Life-shortening and disease incidence in C57Bl mice after single and fractionated gamma and high-energy neutron exposure

C57Bl Cnb mice were exposed to single or fractionated d(50)+Be neutrons or 137Cs gamma-ray exposure at 12 weeks of age and were followed for life-shortening and disease incidence. The data were analyzed by the Kaplan-Meier procedure using as criteria cause of death and possible cause of death. Individual groups were compared by a modified Wilcoxon test according to Hoel and Walburg, and entire sets of different doses from one radiation schedule were evaluated by the procedure of Peto and by the Cox proportional hazard model. No significant difference was found in life-shortening of C57Bl mice between a single gamma and neutron exposure. Gamma fractionation was clearly less effective in reducing survival time than a single exposure. On the contrary, fractionation of neutrons was slightly although not significantly more effective in reducing life span than a single exposure. Life-shortening appeared to be a linear function of dose in all groups studied. The data on causes of death show that malignant tumors, particularly leukemias including thymic lymphoma, and noncancerous late degenerative changes in lung were the principal cause of life-shortening after a high single gamma exposure. Exposure delivered in 8 fractions 3 h apart was more effective in causing leukemias and all carcinomas and sarcomas than one delivered in 10 fractions 24 h apart or in a single session. Following a single neutron exposure, leukemias and all carcinomas and sarcomas appeared to increase somewhat more rapidly with dose than after gamma irradiation. No significant difference in the incidence of leukemias and all carcinomas and sarcomas was noted between a single and a fractionated neutron exposure.     

R 76713, a new specific non-steroidal aromatase inhibitor

The effects of R 76713, a new triazole derivative, on rat ovarian, testicular and adrenal steroidogenesis were investigated both in vitro and in vivo. In vitro R 76713 is a very potent inhibitor of the aromatase enzyme in rat granulosa cells, showing an IC50-value of 3.0 +/- 0.2 nM. The compound is about 1000 times more active than aminoglutethimide which shows an IC50-value of 3900 +/- 2800 nM in the same system. R 76713 is also a highly selective aromatase inhibitor. In cultures of ovarian, testicular and adrenal cells, formation of progesterone, androgens and glucocorticoids was only affected by drug concentrations higher than 1 microM. In vivo, single oral drug doses of 0.05 mg/kg lowered plasma estradiol levels of PMSG-primed female rats by more than 90%. An ED50-value of 0.005 mg/kg could be calculated. A single oral dose of 1 mg/kg suppressed plasma estradiol levels almost completely for 24 h. A dose of 0.1 mg/kg lowered plasma estradiol by more than 90% for 8 h. In vivo, R 76713 also showed a highly selective profile. In LHRH/ACTH-injected rats, plasma levels of testicular and adrenal steroids remained unchanged after administration of a drug dose of 20 mg/kg. R 76713 at drug concentrations of 10 microM, showed no interaction in vitro with estrogen-, progestin-, androgen- and glucocorticoid-receptors. Given orally at 20 mg/kg for 3 days the compound also showed no estrogen or androgen agonistic or antagonistic effects.     

Labor induction with prostaglandin F2α. Influence on psychomotor evolution of the child in the first 30 months

The long-term effects of elective induction of labor at term by amniotomy and the intravenous infusion of prostaglandin F2α were studied in 40 children. No untoward effect of this procedure on the psychomotor development of the children during the first 30 months could be demonstrated.     

Turgor pressure sensing in plant cell membranes

Experimental evidence is reviewed which shows that the cell membrane is compressible by both mechanical and electrical forces. Calculations are given which show that significant changes in the thickness of cell membranes can occur as a result of (a) direct compression due to the turgor pressure; (b) indirect effects due to the stretching of the cell wall; and (c) the stresses induced by the electric field in the membrane.     

Environmentally and behaviourally mediated co‐occurrence of functional traits in bird communities of tropical forest fragments

Two major theories of community assembly – based on the assumption of ‘limiting similarity’ or ‘habitat filtering’, respectively – predict contrasting patterns in the spatial arrangement of functional traits. Previous analyses have made progress in testing these predictions and identifying underlying processes, but have also pointed to theoretical as well as methodological shortcomings. Here we applied a recently developed methodology for spatially explicit analysis of phylogenetic meta‐community structure to study the pattern of co‐occurrence of functional traits in Afrotropical and Neotropical bird species inhabiting forest fragments. Focusing separately on locomotory, dietary, and dispersal traits, we tested whether environmental filtering causes spatial clustering, or competition leads to spatial segregation as predicted by limiting similarity theory. We detected significant segregation of species co‐occurrences in African fragments, but not in the Neotropical ones. Interspecific competition had a higher impact on trait co‐occurrence than filter effects, yet no single functional trait was able to explain the observed degree of spatial segregation among species. Despite high regional variability spanning from spatial segregation to aggregation, we found a consistent tendency for a clustered spatial patterning of functional traits among communities in fragmented landscapes, particularly in non‐territorial species. Overall, we show that behavioural effects, such as territoriality, and environmental effects, such as the area of forest remnants or properties of the landscape matrix in which they are embedded, can strongly affect the pattern of trait co‐occurrence. Our findings suggest that trait‐based analyses of community structure should include behavioural and environmental covariates, and we here provide an appropriate method for linking functional traits, species ecology and environmental conditions to clarify the drivers underlying spatial patterns of species co‐occurrence.     

Rapid, sequential changes in surface morphology of PC12 pheochromocytoma cells in response to nerve growth factor

The effect of nerve growth factor (NGF), a substance that promotes the differentiation and maintenance of certain neurons, was studied via scanning electron microscopy utilizing the PC12 clonal NGF-responsive pheochromocytoma cell line. After 2-4 d of exposure to NGF, these cells acquire many of the properties of normal sympathic neurons. However, by phase microscopy, no changes are discernible within the first 12-18 h. Since the primary NGF receptor appears to be a membrane receptor, it seemed likely that some of the initial responses to the factor may be surface related. PC12 cells maintained without NGF are round to ovoid and have numerous microvilli and small blebs. After the addition of NGF, there is a rapidly initiated sequential change in the cell surface. Ruffles appear over the dorsal surface of the cells with 1 min, become prominent by 3 min, and almost disappear by 7 min. Microvilli, conversely, disappear as the dorsal ruffles become prominent. Ruffles are seen at the the periphery of cell at 3 min, are prominent on most of the cells by 7 min and are gone by 15 min. The surface remains smooth from 15 min until 45 min when large blebs appear. The large blebs are present on most cells at 2 h and are gone by 4 h. The surface remains relatively smooth until 6-7 h of NGF treatment, when microvilli reappear as small knobs. These microvilli increase in both number and length to cover the cell surface by 10 h. These changes were not observed with other basic proteins, with α-bungarotoxin (which binds specifically to PC12 membranes), and were not affected by an RNA synthesis inhibitor that blocks initiation of neurite outgrowth. Changes in the cell surface architecture appear to be among the earlist NGF responses yet detected and may represent or reflect primary events in the mechanism of the factor’s action.     

Asymmetric aldol reaction using boron enolates

The protocol for the preparation of boron enolates and their subsequent reaction with aldehydes is described, providing convenient access to beta-hydroxy ketones in good yields and with high stereoselectivities. The reaction consists of three steps: first, the ketone is rapidly converted to the corresponding boron enolate, by exposure to a chlorodialkylborane and tertiary amine base, which is then reacted in situ with the aldehyde. Finally, oxidative workup of the resultant boron aldolate provides aldol adduct. The reaction procedure requires approximately 28 h to complete over a 2-d period, consisting of 5 h to set up the reaction, whereupon the reaction mixture is left at -20 degrees C overnight (16 h), followed by 7 h for workup and purification.     

The design,synthesis, and anti-inflammatory evaluation of a drug-like library based on the natural product valerenic acid

The plant natural product, valerenic acid (1) was chosen as a desirable scaffold for the generation of a novel screening library due to its drug-like physicochemical parameters (such as Log P, hydrogen bond donor/acceptor counts, and molecular weight). An 11-membered amide library (2–12) was subsequently generated using parallel solution-phase synthesis and Ghosez’s reagent. The chemical structures of all semi-synthetic analogues (2–12) were elucidated following analysis of the NMR, MS, UV and IR data. The structures of compounds 8 and 11 were also confirmed by X-ray crystallographic analysis. All library members were evaluated for their ability to inhibit the release of IL-8 and TNF-α. Six analogues showed moderate activity in the IL-8 assay with IC₅₀ values of 2.8–8.3 μM, while none of the tested compounds showed any significant effect on inhibiting TNF-α release.     

Effects of singlet oxygen on membrane sterols in the yeast Saccharomyces cerevisiae.

Photodynamic treatment of the yeast Saccharomyces cerevisiae with the singlet oxygen sensitizer toluidine blue and visible light leads to rapid oxidation of ergosterol and accumulation of oxidized ergosterol derivatives in the plasma membrane. The predominant oxidation product accumulated was identified as 5alpha, 6alpha-epoxy-(22E)-ergosta-8,22-dien-3beta,7a lpha-diol (8-DED). 9(11)-dehydroergosterol (DHE) was identified as a minor oxidation product. In heat inactivated cells ergosterol is photooxidized to ergosterol epidioxide (EEP) and DHE. Disrupted cell preparations of S. cerevisiae convert EEP to 8-DED, and this activity is abolished in a boiled control indicating the presence of a membrane associated enzyme with an EEP isomerase activity. Yeast selectively mobilizes ergosterol from the intracellular sterol ester pool to replenish the level of free ergosterol in the plasma membrane during singlet oxygen oxidation. The following reaction pathway is proposed: singlet oxygen-mediated oxidation of ergosterol leads to mainly the formation of EEP, which is enzymatically rearranged to 8-DED. Ergosterol 7-hydroperoxide, a known minor product of the reaction of singlet oxygen with ergosterol, is formed at a much lower rate and decomposes to give DHE. Changes of physical properties of the plasma membrane are induced by depletion of ergosterol and accumulation of polar derivatives. Subsequent permeation of photosensitizer through the plasma membrane into the cell leads to events including impairment of mitochondrial function and cell inactivation.