nicotine uptake by the determination of cotinine in body fluids, was checked by a competitive ELISA for its cross-reactivity with nine nicotine metabolites. The highest percentage of relative cross-reactivity (about 30%) was observed with trans-3'-hydroxycotinine, a metabolite which is known to be excreted in 3-fold higher amounts than cotinine in the urine of human smokers. Therefore, it is possible that cotinine determinations performed by immunochemical methods--especially in urine--may yield overestimated cotinine concentrations.

Animals↗