Relating aromatic hydrocarbon-induced DNA adducts and c-H-ras mutations in mouse skin papillomas: the role of apurinic sites.

Mouse skin tumors contain activated c-H-ras oncogenes, often caused by point mutations at codons 12 and 13 in exon 1 and codons 59 and 61 in exon 2. Mutagenesis by the noncoding apurinic sites can produce G-->T and A-->T transversions by DNA misreplication with more frequent insertion of deoxyadenosine opposite the apurinic site. Papillomas were induced in mouse skin by several aromatic hydrocarbons, and mutations in the c-H-ras gene were determined to elucidate the relationship among DNA adducts, apurinic sites, and ras oncogene mutations. Dibenzo[a,l]pyrene (DB[a,l]P), DB[a,l]P-11,12-dihydrodiol, anti-DB[a,l]P-11,12-diol-13,14-epoxide, DB[a,l]P-8,9-dihydrodiol, 7,12-dimethylbenz[a]anthracene (DMBA), and 1,2,3,4-tetrahydro-DMBA consistently induced a CAA-->CTA mutation in codon 61 of the c-H-ras oncogene. Benzo[a]pyrene induced a GGC-->GTC mutation in codon 13 in 54% of tumors and a CAA-->CTA mutation in codon 61 in 15%. The pattern of mutations induced by each hydrocarbon correlated with its profile of DNA adducts. For example, both DB[a,l]P and DMBA primarily form DNA adducts at the N-3 and/or N-7 of deoxyadenosine that are lost from the DNA by depurination, generating apurinic sites. Thus, these results support the hypothesis that misreplication of unrepaired apurinic sites generated by loss of hydrocarbon-DNA adducts is responsible for transforming mutations leading to papillomas in mouse skin.

Hairpins are formed by the single DNA strands of the fragile X triplet repeats: structure and biological implications.

Inordinate expansion and hypermethylation of the fragile X DNA triplet repeat, (GGC)n.(GCC)n, are correlated with the ability of the individual G- and C-rich single strands to form hairpin structures. Two-dimensional NMR and gel electrophoresis studies show that both the G- and C-rich single strands form hairpins under physiological conditions. This propensity of hairpin formation is more pronounced for the C-rich strand than for the G-rich strand. This observation suggests that the C-rich strand is more likely to form hairpin or "slippage" structure and show asymmetric strand expansion during replication. NMR data also show that the hairpins formed by the C-rich strands fold in such a way that the cytosine at the CpG step of the stem is C.C paired. The presence of a C.C mismatch at the CpG site generates local flexibility, thereby providing analogs of the transition to the methyltransferase. In other words, the hairpins of the C-rich strand act as better substrates for the human methyltransferase than the Watson-Crick duplex or the G-rich strand. Therefore, hairpin formation could account for the specific methylation of the CpG island in the fragile X repeat that occurs during inactivation of the FMR1 gene during the onset of the disease.

Segmentação de imagens pela transformada imagem-floresta com faixa de restrição geodésica

Vários métodos tradicionais de segmentação de imagens, como a transformada de watershed de marcado- res e métodos de conexidade fuzzy (Relative Fuzzy Connectedness- RFC, Iterative Relative Fuzzy Connected- ness - IRFC), podem ser implementados de modo eficiente utilizando o método em grafos da Transformada Imagem-Floresta (Image Foresting Transform - IFT). No entanto, a carência de termos de regularização de fronteira em sua formulação fazem com que a borda do objeto segmentado possa ser altamente irregular. Um modo de contornar isto é por meio do uso de restrições de forma do objeto, que favoreçam formas mais regulares, como na recente restrição de convexidade geodésica em estrela (Geodesic Star Convexity - GSC). Neste trabalho, apresentamos uma nova restrição de forma, chamada de Faixa de Restrição Geodésica (Geodesic Band Constraint - GBC), que pode ser incorporada eficientemente em uma sub-classe do fra- mework de corte em grafos generalizado (Generalized Graph Cut - GGC), que inclui métodos pela IFT. É apresentada uma prova da otimalidade do novo algoritmo em termos de um mínimo global de uma função de energia sujeita às novas restrições de borda. A faixa de restrição geodésica nos ajuda a regularizar a borda dos objetos, consequentemente melhorando a segmentação de objetos com formas mais regulares, mantendo o baixo custo computacional da IFT. A GBC pode também ser usada conjuntamente com um mapa de custos pré estabelecido, baseado em um modelo de forma, de modo a direcionar a segmentação a seguir uma dada forma desejada, com grau de liberdade de escala e demais deformações controladas por um parâmetro único. Essa nova restrição também pode ser combinada com a GSC e com as restrições de polaridade de borda sem custo adicional. O método é demonstrado em imagens naturais, sintéticas e médicas, sendo estas provenientes de tomografias computadorizadas e de ressonância magnética.

Nd isotope ratios of surface sediments from the Pacific Ocean (Table 2)

The neodymium isotopic composition of the silicate fraction of Holocene pelagic sediments from the North Pacific define two provinces: a central North Pacific province characterized by unradiogenic and remarkably homogeneous end (-10.2 +/- 0.5) and a narrow circum-Pacific marginal province characterized by more radiogenic and variable end (-4.2 +/- 3.8). The silicate fraction in the central North Pacific is exclusively eolian; based on prevailing wind patterns, meteorological data, and neodymium isotopic data, the only significant sediment source is Chinese loess. Leaching experiments on Chinese loess confirm that leachable Nd is isotopically indistinguishable from bulk and residual silicate Nd. Silicates in the circum-North Pacific marginal province comprise eolian loess, volcanic ash, and hemipelagic sediments derived from volcanic arcs. A compilation of Pacific seawater and Mn nodule epsilon-Nd data shows no clear spatial variation except for a general decrease from surface to deep waters from -3 to -4 and slightly lower epsilon-Nd in bottom waters along the western North Pacific due to the incursion of Antarctic Bottom Water. The relative homogeneity of bottom water epsilon-Nd, which contrasts sharply with the distinctive variation in sediment epsilon-Nd, plus the large difference between the average end of bottom waters and the central North Pacific eolian silicates (-4 vs. -10), suggests that any contribution of REE to seawater from eolian materials is insignificant. Furthermore, leaching of REE from eolian particles as they sink though the water column must be insignificant because Nd in shallow waters is more radiogenic than Nd in deeper waters. That there is no contrast in the Nd isotopic composition of bottom waters that overlie the central and marginal sediment provinces suggests that the ash and hemipelagic sediments derived from Pacific rim volcanic arcs also contribute minimal REE to seawater. The elimination of eolian, ash, and hemipelagic sediments leaves only near-shore riverine particulates as a possibly significant particulate source of REE to seawater.

(Table 1) Age determination of western North Atlantic sediment cores

Foraminiferal abundance, 14C ventilation ages, and stable isotope ratios in cores from high deposition rate locations in the western subtropical North Atlantic are used to infer changes in ocean and climate during the Younger Dryas (YD) and Last Glacial Maximum (LGM). The d18O of the surface dwelling planktonic foram Globigerinoides ruber records the present-day decrease in surface temperature (SST) of ~4°C from Gulf Stream waters to the northeastern Bermuda Rise. If during the LGM the modern d18O/salinity relationship was maintained, this SST contrast was reduced to 2°C. With LGM to interglacial d18O changes of at least 2.2 per mil, SSTs in the western subtropical gyre may have been as much as 5°C colder. Above ~2.3 km, glacial d13C was higher than today, consistent with nutrient-depleted (younger) bottom waters, as identified previously. Below that, d13C decreased continually to -0.5 per mil, about equal to the lowest LGM d13C in the North Pacific Ocean. Seven pairs of benthic and planktonic foraminiferal 14C dates from cores >2.5 km deep differ by 1100 ± 340 years, with a maximum apparent ventilation age of ~1500 years at 4250 m and at ~4700 m. Apparent ventilation ages are presently unavailable for the LGM < 2.5 km because of problems with reworking on the continental slope when sea level was low. Because LGM d13C is about the same in the deep North Atlantic and the deep North Pacific, and because the oldest apparent ventilation ages in the LGM North Atlantic are the same as the North Pacific today, it is possible that the same water mass, probably of southern origin, flowed deep within each basin during the LGM. Very early in the YD, dated here at 11.25 ± 0.25 (n = 10) conventional 14C kyr BP (equal to 12.9 calendar kyr BP), apparent ventilation ages <2.3 km water depth were about the same as North Atlantic Deep Water today. Below ~2.3 km, four YD pairs average 1030 ± 400 years. The oldest apparent ventilation age for the YD is 1600 years at 4250 m. This strong contrast in ventilation, which indicates a front between water masses of very different origin, is similar to glacial profiles of nutrient-like proxies. This suggests that the LGM and YD modes of ocean circulation were the same.