Effects of ABCA1 SNPs, including the C-105T novel variant, on serum lipids of Brazilian individuals

Background: ABCA1 plays an important role in HDL metabolism. Single nucleotide polymorphisms (SNPs) in ABCA1 gene were associated with variation in plasina HDL-c. Methods: The effect of the ABCA1 SNPs C-14T, R219K and of a novel variant C-105T on serum lipids was investigated in 367 unrelated Brazilian individuals (224 hypercholesterolemic and 143 normolipidemic). The relation between ABCA1 SNPs and the lipid-lowering response to atorvastatin (10 mg/day/4 weeks) was also evaluated in 141 hypercholesterolemic (HC) individuals. The polymorphisms were detected by PCRR_FLP and confirmed by DNA sequencing. Results: Linkage disequilibrium was found between the SNPs C-105T and C-14T in the HC group. HC individuals carrying - 105CT/TT genotypes had higher serum HDL-c and lower triglyceride and VLDL-c concentrations as well as lower TG/HDL-c ratio compared to the -105CC carriers (p<0.05). The R219K SNP was associated with reduced serum triglyceride, VLDL-c and TG/HDL-c ratio in the HC group (p<0.05), and with an increased serum apoAI in NL individuals. The effects of ABCA1 SNPs on basal serum lipids of HC individuals were not modified by atorvastatin treatment. Conclusions: The ABCA1 SNPs R219K and C-105T were associated with a less atherogenic lipid profile but not with the lowering-cholesterol response to atorvastatin in a Brazilian population. (C) 2007 Elsevier B.V. All rights reserved.

The rise and evolution of the cambial variant in Bignonieae (Bignoniaceae)

Cambial variants represent a form of secondary growth that creates great stem anatomical diversity in lianas. Despite the importance of cambial variants, nothing is known about the developmental mechanisms that may have led to the current diversity seen in these stems. Here, a thorough anatomical analysis of all genera along the phylogeny of Bignonieae (Bignoniaceae) was carried out in order to detect when in their ontogeny and phylogeny there were shifts leading to different stem anatomical patterns. We found that all species depart from a common developmental basis, with a continuous, regularly growing cambium. Initial development is then followed by the modification of four equidistant portions of the cambium that reduce the production of xylem and increase the production of phloem, the former with much larger sieve tubes and an extended lifespan. In most species, the formerly continuous cambium becomes disjunct, with cambial portions within phloem wedges and cambial portions between them. Other anatomical modifications such as the formation of multiples of four phloem wedges, multiple-dissected phloem wedges, and included phloem wedges take place thereafter. The fact that each novel trait raised on the ontogenetic trajectory appeared in subsequently more recent ancestors on the phylogeny suggests a recapitulatory history. This recapitulation is, however, caused by the terminal addition of evolutionary novelties rather than a truly heterochronic process. Truly heterochronic processes were only found in shrubby species, which resemble juveniles of their ancestors, as a result of a decelerated phloem formation by the variant cambia. In addition, the modular evolution of phloem and xylem in Bignonieae seems to indicate that stem anatomical modifications in this group occurred at the level of cambial initials.

Functional and immunological characterization of a natural polymorphic variant of a heat-labile toxin (LT-I) produced by enterotoxigenic Escherichia coli (ETEC)

Heat-labile toxins (LT) encompass at least 16 natural polymorphic toxin variants expressed by wild-type enterotoxigenic Escherichia coli (ETEC) strains isolated from human beings, but only one specific form, produced by the reference ETEC H10407 strain (LT1), has been intensively studied either as a virulence-associated factor or as a mucosal/transcutaneous adjuvant. In the present study, we carried out a biological/immunological characterization of a natural LT variant (LT2) with four polymorphic sites at the A subunit (S190L, G196D, K213E, and S224T) and one at the B subunit (T75A). The results indicated that purified LT2, in comparison with LT1, displayed similar in vitro toxic activities (adenosine 3`,5`-cyclic monophosphate accumulation) on mammalian cells and in vivo immunogenicity following delivery via the oral route. Nonetheless, the LT2 variant showed increased adjuvant action to ovalbumin when delivered to mice via the transcutaneous route while antibodies raised in mice immunized with LT2 displayed enhanced affinity and neutralization activity to LT1 and LT2. Taken together, the results indicate that the two most frequent LT polymorphic forms expressed by wild ETEC strains share similar biological features, but differ with regard to their immunological properties.