Neural coding in antennal olfactory cells of tsetse flies (Glossina spp.)

Spike trains from individual antennal olfactory cells of tsetse flies (Glossina spp.) obtained during steady-state conditions (spontaneous as well as during stimulation with 1-octen-3-ol) and dynamic stimulation with repetitive pulses of 1-octen-3-ol were investigated by studying the spike frequency and the temporal structure of the trains. In general, stimulation changes the intensity of the spike activity but leaves the underlying stochastic structure unaffected. This structure turns out to be a renewal process. The only independently varying parameter in this process is the mean interspike interval length, suggesting that olfactory cells of tsetse flies may transmit information via a frequency coding. In spike records with high firing rates, however, the stationary records had significant negative first- order serial correlation coefficients and were non-renewal. Some cells in this study were capable of precisely encoding the onset of the odour pulses at frequencies up to at least 3 Hz. Cells with a rapid return to pre-stimulus activity at the end of stimulation responded more adequately to pulsed stimuli than cells with a long increased spike frequency. While short-firing cells process information via a frequency code, long-firing cells responded with two distinctive phases: a phasic, non-renewal response and a tonic, renewal response which may function as a memory of previous stimulations.      

Reactions of stereoisomeric and structurally related bay region diol epoxide derivatives of benz[a]anthracene with DNA. Conformations of noncovalent complexes and covalent carcinogen-DNA adducts

The modes of reaction of the tumorigenic bay region diol epoxide anti-BADE [+/-)-trans-3,4-diol-anti-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthr acene) and the less potent tumor initiating diastereomer syn-BADE [+/-)-trans-3,4-diol-syn-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthra cene) with native, double-stranded DNA were compared. The bay-region diol epoxide derived from 3-methylcholanthrene (3-MCDE, racemic trans-9,10-diol-anti-7,8-epoxy-7,8,9,10-tetrahydromethylcholanthrene+ ++) was included in this study in order to assess the effects of the methyl and methylene substituents on the reactivity with DNA. Utilizing linear dichroism and other spectroscopic methods, it is shown that all three diol epoxides forn non-covalent complexes with DNA. The diastereomers anti-BADE and syn-BADE form intercalative physical complexes, but the association constant K of the syn-diastereomer is about 6-7 times smaller than for anti-BADE; this effect is ascribed to the bulky quasi-diaxial conformation of the diol epoxide ring in the syn diastereomer. The value of K (4000 M-1) is similar for anti-BADE and 3-MCDE, although the latter is not intercalated in the classical sense since the short axis of the molecule is tilted closer to the axis of the DNA double helix. The conformations of the covalent DNA adducts are interpreted in terms of a quasi-intercalative conformation (site I), and a conformation in which the long axes of the polycyclic molecules are tilted closer to the axis of the helix (site II). Both tumorigens, anti-BADE and 3-MCDE, undergo a marked re-orientation from a non-covalent site I to a covalent site II conformation upon binding chemically with the DNA bases, although a small fraction of the covalent anti-BADE adducts remains quasi-intercalated; in contrast, the alkyl substituents in 3-MCDE not only prevent the formation of intercalative physical complexes, but also the formation of site I covalent adducts. In the case of the less tumorigenic syn-BADE, both the non-covalent complexes and the covalent adducts are of the site I-type. The bay-region diol epoxide of benz[a]anthracene and of 3-methylcholanthrene display a similar pattern of reactivities and covalent adduct conformations as the bay region diol epoxide derivatives of benz[a]pyrene, suggesting that adduct conformation might be an important factor in determining the levels of mutagenic and tumorigenic activities of this class of compounds.     

Inactivation of viruses in red cell and platelet concentrates with aluminum phthalocyanine (AIPc) sulfonates.

Aluminum phthalocyanine tetrasulfonates (AIPcS) are photoactive compounds with absorption maxima at 665-675 nm. The inactivation of viruses (vesicular stomatitis virus, VSV; human immunodeficiency virus, HIV) added to either whole blood or red blood cell concentrates (RBCC) and platelet concentrates (PC) on treatment with tetrasulfonated AIPc (AIPcS4) was evaluated. Treatment of RBCC with 10 microM AIPcS4 and 44 J/cm2 visible light resulted in the inactivation of greater than or equal to 10(5.5) infectious doses (TCID50) of cell-free VSV, greater than or equal to 10(5.6) TCID50 of cell-associated VSV, and greater than or equal to 10(4.7) TCID50 of cell-free sindbis virus. Both greater than or equal to 10(4.2) TCID50 of cell-free and greater than or equal to 10(3.6) TCID50 of cell-associated forms of HIV were also shown to be inactivated. Encephalomyocarditis virus, used as a model for nonenveloped viruses, was not inactivated. Equivalent virus kill with Photofrin II required a substantially higher concentration of dye and longer exposure to visible light. Following AIPcS4 treatment, red cell integrity was well maintained as judged by the low level (less than 2%) of hemoglobin release immediately following treatment and on subsequent storage, by measurements of erythrocyte osmotic fragility, and by the normal recovery and circulatory survival on infusion of treated, autologous red blood cells in baboons. Treatment of PC with 10 microM AIPcS4 and 44 J/cm2 visible light also resulted in effective virus kill (greater than or equal to 10(5.5) TCID50) of VSV; however, both the rate and extent of platelet aggregation in response to collagen addition declined by at least 50%. Based on these results, further characterization of AIPcS4-treated RBCC is justified.