Regulation of telomeres length: making the telomeres accessible?

Under a normal state, the extremities of chromosomes, telomeres, are protected against undesired fusion events. Alterations of the telomere structure are associated with genetic instability, while erosion of the telomeric repeats, occurring at each cell division, provides a mechanism controlling the long-term proliferation of somatic cells. Although the structure and composition of the human telomerase enzyme are now well characterized, the protein partners regulating the stability and conformation of its DNA substrate, the telomeric end, are much less known. A functional link has been recently evidenced between proteins that bind the double-stranded telomere repeats and those recruited at the 3' G-rich telomeric overhang. This review presents an update on these telomeric factors controlling telomere lengthening and discuss the actual models proposed for its regulation.     

A nutritional intervention promoting the Mediterranean food pattern is associated with a decrease in circulating oxidized LDL particles in healthy women from the Québec City metropolitan area

The aim of the present study was to evaluate the effect of a nutritional intervention promoting the Mediterranean food pattern under free-living conditions on circulating oxidized LDL (ox-LDL) in a group of 71 healthy women from the Quebec City metropolitan area. The 12-wk nutritional intervention consisted of 2 courses on nutrition and 7 individual sessions with a dietitian. A score based on the 11 components of the Mediterranean pyramid was established to determine the women's adherence to the Mediterranean food pattern. Plasma ox-LDL concentrations were measured by a monoclonal antibody mAb-4E6-based competition ELISA. Among all women, plasma ox-LDL decreased by 11.3% after 12 wk of nutritional intervention (P < 0.0001) despite a lack of change in plasma LDL cholesterol (LDL-C). Also, an increase in the Mediterranean dietary score was significantly correlated with a decrease in ox-LDL concentrations (r = -0.30; P = 0.01). More specifically, increases in servings of fruits (r = -0.25; P < 0.05) and vegetables (r = -0.24; P < 0.05) were associated with decreases in ox-LDL concentrations. Changes in the food pattern in response to a nutritional intervention promoting the Mediterranean food pattern were accompanied by beneficial effects in circulating ox-LDL concentrations in healthy women.     

Prevalence of lymph nodes in the apex of level V: a plea against the necessity to dissect the apex of level V in mucosal head and neck cancer

BACKGROUND: We assessed the prevalence of histologically proven normal or invaded lymph nodes in the apex of level V. METHODS: Seventy neck dissections were performed in 41 patients with mucosal head and neck squamous cell carcinoma (SCC). Fifty-one neck dissections were performed in 30 previously untreated patients (group 1); 19 neck dissections were carried out in 11 patients previously irradiated (group 2). RESULTS: Pathologic analysis was unable to identify any lymph node in 70% of the apex specimens. In group 1, no lymph nodes were detected in 63%, whereas one or more noninvaded lymph nodes were present in 37%; in group 2, no lymph nodes were identified in 89%, whereas one or more normal lymph nodes were found in 11% (p = .03). Metastatic lymph nodes were never identified. CONCLUSIONS: The prevalence of lymph nodes in the apex was 30%. No invaded lymph nodes were identified. In addition to anatomic evidence, these results suggest that dissection of the apex is not necessary in mucosal head and neck SCC.     

Olanzapine versus risperidone in the treatment of post-psychotic depression in schizophrenic patients

OBJECTIVE: To compare the efficacy of two atypical antipsychotic drugs, olanzapine and risperidone, in schizophrenic patients with post-psychotic depression. RESULTS: A clinically significant decrease of MADRS scores occurred in patients treated with both drugs for 8 weeks. CONCLUSION: Atypical antipsychotic drugs may be particularly appropriate when treating schizophrenic patients with depression.     

Calculation of absolute protein-ligand binding free energy from computer simulations

A general methodology for calculating the equilibrium binding constant of a flexible ligand to a protein receptor is formulated on the basis of potentials of mean force. The overall process is decomposed into several stages that can be computed separately: the free ligand in the bulk is first restrained into the conformation it adopts in the bound state, position, and orientation by applying biasing potentials, then it is translated into the binding site, where it is released completely. The conformational restraining potential is based on the root-mean-square deviation of the peptide coordinates relative to its average conformation in the bound complex. Free energy contributions from each stage are calculated by means of free energy perturbation potential of mean force techniques by using appropriate order parameters. The present approach avoids the need to decouple the ligand from its surrounding (bulk solvent and receptor protein) as is traditionally performed in the double-decoupling scheme. It is believed that the present formulation will be particularly useful when the solvation free energy of the ligand is very large. As an application, the equilibrium binding constant of the phosphotyrosine peptide pYEEI to the Src homology 2 domain of human Lck has been calculated. The results are in good agreement with experimental values.