Biologic markers in ethylene oxide-exposed workers and controls

Ethylene oxide (EtO) is an alkylating agent and a model direct-acting mutagen and carcinogen. This study has evaluated a panel of biologic markers including EtO-hemoglobin adducts (EtO-Hb), sister-chromatid exchanges (SCEs), micronuclei, chromosomal aberrations (CAs), DNA single-strand breaks (SSB) and an index of DNA repair (ratio of UDS to NA-AAF-DNA binding) in the peripheral blood cells of 34 workers at a sterilization unit of a large university hospital and 23 controls working in the university library. Comprehensive environmental histories were obtained on each subject including detailed occupational and smoking histories. Industrial hygiene data obtained prior to the study and personal monitoring during the 8 years preceding the study showed that workers were subject to low-level exposure near or below the current Occupational Safety and Health Administration (OSHA) standard of 1 ppm (TWA). Personal monitoring data obtained during 2 weeks prior to blood sampling were uniformly less than 0.3 ppm (TWA). After adjusting for smoking, EtO workplace exposure was significantly (p less than 0.001) associated with EtO-Hb (a carcinogen-protein adduct) and 2 measures of SCEs [the average number of SCEs/cell (SCE50) and the number of high frequency cells (SCEHFC)]. There was an apparent suppression of DNA repair capacity in EtO-exposed individuals as measured by the DNA repair index; i.e., the ratio of unscheduled DNA synthesis (UDS) and NA-AAF-DNA binding (p less than 0.01). No association of DNA repair index with smoking was found. Another important finding of this study is the highly significant correlation between EtO-Hb adduct levels and SCEHFC (p less than 0.01) and SCEs (p less than 0.02) which provides evidence of a direct link between a marker of biologically effective dose and markers of genotoxic response. In contrast, micronuclei, CAs and SSBs were not significantly elevated in the workers. The activity of the u-isoenzyme of glutathione-S-transferase (GT) was measured as a possible genetic marker of susceptibility and a modulator of biomarker formation. However, possibly because of confounding by age, no significant relationships were found between GT and any of the exposure-related markers by ANOVA or among other independent variables by regression. This study demonstrates significant effects of low-level EtO exposure, independent of smoking history, near or below 1 ppm on multiple biomarkers and suggests that the current OSHA standard may not be adequately protective. Previously described effects of smoking on EtO-Hb adducts, SCEs and SCEHFC were also seen in this study.(ABSTRACT TRUNCATED AT 400 WORDS)     

Environmental effects on variation and covariation in reproductive traits of Western Bluebirds

Summary Environmental conditions can influence the expression and correlations of phenotypic traits. I studied phenotypic plasticity in reproductive traits of Western Bluebirds breeding in northern Arizona. Data collected over 4 years on two contrasting habitats identified significant spatial and temporal variation in bluebird reproduction. Clutch size was similar over different environmental conditions whereas timing of clutch initiation, percent fledging success, and frequency of second nest attempts were flexible. Correlations between traits varied widely—often changing sign—among samples from different years or habitats. Correlations of traits with reproductive success were also dependent on environmental conditions. Variation in traits reflected behavioral responses by nesting adults to differences in time for breeding and feeding conditions. Density of trees differed between habitats and had opposing effects on these environmental variables; breeding seasons were generally longer, but feeding rates to nestlings were lower on the more open habitat. Late Spring snows delayed reproduction and increased the importance of limited time for breeding; feeding conditions were more influential following a dry Spring. This and other studies illustrate that data on phenotypic plasticity are important when evaluating the ecological and evolutionary forces underlying life histories.     

Effects of rapid changes in oxygen concentration on the respiration of carrot roots

Rates of CO₂ production and O₂ consumption from aged disks of carrot ( Daucus carota L.) root tissues were measured for 4 h after they were transferred from 21% to 0, 1, 2, 4 or 8% O₂ in gas mixtures. A transient peak in the rate of CO₂ production started 5 to 7 min after transfer to 2% or lower O₂ mixtures and peaked at 50 min. After the peaks in CO₂ production from the 0, 1 and 2% O₂ treatments and after the stable production from the 4 and 8% O₂ treatments, the rate of CO₂ production from all low O₂ treatments started to decline at 50 min, reaching stable rates by 160 to 240 min. Concentrations of lactate and ethanol that were significantly higher than the 21% O₂ controls had started to accumulate in disks between 10 and 50 min after exposure to atmospheres containing 2% or less O₂. Production of CO₂ started to increase 5 to 7 min after transfer to 0, 1 and 2% O₂, while the initial decline and then rise in pH and the accumulation of ethanol did not occur until 30 min after the change in atmosphere. Ethanol accumulation paralleled the increase in pH; first at 0.4 μmol g⁻¹ h⁻¹ from 30 to 60 min as the pH shifted from 5.97 to 6.11, and then at 0.08 μmol g⁻¹ h⁻¹ from 60 to 100 min as the pH stablized around 6.12. The peak at 50 min in CO₂ production roughly coincided with the shift from the rapid to the slow change in pH and ethanol accumulation.     

The influence of topography on the nature of humic substances in soil organic matter at a site in the Atlantic Coastal Plain of South Carolina

The effect of topography on the nature of humic substances, isolated as water soluble organic carbon (WSOC), fulvic acid (FA), and humic acid (HA) was evaluated by comparing relative proportion and chemical characteristics of these fractions in upland and bottomland Coastal Plain soils in South Carolina. The fractions were characterized by elemental analysis and¹³C cross-polarization magic angle spinning nuclear magnetic resonance (CPMAS NMR) spectroscopy. The majority of humic substances occur as humic acids, with bottomland soils having higher HA/FA ratios when compared to upland soils. We found no significant differences between upland and bottomland humic substances with respect to yields of WSOC and fulvic acids, and in the C and N content of humic and fulvic acids. Carbon-13 CPMAS NMR spectroscopy revealed that the WSOC and fulvic acid fractions were composed largely of O-alkyl-C structures with bottomland soils having higher amounts of these groups. Humic acid C distribution was similar between upland and bottomland soils and was largely composed of aromatic groups. Our results demonstrate that topography influences the formation of humic acid and the structural and chemical properties of the various humic fractions.requests for offprints     

A method for determining overall protein fold from NMR distance restraints

Summary We describe a simple method for determining the overall fold of a polypeptide chain from NOE-derived distance restraints. The method uses a reduced representation consisting of two particles per residue, and a force field containing pseudo-bond and pseudo-angle terms, an electrostatic term, but no van der Waals or hard shell repulsive terms. The method is fast and robust, requiring relatively few distance restraints to approximate the correct fold, and the correct mirror image is readily determined. The method is easily implemented using commercially available molecular modeling software.     

The sinking ark: pollution and the worldwide loss of biodiversity

Humans are making increasing demands on natural ecosystems. One recent study has concluded that our species is consuming or diverting some 40% of the net photosynthetic productivity of our planet. Many habitats are being converted to simpler systems which provide more harvestable goods to people. As a result, genetic diversity, species and whole ecosystems are disappearing; some scientists suggest that as many as 25% of the world's species could be lost in the next several decades.The sinking ark is usually characterized in terms of pollution, habitat loss, poaching, introduced species and illegal trade in wildlife products, but these are symptoms rather than causes. At a more fundamental level, many of the same factors which have enabled pollution to become such a problem have also been responsible for the loss in biodiversity; the most important factor is that the effects of pollutants on biodiversity have been considered an externality, an unintended side effect of industrial activity which brought measurable benefits to people. Development activities which have depleted biodiversity have proven profitable only because the real costs have been hidden.Keeping the ark afloat will require the Five-I Approach: investigation (learning how natural systems function); information (ensuring that the facts are available to inform decisions); incentives (using economic tools to help conserve biodiversity); integration (promoting a cross-sectoral approach to conserving biodiversity); and international support (building productive collaboration for conserving biodiversity).     

A general approach toward the design of inhibitors of serine proteinases: inhibition of human leukocyte elastase by substituted dihydrouracils

A general approach toward the rational design of potential inhibitors of serine proteinases is described. The approach is exemplified and validated through the use of appropriate heterocyclic systems in inhibiting human leukocytes elastase (HLE).     

Genomic targets of the serendipity beta and delta zinc finger proteins and their respective DNA recognition sites.

The closely related Drosophila serendipity (sry) beta (beta) and delta (delta) Cys2-His2 zinc finger proteins show partly overlapping in vitro DNA binding specificities and distinct patterns of binding sites on polytene chromosomes. Using a newly developed procedure, we identified genomic DNA targets for these two proteins. Both the sry beta and delta proteins protect an 18-22 base region from DNase I digestion within each analysed genomic binding site, that includes a 13 bp consensus sequence. The consensus recognition sites sry beta 5'-YCAGAGATGCGCA-3' and sry delta 5'-YTAGAGATGGRAA-3' thus differ by nucleotides at four out of 13 positions. They are determinant for specific binding of the sry beta and delta proteins, respectively, produced in Escherichia coli or present in Drosophila embryos. We further show that sry beta is the major (if not exclusive) Drosophila nuclear protein that specifically binds the 5'-CAGAGTGCGC-3' sequence. The identified sry beta genomic targets are all contained within single-copy DNA in euchromatic regions of the genome. Two out of the five characterized in detail map at cytological positions coincident with binding sites of the native sry beta protein on polytene chromosomes.