Interaction of olive oil phenol antioxidant components with low-density lipoprotein

Phenolic compounds have shown to inhibit LDL oxidation in vitro and ex vivo; however, they are hydrosoluble compounds while LDL is a lipoprotein. Analysis of phenolic compounds in LDLs by HPLC is necessary to demonstrate their binding capacity to lipoproteins. We developed and validated a solid phase extraction method (SPE) that allowed us the purification of LDL samples and their analysis by HPLC. This methodology allowed us to demonstrate the in vitro binding capacity of tyrosol, one of the main phenolic compounds in olive oil, to LDL. In the intervention dietary study with volunteers, food rich in phenolic compounds affected LDL composition. Changes in LDL phenolics composition are not observed after the short-term ingestion of food rich in phenolic compounds. However, after one week of olive oil consumption and Mediterranean diet there was an increase in phenolics (p=0.021). An accumulative effect seems necessary to observe significative differences in LDL phenolic composition.     

Divergent role of ceramide generated by exogenous sphingomyelinases on NF-kappa B activation and apoptosis in human colon HT-29 cells

A novel branch of the Ras family, Rit, was recently identified. Rit exhibits a distinct C-terminus and effector domain, and does not activate mitogen-activated protein kinase (MAPK) but can cooperate with Raf to transform fibroblasts. Here, we found that when overexpressed, activated mutants of Rit transform NIH 3T3 cells efficiently, and stimulate p38gamma but not MAPK, p38alpha, p38gamma, p38delta, or ERK5. Furthermore, we provide evidence that p38gamma activation is required for the ability of Rit to stimulate gene expression and cellular transformation. These findings suggest that this unique GTPase stimulates proliferative pathways distinct from those regulated by other Ras family members.     

Novel small renin inhibitors containing 4,5- or 3,5-dihydroxy-2-substituted-6-phenylhexanamide replacements at the P2P3 sites

Renin inhibitors containing a 4,5- or a 3,5-dihydroxy-2-substituted-6-phenylhexanamide fragment at the P₂---P₃ sites have been prepared and evaluated. The four possible diastereomeric diols of the two series of inhibitors were synthesized to determine the optimal configuration of the carbinol centers for these replacements. The most potent inhibitors of each series, 1a and 2c have a molecular weight of only 503 and IC₅₀ values of 23 and 20 nM in a human plasma renin assay at pH 6.0. Their very low aqueous solubility limited their further evaluation. The efficacy of these P₂---P₃ replacements is a result of their ability to maintain the important hydrogen-bonds with the enzyme. Due to conformational differences with the dipeptide, adjustment at the P₂ side chain was required. These 4,5- and 3,5-dihydroxyhexanamide segments could be seen as novel N-terminal dipeptide replacements.     

A simple method for N-15 labelling of exocyclic amino groups in synthetic oligodeoxynucleotides

The use of the ammonia deprotection step to introduce ¹⁵N labels at specific exocyclic amino positions of adenine, cytosine, guanine or 2-aminopurine of oligodeoxynucleotides is described.     

Relevance of CD6-mediated interactions in T cell activation and proliferation

CD6 is a cell surface receptor expressed on immature thymocytes and mature T and B1a lymphocytes. The ultimate function of CD6 has not been deciphered yet, but much evidence supports a role for CD6 in T cell activation and differentiation. In this study, we show that a fraction of CD6 molecules physically associates with the TCR/CD3 complex by coimmunoprecipitation, cocapping, and fluorescence resonance energy transfer experiments. Image analysis of Ag-specific T-APC conjugates demonstrated that CD6 and its ligand, activated leukocyte cell adhesion molecule (CD166), colocalize with TCR/CD3 at the center of the immunological synapse, the so-called central supramolecular activation cluster. The addition of a soluble rCD6 form significantly reduced the number of mature Ag-specific T-APC conjugates, indicating that CD6 mediates early cell-cell interactions needed for immunological synapse maturation to proceed. This was in agreement with the dose-dependent inhibition of CD3-mediated T cell proliferation induced by soluble rCD6. Taken together, our data illustrate the important role played by the intra- and intercellular molecular interactions mediated by CD6 during T cell activation and proliferation processes.     

Synthesis and structure-activity relationships of piperidinylpyrrolopyridine derivatives as potent and selective H1 antagonists

The synthesis and structure-activity relationships of piperidinylpyrrolopyridines as potent and selective H(1) antagonists are discussed. It was found that the nature of the acid chain bonded to piperidine was a key feature for maintaining both the duration of action in vivo and lack of sedative properties.     

Molecular Cytogenetic Analysis of the European Hake Merluccius merluccius (Merlucciidae,Gadiformes): U1 and U2 snRNA Gene Clusters Map to the Same Location

The European hake (Merluccius merluccius) is a highly valuable and intensely fished species in which a long-term alive stock has been established in captivity for aquaculture purposes. Due to their huge economic importance, genetic studies on hakes were mostly focused on phylogenetic and phylogeographic aspects; however chromosome numbers are still not described for any of the fifteen species in the genus Merluccius. In this work we report a chromosome number of 2n = 42 and a karyotype composed of three meta/submetacentric and 18 subtelo/telocentric chromosome pairs. Telomeric sequences appear exclusively at both ends of every single chromosome. Concerning rRNA genes, this species show a single 45S rDNA cluster at an intercalary location on the long arm of subtelocentric chromosome pair 12; the single 5S rDNA cluster is also intercalary to the long arm of chromosome pair 4. While U2 snRNA gene clusters map to a single subcentromeric position on chromosome pair 13, U1 snRNA gene clusters seem to appear on almost all chromosome pairs, but showing bigger clusters on pairs 5, 13, 16, 17 and 19. The brightest signals on pair 13 are coincident with the single U2 snRNA gene cluster signals. Therefore, the use of these probes allows the unequivocal identification of at least 7 of the chromosome pairs that compose the karyotype of Merluccius merluccius thus opening the way to integrate molecular genetics and cytological data on the study of the genome of this important species.