Enhancement of goldfish virus-2 in vitro replication by the pesticides carbaryl and toxaphene.

Goldfish virus-2 replication was enhanced in vitro by pretreatment of CAR cells with subcytotoxic concentrations of carbaryl and toxaphene. This phenomenon was time and temperature dependent. Shortening of pretreatment with carbaryl eliminated enhancement, which was observed for toxaphene only with substantially increased concentrations. Decreasing the temperature of pretreatment (4 degrees C) abrogated any enhancement by carbaryl and resulted in enhancement by toxaphene only at increased concentrations. Increased absorption of input virus was ruled out as a mechanism for enhancement, as was stimulation of cell division in the presence of pesticides over that of control cultures. Pretreatment of virus rather than cells did not result in enhancement.     

Polydactyly and Other Minor Stigmata Associated with 46,XX/47, XX,D+ Mosaicism

Mosaicism for normal and D-trisomic cells was found in a female child whose presenting abnormalities at birth were polydactyly of the left hand and foot, hemangiomata on the forehead and lumbosacral region, slightly peculiar facies and unusual dermal patterns. Her course during the first 27 months of life was characterized by normal growth, absence of clinical evidence of congenital heart disease, moderate developmental retardation, tonguetie and toe-walking. Trisomic cells were more numerous than normal cells in skin cultures, whereas the reverse was true for peripheral leukocytes.     

Tooth scaling and evolutionary dwarfism: an investigation of allometry in human pygmies

Gould has predicted that in rapidly dwarfed lineages the postcanine teeth exhibit a different scaling pattern than is the normal interspecific trend. His prediction of strong negative allometry has not been frequently tested in quantitative detail. Here we present results of scaling analyses of the molar teeth in African pygmies compared with other Africans of larger size and in Philippine pygmies compared with Filipinos of larger size. We find a pattern of strong negative allometry of tooth size to skull and body size in both these comparisons. This scaling pattern is explained by recourse to the developmental bases (known or inferred) of dwarfing in these populations. Body size decrease is related to low levels of the growth control substance insulin-like growth factor I (IGF-I), which does not appear to affect the size of the dentition. The implications of such developmental information for our understanding of allometric patterns in general, and dwarfing events in particular, are discussed.     

Dietary deficiency increases presenilin expression, gamma-secretase activity, and Abeta levels: potentiation by ApoE genotype and alleviation by S-adenosyl methionine

Apolipoprotein E4 (ApoE4) is a risk factor for Alzheimer's disease (AD). Whether this risk arises from a deficient function of E4 or the lack of protection provided by E2 ir E3 is unclear. Previous studies demonstrate that deprivation of folate and vitamin E, coupled with dietary iron as a pro-oxidant, for 1 month displayed increased presenilin 1 (PS-1) expression, gamma-secretase, and Abeta generation in mice lacking ApoE (ApoE−/− mice). While ApoE−/− mice are a model for ApoE deficiency, they may not reflect the entire range of consequences of E4 expression. We therefore compared herein the impact of the above deficient diet on mice expressing human E2, E3, or E4. As folate deficiency is accompanied by a decrease in the major methyl donor, S -adenosyl methionine (SAM), additional mice received the deficient diet plus SAM. E2 was more protective than murine ApoE or E3 and E4. Surprisingly, PS-1 and gamma-secretase were over-expressed in E3 to the same extent as in E4 even under a complete diet, and were not alleviated by SAM supplementation. Abeta increased only in E4 mice maintained under the complete diet, and was alleviated by SAM supplementation. These findings suggest dietary compromise can potentiate latent risk factors for AD.     

Molecular recognition between oligopeptides and nucleic acids. Specificity of binding of a monocationic bis-furan lexitropsin to DNA deduced from footprinting and 1H NMR studies

MPE-Fe(EDTA) footprinting of a novel monocationic bis-furan lexitropsin 6 on a HindIII/EcoRI restriction fragment of pBR322 DNA revealed a series of four-base binding sites (all 5'----3') of (primary) TGTA, TGAA, AAAT, ACAA, TTAT, and (secondary) CTAA, TCGT, TGTA, GTCA, and GGTT. Thus 6 can accept a GC pair at positions 1, 2 or 3 of the binding site with a strict 3' (4 position) AT requirement. Marked enhancement of cleavage, particularly at GC rich sequences, is observed at regions flanking or even up to 18 base pairs remote from a given binding site. The non-exchangeable and imino 1H NMR resonances of the 1:1 complex and d-[CATGGCCATG]2 were assigned using a combination of NOE differences, NOESY and COSY techniques. 1H NMR studies (ligand induced chemical shifts and NOE differences) of Lexitropsin 6 with d-[CATGGCCATG]2 show unambiguously the location and orientation of the N to C termini of 6 on the sequence 5'-G5C6C7A8-3', with the C terminus oriented to A8. This orientation of 6 in the minor groove of 5'-GCCA is confirmed by an NOE observed between H1 2a of 6 and AH8(8). This preference for binding of 6 to the sequence 5'-GCCA when challenged with d-[CATGGCCATG]2 is in accord with the conclusions of the footprinting experiments wherein GC base pairs can be accepted in the first three positions and with a strict 3' terminus AT reading requirement. Collectively the data support the inference of a GC recognizing capacity for a 2,5-substituted furan moiety within a lexitropsin. The 1H NMR data indicate that the decadeoxyribonucleotide duplex exists in the B conformation in both the 1:1 complex and the free form. The apparent binding constant of 6 to calf thymus DNA is 1.68 X 10(5) M-1 whereas netropsin under similar conditions gives a value of 1.85 X 10(7) M-1. This suggests that if advantage is to be taken of the GC recognizing property of a 2,5-substituted furan in longer lexitropsins it should be flanked by more strongly bound moieties.