Microbial metabolism in surface sediments and its role in the immobilization of phosphorus in oligotrophic lake sediments

Rapid microbial metabolism and a large phosphorus uptake potential were observed in surface sediments of Lake George, New York. This sediment (termed the flocculent layer) also exhibited a phosphorus limited condition and a large reservoir of inorganic phosphorus associated with humic substances. These observations suggest that the empirically observed phosphorus retention in oligotrophic lake sediments may be promoted by a rapid cycling of phosphorus between microflora and its associated organic matter.     

In vitro micronucleus assay with Chinese hamster V79 cells - results of a collaborative study with in situ exposure to 26 chemical substances

A collaborative study with 10 participating laboratories was conducted to evaluate a test protocol for the performance of the in vitro micronucleus (MN) test using the V79 cell line with one treatment and one sampling time only. A total of 26 coded substances were tested in this study for MN-inducing properties. Three substances were tested by all 10 laboratories and 23 substances were tested by three or four laboratories in parallel. Six aneugenic, 7 clastogenic and 6 non-genotoxic chemicals were uniformly recognised as such by all laboratories. Three chemicals were tested uniformly negative by three laboratories although also clastogenic properties have been reported for these substances. Another set of three clastogenic substances showed inconsistent results and one non-clastogenic substance was found to be positive by one out of three laboratories. Within the study, the applicability of the determination of a proliferation index (PI) as an internal cytotoxicity parameter in comparison with the determination of the mitotic index (MI) was also evaluated. Both parameters were found to be useful for the interpretation of the MN test result with regard to the control of cell cycle kinetics and the mode of action for MN induction. The MN test in vitro was found to be easy to perform and its results were mainly in accordance with results from chromosomal aberration tests in vitro.     

2,4,5-Triphenylisothiazol-3 (2H)-one 1,1-dioxides as inhibitors of human leukocyte elastase

A series of substituted 2,4,5-triphenylisothiazol-3(2H)-one 1,1-dioxides 9 was synthesized and investigated as inhibitors of human leukocyte elastase (HLE). All compounds were found to inhibit HLE in a time-dependent manner and most of them exhibited kobs/[I] values > 300M(-1)s(-1). The most potent 3-oxosultam of this series was 91 (kobs/[I] = 2440 M(-1)s(-1)). Kinetic investigations performed with 9g and different substrate concentrations did not allow to clearly distinguish between a competitive or noncompetitive mode of inhibition. A more complex interaction is supported by the failure of a linear dependency of kobs values on the inhibitor concentration.     

Predicting spatial occurrence of beetles and pseudoscorpions in hollow oaks in southeastern Sweden

We modelled presence/absence per tree of beetles and pseudoscorpions living in tree hollows in relation to trunk circumference, habitat openness, and connectivity (= density of hollow oaks in the surrounding area), using data from 281 oaks. The presence/absence models were then used to predict species’ occurrences in a county (11,600 km²) in southeastern Sweden. For eight of the nine species, the most parsimonious occupancy model included a positive relationship with connectivity and at least one tree characteristic. Occupancy underestimates from occurrence records—the ratio of the area of occupancy based on our predictive model to the area of occupancy based on occurrence records—varied between 3 and 83 among species when using occurrence records up to 1993, with significantly larger underestimates for smaller beetle species. Today (after extensive surveys), underestimation has decreased to 1.3–25, confirming that calculations solely based on species occurrence records greatly underestimate the area of occupancy. We suggest this should be taken into account to a greater extent and in a clearer way than today when constructing red lists. The radius of the connectivity measure that generated the best fit varied between 135 and 2,857 m among species, with longer distances for more threatened species. Consequently, preservation of the most threatened species (Elater ferrugineus and Tenebrio opacus) requires conservation efforts at larger spatial scales than required to protect Osmoderma eremita, which frequently has been used as an indicator and umbrella species.     

Investigation of the mode of binding of a novel series of N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamides to the hepatitis C virus polymerase

Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.