Structural alignment of the (+)-trans-anti-benzo[a]pyrene-dG adduct positioned opposite dC at a DNA template-primer junction

This study reports on the solution conformation of the covalent (+)-trans-anti-[BP]dG adduct (derived from the binding of the highly mutagenic and tumorigenic (+)-anti-benzo[a]pyrene diol epoxide to the N2 of deoxyguanosine) positioned opposite dC at a junctional site in the d(A1-A2-C3-[BP]G4-C5- T6-A7-C8-C9-A10-T11-C12-C13).d(G14-G15-A16-T17-+ ++G18-G19-T20-A21-G22-C23) 13/10-mer DNA sequence. The 13-mer represents the template strand containing the junction [BP]dG4 lesion while the complementary 10-mer models a primer strand which extends upto and is complementary to the modified dG4 residue. The solution conformation has been determined by initially incorporating intramolecular and intermolecular proton-proton distances defined by lower and upper bounds deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space and subsequently through restrained molecular dynamics calculations based on a NOE distance and intensity refinement protocol. The duplex segment retains a minimally perturbed B-DNA conformation with all base pairs, including the junctional [BP]dG4.dC23 pair, in Watson-Crick hydrogen-bonded alignments. The pyrenyl ring is not stacked over the adjacent dC5.dG22 base pair but is positioned on the minor groove-side of the [BP]dG moiety and directed toward the 5'-end of the template strand. The pyrenyl ring stacks over the base of the non-adjacent dA2 residue in one direction and the sugar ring of dC23 in the other direction. The solution structure of the (+)-trans-anti-[BP]dG adduct opposite dC in the 13/10-mer in which the modified deoxyguanosine adopts an anti glycosidic torsion angle (this study) is in striking contrast to the structure of the same (+)-trans-anti-[BP]dG moiety in a 13/9-mer of the same sequence but without the dC23 residue positioned opposite the adduct site [Cosman, M., et al. (1995) Biochemistry 34, 15334-15350]. For the latter case, the aromatic portion of the BP residue stacks over the adjacent dC5.dG22 base pair, the modified deoxyguanosine adopts a syn glycosidic torsion angle and is displaced toward the major groove direction. Insights into the factors that affect the sequence and context dependent conformations of stereoisomeric [BP]dG lesions have emerged following comparison of these two structures with the minor groove conformations of the same (+)-trans-anti-[BP]dG lesion in the fully complementary 11-mer duplex [Cosman, M., et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1914-1918] and in the base displaced-intercalative conformation of the 11/10-mer deletion duplex containing a -1 deletion site opposite the lesion [Cosman, M., et al. (1994) Biochemistry 33, 11507-11517]. The contributing factors where applicable include Watson-Crick base pairing at the site of the lesion, positioning of the carcinogen within the floor of the minor groove, and the tendency of the bulky hydrophobic aromatic BP residue to assume stacked or intercalative conformations.     

Potent piperazine hydroxyethylamine HIV protease inhibitors containing novel P3 ligands

The 2-isopropyl thiazolyl group is a highly optimized P3 ligand for C2 symmetry-based HIV protease inhibitors, as exemplified in the drug ritonavir. Here we report that incorporation of this P3 ligand into a piperazine hydroxyethylamine series also yielded novel, highly potent inhibitors. In tissue culture assays, the presence of human serum was less deleterious to the activity of these inhibitors than to that of ritonavir. Furthermore, potent activity against ritonavir resistant HIV was observed.     

Peak bone mineral accrual and age at menarche in adolescent girls: a 6-year longitudinal study

To study the effect of a high radiation background on the structure and function of the T-complex, we used laboratory mice carrying t-haplotypes of four complementation groups (t0, t12, tw1, and tw5). In 1987-1989, the animals were kept each year for a month within a 30-kilometer zone of Chernobyl Nuclear Power Station in regions with different degrees of pollution. Subsequent genetic analysis revealed a decrease in fertility, fecundity, and the index of preferable transmission of t-carrying chromosomes in radiated animals and some of their progeny. The effect of different radiation doses on these parameters was different in animals with various t-haplotypes. A lack of complementation or a decrease in the complementation effect was revealed in a number of crosses involving the progeny of irradiated animals. The frequency of complementation distortion was about 8 x 10(-2), which is more than an order higher than the usual recombination frequency characteristic of these t-haplotypes.     

Characterization of a high capacity calcium transport system in mitochondria of the yeast Endomyces magnusii

The Ca2+ transport system of Endomyces magnusii mitochondria has been shown previously to be activated by spermine. Here we report it to be regulated also by low, physiological ADP concentrations, by the intramitochondrial NADH/NAD+ ratio, and by Ca2+ ions. The combination of all these physiological modulators induced high initial rates of Ca2+ uptake and high Ca2+-buffering capacity of yeast mitochondria, enabling them to lower the medium [Ca2+] to approximately 0.2 microM. The mechanisms of stimulation by these agents are discussed.     

Spatial organization of electrical processes in the brain: problems and solutions

Theoretical questions of the spatial organization of electrical activity in the brain are discussed in terms of a multilevel realization of the synergetic principle for formation of functional systems underlying behavior and mental function. The role of the spatial-temporal superimposition of coherent structures of biopotentials in generating fields of increased activity in the cerebral cortex is discussed, these being responsible for integrative and associative functions. A hypothesis is proposed regarding the relationship between the energy and information factors of coherent structures as one of the important characteristics describing the efficiency of energy-informational processes. Emphasis is placed on the need for considering not only linear, but also nonlinear associations of biopotentials in considerations of the form and functional sense of their spatial organization.     

45Ca exchange in rat cortex slices in conditions of long-term potentiation

OBJECTIVE: An attempt was made to find out how many operations were performed in Europe in 1995 for congenital heart disease. METHODS: Representatives from the 20 most active European countries which could supply reliable information were contacted. They were asked to contact all surgeons performing significant numbers of operations for congenital heart disease in their country. The numbers of operations on children under and over 1 year operated on with and without cardiopulmonary bypass were collected. No attempt was made to collect more detailed information such as operative mortality as it was felt that many surgeons would be reluctant to give their results and the data would be incomplete. RESULTS: A total of 27,976 operations were recorded, of which 20,318 were performed with cardiopulmonary bypass and 7658 without. The total population of the 20 European countries was 448 million and the mean number of operations performed with cardiopulmonary bypass per million was 45.4. However, the rate varied from 9.1 to 70.1. The percentage of operations on cardiopulmonary bypass performed in the first year of life varied from 9.4% to 44.4%. CONCLUSIONS: The total of nearly 28,000 operations in 1995 is probably an underestimate, but it has been difficult to collect this data at all. Obviously many smaller countries have not been included, and some older patients undergoing operations such as atrial septal defect closure in adult units have been missed. The number of open heart operations per million vary in different countries and this presumably represents differing referral patterns. If their numbers are low in some countries, these results may be helpful in persuading their governments that more resources are needed for congenital heart surgery. It is also interesting to see the variation in the number of operations performed in the first year of life. Those countries with a lower rate may have a backlog of older patients who were previously palliated, or their surgeons may still prefer initial palliation and later correction in some conditions rather than early correction. It is hoped that with better prospective data collection, an assessment can be repeated in 2000.     

D1S80 allele frequencies in a Chinese population

Allele frequencies for the VNTR locus D1S80 were determined in a Chinese population sample using the polymerase chain reaction and subsequent analysis of the amplified products by polyacrylamide gel electrophoresis and silver staining. A total of 18 nominal D1S80 alleles were observed in 105 unrelated Chinese. The data demonstrate that D1S80 is highly polymorphic in Chinese with a heterozygosity of 90.5%. The D1S80 frequency distribution meets Hardy-Weinberg expectations. This D1S80 data can be used in forensic analyses and paternity tests to estimate the frequency of a DNA profile in a Chinese population.     

Campus courtship behavior and fear of human immunodeficiency virus infection by university students

Data were collected by telephone from a random sample of 762 students at the University of Northern Colorado to examine students' fear of human immunodeficiency virus (HIV) infection and their suggested approaches to prevent the spread of the disease. Of the 762 students interviewed, 177 (24.1%) believed that HIV/acquired immunodeficiency syndrome (AIDS) was a threat to socialization on campus. Fourteen percent of the female students considered HIV/AIDS to be a threat compared with 10.1% of their male counterparts. Among all interviewees, 573 (76.7%) believed HIV/AIDS was a threat to romance at the university. Statistically significant association was found between the perceived fear of HIV/AIDS and gender. With regard to actual sexual intercourse, 86.4% of the students believed that HIV/AIDS was a major threat compared with 13.6% who did not. The association between the perception about HIV/AIDS as a threat to on-campus sexual intercourse and gender was statistically significant. Of the entire sample, 69.3% suggested abstinence as an approach to avoid HIV infection. Slightly more than 24% suggested condom use. Eighteen (10.8%) students advised that sexual contact should be only with a trusted partner. More information about HIV/AIDS should be provided to all students, especially women, in institutions of higher learning. More information can reduce the fear associated with this deadly disease.